Non-severe Events Research Articles

Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Severe Urinary Tract Infections: A Population-Based Cohort Study.

Prior studies evaluating risk for severe urinary tract infections (UTIs) with sodium-glucose cotransporter-2 (SGLT-2) inhibitors have reported conflicting findings. To assess whether patients initiating use of SGLT-2 inhibitors were at increased risk for severe UTI events compared with those initiating use of dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide-1 receptor (GLP-1) agonists. Population-based cohort study. 2 large, U.S.-based databases of commercial claims (March 2013 to September 2015). Within each database, 2 cohorts were created and matched 1:1 on propensity score. Patients were aged 18 years or older, had type 2 diabetes mellitus, and were initiating use of SGLT-2 inhibitors versus DPP-4 inhibitors (cohort 1) or GLP-1 agonists (cohort 2). The primary outcome was a severe UTI event, defined as a hospitalization for primary UTI, sepsis with UTI, or pyelonephritis; the secondary outcome was outpatient UTI treated with antibiotics. Hazard ratios (HRs) were estimated in each propensity score-matched cohort, with adjustment for more than 90 baseline characteristics. After 1:1 matching on propensity score, 123752 patients were identified in cohort 1 and 111978 in cohort 2 in the 2 databases. In cohort 1, persons newly receiving SGLT-2 inhibitors had 61 severe UTI events (incidence rate [IR] per 1000 person-years, 1.76), compared with 57 events in the DPP-4 inhibitor group (IR, 1.77) (HR, 0.98 [95% CI, 0.68 to 1.41]). In cohort 2, those receiving SGLT-2 inhibitors had 73 events (IR, 2.15), compared with 87 events in the GLP-1 agonist group (IR, 2.96) (HR, 0.72 [CI, 0.53 to 0.99]). Findings were robust across sensitivity analyses; within several subgroups of age, sex, and frailty; and for canagliflozin and dapagliflozin individually. In addition, SGLT-2 inhibitors were not associated with increased risk for outpatient UTIs (cohort 1: HR, 0.96 [CI, 0.89 to 1.04]; cohort 2: HR, 0.91 [CI, 0.84 to 0.99]). Generalizability of the study findings may be limited to patients with commercial insurance. In a large cohort of patients seen in routine clinical practice, risk for severe and nonsevere UTI events among those initiating SGLT-2 inhibitor therapy was similar to that among patients initiating treatment with other second-line antidiabetic medications. Brigham and Women's Hospital, Division of Pharmacoepidemiology and Pharmacoeconomics.

1091-P: Association between Mild and Severe Hypoglycemia in People with T1 and T2 Diabetes Enrolled in Randomized Controlled Trials for Assessing Insulin Therapy

Background and Aims: Hypoglycemia is a major threat of insulin therapy, but only severe events are often considered as valid endpoints. Surrogates are required; mild events are logical candidates. The International Hypoglycemia Study Group (IHSG) proposed thresholds (3.9 and 3.0 mmol/L) for representative mild events, but evidence is scarce. Materials and Methods: We studied the correlation of the rate (or the incidence) of non-severe events with the rate (or the incidence) of severe events in a study-level systematic analysis of published data (1/1/00-6/1/18) in insulin-treated patients. Mild event was defined as either “any hypoglycemia,” or “severe or confirmed <3.9 mmol/L,” or “severe or confirmed <3.0,” with a tolerance of +/-0.4 mmol/L to manage the multiplicity of definitions. Nocturnal period was defined as per study design, therefore not homogeneously. Severe events were mostly defined as per IHSG. Results and Conclusion: 127 out of 15570 studies were eventually included. Pearson R² are presented (Figure). The mild hypoglycemia were usually better correlated with incidence rather than rate of severe events. Incidence of severe or confirmed <3.0 mmol/L, especially if limited to the night, appeared to be the best surrogate for incidence of severe events. Disclosure R. Roussel: Advisory Panel; Self; Merck Sharp & Dohme Corp., Sanofi. Consultant; Self; Abbott, AstraZeneca, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Physiogenex. Research Support; Self; Janssen Pharmaceuticals, Inc. A. Moutairou: None. J. Riveline: Board Member; Self; Abbott, Lilly Diabetes, Novo Nordisk Inc. Consultant; Self; Novo Nordisk Inc. Research Support; Self; Air Liquide, Amgen Inc. Speaker's Bureau; Self; Abbott, Lilly Diabetes, Sanofi. J. Gautier: None. L. Potier: Advisory Panel; Self; Merck Sharp & Dohme Corp. Consultant; Self; Sanofi. Funding Sanofi

Impaired awareness of hypoglycaemia: A new risk factor for adverse pregnancy outcomes in type 1 diabetes.

