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The lack of adequate glycaemic control for patients with type 2 diabetes mellitus (T2DM), especially with existing second-line therapies, represents an unmet medical need. Of the newer therapies, the incretin-based medicines, such as saxagliptin, look promising to consolidate second-line pharmacotherapy.This study evaluates the long-term economic consequences of saxagliptin versus sulfonylurea (glipizide) as second-line therapy when used in combination with metformin after failure of monotherapy treatment with metformin, in patients with T2DM in Germany.A published discrete event simulation model with a fixed-time increment was used to model the effects of different treatment scenarios over a 40-year (life-) time horizon. Disease progression was modelled using evidence from the United Kingdom Prospective Diabetes Study (UKPDS) 68. The treatment sequence matched that of published German guidelines, and efficacy and safety data were derived from published sources. The model assumes that quality-adjusted life-years (QALYs) are affected by complications, hypoglycaemic events and weight change over a lifetime. Costs were specific to the German setting, where sulfonylureas are generic. Costs and effects were discounted annually at 3%. The extended perspective of the national sick funds was adopted, and recommendations from the Institute for Quality and Efficiency in Health Care (IQWiG) were considered.In the base-case analysis, treatment with saxagliptin plus metformin was associated with a lower incidence of both symptomatic and severe hypoglycaemic events, resulting in an incremental benefit of 0.12 QALYs and an incremental cost-effectiveness ratio (ICER) of €13,931 per QALY gained compared with sulfonylurea plus metformin (year of costing 2009). Modest reductions in all macro- and microvascular complications were seen in those receiving saxagliptin plus metformin compared with sulfonylurea plus metformin. Sensitivity analysis showed that treatment-related weight changes, as a risk factor for complications, represent the most influential driver of cost effectiveness.The study demonstrated improved outcomes with saxagliptin at a cost that would likely be considered acceptable in the German setting. Furthermore, the findings of the sensitivity analysis suggest that the results are robust to various assumptions concerning input variables and modelling assumptions.

This study compared the health and economic benefits of saxagliptin versus insulin as second-line therapy with either metformin (MET) or sulfonylurea (SU) after failure of the respective monotherapies for patients with type 2 diabetes in Poland.The cost-effectiveness was assessed using a previously published diabetes model. Disease progression, utilities, and effects of changes in glycosylated hemoglobin (HbA1c), weight, and hypoglycemic events were taken from published studies, and Polish sources were used where possible.MET + saxagliptin reduced severe hypoglycemic complications and weight versus MET + insulin, with an incremental benefit of 0.13 quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) of 27,454 Polish zloty (PLN) ($9,966 U.S.) per QALY gained. SU + saxagliptin showed an incremental benefit of 0.14 QALYs and ICER of 24,663 PLN ($8,953 U.S.) per QALY gained versus SU + insulin, with reduced incidence of symptomatic and severe hypoglycemias. Results were most sensitive to disutilities associated with weight gain, hypoglycemia, injection fear, HbA1c changes, threshold for switching treatment, and patients' age. Results were robust to various model assumptions and inputs. Using a willingness-to-pay threshold of 100,000 PLN ($36,300 U.S.) per QALY gained, the probability that saxagliptin is cost-effective in these analyses was 74% (MET) and 76% (SU).Saxagliptin in combination with MET or SU is likely to represent a cost-effective treatment option in Polish patients with type 2 diabetes failing first-line treatment.

