ABSTRACT OBJECTIVE: To perform a cost-benefits analysis of a clinical pharmacy (CP) service implemented in a Neurology ward of a tertiary teaching hospital. METHODS: This is a cost-benefit analysis of a single arm, prospective cohort study performed at the adult Neurology Unit over 36 months, which has evaluated the results of a CP service from a hospital and Public Health System (PHS) perspective. The interventions were classified into 14 categories and the costs identified as direct medical costs. The results were analyzed by the total and marginal cost, the benefit-cost ratio (BCR) and the net benefit (NB). RESULTS: The total 334 patients were followed-up and the highest occurrence in 506 interventions was drug introduction (29.0%). The marginal cost for the hospital and avoided cost for PHS was US$182±32 and US$25,536±4,923 per year; and US$0.55 and US$76.4 per patient/year. The BCR and NB were 0.0, -US$26,105 (95%CI −31,850 − –10,610), -US$27,112 (95%CI −33,160–11,720) for the hospital and; 3.0 (95%CI 1.97–4.94), US$51,048 (95%CI 27,645–75,716) and, 4.6 (95%CI 2.24–10.05), US$91,496 (95%CI 34,700–168,050; p < 0.001) for the PHS, both considering adhered and total interventions, respectively. CONCLUSIONS: The CP service was not directly cost-benefit at the hospital perspective, but it presented savings for forecast cost related to the occurrence of preventable morbidities, measuring a good cost-benefit for the PHS.

Cardiovascular disease (CVD) is a common comorbidity in type 2 diabetes (T2DM). CVD’s prevalence has been growing over time.

To assess the value of implementation of pharmaceutical care (PC) for cardiovascular diseases in low-middle-income countries (LMICs). This is a health care use and policy study based on health care management, which has evaluated the value of implementation (VOI) of PC from a societal and Brazilian Public Health System (BPHS) perspective. During 2009, a PC program enlisted 104 patients covered by the BPHS. Direct medical and non-medical costs and social costs were considered. Markov modeling projected over 10-years systemic arterial hypertension complications (ischemic heart disease, stroke, peripheral arterial disease, heart failure, chronic kidney disease). The treatment effect was calculated by comparing PC and conventional care and discount rates of 5% and 3% were applied to costs/outcomes, respectively. In a cash flow model, the net present value based on the return on investment (ROI) over 10 years was calculated, which represented a quantitative measure of the pharmaceutical care (PC) acceptance effect, and was converted into a net health benefit (NHB). The systematizing of the epidemiological and NHB impact provided the calculation and sensitivity analysis of VOI according to the variation for 10,000 Monte Carlo’s iterations of 38 inputs from the expected value of PC implementation. The ROI was USD $1,712,710 (95%CI 1,146,000-2,216,000), which represented a cost-benefit ratio of 30.03 (95%CI, 26.74–34.28). The social variables presented an important impact on NHB, they were able to change the ROI from USD $1,283,206 to USD $1,962,401. Lambda was estimated as the largest limit of willingness to pay for QALY, usually in LMICs; in Brazil it is three times the GDP, USD $28,000. Thus, the calculated NHB was 2.8 per patient (95%CI 2.67 - 3.04) and NHB ROI=5.41%. The impact of implementation was higher than implementation of net beneficial technology, which presents a great opportunity cost for PC.

