Twelve-month results of the ADAPT randomized controlled trial: Reproducibility and sustainability of advanced hybrid closed-loop therapy outcomes versus conventional therapy in adults with type 1 diabetes.

AIMS: To reassess the 6-month efficacy and to assess the 12-month sustained efficacy of the MiniMed™ 780G advanced hybrid closed-loop automated insulin delivery (AID) system compared to multiple daily injections plus intermittently scanned glucose monitoring (MDI+isCGM) in people with type 1 diabetes not meeting glucose targets. METHODS: The ADAPT study was a prospective, multicentre, open-label, randomized control trial in people with type 1 diabetes, with a glycated haemoglobin (HbA1c) concentration of at least 8.0% (64 mmol/mol), on MDI+isCGM therapy. After a 6-month study phase, participants randomized at baseline to MDI+isCGM switched to AID (SWITCH) while the others continued AID therapy (SUSTAIN) for an additional 6 months. The primary endpoint of this continuation phase was the within-group change in mean HbA1c between 6 and 12 months, with superiority in the SWITCH group and noninferiority in the SUSTAIN group (ClinicalTrials.gov: NCT04235504). RESULTS: A total of 39 SWITCH and 36 SUSTAIN participants entered the continuation phase. In the SWITCH group, HbA1c was significantly decreased by -1.4% (95% confidence interval [CI] -1.7% to -1.1%; P < 0.001) from a mean ± SD of 8.9% ± 0.8% (73.9 ± 8.6 mmol/mol) at 6 months to 7.5% ± 0.6% (58.5 ± 6.9 mmol/mol) at 12 months. Mean HbA1c increased by 0.1% (95% CI -0.05% to +0.25%), from 7.3% ± 0.6% (56.5 ± 6.7 mmol/mol) to 7.4% ± 0.8% (57.7 ± 9.1 mmol/mol) in the SUSTAIN group, meeting noninferiority criteria. Three severe hypoglycaemia events occurred in two SWITCH participants during the continuation phase. CONCLUSION: ADAPT study phase glycaemic improvements were reproduced and sustained in the continuation phase, supporting the early adoption of AID therapy in people with type 1 diabetes not meeting glucose targets on MDI therapy.

Factors associated with improved glycemic control following continuous subcutaneous insulin infusion therapy in patients with type 2 diabetes uncontrolled with bolus-basal insulin regimens: An analysis from the OpT2mise randomized trial.

This analysis investigated factors associated with the decrease in HbA1c in patients receiving continuous subcutaneous insulin infusion (CSII) in the OpT2mise randomized trial. In this study, patients with type 2 diabetes and HbA1c >8% following multiple daily injections (MDI) optimization were randomized to receive CSII (n = 168) or MDI (n = 163) for 6 months. Patient-related and treatment-related factors associated with decreased HbA1c in the CSII arm were identified by univariate and multivariate analyses. CSII produced a significantly greater reduction in HbA1c than MDI, and the treatment difference increased with baseline HbA1c. In the CSII arm, the only factors significantly associated with decreased HbA1c were higher baseline HbA1c (P < .001), geographical region (P < .001), higher educational level (P = .012), higher total cholesterol level (P = .002), lower variability of baseline glucose values on continuous glucose monitoring (P < .001) and the decrease in average fasting self-monitored blood glucose at 6 months (P < .001). These findings suggest that CSII offers an option to improve glycemic control in a broad range of patients with type 2 diabetes in whom control cannot be achieved with MDI. OpT2mise ClinicalTrials.gov number: NCT01182493 (https://clinicaltrials.gov/).

Long-term costs and outcomes in psoriatic arthritis patients not responding to conventional therapy treated with tumour necrosis factor inhibitors: the extension of the Psoriatic Arthritis Cost Evaluation (PACE) study.

