Nurses' preferences regarding MenACWY conjugate vaccines attributes: a discrete choice experiment in Spain.

OBJECTIVES: Immunisation against preventable diseases as meningitis is crucial from a public health perspective to face challenges posed by these infections. Nurses hold a great responsibility for these programs, which highlights the importance of understanding their preferences and needs to improve the success of campaigns. This study aimed to investigate nurses' preferences regarding Meningococcus A, C, W, and Y (MenACWY) conjugate vaccines commercialised in Spain. STUDY DESIGN: A national-level discrete choice experiment (DCE) was conducted. METHODS: A literature review and a focus group informed the DCE design. Six attributes were included: pharmaceutical form, coadministration evidence, shelf-life, package contents, single-doses per package, and package volume. Conditional logit models quantified preferences and relative importance (RI). RESULTS: Thirty experienced primary care nurses participated in this study. Evidence of coadministration with other vaccines was the most important attribute (RI = 43.78%), followed by package size (RI = 22.17%), pharmaceutical form (RI = 19.07%), and package content (RI = 11.80%). There was a preference for evidence of coadministration with routine vaccines (odds ratio [OR] = 2.579, 95% confidence interval [95%CI] = 2.210-3.002), smaller volumes (OR = 1.494, 95%CI = 1.264-1.767), liquid formulations (OR = 1.283, 95%CI = 1.108-1.486) and package contents including only vial/s (OR = 1.283, 95%CI = 1.108-1.486). No statistical evidence was found for the remaining attributes. CONCLUSIONS: Evidence of coadministration with routine vaccines, easy-to-store packages, and fully liquid formulations were drivers of nurses' preferences regarding MenACWY conjugate vaccines. These findings provide valuable insights for decision-makers to optimize current campaigns.

Systematic review of the evidence on the epidemiology of herpes zoster: incidence in the general population and specific subpopulations in Spain.

OBJECTIVES: Herpes zoster (HZ) is an important cause of morbidity around the world, especially among the adult population aged >50 years. STUDY DESIGN: A systematic review of the literature (up to October 31, 2016) was performed to identify available evidence on incidence of HZ in the general population and in a specific subpopulation in Spain. METHODS: PubMed and Embase databases were searched, combining the following search terms: 'herpes zoster', 'diabetes mellitus (DM)', 'chronic obstructive pulmonary disease (COPD)', 'chronic heart failure', 'mental disorders' and 'immunocompromised'. Supplements for local scientific congresses, non-indexed Spanish journals and official epidemiological reports, potentially HZ related, were also manually searched. The inclusion criteria were the following: English or Spanish publications reporting incidence of HZ in the Spanish general population and/or specific subpopulations. No restrictions were applied on the study design or population age. RESULTS: Among 269 references retrieved (48 PubMed, 148 Embase and 73 manual searching), 34 were finally included. Incidence of HZ in the general population ranged from 2.1 to 5.5/1000 person-years. HZ incidence ranged from 9.4 to 15.3/1000 patients with DM and from 11.0 to 11.4/1000 population with COPD or cardiovascular disease. In asthmatic patients, 6.9 HZ cases/1000 subjects were reported. The highest HZ incidence (1.3-400.0/1000 person-years) was in immunocompromised persons (10.0/1000 patients with cancer, 12.5/1000 patients with AIDS, from 5.0 to 240.0/1000 transplanted patients and from 6.6 to 27.0/1000 population with rheumatic diseases). Three studies estimated an increased risk of HZ in comparison with general population, for patients with DM (24%), COPD (39%) and COPD receiving inhaled corticosteroids (61%). CONCLUSIONS: The results suggest a high risk of HZ in certain age groups and specific subpopulations. This study could contribute to identify target age populations and at-risk groups if implementation of HZ vaccination programmes in Spain would be considered.

Understanding the reaction mechanism of the oxidative addition of ammonia by (PXP)Ir(i) complexes: the role of the X group.

