Search

Aims: To find the knowledge and attitude among physiotherapy interns towards physiotherapy and total knee replacement in case of osteoarthritis of knee. Material and Methods : A cross-sectional observational study was carried out using a structured questionnaire. The structured questionnaire was designed to assess the knowledge and attitude among physiotherapy interns towards physiotherapy and total knee replacement in case of osteoarthritis of knee across the colleges in Gujarat. The data was analyzed by using the Statistical Package for Social Sciences (SPSS) statistical software, version 16. Results: Total 250 Interns students were participated in the study. Majority of Physiotherapy students believed 75-100% successful in improving functional mobility. Physiotherapy is effective in mild and moderate stage of osteoarthritis knee. Physiotherapy was considered as an alternative to total knee replacement by 85% of Interns, and they think that it can delay or avoid total knee replacement in patient with minimal symptoms, and if patient with minimal symptoms are advised for total knee replacement then they take an effort as to discuss with the orthopedic surgeons to take physiotherapy as first treatment option. Conclusion: Interns knowledge and attitude on Physiotherapy for osteoarthritis knee concludes that physiotherapy is effective in mild to moderate stage of osteoarthritis knee for improving functional mobility .Their opinion for advising criteria of total knee replacement to the individual having NPRS 8-10, Flexion range of motion restriction of 45-90 degrees, Extension range of motion restriction 0-45 degrees, Fixed flexion deformity, Medial Instability and ADL’s affection i.e. Getting out from chair, sit to stand, crossed leg sitting, squatting etc. Keywords : Osteoarthritis of knee, total knee replacement, Interns physiotherapy students. Physiotherapy.

Soham Shukla,1 Dhvani Shah,2 Alan Martin,3 Nancy A Risebrough,4 Robyn Kendall,5 Claus F Vogelmeier,6 Isabelle Boucot,3 Lee Tombs,7 Leif Bjermer,8 Paul W Jones,3 Edward Kerwin,9 Chris Compton,3 François Maltais,10 David A Lipson,11,12 Afisi S Ismaila1,13 1Value Evidence and Outcomes, GSK, Collegeville, PA, USA; 2ICON, New York, NY, USA; 3Value Evidence and Outcomes, GSK, Brentford, Middlesex, UK; 4Global Health Economics, and Outcomes Research and Epidemiology, ICON, Toronto, ON, Canada; 5Global Health Economics, and Outcomes Research and Epidemiology, ICON, Vancouver, BC, Canada; 6Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Member of the German Center for Lung Research (DZL), Marburg, Germany; 7Precise Approach Ltd, Contingent Worker on Assignment at GSK, Brentford, Middlesex, UK; 8Respiratory Medicine and Allergology, Lund University, Lund, Sweden; 9Altitude Clinical Consulting and Clinical Research Institute of Southern Oregon, Medford, OR, USA; 10Centre de Pneumologie, Institut universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec, QC, Canada; 11Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; 12Respiratory Clinical Sciences, GSK, Collegeville, PA, USA; 13Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Afisi S IsmailaValue Evidence and Outcomes, GlaxoSmithKline 1250 South Collegeville Road, Collegeville, PA, 19426-0989, USATel +1 919 315 8229Email afisi.s.ismaila@gsk.comIntroduction: Dual bronchodilators are recommended as maintenance treatment for patients with symptomatic COPD in the UK; further evidence is needed to evaluate cost-effectiveness versus monotherapy. Cost-effectiveness of umeclidinium/vilanterol versus umeclidinium and salmeterol from a UK healthcare perspective in patients without exacerbations in the previous year was assessed using post hoc EMAX trial data.Methods: The validated GALAXY model was populated with baseline characteristics and treatment effects from the non-exacerbating subgroup of the symptomatic EMAX population (COPD assessment test score ≥ 10) and 2020 UK healthcare and drug costs. Outputs included estimated exacerbation rates, costs, life-years (LYs), and quality-adjusted LYs (QALYs); incremental cost-effectiveness ratio (ICER) was calculated as incremental cost/QALY gained. The base case (probabilistic model) used a 10-year time horizon, assumed no treatment discontinuation, and discounted future costs and QALYs by 3.5% annually. Sensitivity and scenario analyses assessed robustness of model results.Results: Umeclidinium/vilanterol treatment was dominant versus umeclidinium and salmeterol, providing an additional 0.090 LYs (95% range: 0.035, 0.158) and 0.055 QALYs (− 0.059, 0.168) with total cost savings of £ 690 (£ 231, £ 1306) versus umeclidinium, and 0.174 LYs (0.076, 0.286) and 0.204 QALYs (0.079, 0.326) with savings of £ 1336 (£ 1006, £ 2032) versus salmeterol. In scenario and sensitivity analyses, umeclidinium/vilanterol was dominant versus umeclidinium except over a 5-year time horizon (more QALYs at higher total cost; ICER=£ 4/QALY gained) and at the lowest estimate of the St George’s Respiratory Questionnaire treatment effect (fewer QALYs at lower total cost; ICER=£ 12,284/QALY gained); umeclidinium/vilanterol was consistently dominant versus salmeterol. At willingness-to-pay threshold of £ 20,000/QALY, probability that umeclidinium/vilanterol was cost-effective in this non-exacerbating subgroup was 95% versus umeclidinium and 100% versus salmeterol.Conclusion: Based on model predictions from a UK perspective, symptomatic patients with COPD and no exacerbations in the prior year receiving umeclidinium/vilanterol are expected to have better outcomes at lower costs versus umeclidinium and salmeterol.Keywords: COPD treatment, cost-effectiveness, umeclidinium, salmeterol, umeclidinium/vilanterol