OBJECTIVES: Poor information on long-term outcomes and costs on tumour necrosis factor (TNF) inhibitors in psoriatic arthritis (PsA) are available. Our aim was to evaluate long-term costs and benefits of TNF- inhibitors in PsA patients with inadequate response to conventional treatment with traditional disease-modifying anti-rheumatic drugs (tDMARDs). METHODS: Fifty-five out of 107 enrolled patients included in the study at one year, completed the 5-year follow-up period. These patients were enrolled in 8 of 9 centres included in the study at one year. Patients aged older than 18 years, with different forms of PsA and failure or intolerance to tDMARDs therapy were treated with anti-TNF agents. Information on resource use, health-related quality of life (HRQoL), disease activity, function and laboratory values were collected at baseline and through the 5 years of therapy. Costs (expressed in Euro 2011) and utility (measured by EQ-5D instrument) before TNF inhibitor therapy and after 1 and 5 years were compared. RESULTS: The majority of patients (46 out of 55; 83.6%) had a predominant or exclusive peripheral arthritis and 16.4% had predominant or exclusive axial involvement. There was a statistically significant improvement of the most important clinical variables after 1 year of follow-up. These improvements were maintained also after 5 years. The direct costs increased by approximately €800 per patient-month after 1 year, the indirect costs decreased by €100 and the overall costs increased by more than €700 per patient-month due to the cost of TNF inhibitor therapy. Costs at 5 year were similar to the costs at 1 year. The HRQoL parameters showed the same trends of the clinical variables. EQ-5D VAS, EQ-5D utility and SF-36 PCS score showed a significant improvement after 1 year, maintained at 5 years. SF-36 MCS showed an improvement only at 5 years. CONCLUSIONS: The results of our study suggest that TNF blockers have long-term efficacy. The higher cost of TNF inhibitor therapy was balanced by a significant improvement of HRQoL, stable at 5 years of follow-up. Our results need to be confirmed in larger samples of patients.

The Health Economics of Automated Insulin Delivery Systems and the Potential Use of Time in Range in Diabetes Modeling: A Narrative Review.

Intensive therapy with exogenous insulin is the treatment of choice for individuals living with type 1 diabetes (T1D) and some with type 2 diabetes, alongside regular glucose monitoring. The development of systems allowing (semi-)automated insulin delivery (AID), by connecting glucose sensors with insulin pumps and algorithms, has revolutionized insulin therapy. Indeed, AID systems have demonstrated a proven impact on overall glucose control, as indicated by effects on glycated hemoglobin (HbA1c), risk of severe hypoglycemia, and quality of life measures. An alternative endpoint for glucose control that has arisen from the use of sensor-based continuous glucose monitoring is the time in range (TIR) measure, which offers an indication of overall glucose control, while adding information on the quality of control with regard to blood glucose level stability. A review of literature on the health-economic value of AID systems was conducted, with a focus placed on the growing place of TIR as an endpoint in studies involving AID systems. Results showed that the majority of economic evaluations of AID systems focused on individuals with T1D and found AID systems to be cost-effective. Most studies incorporated HbA1c, rather than TIR, as a clinical endpoint to determine treatment effects on glucose control and subsequent quality-adjusted life year (QALY) gains. Likely reasons for the choice of HbA1c as the chosen endpoint is the use of this metric in most validated and established economic models, as well as the limited publicly available evidence on appropriate methodologies for TIR data incorporation within conventional economic evaluations. Future studies could include the novel TIR metric in health-economic evaluations as an additional measure of treatment effects and subsequent QALY gains, to facilitate a holistic representation of the impact of AID systems on glycemic control. This would provide decision makers with robust evidence to inform future recommendations for health care interventions.

A European Cost-Utility Analysis of the MiniMed™ 780G Advanced Hybrid Closed-Loop System Versus Intermittently Scanned Continuous Glucose Monitoring with Multiple Daily Insulin Injections in People Living with Type 1 Diabetes.