Background: Cardiovascular diseases (CVDs) constitute major comorbidities in type 2 diabetes mellitus (T2DM), contributing substantially to treatment costs for T2DM. An updated overview of the economic burden of CVD in T2DM has not been presented to date. Objective: To systematically review published articles describing the costs associated with treating CVD in people with T2DM. Methods: Two reviewers searched MEDLINE, Embase, and abstracts from scientific meetings to identify original research published between 2007 and 2017, with no restrictions on language. Studies reporting direct costs at either a macro level (e.g., burden of illness for a country) or a micro level (e.g., cost incurred by one patient) were included. Extracted costs were inflated to 2016 values using local consumer price indexes, converted into US dollars, and presented as cost per patient per year. Results: Of 81 identified articles, 24 were accepted for analysis, of which 14 were full articles and 10 abstracts. Cardiovascular comorbidities in patients with T2DM incurred a significant burden at both the population and patient levels. From a population level, CVD costs contributed between 20% and 49% of the total direct costs of treating T2DM. The median annual costs per patient for CVD, coronary artery disease, heart failure, and stroke were, respectively, 112%, 107%, 59%, and 322% higher compared with those for T2DM patients without CVD. On average, treating patients with CVD and T2DM resulted in a cost increase ranging from $3418 to $9705 compared with treating patients with T2DM alone. Conclusions: Globally, CVD has a substantial impact on direct medical costs of T2DM at both the patient and population levels.

Background: Biologics used to treat Crohn's disease (CD) may lose their effect over time, requiring dose escalation. Little information is available on this topic.Aim: To summarize rates of dose escalation, duration, de-escalation in observational studies of CD in adults treated with adalimumab, infliximab, and vedolizumab in Europe.Methods: Two independent investigators searched Medline and Embase for observational studies published in 1998-2015 and proceedings from four major scientific meetings. Rates were summarized descriptively.Results: In total, 58 articles from 12 European countries were analyzed (49 full articles, nine abstracts), providing 65 reports with 7,850 patients; 35 reported on 3,830 patients with adalimumab (ADA), and 30 on 4,020 patients with infliximab (IFX). Overall, 29.9%3.5% of patients required dose escalation; 32.8%+/- 6.2% with ADA and 25.2%+/- 2.4% with IFX (p=.35 between drugs). Rates increased according to line of treatment: 19% for first line, 37% second, and 41% third. The median time to loss of response was 12 months, and the weighted average was 15.1 +/- 5.9 months. Median time to escalation was 6.7 months; 6.7 months for ADA and 7.5 for IFX (p=.86). Short-term response rates to escalation were 63% for ADA and 45% for IFX (p=.08). There were no papers available for vedolizumab.Conclusions: A substantial proportion of patients receiving ADA or IFX for Crohn's disease require dose escalation after a short period of time.

Abstract Background: Differences between interferons have been evaluated for over 20 years. While randomized controlled trial (RCT) data is mainly used for assessments and strong data for causal inferences, it does not necessarily reflect everyday practice. Real-world data may provide additional information. Purpose: To assess the results, quality, and representativeness of observational studies directly comparing interferons (IFNs) in RRMS. Methods: Medline and Embase were searched for observational studies comparing IFN-beta-1a 30 mcg IM (Avonex1), IFN-beta-1a 44 mcg SC (Rebif2) and/or IFN-beta-1b 250 mcg SC (Betaseron3). Outcomes included annualized relapse rate (ARR), proportions relapse free, confirmed progression free, treatment persistence, and neutralizing antibodies rates (NABs) measured up to 5 years of treatment. Data was combined using random effects meta-analyses. Categorical values were analyzed using chi-squared and Mann–Whitney tests. Results: Thirty-six studies examining 32,026 patients (72.5% females, age = 39.2 ± 3.7 years, disease duration = 5.6 ± 2.0 years) were identified. Thirty-three studies investigated IFN-beta-1a IM (N = 11,925), 30 IFN-beta-1a SC (N = 10,684) and 34 IFN-beta-1b SC (N = 9417). Baseline ARRs were similar (1.37 ± 0.35, 1.51 ± 0.27 and 1.55 ± 0.23, respectively; P = .101) as were EDSS scores (2.24 ± 0.39, 2.33 ± 0.30, 2.55 ± 0.38; P = .070) and >75% were naïve to IFNs. On treatment, ARRs were comparable (IFN-beta-1a IM 0.52 ± 0.27, IFN-beta-1a SC 0.51 ± 0.24, IFN-beta-1b SC 0.55 ± 0.23; P = .595). Proportions of relapse-free patients were similar between drugs (P > .05 for all data points), except that IFN-beta-1a SC was superior to IFN-beta-1b SC in years 3–5 (all P ≤ .001). After 1 year, EDSS scores were comparable; after 2 years, IFN-beta-1a IM and IFN-beta-1a SC incurred less disease progression than IFN-beta-1b SC (P < .02). Confirmed progression-free rates and persistence were similar over 5 years. Fewer patients developed NABs with IFN-beta-1a IM (4.7 ± 1.5%) versus IFN-beta-1a SC (21.4 ± 2.8%) (P < 0.001) or IFN-beta-1b SC (32.2% ± 3.3%) (P < .001). Conclusions: In this comprehensive meta-analysis of real-world studies in RRMS, IFN-beta-1a IM, IFN-beta-1a SC and IFN-beta-1b SC had similar clinical profiles. When selecting an IFN, practitioners should consider observational data in their decision making process.

