Validation of the clinical utility of sGaw as a response variable in methacholine challenge testing

Background and Objective

Airway hyperresponsiveness (AHR) is commonly assessed by a methacholine challenge test (MCT), during which a provocative concentration causing a 20% reduction in forced expiratory volume in 1 second (FEV₁) (PC₂₀) < 8 mg/ml is considered a positive response. However, a fall in specific airway conductance (sGaw) may also have clinical significance. The purpose of this study was to assess whether AHR determined by a provocative concentration causing a 40% reduction in sGaw (PC₄₀) < 8 mg/ml corresponds to a clinical diagnosis of asthma.

Methods

We analysed the changes in spirometry, lung volumes and sGaw during MCT in 211 randomly selected patients being evaluated for AHR to support a clinical diagnosis of asthma.

Results

The mean (SD) age of the group was 53 (15) years, with 141 women (67%). Overall lung function was normal, with FEV₁ = 92 (15) % predicted, total lung capacity = 97 (13) % predicted and sGaw = 0.19 (0.15–0.23) L/s/cm H₂O/L, (median, 25–75 IQR). There were many more patients who responded by PC₄₀ only (n = 120) than who responded by PC₂₀ (n = 52). There was no significant difference in asthma diagnosis between the PC₂₀ (98%) and PC₄₀ (93%) groups, and we estimate 34% of patients with a diagnosis of asthma would have been classified as having no AHR if only the FEV₁ criterion was used.

Conclusion

Changes in sGaw during MCT indicate clinically significant AHR in support of a clinical diagnosis of asthma among patients being evaluated for asthma.     

A reappraisal of the medical therapy with steroidogenesis inhibitors in Cushing's syndrome

Objective

To evaluate the outcome of preoperative therapy with ketoconazole (KTZ) and/or metyrapone (MTP) in previously untreated patients with Cushing's syndrome (CS).

Design and patients

Sixty‐two patients with CS (85% ACTH dependent), treated with steroidogenesis inhibitors prior to surgery between 1983 and 2010, were retrospectively studied. T₀ and t₁ defined baseline and end of preoperative medical treatment.

Results

Outcomes were based upon clinical and biochemical (normal UFC) control of hypercortisolism at t₁: group CO (controlled) included 20 patients (32%) with eucortisolism and significant clinical improvement; group NC (not controlled) 30 (48%) with persistent hypercortisolism and no control of symptoms; and group PC (partially controlled) 12 patients (19%) who despite eucortisolism had no real clinical improvement. Median duration of treatment was 4 months (range: 1–30·7), and median cumulative dose of KTZ and MTP was 57 g (range: 3·6–240) and 120 g (range: 7·5–1215). CO patients were treated more with KTZ alone than the other groups (P < 0·05). MTP alone was administered more in PC than in CO patients (P < 0·01). No clinical differences were observed between groups at baseline. Systolic blood pressure at t₁ was higher in PC than in NC patients (P < 0·05). Hypertension persisted more in PC patients than in the other groups (P < 0·05) after a median postsurgery follow‐up of 108 months (range: 4–276).

Conclusions

Preoperative administration of KTZ, MTP or both normalized UFC in 52% of patients with CS, but concomitant clinical improvement did not always follow. Larger, multicentre studies are needed to individualize preoperative medical treatment and improve outcome in patients with CS.     

Efficacy and Safety of Prucalopride in Patients with Chronic Noncancer Pain Suffering from Opioid-Induced Constipation

Background  

Opioid-induced constipation (OIC) has negative effects on quality of life (QOL). Prucalopride is a new, selective 5-HT₄ agonist and enterokinetic with strong clinical data in chronic constipation. This study investigated the efficacy, safety, and tolerability of prucalopride in patients with noncancer pain and OIC.     

Ivacaftor: Five-year outcomes in the West of Scotland cystic fibrosis population

Introduction

Ivacaftor has shown to be effective in patients with cystic fibrosis (CF) with a G551D mutation.

Objectives

This work aims to evaluate ivacaftor's effectiveness and safety in the real world, over 5 years, in the West of Scotland CF population.

Methods

We evaluated ivacaftor's effect on pulmonary function, body mass index (BMI), hospital bed occupancy, and adverse effects in patients ≥6 years with at least one G551D mutation.