Background: Advanced hybrid closed-loop (AHCL) automated insulin delivery systems are the most effective therapy in terms of assisting people with type 1 diabetes (T1D) to achieve glycemic targets; however, the cost can represent a barrier to uptake. In this study, a cost-utility analysis of the MiniMed™ 780G AHCL system (MM780G) versus intermittently scanned continuous glucose monitoring (is-CGM) plus multiple daily insulin injections (MDI) in people with T1D not achieving glycemic goals was performed across six European countries. Methods: Clinical input data were sourced from the ADAPT trial. Assuming a baseline HbA1c of 9.04%, HbA1c reductions of 1.54% for AHCL and 0.2% for is-CGM+MDI were modeled. The analyses were performed from a payer perspective over a time horizon of 40 years and an annual discount rate of 3% was applied. Results: Across all countries, the use of AHCL was projected to result in an incremental gain in quality-adjusted life expectancy of >2 quality-adjusted life years (QALYs) versus is-CGM+MDI. Lifetime direct costs were higher with AHCL resulting in incremental cost-utility ratios for AHCL versus is-CGM+MDI ranging from EUR 11,765 per QALY gained in Austria to EUR 43,963 per QALY gained in Italy. Conclusions: For people with T1D managed with is-CGM+MDI not achieving glycemic targets, initiation of the MM780G system was projected to improve long-term clinical outcomes; however, due to differences in health care costs between countries, the health economic outcomes differed. In all included countries, AHCL is likely to be cost-effective relative to is-CGM+MDI for people not achieving glycemic goals with is-CGM+MDI. The ADAPT trial is registered with ClinicalTrials.gov, NCT04235504.

Advanced Hybrid Closed Loop in Adult Population With Type 1 Diabetes: A Substudy From the ADAPT Randomized Controlled Trial in Users of Real-Time Continuous Glucose Monitoring.

BACKGROUND: This analysis reports the findings from a predefined exploratory cohort (cohort B) from the ADAPT (ADvanced Hybrid Closed Loop Study in Adult Population with Type 1 Diabetes) study. Adults with type 1 diabetes (T1D) with suboptimal glucose control were randomly allocated to an advanced hybrid closed-loop (AHCL) system or multiple daily injections of insulin (MDI) plus real-time continuous glucose monitoring (RT-CGM). METHODS: In this prospective, multicenter, exploratory, open-label, randomized controlled trial, 13 participants using MDI + RT-CGM and with HbA1c ≥8.0% were randomized to switch to AHCL (n = 8) or continue with MDI + RT-CGM (n = 5) for six months. Prespecified endpoints included the between-group difference in mean change from baseline in HbA1c, CGM-derived measures of glycemic control, and safety. RESULTS: The mean HbA1c level decreased by 1.70 percentage points in the AHCL group versus a 0.60 percentage point decrease in the MDI + RT-CGM group, with a model-based treatment effect of -1.08 percentage points (95% confidence interval [CI] = -2.17 to 0.00 percentage points; P = .0508) in favor of AHCL. The percentage of time spent with sensor glucose levels between 70 and 180 mg/dL in the study phase was 73.6% in the AHCL group and 46.4% in the MDI + RT-CGM group; model-based between-group difference of 28.8 percentage points (95% CI = 12.3 to 45.3 percentage points; P = .0035). No diabetic ketoacidosis or severe hypoglycemia occurred in either group. CONCLUSIONS: In people with T1D with HbA1c ≥8.0%, the use of AHCL resulted in improved glycemic control relative to MDI + RT-CGM. The scale of improvement suggests that AHCL should be considered as an option for people not achieving good glycemic control on MDI + RT-CGM.

Randomised controlled trial of Advanced Hybrid Closed Loop in an Adult Population with Type 1 Diabetes (ADAPT): study protocol and rationale.

