Acceptability of multimodal and multidisciplinary group-based program for chronic low back pain: a qualitative study.

BACKGROUND: The Programa d'Atenció Integral pels Pacients amb Dolor Crònic (PAINDOC) is a multimodal and multidisciplinary group-based program that integrates pain neuroscience education, mindfulness meditation, pain psychotherapy, Empowered Relief, and therapeutic exercise. It serves as a therapeutic option for individuals with chronic low back pain, providing them with comprehensive adaptive strategies for pain management. OBJECTIVE: This qualitative study explores participants' retrospective acceptability of the PAINDOC Program. METHODS: To ensure demographic variability and information power, a purposive sampling approach was applied. Twelve participants were interviewed through three focus groups, supplemented with four individual semi-structured interviews. Data was analyzed using reflexive thematic analysis and evaluated based on the Therapeutic Framework of Acceptability. RESULTS: Participants provide positive feedback regarding active pain coping strategies and improved self-management. While certain aspects of the Program were more emphasized, participants integrated tools from all components. Strategies included pain reconceptualization, positive self-talk, or problem-solving. The Program's ethicality was closely linked to individual values and may also be influenced by time constraints of certain program elements, the immediate effects of specific approaches, participant perceptions, and individual preferences. CONCLUSIONS: The findings provide valuable insights into the acceptability of the PAINDOC Program, guiding future improvements and the development of similar interventions.

Multidisciplinary approaches to chronic pain management have been explored and are recognized as an effective way to address the complexity of chronic pain conditions. These approaches often involve the collaboration of healthcare professionals from various disciplines.Multimodal pain management programs typically combine various treatment modalities, including physical therapy, cognitive-behavioral therapy, medication, and exercise.Studies have shown that multidisciplinary and multimodal interventions can be effective in reducing pain intensity, improving physical function, and enhancing quality of life in chronic low back pain patients. What does this study add? The multidisciplinary and multimodal group-based PAINDOC Program is acceptable for chronic low back pain patients.Participants noted the effectiveness of the program in helping them adopt active pain coping strategies and improve self-management.The ethicality of the multimodal Program depends on individual personal value systems, as certain program components may be less suitable for some participants.There might be some barriers to program adherence, including limited available time, the higher physical demands of exercise, the immediate effects of certain approaches, participants' perceptions, and individual needs and preferences.

High life satisfaction reported among small-scale societies with low incomes.

Global polls have shown that people in high-income countries generally report being more satisfied with their lives than people in low-income countries. The persistence of this correlation, and its similarity to correlations between income and life satisfaction within countries, could lead to the impression that high levels of life satisfaction can only be achieved in wealthy societies. However, global polls have typically overlooked small-scale, nonindustrialized societies, which can provide an alternative test of the consistency of this relationship. Here, we present results from a survey of 2,966 members of Indigenous Peoples and local communities among 19 globally distributed sites. We find that high average levels of life satisfaction, comparable to those of wealthy countries, are reported for numerous populations that have very low monetary incomes. Our results are consistent with the notion that human societies can support very satisfying lives for their members without necessarily requiring high degrees of monetary wealth.

Effectiveness and safety of tildrakizumab for the treatment of psoriasis in real-world settings at 24 weeks: A retrospective, observational, multicentre study by the Spanish Psoriasis Group.

BACKGROUND: Tildrakizumab is a humanized, IgG1/κ antibody that interacts with the p19 subunit of interleukin 23. It is approved for the treatment of moderate-to-severe plaque psoriasis. Real-world evidence on the effectiveness and safety of tildrakizumab is limited. OBJECTIVES: To assess the effectiveness and safety of tildrakizumab at 24 weeks in patients with moderate-to-severe plaque psoriasis in routine clinical practice. METHODS: Retrospective, observational, multicentre study including adult patients with moderate-to-severe plaque psoriasis treated with tildrakizumab under real-life conditions. Patient data were extracted from anonymized electronic medical records. Statistical analysis was performed using SPSS22. RESULTS: A total of 190 patients were included. About 53.9% were men with a mean age of 51.45 (SD 3.9) and a mean BMI of 29.13 (SD 6.21). About 79.8% (132 out of 190) of patients had previously received biological therapy (BT) and 17.3% (33 out of 191) had psoriatic arthritis. Baseline PASI was 10.7 (SD 6.53). Up to 109 patients reached Week 24 and at this point mean baseline PASI decreased to 1.7 (SD 4.8), representing an 88.79% mean PASI reduction. At 6 months, 87.1% and 40.3% of the treated patients achieved PASI ≤3 and ≤1, respectively. At Week 24 mean BSA decreased from 13.2 (SD 10.07) to 1.6 (SD 4.40) and mean DLQI went from 12.5 (SD 7.12) to 1.2 (SD 3.27). Multivariate analysis showed no differences when effectiveness was correlated with gender, obesity, psoriatic arthritis or prior exposure to BT. The rate of adverse events (AE) was 5.9% (11 out of 190), where infections were the most frequent AE (4 out of 11). One patient suffered a haemorrhagic ictus and one patient died due to causes unrelated to the study. CONCLUSION: Tildrakizumab was effective and safe in a large cohort of patients with moderate-to-severe plaque psoriasis treated in a routine clinical setting.