Background: A 3-month long treatment of paliperidone palmitate (PP3M) has been introduced as an option for treating schizophrenia. Its cost-effectiveness in Spain has not been established.Aims: To compare the costs and effects of PP3M compared with once-monthly paliperidone (PP1M) from the payer perspective in Spain.Methods: This study used the recently published trial by Savitz etal. as a core model over 1 year. Additional data were derived from the literature. Costs in 2016 Euros were obtained from official lists and utilities from Osborne etal. The authors conducted both cost-utility and cost-effectiveness analyses. For the former, the incremental cost per quality-adjusted life-year (QALY) gained was calculated. For the latter, the outcomes were relapses and hospitalizations avoided. To assure the robustness of the analyses, a series of 1-way and probability sensitivity analyses were conducted.Results: The expected cost was lower with PP3M (4,780Euro) compared with PP1M (5,244Euro). PP3M had the fewest relapses (0.080 vs 0.161), hospitalizations (0.034 v.s 0.065), and emergency room visits (0.045 v.s 0.096) and the most QALYs (0.677 v.s 0.625). In both cost-effectiveness and cost-utility analyses, PP3M dominated PP1M. Sensitivity analyses confirmed base case findings. For the primary analysis (cost-utility), PP3M dominated PP1M in 46.9% of 10,000 simulations and was cost-effective at a threshold of 30,000Euro/QALY gained.Conclusions: PP3M dominated PP1M in all analyses and was, therefore, cost-effective for treating chronic relapsing schizophrenia in Spain. For patients who require long-acting therapy, PP3M appears to be a good alternative anti-psychotic treatment.

Background: A new depot formulation of paliperidone has been developed that provides effective treatment for schizophrenia for 3 months (PP3M). It has been tested in phase-3 trials, but no data on its cost-effectiveness have been published.Purpose: To determine the cost-effectiveness of PP3M compared with once-monthly paliperidone (PP1M), haloperidol long-acting therapy (HAL-LAT), risperidone microspheres (RIS-LAT), and oral olanzapine (oral-OLZ) for treating chronic schizophrenia in The Netherlands.Methods: A previous 1-year decision tree was adapted, based on local inputs supplemented with data from published literature. The primary analysis used DRG costs in 2016 euros from the insurer perspective, as derived from official lists. A micro-costing analysis was also conducted. For the costing scenario, official list prices were used. Clinical outcomes included relapses (treated as outpatients, requiring hospitalization, total), and quality-adjusted life-years (QALYs). Rates and utility scores were derived from the literature. Economic outcomes were the incremental cost/QALY-gained or relapse-avoided. Model robustness was examined in scenario, 1-way, and probability sensitivity analyses.Results: The expected cost was lowest with PP3M (8,781Euro), followed by PP1M (10,325Euro), HAL-LAT (11,278Euro), RIS-LAT (11,307Euro), and oral-OLZ (13,556Euro). PP3M had the fewest total relapses/patient (0.36, 0.94, 1.39, 1.21, and 1.70, respectively), hospitalizations (0.11, 0.46, 0.40, 0.56, and 0.57, respectively), emergency room visits (0.25, 0.48. 0.99, 0.65, and 1.14, respectively) and the most QALYs (0.847, 0.735, 0.709, 0.719, and 0.656, respectively). In both cost-effectiveness and cost-utility analyses, PP3M dominated all other drugs. Sensitivity analyses confirmed base case findings. In the costing analysis, total costs were, on average, 31.9% higher than DRGs.Conclusions: PP3M dominated all commonly used drugs. It is cost-effective for treating chronic schizophrenia in the Netherlands. Results were robust over a wide range of sensitivity analyses. For patients requiring a depot medication, such as those with adherence problems, PP3M appears to be a good alternative anti-psychotic treatment.

