PURPOSE: The purpose of this analysis of patient-reported outcomes from the ELECT (Evaluation of Lanreotide Depot/Autogel Efficacy and Safety as a Carcinoid Syndrome Treatment) trial (NCT00774930) was to explore the effect of lanreotide on symptoms of carcinoid syndrome. Specifically, this post hoc analysis was designed to identify the most important patient-reported outcomes for patients in ELECT. METHODS: The post hoc analysis of ELECT, a placebo-controlled study of lanreotide in patients with neuroendocrine tumors, evaluated patient-reported outcomes during the double-blind phase of the trial, specifically daily diarrhea and flushing symptoms, octreotide rescue use, and the EORTC QLQ-C30 and QLQ-GINET21 questionnaires at baseline and week 12. Principal component (PC) analysis was applied on baseline data to identify independent variable clusters and clinically meaningful summary measures that highly correlated to these PCs. From those, the minimum clinical important differences were derived so to perform a responder analysis. RESULTS: The three largest PCs captured 42.9% of the variation among baseline variables. The C30 summary score (C30-SS), diarrhea burden, and flushing burden were highly correlated with PC1, PC2, and PC3, respectively. Lanreotide patients were more likely to experience an improvement on the C30-SS (risk ratio [RR] 2.42; P=0.023), diarrhea burden (RR 2.85; P=0.005), and flushing burden (RR 1.39; P=0.31) compared to placebo patients. Lanreotide-treated patients have a higher probability of being a responder on at least one of the three domains of C30-SS, diarrhea burden, or flushing burden compared to placebo patients (RR 1.48; P=0.06). CONCLUSION: The higher response rates in the diarrhea burden are consistent with the previously reported effects of lanreotide on octreotide rescue medication use, while the findings of a greater efficacy of lanreotide vs placebo in the quality-of-life domains represent a novel aspect in the benefits of lanreotide. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00774930.

PURPOSE: Vitreomacular traction (VMT) is a disease in which the vitreous exerts abnormally strong traction on the macula, the area of the eye responsible for detailed central vision. If this traction significantly distorts the macula then VMT can lead to troublesome distorted vision (metamorphopsia), sometimes occurring despite relatively preserved visual acuity. Ocriplasmin, administered as a single intravitreal injection, aims to release VMT and improve vision. While the effect of ocriplasmin on traction release and visual acuity is well characterized, the effect of symptoms like metamorphopsia is not. METHODS: A systematic review and synthesis of the literature on patient reported outcomes (PRO) in relation to the use of ocriplasmin for the treatment of VMT was undertaken using MED-LINE and Embase databases, and the Cochrane central register of controlled trials (CENTRAL). RESULTS: The review identified PRO data from 870 patients across three randomized controlled trials. The most commonly reported PROs were the 25-item National Eye Institute Visual Function Questionnaire (VFQ-25), a broad measure of vision-related quality of life, and Visual Function Response (VFR), an outcome combining quality of life and visual acuity outcomes. Treatment with ocriplasmin produced significant patient benefit vs control (sham or placebo-injection). Ocriplasmin was associated with a higher proportion of patients experiencing a clinically meaningful improvement in visual functioning with a difference of 11.8% for VFQ-25 and 23.2% for VFR responder analyses, respectively. CONCLUSION: Patients with VMT have material impairment in visual functioning and quality of life, relative to their reduction in visual acuity. Ocriplasmin results in a significant improvement in visual functioning. Future research could include the development of new PROs specific to VMT.

