Non-severe Episodes Research Articles

380-P: Towards Prevention of Nonsevere Hypoglycemia in Type 1 Diabetes with Oral Glucose at a Higher Blood Glucose Threshold—The REVERSIBLE Trial

Background: Current guidelines recommend initiating the treatment of non-severe (NS) hypoglycemia with 15g of carbohydrates (CHO) at 15 minutes intervals when blood glucose (BG) reaches <72 mg/dl. Despite this recommendation, NS hypoglycemia management remains challenging for people living with type 1 diabetes (pwT1D) and more optimal treatment strategies are required. We aim to assess the efficacy of 15g of CHO at higher treatment thresholds. Methods: The REVERSIBLE Trial is an open-label, randomized, three interventions x three periods cross-over study. Following inpatient insulin-induced decrease in BG, 16g of oral carbohydrates is administered at a plasma glucose threshold of <72 mg/dl, ≤81 mg/dl or ≤90 mg/dl. The primary outcome is the time (in minutes) spent in hypoglycemia (<72 mg/dl) after the initial correction. Results: Participants (n=29) characteristics are 52% male, 46.8±16.3 years old, BMI of 26.4±3.9 kg/m2, diabetes duration of 26.2±15.9 years, A1c of 53.4±15.5 mmol/mol and 62% insulin pump users. When comparing <72 mg/dl (control) to ≤81 mg/dl and ≤90 mg/dl treatment thresholds, 100% vs. 86% (p=0.1201) vs. 34% (p<0.0001) of participants had hypoglycemia. These hypoglycemic events lasted 26.0±12.6 vs. 17.9±14.7 (p=0.026) vs. 7.1±11.8 (p=0.002) minutes, with a blood glucose nadir of 56.5±9.9 vs. 63.5±7.9 (p=0.008) vs. 73.4±9.7 mg/dl (p=0.002) respectively. In the control group, 69% of participants required more than one treatment to reach or maintain normoglycemia (≥ 72 mg/dl) compared to 52% in the ≤81 mg/dl group and 31% in the ≤90 mg/dl group with no significant rebound hyperglycemia (>180mg/dl) within the first hour. Conclusion: Compared with <72 mg/dl, consuming 16g of oral carbohydrates at ≤81 mg/dl and ≤90 mg/dl shortened the time spent in hypoglycemia, lessened the glucose nadir and reduced the need for repetitive treatments. For some NS episodes, pwT1D could benefit from CHO intake at a higher BG threshold. Disclosure R.Cheng: None. N.Taleb: Consultant; Viatris Inc. Z.Wu: Other Relationship; Eli Lilly and Company. V.Messier: None. R.Rabasa-lhoret: Consultant; Dexcom, Inc., Abbott, Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi, Lilly, Tandem Diabetes Care, Inc., Insulet Corporation. Funding JDRF (4-SRA-2018-651-Q-R); Canadian Institutes of Health Research (JT1-157204)

Cinematic rendering of leiomyosarcoma of the superior mesenteric vein.

Investigate the effectiveness of IDegLira, a fixed-ratio combination of insulin degludec/liraglutide, in a real-world setting in patients with type 2 diabetes mellitus in the United Arab Emirates.This non‐interventional study enrolled adults switching to IDegLira from basal insulin (BI) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with/without concomitant oral antidiabetic drugs (OADs). Primary endpoint was change in HbA1c from baseline, assessed using a mixed model for repeated measurements.Among 263 patients (BI ± OADs, n=206; GLP-1 RA ± OADs, n=57), mean baseline HbA1c was 9.29% (78 mmol/mol). After 26 weeks, HbA1c was significantly reduced (BI ± OADs, –0.83% [–9.0 mmol/mol] and GLP-1 RA ± OADs, –1.24% [–13.5 mmol/mol]; both p<0.0001). Fasting plasma glucose (FPG) was significantly reduced (–39.48 mg/dL [BI ± OADs] and –82.49 mg/dL [GLP-1 RA ± OADs]; both p<0.0001). Before treatment initiation, 3/263 patients experienced ≥1 severe hypoglycaemic episode and 7/263 patients experienced ≥1 non-severe hypoglycaemic episode compared with 1/263 patients who had ≥1 severe and 1/263 who had ≥1 non-severe episode at end of study. Body weight decreased significantly among patients switching from BI ± OADs (–1.05 kg [p<0.0001]). Treatment was well tolerated.IDegLira significantly reduced HbA1c and FPG in this real-world setting, along with less frequent episodes of hypoglycaemia. Switching to IDegLira offers effective treatment intensification for type 2 diabetes patients with inadequate glycaemic control.