To summarize prevalence rates globally for cardiovascular disease (CVD) in persons with type 2 diabetes (T2DM) published within the last 10 years (2007-2017). We searched Medline, Embase, and proceedings of scientific meetings to identify published studies documenting the prevalence of CVD among people with T2DM. Search terms included stroke, myocardial infarction, angina, heart failure, ischemic heart disease, cardiovascular disease, coronary heart/artery disease (CAD), atherosclerosis, and cardiovascular death. No restrictions were placed on country of origin or publication language. Two reviewers independently searched for articles and abstracted data, with results adjudicated through consensus. Data were summarized descriptively. Risk of bias was explored by applying the checklist from the STROBE Initiative. We analyzed data from 57 articles with 4,549,481 persons having T2DM. Overall, 51.8% were male, 47.0% obese, 63.6±6.9 years old, with T2DM duration of 10.4±3.7 years. CVD affected 32.2% overall (53 studies, N=4,289,140); 29.1% had atherosclerosis in four studies (N=1,153), 21.2% had CAD (42 articles, N=3,833,200), 14.9% heart failure (14 studies, N=601,154), 14.6% angina (4 studies, N=354,743), 10.0% myocardial infarction (13 studies, N=3,518,833), and 7.6% stroke (40 studies, N=3,901,505). Males had higher rates than females for stroke (6.7% vs. 5.9%), myocardial infarction (11.9% vs. 9.8%), angina (21.1% vs. 17.4%), and CAD (18.7% vs. 14.3%). CVD was cause of death in 9.9% of all T2DM patients (representing 50.3% of all deaths), with CAD responsible for 6.3% (29.7% of all deaths) and cerebrovascular disease for 1.5% (11.0% of all deaths). Risk of death in T2DM doubled with CVD (OR=2.09; CI95%:1.56-2.80) and nearly tripled with concomitant CAD (OR=2.97; CI95%:2.18-4.06). Europe produced the most articles (49%), followed by the Western Pacific/China (19%), and North America (14%). Risk of bias was low, as 80%±12% of the Strobe checklist items were adequately addressed. Globally, CVD affects approximately 32.2% of all persons with T2DM.

BACKGROUND:Respiratory diseases exert a substantial burden on society, with newer drugs increasingly adding to the burden. Economic models are often used, but seldom reviewed. PURPOSE:To summarize economic models used in economic analyses of drugs treating moderate-to-severe/very severe asthma or chronic obstructive pulmonary disease (COPD). METHODS:This study searched Medline and Embase from inception to the end of February 2015 for cost-effectiveness/utility analyses that examined at least one drug against placebo, another drug, or other standard therapy in asthma or COPD. Two reviewers independently searched and extracted data with differences adjudicated via consensus discussion. Data extracted included model used and its qualities, validation methods, treatments compared, disease severity, analytic perspective, time horizon, data collection (pro- or retrospective), input rates and sources, costs and sources, planned sensitivity analyses, criteria for cost-effectiveness, reported outcomes, and sponsor. RESULTS:This study analyzed 53 articles; 14 (25%) on asthma and 39 (75%) COPD. Markov models were commonly used for both asthma and COPD-related economic evaluations. Relatively few studies validated their model. For asthma-related studies, 10 examined inhaled corticosteroids and nine studied omalizumab. Placebo or standard therapy was the comparison in 11 studies and active drugs in the remainder. CONCLUSIONS:Few studies include validation of their models. Furthermore, controversy concerning some results was uncovered in this study, which needs to be avoided in the future.