OBJECTIVES: To report the prevalence and severity of metamorphopsia, estimate its impact on vision-related quality of life (VRQoL) and evaluate predictors of VRQoL in patients with vitreomacular traction (VMT). PATIENTS AND METHODS: A prospective, cross-sectional multi-centre study in the United Kingdom of 185 patients with VMT, with or without a full thickness macular hole (FTMH). Self-reported metamorphopsia was determined using the metamorphopsia questionnaire. VRQoL was assessed using the Visual Function Questionnaire (VFQ-25). Physicians recorded clinical and ocular characteristics in both eyes including a physician assessment of metamorphopsia. ANOVA and predicted least-squares means were used to estimate the impact of metamorphopsia on VRQoL. Predictors of VRQoL were assessed using ordinary-least-squares regression adjusting for clinically important variables. RESULTS: The prevalence of self-reported metamorphopsia was 69.7% (95% CI 62.6-76.3%) and was higher in eyes with a concomitant FTMH vs. without FTMH (85.4% vs. 64.2%). Physician assessment of metamorphopsia was 53.0% (95% CI: 45.5-60.3%). Comparing eyes with metamorphopsia vs. without metamorphopsia, the VFQ-25 composite score was lower (82.3 vs. 91.4), and mean VA (LogMAR) was worse (0.44 vs. 0.33). The largest difference in VFQ-25 scores was observed for near activities (metamorphopsia: 75.3, No metamorphopsia: 90.2). The adjusted model showed that metamorphopsia severity and age were significantly associated with lower VFQ-25 scores. CONCLUSION: Metamorphopsia was highly prevalent in patients with VMT and associated with significantly lower VRQoL. Physician assessment of symptoms underestimated the self-reported presence of metamorphopsia. Metamorphopsia severity acts as a predictor of impaired VRQoL, over and above decrements due to reduced vision.

PURPOSE: To assess the effect of ocriplasmin on visual function response (VFR) measured using visual acuity (VA) and vision-related quality of life, and to quantify the association between release of vitreomacular adhesion (VMA) at day 28 and VFR. METHODS: Prespecified analysis of secondary endpoints from a randomized controlled trial. Of 220 participants with symptomatic VMA/vitreomacular traction (VMT), including VMT associated with a macular hole up to 400 μm, 146 received a single intravitreal injection of 125 μg ocriplasmin and 74 a sham injection. Based on principal components analysis results, a VFR was defined as either a VA improvement of ≥2 lines or an improvement exceeding the minimal clinically important difference (MCID) in the composite or the mental health subscale scores of the Visual Function Questionnaire (VFQ-25). The MCID was estimated using the standard error of measurement approach. The main outcome measure was the VFR at month 6, with further assessments at months 12 and 24. RESULTS: The MCID was estimated at 3.71 points for the VFQ-25 composite score and 10.71 for the VFQ-25 mental health subscale score. A VFR occurred in 51.0% of ocriplasmin versus 23.3% of sham participants (P = 0.0001). The VFR was maintained through months 12 and 24: 53.1% and 50.3% in ocriplasmin versus 21.9% and 20.5% in sham participants, respectively (P < 0.0001). Resolution of VMA at day 28 significantly increased the odds of a VFR at each assessment period. CONCLUSIONS: Treatment with ocriplasmin compared with sham resulted in a significant improvement in VFR. The 6-month treatment effect was sustained at months 12 and 24.

PURPOSE: To examine the association between visual function response (VFR) and inflammation reduction in active noninfectious uveitis of the posterior segment (NIU-PS). METHODS: Phase 3 SAKURA Study 1 randomized 347 subjects in a double-masked fashion to receive injections of intravitreal sirolimus 44 μg (n = 117); 440 μg (n = 114); or 880 μg (n = 116) every other month. Vitreous haze (VH) response, a measure of inflammation reduction, was defined as a VH score of 0 or 0.5+ at month 5 based on the modified Standardized Uveitis Nomenclature Scale. Visual function was assessed with best-corrected visual acuity (BCVA) and the National Eye Institute (NEI) Visual Function Questionnaire-25 (VFQ-25). In this post-hoc analysis, principal component analysis was used to reduce the information in the multidimensional visual function outcome to a restricted number of independently relevant VFR measures. Minimal clinically important differences (MCID) for the VFQ-25-derived components were based on the standard error of measurements. Overall VFR was defined as either a BCVA improvement of ≥2 lines, or an improvement exceeding the MCID in the VFQ-25 based visual function measures. RESULTS: The VFQ-25 composite score (VFQCS) and mental health subscale score (VFQMHS) were retained as relevant VFRs, with MCIDs of 4.3 and 11.7 points, respectively. A vitreous haze response was significantly associated with each VFR measure: VFQCS (odds ratio [OR] = 2.23; P = 0.0004); VFQMHS (OR = 2.84; P < 0.0001); BCVA (OR = 2.60; P = 0.0009), and overall VFR (OR = 2.65; P < 0.0001). CONCLUSIONS: Inflammation reduction to a VH score of 0 or 0.5+ was significantly associated with improved visual function. Achieving a VH response of 0 or 0.5+ is a patient-relevant outcome.