Study objectives To develop and validate a patient-based outcome measure to evaluate symptoms in patients with community-acquired pneumonia (CAP). Design A psychometric study within an international, prospective, randomized, double-blind study. The CAP-symptom questionnaire (CAP-Sym) is a new, 18-item, patient-reported outcome measure that evaluates the bothersomeness of CAP-related symptoms during the past 24 h using a 6-point Likert scale. We used "gold standard" psychometric methods to comprehensively evaluate the acceptability, reliability, validity, and responsiveness of the CAP-Sym. Setting Sixty-four centers in 13 countries (France, Germany, Hungary, Israel, Italy, Norway, Poland, Portugal, South Africa, Spain, Sweden, Switzerland, United Kingdom). Patients Five hundred fifty-six patients with CAP, recruited from outpatient clinics, general practice, and hospital centers. Interventions Randomization 1:1 to moxifloxacin (400 mg once daily), oral or standard oral treatment (amoxicillin, 1 g tid, or clarithromycin, 500 mg bid), alone or in combination, for up to 14 days. Results Standard psychometric tests confirmed the acceptability (item nonresponse, item-endorsement frequencies, item/scale floor and ceiling effects), reliability (internal consistency, item-total and inter-item correlations, test-retest reliability), validity (content, construct, convergent, discriminant, known groups), and responsiveness of the CAP-Sym. Conclusions The CAP-Sym is a practical and scientifically sound patient-based outcome measure of CAP-related symptoms that has been developed using "gold standard" methods. As the only fully validated measure of symptoms in patients with CAP, which is quick and easy to administer and is more responsive than the generic Medical Outcomes Study 36-Item Short-Form Health Survey, the CAP-Sym provides a practical and rigorous method for improving the evaluation of outcomes in clinical trials and audit.

The MOSAIC study compared moxifloxacin with three standard antibiotic regimens in patients with Anthonisen type 1 acute exacerbations of chronic bronchitis (AECB). Further exploratory analyses were performed to identify prognostic factors of short and long term clinical outcomes and their value for clinical research.Outpatients agedor =45 years were screened between AECB episodes, randomised to treatment upon presenting with an AECB, assessed 7-10 days after study treatment, and followed monthly until a new AECB or for up to 9 months. Logistic regression assessed the predictive factors for clinical cure (return to pre-AECB status) and clinical success (cure or improvement), and a stepwise Cox regression model time to a composite event (failure of study treatment, new AECB, or further antibiotic treatment for AECB).In multivariate analyses, clinical cure was positively influenced by treatment with moxifloxacin (odds ratio (OR) 1.49; 95% CI 1.08 to 2.04) while cardiopulmonary disease (OR 0.59; 95% CI 0.38 to 0.90), forced expiratory volume in 1 second (FEV1)50% predicted (OR 0.48; 95% CI 0.35 to 0.67), andor =4 AECBs in the previous year (OR 0.68; 95% CI 0.48 to 0.97) predicted a poorer outcome. For clinical success, treatment with moxifloxacin had a positive influence (OR 1.57; 95% CI 1.03 to 2.41) while cardiopulmonary disease (OR 0.41; 95% CI 0.25 to 0.68) and use of acute bronchodilators (OR 0.50; 95% CI 0.30 to 0.84) predicted a poorer outcome. The occurrence of the composite event was influenced by antibiotic treatment (hazard ratio (HR) 0.82; 95% CI 0.68 to 0.98), ageor =65 years (HR 1.22; 95% CI 1.01 to 1.47), FEV150% predicted (HR 1.27; 95% CI 1.05 to 1.53),or =4 AECBs in previous year (HR 1.63; 95% CI 1.34 to 1.99), and acute bronchodilator use (HR 1.48; 95% CI 1.17 to 1.87). For the composite event the beneficial effect of moxifloxacin was primarily seen in patients agedor =65 years.Despite selection of a homogeneous population of patients with chronic bronchitis, between group differences relating to antibiotic treatment could still be confounded by factors related to medical history, severity of disease, and use of concomitant medications. The design of future clinical trials should take these factors into account.

The purpose of the study is to compare a generic and a specific quality of life (QoL) instrument in the assessment of QoL in chronic bronchitis. Data from 320 patients were collected at acute exacerbation of chronic bronchitis (AECB), and from 230 patients during a subsequent stable phase (non-AECB), utilising both the specific St George's respiratory questionnaire (SGRQ) and the generic Nottingham health profile (NHP). Patients (maximum n = 200) reported significantly poorer QoL at AECB than at non-AECB for all domains except the SGRQ symptom domain (SRM = 0.02). The SGRQ was more sensitive than the NHP to QoL differences between patients. The correlations between the scores across the two assessments were generally higher for the SGRQ, with the correlations between the NHP and SGRQ being lower at AECB, suggesting that the instruments are measuring different constructs at AECB, with the SGRQ being less responsive to QoL change. Indeed, the NHP was generally more responsive to QoL change in terms of 'risk' and clinical factors, with the SGRQ symptom domain appearing particularly non-responsive. In conclusion, this study suggests that the condition-specific SGRQ, and particularly its symptom domain, is less responsive than the generic NHP to QoL change accompanying AECB. This reflects the construct of the symptom domain which measures chronic bronchitis symptoms over the previous year.