Biologic therapies used to treat Crohn’s disease (CD) may lose their effect over time, requiring dose escalation. Practitioners and decision makers need such information, which is presently scarce. We summarized published rates of dose escalation in observational studies of CD in adults treated in the United Kingdom. Two independent reviewers searched Medline, Embase and proceedings from four major gastroenterology meetings from 1990-2015, hand searching references and relevant UK sites. We accepted full peer-reviewed articles, peer-reviewed abstracts of oral/poster presentations at scientific congresses, or audits. No restrictions were placed on publication date or language. Patients could be treated with any biologic with or without adjunctive therapy for any duration. Required data included number of patients treated, drug(s) used, treatment regimens, numbers or rates requiring dose escalation and proportions receiving co-medications. Data were tabulated and summarized descriptively. Thirteen publications were accepted for analysis, including ten full peer-reviewed articles, two poster abstracts and one audit. A total of 5,358 patients from across the UK were treated, mainly in referral centres; 51% were females and 49% males. Average age was 34.2 years; duration of CD was 6.4 years. Five publications (38%) reported on adalimumab, 3 (23%) on infliximab and 5 (38%) combined both drugs. No observational studies from the UK were found that examined vedolizumab. 73% of the patients analysed received therapy as first line biologic treatment, 15% second line and 12% did not report prior exposure. The overall rate of dose escalation was 12%; 19% in those treated with adalimumab and 8% with infliximab, after an average of 8.4 months. Doses were escalated in 7% of those receiving first line treatment (adalimumab 8%, infliximab 7%), and 22% for second line (all adalimumab); 59% of patients were administered co-medications. An appreciable proportion requires dose escalation, which increases by treatment line.

Background: Undetected/uncontrolled diabetes is associated with substantial morbidity and mortality and consequent costs. Early detection through screening identifies patients at risk, allowing for earlier treatment initiation.Objectives: To determine the economic impact of screening for type 2 diabetes (T2DM).Data sources: We systematically reviewed health economic analyses of screening programs for T2DM/ pre-diabetes.Study eligibility criteria: Published between 2000 and 2015 in any language. Articles must have reported costs of screening, test/patient outcomes and cost-effectiveness. Participants and interventions: Any type of screening (universal, targeted, opportunistic) was accepted.Methods: Data were extracted from Scopus/Medline/Embase, then tabulated.Results: There were 137 studies identified, 108 rejected; 29 were analyzed. Screening types included 18 universal, 8 targeted and 8 opportunistic. One study screened for pre-diabetes, 16 for T2DM and 12 examined both. Fourteen (48%) reported costs of screening only, 9 (31%) costs of screening combined with interventions and 6 (21%) presented all costs separately. Screening was compared to no screening in 13 studies (45%); screening was cost- effective in 8 (62%), not cost- effective in 4 (31%) and neither in 1 (8%). When comparing different screening methods, 6 found targeted screening was cost-effective compared with universal screening (none found the opposite), 2 found opportunistic superior to universal. Sensitivity analyses generally confirmed primary findings. Cost drivers included prevalence of T2DM/pre-diabetes, type of blood test used and uptake of testing. For optimal cost-effectiveness, screening for both T2DM and pre-diabetes should be initiated around age 45-50, with repeated testing every 5 years.Conclusions/implications: Targeted screening appears to be cost-effective compared to universal screening.