Background We assessed the cost-effectiveness of single-inhaler fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) versus FF/VI or UMEC/VI from a Canadian public healthcare perspective, incorporating data from the IMPACT trial in chronic obstructive pulmonary disease (COPD) (NCT02164513). Methods Baseline inputs and treatment effects from IMPACT were populated into the validated GALAXY-COPD disease progression model. Canadian unit costs and drug costs (Canadian dollars [C$], 2017) were applied to healthcare resource utilization and treatments. Future costs and health outcomes were discounted at 1.5% annually. Analyses were probabilistic, and outputs included exacerbation rates, costs, and life years (LYs) and quality-adjusted life years (QALYs) gained. Results Compared with FF/VI and UMEC/VI over a lifetime horizon, the analyses predicted that treatment with FF/UMEC/VI resulted in fewer moderate and severe exacerbations, more LYs and more QALYs gained, with a small incremental cost. The base-case incremental cost-effectiveness ratio (ICER) per QALY gained was C$18,989 (95% confidence interval [CI]: C$14,665, C$25,753) versus FF/VI and C$13,776 (95% CI: C$9787, C$19,448) versus UMEC/VI. FF/UMEC/VI remained cost-effective versus both FF/VI and UMEC/VI in all sensitivity analyses, including in scenario analyses that considered different intervention and comparator discontinuation rates, and treatment effects for subsequent therapy. Conclusion Treatment with FF/UMEC/VI was predicted to improve outcomes and be a cost-effective treatment option for patients with symptomatic COPD and a history of exacerbations compared with FF/VI or UMEC/VI, in Canada.

Aims: Heart failure with reduced ejection fraction (HFrEF) has a substantial impact on costs and patients’ quality-of-life. This study aimed to estimate the cost-effectiveness of implantable cardioverter defibrillators (ICD), cardiac resynchronization therapy pacemakers (CRT-P), cardiac resynchronization therapy defibrillators (CRT-D), and optimal pharmacologic therapy (OPT) in patients with HFrEF, from a US payer perspective. Materials and methods: The analyses were conducted by adapting the UK-based cost-effectiveness analyses (CEA) to the US payer perspective by incorporating real world evidence (RWE) on baseline hospitalization risk and Medicare-specific costs. The CEA was based on regression equations estimated from data from 13 randomized clinical trials (n = 12,638). Risk equations were used to predict all-cause mortality, hospitalization rates, health-related quality-of-life, and device-specific treatment effects (vs. OPT). These equations included the following prognostic characteristics: age, QRS duration, New York Heart Association (NYHA) class, ischemic etiology, and left bundle branch block (LBBB). Baseline hospitalization rates were calibrated based on RWE from Truven Health Analytics MarketScan data (2009–2014). A US payer perspective, lifetime time horizon, and 3% discount rates for costs and outcomes were used. Benefits were expressed as quality-adjusted life-years (QALYs). Incremental cost-effectiveness analysis was conducted for 24 sub-groups based on LBBB status, QRS duration, and NYHA class. Results: Results of the analyses show that CRT-D was the most cost-effective treatment at a $100,000/QALY threshold in 14 of the 16 sub-groups for which it is indicated. Results were most sensitive to changes in estimates of hospitalization costs. Limitations: Study limitations include small sample sizes for NYHA I and IV sub-groups and lack of data availability for duration of treatment effect. Conclusions: CRT-D has higher greater cost-effectiveness across more sub-groups in the indicated patient populations against as compared to OPT, ICD, and CRT-P, from a US payer perspective.