Results

Statistically significant increases from baseline were observed in mean per cent predicted forced expiratory volume in 1 s (FEV₁) at year 1 (which was maintained at years 2 and 5) and BMI over 5 years in our adolescent/adult cohort. Improvements were observed in per cent predicted FEV₁ within the paediatric cohort with a suggestion of a plateau effect. The increase in paediatric BMI z-score was nonstatistically significant. There was a reduction in the number of pulmonary exacerbations requiring intravenous antibiotics and hospital bed occupancy. Ivacaftor was well tolerated.

Conclusion

Ivacaftor was effective in our population.     

Does therapeutic drug monitoring (TDM) of trough concentrations suffice for optimizing preemptive therapy with ganciclovir of cytomegalovirus infections in non-renal solid organ transplant recipients?

Objectives

The aim of this study is to explore the relationship between ganciclovir exposure and clinical efficacy and/or safety in non-renal solid organ transplant (SOT) recipients receiving preemptive therapy with ganciclovir/valganciclovir and undergoing therapeutic drug monitoring (TDM)-guided dosing optimization.

Methods

Non-renal SOT recipients admitted to IRCCS Azienda Ospedaliero-Universitaria of Bologna receiving preemptive therapy with ganciclovir or valganciclovir for active cytomegalovirus (CMV) infection and who underwent at least one TDM were included. Desired ganciclovir C_min range was set at 1–3 mg/L, and average ganciclovir trough concentrations (C_min) were calculated for each patient. Reduced CMV viral load below the lower limit of quantification (LLQ) at 30 days and occurrence of myelotoxicity were selected as the primary outcome. Univariate analysis was performed by comparing patients with average C_min below or above 1 or 3 mg/L. Receiver operating characteristic (ROC) curve analysis was performed to identify the average ganciclovir C_min cut-off predictive for clinical efficacy or toxicity.

Results

Twenty-nine out of 89 retrieved patients met the inclusion criteria, with a median (interquartile [IQR]) baseline CMV viral load of 27,163 copies/mL (IQR 13 159.75–151 340.25 copies/mL). Reduced CMV viral load below the LLQ at 30 days was found in 17 patients (58.6%). No difference was found in the primary outcome between patients showing average C_min below or above 1 mg/L (100.0% vs. 53.8%; p = .25) and/or 3 mg/L (65.2% vs. 33.3%; p = .20). ROC analysis did not allow to identify an average C_min cut-off predictive of clinical efficacy or toxicity.

Conclusions

No clear relationship between ganciclovir C_min and neither CMV eradication nor safety issues was identified.

     

Peri-conception hyperglycaemia and nephropathy are associated with risk of congenital anomaly in women with pre-existing diabetes: a population-based cohort study

Aims  

The aim of this study was to quantify the risk of major congenital anomaly, and to assess the influence of peri-conception HbA_1c and other clinical and socio-demographic factors on the risk of congenital anomaly occurrence in offspring of women with type 1 and type 2 diabetes diagnosed before pregnancy.     

Assessing the economic value of maintained improvements in Type 1 diabetes management,in terms of HbA1c,weight and hypoglycaemic event incidence

Aims

Insulin therapy is indicated for people with Type 1 diabetes mellitus; however, treatment‐related weight gain and hypoglycaemia represent barriers to optimal glycaemic management. This study assessed the health economic value of maintained reductions in HbA_1c, BMI and hypoglycaemia incidence among the UK Type 1 diabetes population.

Methods

The Cardiff Type 1 Diabetes Model was used to estimate lifetime costs, life‐years and quality‐adjusted life‐years (QALYs) for individuals with Type 1 diabetes at different baseline HbA_1c, BMI and hypoglycaemic event rates. Results were discounted at 3.5%, and the net monetary benefit associated with improving Type 1 diabetes management was derived at £20 000/QALY gained. Per‐person outputs were inflated to national levels using UK Type 1 diabetes prevalence estimates.

Results

Modelled subjects with an HbA_1c of 86 mmol/mol (10.0%) were associated with discounted lifetime per‐person costs of £23 795; £12 649 of which may be avoided by maintaining an HbA_1c of 42 mmol/mol (6.0%). Combined with estimated QALY gains of 2.80, an HbA_1c of 42 mmol/mol (6.0%) vs. 86 mmol/mol (10.0%) was associated with a £68 621 per‐person net monetary benefit. Over 1 year, unit reductions in BMI produced £120 per‐person net monetary benefit, and up to £197 for the avoidance of one non‐severe hypoglyceamic event.