INTRODUCTION: For many people with type 1 diabetes who struggle to achieve glycaemic control with multiple daily injections of insulin (MDI) plus self-monitoring of blood glucose, MDI plus intermittently scanned continuous glucose monitoring (IS-CGM) or real-time continuous glucose monitoring (RT-CGM), or insulin administration using insulin pump therapy represent optimised care in many regions. Through technological advances an advanced hybrid closed loop (AHCL) system has been developed; studies of incremental effects relative to MDI plus IS-CGM are lacking. METHODS AND ANALYSIS: The Advanced Hybrid Closed Loop study in Adult Population with Type 1 Diabetes (ADAPT) study is a multinational, prospective, open-label, confirmatory and exploratory randomised controlled trial to examine outcomes with the MiniMed 670G version 4.0 AHCL system (with an equivalent algorithm and commercialised as the MiniMed 780G system, referred to as AHCL) relative to MDI plus IS-CGM in adults with baseline HbA1c≥8.0%. An exploratory cohort will compare AHCL with MDI plus RT-CGM. The study will be conducted in approximately 124 adults on MDI plus either IS-CGM or RT-CGM for at least 3 months prior to screening. The primary endpoint will be the difference in mean HbA1c change from baseline to 6 months between the AHCL and the MDI plus IS-CGM arms. Secondary endpoints will include proportion of time spent in hypoglycaemic, euglycaemic and hyperglycaemic ranges. ETHICS AND DISSEMINATION: The ADAPT study will be conducted in accordance with the requirements of the Declaration of Helsinki and local laws and regulations, and has been approved by ethics committees. The trial will provide valuable information on the incremental benefits that may be provided by AHCL for patients failing to achieve glycaemic targets on MDI plus IS-CGM or RT-CGM and form a basis for health economic evaluations to support market access. TRIAL REGISTRATION NUMBER: NCT04235504; Pre-results.

Cost-Effectiveness Analysis of an Advanced Hybrid Closed-Loop Insulin Delivery System in People with Type 1 Diabetes in Greece.

AbstractIntroduction: Usage of automated insulin delivery systems is increasing for the treatment of people with type 1 diabetes (T1D). This study compared long-term cost-effectiveness of the Advanced Hybrid Closed Loop MiniMed 780G (AHCL) system versus sensor augmented pump (SAP) system with predictive low glucose management (PLGM) or multiple daily injections (MDI) plus intermittently scanned continuous glucose monitoring (isCGM) in people with T1D in Greece. Methods: Analyses were performed using the IQVIA CORE Diabetes Model, with clinical input data sourced from various studies. In the AHCL versus SAP plus PLGM analysis, patients were assumed to have 7.5% baseline glycated hemoglobin (HbA1c), when comparing AHCL with MDI plus isCGM baseline HbA1c was assumed to be 7.8%. HbA1c was reduced to 7.0% following AHCL treatment initiation but remained at baseline levels in the comparator arms. Analyses were performed from a societal perspective over a lifetime time horizon. Future costs and clinical outcomes were discounted at 1.5% per annum. Results: AHCL was associated with increased quality-adjusted life expectancy of 0.284 quality-adjusted life years (QALYs) and EUR 10,173 lower mean total lifetime costs with SAP plus PLGM. Compared with MDI plus isCGM, AHCL was associated with increased quality-adjusted life expectancy of 2.708 QALYs, EUR 76,396 higher mean total lifetime costs, and an incremental cost-effectiveness ratio of EUR 29,869 per QALY. Extensive sensitivity analysis confirmed the robustness of results. Conclusions: Over patient lifetime, the MiniMed 780G system is likely to be cost saving compared with the SAP plus PLGM system and cost-effective compared with MDI plus isCGM in people with T1D in Greece.

Cost-Effectiveness of Hybrid Closed Loop Insulin Pumps Versus Multiple Daily Injections Plus Intermittently Scanned Glucose Monitoring in People With Type 1 Diabetes in The Netherlands.

INTRODUCTION: Hybrid closed loop (HCL) insulin pump systems and intermittently scanned continuous glucose monitoring (IS-CGM) are increasingly used by individuals with type 1 diabetes (T1D). The aim of the analysis was to compare the long-term cost-effectiveness of the MiniMed 670G HCL system versus IS-CGM plus multiple daily injections of insulin (MDI) or continuous subcutaneous insulin infusion (CSII) in adults with T1D in the Netherlands. METHODS: The analysis was performed using the IQVIA CORE Diabetes Model with clinical input data sourced from observational studies. Simulated patients were assumed to have a baseline HbA1c of 7.8%. Use of the MiniMed 670G system was assumed to reduce HbA1c by 0.4% and confer a quality-of-life (QoL) benefit through reduced fear of hypoglycemia (FoH). The analysis was performed from a societal perspective over a lifetime time horizon; future costs and clinical outcomes pertaining to the Netherlands were used and discounted at 4% and 1.5% per annum, respectively. RESULTS: Use of the MiniMed 670G HCL system was projected to improve mean quality-adjusted life expectancy by 2.231 quality-adjusted life years (QALYs) versus IS-CGM. Total mean lifetime costs were EUR 13,683 higher with the MiniMed 670G system resulting in an ICER of EUR 6133 per QALY gained. Sensitivity analyses revealed findings to be sensitive to changes in assumptions around severe hypoglycemic event rates and the (QoL) benefit associated with reduced FoH. CONCLUSIONS: Over patient lifetimes, for adults with long-standing T1D in the Netherlands, use of the MiniMed 670G system is projected to be cost-effective versus IS-CGM plus MDI or CSII.