Introduction The cost-effectiveness of long-acting muscarinic antagonist (LAMA) umeclidinium bromide (UMEC) 62.5 μg as add-on therapy to other maintenance COPD treatments is unknown. Methods This analysis assessed the cost-effectiveness of the following in COPD: UMEC + fluticasone furoate/vilanterol 100/25 μg (FF/VI); UMEC + fluticasone propionate/salmeterol 250/50 μg (FP/SAL); and UMEC + several alternative choices of inhaled corticosteroid/long-acting β2-agonist (ICS/LABA). The model was informed with direct and indirect data from previously published studies, with a UK perspective and a lifetime horizon. Sensitivity analyses were also performed. Results For the lifetime horizon, compared with FF/VI, FP/SAL and ICS/LABAs, addition of UMEC was associated with incremental costs per quality-adjusted life-years (QALY) of £4050, £7210 and £5780, respectively, and incremental costs per life year gain of £3380, £6020 and £4940. All UMEC-containing regimens resulted in numerically lower exacerbation rates versus comparator regimens over a lifetime horizon. Conclusions Addition of UMEC to various ICS/LABA treatments was associated with higher cost than ICS/LABA alone, but was cost-effective in most scenarios.

Introduction and objective Exacerbations associated with chronic obstructive pulmonary disease (COPD) are costly and affect health related quality of life (HRQoL) for patients. An economic model was developed to estimate the cost-effectiveness of once-daily single-inhaler triple-therapy, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) Trelegy®, 100 µg/62.5 µg/22 µg and dual therapy, umeclidinium/vilanterol (UMEC/VI) Anoro®, 55 µg/22 µg from a UK NHS perspective using results from the IMPACT study (NCT02164513). Patients and methods The model combines a decision tree for the within-trial period (52 weeks) and a Markov model to predict lifetime costs and outcomes of FF/UMEC/VI compared with UMEC/VI. Risk equations for prediction of exacerbations (by severity of COPD) and FEV1 decline (based on exacerbation history) were derived using data from the TORCH study (NCT00268216). Baseline characteristics, efficacy and medication use were based on data from IMPACT. Direct costs, including drug acquisition costs were calculated using UK NHS reference costs and drug prices. Healthcare resource utilisation was based on published sources. Costs (2018 £) and health outcomes were discounted at 3.5% and modelled on a lifetime horizon. Sensitivity analyses were performed to evaluate the robustness of the model to variations in the underlying input parameters and assumptions. Results Patients treated with FF/UMEC/VI had fewer moderate and severe exacerbations, more life years gained, improved HRQoL and higher total costs compared with patients treated with UMEC/VI based on deterministic analyses (table 1). The incremental cost-effectiveness ratio (ICER) was £7451 per QALY gained. Sensitivity analyses identified that results were most sensitive to drug acquisition cost, utilities associated with moderate COPD and severe COPD, mortality risk in very severe COPD, and exacerbation rates. The ICERs ranged from £1110 to £13 793 per QALY. Probabilistic sensitivity analysis indicated a 73% chance that FF/UMEC/VI is cost-effective versus UMEC/VI at a willingness to pay threshold of £20 000 per QALY. Funding GSK (study number HO-17–17596). ICON Health Economics received funding from GSK to conduct the study only.