The use of long-acting insulin degludec in adult patients with type 2 diabetes mellitus in real clinical practice in Russia

BACKGROUND: Effective glycaemic control remains the most important task in managing the risks of Diabetes type 2 complications development. In this regard, the choice of insulin preparations with minimal variability of action is of utmost importance since this approach allows achieving the maximum treatment effectiveness and adequate safety level.AIM: The aim of this study was to investigate insulin degludec treatment effect on glycemic control in adult patients with Diabetes Mellitus (DM) type 2 in a real-world clinical setting in the Russian Federation.MATERIALS AND METHODS: The open prospective study was conducted in 2020–2021 in 35 clinical centers in 31 cities of the Russian Federation. The study included adult patients with type 2 DM treated according to Russian routine clinical practice. The prospective follow-up period was 26 weeks. The main study endpoints were changes in HbA1c level, fasting plasma glucose, insulin daily doses, number, and characteristics of different types of hypoglycaemia episodes and adverse events (AEs), and patient preferences compared to previous treatment.RESULTS: The study enrolled 494 patients. By the end of follow-up period:The mean HbA1c decrease was 1.6% (p&lt;0.0001).Fasting plasma glucose level decreased by 3.4 mmol/L (p&lt;0.0001).Daily basal and prandial insulin doses decreased by 1.6 IU/day (p&lt;0.0001) and 2.1 IU/day (p&lt;0.01), respectively.Severe episodes of hypoglycemia did not occur, while the incidence of nonsevere episodes decreased significantly.76 patients (15.4%) had 105 AEs, of which 41 (in 33 patients, 6.7%) were serious.COVID-19 was the most frequent AE reported in 21 patients (4.3%).Only in one case insulin degludec was withdrawn due to the patient’s pregnancy and the AEs that arose from it.Most patients (98.6%) preferred insulin degludec to previous treatment.CONCLUSION: The study demonstrated a statistically significant improvement in glycemic control, accompanied by basal insulin dose decrease combined with the absence of severe episodes of hypoglycemia, and significant decrease of nonsevere episodes (total and nocturnal). These results led to a large proportion of patients wanting to continue insulin degludec treatment preferring the medicine over previous treatment.

Switching to a fixed-ratio combination of insulin degludec/liraglutide (IDegLira) is associated with improved glycaemic control in a real-world population with type 2 diabetes mellitus in the United Arab Emirates: Results from the multicentre, prospective INTENSIFY study

AimInvestigate the effectiveness of IDegLira, a fixed-ratio combination of insulin degludec/liraglutide, in a real-world setting in patients with type 2 diabetes mellitus in the United Arab Emirates. MethodsThis non‐interventional study enrolled adults switching to IDegLira from basal insulin (BI) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with/without concomitant oral antidiabetic drugs (OADs). Primary endpoint was change in HbA1c from baseline, assessed using a mixed model for repeated measurements. ResultsAmong 263 patients (BI ± OADs, n = 206; GLP-1 RA ± OADs, n = 57), mean baseline HbA1c was 9.29 % (78 mmol/mol). After 26 weeks, HbA1c was significantly reduced (BI ± OADs, −0.83 % [−9.0 mmol/mol] and GLP-1 RA ± OADs, −1.24 % [−13.5 mmol/mol]; both p < 0.0001). Fasting plasma glucose (FPG) was significantly reduced (−39.48 mg/dL [BI ± OADs] and −82.49 mg/dL [GLP-1 RA ± OADs]; both p < 0.0001). Before treatment initiation, 3/263 patients experienced ≥ 1 severe hypoglycaemic episode and 7/263 patients experienced ≥ 1 non-severe hypoglycaemic episode compared with 1/263 patients who had ≥ 1 severe and 1/263 who had ≥ 1 non-severe episode at end of study. Body weight decreased significantly among patients switching from BI ± OADs (−1.05 kg [p < 0.0001]). Treatment was well tolerated. ConclusionsIDegLira significantly reduced HbA1c and FPG in this real-world setting, along with less frequent episodes of hypoglycaemia. Switching to IDegLira offers effective treatment intensification for type 2 diabetes patients with inadequate glycaemic control.

810-P: Real-World Performance of IDegAsp over Six Years in Asian-Indian Population

There is scarce data on the long-term safety and efficacy of IDegAsp in Asian Indians in a real-world (RW) setting. IDegAsp is a co-formulation of an ultra-long-acting insulin Degludec and a rapid acting insulin Aspart. A multi-centric, retrospective observational study was conducted to evaluate long-term efficacy and safety of IDegAsp in T2D on regular follow up for &amp;gt;5 years. Baseline clinical data of 535 T2D (78.7% males; avg. age= 53.41 ± 12.yrs; HbA1c= 8.88 ±1.96 %; avg. duration of diabetes: 11.34 ± 7.57yrs) , previously on treatment (90.1 %) which included various OADs±insulin regimen, or treatment-naive (9.9 %) , who were switched to or initiated on IDegAsp respectively, from December 2014 - 2021 were analyzed. Significant improvements (P&amp;lt;0.05) in clinical parameters were observed from baseline (Table 1) . The TDD was 15.45 ± 10.53 units/day (at 3 months) which increased (p&amp;lt;o.oo1) to 20.03 ± 11.units/day post-treatment (67 months) . 65.2 % continued twice daily IDegAsp and 3.9 % switched from twice daily to once daily IDegAsp during treatment. 30.9% continued once daily IDegAsp. A total of non-severe hypoglycemic episodes were observed. In this RW study involving T2D from Asia, IDegAsp significantly improved A1C and a range of clinical profiles, with negligible hypoglycemia. Unlike conventional premix/basal bolus regimen, IDegAsp offers a less complex, more physiological, safe and effective solution for glycemic control. Disclosure J.Kesavadev: None. B.D.Saboo: None. A.Shankar: None. G.Krishnan: None. A.Basanth: None. A.Ashik: None. A.David: None. S.Jothydev: None.