Advanced hybrid closed loop therapy versus conventional treatment in adults with type 1 diabetes (ADAPT): a randomised controlled study.

BACKGROUND: Adults with type 1 diabetes who are treated with multiple daily injections of insulin plus intermittently scanned continuous glucose monitoring (isCGM) can have suboptimal glucose control. We aimed to assess the efficacy of an advanced hybrid closed loop (AHCL) system compared with such therapy in this population. METHODS: The Advanced Hybrid Closed Loop Study in Adult Population with Type 1 Diabetes (ADAPT) trial is a prospective, multicentre, open-label, randomised controlled trial that involved 14 centres in three European countries (France, Germany, and the UK). We enrolled patients who were at least 18 years of age, had a type 1 diabetes duration of at least 2 years, HbA1c of at least 8% (64 mmol/mol), and were using multiple daily injections of insulin plus isCGM (cohort A) or real time continuous glucose monitoring (cohort B) for at least 3 months. Here, only results for cohort A are reported. Participants were randomly allocated 1:1 to AHCL therapy or continuation of multiple daily injections of insulin plus continuous glucose monitoring for 6 months with an investigator-blinded block randomisation procedure. Participants and treating clinicians could not be masked to the arm assignment. The primary endpoint was the between-group difference in mean HbA1c change from baseline to 6 months in the intention-to-treat population using AHCL therapy and those using multiple daily injections of insulin plus isCGM. The primary endpoint was analysed using a repeated measures random-effects model with the study arm and period as factors. Safety endpoints included the number of device deficiencies, severe hypoglycaemic events, diabetic ketoacidosis, and serious adverse events. This study is registered with ClinicalTrials.gov, NCT04235504. FINDINGS: Between July 13, 2020, and March 12, 2021, 105 people were screened and 82 randomly assigned to treatment (41 in each arm). At 6 months, mean HbA1c had decreased by 1·54% (SD 0·73), from 9·00% to 7·32% in the AHCL group and 0·20% (0·80) in the multiple daily injections of insulin plus isCGM from 9·07% to 8·91% (model-based difference -1·42%, 95% CI -1·74 to -1·10; p<0·0001). No diabetic ketoacidosis, severe hypoglycaemia, or serious adverse events related to study devices occurred in either group; two severe hypoglycaemic events occurred in the run-in phase. 15 device-related non-serious adverse events occurred in the AHCL group, compared with three in the multiple daily injections of insulin plus isCGM group. Two serious adverse events occurred (one in each group), these were breast cancer (in one patient in the AHCL group) and intravitreous haemorrhage (in one patient in the multiple daily injections of insulin plus isCGM group). INTERPRETATION: In people with type 1 diabetes using multiple daily injections of insulin plus isCGM and with HbA1c of at least 8%, the use of AHCL confers benefits in terms of glycaemic control beyond those that can be achieved with multiple daily injections of insulin plus isCGM. These data support wider access to AHCL in people with type 1 diabetes not at target glucose levels. FUNDING: Medtronic International Trading Sàrl.

Pharmaco-economic consequences of losartan therapy in patients undergoing diabetic end stage renal disease in EU and USA.

