Adverse Outcomes, Healthcare Resource Utilization, and Costs Associated with Systemic Corticosteroid use Among Adults with Systemic Lupus Erythematosus in the UK.

INTRODUCTION: This analysis was conducted to assess the incidence of adverse clinical outcomes, healthcare resource use (HCRU), and the costs associated with systemic corticosteroid (SCS) use in adults with systemic lupus erythematosus (SLE) in the UK. METHODS: We identified incident SLE cases using the Clinical Practice Research Datalink GOLD, Hospital Episode Statistics-linked healthcare, and Office for National Statistics mortality databases from January 1, 2005, to June 30, 2019. Adverse clinical outcomes, HCRU, and costs were captured for patients with and without prescribed SCS. RESULTS: Of 715 patients, 301 (42%) had initiated SCS use (mean [standard deviation (SD)] 3.2 [6.0] mg/day) and 414 (58%) had no recorded SCS use post-SLE diagnosis. Cumulative incidence of any adverse clinical outcome over 10-year follow-up was 50% (SCS group) and 22% (non-SCS group), with osteoporosis diagnosis/fracture most frequently reported. SCS exposure in the past 90 days was associated with an adjusted hazard ratio of 2.41 (95% confidence interval 1.77-3.26) for any adverse clinical outcome, with increased hazard for osteoporosis diagnosis/fracture (5.26, 3.61-7.65) and myocardial infarction (4.52, 1.16-17.71). Compared to low-dose SCS (< 7.5 mg/day), patients on high-dose SCS (≥ 7.5 mg/day) had increased hazard for myocardial infarction (14.93, 2.71-82.31), heart failure (9.32, 2.45-35.43), osteoporosis diagnosis/fracture (5.14, 2.82-9.37), and type 2 diabetes (4.02 1.13-14.27). Each additional year of SCS use was associated with increased hazard for any adverse clinical outcome (1.15, 1.05-1.27). HCRU and costs were greater for SCS users than non-SCS users. CONCLUSIONS: Among patients with SLE, there is a higher burden of adverse clinical outcomes and greater HCRU in SCS versus non-SCS users.

Healthcare Resource Use and Costs Associated with Organ Damage in Newly Diagnosed Adults with Systemic Lupus Erythematosus in the UK.

INTRODUCTION: This analysis compared healthcare resource use (HCRU) and costs associated with incident organ damage in a cohort of adult patients with systemic lupus erythematosus (SLE). METHODS: Incident SLE cases were identified (Clinical Practice Research Datalink [CPRD] and Hospital Episode Statistics-linked healthcare databases; January 1, 2005-June 30, 2019). Annual incidence of 13 organ damage domains was calculated from SLE diagnosis through follow-up. Annualized HCRU and costs were compared between organ damage and non-organ damage patient groups using generalized estimating equations. RESULTS: A total of 936 patients met the inclusion criteria for SLE. Mean age was 48.0 (standard deviation [SD] 15.7) years and 88% were female. Over a median follow-up period of 4.3 (interquartile range [IQR] 1.9-7.0) years, 59% (315/533) had evidence of post-SLE diagnosis incident organ damage (≥ 1 type), which was greatest for musculoskeletal (146/819 [18%]), cardiovascular (149/842 [18%]), and skin (148/856 [17%]) domains. Patients with organ damage had greater resource use for all organ systems, excluding gonadal, versus those without it. Overall, mean (SD) annualized all-cause HCRU was greater in patients with organ damage versus those without it (inpatient, 1.0 versus 0.2; outpatient, 7.3 versus 3.5; accident and emergency, 0.5 versus 0.2 days; primary care contacts, 28.7 versus 16.5; prescription medications, 62.3 versus 22.9). Adjusted mean annualized all-cause costs were significantly greater in both post- and pre-organ damage index periods for patients with organ damage versus those without it (all P < 0.05, excluding gonadal). Overall organ damage was associated with significantly increased adjusted mean annualized per-patient cost (£4442 greater [P < 0.0001]) ranging between £2709 and £7150 greater depending on the organ damage type. CONCLUSION: Organ damage was associated with higher HCRU and healthcare costs, before and after SLE diagnosis. More effective SLE management may slow disease progression, prevent organ damage onset, improve clinical outcomes, and reduce healthcare costs.