Conclusions

Maintained reductions in HbA_1c significantly alleviate the burden associated with Type 1 diabetes in the UK. Given the influence of weight and hypoglycaemia on health economic outcomes, they must also be key considerations when assessing the value of Type 1 diabetes technologies in clinical practice.     

Systematic review and meta‐analysis of psychological interventions in people with diabetes and elevated diabetes‐distress

Aims

The clinical relevance of diabetes‐distress is increasingly recognized, but little is known about the efficacy of interventions specifically targeted to treat elevated diabetes‐distress. Therefore, this systematic review sought to determine the efficacy of psychological interventions aimed at treating elevated diabetes‐distress in people with Type 1 or Type 2 diabetes.

Methods

We systematically searched literature from five databases. Randomized controlled trials (RCTs) with an English abstract, describing the results of a psychological intervention in adults with diabetes were included. Articles were eligible for inclusion if the primary outcome was diabetes‐distress measured by the Problem Areas in Diabetes Scale (PAID‐5/PAID‐20) or the Diabetes Distress Scale (DDS‐17). Only mean group diabetes‐distress values above cut‐off at baseline or the results of a subgroup above cut‐off (PAID‐5 ≥ 8, PAID‐20 ≥ 40 or DDS‐17 ≥ 3) were included.

Results

The search yielded 8907 articles. After removing 2800 duplicates, 6107 articles remained. Titles and abstracts were screened, leaving 394 potential articles of interest, nine of which were RCTs. In a random‐effects meta‐analysis, the pooled effect size for diabetes‐distress was 0.48 (Cohen's d), Z = 3.91, P < 0.0001. Statistical heterogeneity was I² = 46.67% (confidence intervals 45.06% to 48.28%). Diabetes‐tailored psychological interventions reduced HbA_1c (Cohen's d = 0.57), whereas mindfulness‐based interventions did not (Cohen's d = 0.11).

Conclusions

This systematic review shows that specifically diabetes‐tailored psychological interventions are effective in reducing elevated diabetes‐distress and HbA_1c. More rigorous studies are warranted to establish the full potential of these interventions. PROSPERO database registration ID: CRD42017075290.     

Low doses of anti-CD3, ciclosporin A and the vitamin D analogue, TX527, synergise to delay recurrence of autoimmune diabetes in an islet-transplanted NOD mouse model of diabetes

Aims/hypothesis  

Anti-CD3 monoclonal antibodies remain the most promising immune therapy for reversing recent-onset type 1 diabetes. However, current clinical trials have revealed their major drawback, namely the narrow therapeutic window in which low doses are ineffective and higher doses that preserve functional beta cell mass cause side effects. Strategies that sidestep these limitations while preserving or improving anti-CD3’s therapeutic efficiency are essential. We hypothesised that combining a potent vitamin D₃ analogue (TX527), ciclosporin A (CsA) and anti-CD3 would act to lower the dose while maintaining or even boosting therapeutic efficacy to counteract autoimmune destruction of transplanted islets.     

Mecamylamine treatment for alcohol dependence: a randomized controlled trial

Background and aims

The nicotinic acetylcholine receptor antagonist, mecamylamine, is a potential novel pharmacotherapy for alcohol use disorder. The aims were to compare alcohol consumption between mecamylamine and placebo and test if smoking status modified treatment effects.

Design

Out‐patient, randomized, double‐blind clinical trial for 12 weeks of treatment with mecamylamine (10 mg) (n = 65) versus placebo (n = 63).

Setting

Connecticut, USA.

Participants

Individuals had current alcohol dependence (n = 128), had an average age of 48.5 [standard deviation (SD) = 9.4], 110 (85.9%) were men, and included 74 smokers (57.8%) and 54 non‐smokers (42.2%). Participants were randomized to mecamylamine 10 mg per day or placebo. All subjects also received medical management therapy administered by trained research personnel.

Measurements

Primary outcome was percentage of heavy drinking days during the last month of treatment; other outcomes included drinking days, drinks per drinking days, alcohol craving, smoking, symptoms of nicotine withdrawal and side effects.

Findings

There were no significant differences in the percentage of heavy drinking days at 3 months between the mecamylamine (mean = 18.4, SD = 29.0) and placebo treatment groups (mean = 20.4, SD = 29.2) [F_{1, 100} = 1.3, P = 0.25; effect size d = 0.07; mean difference = 2.06, 95% confidence interval (CI) = ?8.96 to 13.08]. There were no significant differences in percentage of drinking days or in drinks per drinking day at month 3 between the mecamylamine and placebo groups; there were no significant interactions.