Diabetic nephropathy is the most frequent cause of end stage renal disease (ESRD). As ESRD incidence increases continuously, more resources are needed for treatment. The objective was to evaluate the economic impact of losartan added to the standard care administered to diabetic subjects with ESRD. The analysis has involved more than 500 million inhabitants. Standard methods have been used in order to conduct an economic evaluation comparing the economic outcomes deriving from the administration of losartan added to standard care versus standard care alone in patients with type 2 diabetes mellitus (DM) and nephropathy over 3.4 years. The study was hence conducted from the perspective of the third-party payer. The clinical outcome data were based on the results from the Reduction of Endpoints in Non-Insulin Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL) trial. Direct medical costs are referred to the purchase costs of losartan and to the costs of hospitalization. The costs were discounted back at an annual rate of 3%. Also sensitivity analysis was performed. The RENAAL study showed that losartan confers strong renal protection in patients with DM and nephropathy. Losartan results into cost saving in all countries considered: 3,602.98€/Italy, 4,531.35€/France, 3,019.66€/Germany, 3,949.50€/Switzer-land, and 3,855.50€/US per patient. Results are not sensitive to both clinical and economic variables. In addition to the medical benefits, this analysis demonstrates the economic relevance of the treatment with losartan in DM patients affected by nephropathy.

Cost-effectiveness of a novel hybrid closed-loop system compared with continuous subcutaneous insulin infusion in people with type 1 diabetes in the UK.

AIMS: The MiniMed 670 G insulin pump system is the first commercially available hybrid closed-loop (HCL) insulin delivery system and clinical studies have shown that this device is associated with incremental benefits in glycemic control relative to continuous subcutaneous insulin infusion (CSII) with or without continuous glucose monitoring (CGM). The aim was to evaluate the long-term cost-effectiveness of the MiniMed 670 G system versus CSII alone in people with type 1 diabetes (T1D) in the UK. MATERIALS AND METHODS: Cost-effectiveness analysis was performed using the IQVIA CORE Diabetes Model. Clinical input data were sourced from a clinical trial of the MiniMed 670 G system in 124 adults and adolescents with T1D. The analysis was performed over a lifetime time horizon and both future costs and clinical outcomes were discounted at 3.5% per annum. The analysis was performed from a healthcare payer perspective. RESULTS: The use of the MiniMed 670 G system led to an improvement in quality-adjusted life expectancy of 1.73 quality-adjusted life years (QALYs), relative to CSII. Total lifetime direct costs were GBP 35,425 higher with the MiniMed 670 G system than with CSII resulting in an incremental cost-effectiveness ratio (ICER) of GBP 20,421 per QALY gained. Sensitivity analyses revealed that the ICER was sensitive to assumptions around glycemic control and assumptions relating to the quality-of-life benefit associated with a reduction in fear of hypoglycemia. LIMITATIONS: Long-term projections from short-term data are inherently associated with uncertainty but represent arguably the best available evidence in lieu of long-term clinical trials. CONCLUSIONS: In the UK, over patient lifetimes, the incremental clinical benefits associated with the use of MiniMed 670 G system means that it is likely to be cost-effective relative to the continued use of CSII in people with T1D, particularly for those with a fear of hypoglycemia or poor baseline glycemic control.

Cost-effectiveness analysis of TNF-alpha blockers for the treatment of chronic plaque psoriasis in the perspective of the Italian health-care system.

The cost-effectiveness of biological treatments for psoriasis is not well determined and may vary from country to country. The objectives of this study was to perform a cost-effectiveness analysis of infliximab compared with other anti-tumor necrosis factor-alpha agents for the treatment of psoriasis in Italy. The incremental cost-effectiveness ratio per patients achieving at least 75% improvement in the psoriasis area and severity index assessed over 24- and 48-50-week periods was calculated. Efficacy data were drawn from randomized controlled trials when available or from open label studies. Considering patients achieving psoriasis area and severity index at week 24 and 48-50, infliximab was dominant (more effective and less costly) over etanercept given at 50 mg twice weekly. In contrast, infliximab was not dominant over etanercept at other dosages or over adalimumab. When considering the impact of therapy on quality of life at Week 12 using the Dermatology Life Quality Index equal to zero, infliximab resulted more effective and less costly than etanercept. Therefore, infliximab seems to be cost-effective in the therapy of psoriasis. Further cost-efficacy evaluations based on head-to-head trials are necessary to address health economic considerations.