The aim of this study is to evaluate the impact of impaired awareness of hypoglycaemia (IAH) on metabolic control and pregnancy outcomes in women with type 1 diabetes. This was a single-centre prospective cohort study of singleton pregnant women with type 1 diabetes. IAH was assessed at the first antenatal visit using Clarke's test (score≥3). Data on metabolic control, hypoglycaemic events, and the lipid profile were collected from prior to pregnancy and in each trimester of gestation. Pregnancy outcomes were also recorded. A total of 77 patients with type 1 diabetes were included; 24 (31.2%) were classified as having IAH. Compared with the normal awareness of hypoglycaemia (NAH) group, the IAH group did not show differences in HbA1c , weight gain, insulin doses, or severe and nonsevere hypoglycaemia events throughout pregnancy. IAH was associated with higher triglyceride concentrations in the second trimester (IAH: 154.8±61.1mg/dL, NAH: 128.6±31.2mg/dL, P=.034) and an increased risk of neonatal respiratory distress (odds ratio [OR] 11.24; 95% CI, 1.01-124.9, P=.041) in adjusted models. Increased risk of pre-eclampsia was related to higher second trimester triglyceride concentrations (OR 1.028; 95% CI, 1.004-1.053, P=.023) adjusted for confounders. The IAH was associated with increased risk of neonatal respiratory distress and pre-eclampsia, despite showing no differences in metabolic control. Hypoglycaemia awareness in the first antenatal visit should be assessed to identify the subgroup of pregnant women with increased risk of complications.

Clinical Analysis of 161 Cases of Surgical Treatment of Infective Endocarditis.

Objective: To evaluate the diagnostic criteria, surgical indications, and prognostic factors in the surgical treatment of infective endocarditis (IE). Methods: A total of 161 cases of post-operative IE treated at our hospital from January 2007 to December 2016 were included. The IE was diagnosed by the modified Duke criteria. Echocardiography and standard blood cultures were performed. These cases were divided into severe and non-severe adverse event groups. The association between prognostic factors and severe versus non-severe outcomes was examined using logistic regression. Results: Thirty patients (20.1%) with post-operative IE had positive pre-operative blood cultures, and 130 patients (80.7%) had valve vegetations. Four patients (2.5%) died within 30 days post-operatively. Twenty-two patients experienced severe adverse events. There were significant differences between the two groups regarding their serum albumin and creatinine concentrations, ejection fraction, and hospitalization, cardiopulmonary bypass, aortic cross-clamp, intensive care unit (ICU), and ventilation times (all p < 0.05). The bypass time, aortic cross-clamp time, and ICU time were identified as prognostic factors for severe adverse events. Conclusion: Echocardiography is an important diagnostic method for IE, and repeated tests might improve the sensitivity of diagnosis. Cardiac surgery seems to be an effective treatment for IE. Patient screening and reducing the operative time may improve the prognosis for patients who undergo surgical treatment for IE.

PDB64 ASSOCIATION BETWEEN CARDIOVASCULAR DISEASE RISK FACTORS AND HYPOGLYCAEMIC EVENTS IN TYPE 2 DIABETES USING THE IQVIA CORE DIABETES MODEL

There is clinical evidence that having a hypoglycemic event increases the risk of cardiovascular disease and mortality. In version 9.5 of the IQVIA Core Diabetes Model (CDM), an association relative risk factor (RR) of developing Cardiovascular Disease (CVD) and CVD mortality events related to non-severe (NSHE) and severe (SHE) hypoglycemic events over an adjustable duration were included. CVD conditions are Myocardial Infarction (MI), Stroke, Congestive Heart Failure (CHF) and angina. The current study compared the model outcomes obtained with and without applying a variable RR. The observational EDGE study comparing metformin + vildagliptin (M+V) versus metformin + sulphonylurea (M+S) was used as a base case. Basal insulin rescue therapy was applied to both arms when an HbA1c level of 7.5% was reached. Mean age at study start was 57.8 years and duration of diabetes 6 years. NSHE and SHE rate were applied as 13.94 per 100 patient-years (100 pt/year), 2.46 (100 pt/year) for M+S and 1.785, 0.315 (100 pt/year) for M+V. A RR of 1.1 was applied for all CVD conditions over a five-year period. UK 2018 costs were applied; costs and health benefits were discounted at 3.5%. Using RR increase of 1.1 for CVD and mortality due to SHE and NSHE, changed life expectancy (LE) and QALY with -1.68 and -1.55% (LY: from 11.961 to 11.760; QALY: 8.335 to 8.91) for M+V and -1.55 and -1.50% (LY: from 11.959 to 11.716; QALY: 8.217 to 8.052) for M+S. ICER decreased with -77% (66,336 to 15,086). Small increase in lifelong CVD event rates was seen. The impact of applying RR on CVD and mortality can be considerable depending on the absolute hypoglycemia rates, and thus more in type 1 than in type 2 diabetes.