Undetected/uncontrolled type-2 diabetes (T2DM) is associated with substantial morbidity and mortality and consequent costs. Early detection though screening helps identify patients at risk, allowing for sooner initiation of treatment. Our objective was to determine the economic impact of screening for T2DM and pre-diabetes. We searched Scopus/Medline/Embase for papers published between 2000 and 2015 in any language. Interventions included any type of screening (universal, targeted, and opportunistic). Articles must have reported both costs of screening and outcomes, including cost-effectiveness. Two reviewers independently identified articles and extracted data; results were adjudicated using consensus discussion. Data were analyzed descriptively. We identified 137 studies; 108 were rejected, 29 (from 12 countries) were analyzed. Screening types included 18 universal, 8 targeted and 8 opportunistic. One study screened for pre-diabetes only, 16 T2DM only and 12 examined both T2DM and pre-diabetes. Fourteen (48%) reported costs of screening only, 9 (31%) costs of screening combined with interventions and 6 (21%) presented all costs separately. Screening was compared to no screening in 12 studies (41%), in which screening was found cost-effective in 8 (67%), not cost-effective in 4 (33%) and neither in 1 (8%). In studies comparing different screening methods, 6 found that targeted screening was cost-effective compared with universal screening (none found the opposite), and 1 found opportunistic screening superior to universal. Sensitivity analyses generally confirmed primary findings. Costs were lower when both T2DM and prediabetes were screened compared with T2DM only. Major cost drivers included prevalence of T2DM/pre-diabetes, type of blood test used and rate of uptake of testing. For optimal cost-effectiveness, screening for both T2DM and pre-diabetes should be initiated around age 45-50, with repeated testing every 5 years. Targeted screening is cost-effective compared to universal screening. Efficiency is optimized and costs are minimized when screening for both prediabetes and T2DM.

Objective: Patients with chronic schizophrenia suffer a huge burden, as do their families/caregivers. Treating schizophrenia is costly for health systems. The European Medicines Agency has approved paliperidone palmitate (PP-LAI; Xeplion), an atypical antipsychotic depot; however, its pharmacoeconomic profile in Portugal is unknown. A cost-effectiveness analysis was conducted from the viewpoint of the Portuguese National Health Service.Methods: PP-LAI was compared with long acting injectables risperidone (RIS-LAI) and haloperidol (HAL-LAI) and oral drugs (olanzapine; oral-OLZ) adapting a 1-year decision tree to Portugal, guided by local experts. Clinical information and costs were obtained from literature sources and published lists. Outcomes included relapses (both requiring and not requiring hospitalization) and quality-adjusted life-years (QALYs). Costs were expressed in 2014 euros. Economic outcomes were incremental cost-effectiveness ratios (ICERs); including cost-utility (outcome=QALYs) and cost-effectiveness analyses (outcomes = relapse/hospitalization/emergency room (ER) visit avoided).Results: The base-case cost of oral-OLZ was 4447(sic) (20% drugs/20% medical/60% hospital); HAL-LAI cost 4474(sic) (13% drugs/13% medical/74% hospital); PP-LAI cost 5326(sic) (49% drugs/12% medical/39% hospital); RIS-LAI cost 6223(sic) (44% drugs/12% medical/44% hospital). Respective QALYs/hospitalizations/ER visits were oral-OLZ: 0.761/0.615/0.242; HAL-LAI: 0.758/0.623/0.250; PP-LAI: 0.823/0.288/0.122; RIS-LAI: 0.799/0.394/0.168. HAL-LAI was dominated by oral-OLZ and RIS-LAI by PP-LAI for all outcomes. The ICER of PP-LAI over oral-OLZ was 14,247(sic)/QALY, well below NICE/Portuguese thresholds (approximate to 24,800(sic)/30,000(sic)/QALY). ICERs were 1973(sic)/relapse avoided and 2697(sic)/hospitalization avoided. Analyses were robust against most variations in input values, as PP-LAI was cost-effective over oral-OLZ in >99% of 10,000 simulations.Conclusion: In Portugal, PP-LAI dominated HAL-LAI and RIS-LAI and was cost-effective over oral-OLZ with respect to QALYs gained, relapses avoided, and hospitalizations avoided.