IDF21-0679 INTENSIFY: effectiveness of insulin degludec/liraglutide (IDegLira) in a real-world T2DM population in the UAE

Background: In patients with type 2 diabetes mellitus (T2DM) and inadequate glycaemic control, combining a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with basal insulin (BI) offers an effective treatment-intensification strategy. A fixed-ratio combination of insulin degludec and liraglutide (IDegLira; Novo Nordisk) was launched in the United Arab Emirates (UAE) in 2018. Aim: To investigate the effect of IDegLira in a real-world population of patients with T2DM switching from BI or GLP-1 RA (± oral antidiabetic drugs [OADs]) in routine clinical practice in the UAE. Method: INTENSIFY was a 26–38-week, multicentre, prospective, non-interventional, real-world study. T2DM patients (≥18 years) with inadequate glycaemic control on BI or GLP-1 RA (± OADs) were eligible if a switch to IDegLira had been planned. The primary endpoint was change in laboratory measured HbA1c from baseline to end of the study. Secondary endpoints included overall change in fasting plasma glucose (FPG); change in body weight; incidence of hypoglycaemic episodes in the 4-week (non-severe and nocturnal non-severe episodes) and 26-week (severe episodes) periods before end of study (EOS) versus before initiation of IDegLira treatment. Treatment preference and safety were also assessed. ClinicalTrials.gov identifier: NCT03823339 Results: Among 263 patients, 206 (78.3%) and 57 (21.7%) patients had previously received BI ± OADs and GLP-1 RA ± OADs, respectively. Baseline mean HbA1c was 9.29%. Switching to IDegLira was associated with a significant overall reduction in HbA1c, with an estimated mean (SE) change from baseline of –0.9% (0.1%), 95% CI, –1.1 to –0.7 (p<0.0001). There was also a significant reduction in FPG: overall mean (SE) change from baseline was –48.2 (5.9) mg/dL, 95% CI, –59.9 to –36.5 (p<0.0001). A significant reduction in body weight was achieved among patients previously treated with BI ± OADs,with an estimated mean (SE) change from baseline of –1.1 (0.2) kg, 95% CI, –1.5 to –0.6 (p<0.0001). The estimated incidence of hypoglycaemic episodes was numerically lower in the periods before EOS versus before initiation of IDegLira treatment (2 vs. 13, 2 vs. 6, and 2 vs. 4 episodes for non-severe, nocturnal non-severe, and severe hypoglycaemia, respectively). Overall, the number of IDegLira dose steps increased significantly (mean [SE] change, 6.1 [0.6] steps, 95% CI, 5.0–7.2 [p<0.0001]). Most patients (86%) preferred IDegLira over previous treatments. IDegLira was well tolerated with no unexpected safety findings. Discussion: Switching from BI or GLP-1 RA (± OADs) to IDegLira significantly improved glycaemic control in adults with T2DM. There were significant overall reductions in HbA1c and FPG; a significant reduction in body weight among patients previously on BI ± OADs, and a reduction in hypoglycaemic events. Conservative dose titration (an increase of approximately 1 dose step per month) was identified in the INTENSIFY study. A stricter titration schedule and frequent interaction between patients and investigators may have led to greater improvement in both primary and secondary endpoints.

Interim analysis of a multicenter registry study of COVID-19 patients with inflammatory bowel disease in Japan (J-COSMOS)

BackgroundThe spread of coronavirus disease 2019 (COVID-19) had a major impact on the health of people worldwide. The clinical background and clinical course of inflammatory bowel disease (IBD) among Japanese patients with COVID-19 remains unclear.MethodsThis study is an observational cohort of Japanese IBD patients diagnosed with COVID-19. Data on age, sex, IBD (classification, treatment, and activity), COVID-19 symptoms and severity, and treatment of COVID-19 were analyzed.ResultsFrom 72 participating facilities in Japan, 187 patients were registered from June 2020 to October 2021. The estimated incidence of COVID19 in Japanese IBD patients was 0.61%. The majority of IBD patients with COVID-19 (73%) were in clinical remission. According to the WHO classification regarding COVID-19 severity, 93% (172/184) of IBD patients had non-severe episodes, while 7% (12/184) were severe cases including serious conditions. 90.9% (165/187) of IBD patients with COVID-19 had no change in IBD disease activity. A logistic regression analysis stepwise method revealed that older age, higher body mass index (BMI), and steroid use were independent risk factors for COVID-19 severity. Six of nine patients who had COVID-19 after vaccination were receiving anti-tumor necrosis factor (TNF)-α antibodies.ConclusionAge, BMI and steroid use were associated with COVID-19 severity in Japanese IBD patients.