Reducing carbon footprint by switching to reusable soft-mist inhalers.

Objective: Inhalation therapy is the cornerstone of COPD, together with non-pharmacological treatments. Long-acting muscarinic antagonists (LAMAs), alone or in combination with long-acting ß-agonists (LABAs), are commonly used. Pressurised metered-dose inhalers (pMDIs), dry powder inhalers (DPIs) and soft-mist inhalers (SMIs) are used, each with different carbon footprints. This study aimed to assess the carbon footprint of hypothetically replacing LAMA or LAMA/LABA inhalers with an SMI, Respimat Reusable, within the same therapeutic class. Methods: An environmental impact model was established to assess the change in carbon footprint of replacing pMDIs/DPIs with Respimat Reusable within the same therapeutic class (LAMA or LAMA/LABA) across 12 European countries and the USA over 5 years. Inhaler use for country and disease-specific populations was derived from international prescribing data and the associated carbon footprint (CO2 equivalents (CO2e)) was identified from published sources. Results: Over 5 years and across all countries, replacing LAMA inhalers with Spiriva Respimat Reusable reduced CO2e emissions by 13.3-50.9%, saving 93-6228 tonnes of CO2e in the different countries studied. Replacing LAMA/LABA inhalers with Spiolto Respimat Reusable reduced CO2e emissions by 9.5-92.6%, saving 31-50 843 tonnes of CO2e. In scenario analyses, which included total replacement of DPIs/pMDIs, consistent CO2e savings were estimated. Sensitivity analyses showed that results were sensitive to changes in several parameters including varying assumptions around reusability of inhalers and potential CO2e impact. Conclusion: Replacement of pMDIs and DPIs with Respimat Reusable within the same therapeutic class would result in substantial reductions in CO2e emissions.

Costs and Clinical Consequences of Compliance with COPD GOLD Recommendations or National Guidelines Compared with Current Clinical Practice in Belgium, Germany, Sweden, and the United States.

Purpose: The objective of this study was to assess the clinical and cost benefits of treating patients with chronic obstructive pulmonary disease (COPD) according to global and national guidelines compared to real-life clinical practice in the United States and three European countries (Belgium, Germany, Sweden). Patients and Methods: A cost-consequence model was developed to compare current prescribing patterns with two alternative scenarios, the first aligned with the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2022) recommendations and the second with national guidelines. Costs and clinical outcomes were modeled for these alternative scenarios over a time horizon of one year, based on real-world evidence and health insurance data. Results: Current clinical practice in each of the countries was inconsistent with published recommendations. A redistribution to prescribing patterns according to global and national recommendations led to a substantial decrease in the use of inhaled corticosteroid (ICS) containing therapies of more than 80% and 44%, respectively. There was a reduced incidence of up to 16% of mild-to-moderate pneumonia and up to 29% of severe pneumonia. Exacerbations decreased across all countries apart from Sweden, where a small increase in the rate of exacerbations was due to the redistribution of some patients currently undergoing inhaled triple therapy to non-ICS-containing therapies. Adapting treatment to recommendations could provide potential cost savings of up to 13% in estimated annual direct costs, resulting predominantly from the reduction in cost of healthcare resource use, including hospitalization associated with treating incident pneumonia, particularly severe pneumonia. Cost savings for prevalent adult patients with COPD on long-acting inhaler therapy ranged from €31 to €675 per patient per year. Conclusion: Redistribution of COPD patients from current clinical practice to treatment according to published recommendations would provide clinical benefits and substantial cost savings.

The Burden of Progressive-Fibrosing Interstitial Lung Diseases.