MON-017 Impact of Hypoglycemia on Behaviors of Patients with Type 2 Diabetes (T2D): A Focus Group Study

BACKGROUND: Hypoglycemia is a common side effect of glucose-lowering therapy, especially insulin and sulfonylureas, which can lead to serious complications including death. The prevalence of hypoglycemia reported in observational studies has been low, likely because only severe events are captured. As non-severe hypoglycemia events are frequently not reported by patients, there is a need to better understand how patients describe hypoglycemia, what they do when they experience it, and how it impacts their daily lives. METHODS: This was a qualitative study consisting of four focus groups conducted in May 2018 among T2D patients who experienced hypoglycemia in the past 6 months. Adult T2D patients treated with insulin and/or sulfonylureas who resided in NYC and Atlanta were identified and recruited from the HealthCore Integrated Research Database (HIRD®) as well as from patient research panels maintained by the focus group facilities. Focus groups were 90-minutes long and led by an experienced moderator who used a study-specific discussion guide. Patients’ insights regarding how they defined hypoglycemia, its impact on their daily lives, and opportunities for intervention were grouped into common themes. RESULTS: Of 27 participants (14 NYC/13 Atlanta), 52% were female, mean age 39 years, 48% African-American, and mean time from T2D diagnosis 11.3 years. Two-thirds of patients (67%) tested their blood glucose ≥5 times a week and 52% on a daily basis; 85% of patients reported their most recent fasting blood sugar to be <250mg/dL and 37% <125mg/dL. Patients reported feeling symptoms at a glucose level of 60-70 mg/dL. Most participants described hypoglycemia as ‘scary’ and ‘uncomfortable’ but minimized its impact on their daily activities; greater concern was expressed with nocturnal than with daytime hypoglycemia due to sleep disruption, challenges in monitoring blood sugar at night, and fear of sleeping alone. Several participants admitted adjusting or skipping medication at night to avoid hypoglycemia. Most participants reported symptoms at least once per month; however, they admitted not talking to their doctors about hypoglycemia. Instead, they attributed hypoglycemia to improper diet and exercise or too much medication, and sought to manage on their own through social/family support and alignment of meal time with medication. CONCLUSIONS: Patients expressed greatest concern about nocturnal hypoglycemia. Although they minimized the effect of hypoglycemia, hypoglycemic events changed their behaviors in ways, such as dose skipping, that hinder optimal glycemic control. Most patients do not attribute hypoglycemia to their glucose-lowering medication(s), suggesting opportunities to better study the impact of alternative glucose-lowering treatments that lower hypoglycemia risk.

Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Atrial Fibrillation Patients With Intracerebral Hemorrhage.