Evaluating the Incidence and Risk Factors Associated With Mild and Severe Hypoglycemia in Insulin-Treated Type 2 Diabetes

ObjectivesThis study to assess the incidence rates and risk factors of hypoglycemia in a wide real-life sample of patients with insulin-treated type 2 diabetes mellitus. MethodsIn a prospective epidemiological study, data from 817 subjects were collected from medical records and via interviews. Over a 3-month period, hypoglycemic episodes were recorded via self-measurement of glucose levels at least twice daily. Cox proportional and negative binomial multivariable models were applied to estimate adjusted and unadjusted hazard ratios and incidence rate ratios of hypoglycemic events. ResultsOf the 817 patients, 52.9% experienced hypoglycemia, 38.1% had only nonsevere episodes, and 14.8% had at least 1 severe episode. Total events per patient-year were estimated at 13.3 (±24.8), with 11.8 (±21.6) and 1.4 (±4.7) being nonsevere and severe, respectively. History of hypoglycemia and severe hypoglycemia were consistent risk factors of hypoglycemia. Intensification of therapy was associated with higher incidence rates, whereas the effect on the hazard rates was more moderate. Longer duration of insulin therapy and the presence of congestive heart failure were associated with a higher risk of developing and frequency of hypoglycemia. Hypoglycemia awareness was found to independently affect only mild hypoglycemia. ConclusionsHypoglycemia is a common complication in patients with insulin-treated type 2 diabetes mellitus. The risk factors of developing hypoglycemia are to some extent different from those of the frequency of hypoglycemic episodes. Particular attention is required for patients with recurrent hypoglycemic events and on intensive antidiabetic therapy.

Cost of illness for severe and non-severe diarrhea borne by households in a low-income urban community of Bangladesh: A cross-sectional study.

The illness cost borne by households, known as out-of-pocket expenditure, was 74% of the total health expenditure in Bangladesh in 2017. Calculating economic burden of diarrhea of low-income urban community is important to identify potential cost savings strategies and prioritize policy decision to improve the quality of life of this population. This study aimed to estimate cost of illness and monthly percent expenditure borne by households due diarrhea in a low-income urban settlement of Dhaka, Bangladesh. We conducted this study in East Arichpur area of Tongi township in Dhaka, Bangladesh from September 17, 2015 to July 26, 2016. We used the World Health Organization (WHO) definition of three or more loose stool in 24 hours to enroll patients and enrolled 106 severe patients and 158 non-severe patients from Tongi General Hospital, local pharmacy and study community. The team enrolled patients between the first to third day of the illness (≤ 72 hours) and continued daily follow-up by phone until recovery. We considered direct and indirect costs to calculate cost-per-episode. We applied the published incidence rate to estimate the annual cost of diarrhea. The estimated average cost of illness for patient with severe diarrhea was US$ 27.39 [95% CI: 24.55, 30.23] (2,147 BDT), 17% of the average monthly income of the households. The average cost of illness for patient with non-severe diarrhea was US$ 6.36 [95% CI: 5.19, 7.55] (499 BDT), 4% of the average monthly income of households. A single diarrheal episode substantially affects financial condition of low-income urban community residents: a severe episode can cost almost equivalent to 4.35 days (17%) and a non-severe episode can cost almost equivalent to 1 day (4%) of household’s income. Preventing diarrhea preserves health and supports financial livelihoods.

Systemic Inflammation during and after Bronchiectasis Exacerbations: Impact of Pseudomonas aeruginosa.

Bronchiectasis is a chronic structural disease associated with exacerbations that provoke systemic inflammation. We aimed to evaluate the systemic acute proinflammatory cytokine and its biomarker profiles during and after exacerbations and its relationship with the severity of episode, microbiological findings, and the bronchiectasis severity index. This prospective observational study compared exacerbation and stable groups. Cytokine (interleukins (IL)-17a, IL-1β, IL-6, IL 8; tumor necrosis factor-alpha (α)) and high-sensitivity C-reactive protein (hsCRP) levels were determined by multiplex analysis on days 1, 5, 30, and 60 in the exacerbation group and on day 1 in the stable group. We recruited 165 patients with exacerbations, of which 93 were severe (hospitalized). Proinflammatory systemic IL-17a, IL-1β, IL-8, and tumor necrosis factor-α levels increased similarly on days 1 and 5 in severe and non-severe episodes, but on day 30, IL-17a, IL-8, and IL-6 levels were only increased for severe exacerbations. The highest IL-17a level occurred in patients with chronic plus the acute isolation of Pseudomonas aeruginosa. At 30 days, severe exacerbations were independently associated with higher levels of IL-17 (Odds ratio (OR) 4.58), IL-6 (OR 4.89), IL-8 (OR 3.08), and hsCRP (OR 6.7), adjusted for age, the bronchiectasis severity index, and treatment duration. Exacerbations in patients with chronic P. aeruginosa infection were associated with an increase in IL-17 and IL-6 at 30 days (ORs 7.47 and 3.44, respectively). Severe exacerbations elicit a higher systemic proinflammatory response that is sustained to day 30. Patients with chronic P. aeruginosa infection had impaired IL-17a reduction. IL-17a could be a useful target for measuring systemic inflammation.