Introduction and objectives The IMPACT trial (NCT02164513) showed superior exacerbation reduction and lung function improvement with once-daily single inhaler triple therapy, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/22 µg, compared with once-daily FF/VI 100/22 µg, for patients with symptomatic COPD and a history of exacerbations. An economic model was developed to assess the cost-effectiveness of FF/UMEC/VI vs FF/VI from a UK NHS perspective, using results from IMPACT. Methods The model combined a decision-tree for the trial period, with longer-term outcomes extrapolated via a Markov model with health states reflecting COPD severity and exacerbation history. Disease progression and exacerbation rates were determined by risk equations based on the 3 year Towards a Revolution in COPD Health study (TORCH, NCT00268216). The model was populated with baseline characteristics, efficacy and medication use from IMPACT, while healthcare resource use and utility estimates came from the literature. Medication and healthcare resource use were costed using UK drug prices and unit costs (2018 £). Results are for a lifetime horizon with costs and health outcomes (except life-years) discounted at 3.5%. Results Treatment with FF/UMEC/VI, compared with FF/VI, resulted in fewer moderate and severe exacerbations (6.460 and 1.501 vs 6.686 and 1.528), more life-years (8.874 vs 8.577) increased quality-adjusted life years (QALYs, 6.565 vs 6.291) and higher total costs (£24 843 vs £23,549). Patients receiving FF/UMEC/VI gained an additional 0.275 QALYs for an additional cost of £1,294, compared to those receiving FF/VI, to give an incremental cost-effectiveness ratio (ICER) of £4712 per QALY gained. In deterministic sensitivity/scenario analyses, ICERs ranged from dominant to £7502 per QALY gained, with results most sensitive to drug acquisition costs, utility associated with moderate COPD, duration of treatment effect and time horizon. In probabilistic sensitivity analysis, the probability of FF/UMEC/VI being cost-effective vs FF/VI was 95% at a willingness-to-pay threshold of £20 000 per QALY. Conclusions Treatment with FF/UMEC/VI was predicted to improve health outcomes and to be a cost-effective option for patients with symptomatic COPD and a history of exacerbations, when compared with FF/VI, in the UK. Funding GSK (study number HO-17–17596). ICON Health Economics received funding from GSK to conduct the study only.

Background: IMPACT (InforMing the PAthway of COPD Treatment, NCT02164513), showed superior exacerbation reduction and lung function improvement with single inhaler, once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/22μg vs once-daily FF/VI 100/22μg, for patients with moderate/severe COPD. Objectives: The cost-effectiveness of FF/UMEC/VI vs FF/VI was assessed, from a Canadian public payer perspective. Methods: A validated linked risk equation model (Briggs, Med Decis Making 37;4 2017), which predicts COPD disease progression, associated healthcare costs and health outcomes, was populated with baseline characteristics, efficacy and medication use from IMPACT. Canadian healthcare resource unit costs and drug costs were applied, with future costs and health outcomes discounted at 1.5% annually. Analysis was probabilistic, with a lifetime horizon and outputs including exacerbation rates, costs (2017 CAD), quality-adjusted life years (QALYs) gained and incremental cost effectiveness ratio (ICER) per QALY. Results: Compared with FF/VI, FF/UMEC/VI treatment resulted in fewer moderate and severe exacerbations (10.52 and 3.38 vs 11.13 and 3.48), mean (95% CI) incremental costs and QALYs of $2,598 ($2,010, $3,268) and 0.13 (0.09, 0.18), and an ICER of $19,649 per QALY ($15,406, $26,454). The probability of FF/UMEC/VI being cost-effective vs FF/VI was 100% at a willingness-to-pay threshold of $50,000 per QALY. Results were most sensitive to time horizon, and efficacy of treatment post-discontinuation. Conclusions: FF/UMEC/VI was predicted to improve health outcomes and to be a cost-effective option for treatment of moderate/severe COPD compared with FF/VI, in Canada.

Background Cost-effectiveness of once-daily umeclidinium bromide (UMEC) was compared with once-daily tiotropium (TIO) and once-daily glycopyrronium (GLY) in patients with chronic obstructive pulmonary disease (COPD) from a UK National Health Service (NHS) perspective. Methods A linked-equation model was implemented to estimate COPD progression, associated healthcare costs, exacerbations rates, life years (LY) and quality-adjusted LY (QALYs). Statistical risk equations for endpoints and resource use were derived from the ECLIPSE and TORCH studies, respectively. Treatment effects [mean (standard error)] at 12 weeks on forced expiratory volume in 1 s and St George’s Respiratory Questionnaire score were obtained from the intention-to-treat populations of two head-to-head studies [GSK study identifiers 201316 (NCT02207829) and 201315 (NCT02236611)] which compared UMEC 62.5 mcg with TIO 18 mcg and UMEC 62.5 mcg with GLY 50 mcg, respectively. Treatment costs reflect UK list prices (2016) and NHS unit costs; UMEC and GLY prices being equal and less than TIO. A lifetime horizon, discounted costs and effects at 3.5% were used. Sensitivity analyses were performed to evaluate the robustness of variations in input parameters and assumptions in the model. Results Over a lifetime horizon, UMEC was predicted to increase LYs (+ 0.195; 95% confidence interval [CI]: 0.069, 0.356) and QALYs (+ 0.118; 95% CI: 0.055, 0.191) and reduce the number of annual exacerbations (− 0.053; 95% CI: − 0.171, 0.028) compared with TIO, with incremental cost savings of £460/patient (95% CI: − £645, − £240). Compared with GLY, UMEC increased LYs (+ 0.124; 95% CI: 0.015, 0.281) and QALYs (+ 0.101; 95% CI: 0.043, 0.179) and reduced annual exacerbation (− 0.033; 95% CI: − 0.135, 0.017) at an additional cost of £132/patient (95% CI: £12, £330), resulting in an incremental cost-effectiveness ratio of £1310/QALY (95% CI: £284, £2060). Similar results were observed in alternative time horizons and additional sensitivity analyses. Conclusions For treatment of patients with COPD in the UK over a lifetime horizon, treatment with UMEC dominates treatment with TIO, providing both improved health outcomes and cost savings. In comparison with GLY, treatment with UMEC achieved improved health outcomes but was associated with a higher cost. Trial registration 201316, NCT02207829; 201315, NCT02236611