Conclusions

Mecamylamine 10 mg per day did not reduce alcohol consumption significantly in treatment‐seeking smokers and non‐smokers with alcohol use disorder.     

A phase II,open-label,multicentre study to evaluate the immunogenicity and safety of an adjuvanted prepandemic (H5N1) influenza vaccine in healthy Japanese adults

Background  

Promising clinical data and significant antigen-sparing have been demonstrated for a pandemic H5N1 influenza split-virion vaccine adjuvanted with AS03_A, an α-tocopherol-containing oil-in-water emulsion-based Adjuvant System. Although studies using this formulation have been reported, there have been no data for Japanese populations. This study therefore aimed to assess the immunogenicity and tolerability of a prepandemic (H5N1) influenza vaccine adjuvanted with AS03_A in Japanese adults.     

Impact of using elastic stains for detection of venous invasion in the prognosis of patients with lymph node negative colorectal cancer

Purpose and methods  

Patients with nodal negative colorectal cancer (CRC) suffer recurrent or metastatic disease in 40% of cases after surgical resection. To investigate a potential prognostic impact of vascular tumor infiltration, we retrospectively analyzed 185 nodal negative stage I and II CRC specimens for the presence of intra- and/or extramural venous invasion (V1_IM/V1_EM) using elastic stains of all tumor sections and correlated our findings with the clinical follow-up.     

Synergistic growth inhibition in HL-60 cells by the combination of acyclic retinoid and vitamin K<Subscript>2</Subscript>

Purpose  

The aim of this study was to assess the effects of acyclic retinoid (ACR) and vitamin K₂ (VK₂) in HL-60 cells.     

Effect of Smoking and Gender on Pulmonary Function and Clinical Features in Sarcoidosis

Background

The effect of cigarette smoking on the clinical manifestations and progression of sarcoidosis is not well characterized. We sought to determine the effects of smoking in sarcoidosis patients and to evaluate for gender-specific differences.

Methods

We examined the effects of cigarette smoking in 518 patients seen at the Sarcoidosis and Interstitial Lung Disease Center at Wayne State University using radiographic pattern, pulmonary function testing, and clinical features of the disease. We performed a separate analysis to evaluate for gender-specific differences based on smoking history.

Results

We found that smokers had significantly lower FEV₁ and FEV₁/FVC values. Total lung capacity was not significantly different between smokers and nonsmokers, but diffusion capacity for carbon monoxide (DL_CO) was significantly reduced in smokers. Gender-based statistical analysis showed a marked decrease in DL_CO values among female smokers. Smokers were also found to have a higher incidence of extrapulmonary involvement as multivariate regression analysis demonstrated that both smoking and female gender are significantly associated with the development of extrapulmonary manifestations.

Conclusions

Our data indicate that both cigarette smoking and gender are important in shaping the clinical manifestations of sarcoidosis. The nature of the gender difference requires further study and may be related to differences in inflammatory response.     

Break‐through bleeding in relation to pharmacokinetics of Factor VIII in paediatric patients with severe haemophilia A

Introduction

As the pharmacokinetics (PK) of factor VIII (FVIII) is individualized in children with haemophilia A (HA), PK parameters may be indicators of patients' bleeding phenotype and instruction for their personalized replacement program.

Aim

The aim of this study was to investigate the possible relationship between PK/FVIII level and bleeding frequency in Chinese paediatric patients with severe (HA).

Methods

A total of 24 patients were enrolled in Beijing Children's Hospital from February to October 2015, all of whom were given 50 IU/kg of FVIII concentrates after a 72‐hours washout period. Samples' activities (FVIII:C) were tested at 5 time points, using WinNonlin software for PK testing, and then the individual half‐life(t_1/2) and the time (h) of FVIII concentrations <1 IU/dL within a week during prophylaxis were calculated. Baseline and the annual bleeding rate (ABR), annual joint bleeding rate (AJBR) were recorded and analyzed.

Results

The mean t_1/2 of FVIII was 10.20 ± 2.72 hours and the mean time of FVIII <1 IU/dL in 1 week was 44.7 hours (?38.56 to 102.33 hours). A significant relationship between t_1/2 of FVIII and ABR₀/AJBR₀ (baseline bleeding) was found (R² = 0.75 and 0.62, P < .001). Besides, baseline and the annual bleeding rate during prophylactic treatment of haemophilia had a positive correlation with the time (hours) of FVIII <1 IU/dL in 1 week (R² = 0.67 and 0.52, P < .001).