1166-P: Cost Analysis of a Flash Glucose Monitoring System in Type 2 Diabetes Receiving ≥2 Insulin Doses a Day in Spain

FreeStyle Libre2 system is a sensor-based flash monitoring (FM) system, which assesses interstitial fluid glucose. The study aimed to estimate the cost associated with the use of FM compared to self-monitoring of blood glucose (SMBG) in type 2 diabetes mellitus (T2DM) population from the Spanish National Health System perspective. The cost for glucose monitoring in T2DM patients treated with ≥2 insulin doses a day was modelled. The cost estimation considered the annual resource consumption for glucose monitoring (strips, lancets and FM sensors) and clinical management of hypoglycemia episodes. Severe hypoglycemia episodes (SHE) and non-severe hypoglycemia episodes (NSHE) published event rates (2.5 and 17.0 episodes/patient/year) were considered. Event reductions associated to FM system use were applied (48.8% [SHE]; 27.7% [NSHE]), derived from REPLACE trial findings. Based on published evidence, hospital attendance was required in 20.5% of SHEs (further hospitalization in 16.0%). Daily strip and lancet-consumption in T2DM patients was fixed at 4.81 for SMBG users, and 0.2 for FM system users according the REPLACE findings. FM sensor annual consumption per patient was 26. Unitary costs (€,2019 excluding VAT) derived from national databases and literature were: €0.28/strip; €0.09/lancet; €3.09/daily FM sensor; €3,774/hospitalized SHE; €1,779/hospital-attended non-admitted SHE; €385/community attended SHE and €15/NSHE. Yearly cost was €2,779 and €2,295 per patient using SMBG or FM system, respectively. For a cohort of 1,000 T2DM patients using ≥2 insulin doses a day; 1,221 SHEs (48 hospitalizations for SHE) and 4,715 NSHEs, yearly could be avoided with FM use. The use of the FM system in 1,000 patients could generate annual cost-savings up to €483,031 compared to SMBG (-17.4% of cost reduction). In conclusion, FM system is a potential cost-saving strategy in T2DM patients treated with ≥2 insulin doses a day, in Spain. Disclosure F. Gomez-Peralta: Advisory Panel; Self; Abbott, Menarini Group, Novartis AG, Sanofi. Speaker’s Bureau; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novartis AG, Novo Nordisk A/S, Sanofi. I. Oyagüez: None. S. Artola: None. F. Carrasco: None. J. Carretero Gomez: None. F. Garcia-Soidan: None. R. Gomez-Huelgas: None. J. Merino Torres: None. A. Pérez: None. Funding Abbott Diabetes Care

Assessing Prevalence of Hypoglycemia in a Medical Transcription Database.

PurposeThe prevalence of hypoglycemia in patients with diabetes mellitus is likely underreported, particularly with regard to non-severe episodes, and representative estimates require more detailed data than claims or typical electronic health record (EHR) databases provide. This study examines the prevalence of hypoglycemia as identified in a medical transcription database.Patients and MethodsThe Amplity Insights database contains medical content dictated by providers detailing patient encounters with health care professionals (HCPs) from across the United States. Natural language processing (NLP) was used to identify episodes of hypoglycemia using both symptom-based and non-symptom-based definitions of hypoglycemic events. This study examined records of 41,688 patients with type 1 diabetes mellitus and 317,399 patients with type 2 diabetes mellitus between January 1, 2016, and April 30, 2018.ResultsUsing a non-symptom-based definition, the prevalence of hypoglycemia was 18% among patients with T1DM and 8% among patients with T2DM. These estimates show the prevalence of hypoglycemia to be 2- to 9-fold higher than the 1% to 4% prevalence estimates suggested by claims database analyses.ConclusionIn this exploration of a medical transcription database, the prevalence of hypoglycemia was considerably higher than what has been reported via retrospective analyses from claims and EHR databases. This analysis suggests that data sources other than claims and EHR may provide a more in-depth look into discrepancies between the mention of hypoglycemia events during a health care visit and documentation of hypoglycemia in patient records.

Comparative Effectiveness of Vancomycin and Metronidazole for the Initial Episode of Nonsevere Clostridium Difficle Infection

The infection with Clostridium difficile (CDI), which appeared at epidemic level, after acquiring the germ of some fluoroquinolone resistance genes, initially considered nosocomial infection and adverse effect post-antibiotic therapy, is affecting more and more people without risk factors and extending into the community. This paper proposes an analysis of the two main antibiotics used in therapy: metronidazole and vancomycin, the evidence of efficacy in the literature and the chemical stability of antibiotics in simulated gastrointestinal fluid. Based on UV-Vis absorption spectra, it can be considered that there are no major changes in the chemical structure of the investigated drugs in the presence of gastro-duodenal conditions. Clinical impact of comparative treatment with metronidazole and vancomycin has also been studied, in a group of 720 CDI patients hospitalized during the period 1.01.2017-31.12.2018 in the Clinical Hospital St. Parascheva of Infectious Diseases Galati. From this group, two subgroups were selected, one of 284 patients receiving oral vancomycin treatment and one group of 62 patients receiving oral metronidazole for an initial nonsevere episode of CDI. The number of days from the beginning of the treatment until the normalization of the stool, the length of hospitalization, the number of days of antibiotic treatment and the percentage of relapses were comparable in the two groups, the percentage of deaths in the first 30 days from the episode of CDI was higher in the vancomycin-treated group, probably due mainly to the severe comorbidities of these patients. The conclusion of the study is that the treatments with metronidazole and vancomycin, of the initial episode, nonsevere of CDI are comparable as a therapeutic response, provided that the patients treated with metronidazole do not associate hepatic, renal or neurological impairment due to the risk of adverse reactions.