PURPOSE: To assess the effect of an intravitreal ocriplasmin injection on visual function, measured using visual acuity (VA) and vision-related quality of life. METHODS: Post hoc analysis of prespecified secondary end-points in two multicentre, randomized, double-masked, phase 3 clinical trials. A total of 652 participants with symptomatic vitreomacular adhesion were enrolled, of whom 464 received a single intravitreal injection of 125 μg ocriplasmin and 188 received a single intravitreal placebo injection. Based on principal components analysis results, visual function response (VFR) was defined as either a VA improvement of ≥2 lines; or an improvement in the composite score of the National Eye Institute Visual Function Questionnaire (VFQ-25) exceeding the minimal clinically important difference (MCID), estimated using the standard error of measurement approach; or an improvement in the VFQ-25 driving subscale score exceeding the MCID. The main outcome measure was VFR at 6 months. RESULTS: A VFR occurred in 55.1% of the ocriplasmin group versus 34.2% of the placebo injection group (p < 0.0001). This comprised 23.7% versus 11.2% (p = 0.0003) with a ≥ 2-line VA improvement, 35.9% versus 22.7% (p = 0.0016) for the VFQ-25 composite score, and 10.2% versus 6.2% (p = 0.1697) for the driving subscale. CONCLUSION: Ocriplasmin produces a clinically meaningful visual function benefit.

BACKGROUND: If left untreated, vitreomacular traction (VMT) will infrequently improve through spontaneous resolution of vitreomacular adhesion (VMA), and patients remain at risk of further deterioration in vision. The mainstay of treatment for VMT is vitrectomy, an invasive procedure that carries the risk of rare but serious complications and further vision loss. As such, a 'watch and wait' approach is often adopted before this surgical intervention is performed. Ocriplasmin (microplasmin) is a potential alternative treatment for patients with symptomatic VMT that may remove the requirement for vitrectomy. OBJECTIVE: The purpose of this study was to evaluate the cost-effectiveness of ocriplasmin for the treatment of VMT in comparison to standard of care. STUDY DESIGN: A cohort-based computer simulation model was developed, capturing three mutually exclusive subgroups: 1) VMT without epiretinal membrane (ERM) or full thickness macular hole (FTMH), 2) VMT with ERM but no FTMH, and 3) VMT with FTMH. Transition probabilities between health states, utilities, and resource utilisation were estimated based on clinical trial results, the literature, and expert opinion. The cost per quality-adjusted life year (QALY) gained was estimated over a lifetime, using UK unit costs and utilities associated with visual acuity, adverse events, metamorphopsia, and surgical interventions. SETTING: Analyses were conducted from a UK payer perspective. POPULATION: Transition probabilities for the model were primarily estimated from patient-level data from the combined Phase 3 MIVI-TRUST trials in patients with symptomatic VMA/VMT, including when associated with a FTMH ≤400 µm. INTERVENTION: Ocriplasmin (microplasmin) is a one-time intravitreal injection designed specifically to release the abnormal traction between the macula and the vitreous and thereby treat VMT, as well as macular hole with persistent vitreous attachment. MAIN OUTCOME MEASURE: The main outcome measure of the economic evaluation was cost per QALY. RESULTS: In all subgroups, ocriplasmin management generated more QALYs: 1) VMT without ERM or FTMH (0.105, (0.036, 0.191)); 2) VMT with ERM but no FTMH (0.041, (0.011, 0.131)); and 3) VMT with FTMH (0.053, (-0.002, 0.113)). The initial treatment costs were partially offset by later savings and net costs were estimated at £1,901 (£1,325, £2,474), £2,491 (£1,067, £2,511), and £1,912 (£1,233, £2,506), respectively. Costs per QALY were estimated at £18,056 (£8,241, £64,874), £61,059 (£8,269, £168,664), and £36,250 (-£144,788, £290,338), respectively. Short-term efficacy parameters were found to be key drivers of results. CONCLUSION: Ocriplasmin is most cost-effective in VMT patients without either ERM or FTMH.