Background and Purpose- Recurrent bleeding associated with oral anticoagulants (OACs) causes a dilemma in patients with atrial fibrillation (AF) sustaining an intracerebral hemorrhage. Treatment recommendations guiding clinical practice on optimal OAC agent selection in this population are lacking. This study aimed to investigate the comparative effectiveness and safety of non-vitamin K antagonist OAC (NOAC) versus warfarin in patients with AF sustaining an intracerebral hemorrhage. Methods- We conducted a nationwide observational cohort study including patients with AF sustaining an intracerebral hemorrhage and who subsequently claimed an OAC prescription. Contrasts of 1-year risks for ischemic stroke and intracerebral hemorrhage risks were obtained and evaluated by inverse probability treatment weighted absolute risk reduction and risk ratios. Results- Among 622 AF patients with intracerebral hemorrhage, 274 claimed a warfarin prescription and 348 a NOAC prescription. Mean age was 76 years (39% females); 72% had an index nonsevere event and 28% moderate to severe index event according to the Scandinavian Stroke Severity scale. The 1-year ischemic stroke risk was 7.85% for warfarin and 4.01% for NOACs, with a weighted absolute risk reduction of 3.78% (95% CI, -0.15% to 7.71%); the weighted risk ratio was 0.52 (0.27-1.00). For recurrent intracerebral hemorrhage, the risk was 7.00% for warfarin and 5.07% for NOACs. The absolute risk reduction was 1.93% (-2.02% to 5.87%), with an a weighted risk ratio of 0.72 (0.38-1.38). Conclusions- NOACs were associated with a nonsignificant lower risk of ischemic stroke and recurrent intracerebral hemorrhage compared with warfarin. The results add to current recommendations of selecting a NOAC agent for stroke prophylaxis treatment in patients with AF, including those with sustaining an intracerebral hemorrhage.

Management of Venous Thromboembolism (VTE) in Thrombocytopenic Patients Undergoing Induction Chemotherapy for Acute Leukemia

Introduction: Management of VTE in patients with hematological malignancies is challenging as these patients often have thrombocytopenia and are at increased risk for bleeding. The International Society of Thrombosis and Hemostasis (ISTH) guidance statement recommends adjusting anticoagulation based on the severity and acuity of VTE and considering platelet transfusion support to maintain platelet counts above >50K/µL to facilitate full-dose anticoagulation (AC) in patients with acute VTE with high-risk features. For acute VTE with low-risk features, a dose-modified strategy such as half- or prophylactic-dose AC, depending on platelet count, is recommended. While the risk of AC with supportive platelet transfusions may be justified in patients with severe VTE, lower-dose AC without platelet transfusion support may be adequate for patients with non-severe VTE and may reduce the risk for development of platelet alloantibodies. To better understand practice patterns at our institution, we reviewed the management of VTE in patients with acute leukemia over an 8-year period.Methods: We retrospectively reviewed all patients with acute leukemia who developed acute VTE during induction chemotherapy at Dartmouth-Hitchcock Medical Center for the 8-year period (2006-2013). Primary outcomes were 1) objectively confirmed, recurrent symptomatic VTE, and 2) clinically significant bleeding within 1 month after diagnosis of the index VTE. Secondary outcomes included IVC filter use and platelet alloantibody development within 3 months after diagnosis of VTE. We classified VTE events as acute or subacute/chronic and severe or non-severe. An acute event was defined as a new VTE diagnosed during the index hospitalization, while a subacute/chronic event was defined as a VTE that occurred prior to the index hospitalization for which the patient was being treated with AC during the hospitalization. A severe VTE was defined as a DVT involving femoral or more proximal vein segments, the SVC, cerebral veins or any PE. Non-severe events included UE DVT and distal DVT. We classified treatment at the time of diagnosis of VTE into one of the following categories: 1) full-dose AC with platelet transfusion to maintain platelet count >25-50K/µL, 2) half-dose AC with platelet transfusion to maintain platelet count >25-50K/µL, 3) prophylactic-dose AC without additional platelet transfusion beyond the standard of care, 4) no anticoagulation. We recorded the number of IVC filters inserted in each category. Descriptive statistics, including mean and standard deviation for continuous variables, and percentage and frequency for categorical variables, were calculated.Results: 40 subjects met entry criteria (55% male) with median age of 57.5 years. The majority (88%) had acute myeloid leukemia. Acute VTE was identified in 80% and VTE was severe in 55%. The degree of thrombocytopenia at the time of VTE diagnosis was <10K/µL (2.5%), 10-25K/µL (25%), 25-50K/µL (40%), and >50K/µL (32.5%). Subjects were initially treated with full-dose AC (60%), half-dose AC (5%), prophylactic-dose AC (12%) or no AC (22.5%). An IVC filter was inserted in 10 subjects (25%), and five subjects (12%) developed platelet alloantibodies. Seventeen subjects (42%) experienced bleeding complications within the first month of VTE diagnosis, six of which (35%) were clinically significant. Half of these were on full-dose AC, and half underwent insertion of an IVC filter. Two subjects (5%) had VTE recurrence within 1 month, and in both cases, AC had been discontinued prior to the recurrence due to bleeding complications.Conclusion: We found that management of VTE in patients with acute leukemia and thrombocytopenia varies and that the risk for bleeding complications was high irrespective of AC dose. We also uncovered the problem of VTE recurrence due to premature discontinuation of AC as a result of bleeding and observed a surprisingly high incidence of platelet alloimmunization. Dose-modified AC without platelet transfusion support may be an attractive alternative for treatment of VTE in this population, but further study is required to balance bleeding and thrombosis risk. DisclosuresNo relevant conflicts of interest to declare.