Despite conventional treatment, a proportion of interstitial lung disease (ILD) patients develop a progressive phenotype known as "fibrosing ILD with a progressive phenotype" (PF-ILD), characterized by worsening respiratory symptoms, decline in lung function, and early mortality. This review describes the epidemiology, and the humanistic and economic burden of PF-ILDs other than idiopathic pulmonary fibrosis (non-IPF PF-ILD). A structured review of the literature was conducted, using predefined search strategies in Ovid MEDLINE and EMBASE, and supplemented with gray literature searches. The search identified 3,002 unique articles and an additional 3 sources were included from the gray literature; 21 publications were included. The estimated prevalence of non-IPF PF-ILD ranges from 6.9 to 70.3/100,000 persons and the estimated incidence from 2.1 to 32.6/100,000 person-years. Limited evidence demonstrates that PF-ILD has a significant impact on patients' quality of life, affecting their daily lives, psychological well-being, careers, and relationships. PF-ILD is also associated with significant economic burden, demonstrating higher healthcare resource use and direct costs compared with the non-progressive phenotype, and indirect costs, which include job losses. This review indicates that PF-ILD places a considerable humanistic burden on both patients and caregivers, and a substantial economic burden on healthcare systems, patients, and society.

Cost-consequence analysis of COPD treatment according to NICE and GOLD recommendations compared with current clinical practice in the UK.

OBJECTIVES: The objective of this study was to model the clinical and economic impact of adapting current clinical practice in the management of patients with chronic obstructive pulmonary disease (COPD) to treatment according to national and international guideline recommendations. DESIGN: Treatment mapping was undertaken to hypothetically redistribute patients from current clinical practice, representing actual prescribing patterns in the UK, to an alternative recommendation-based treatment scenario, representing prescribing in accordance with either National Institute for Health and Care Excellence (NICE) guidance [NG115] or Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020 strategy. SETTING: Primary care practices in the UK (1-year time horizon). PARTICIPANTS: Adults with COPD undergoing long-acting inhaler maintenance therapy in the UK (N=1 067,531). INTERVENTIONS: Inhaler maintenance therapy. OUTCOME MEASURES: Costs and clinical outcomes (type of treatment, rates of moderate and/or severe exacerbations, and mild-to-moderate and/or severe pneumonia events) were modelled for the two alternative pathways. RESULTS: Compared with current clinical practice, treating patients according to NICE guidance resulted in an estimated annual reduction in expenditure of £46.9 million, and an estimated annual reduction in expenditure of over £43.7 million when patients were treated according to GOLD 2020 strategy. Total cost savings of up to 8% annually could be achieved by treatment of patients according to either of these recommendations. Cost savings arose from a reduction in the rates of pneumonia, with an associated decrease in costs associated with antibiotic use and hospitalisation. Savings were achieved overall despite a small increase in the rate of exacerbations due to the redistribution of certain patients currently undergoing triple inhaled therapy to therapies not containing inhaled corticosteroids. CONCLUSION: Redistribution of patients with COPD from current clinical practice to treatment according to published recommendations would provide substantial cost savings over the first year.

Health-care utilization and costs in adults with systemic lupus erythematosus in the United Kingdom: a real-world observational retrospective cohort analysis.

OBJECTIVE: The aim was to describe direct health-care costs for adults with SLE in the UK over time and by disease severity and encounter type. METHODS: Patients aged ≥18 years with SLE were identified using the linked Clinical Practice Research Datalink-Hospital Episode Statistics database from January 2005 to December 2017. Patients were classified as having mild, moderate or severe disease using an adapted claims-based algorithm based on prescriptions and co-morbid conditions. We estimated all-cause health-care costs and incremental costs associated with each year of follow-up compared with a baseline year, adjusting for age, sex, disease severity and co-morbid conditions (2017 UK pounds). RESULTS: We identified 802 patients; 369 (46.0%) with mild, 345 (43.0%) moderate and 88 (11.0%) severe disease. The mean all-cause cost increased in the 3 years before diagnosis, peaked in the first year after diagnosis and remained high. The adjusted total mean annual increase in costs per patient was £4476 (95% CI: £3809, £5143) greater in the year of diagnosis compared with the baseline year (P < 0.0001). The increase in costs per year was 4.7- and 1.6-fold higher among patients with severe SLE compared with those with mild and moderate SLE, respectively. Primary care utilization was the leading component of costs during the first year after diagnosis. CONCLUSION: The health-care costs for patients with SLE in the UK are substantial, remain high after diagnosis and increase with increasing severity. Future research should assess whether earlier diagnosis and treatment might reduce disease severity and associated high health-care costs.