BACKGROUND: To date no network meta-analysis (NMA) has accounted for baseline variations in viral load when assessing the relative efficacy of interventions for chronic hepatitis B (CHB). We undertook baseline-adjusted and unadjusted analyses using the same data to explore the impact of baseline viral load (BVL) on CHB treatment response. METHODS: We searched Embase, Medline, Medline in Process and the Cochrane CENTRAL databases for randomised clinical trials (RCTs) of monotherapy interventions at licensed doses for use in CHB. Search strategies comprised CHB disease and drug terms (a combination of controlled vocabulary and free text terms) and also a bespoke RCT filter.The NMA was undertaken in WinBUGs using fixed and random effects methods, using data obtained from a systematic review. Individual patient data (IPD) from an entecavir clinical trial were used to quantify the impact of different baseline characteristics (in particular undetectable viral load (UVL) at 1 year) on relative treatment effect. Study level mean baseline values from all identified studies were used. Results were generated for UVL and presented as relative risks (RRs) and 95% credible intervals (CrIs) using entecavir as reference treatment. RESULTS: Overall, for all eight relevant interventions we identified 3,000 abstracts. Following full text review a total of 35 (including the contents of six clinical study reports) met the inclusion critera; 19 were in hepatitis B e antigen (HBeAg)-positive patients and 14 of the 19 contained outcome information of relevance to the NMA.Entecavir and tenofovir studies had heterogeneous patient populations in terms of BVL (mean values 9.29 and 8.65 log10 copies/ml respectively). After adjusting UVL for BVL using an informative prior based on the IPD analysis, the difference between entecavir and tenofovir was not statistically significant (RR 1.27, 95% CrI 0.96 to 1.47-fixed effects). A similar conclusion was found in all sensitivity analyses. Adjusted tenofovir results were more consistent with observed clinical trial response rates. CONCLUSIONS: This study demonstrates the importance of adjusting for BVL when assessing the relative efficacy of CHB interventions in achieving UVL. This has implications for both clinical and economic decision making.

BACKGROUND: The World Health Organization has called for global and regional assessments of the burden of hepatitis C (HCV) along with country-specific patient profiles to better inform healthcare policy. The present investigated the characteristics and burden of patients reporting a diagnosis of HCV infection in the US, France, Germany, Italy, Spain, the UK, urban China, and Japan using a consistent methodology of patient-reported surveys. METHODS: The 2010 5EU (N = 57,805), 2009 US (N = 75,000), 2008/2009 Japan (N = 37,683), and 2009/2010 urban China (N = 33,261) waves of the National Health and Wellness Survey were used as the data source. Within each country, patients with a self-reported diagnosis of HCV were compared with those who did not report a diagnosis of HCV on sociodemographics, health behaviors, comorbidities, and health outcomes (e.g., Short Form-12v2). The effect of HCV was examined using regression analysis applying sampling weights. RESULTS: The prevalence of HCV ranged from 0.26% (China) to 1.42% (Italy). Patients in Japan and Italy (61.60 and 61.02 years, respectively) were the oldest, while patients in the US were the most likely to be obese (39.31%) and have concomitant anxiety (38.43%) and depression (46.05%) compared with other countries. Pooling countries and adjusting for sociodemographics, health behaviors, and comorbidities, HCV was associated with significantly lower physical component summary scores (b = -2.51) and health utilities (b = -0.04) and greater overall work impairment (b = 8.79), physician visits (b = 2.91), and emergency department visits (b = 0.30) (all p<.05). The effects on health status were strongest in the US and UK while the effects on healthcare resource use were strongest in Japan. CONCLUSIONS: HCV was associated with a significant humanistic and economic burden. These results suggest that the manifestation of the HCV burden, and the profile of the patients themselves, varied dramatically by country. Successful disease management should be cognizant of region-specific unmet needs.