Comparative Effectiveness of Vancomycin and Metronidazole for the Initial Episode of Nonsevere Clostridium Difficle Infection

The infection with Clostridium difficile (CDI), which appeared at epidemic level, after acquiring the germ of some fluoroquinolone resistance genes, initially considered nosocomial infection and adverse effect post-antibiotic therapy, is affecting more and more people without risk factors and extending into the community. This paper proposes an analysis of the two main antibiotics used in therapy: metronidazole and vancomycin, the evidence of efficacy in the literature and the chemical stability of antibiotics in simulated gastrointestinal fluid. Based on UV-Vis absorption spectra, it can be considered that there are no major changes in the chemical structure of the investigated drugs in the presence of gastro-duodenal conditions. Clinical impact of comparative treatment with metronidazole and vancomycin has also been studied, in a group of 720 CDI patients hospitalized during the period 1.01.2017-31.12.2018 in the Clinical Hospital St. Parascheva of Infectious Diseases Galati. From this group, two subgroups were selected, one of 284 patients receiving oral vancomycin treatment and one group of 62 patients receiving oral metronidazole for an initial nonsevere episode of CDI. The number of days from the beginning of the treatment until the normalization of the stool, the length of hospitalization, the number of days of antibiotic treatment and the percentage of relapses were comparable in the two groups, the percentage of deaths in the first 30 days from the episode of CDI was higher in the vancomycin-treated group, probably due mainly to the severe comorbidities of these patients. The conclusion of the study is that the treatments with metronidazole and vancomycin, of the initial episode, nonsevere of CDI are comparable as a therapeutic response, provided that the patients treated with metronidazole do not associate hepatic, renal or neurological impairment due to the risk of adverse reactions. Keywords: Clostridium difficile, metronidazole, vancomycine, chemical stability, UV-Vis spectra

PDB58 A LITERATRUE REVIEW OF THE ECONOMIC BURDEN OF HYPOGLYCEMIA IN PATIENTS WITH DIABETES MELLITUS IN CHINA

Hypoglycemia is one of the most common acute complications during diabetes treatments. This study reviews and assesses economic burden of hypoglycemia in patients with diabetes mellitus (DM) in China. A literature review was conducted by key words including cost, economic burden, healthcare utilization, and/or health-related expenditure associated with hypoglycemia in patients with DM in China, published in either Chinese or English. PubMed, China National Knowledge Infrastructure (CNKI), Wanfang Data, and academic conference abstracts were searched through April 2019. There were 15 publications identified; 4 articles and 4 abstracts were selected; 7 publications were excluded with criteria of non-peer reviews and non-original data. All study designs were retrospective. The data sources of patient surveys, hospital electronic medical records, and medical insurance claims data were applied. In summary, current available evidence revealed hypoglycemia significantly consumed healthcare resources and induced non-medical costs including work absences and transportation fees. The total cost per patient of hypoglycemia was 1,513∼5,560.76 CNY/event or 658.1∼5985.8 CNY/year based on severity and frequency. Medical costs for DM with hypoglycemia episodes were considerable (667∼925 CNY/outpatient visit, 5,904∼20,140 CNY/inpatient visit) and higher than non-DM (increased 414 and 1,113 CNY respectively). By controlling confounding factors and comparing with non-hypoglycemia cohort, the associations of hypoglycemia with healthcare resource utilization and cost were further estimated. The facts were confirmed that patients experiencing hypoglycemia had significant higher all-cause cost (increased 4,526∼8,358 CNY/person/year for all event, Incremental 10,873 USD/person/year or 28,364 CNY/person/year for severe vs. non-severe episodes), diabetes-specific cost (increased 1,663 CNY/visit or 3,424 CNY/person/year), outpatient visits (increased 1.87∼3.2 times/year and 234∼7,153 CNY/visit), and hospitalization (increased proportion by 5.6%∼25.66% and admission cost by 2,500∼17,284 CNY, prolonged length of stay by 2.5 days). Hypoglycemia events significantly increase cost and healthcare resource utilization for DM in China.