An analysis of the electronic rearrangements for the oxidative addition of ammonia to a set of five representative (PXP)Ir pincer complexes (X = B, CH, O, N, SiH) is performed. We aim to understand the factors controlling the activation and reaction energies of this process by combining different theoretical strategies based on DFT calculations. Interestingly, complexes featuring higher activation barriers yield more exothermic reactions. The analysis of the reaction path using the bonding evolution theory shows that the main chemical events, N-H bond cleavage and Ir-H bond formation, take place before the transition structure is reached. Metal oxidation implies an electron density transfer from non-shared Ir pairs to the Ir-N bond. This decrement in the atomic charge of the metal provokes different effects in the ionic contribution of the Ir-X bonding depending on the nature of the X atom as shown by the interacting quantum atoms methodology.

Local plant responses to global problems: Dactylis glomerata responses to different traffic pollutants on roadsides.

The growing number of road vehicles is a major source of regional and global atmospheric pollution increasing concentrations of CO2 in the air, and levels of metals in air and soil. Nevertheless, the effects of these pollutants on plants growing at roadsides are poorly documented. We carried out an observational study of unmanipulated plants growing by the road, to identify the morpho-physiological responses in a perennial grass Dactylis glomerata. Firstly, we wanted to know the general effect of traffic intensity and ambient CO2 and its interactions on different plant traits. Accordingly, we analyzed the photosynthetic response by field A/Ci Response Curves, SLA, pigment pools, foliar nitrogen, carbohydrates and morphological traits in plants at three distances to the road. Secondly, we wanted to know if Dactylis glomerata plants can accumulate metals present on the roadside (Pb, Zn, Cu, and Sr) in their tissues and rhizosphere, and the effect of these metals on morphological traits. The MANCOVA whole model results shown: 1) a significant effect of road ambient CO2 concentration on morphological traits (not affected by traffic intensity, P interaction CO2 x traffic intensity>0.05), that was mainly driven by a significant negative relationship between the inflorescence number and ambient CO2; 2) a positive and significant relationship between ambient CO2 and the starch content in leaves (unaffected by traffic intensity); 3) a reduction in Jmax (electron transport rate) at high traffic intensity. These lines of evidences suggest a decreased photosynthetic capacity due to high traffic intensity and high levels of ambient CO2. In addition, Pb, Cu, Zn and Sr were detected in Dactylis glomerata tissues, and Cu accumulated in roots. Finally, we observed that Dactylis glomerata individuals growing at the roadside under high levels of CO2 and in the presence of metal pollutants, reduced their production of inflorescences.

Cost-effectiveness analysis of ledipasvir/sofosbuvir in patients with chronic hepatitis C: Treatment of patients with absence or mild fibrosis compared to patients with advanced fibrosis.

To evaluate the cost-effectiveness of ledipasvir/sofosbuvir (LDV/SOF) in treatment-naïve patients with chronic hepatitis C (CHC) genotype 1 (GT1) in the absence or mild fibrosis (F0-F1) versus advanced fibrosis (F2-F4), from the perspective of the Spanish Health System. A Markov model was developed to simulate disease progression, estimating costs and outcomes [life years gained (LYG) and quality-adjusted life years (QALY)] derived from starting with LDV/SOF in patients with F0-F1 compared with F2-F4. Therapy duration was 8 weeks in noncirrhotic patients with viral load <6 million IU/mL and 12 weeks in the remaining patients. Sustained virologic response rates were obtained from real-world cohort studies. Transition probabilities, utilities and direct costs were obtained from the literature. A 3% annual discount rate was applied to costs and outcomes. Sensitivity analyses were performed. LDV/SOF in F0-F1 patients was a dominant strategy, being more effective (19.85 LYG and 19.80 QALY) than beginning treatment in F2-F4 patients (18.63 LYG and 16.25 QALY), generating savings of €9228 per patient (€3661 due to disease management and monitoring). In a cohort of 1000 patients, LDV/SOF in F0-F1 patients decreased the number of cases of decompensated cirrhosis (93%), hepatocellular carcinoma (97%) and liver-related deaths (95%) and prevented 6 liver transplants compared to initiating LDV/SOF in F2-F4 patients. In CHC treatment-naïve GT1 patients, starting treatment with LDV/SOF in patients with F0-F1 compared to those with F2-F4 increases effectiveness by 1.22 LYG and 3.55 QALY gained and reduces disease burden and it is associated with cost savings.