Estimating the utility value of hypoglycaemia according to severity and frequency using the visual analogue scale (VAS) and time trade-off (TTO) survey.

The primary objective of this study was to estimate the health utility values for hypoglycaemia events according to their severity and frequency. The secondary objective was to compare the health utilities between those with Type 2 Diabetes Mellitus and the general population. The health utilities of hypoglycaemia event were measured using Visual Analogue Scale (VAS) and Time Trade-Off (TTO) methods among conveniently sampled consenting adults (>18years and literate in either English or Malay language), which were then divided into two groups: those in the general population (GP) and those with Type 2 Diabetes Mellitus (T2DM). Each respondent was required to value 13 different health states, including frequencies of daytime hypoglycaemia and nocturnal hypoglycaemia, each depending on its severity (non-severe or severe). 256 respondents from the GP and 99 respondents with T2DM completed the survey. The T2DM group gave higher VAS-values compared to the GP group. The highest mean VAS-utility value for non-severe nocturnal hypoglycaemia occurring once monthly was 0.543 (SD 0.161), and for severe daytime hypoglycaemia occurring once quarterly was 0.293 (SD 0.162) which was the lowest utility value compared to other health states. However, non-severe nocturnal hypoglycaemia occurring once quarterly was 0.537 (SD 0.284) and has the highest TTO-utility value. Severe nocturnal hypoglycaemia occurring once quarterly has the lowest utility value which was -0.104 (SD 0.380). Daytime hypoglycaemia has lower utility value compared to nocturnal hypoglycaemia. Severe hypoglycaemia has a greater disutility compared with the non-severe hypoglycaemia in both studied groups. The findings show that as a health utility, hypoglycaemia has a substantial impact on utility with severe hypoglycaemia having a greater negative impact compared to non-severe events across the board. This highlights the importance of preventing development of severe hypoglycaemia in patients with Type 2 Diabetes Mellitus at any time of the day.

PSY62 - DIRECT COST OFFSETS RELATED TO BELIMUMAB SUBCUTANEOUS ADMINISTRATION IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS IN SPAIN

To estimate the direct costs related to belimumab SC in the treatment of adult patients with Systemic Lupus Erythematosus (SLE) with high disease activity and auto-antibody-positive despite standard therapy. A pharmacoeconomic study was conducted for an average of 3,995 SLE patients over 5 years from Spanish National Health System perspective. The budget impact model compared the cost difference in each year under two market scenarios: current market (Standard Therapy (ST) and belimumab IV without belimumab SC) and other market, in which patients switched from belimumab IV to belimumab SC until reaching 17% of total market share. Patients' characteristics, rate of flares and severity, and healthcare consumption were evaluated. Flares per patient per year were based on RCT data (non-severe flares RR: 0.86, average 2.5 for patients on ST and 2.14 on belimumab; severe flares RR: 0.54, average 1.01 for patients on ST and 0.54 on belimumab). Epidemiological, clinical and resource use data were obtained from published literature and expert interviews. Deterministic sensitivity analysis was conducted. ST encompassed 83% Corticosteroids, 83% Anti-Malarials, 52% Non-biological Immunosuppressives, 20% NSAIDs, 13% others Biologic Immunosuppressives, 2% Intravenous Immunoglobulins and 0.07% Therapeutic Plasma Exchange. Belimumab IV annual administration cost was 3,910.07€ for the first year and 3,388.72€ for the next years; and 205.62€ for ST. Based on 547.12€ per non-severe flare event, annual cost of non-severe flares for ST patients was 1,367.81€ and 1,172.41€ for belimumab patients. Additionally, annual cost of severe flares for ST patients was 4,889.30€ and 2,640.22€ for belimumab patients (4,840.89€ per event). On this basis the annual cost saving was estimated to be 2 million euros. This study provides a health economic rationale related to belimumab SC prescription, due to the reduction of clinical events rate and direct cost savings. This study was funded by GlaxoSmithKline (Study code: HO-17-18309).