11-LB: Nonsevere Hypoglycemia Predicts Increased Risk of Subsequent Severe Events in Patients with Type 2 Diabetes

It is well-known that higher rates of non-severe hypoglycemic episodes (NSHEs) associate with a greater risk of severe hypoglycemic episodes (SHEs) in patients with type 1 diabetes. We investigated whether a similar association existed in patients with type 2 diabetes (T2D). We explored if annual rate of NSHEs was associated with time to first SHE, cardiovascular (CV) death, time to first major adverse CV event (MACE), and all cause death in patients with T2D using data from LEADER, a CV outcomes trial with 9340 patients with T2D.We used a Cox proportional hazards model adjusted for randomized treatment arm, and annual rate of NSHE as a time-dependent covariate with three levels; A: &amp;lt;2 NSHEs per year (reference), B: 2−11 NSHEs, or C: ≥12 NSHEs. Hazard ratios were used to estimate the association between NSHE and each of the outcomes. Higher rates of NSHE were associated with a higher rate of severe hypoglycemia, MACE, CV death, and all-cause death in patients with T2D (Figure); our results suggest that in this T2D population, a high rate of NSHEs may be associated with more harmful outcomes. Disclosure S.R. Heller: Advisory Panel; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi-Aventis, Takeda Pharmaceutical Company Limited, Zealand Pharma A/S. Consultant; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S. E. Hachmann-Nielsen: Employee; Self; Novo Nordisk A/S. K. Kvist: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Funding Novo Nordisk

Efficacy of Oral Antibiotics for Non-Severe Exacerbations of Bronchiectasis in Children (BEST 1): A Multi-Centre, Double-Blind, Double-Dummy, Randomised Placebo-Controlled Trial

Background: Bronchiectasis guidelines recommend antibiotics for treating acute respiratory exacerbations, but placebo-controlled, randomised-controlled trials (RCTs) are lacking in children. Since many exacerbations are virus-triggered, antibiotics may be unnecessary for non-severe (non-hospitalised) episodes. We hypothesised that oral amoxicillin-clavulanate and azithromycin are both superior to placebo for achieving symptom resolution by day-14 when treating non-severe exacerbations in children. Methods: In this multicentre (n=4), parallel, double-dummy, double-blind, placebo-controlled three-arm RCT, children aged 1-19 years were randomised at exacerbation onset to receive: (a) amoxicillin-clavulanate (45mg/kg/day)/azithromycin-placebo, (b) azithromycin (5mg/kg/day)/amoxicillin-clavulanate-placebo, or (c) placebo/placebo for 14-days (Australian-New Zealand Registry, ACTRN12612000011886). The primary outcome was exacerbation resolution by day-14. Secondary outcomes included exacerbation duration, time-to-next exacerbation, parent cough-specific quality-of-life, laboratory and spirometry assessments and nasopharyngeal microbiology. Treatment arms were compared using generalised-linear-models. Statistical significance was set at p<0·0245. Findings: Between April 2012 and December 2017, 197 children were randomised (amoxicillin-clavulanate n=63, azithromycin n=67, placebo n=67). By day-14, exacerbations had resolved in 41 (65%), 41 (61%) and 29 (43%) children in the respective groups. Compared to placebo, the relative risk of resolution by day-14 for amoxicillin-clavulanate was 1·50 (95% confidence interval [CI] 1·08-2·09; p=0·02, number needed-to-treat-for-benefit=5, 95%CI 3-20) and for azithromycin 1·41 (95%CI 1·01-1·97; p=0·04). Compared to placebo, the median exacerbation duration was significantly shorter in the amoxicillin-clavulanate (7 versus 10-days, p=0·02), but not the azithromycin group (8 vs 10-days, p=0·24). Other secondary between-group outcomes were not significantly different. Azithromycin was associated with increased nasopharyngeal carriage of macrolide-resistant-bacteria, while respiratory viruses were identified in 53% of exacerbations. Interpretation: Amoxicillin-clavulanate and azithromycin both showed benefit compared to placebo for treating non-severe exacerbations of bronchiectasis in children. However, azithromycin was associated with increased carriage of antibiotic-resistant bacteria. Consequently, amoxicillin-clavulanate should remain the first-line oral antibiotic for treating non-severe exacerbations of bronchiectasis in children. Funding: This work was supported by the Australian National Health and Medical Research Council (NHMRC; project grant number 1019834,) the NHMRC Centre for Research Excellence in Lung Health of Aboriginal and Torres Strait Islander Children (1040830), and Cure Kids, Auckland, New Zealand (3702764/3539). VG was supported by an NHMRC post-graduate scholarship (1075119). ABC is supported by an NHMRC practitioner fellowship (1058213). KFO and HSV were supported by NHMRC CRE in Children’s Indigenous Lung Health fellowships (10450830). MB is supported by a NHMRC Hot North Fellowship (1131932). Declaration of Interest: We declare that we have no conflicts of interest. Ethical Approval: The protocol has received ethical approval from the respective Human Research Ethics Committees of all the participating institutions (Darwin: Department of Health and Families and Menzies School of Health Research; Brisbane: Children’s Health Services (Royal Children’s Hospital) and University of Queensland; Perth: Princess Margaret Hospital; Melbourne: Royal Children’s Hospital; Auckland: Northern Ethics Committee, Ministry of Health and Starship Children’s Health local ethics committee). The study is being conducted under Australia’s Therapeutic Goods Administration Clinical Trial Notification scheme.