To determine the cost-utility of ustekinumab (UST) administered subcutaneously every 12 weeks (after induction), compared with adalimumab (ADA) administered subcutaneously every two weeks, and infliximab (INF), administered intravenously every eight weeks (after induction) in treating moderate-to-severe psoriatic arthritis (PsA) in Russia. A Markov model was developed with expert panel input. Biologic-naïve patients entered the model, progressing over the 10-year analytic horizon in annual cycles according to observed transition probabilities. Six sequences of 1st line/2nd line/3rd line treatment were simulated: UST/ADA/INF, UST/INF/ADA, ADA/UST/INF, ADA/INF/UST, INF/ADA/UST, and INF/UST/ADA, with best supportive care used when all three failed. Retention rates were extracted from PSOLAR database. Utilities for UST successes/failures were derived directly from PSUMMIT-1&2 trials using the HAQ-DI mapped to EQ-5D using Rodgers’ equation; INF and ADA utilities were obtained from Yang’s NICE submission (2012). Costs from the Russian Ministry of Health perspective were obtained from standard lists, converted to 2014 euros and discounted at 5%, as per Russian pharmacoeconomic guidelines. Robustness was tested using one-way and probabilistic sensitivity analyses with 10,000 iterations. Respective expected costs were 132,730€, 135,187€, 135,413€, 138,412€, 151,457€ and 165,636€; respective QALYs were 6.598, 6.673, 6.656, 6.690, 6.760 and 6.832. UST/ADA/INF had the lowest cost. UST/INF/ADA and ADA/INF/UST were dominated. ICERs for the remaining strategies were ADA/UST/INF:32,568€, INF/ADA/UST:187,113€ and INF/UST/ADA:197,929€. Despite adding a few more QALYs, all ICERs fell well above the 2014 NICE threshold for cost-effectiveness (24,800€). Overall, the model was sensitive to changes in drug prices. Starting with UST potentially saves 41.7€ million over starting with ADA and 318€ million over starting with INF in the 17,000 patients eligible for biologicals. In Russia, the cost-effective approach for patients with moderate-to-severe PsA that failed DMARDs is to initiate biologic therapy with UST, use ADA as second line and INF as third line.

Background Management of chronic incurable diseases such as chronic obstructive pulmonary disease (COPD) and asthma is difficult. Incorporation of patient preferences is widely encouraged. Purpose To summarize original research articles determining patient preference in moderate-to-severe disease. Methods Acceptable articles consisted of original research determining preferences for any aspect of care in patients with COPD/asthma. The target population included those with severe disease; however, articles were accepted if they separated outcomes by severity or if the majority had at least moderate-to-severe disease. We also accepted simulation research based on scenarios describing situations involving moderate-to-severe disease that elicited preferences. Two reviewers searched Medline and Embase for articles published from the date of inception of the databases until the end of November 2014, with differences resolved through consensus discussion. Data were tabulated and analyzed descriptively. Results About 478 articles identified, 448 were rejected and 30 analyzed. There were 25 on COPD and five on asthma. Themes identified as most important in COPD were symptom relief (dyspnea/breathlessness), a positive patient–physician relationship, quality-of-life impairments, and information availability. Patients strongly preferred sponsors’ inhalers. At end-of-life, 69% preferred receiving CPR, 70% wanted noninvasive, and 58% invasive mechanical intervention. While patients with asthma preferred treatments that increased symptom-free days, they were willing to trade days without symptoms for a reduction in adverse events and greater convenience. Asthma patients were willing to pay for waking up once and not needing their inhaler over waking up once overnight and needing their inhaler. Conclusion Few studies have examined patient preference in these diseases. More research is needed to fill in knowledge gaps.