Bias correction of RCM outputs using mixture distributions under multiple extreme weather influences

The frequency and magnitude of water-related disasters such as floods and landslides have intensified due to climate change, especially over East Asia, including the South Korea region. In this region, extreme precipitation events originate from multiple sources, such as tropical cyclones (i.e., typhoons) and frontal synoptic systems. Climate scenarios generated by global climate models (GCMs) are employed to assess the future variations of extreme precipitation. Precipitation outputs from GCM scenarios must be localized via dynamic downscaling through regional climate models (RCMs). Bias correction is required to eliminate the biases between the RCM outputs and local observations. Quantile mapping, in which RCM output values are mapped by quantiles onto historical observed data of all precipitation except zero values by fitting a probabilistic distribution to each dataset, has been a popular technique for bias correction. In the current study, we tested several probabilistic distribution models. Additionally, we tested several mixture probabilistic distributions, combinations of traditionally employed distributions, because extreme precipitation events over South Korea can develop from multiple weather systems. We also tested traditionally employed distributions, such as exponential, gamma, and GEV distributions for precipitation values except zero values. Their performances were evaluated with various statistics, especially for extreme events, because the bias-corrected data should be used for the assessment of future variations of extreme precipitation. The results indicate that the tested mixture distributions are superior to traditional non-mixture distributions. The gamma-Gumbel mixture distribution showed the best performance in reproducing the statistical characteristics of especially extreme precipitation in a way that the majority of non-severe precipitation events are fitted to the gamma distribution, whose tail is light, and the extreme events are fitted to the Gumbel distribution. The future variations of extreme precipitation from climate scenarios such as RCP 4.5 and RCP 8.5 showed clear differences between probabilistic distribution models, indicating that the selection of an appropriate distribution is critical in the reasonable assessment of future extreme precipitation.

Evaluating the cost-effectiveness of insulin detemir versus neutral protamine Hagedorn insulin in patients with type 1 or type 2 diabetes in the UK using a short-term modeling approach.

BackgroundTo estimate the short-term cost-effectiveness of insulin detemir (IDet) versus neutral protamine Hagedorn (NPH) insulin based on the incidence of non-severe hypoglycemia and changes in body weight in subjects with type 1 diabetes (T1D) or type 2 diabetes (T2D) in the UK.MethodsA model was developed to evaluate cost-effectiveness based on non-severe hypoglycemia, body mass index, and pharmacy costs over 1 year. Published rates of non-severe hypoglycemia were employed in the T1D and T2D analyses, while reduced weight gain with IDet was modeled in the T2D analysis only. Effectiveness was calculated in terms of quality-adjusted life expectancy using published utility scores. Pharmacy costs were captured using published prices and defined daily doses. Costs were expressed in 2016 pounds sterling (GBP). Sensitivity analyses were performed (including probabilistic sensitivity analysis).ResultsIn T1D, IDet was associated with fewer non-severe hypoglycemic events than NPH insulin (126.7 versus 150.8 events per person-year), leading to an improvement of 0.099 quality-adjusted life years (QALYs). Costs with IDet were GBP 60 higher, yielding an incremental cost-effectiveness ratio (ICER) of GBP 610 per QALY gained. In T2D, mean non-severe hypoglycemic event rates and body weight were lower with IDet than NPH insulin, leading to a total incremental utility of 0.120, accompanied by an annual cost increase of GBP 171, yielding an ICER of GBP 1,422 per QALY gained for IDet versus NPH insulin.ConclusionShort-term health economic evaluation showed IDet to be a cost-effective alternative to NPH insulin in the UK due to lower rates of non-severe hypoglycemia (T1D and T2D) and reduced weight gain (T2D only).

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.

A cost of illness study of hypoglycaemic events in insulin-treated diabetes in the Netherlands

ObjectivesPatients with diabetes mellitus are at a risk for hypoglycaemia. Besides the burden of hypoglycaemia for patients, hypoglycaemia poses an economic burden to society. The aim of this study was...

Frequency and Characterization of Tracheal Intubation Adverse Events in Pediatric Sepsis.