Risk of malignancy in patients with systemic lupus erythematosus: Systematic review and meta-analysis.

BACKGROUND: Malignancy is a potential comorbidity in patients with systemic lupus erythematosus (SLE). However, risk by malignancy type remains to be fully elucidated. We evaluated the risk of malignancy type in SLE patients in a systematic review and meta-analysis. METHODS: MEDLINE and EMBASE were searched from inception to July 2018 to identify observational studies that evaluated malignancy risk in adult SLE patients compared with the general population. Random-effects models were used to calculate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Heterogeneity was quantified using the I2 test. FINDINGS: Forty-one studies reporting on 40 malignancies (one overall, 39 site-specific) were included in the meta-analysis. The pooled RR for all malignancies from 3694 events across 80 833 patients was 1.18 (95% CI: 1.00-1.38). The risk of 24 site-specific malignancies (62%) was increased in SLE patients. For malignancies with ≥6 studies, non-Hodgkin lymphoma and Hodgkin lymphoma risk was increased >3-fold; myeloma and liver >2-fold; cervical, lung, bladder, and thyroid ≥1.5-fold; stomach and brain >1.3-fold. The risk of four malignancies (breast, uterine, melanoma, prostate) was decreased, whereas risk of 11 other malignancies did not differ between SLE patients and the general population. Heterogeneity ranged between 0% and 96%, and 63% were non-significant. INTERPRETATION: The risk of overall and some site-specific malignancies is increased in SLE compared with the general population. However, the risk for some site-specific malignancies is decreased or did not differ. Further examination of risk profiles and SLE patient phenotypes may support guidelines aimed at reducing malignancy risk. FUNDING: AstraZeneca. SYSTEMATIC REVIEW REGISTRATION: PROSPERO number: CRD42018110433.

Disease severity, flares and treatment patterns in adults with systemic lupus erythematosus in the UK: a real-world observational retrospective cohort analysis.

OBJECTIVES: The aim was to characterize disease severity, clinical manifestations, treatment patterns and flares in a longitudinal cohort of adults with SLE in the UK. METHODS: Adults with SLE were identified in the Clinical Practice Research Datalink-Hospital Episode Statistics database (1 January 2005-31 December 2017). Patients were required to have ≥12 months of data before and after the index date (earliest SLE diagnosis date available). SLE disease severity and flares were classified using adapted claims-based algorithms, which are based on SLE-related conditions, medications and health-service use. RESULTS: Of 802 patients, 369 had mild, 345 moderate and 88 severe SLE at baseline. A total of 692 initiated treatment in the first year after diagnosis. Five hundred and fifty-seven received antimalarials, 203 immunosuppressants and 416 oral CSs. Information on biologic use in hospitals was unavailable. The mean (S.d.) time to initiating any medication was 177 (385.3) days. The median time to first flare was 63 days (95% CI: 57, 71). At least one flare was experienced by 750 of 802 patients during follow-up; the first flare was mild for 549 of 750, moderate for 116 of 750 and severe for 85 of 750. The mean (S.d.) annual overall flare rate (year 1) was 3.5 (2.5). A shorter median time to first flare was significantly associated with moderate/severe disease (P < 0.001) and clinical manifestations (P < 0.001). CONCLUSION: Our findings suggest some delay in the initiation of SLE treatment. Most patients experience a flare within 2 months of diagnosis. Early treatment might delay or reduce the severity of the first SLE flare and might translate to slower disease progression, lower accrual of organ damage and better outcomes.

Impact of health technology assessment on prescribing patterns of inhaled fixed-dose combination triple therapy in chronic obstructive pulmonary disease.