Introduction: The cost-effectiveness of treatments for chronic obstructive pulmonary disease (COPD) is needed. Objectives To evaluate the cost effectiveness of once-daily umeclidinium bromide 62.5 µg (UMEC) in combination with inhaled corticosteroids/long-acting β2-agonists (ICS/LABA) versus other long-acting muscarinic antagonists (LAMA)+ICS/LABA triple therapy combinations in the United Kingdom (UK). Methods: A linked-equation model estimated the disease progression, associated health service costs, and impact on quality-adjusted life-years and survival (Briggs et al. Med Decis Making 2016). Statistical risk equations for clinical endpoints and resource use were derived from the ECLIPSE and TORCH studies, respectively. Model baseline inputs and treatment effects were obtained from a network meta-analysis (Chounta et al. ATS 2016). For the base case, a lifetime horizon was used and costs and effects were discounted at 3.5%. Analyses were performed from the UK National Health Service perspective. Results: UMEC+ICS/LABA improved health outcomes versus other LAMA+ICS/LABA combinations with lower costs over the lifetime. Results remained consistent at a 5- or 10-year time horizon. Sensitivity analyses showed that variation in main parameters did not alter the results. Conclusions In COPD, UMEC+ICS/LABA is cost saving and improves health outcomes versus other LAMA+ICS/LABA triple combinations in the UK. Funding GSK (HO-15-8059)

Introduction: Information about the cost effectiveness of add-on treatments for chronic obstructive pulmonary disease (COPD) is needed. Objectives To evaluate the cost effectiveness of once-daily umeclidinium bromide 62.5μg (UMEC) added to inhaled corticosteroids/long-acting β2-agonists (ICS/LABA) versus ICS/LABA in the United Kingdom (UK). Methods: A linked-equation model estimated disease progression, associated health service costs, and impact on quality-adjusted life-years and survival. Statistical risk equations for clinical endpoints and resource use were derived from the ECLIPSE and TORCH studies, respectively. Model baseline inputs and treatment effects were obtained from GSK trials (Siler et al. COPD 2016;13:1–10; Siler et al. Respir Med 2015;109:1155–63) and discontinuation rates from the UPLIFT study. A lifetime horizon was used and costs and effects were discounted at 3.5%. Analyses were performed from the UK National Health Service perspective. Results: Against slightly higher costs, UMEC added to ICS/LABA resulted in improved outcomes. Incremental cost-effectiveness ratios remained within recognised cost-effectiveness thresholds. Sensitivity analyses showed that variation in main parameters did not alter the results including at shorter time horizons of 5 and 10 years. Conclusions Against slightly higher costs, UMEC improves health outcomes when added to ICS/LABA in COPD in the UK. Funding GSK (HO-15-8059)

Acetaminophen is a commonly-used analgesic in the US and, at doses of more than 4 g/day, can lead to serious hepatotoxicity. Recent FDA and CMS decisions serve to limit and monitor exposure to high-dose acetaminophen. This literature review aims to describe the exposure to and consequences of high-dose acetaminophen among chronic pain patients in the US. Each year in the US, approximately 6% of adults are prescribed acetaminophen doses of more than 4 g/day and 30,000 patients are hospitalized for acetaminophen toxicity. Up to half of acetaminophen overdoses are unintentional, largely related to opioid-acetaminophen combinations and attempts to achieve better symptom relief. Liver injury occurs in 17% of adults with unintentional acetaminophen overdose.