Conclusion

t_1/2 was an important indicator to prevent bleeding in severe HA; the frequency of bleeding will be reduced with the increased of t_1/2 of FVIII. The data also demonstrates that increasing the time with a FVIII<1 IU/dL is associated with an increased rate of bleeding during prophylaxis.     

Recovery of pulmonary functions,exercise capacity,and quality of life after pulmonary rehabilitation in survivors of ARDS due to severe influenza A (H1N1) pneumonitis

Background

Acute respiratory distress syndrome (ARDS) due to severe influenza A H1N1 pneumonitis would result in impaired pulmonary functions and health‐related quality of life (HRQoL) after hospital discharge.

Objectives

The recovery of pulmonary functions, exercise capacity, and HRQoL in the survivors of ARDS due to 2009 pandemic influenza A H1N1 pneumonitis (H1N1‐ARDS) was evaluated in a tertiary teaching hospital in northern Taiwan between May 2010 and June 2011.

Patients and Methods

Data of spirometry, total lung capacity (TLC), diffusing capacity of carbon monoxide (DL_CO), and 6‐minute walk distance (6MWD) in the patients survived from H1N1‐ARDS were collected 1, 3, and 6 months post‐hospital discharge. HRQoL was evaluated with St. George respiratory questionnaire (SGRQ).

Results

Nine survivors of H1N1‐ARDS in the study period were included. All these patients received 2 months’ pulmonary rehabilitation program. Pulmonary functions and exercise capacity included TLC, forced vital capacity (FVC), forced expiratory volume in the first second (FEV₁), DL_CO, and 6MWD improved from 1 to 3 months post‐hospital discharge. Only TLC had further significant improvement from 3 to 6 months. HRQoL represented as the total score of SGRQ had no significant improvement in the first 3 months but improved significantly from 3 to 6 months post‐discharge.

Conclusion

The impaired pulmonary functions and exercise capacity in the survivors of H1N1‐ARDS improved soon at 3 months after hospital discharge. Their quality of life had keeping improved at 6 months even though there was no further improvement of their pulmonary functions and exercise capacity.     

Clinical and socio‐demographic factors associated with diabetic ketoacidosis hospitalization in adults with Type 1 diabetes

Aim

To identify the clinical and socio‐demographic factors associated with hospitalization for diabetic ketoacidosis in adults with Type 1 diabetes.

Methods

We combined clinical and administrative health data from a large urban diabetes clinic to perform a data linkage study. We identified adults (aged ≥ 18 years old) with Type 1 diabetes and linked to hospital discharge abstracts to assess for diabetic ketoacidosis hospitalization. The study period was between 1 January 2004 and 31 December 2009, with all individuals living in the same geographic area. Multivariate logistic regression was used to identify potential predictors of diabetic ketoacidosis hospitalization.

Results

We identified 255 individuals with a diabetic ketoacidosis hospitalization and 1739 without a diabetic ketoacidosis hospitalization. Mean (standard deviation) age was 40.0 (15.8) years, 51.7% were men and mean duration of diabetes was 17.8 (12.9) years. Diabetic ketoacidosis hospitalization was associated with shorter duration of diabetes (odds ratio 0.96 per year; 95% confidence interval 0.95–0.98), gastroparesis (odds ratio 4.13; 95% confidence interval 1.82–9.35), psychiatric diagnosis (odds ratio 1.98; 95% confidence interval 1.22–3.19), and higher HbA_1c (odds ratio 1.25 per 1% increase; 95% confidence interval 1.16–1.35).

Conclusions

This study identifies specific clinical factors associated with diabetic ketoacidosis hospitalization in adults with Type 1 diabetes. This information can help to inform the detection of high‐risk patients, for whom special attention and interventions may be warranted to prevent diabetic ketoacidosis.     

Imaging sublingual microcirculatory perfusion in pediatric patients receiving procedural sedation with propofol: A pilot study

Objective

Procedural sedation with propofol is widely used in the pediatric population. A well‐known side effect of propofol is a decrease in peripheral vascular resistance resulting in hypotension, but little is known about the effects on microcirculation in humans. We aimed to evaluate the effects of propofol on the sublingual microcirculatory perfusion by continuous video imaging in pediatric patients undergoing procedural sedation.