Background: Evidence suggests that triple therapy for patients with chronic obstructive pulmonary disease (COPD) is being used in a broader range of patients than recommended by guidelines, which may have health and cost implications. Objective: To explore the relationship between national health technology assessment (HTA) agency appraisals and market penetration of two fixed-dose combination (FDC) triple therapies. Study design: HTAs from Q3 2017 to Q1 2020 from 10 countries were evaluated. Intervention: Glycopyrronium bromide/formoterol fumarate/beclomethasone (Trimbow®) and umeclidinium/vilanterol/fluticasone furoate (Trelegy™ Ellipta®). Main outcome measure: HTA restrictions and prescribing rates (days of therapy). Results: Seven countries (70%) imposed restrictions on use including prescription only for patients stable on free-combination triple therapy or not controlled on dual therapy, requirement of a specialist prescription or therapeutic plan, prescription only for patients with severe COPD, and use as second-line therapy or later. In general, countries that have imposed restrictions on the use of FDC triple therapies have seen a lower than average uptake. Conclusion: Payer guidance on prescribing FDC triple therapy may potentially support more appropriate prescribing in line with clinical guidelines. It is important for payers to consider which restrictions would ensure the most efficient use of scarce resources.

The risk of infections in adult patients with systemic lupus erythematosus: systematic review and meta-analysis.

OBJECTIVES: We conducted a systematic review and meta-analysis to determine the magnitude of infection risk in patients with SLE and evaluate the effect of general and SLE-related factors on infection risk. METHODS: We searched MEDLINE and Embase from inception to July 2018, screening for observational studies that evaluated infection risk in patients with SLE compared with the general population/healthy controls. Outcomes of interest included overall severe infection, herpes zoster infection/reactivation, opportunistic infections, pneumonia and tuberculosis. Random-effects models were used to calculate pooled risk ratios (RRs) for each type of infection. Sensitivity analysis assessed the impact of removing studies with high risk of bias. RESULTS: Eleven retrospective or prospective cohort studies were included in the meta-analysis: overall severe infection (n = 4), pneumonia (n = 6), tuberculosis (n = 3) and herpes zoster (n = 2). Pooled RRs for overall severe infection significantly increased for patients with SLE compared with the general population/healthy controls [RR 2.96 (95% CI 1.28, 6.83)]. Pooled RRs for pneumonia, herpes zoster and tuberculosis showed significantly increased risk compared with the general population/healthy controls [RR 2.58 (1.80, 3.70), 2.50 (2.36, 2.65) and 6.11 (3.61, 10.33), respectively]. Heterogeneity and evidence of publication bias were present for all analyses, except herpes zoster. Sensitivity analyses confirmed robustness of the results. CONCLUSION: Patients with SLE have significantly higher risk of infection compared with the general population/healthy controls. Efforts to strengthen strategies aimed at preventing infections in SLE are needed. PROTOCOL REGISTRATION: PROSPERO number: CRD42018109425.

Systemic lupus erythematosus; stroke and myocardial infarction risk: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the risk of stroke and myocardial infarction (MI) in adult patients with systemic lupus erythematosus (SLE) through a systematic review and meta-analysis. METHODS: We searched MEDLINE and EMBASE from inception to May 2020 to identify observational studies (cohort and cross-sectional) that evaluated risk of stroke and MI in adult patients with SLE compared with the general population or healthy controls. Studies were included if they reported effect-size estimates that could be used for calculating pooled-effect estimates. Random-effects models were used to calculate pooled risk ratios (RRs) and 95% CIs for stroke and MI. Heterogeneity quantified by the I2 test and sensitivity analyses assessed bias. RESULTS: In total, 26 studies were included in this meta-analysis: 14, 5 and 7 studies on stroke, MI and both stroke and MI, respectively. The pooled RR for ischaemic stroke was 2.18 (95% CI 1.78 to 2.67; I2 75%), intracerebral haemorrhage 1.84 (95% CI 1.16 to 2.90; I2 67%), subarachnoid haemorrhage 1.95 (95% CI 0.69 to 5.52; I2 94%), composite stroke 2.13 (95% CI 1.73 to 2.61; I2 88%) and MI 2.99 (95% CI 2.34 to 3.82; I2 85%). There was no evidence for publication bias, and sensitivity analyses confirmed the robustness of the results. CONCLUSIONS: Overall, patients with SLE were identified to have a twofold to threefold higher risk of stroke and MI. Future research on the interaction between known SLE-specific modifiable risk factors and risk of stroke and MI to support development of prevention and treatment strategies are needed. PROSPERO REGISTRATION NUMBER: CRD42018098690.