BACKGROUND: In Europe, health-care policies are determined at a national level and differ between countries. This analysis from a prospective, longitudinal, non-interventional study aimed to describe patterns in the clinical monitoring and treatment of chronic hepatitis B (CHB) in five European countries. METHODS: Country-specific cohorts of adult patients with compensated CHB managed in clinics in Germany, France, Poland, Romania and Turkey were followed for up to 2 years between March 2008 and December 2010. RESULTS: A total of 1,267 patients were included. Baseline age and gender distribution were similar across countries for patients who were treated (n=567) and untreated (n=700) at baseline. Most treated patients were receiving monotherapy at baseline, most frequently with entecavir or tenofovir in Germany, France and Turkey, and with lamivudine in Poland and Romania. Use of pegylated interferon was more frequent in Poland and Romania than in other countries. In Romania monotherapy with entecavir increased after it became reimbursed in 2008. Hospitalizations during follow-up were more frequent in Romania (1.45 hospital days/patient-year) and Poland (1.81 days/patient-year) than in Turkey, France and Germany (0.00, 0.05 and 0.10 days/patient-year, respectively); clinic visits were more frequent in Poland (3.20 versus 0.30-1.78 visits/patient-year across other countries). CONCLUSIONS: These results illustrate country-specific patterns in the management of CHB patients across Europe. Observed monitoring patterns, hospitalization rates and other health-care utilization may be related to cost and reimbursement issues; however, further study in individual countries would be required to confirm these (post hoc) observations.

In Europe, healthcare systems differ between countries and different factors may influence Chronic hepatitis B (CHB) treatment choices in different counties. This analysis from a prospective, longitudinal, non-interventional study in five EU countries aimed to explore determinants associated with treatment initiation or switch in patients with CHB. A total of 1267 adult patients with compensated CHB in Germany, France, Poland, Romania and Turkey were prospectively followed for up to 2 years (March 2008-December 2010). Determinants of treatment initiation or switch were analysed using multivariate Cox proportional hazards regression. Median time since CHB diagnosis was 2.6 (0-37.7) years. Among 646 treatment-naïve patients, the probability of treatment initiation during follow-up was higher: in Germany (P = 0.0006), Poland (P < 0.0001) and Romania (P = 0.0004) compared with Turkey; in patients with alanine transaminase (ALT) 1-2 × upper limit of normal (ULN) (P = 0.0580) or >2 × ULN (P = 0.0523) compared with ALT ≤ 1 × ULN; and in patients with hepatitis B virus (HBV) DNA ≥ 2000 IU/mL (P < 0.0001) compared with HBV DNA <2000 IU/mL or undetectable. Among 567 treated patients, 87 switched treatment during follow-up. The probability of treatment switch was higher: in France (P = 0.0029), Germany (P = 0.0078) and Poland (P = 0.0329) compared with Turkey; and in patients with HBV DNA <2000 (P < 0.0001) or ≥ 2000 IU/mL (P < 0.0001), compared with undetectable. Viral load and ALT level were identified as the major drivers of treatment initiation. HBV DNA level was also a significant determinant of treatment switch. Results were statistically different across EU countries.

BACKGROUND: Chronic hepatitis B (CHB) is an important health concern, but there are few studies describing its management in different countries. This prospective, longitudinal, non-interventional study aimed to assess differences in CHB management in five European countries (Germany, France, Poland, Romania and Turkey). METHODS: Data were collected from CHB patients' records between 2008 and 2010. Patients were stratified by treatment status at baseline (treated or untreated). The primary objective was to estimate the probability of a CHB management modification (treatment initiation or change) among patients from each country during a 2-year follow-up. RESULTS: A total of 1,267 patients were included (567 treated, 700 untreated). Baseline characteristics between countries and treatment status groups were broadly comparable. Most patients had an alanine aminotransferase measurement in the 12 months prior to baseline; proportions of patients with an HBV DNA assessment varied by country and treatment status. The Kaplan-Meier-estimated probability of any treatment modification ranged from 9.4% (Turkey) to 30.1% (Poland) at 12 months and 10.0% (Turkey) to 40.0% (Poland) at 24 months. Modifications were more common in treated than untreated patients. The most frequently reported reasons for modifying treatment were HBV-DNA-related. The majority of treated patients were treated with monotherapy; however, choice of therapy differed between countries. CONCLUSIONS: This is the first longitudinal study describing CHB management in European countries. Differences were observed in treatment and monitoring between countries, but alanine aminotransferase and HBV DNA levels consistently emerged as key tests in the management of CHB in all five countries.