Real-world cost-effectiveness of infliximab, etanercept and adalimumab in rheumatoid arthritis patients: results of the CREATE registry.

Biological drugs have proven efficacy and effectiveness in treatment of rheumatoid arthritis (RA), although none has been shown to be superior. Few studies have evaluated the cost-effectiveness of biological drugs in real-life clinical conditions. The objective of this study was to compare the cost-effectiveness of infliximab, etanercept and adalimumab in achieving clinical remission (DAS28 < 2.6) when used as initial biological therapy. Patients were diagnosed with RA who began treatment with infliximab, etanercept or adalimumab in the Reina Sofia Hospital (Cordoba, Spain) between January 1, 2007, and December 31, 2012. Effectiveness was measured as the percentage of patients who achieved clinical remission after 2 years. The cost analysis considered the use of direct health resources (perspective of the healthcare system). Cost-effectiveness was calculated by dividing the total mean cost of each treatment by the percentage of patients who achieved remission. One hundred and thirty patients were included: 55 with infliximab, 44 with adalimumab and 31 with etanercept. After 2 years, 45.2 % of patients with adalimumab achieved clinical remission, versus 29.1 % with infliximab (p = 0.133) and 22.7 % with etanercept (p = 0.040), with no differences between etanercept and infliximab (p = 0.475). The average total cost at 2 years was €29,858, €25,329 and €23,309 for adalimumab, infliximab and etanercept, respectively, while the mean cost (95 %CI) to achieve remission was €66,057 (48,038­84,076), €87,040 (78,496­95,584) and €102,683 (94,559­110,807), respectively. Adalimumab was more efficient than etanercept (p < 0.001) and infliximab (p = 0.026), with no differences between etanercept and infliximab (p = 0.086). Adalimumab was the most cost-effective treatment in achieving clinical remission in real-life clinical conditions in RA patients during the study period.

The Cost of Psoriasis and Psoriatic Arthritis in 5 European Countries: A Systematic Review. / Coste de la psoriasis y artritis psoriásica en cinco países de Europa: una revisión sistemática.

INTRODUCTION: While the introduction of biologics has improved the quality of life of patients with psoriasis and psoriatic arthritis, it may have increased the economic burden of these diseases. OBJECTIVE: To perform a systematic review of studies on the costs associated with managing and treating psoriasis and psoriatic arthritis in 5 European countries: Germany, Spain, France, Italy, and the United Kingdom. METHODS: We undertook a systematic review of the literature (up to May 2015) using the MEDLINE and EMBASE databases. The methodological quality of the studies identified was evaluated using the Consolidated Health Economic Evaluation Reporting Standards checklist. We considered both direct costs (medical and nonmedical) and indirect costs, adjusted for country-specific inflation and converted to international dollars using purchasing power parity exchange rates for 2015 ($US PPP). RESULTS: The search retrieved 775 studies; 68.3% analyzed psoriasis and 31.7% analyzed psoriatic arthritis. The total annual cost per patient ranged from US $2,077 to US $13,132 PPP for psoriasis and from US $10,924 to US $17,050 PPP for psoriatic arthritis. Direct costs were the largest component of total expenditure in both diseases. The severity of these diseases was associated with higher costs. The introduction of biologics led to a 3-fold to 5-fold increase in direct costs, and consequently to an increase in total costs. CONCLUSIONS: We have analyzed the economic burden of psoriasis and psoriatic arthritis and shown that costs increase with the treatment and management of more severe disease and the use of biologics.

Cost analysis of prophylaxis with activated prothrombin complex concentrate vs. on-demand therapy with activated factor VII in severe haemophilia A patients with inhibitors, in Spain.