Single-inhaler triple therapy in patients with chronic obstructive pulmonary disease: a systematic review.

BACKGROUND: Guidelines recommend that treatment with a long-acting ß2 agonist (LABA), a long-acting muscarinic antagonist (LAMA), and inhaled corticosteroids (ICS), i.e. triple therapy, is reserved for a select group of symptomatic patients with chronic obstructive pulmonary disease (COPD) who continue to exacerbate despite treatment with dual therapy (LABA/LAMA). A number of single-inhaler triple therapies are now available and important clinical questions remain over their role in the patient pathway. We compared the efficacy and safety of single-inhaler triple therapy to assess the magnitude of benefit and to identify patients with the best risk-benefit profile for treatment. We also evaluated and compared study designs and population characteristics to assess the strength of the evidence base. METHODS: We conducted a systematic search, from inception to December 2018, of randomised controlled trials (RCTs) of single-inhaler triple therapy in patients with COPD. The primary outcome was the annual rate of moderate and severe exacerbations. RESULTS: We identified 523 records, of which 15 reports/abstracts from six RCTs were included. Triple therapy resulted in the reduction of the annual rate of moderate or severe exacerbations in the range of 15-52% compared with LAMA/LABA, 15-35% compared to LABA/ICS and 20% compared to LAMA. The patient-based number needed to treat for the moderate or severe exacerbation outcome ranged between approximately 25-50 (preventing one patient from having an event) and the event-based number needed to treat of around 3-11 (preventing one event). The absolute benefit appeared to be greater in patients with higher eosinophil counts or historical frequency of exacerbations and ex-smokers. In the largest study, there was a significantly higher incidence of pneumonia in the triple therapy arm. There were important differences in study designs and populations impacting the interpretation of the results and indicating there would be significant heterogeneity in cross-trial comparisons. CONCLUSION: The decision to prescribe triple therapy should consider patient phenotype, magnitude of benefit and increased risk of adverse events. Future research on specific patient phenotype thresholds that can support treatment and funding decisions is now required from well-designed, robust, clinical trials. TRIAL REGISTRATION: PROSPERO #CRD42018102125 .

Transparency in Decision Modelling: What, Why, Who and How?

Transparency in decision modelling is an evolving concept. Recently, discussion has moved from reporting standards to open-source implementation of decision analytic models. However, in the debate about the supposed advantages and disadvantages of greater transparency, there is a lack of definition. The purpose of this article is not to present a case for or against transparency, but rather to provide a more nuanced understanding of what transparency means in the context of decision modelling and how it could be addressed. To this end, we review and summarise the discourse to date, drawing on our collective experience. We outline a taxonomy of the different manifestations of transparency, including reporting standards, reference models, collaboration, model registration, peer review and open-source modelling. Further, we map out the role and incentives for the various stakeholders, including industry, research organisations, publishers and decision makers. We outline the anticipated advantages and disadvantages of greater transparency with respect to each manifestation, as well as the perceived barriers and facilitators to greater transparency. These are considered with respect to the different stakeholders and with reference to issues including intellectual property, legality, standards, quality assurance, code integrity, health technology assessment processes, incentives, funding, software, access and deployment options, data protection and stakeholder engagement. For each manifestation of transparency, we discuss the 'what', 'why', 'who' and 'how'. Specifically, their meaning, why the community might (or might not) wish to embrace them, whose engagement as stakeholders is required and how relevant objectives might be realised. We identify current initiatives aimed to improve transparency to exemplify efforts in current practice and for the future.

Cost-Effectiveness of Take-Home Naloxone for the Prevention of Overdose Fatalities among Heroin Users in the United Kingdom.