Objectives: The clinical benefit of once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus twice-daily budesonide/formoterol (BUD/FOR) for patients with symptomatic chronic obstructive pulmonary disease (COPD) was demonstrated in a clinical trial setting (FULFIL [NCT02345161]). The lifetime cost-effectiveness analysis of FF/UMEC/VI versus BUD/FOR, based on FULFIL data, is reported here. Methods: A previously developed and validated GALAXY-COPD linked-risk equation model was used to assess the cost-effectiveness of FF/UMEC/VI from the UK National Health Service (NHS) perspective. Baseline characteristics and efficacy results from FULFIL and UK NHS reference cost data (2017) were included as inputs. Exacerbation rates (undiscounted), costs, life years (LYs; undiscounted) and quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) were calculated over a lifetime horizon. Costs and QALYs were discounted at 3.5% per year, beyond one year, in accordance with National Institute for Health and Care Excellence (NICE) guidelines. Deterministic and probabilistic sensitivity analyses were performed to evaluate the robustness of the results. Results: Predicted cumulative exacerbations per patient over a lifetime were 8.393 with FF/UMEC/VI and 10.456 with BUD/FOR. Patients receiving FF/UMEC/VI gained an additional 0.764 LYs and 0.492 QALYs, at an additional mean cost of £1,652, resulting in an ICER of £3,357 per QALY gained (95% confidence interval: £1,816, £5,194) compared with BUD/FOR. The ICER remained below £6,000 in all but one of the scenario and sensitivity analyses. Conclusions: Compared with BUD/FOR, treatment with FF/UMEC/VI was predicted to improve health outcomes at an additional cost that suggests it would be cost-effective for patients with COPD in the UK. Keywords: Chronic obstructive pulmonary disease, Cost-effectiveness, Long-acting muscarinic antagonist, Inhaled corticosteroid, Long-acting β2-agonist, Economic evaluation

Hepatitis B virus (HBV) during pregnancy presents unique management challenges. Varying aspects of care must be considered, including the effects of HBV on maternal and fetal health, effects of pregnancy on the course of HBV infection, treatment of HBV during and after pregnancy, and prevention of perinatal infection. Antiretroviral therapy has not been associated with increased risk of birth defects or toxicity, but despite studies designed to elucidate the drug efficacy and safety in affected individuals and the developing fetus, recommendations are inconclusive. Clinicians and patients must make individualized decisions after carefully evaluating the risks and benefits summarized in this article.

The rheumatologic manifestations of human immunodeficiency virus (HIV) infection have been recognized since the early days of the epidemic and are characteristic of this disorder. It has been noted that the clinical spectrum of rheumatic disorders in patients with HIV infection has changed since the advent of highly active antiretroviral therapy (HAART) in the mid-1990s. Furthermore, HIV infection may become clinically apparent in rheumatic disease patients during or after they are treated with immunosuppressive therapy. The emergence of manifestations of HIV infection may develop during or after such therapy and may be confused with clinical manifestations known to be associated with the underlying rheumatic disease. In patients with established rheumatologic disease, it is difficult to consider the diagnosis of HIV especially in individuals with few or no known risk factors. In this review, we report 2 cases with established systemic rheumatic disease who developed complications originally thought to be secondary to the underlying inflammatory disorder or antirheumatic therapy. Ultimately, both patients were found to be HIV positive. Recognition of the overlapping signs or symptoms of systemic rheumatic diseases, antirheumatic therapy, and HIV infection can be lifesaving. We propose that all patients with systemic rheumatic diseases, especially those receiving or being considered for disease-modifying antirheumatic therapy, be evaluated systematically for the presence of HIV, taking into consideration the recent Centers for Disease Control and Prevention recommendations for routine opt-out HIV screening in all healthcare settings for those aged 13 to 64 years.