Intubation in critically ill pediatric patients is associated with approximately 20% rate of adverse events, but rates in the high-risk condition of sepsis are unknown. Our objectives were to describe the frequency and characteristics of tracheal intubation adverse events in pediatric sepsis. Retrospective cohort study of a sepsis registry. Two tertiary care academic emergency departments and four affiliated urgent cares within a single children's hospital health system. Children 60 days and older to 18 years and younger who required nonelective intubation within 24 hours of emergency department arrival. Exclusion criteria included elective intubation, intubation prior to emergency department arrival, presence of tracheostomy, or missing intubation chart data. Not applicable. The outcome was tracheal intubation adverse event as defined by the National Emergency Airway Registry Tool 4 KIDS. During the study period, 118 of 2,395 registry patients met inclusion criteria; 100% of intubations were successful. First attempt success rate was 57% (95% CI, 48-65%); 59% were intubated in the emergency department, and 28% were intubated in the PICU. First attempts were by a resident (30%), a fellow (42%), attending (6%), and anesthesiologist (13%). Tracheal intubation adverse events were reported in 61 (43%; 95% 43-61%) intubations with severe tracheal intubation adverse events in 22 (17%; 95 CI, 13-27%) intubations. Hypotension was the most common severe event (n = 20 [17%]) with 14 novel occurrences during intubation. Mainstem bronchial intubation was the most common nonsevere event (n = 28 [24%]). Residents, advanced practice providers, and general pediatricians in urgent care settings had the lowest rates of first-pass success. The rates of tracheal intubation adverse events in this study are higher than in nonelective pediatric intubations in all conditions and highlight the high-risk nature of intubations in pediatric sepsis. Further research is needed to identify optimal practices for intubation in pediatric sepsis.

Severity of hypoglycaemia and health-related quality of life, work productivity and healthcare costs in patients with type 2 diabetes in Europe.

SummaryAimsHypoglycaemia in patients with type 2 diabetes mellitus (T2DM) is associated with poor health outcomes, such as reduced health‐related quality of life (HRQoL). This study aimed to assess the impact of hypoglycaemic events by severity on HRQoL, work productivity and healthcare costs in patients with T2DM.Materials and MethodsEuropean patients with T2DM selected from the National Health and Wellness Survey who were currently receiving pharmacologic therapy were stratified into 3 groups based on the reported history and severity of hypoglycaemic events (no event, nonsevere, severe) experienced in the previous 3 months. Patients’ work productivity, HRQoL, healthcare resource use (HCRU) and associated costs were assessed as self‐reported outcomes.ResultsOf 1269 patients included in the study, 652 (51.4%) patients had not experienced an event, while 533 (42.0%) and 84 (6.6%) patients had experienced nonsevere and severe hypoglycaemic events, respectively, in the previous 3 months. An increase in hypoglycaemia severity was associated with a decrease in HRQoL, and an increase in HCRU and healthcare costs.ConclusionsThe impact of hypoglycaemia varies by severity and has a negative impact on HRQoL and overall HCRU and costs.

Rapid Evolution of Cool Season, Low-CAPE Severe Thunderstorm Environments

Abstract Low-CAPE (i.e., CAPE ≤ 1000 J kg−1) severe thunderstorms are common in the greater southeastern United States (including the Tennessee and Ohio valleys). These events are often poorly forecasted, and the environments in which they occur may rapidly evolve. Real-data simulations of 11 low-CAPE severe events and 6 low-CAPE nonsevere events were performed at convection-allowing resolution. Some amount of surface-based destabilization occurred during all simulated events over the 3-h period prior to convection. Most simulated severe events experienced comparatively large destabilization relative to the nonsevere events as a result of surface warming, cooling aloft, and surface moistening. The release of potential instability by large-scale forcing for ascent likely influenced the cooling aloft in some cases. Surface warming was attributable primarily to warm advection and appeared to be an important discriminator between severe and nonsevere simulated events. Severe events were also found to have larger low-level wind shear than nonsevere events, particularly during nocturnal cases. Because of the rapid destabilization that occurred within 3 h in the simulated events, it is evident that 3–6-hourly model output may not be adequate for forecasting severe events in high-shear, low-CAPE environments. Monitoring of high-resolution model forecasts and surface observations may be necessary to identify a rapidly changing severe environment.

Non-severe Hypoglycemia Risk Difference between Sulfonylurea and Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2-I) as an Add-On to Metformin in Randomized Controlled Trials.