BACKGROUND: Heroin overdose is a major cause of premature death. Naloxone is an opioid antagonist that is effective for the reversal of heroin overdose in emergency situations and can be used by nonmedical responders. OBJECTIVE: Our aim was to assess the cost-effectiveness of distributing naloxone to adults at risk of heroin overdose for use by nonmedical responders compared with no naloxone distribution in a European healthcare setting (United Kingdom). METHODS: A Markov model with an integrated decision tree was developed based on an existing model, using UK data where available. We evaluated an intramuscular naloxone distribution reaching 30% of heroin users. Costs and effects were evaluated over a lifetime and discounted at 3.5%. The results were assessed using deterministic and probabilistic sensitivity analyses. RESULTS: The model estimated that distribution of intramuscular naloxone, would decrease overdose deaths by around 6.6%. In a population of 200,000 heroin users this equates to the prevention of 2,500 premature deaths at an incremental cost per quality-adjusted life year (QALY) gained of £899. The sensitivity analyses confirmed the robustness of the results. CONCLUSIONS: Our evaluation suggests that the distribution of take-home naloxone decreased overdose deaths by around 6.6% and was cost-effective with an incremental cost per QALY gained well below a £20,000 willingness-to-pay threshold set by UK decision-makers. The model code has been made available to aid future research. Further study is warranted on the impact of different formulations of naloxone on cost-effectiveness and the impact take-home naloxone has on the wider society.

The importance of the cement spacer for proper crown seating Erratum.

Marginal integrity is important for the longevity of a restoration. An increase in the marginal discrepancy after cementation contributes adversely to the longevity of a restoration. In the past, the preferred method to overcome this discrepancy was to create internal space for the cement by using a number of coats of a die-spacing material. In the digital age, however, this method is no longer the only option. Currently, an amount of die spacer is engineered into the computer program and forms part of the milling process. The present study attempted to identify the optimal setting of the Spacer parameter that a) is necessary for the complete cementation of a Cerec milled all-ceramic crown, and b) does not compromise the strength of the crown postcementation.

A systematic review of health economic models of opioid agonist therapies in maintenance treatment of non-prescription opioid dependence.

BACKGROUND: Opioid dependence is a chronic condition with substantial health, economic and social costs. The study objective was to conduct a systematic review of published health-economic models of opioid agonist therapy for non-prescription opioid dependence, to review the different modelling approaches identified, and to inform future modelling studies. METHODS: Literature searches were conducted in March 2015 in eight electronic databases, supplemented by hand-searching reference lists and searches on six National Health Technology Assessment Agency websites. Studies were included if they: investigated populations that were dependent on non-prescription opioids and were receiving opioid agonist or maintenance therapy; compared any pharmacological maintenance intervention with any other maintenance regimen (including placebo or no treatment); and were health-economic models of any type. RESULTS: A total of 18 unique models were included. These used a range of modelling approaches, including Markov models (n = 4), decision tree with Monte Carlo simulations (n = 3), decision analysis (n = 3), dynamic transmission models (n = 3), decision tree (n = 1), cohort simulation (n = 1), Bayesian (n = 1), and Monte Carlo simulations (n = 2). Time horizons ranged from 6 months to lifetime. The most common evaluation was cost-utility analysis reporting cost per quality-adjusted life-year (n = 11), followed by cost-effectiveness analysis (n = 4), budget-impact analysis/cost comparison (n = 2) and cost-benefit analysis (n = 1). Most studies took the healthcare provider's perspective. Only a few models included some wider societal costs, such as productivity loss or costs of drug-related crime, disorder and antisocial behaviour. Costs to individuals and impacts on family and social networks were not included in any model. CONCLUSION: A relatively small number of studies of varying quality were found. Strengths and weaknesses relating to model structure, inputs and approach were identified across all the studies. There was no indication of a single standard emerging as a preferred approach. Most studies omitted societal costs, an important issue since the implications of drug abuse extend widely beyond healthcare services. Nevertheless, elements from previous models could together form a framework for future economic evaluations in opioid agonist therapy including all relevant costs and outcomes. This could more adequately support decision-making and policy development for treatment of non-prescription opioid dependence.

Comparing comprehensive care and departmental clinical education models: students' perceptions at the University of Tennessee College of Dentistry.