OBJECTIVE: A cost analysis model was developed to compare annual cost of prophylaxis with activated prothrombin complex concentrate (aPCC) vs. on-demand therapy with activated recombinant factor VII (rFVIIa) in severe haemophilia A patients with inhibitors for the Spanish National Health System (NHS). METHODS: Model inputs were drug cost for prophylaxis (aPCC) and for on-demand treatment (rFVIIa or aPCC); bleeding episodes management (excluding bypassing agent cost); surgical costs and disease management (excluding bleeding episodes). Annual bleeding episodes treated on-demand was assumed to be 25, whereas breakthrough bleeds on prophylaxis was 8. Dose for prophylaxis was 75.72 U kg(-1) , three times per week. The total on-demand dose/bleeding episode was 679.66 µg kg(-1) (rFVIIa) and 235.28 U kg(-1) (aPCC). The average bleeding cost (€2998) considered different bleeding sites (62.5% joints, 28.6% muscles and soft tissues, 3.6% mucocutaneous tissues and 5.4% other areas). A 7.5% deduction was applied to ex-factory drug prices. Unitary costs (€2013) derived from local databases. Sensitivity analyses (SA) were performed. RESULTS: Annual cost of aPCC prophylaxis (€524,358) was 16% lower than on-demand treatment with rFVIIa (€627,876). Yearly drug costs were €497,017 for aPCC (€73,166 for on-demand treatment and €423,850 for prophylaxis), and €548,870 for rFVIIa. Disease management cost (€2645 per year) and surgical procedures (€708 per year) were common for both strategies. In the SA prophylactic treatment led to savings between €26,225 and €-1,008,960. CONCLUSION: Prophylaxis with aPCC reduces number of bleeding episodes in severe haemophilia A patients with inhibitors. aPCC prophylaxis resulted in savings in excess of €100,000 per-patient per year, being 16% less costly than on-demand treatment with rFVIIa, for the Spanish NHS.

The costs of stroke in Spain by aetiology: the CONOCES study protocol.

INTRODUCTION: Patients with stroke associated with non-valvular atrial fibrillation (NVAF) are a specific group, and their disease has a considerable social and economic impact. The primary objective of the CONOCES study, the protocol of which is presented here, is to compare the costs of stroke in NVAF patients to those of patients without NVAF in Spanish stroke units from a societal perspective. MATERIALS AND METHODS: CONOCES is an epidemiological, observational, naturalistic, prospective, multicentre study of the cost of the illness in a sample of patients who have suffered a stroke and were admitted to a Spanish stroke unit. During a 12-month follow-up period, we record sociodemographic and clinical variables, score on the NIH stroke scale, level of disability, degree of functional dependency according to the modified Rankin scale, and use of healthcare resources (hospitalisation at the time of the first episode, readmissions, outpatient rehabilitation, orthotic and/or prosthetic material, medication for secondary prevention, medical check-ups, nursing care and formal social care services). Estimated monthly income, lost work productivity and health-related quality of life measured with the generic EQ-5D questionnaire are also recorded. We also administer a direct interview to the caregiver to determine loss of productivity, informal care, and caregiver burden. RESULTS AND CONCLUSIONS: The CONOCES study will provide more in-depth information about the economic and clinical impact of stroke according to whether or not it is associated with NVAF.

Mental health self-assessment in patients with moderate to severe psoriasis: an observational, multicenter study of 1164 patients in Spain (the VACAP Study).

BACKGROUND: Poor self-assessed mental health appears to be related to the severity of psoriasis. OBJECTIVE: To evaluate the impact of psoriasis severity on mood and anxiety disorders. METHODS: A prospective, observational, multicenter study was conducted by 123 dermatologists in Spain. Patients (n=164; mean [SD] age, 45.11 [13.92] years; 60.8% males) with moderate to severe psoriasis were evaluated at baseline and 4 months later. Psoriasis severity was measured using the Psoriasis Area and Severity Index (PASI), with a score range of 0 (mild) to 72 (severe); body surface area involvement (BSA); and physician global assessment (PGA) scores, with a range of 1 (mild) to 7 (severe). Mental health was assessed using the Hospital Anxiety and Depression Scale (HADS), with a total possible score of 0-42 (higher scores representing worse mental health). Mean first and second visit scores were compared. RESULTS: Mean (SD) scores improved between the first and second visit as follows: 13.24 (9.50) to 5.07 (6.03) for PASI, 12.52 (7.92) to 10.78 (7.32) for overall HADS, 7.83 (4.55) to 6.85 (4.21) for the HADS anxiety subscale, and 4.72 (4.12) to 3.95 (3.76) for the HADS depression subscale (P<.001 in all cases). Multivariate analyses showed that the main factors related to anxiety were psoriasis severity, sex, and completion of graduate studies. The independent variables included in the model for depression were psoriasis severity, sex, and psoriasis located on the head. CONCLUSIONS: Reductions in disease severity improve self-assessed mood and anxiety disorders in patients with moderate to severe psoriasis.