Predicting Factors Associated with Hypoglycemia Reduction with Automated Predictive Insulin Suspension in Patients at High Risk of Severe Hypoglycemia: An Analysis from the SMILE Randomized Trial.

Background: This analysis from the SMILE randomized study was performed to identify predictive factors associated with the greatest reductions in hypoglycemia with the Medtronic MiniMed™ 640G Suspend before low feature in adults with type 1 diabetes at high risk of severe hypoglycemia. Methods: Clinical and treatment-related factors associated with decreased sensor hypoglycemia (SH) were identified in participants from the intervention arm by univariate and multivariate analyses. Results: The reduction in SH events <54 mg/dL (<3.0 mmol/L) in the intervention group was significantly (P < 0.0001) associated with the baseline mean number of sensor hypoglycemic events (MNSHE) <54 mg/dL. When excluding continuous glucose monitoring (CGM) factors not readily available (MNSHE, duration of SH events, area under the curve, mean amplitude of glycemic excursions), only the baseline mean time spent <54 mg/dL was found to be a significant independent predictor factor (P < 0.0001). Baseline HbA1c, mean self-monitoring of blood glucose (SMBG), and coefficient of variation of SMBG were significant, although weak, predictors in the absence of any CGM data. Conclusions: The greatest reductions in SH events achieved with the MiniMed 640G system with the Suspend before low feature were seen in participants with higher baseline MNSHE. Measuring these (usually uncollected) events can be a useful tool to predict hypoglycemia reduction. ClinicalTrials.gov Registration Identifier NCT02733991.

Non-invasive assessment of coronary flow reserve and ADMA levels: a case-control study of early rheumatoid arthritis patients.

OBJECTIVE: Plasma concentration of asymmetric dimethylarginine (ADMA), a major endogenous inhibitor of nitric oxide synthase, is considered a novel risk factor for endothelial dysfunction associated with enhanced atherosclerosis. Coronary microcirculation abnormalities have been demonstrated in patients with early rheumatoid arthritis (ERA) without any signs or symptoms of coronary artery disease (CAD). The aim of the study was to compare the ERA and control groups with ADMA, intima-media thickness (IMT) and coronary flow reserve (CFR) levels. It assessed whether ERA patients have more cardiovascular risk (endothelial dysfunction and coronary microvascular abnormalities), and evaluated whether any difference in IMT/CFR between ERA and controls can be explained by any difference in ADMA levels between the groups. METHODS: The study involved 25 ERA patients (female/male 21/4; mean age 52.04 +/- 14.05 years; disease duration

Setting dialysis start at 6.0 ml/min/1.73 m2 eGFR--a study on safety, quality of life and economic impact.

BACKGROUND: End-stage renal disease care requires enormous economic resources. A timely dialysis start could reduce the costs of the renal replacement therapy (RRT). Our aim was to measure the time to dialysis in CKD patients, with an estimated glomerular filtration rate (eGFR)

Emerging role of capecitabine in gastric cancer.

For many years, a regimen of fluorouracil and cisplatin has been the standard of care for the treatment of patients with metastatic gastric cancer. More recently, triplet regimens that incorporate fluorouracil and cisplatin with epirubicin (ECF) or docetaxel are being used in the management of patients with metastatic disease; ECF is also being used as preoperative treatment of resectable disease. Capecitabine, a prodrug of fluorouracil that can be taken orally, has been assessed as an alternative to intravenous fluorouracil and has demonstrated noninferiority to its parent compound. Several trials have demonstrated the safety and efficacy of regimens combining capecitabine with other known active drugs against gastric cancer in doublet and triplet combinations. Oral capecitabine appears to be more convenient to administer than infused fluorouracil because it may obviate the need for central venous access and its associated risk of complications. All of these findings support consideration of capecitabine among the available drug treatment options for patients with metastatic and those with operable gastric cancers.

Psoriatic arthritis: pharmacoeconomic considerations.