In summer 2012, the University of Tennessee Health Science Center College of Dentistry transitioned from a departmental clinical education model to a comprehensive care/group leader model. The aim of this study was to investigate the perspectives of the fourth-year class of dental students who, because the transition took place during their training, had experienced treating patients under both educational models. To achieve this objective, a questionnaire was designed to assess the students' opinions on the efficiency of their effort, availability of specialty faculty, stress, collaboration with classmates, and availability of exposure to different practice styles and techniques under the two systems. The students were also given an opportunity to provide open-ended feedback on the shortcomings and advantages of the systems. The Class of 2013 had 81 students, 55 of whom participated in the survey for a response rate of 67.9%. The majority (86%) of the respondents preferred the comprehensive care model and reported feeling that, in it, they were able to accomplish more comprehensive dentistry with greater consistency of supervision from faculty in a more patient-centered environment than in the departmental model. However, 56 percent considered having the same group leader for two years a disadvantage and recommended rotation of at least one group leader every six months. The results of this survey can help this college and other dental schools that are seeking to optimize their educational model to best serve students' educational experience and the dental needs of their patient population.

The economic and quality-of-life burden of Crohn's disease in Europe and the United States, 2000 to 2013: a systematic review.

BACKGROUND: Crohn's disease (CD) is associated with a substantial healthcare burden that affects the patient, healthcare systems and society in general. AIM: To provide a systematic evaluation of published data relating to the economic and health-related quality-of-life (HRQoL) burden of CD in selected European countries (Germany, France, UK, Italy, Spain) and the USA since 2000. METHODS: We undertook a systematic review of publications relating to CD, its economic burden and impact on HRQoL. Research questions focused on the disease costs from a societal perspective and HRQoL burden in adults and pediatric/adolescent patients according to disease stage/severity. Total, direct and indirect costs were identified, as well as the impact of CD on HRQoL measured using both generic and disease-specific instruments. RESULTS: Overall, 61 publications met the research criteria (38 on costs, 23 on HRQoL). CD in the USA and Europe together was associated with annual total costs of nearly 30 billion, more than half due to indirect costs. HRQoL was consistently and statistically significantly lower among CD patients compared with normal populations, due to physical, emotional and social effects. CONCLUSIONS: CD is a global health problem with high societal costs and substantial HRQoL burden. High-value care pathways including cost-effective therapies will help to induce and maintain remission, reduce complications of disease and improve HRQoL.

Large-scale, prospective, observational studies in patients with psoriasis and psoriatic arthritis: A systematic and critical review.

BACKGROUND: Observational studies, if conducted appropriately, play an important role in the decision-making process providing invaluable information on effectiveness, patient-reported outcomes and costs in a real-world environment. We conducted a systematic review of large-scale, prospective, cohort studies with the aim of (a) summarising design characteristics, the interventions or aspects of the disease studied and the outcomes measured and (b) investigating methodological quality. METHODS: We included prospective, cohort studies which included at least 100 adults with psoriasis or psoriatic arthritis. Studies were identified through searches in electronic databases (Pubmed, Medline, Cochrane library, Centre for Reviews and Dissemination). Information on study characteristics were extracted and tabulated and quality assessment, using a checklist of 18 questions, was conducted. RESULTS: Thirty five papers covering 16 cohorts met the inclusion criteria. There were ten treatment-related studies, only two of which provided a comparison between treatments, and six non-treatment studies which examined a number of characteristics of the disease including mortality, morbidity, cost of illness and health-related quality of life. All studies included a clinical outcome measure and 11 included patient-reported outcomes, however only two studies reported information on patient utilities and two on costs. The quality of the assessed studies varied widely. Studies did well on a number of quality assessment questions including having clear objectives, documenting selection criteria, providing a representative sample, defining interventions/characteristics under study, defining and using appropriate outcomes, describing results clearly and using appropriate statistical tests. The quality assessment criteria least adhered to involved questions regarding sample size calculations, describing potential selection bias, defining and adjusting for confounders and losses to follow-up, and defining and describing a comparison group. CONCLUSION: The review highlights the need for well designed prospective observational studies on the effectiveness, patient-reported outcomes and economic impact of treatment regimes for patients with psoriasis and psoriatic arthritis in a real-world environment.