The Economic Burden of Insulin-Related Hypoglycemia in Adults with Diabetes: An Analysis from the Perspective of the Italian Healthcare System.

IntroductionThe aim of this analysis was to estimate the cost of insulin-related hypoglycemia in adult patients with diabetes in Italy using the Local Impact of Hypoglycemia Tool (LIHT), and to explore the effect of different hypoglycemia rates on budget impact.MethodsDirect costs and healthcare resource utilization were estimated for severe and non-severe hypoglycemic episodes in Italy and applied to the population of adults with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) and their corresponding hypoglycemia episode rates (0.49 severe and 53.3 non-severe episodes per year for T1DM, and 0.09 severe and 9.3 non-severe episodes per year for T2DM). Uncertainty around model inputs was explored through sensitivity and scenario analyses.ResultsThe direct cost of insulin-related hypoglycemia in Italy is estimated at €144.7 million per year, with €65 million attributable to severe episodes and €79.6 million due to non-severe episodes. The total cost of hypoglycemia is approximately 1.7-fold higher for T2DM (€91.7 million) than for T1DM (€53 million). The cost of a hypoglycemic episode ranges from €4.59 for a non-severe event where additional self-monitoring of blood glucose (SMBG) testing is the only cost incurred, to €5790.59 for a severe event that also requires an ambulance, A&E, hospitalization, and a visit to a diabetes specialist. A reduction in hypoglycemia event rates could result in substantial cost savings; for example, a 20% reduction in severe and non-severe hypoglycemia rates could result in a saving of €47,769 per general population of 100,000 people.ConclusionsThe LIHT highlights the substantial economic burden of insulin-related hypoglycemia in Italy, particularly with regards to non-severe hypoglycemia, an aspect of hypoglycemia that is often overlooked. This analysis may aid healthcare decision-making by allowing the costs of insulin therapies or diabetes self-management programs to be balanced with the savings provided by reductions in hypoglycemia.FundingNovo Nordisk, UK.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0418-0) contains supplementary material, which is available to authorized users.

Non-severe hypoglycaemia is associated with weight gain in patients with type 1 diabetes: Results from the Diabetes Control and Complication Trial.

It is unclear whether the frequent non-severe episodes of hypoglycaemia observed during intensive glucose control in individuals with type 1 diabetes (T1D) are associated with subsequent weight gain. We analysed the association between non-severe hypoglycaemia and weight gain in 1441 Diabetes Control and Complication Trial (DCCT) participants. Non-severe hypoglycaemia was assessed by hypo-score (ie, number of blood glucose values <70 mg/dL divided by the total number of measurements during the DCCT quarterly visits). Significant associations were observed between the hypo-score and annual and total weight gain. The annual weight gain by hypo-score tertiles was 0.8 ± 1.2 (T1), 1.3 ± 1.5 (T2) and 1.4 ± 1.3 kg/y (T3), P < .001 for T2 and T3 vs T1, and for T3 vs T2. The odds ratio for a weight gain of 1.8 kg/y was 2.14 (95% CI, 1.56-2.93) for T2, and 2.53 (95%CI, 1.85-3.45) for T3 vs T1. These differences in weight gain and in risk of weight gain remained significant after adjustment for sex, age, duration of diabetes, HbA1c at baseline and treatment arms. In conclusion, our analysis shows a significant association between non-severe hypoglycaemia and weight gain in individuals with T1D from the DCCT.

The Economic Burden of Insulin-Related Hypoglycemia in Spain.

IntroductionAn analysis was conducted to estimate the economic burden of insulin-related hypoglycemia in adults in Spain, derived from a novel concept developed for the UK known as the Local Impact of Hypoglycemia Tool.MethodsCosts per severe and non-severe hypoglycemic episode were calculated for patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM). The costs per episode were applied to the population of adults with T1DM and T2DM using insulin in Spain according to the number of severe and non-severe episodes experienced per year. Costs were calculated using Spanish-specific resource costs and published values for resource utilization, including ambulance, accident and emergency (A&E) department, hospitalization, healthcare professional visits, and extra self-monitoring of blood glucose (SMBG) tests used in the week following the episode. A one-way sensitivity analysis on all model inputs was then performed.ResultsThe cost of insulin-related hypoglycemia in Spain is estimated as €662.0 m per year, €292.6 m of which is due to severe episodes and €369.4 m to non-severe episodes. The cost per episode varies from €1.25 for patients with T1DM and €1.48 for patients with T2DM for a non-severe episode where extra SMBG testing after the episode is the only action taken, to €4378.22 for T1DM and €3005.74 for T2DM for a severe episode that was treated in hospital and requires an ambulance, A&E visit, hospitalization, and a diabetes specialist visit. A reduction in severe and non-severe hypoglycemia rates of just 20% could lead to considerable cost savings of €284,925 per 100,000 general population.ConclusionThis analysis highlights the substantial economic burden of hypoglycemia in Spain, and gives budget holders the ability to assess the costs of new treatments or patient education programs in relation to the potential cost savings due to lower hypoglycemia rates.