Demographic characteristics and health-related quality of life of patients with moderate-to-severe psoriasis: The VACAP study.

BACKGROUND: Psoriasis is associated with a deterioration in the health-related quality of life (HRQoL) of affected patients. The aim of this study was to assess the HRQoL of patients with moderate-to-severe psoriasis. METHODS: A prospective observational study (the VACAP Study) was carried out in 123 centers in Spain with 1217 patients. Patients were evaluated at baseline (visit 1 [V1]) and again four months later (visit 2 [V2]). The severity of psoriasis was determined using the following indices: (i) Psoriasis Area and Severity Index (PASI) (score range 0-72, higher score indicates more severe disease), (ii) the body surface area (BSA) affected, and (iii) the Physicians Global Assessment (PGA) (range 1-7, higher score indicates more severe disease). Four questionnaires were used for the assessment of the HRQoL: (i) the Short-Form 36 quality-of-life questionnaire (SF-36) (score range 0-100, higher score indicates better HRQoL); (ii) Euroqol (EQ-5D) (range from 1 to 3, lower score indicates better HRQoL); (iii) Dermatology Life Quality Index (DLQI) (ranges 0-30; from best to worst HRQoL); and (iv) Psoriasis Disability Index (PDI) (ranges 0-45; higher score indicates better HRQoL). RESULTS: The mean (SD) age of the patients was 45.11 (13.92) years at V1. The mean age at the onset of psoriasis was 26.08 (14.19) years. The majority of patients were female (61%) and were employed (68%). The mean PASI score was 13.24 (9.50) at V1 and 5.07 (6.03) at V2 (P<.001). Scores from the generic HRQoL questionnaires (EQ-5D, SF-36) showed significant improvement between visits in all dimensions measured (P<.001). The disease-specific questionnaires also revealed overall improvements in quality of life over time: the DLQI mean total score was 8.97 (7.28) at V1 and 4.76 (5.72) at V2 (P<.001), and the PDI mean total score was 9.24 (8.76) V1 and 4.88 (6.65) at V2 (P<.001). Multivariate analysis using PDI as the dependent variable showed that the principal factors related to HRQoL were severity of psoriasis as measured by PASI (P<.001), and gender (P=.048). CONCLUSIONS: The principal factor related to HRQoL in patients with psoriasis is the severity of the disease.

Optimal treatment sequencing of abiraterone acetate plus prednisone and enzalutamide in patients with castration-resistant metastatic prostate cancer: A systematic review and meta-analysis.

PURPOSE: To evaluate the impact of the hormonal treatment sequencing including abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) in mCRPC, and determine which sequence provides more benefits for patients. METHODS: Studies published in English between 1 January 2013 and 30 September 2017 were identified in PubMed and EMBASE electronic databases. Studies assessing the efficacy of treatment sequences, based on AAP and ENZ, in mCRPC patients, were eligible for analysis. RESULTS: Seventeen studies met the inclusion criteria. Two assessed both treatment sequences AAP â†’ ENZ and ENZ â†’ AAP; it was found that sequence of AAP â†’ ENZ showed a statistically significantly longer PSA-PFS than the observed in ENZ â†’ AAP (pooled HR: 0,54; 95% CI; 0,36-0,82; p < 0,05). The nine studies analysing Doc â†’ AAP â†’ ENZ sequence, revealed favourable results in terms of PFS. The 5 studies which analysed AAP â†’ ENZ sequence, show a decrease in PSA levels ≥ 50% in 11-41% of patients treated with enzalutamide after previous treatment with AAP. In the two studies that analysed the Doc â†’ ENZ â†’ AAP sequence, PSA response rates were much lower than those reported with Doc â†’ AAP â†’ ENZ, with decreases in PSA ≥ 30 of 3-18% and PSA ≥ 50 of 8-11%. CONCLUSION: Significant clinical efficacy of AAP administered as the first-line treatment in mCRPC patients followed by enzalutamide, delaying disease progression, compared with the ENZ â†’ AAP sequence. However, more studies and randomized trials are needed, to validate the best treatment sequencing.