OBJECTIVE: Hepatitis C virus (HCV) affects 170 million patients worldwide and is the leading cause of liver cirrhosis and hepatocellular carcinoma. The aim of the current study is to examine the burden of HCV in the European Union (EU) from a patient perspective. METHODS: Using data from the 2010 EU National Health and Wellness Survey, patients who reported a diagnosis of HCV (n=332) were compared with a propensity-score-matched non-HCV control group (n=332) on measures of quality of life (using the SF-12v2), work productivity, and healthcare resource utilization in the past 6 months. All analyses applied sampling weights to project to the respective country populations. RESULTS: Projected prevalence estimates of HCV were 0.59% in France, 0.44% in Germany, 1.42% in Italy, 0.82% in Spain, and 0.35% in the UK. HCV patients reported significantly lower levels of emotional role limitations (means=66.4 vs. 70.6, P=0.040), physical functioning (means=63.8 vs. 71.9, P=0.001), general health (means=48.3 vs. 54.4, P=0.004), bodily pain (means=64.3 vs. 70.8, P=0.002), and physical component summary scores (means=42.9 vs. 45.3, P=0.002) than the matched controls. Patients with HCV also reported significantly higher levels of presenteeism (means=27.1 vs. 21.0%, P=0.044) and a greater number of physician visits in the past 6 months (means=9.9 vs. 6.7, P<0.001). CONCLUSION: Using a population-based survey methodology and a propensity-score matching analysis, these results add to the literature by documenting the significant effect that HCV has on a variety of both humanistic and economic outcomes in the EU.

OBJECTIVE: To quantify physicians' preferences among possible outcomes associated with chronic hepatitis B treatments and to determine which outcomes are most important to physicians in making treatment decisions. METHODS: Physicians in five countries who treat chronic hepatitis B patients completed a web-enabled, choice-format, conjoint-analysis survey. The survey presented physicians with four treatment-choice questions for three different patient types. Each treatment-choice question included a pair of hypothetical medication profiles. Medication outcomes included how long the medication has been studied (weight of evidence); the probability that a patient's viral load remains undetectable for 5 years, with a possible histological improvement or reversal of disease progression (long-term efficacy); the 5-year treatment-related risk of fracture; the 5-year treatment-related risk of renal dysfunction; and patient cost. Treatment-choice questions were derived from a predetermined experimental design with known statistical properties. For each country, the random-parameters logit was used to estimate preference weights for all outcome levels and the mean relative importance of each outcome. RESULTS: Long-term efficacy and risk of renal dysfunction were the most important outcomes for the 788 physicians completing the survey, whereas weight of evidence was the least important. However, physicians perceived significant differences in weight of evidence timeframes. Physicians in Germany and France ranked efficacy above side-effect risk, whereas physicians in Spain, Italy, and Turkey ranked side-effect risk above efficacy in importance. CONCLUSION: Physician preferences among treatment profiles indicate systematic differences in the relative importance of treatment outcomes. Physicians require higher efficacy for treatments with higher side-effect risk but somewhat less efficacy for treatments with longer evidence.

No abstract available.

AIMS: To determine efficacy of the analgesic flupirtine in the treatment of overactive bladder syndrome in a proof-of-concept study. METHODS: Double-blind, double-dummy, three-armed comparison of flupirtine extended release (400 mg/day, titrated to 600 mg/day), tolterodine extended release (4 mg/day) and placebo for 12 weeks. RESULTS: When major elevations of liver enzymes (more than three times the upper normal limit) were detected in several flupirtine-exposed patients, the study was prematurely discontinued. Based on study-end data, hepatotoxicity was detected in 31% of patients receiving flupirtine for ≥ 6 weeks. CONCLUSIONS: Unexpected frequent and relevant toxicity can occur when testing an established drug for a new indication.