Tumor necrosis factor (TNF) antagonists provide a clinically and economically efficient treatment option for psoriatic arthritis (PsA). PsA is a chronic inflammatory disease affecting the musculoskeletal system that, if untreated, can be disabling due to the progressive joint damage and the considerable impact on functional status and health-related quality of life. Therapies for PsA have been disappointing until recently. Traditional disease-modifying drugs are used to control symptoms, but there is no evidence that they slow the progression of the damage in peripheral joints. The introduction of the TNF-alpha-blocking agents has revolutionized the therapeutic management of PsA. These drugs lessen symptoms and signs of inflammation, enhance quality of life and functional capacity, and hinder the evolution of structural joint damage. TNF-alpha blockers are very expensive and not easily available to all patients, either depending on a national system or private insurance. Nevertheless, recent pharmacoeconomic studies have demonstrated that TNF-alpha blockers are cost-effective treatment options for the musculoskeletal and cutaneous manifestations of psoriatic disease.

Amlodipine: a pharmacoeconomic review.

OBJECTIVES: To review the pharmacoeconomic impact of the use of amlodipine in coronary artery disease (CAD) patients. METHODS: A review of the available outcome trials evaluating the clinical effectiveness of amlodipine in hypertensive patients or in patients with CAD or diabetic nephropathy was carried out to identify pharmacoeconomic studies that quantified the economic impact of using amlodipine instead of another treatment. RESULTS: A combined analysis of two trials comparing angiotensin receptor blockers (ARBs) with a calcium channel blocker amlodipine suggested that amlodipine provided more protection against stroke and myocardial infarction than ARBs. In addition, in keeping with previous meta-analyses, calcium channel blockade with amlodipine also prevented more stroke than angiotensin-converting enzyme inhibitors and old drug classes. Pharmacoeconomic analysis conducted in the US and Europe demonstrated that the use of amlodipine resulted in fewer hospitalisations and the need for fewer invasive surgical procedures in the short and long term and at a modest incremental cost. The use of amlodipine resulted in improved clinical outcomes as well as slight savings in cost. CONCLUSIONS: Amlodipine is not only cost effective, but predicted to be cost saving when compared with usual care, warranting its consideration as an agent of choice in patients with CAD.

Cost-Effectiveness Analysis of the MiniMed 670G Hybrid Closed-Loop System Versus Continuous Subcutaneous Insulin Infusion for Treatment of Type 1 Diabetes.

BACKGROUND: Hybrid closed-loop (HCL) systems combine continuous glucose monitoring with continuous subcutaneous insulin infusion (CSII) to continuously self-adjust basal insulin delivery. Relative to CSII, HCL improves glycemic control and reduces the risk of hypoglycemia but has higher acquisition costs. The aim of this analysis was to assess the cost-effectiveness of the MiniMed™ 670G HCL system versus CSII in people with type 1 diabetes (T1D) in Sweden. METHODS: Cost-effectiveness analysis, from a societal perspective, was performed over patient lifetimes using the IQVIA CORE Diabetes Model. Clinical data were sourced from a study comparing the MiniMed 670G system with CSII in people with T1D. Cost data, expressed in 2018 Swedish krona (SEK), were obtained from Swedish reference prices and published literature. RESULTS: The MiniMed 670G system was associated with a quality-adjusted life-year (QALY) gain of 1.90 but higher overall costs versus CSII, leading to an incremental cost-effectiveness ratio (ICER) of SEK 164,236 per QALY gained. Use of the HCL system resulted in a lower cumulative incidence of diabetes-related complications. Higher HCL system acquisition costs were partially offset by reduced complication costs and productivity losses. In people with T1D poorly controlled at baseline, the MiniMed 670G system was associated with 2.25 incremental QALYs versus CSII, yielding an ICER of SEK 15,830 per QALY gained. CONCLUSIONS: The MiniMed 670G system was associated with clinical benefits and quality-of-life improvements in people with T1D relative to CSII. At a willingness-to-pay threshold of SEK 300,000 per QALY gained, this HCL system likely represents a cost-effective treatment option for people with T1D in Sweden.