OBJECTIVES: This paper compares the efficacy and tolerability of perampanel (PER) relative to other recently approved anti-epileptic drug (AEDs) - lacosamide (LCS), retigabine (RTG), and eslicarbazepine (ESL) for the adjunctive treatment of partial onset seizures with or without secondary generalization and specifically in the secondary generalization subgroup. MATERIALS AND METHODS: A systematic literature review of all RCTs of PER and selected AEDs in EMBASE, Medline, and the Cochrane Central from 1998 to January 2011 with an update in PubMed in March 2013 was performed. A network meta-analysis was conducted for 50% responder rate for overall seizures; withdrawal due to adverse events; seizure freedom; and 50% responder rate for secondary generalized seizures. RESULTS: Twelve RCTs (three PER, three LCS, three RTG and three ESL) were included. PER performed significantly better than placebo for 'responder rate' (OR 2.151, 95% CrI 1.348-3.472) and 'seizure freedom' (OR 2.507, 95% CrI 1.067-7.429). When compared to other agents, PER was found to be equally effective. For 'withdrawal due to adverse events', PER had the lowest odds ratio vs. placebo compared with other AEDs. In the analysis for the subgroup of patients with secondary generalization, only four RCTs (three PER and one LCS) met the inclusion criteria for one outcome (responder rate) for LCS. In this subgroup, PER was statistically significantly better than placebo (OR 2.448, 95% CrI 1.088-5.828). CONCLUSION: PER was statistically significantly superior to placebo in responder rate, seizure freedom, and responder rate in the secondary generalization population. Though PER had statistically significant greater withdrawal compared to placebo, it had the lowest ORs vs. placebo, suggesting a superior safety profile among the comparators included in this analysis. In patients with partial onset seizure with secondary generalization, PER had a statistically significant effect on responder rate compared to placebo.

294 Background: Economic evaluations in oncology aim to assess the value of new therapies in the long term based on clinical trial data that often have restricted follow-up times (< 5 years) and small sample sizes (< 500 patients). This requires the use of extrapolation assumptions on long-term survival that go beyond the observed data. In this analysis, differences in survival extrapolation methods are tested in samples of sizes and follow-up reflecting typical clinical trials against a background of known survival in prostate cancer from a US based cancer registry. Methods: Data from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) registry on long-term survival in patients with stage IV prostate cancer were employed. The data set comprised those patients diagnosed between 1988 and 2003, with follow-up data available until 2012. Additional survival for those who received surgery (compared to those who did not), was estimated based on extrapolations using standard parametric statistical models (exponential, Weibull, log-logistic, log-normal, Gamma) fitted to the observed data. Survival analyses were run for 5 sample size scenarios (n = 27,670, 1000, 500, 200, 50) and 6 follow-up scenarios (follow-up years = 25, 20, 10, 5, 2, 1) yielding 30 combination scenarios. Performance of the methods was tested relative to the maximum follow-up, maximum sample size scenario (i.e. reference case) from the SEER registry. Results: Log-logistic and log-normal models were associated with flat tails which led to inflated survival estimations. For scenarios with smaller sizes, gamma models often did not converge. Exponential models were the most frequently reported as best model fit (in approximately 50% of scenarios). Also, gains in OS were consistent when exponential models were selected, and closely matched gain in OS from the reference case. Conclusions: Since clinical trials in oncology are often associated with small patient sample sizes and restricted follow-up, selecting an exponential model may lead to the most consistent and stable results based on the experiment constructed here. Further research should confirm these results for other types of cancer.

Objectives To assess, from a Swedish societal perspective, the cost effectiveness of interferon β-1b (IFNB-1b) after an initial clinical event suggestive of multiple sclerosis (MS) (ie, early treatment) compared with treatment after onset of clinically definite MS (CDMS) (ie, delayed treatment). Methods A Markov model was developed, using patient level data from the BENEFIT trial and published literature, to estimate health outcomes and costs associated with IFNB-1b for hypothetical cohorts of patients after an initial clinical event suggestive of MS. Health states were defined by Kurtzke Expanded Disability Status Scale (EDSS) scores. Model outcomes included quality-adjusted life years (QALYs), total costs (including both direct and indirect costs), and incremental cost-effectiveness ratios. Sensitivity analyses were performed on key model parameters to assess the robustness of model results. Results In the base case scenario, early IFNB-1b treatment was economically dominant (ie, less costly and more effective) versus delayed IFNB-1b treatment when QALYs were used as the effectiveness metric. Sensitivity analyses showed that the cost-effectiveness results were sensitive to model time horizon. Compared with the delayed treatment strategy, early treatment of MS was also associated with delayed EDSS progressions, prolonged time to CDMS diagnosis, and a reduction in frequency of relapse. Conclusion Early treatment with IFNB-1b for a first clinical event suggestive of MS was found to improve patient outcomes while controlling costs.