Cost-effectiveness analysis of chronic hepatitis C treatment in the prison population in Spain.

OBJECTIVES: To evaluate the cost-effectiveness of direct-acting antiviral (DAAs) treatment versus non-treatment in prisoners awaiting treatment for chronic hepatitis C (CHC) and to analyse the clinical and economic impact of the treatment on liver complications and mortality. MATERIAL AND METHOD: A lifetime Markov model was developed to simulate treatment and disease progression from an estimated cohort of 4,408 CHC prisoners treated with DAAs over 2 years (50% of patient each year) versus no treatment. In the treated cohort, a sustained viral response of 95% was associated. Patient characteristics, transition probabilities, utilities and costs (pharmacological and healthcare states) were obtained from published literature. The model estimated healthcare costs and benefits, incremental cost-utility ratio (ICUR) based on total costs and the quality-adjusted life year (QALY) and avoided clinical events. A National Healthcare System perspective was adopted with a 3% annual discount rate for both costs and health outcomes. Sensitivity analyses were performed to assess uncertainty. RESULTS: In the DDA treated cohort, the model estimated a decrease of 92% of decompensated cirrhosis and 83% of hepatocellular carcinoma, 88% liver-related mortality cases were reduced, 132 liver transplants were avoided. The treatment achieved an additional 5.0/QALYs (21.2 vs. 16.2) with an incremental cost of €3,473 (€24,088 vs. €20,615) per patient with an ICUR of €690 per QALY gained. DISCUSSION: Considering the willingness-to-pay threshold used in Spain (€22,000-30,000/QALY), DAAs treatment for prisoners with CHC is a highly cost-effective strategy, reduces infection transmission, increases survival and reduces complications due to liver disease, as well as the cost associated with its management.

Is the universal population Hepatitis C virus screening a cost-effective strategy? A systematic review of the economic evidence.

OBJECTIVE: Efficient strategies are needed in order to achieve the objective of the WHO of eradicating Hepatitis C virus (HCV). Hepatitis C infection can be eliminated by a combination of direct acting antiviral (DAA). The problem is that many individuals remain undiagnosed. The objective is to conduct a systematic review of the evidence on economic evaluations that analyze the screening of HCV followed by treatment with DAAs. METHODS: Eleven databases were performed in a 2015-2018-systematic review. Inclusion criteria were economic evaluations that included incremental cost-effectiveness ratio (ICER) in terms of cost per life year gained or quality-adjusted life year. RESULTS: A total of 843 references were screened. Sixteen papers/posters meet the inclusion criteria. Ten of them included a general population screening. Other populations included were baby-boomer, people who inject drugs, prisoners or immigrants. Comparator was "standard of care", other high-risk populations or no-screening. Most of the studies are based on Markov model simulations and they mostly adopted a healthcare payer´s perspective. ICER for general population screening plus treatment versus high-risk populations or versus routinely performed screening showed to be below the accepted willingness to pay thresholds in most studies and therefore screening plus DAAs strategy is highly cost-effective. CONCLUSIONS: This systematic review shows that screening programmes followed by DAAs treatment is cost-effective not only for high risk population but for general population too. Because today HCV can be easily cured and its long-term consequences avoided, a universal HCV screening plus DAAs therapies should be the recommended strategy to achieve the WHO objectives for HCV eradication by 2030.

Cost-effectiveness analysis of treatment sequences containing tofacitinib for the treatment of rheumatoid arthritis in Spain.