Background:Atypical long-acting injectable (LAI) antipsychotics are increasingly available for treating chronic schizophrenia in patients chronically non-adherent to prescribed regimens. Few economic studies have compared these products.Purpose:To determine the cost-effectiveness of aripiprazole (ARI-LAI), paliperidone (PP-LAI), olanzapine (OLZ-LAI), and risperidone (RIS-LAI) in patients with chronic schizophrenia in Finland.Methods:A 1-year decision tree model was adapted with guidance from an expert panel. Patients started hospitalized in relapse; those who responded continued treatment, others were switched to secondary drugs, then clozapine in the event of 2nd line failure. Rates of adherence, stable disease, relapse, and hospitalization were taken from pivotal trials, and utilities from published research. Included were direct costs paid by the Finnish Ministry of Health, in 2015 euros. Outcomes included quality-adjusted life-years (QALYs), hospitalization rates, and rates of relapse not requiring hospitalization. Model robustness was assessed using a series of 1-way and multivariate sensitivity analyses.Results:Expected costs were lowest for PP-LAI at 41,148(sic), followed by 41,543(sic) for ARI-LAI, 42,067(sic) for RIS-LAI and 45,406(sic) for OLZ-LAI. Respective QALYs were 0.683, 0.671, 0.666, and 0.672. Re-hospitalization rates and non-admitted relapses were 23.6% and 3.9% for PP-LAI, 28.5% and 4.1% for ARI-LAI, 28.8% and 5.0% for RIS-LAI, 28.3% and 5.2% for OLZ-LAI. PP-LAI treatment was associated with the most days with stable disease (132.0), followed by OLZ-LAI (125.5), ARI-LAI (122.6), and RIS-LAI (114.4). Sensitive inputs between PP-LAI and ARI-LAI included rates of adherence, dropouts, and relapses plus drug prices; dropout and relapse rates for RIS-LAI; OLZ-LAI results were insensitive. In probability sensitivity analyses, PP-LAI dominated ARI-LAI in 75.8% of the 10,000 iterations, RIS-LAI in 83.1% and OLZ-LAI in 95.7%.Conclusions:PP-LAI dominated the other atypicals. It appears to be the preferred option for treating chronic relapsing schizophrenia.

Background:Asthma and chronic obstructive pulmonary disease (COPD) are incurable diseases that impact quality-oflife.Objective:To summarize original research articles that measured or utilized preference-based utilities or disutilities according to disease severity.Methods:Medline and Embase were searched from inception until the end of November 2014. Two reviewers independently searched the literature with differences settled through discussion. Data extracted included utility scores as determined in original research categorized according to disease severity as well as disutilities associated with exacerbations or comorbidities. Data were tabulated and analyzed descriptively.Results:In total, 862 articles were identified, 790 were rejected, and 69 analyzed. There were 44 dealing with COPD and 25 with asthma. Average utilities determined by research were 0.828 +/- 0.062, 0.765 +/- 0.090, 0.711 +/- 0.120, and 0.607 +/- 0.120 for mild, moderate, severe, and very severe COPD, respectively. Utilities used in economic analyses were 0.866 +/- 0.038, 0.770 +/- 0.024, 0.739 +/- 0.045, and 0.596 +/- 0.075, respectively. Disutilities (annual) ranged from 0.002-0.378; major and minor exacerbations had respective disutilities of 0.287 and 0.108. For asthma patients, utilities were for 0.86 +/- 0.32, 0.83 +/- 0.065, and 0.74 +/- 0.029, for mild, moderate, and severe disease, respectively.Conclusions:Utilities have been summarized according to severity category of asthma and COPD. These values should be useful for researchers undertaking economic analyses of these diseases.

Our objective was to rigorously evaluate the impact of an antimicrobial stewardship audit-and-feedback intervention, via a stepped-wedge randomized trial. An effective intensive care unit (ICU) audit-and-feedback program was rolled out to 6 non-ICU services in a randomized sequence. The primary outcome was targeted antimicrobial utilization, using a negative binomial regression model to assess the impact of the intervention while accounting for secular and seasonal trends. The intervention was successfully transitioned, with high volumes of orders reviewed, suggestions made, and recommendations accepted. Among patients meeting stewardship review criteria, the intervention was associated with a large reduction in targeted antimicrobial utilization (-21%, P = .004); however, there was no significant change in targeted antibiotic use among all admitted patients (-1.2%, P = .9), and no reductions in overall costs and microbiologic outcomes. An ICU day 3 audit-and-feedback program can be successfully expanded hospital-wide, but broader benefits on non-ICU wards may require interventions earlier in the course of treatment.