OBJECTIVE: The aim of this study was to estimate the cost-effectiveness of atazanavir/ritonavir (atazanavir/r) versus lopinavir/ritonavir (lopinavir/r) in treatment-naïve human immunodeficiency virus-1 (HIV-1) patients in Sweden for whom efavirenz is not suitable. METHODS: A Markov model was developed to predict the lifetime outcomes of atazanavir/r and lopinavir/r in terms of quality-adjusted life years (QALYs) and total costs. The model was structured to focus on treatment lines--how patients progress from first- to second-, and then to third-line treatment. Model inputs were derived directly from clinical trials, such as the CASTLE study (a 96-week head-to-head trial in first-line therapy), and from the Framingham risk-equation. The analysis was conducted from a payer perspective and included extensive scenario and probabilistic sensitivity analyses. RESULTS: The model predicted atazanavir/r to save 0.16 (95% confidence interval (CI) 0.00 to 0.33) QALYs and reduce total costs by -202,896 SEK (95% CI -332,156 to -81,644 SEK) over a lifetime horizon. Probabilistic sensitivity analyses showed that atazanavir/r had a 100% probability to be cost-effective at a willingness to pay of 200,000 SEK per QALY. CONCLUSION: The results indicate that atazanavir/r is cost-saving and more effective compared to lopinavir/r for patients who have previously not been exposed to antiretroviral drugs in Sweden.

OBJECTIVES: To evaluate the performance of a one-minute screening test measured against a validated 10-minute screening test for mild cognitive impairment (MCI) in detecting CI in patients aged > or = 65 years with two or more vascular risk factors (VRF). METHODS: Patients (n=1523) aged 65 years or older without documented CI symptoms or dementia with two or more VRF participated in this study set in Canadian primary care practice. Baseline data was collected, followed by the 1-minute animal fluency (AF) test and the 10-minute Montreal Cognitive Assessment (MoCA). Physicians (n=122) completed case reports during patient interviews and reported their diagnostic impression. AF test sensitivity, specificity, and accuracy in predicting a positive MoCA was assessed. RESULTS: Study sample mean age was 79.7 years, 55% were female, 97.6% were Caucasian and 75% had < or = 12 years of education. The AF test and MoCA detected CI in 52 and 56 percent of the study population, respectively. The AF test demonstrated sensitivity, specificity, and accuracy in predicting a positive MoCA of 67 percent each. Physicians diagnostic impression of MCI was reported for 37% of patients, and of dementia for 6%. CONCLUSION: In an elderly population with at least two VRF, using AF can be useful in detecting previously unknown symptoms of CI or dementia. Screening for CI in this high risk population is warranted to assist physician recognition of early CI. The short AF administration time favours its incorporation into clinical practice.

No abstract available.

BACKGROUND: Visceral adipose tissue accumulates during antiretroviral therapy in many patients who are infected with the human immunodeficiency virus (HIV); this process is associated with an increased cardiovascular risk. We assessed the use of a growth hormone-releasing factor analogue, tesamorelin, to decrease visceral adiposity. METHODS: We randomly assigned 412 patients with HIV (86% of whom were men) who had an accumulation of abdominal fat to receive a daily subcutaneous injection of either 2 mg of tesamorelin or placebo for 26 weeks. The primary end point was the percent change from baseline in visceral adipose tissue as shown on computed tomography. Secondary end points included triglyceride levels, the ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol, the level of insulin-like growth factor I (IGF-I), and self-assessed body image. Glycemic measures included glucose and insulin levels. RESULTS: The measure of visceral adipose tissue decreased by 15.2% in the tesamorelin group and increased by 5.0% in the placebo group; the levels of triglycerides decreased by 50 mg per deciliter and increased by 9 mg per deciliter, respectively, and the ratio of total cholesterol to HDL cholesterol decreased by 0.31 and increased by 0.21, respectively (P<0.001 for all comparisons). Levels of total cholesterol and HDL cholesterol also improved significantly in the tesamorelin group. Levels of IGF-I increased by 81.0% in the tesamorelin group and decreased by 5.0% in the placebo group (P<0.001). Adverse events did not differ significantly between the two study groups, but more patients in the tesamorelin group withdrew from the study because of an adverse event. No significant differences were observed in glycemic measures. CONCLUSIONS: Daily tesamorelin for 26 weeks decreased visceral fat and improved lipid profiles, effects that might be useful in HIV-infected patients who have treatment-associated central fat accumulation. (ClinicalTrials.gov number, NCT00123253 [ClinicalTrials.gov] .).