OBJECTIVE: To assess the cost-effectiveness of tofacitinib-containing treatment sequences versus sequences containing only standard biological therapies in patients with moderate-to-severe rheumatoid arthritis (RA) after the failure of conventional synthetic disease-modifying antirheumatic drugs (csDMARD-IR population) and in patients previously treated with methotrexate (MTX) who show an inadequate response to second-line therapy with any tumour necrosis factor inhibitor (TNFi-IR population). METHODS: A patient-level microsimulation model estimated, from the perspective of the Spanish Public NHS, lifetime costs and quality-adjusted life years (QALY) for treatment sequences starting with tofacitinib (5 mg twice daily) followed by biological therapies versus sequences of biological treatments only. Concomitant treatment with MTX was considered. Model's parameters comprised demographic and clinical inputs (initial Health Assessment Questionnaire [HAQ] score and clinical response to short- and long-term treatment). Efficacy was measured by means of HAQ score changes using mixed treatment comparisons and data from long-term extension (LTE) trials. Serious adverse events (SAEs) data were derived from the literature. Total cost estimation (€, 2018) included drug acquisition, parenteral administration, disease progression and SAE management. RESULTS: In the csDMARD-IR population, sequences starting with tofacitinib proved dominant options (more QALYs and lower costs) versus the corresponding sequences without tofacitinib. In the TNFi-IR population, first-line treatment with tofacitinib+MTX followed by scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX proved dominant versus scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX; and tofacitinib+MTX➔scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX versus scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX was less effective but remained a cost-saving option. CONCLUSIONS: Inclusion of tofacitinib seems a dominant strategy in moderate-to-severe RA patients after csDMARDs failure. Tofacitinib, as initial third-line therapy, proved a cost-saving strategy (€- 337,489/QALY foregone) in moderate-to-severe TNFi-IR RA patients. Key points • Therapeutical approach in rheumatoid arthritis (RA) consisted in sequences of several therapies during patient lifetime. • Treatment sequences initiating with tofacitinib followed by biological drugs provided higher health effects in csDMARDs-IR population, compared with sequences containing only biological drugs. • In both csDMARD-IR and TNFi-IR RA populations, initiating treatment with tofacitinib was associated to lower treatment costs for the Spanish National Health System.

[Usefulness of labelled red-cell scintigraphy in Blue Rubber-Bleb Nevus syndrome]. / Utilidad de la gammagrafía con hematíes marcados en el síndrome de Blue Rubber Bleb Nevus.

Blue Rubber Bleb Nevus syndrome is a rare disorder characterized by distinctive cutaneous and gastrointestinal venous malformations that usually cause episodes of occult gastrointestinal haemorrhage and iron deficiency anaemia. We describe an 8-year-old girl who had multiple cutaneous venous malformations since birth. She also suffered from several episodes of severe chronic iron deficiency anaemia and required blood transfusions. To evaluate the presence of gastrointestinal bleeding secondary to intestinal angiomatosis, we decided to perform 99mTc-labelled red blood cell scintigraphy, which confirmed cutaneous venous malformations and also showed gastrointestinal vascular lesions that suggested the diagnosis of Blue Rubber Bleb Nevus Syndrome.

Real World Patient-reported Outcomes in HIV-infected Adults Switching to EVIPLERA®, Because of a Previous Intolerance to cART. PRO-STR Study.