Non-severe hypoglycemia reduces well-being, lowers quality of life, reduces productivity and increases treatment costs. The non-severe hypoglycemia rate, attributable to sulfonylurea (SU) utilization compared with newer classes such as SGLT2-I, could be of clinical significance. To explore the non-severe hypoglycemia risk difference (RD) for SU use compared with SGLT2-I in randomized controlled trials (RCTs) as an add on to metformin. A search was conducted for RCTs of SGLT2-I. PubMed database were utilized for this search. The search was limited to RCTs reported in English language for canagliflozin, dapagliflozin, and empagliflozin. SU dose comparison was utilized to convert the dose of SUs to glimepiride equivalent doses. Totally, 118 RCTs were reviewed; 6 articles had an arm for a SU as add on to metformin. Six articles belong to 3 RCTs, which reported results for 52 weeks and 104 weeks. Average non-severe hypoglycemia rate for SU arm was 30% (5.5%) [Mean (SD)] for 52 weeks and 35.6% (6.1%) for 104 weeks. RD for non-severe hypoglycemia events for SU compared to SGLT2-I was 26.7% (4.9%) for 52 weeks (p-value less than 0.001) and 30.6% (5.5%) for 104 weeks (p-value less than 0.001). There was a significant correlation between dose of SU and hypoglycemia rate (Pearson correlation 0.995; R-square 99%). This study illustrated that a large proportion of patients who had exposure to SU in RCTs of SGLT2-I experienced non-severe hypoglycemia compared to SGLT2-I. There was a close relation between SU dose and increased probability of non-severe hypoglycemia events.

Composite Environments of Severe and Nonsevere High-Shear, Low-CAPE Convective Events

Abstract Severe convection occurring in environments characterized by large amounts of vertical wind shear and limited instability (high-shear, low-CAPE, or “HSLC,” environments) represents a considerable forecasting and nowcasting challenge. Of particular concern, NWS products associated with HSLC convection have low probability of detection and high false alarm rates. Past studies of HSLC convection have examined features associated with single cases; the present work, through composites of numerous cases, illustrates the attributes of “typical” HSLC severe and nonsevere events and identifies features that discriminate between the two. HSLC severe events across the eastern United States typically occur in moist boundary layers within the warm sector or along the cold front of a strong surface cyclone, while those in the western United States have drier boundary layers and more typically occur in the vicinity of a surface triple point or in an upslope regime. The mean HSLC severe event is shown to exhibit stronger forcing for ascent at all levels than its nonsevere counterpart. The majority of EF1 or greater HSLC tornadoes are shown to occur in the southeastern United States, so this region is subjected to the most detailed statistical analysis. Beyond the documented forecasting skill of environmental lapse rates and low-level shear vector magnitude, it is shown that a proxy for the release of potential instability further enhances skill when attempting to identify potentially severe HSLC events. This enhancement is likely associated with the local, in situ CAPE generation provided by this mechanism. Modified forecast parameters including this proxy show considerably improved spatial focusing of the forecast severe threat when compared to existing metrics.

Economic impact of hypoglycemia among insulin-treated patients with diabetes

Objective: The objective of this study was to assess the cost of hypoglycemic events among insulin-treated patients with diabetes and the potential cost savings to a hypothetical US health plan and employer of reducing hypoglycemic events with a device intervention.Methods: A cost-calculator model was developed to estimate the direct costs of hypoglycemic events, accounting for diabetes type, age, and event severity. Model inputs were derived from published incidence rates of hypoglycemic events and direct medical costs. Assumed intervention efficacy was based on published studies of an emerging technology which yielded 72.2% (LGS Trial; ACTRN12610000024044) and 31.8% (ASPIRE Trial; NCT01497938) reductions in severe and non-severe hypoglycemic events, respectively. Model outcomes—including the number of severe (requiring medical assistance) and non-severe events, and direct/indirect medical costs (excluding intervention costs)—were evaluated over a 1-year period for a hypothetical health plan and employer perspectives.Results: In a health plan with 10 million enrollees, patients without the intervention would have experienced 0.09 and 14.60 severe and non-severe hypoglycemic events per patient per year (PPPY), respectively (vs 0.02 severe and 9.96 non-severe events with the intervention). This translated into total direct medical cost savings of $45 million ($177 PPPY) for the health plan. For an employer with 100,000 employees, the intervention would have yielded additional savings of $492 PPPY in indirect costs.Conclusion: Insulin-treated patients experience hypoglycemic events, which are associated with substantial direct and indirect medical costs. The cost savings of reducing hypoglycemic events need to be weighed against the costs of using diabetes device interventions.