Methods

Patients admitted to the Pediatric Intensive Care Unit for procedural sedation were recruited. Oral microcirculation was measured employing a continuous monitoring strategy with incident dark‐field illumination imaging. Measurements were obtained before and 3 minutes after propofol induction. Total and perfused vessel densities, proportion of perfused vessels, microvascular flow index, blood vessel diameter (Ø_bv), and systemic hemodynamics were analyzed.

Results

Continuous measurements were achieved in seven patients. Three minutes after propofol induction mean arterial pressure decreased (P = 0.028) and total and perfused vessel densities increased by 12% (P = 0.018) and 16% (P = 0.018), respectively. MFI was unaltered and mean Ø_bv increased but not significantly.

Conclusions

Propofol induction induces a reduction in mean arterial pressure and a rise in sublingual microvascular perfusion. The observed effects of propofol on the sublingual microcirculation may be due to a decrease in microvascular resistance.     

Electrocardiographic features of failed and recurrent right ventricular outflow tract catheter ablation of idiopathic ventricular arrhythmias

1 Introduction

Various ECG algorithms have been proposed to identify the origin of idiopathic outflow tract (OT)‐ventricular arrhythmia (VA). However, electrocardiographic features of failed and recurrent right ventricular outflow tract (RVOT) ablation of idiopathic OT‐VAs have not been clearly elucidated.

2 Methods and results

A total of 264 consecutive patients (mean age: 44.0 ± 13.0 years, 96 male) undergoing RVOT ablation for OT‐VAs with a transition ≥V₃, including 241 patients (91.6%) with initially successful procedures and 23 patients (8.4%) with failed ablation. Detailed clinical characteristics and ECG features were analyzed and compared between the two groups. VAs with failed RVOT ablation had larger peak deflection index (PDI), longer V₂ R wave duration (V₂Rd), smaller V₂ S wave amplitude, higher R/S ratio in V₂, higher V₃ R wave amplitude, and larger V₂ transition ratio than those with successful ablation. Multivariate analysis demonstrated that PDI, V₂Rd, V₂ transition ratio, and pacemapping score acquired during mapping independently predicted failed ablation (P  =  0.01, P  =  0.01, P  =  0.01, and P < 0.001, respectively). In 31 recurrent cases (12.8%) after initially successful ablation, multivariate Cox regression analysis showed that only the earliest activation time acquired during mapping predicted the recurrences after successful ablation (P  =  0.001). The recurrent cases displayed different ECG features comparing with those with failed ablation.

3 Conclusion

The electrocardiographic features of failed RVOT ablation of idiopathic OT‐VAs with a transition ≥V₃ were characterized by PDI, V₂Rd, V₂ transition ratio, and pacemapping score acquired during mapping, unlike the recurrent RVOT ablation.     

Cost-utility analysis of indacaterol in Germany: A once-daily maintenance bronchodilator for patients with COPD

Introduction

Indacaterol is a novel inhaled once-daily long-acting beta₂-agonist (LABA) for the maintenance treatment of COPD that has been compared to existing inhaled monotherapies on a number of symptomatic endpoints in clinical studies. With constrained healthcare budgets, the objective of this analysis was to evaluate the cost-effectiveness of indacaterol 150 μg, the approved starting dose for maintenance therapy, from a German heath service perspective against the most widely used bronchodilator tiotropium, and the twice-daily LABA, salmeterol.

Methods

A Markov model was developed with the following main health states: Mild, Moderate, Severe, and Very Severe COPD, based on pre-bronchodilator FEV₁ measures reported in the indacaterol clinical trials, and death. Each disease severity health state had two associated health states for severe or non-severe exacerbation. The model considered patients with moderate to severe COPD, with a mean age of 64 years. The base case time horizon was three years, with discounting set at 3% for costs and benefits. Selected clinical inputs and health state utilities were derived from indacaterol clinical trials, while costs were based on publicly available drug prices and tariffs or published sources. Inputs describing disease progression were based on published data on the rate of FEV₁ decline.

Results

Point-estimates show that indacaterol 150 μg is dominant (lower total costs and better outcomes) against tiotropium and salmeterol. An alternative analysis comparing indacaterol 300 μg (maximum dose) against tiotropium, showed an incremental cost-effectiveness ratio (ICER) of approximately €28,300 per QALY.

Conclusion

Indacaterol is cost-effective compared to tiotropium and salmeterol.