BACKGROUND: To investigate the impact of switching from stable Combined Antiretroviral Therapy (cART) to single-tablet regimen (RPV/FTC/TDF=EVIPLERA® /COMPLERA®) on patient- reported outcomes in HIV-infected adults who cannot tolerate previous cART, in a real-world setting. METHODS: PRO-STR is a 48-week observational, prospective, multicenter study. Presence and magnitude of symptoms (main endpoint), health-related quality-of-life (HRQoL), adherence, satisfaction with treatment and patient preferences were assessed. RESULTS: Three hundred patients with 48-week follow-up, who switched to EVIPLERA® (mean age: 46.6 years; male: 74.0%; 74.7% switched from a non-nucleoside reverse-transcriptase-inhibitor, 25.3% from a protease inhibitor + ritonavir) were included. There was no statistical difference in median CD4+ cell count (baseline: 678.5 cells/mm3; 48-week: 683.0 cells/mm3) neither in virological suppression (≤50 copies/mL) (baseline: 98.3%; 48-week: 95.3%). The most frequent reasons for switching were neuropsychiatric (62.3%), gastrointestinal (19.3%) and biochemical/metabolic (19.3%) events. Only 7.7% of patients permanently discontinued therapy. At 48-week, all outcomes showed an improvement compared to baseline. Overall, there was a significant decrease (pvalue≤ 0.05) in number and magnitude of symptoms, while HRQoL, satisfaction and adherence improved significantly. Most patients prefered EVIPLERA® than previous cART. According to the type of intolerance, HRQoL was improved, but only significantly in patients with neuropsychiatric and gastrointestinal symptoms. Adherence improved significantly in patients with metabolic disturbances and satisfaction with EVIPLERA® was higher in the three groups. CONCLUSION: Switching to EVIPLERA® from non-nucleoside reverse-transcriptase-inhibitor or protease inhibitor-based regimens due to toxicity, improved the presence/magnitude of symptoms, HRQoL, and preference with treatment. EVIPLERA® maintained a virological response, CD4+ cell count and maintained or improved adherence.

Evaluating the cost of sustained virologic response in naïve chronic hepatitis C patients treated à la carte.

BACKGROUND: There is a tendency to individualize treatment in chronic hepatitis C patients depending on viral load and rapid clearance of HCV-RNA. AIM: To evaluate the cost (euro, 2006) per sustained virologic response in naïve patients with therapy à la carte compared with standard combination therapy. METHODS: A decision analysis model was used to compare standard therapy with peginterferon alpha and ribavirin for 24 weeks for genotype (G) 2/3, and 48 weeks for G1 and therapy à la carte with the same drugs but different durations: G1 high viral load for 48 weeks, G1 low viral load with rapid virologic response for 24 weeks, and without rapid virologic response for 48 weeks, and G2/3 with rapid virologic response for 12 weeks, and without rapid virologic response for 24 weeks. RESULTS: Sustained virologic response was similar in both strategies. The cost per successfully treated patient for standard therapy is 17,812 euros and for therapy à la carte 12,313 euros. Assuming that 13,309 patients with standard therapy and 14,450 patients with therapy à la carte achieve sustained virologic response, therapy à la carte has an overall cost-saving of 59.13 million euros. CONCLUSION: Therapy à la carte is a cost-saving strategy for chronic hepatitis C infection compared to standard therapy, with lower investment requirement per patient to achieve sustained virologic response.

Resource use in patients with Crohn's disease treated with infliximab.

AIM: To estimate the impact of infliximab (IFX) on hospital resources for patients with Crohn's disease. METHODS: Resource use data for at least 1 year before (B-IFX) and after (A-IFX) infliximab administration were retrospectively collected for all patients treated with IFX at the Hospital Cabueñes (Spain). Direct costs calculated were: hospital-stays, surgeries, out-patient visits, diagnostic and laboratory tests, pharmacological treatments, and day-care hospitalization for IFX administration. RESULTS: Patients (n = 34; mean age at treatment: 43.6 years) with 9.8 and 4.3 years (B-IFX and A-IFX, respectively) had their costs estimated. Partial or complete response was achieved in 82% of patients. Total annual B-IFX costs per patient were Euro 4,464, of which 62.4% was for hospitalization, 3.1% for surgery, 8.7% for consultation visits, 16.2% for diagnostic and laboratory tests, and 9.6% for other treatments. Total annual A-IFX costs per patient were Euro 10,594; of which 6.4% was for hospitalization, 0.8% for surgery, 4.2% for consultation visits, 7.6% for diagnostic and laboratory tests, 5.5% for other treatments, and 75.5% for IFX and its administration. The primary cost item was hospitalization (Euro 2,783) during the B-IFX period as opposed to IFX itself (Euro 7,996) during the subsequent A-IFX period. CONCLUSIONS: In routine practice, IFX appears to be an effective treatment by reducing hospital-stays, but increases overall budgetary cost for patients with Crohn's disease.