s: To develop and validate a patient-based outcome measure to evaluate symptoms in patients with community-acquired pneumonia (CAP).A psychometric study within an international, prospective, randomized, double-blind study. The CAP-symptom questionnaire (CAP-Sym) is a new, 18-item, patient-reported outcome measure that evaluates the bothersomeness of CAP-related symptoms during the past 24 h using a 6-point Likert scale. We used "gold standard" psychometric methods to comprehensively evaluate the acceptability, reliability, validity, and responsiveness of the CAP-Sym.Sixty-four centers in 13 countries (France, Germany, Hungary, Israel, Italy, Norway, Poland, Portugal, South Africa, Spain, Sweden, Switzerland, United Kingdom).Five hundred fifty-six patients with CAP, recruited from outpatient clinics, general practice, and hospital centers.Randomization 1:1 to moxifloxacin (400 mg once daily), oral or standard oral treatment (amoxicillin, 1 g tid, or clarithromycin, 500 mg bid), alone or in combination, for up to 14 days.Standard psychometric tests confirmed the acceptability (item nonresponse, item-endorsement frequencies, item/scale floor and ceiling effects), reliability (internal consistency, item-total and inter-item correlations, test-retest reliability), validity (content, construct, convergent, discriminant, known groups), and responsiveness of the CAP-Sym.The CAP-Sym is a practical and scientifically sound patient-based outcome measure of CAP-related symptoms that has been developed using "gold standard" methods. As the only fully validated measure of symptoms in patients with CAP, which is quick and easy to administer and is more responsive than the generic Medical Outcomes Study 36-Item Short-Form Health Survey, the CAP-Sym provides a practical and rigorous method for improving the evaluation of outcomes in clinical trials and audit.

Background To compare the first-in-class sodium glucose co-transporter 2 (SGLT2) inhibitor, dapagliflozin, with existing type 2 diabetes mellitus (T2DM) treatment options available within the European Union (EU) for add-on therapy to sulfonylureas (SUs). Methods A systematic review was conducted to identify randomised controlled trials (RCTs) in T2DM patients inadequately controlled by SU monotherapy. Direct meta-analysis, Bucher indirect comparisons and Bayesian network meta-analysis (NMA) were conducted on studies meeting predefined inclusion criteria. Sufficient data were available to assess three clinical endpoints at 24 (+/- 6) weeks follow-up: mean change in HbA1c from baseline, mean change in weight from baseline, and the proportion of patients experiencing at least one episode of hypoglycaemia. The effect of confounding baseline factors was explored through covariate analyses. Results The search identified 1,901 unique citations, with 1,870 excluded based on title/abstract. From reviewing full-texts of the remaining 31 articles, 5 studies were considered eligible for analysis. All studies were comparable in terms of baseline characteristics, including: HbA1c, age and body mass index (BMI). In addition to dapagliflozin, sufficient data for meta-analysis was available for three dipeptidyl peptidase-4 (DPP-4) inhibitors and one glucagon-like peptide-1 (GLP-1) analogue. Based on fixed-effect NMA, all treatment classes resulted in statistically significant decreases in HbA1c at follow-up compared to placebo. Dapagliflozin treatment resulted in significantly decreased weight at follow-up compared to placebo (-1.54 kg; 95% CrI -2.16, -0.92), in contrast to treatment with GLP-1 analogues (-0.65 kg; 95% CrI -1.37, 0.07) and DPP-4 inhibitors (0.57 kg; 95% CrI 0.09, 1.06). The odds of hypoglycaemia were similar to placebo for dapagliflozin and DPP-4 inhibitor add-on treatment, but significantly greater than placebo for GLP-1 analogue add-on treatment (10.89; 95% CrI 4.24, 38.28). Assessment of NMA model heterogeneity was hindered by the small size of the network. Conclusions Dapagliflozin, DPP-4 inhibitors and GLP-1 analogues, in combination with SU, all provided better short-term glycaemic control compared to SU monotherapy. Dapagliflozin was the only add-on therapy that had both a favourable weight and hypoglycaemia profile compared to the other classes of treatment evaluated.