Bimekizumab in the Treatment of Plaque Psoriasis: Focus on Patient Selection and Perspectives.

Psoriasis is a chronic systemic inflammatory disease that significatively impairs patients' quality of life. Biological treatments are highly effective and safe and have led to breakthroughs in the management of patients with moderate-to-severe psoriasis. However, therapeutic response can be unsatisfactory or lost with time, leading to discontinuation of treatment. Bimekizumab is a humanized monoclonal antibody that specifically inhibits both interleukin (IL)-17A and IL-17F. The efficacy and safety of bimekizumab in moderate-to-severe plaque psoriasis has been demonstrated in Phase 2 and Phase 3 clinical trials. Bimekizumab may offer some advantages over other biological treatments, making it especially indicated for certain patients. This narrative review aims to summarize the latest published evidence on the use of bimekizumab for the treatment of moderate-severe plaque psoriasis, focusing on patient selection and therapeutic perspectives. Bimekizumab has been shown to be more efficacious than adalimumab, secukinumab and ustekinumab in clinical trials, with high estimated probabilities of achieving complete (approximately 60%) or almost complete clearance (approximately 85%) of psoriasis at weeks 10-16, and a good safety profile. Response to bimekizumab is usually fast and maintained in the long term for both biologic-naive patients and those resistant to previous biologic treatments. The usual maintenance dose of 320 mg every 8 weeks makes bimekizumab especially convenient for non-compliant patients. Moreover, the efficacy and safety of bimekizumab have also been demonstrated in psoriasis affecting challenging-to-treat areas, psoriatic arthritis and hidradenitis suppurativa. In conclusion, dual inhibition of IL-17A and IL-17F with bimekizumab is a good therapeutic option for moderate-to-severe psoriasis.

Local indicators of climate change impacts described by indigenous peoples and local communities: Study protocol.

INTRODUCTION: In the quest to improve the understanding of climate change impacts on elements of the atmospheric, physical, and life systems, scientists are challenged by the scarcity and uneven distribution of grounded data. Through their long history of interaction with the environment, Indigenous Peoples and local communities have developed complex knowledge systems that allow them to detect impacts of climate change in the local environment. The study protocol presented here is designed 1) to inventory climate change impacts on the atmospheric, physical, and life systems based on local knowledge and 2) to test hypotheses on the global spatial, socioeconomic, and demographic distribution of reported impacts. The protocol has been developed within the framework of a project aiming to bring insights from Indigenous and local knowledge systems to climate research (https://licci.eu). METHODS: Data collection uses a mixed-method approach and relies on the collaboration of a team of 50 trained partners working in sites where people's livelihood directly depend on nature. The data collection protocol consists of two steps. Step 1 includes the collection of secondary data (e.g., spatial and meteorological data) and site contextual information (e.g., village infrastructure, services). Step 1 also includes the use of 1) semi-structured interviews (n = 20-30/site) to document observations of environmental change and their drivers and 2) focus group discussions to identify consensus in the information gathered. Step 2 consist in the application of a household (n from 75 to 125) and individual survey (n from 125 to 175) using a standardized but locally adapted instrument. The survey includes information on 1) individual and household socio-demographic characteristics, 2) direct dependence on nature, 3) household's vulnerability, and 4) individual perceptions of climate change impacts. Survey data are entered in a specifically designed database. EXPECTED RESULTS: This protocol allows the systematic documentation and analysis of the patterned distribution of local indicators of climate change impacts across climate types and livelihood activities. Data collected with this protocol helps fill important gaps on local climate change impacts research and can provide tangible outcomes for local people who will be able to better reflect on how climate change impacts them.

Efficacy and safety clinical trial with efavirenz in patients diagnosed with adult Niemann-pick type C with cognitive impairment.

BACKGROUND: Niemann-Pick disease Type C (NPC) is a genetic, incurable, neurodegenerative disorder. This orphan disease is most frequently caused by mutations in the NPC1 protein, resulting in intralysossomal cholesterol accumulation. NPC1 is found in neuronal cell bodies, axon terminals and synaptosomes, suggesting it plays a role in lysosomal degradation pathway and in synaptic transmission. Neuronal function is especially vulnerable to NPC1 deficiency and synaptic changes seem a key element in disease development. Currently, Miglustat (Zavesca®) is the only approved treatment for NPC. However, preclinical evidence showed that low-dose Efavirenz reverted synaptic defects through pharmacological activation of the enzyme CYP46. METHODS: This is a single-center, phase II clinical trial to evaluate the efficacy and safety of Efavirenz in addition to standard of care in patients diagnosed with adult or late juvenile-onset NPC with cognitive impairment. All enrolled patients will be treated orally with 25 mg/d of Efavirenz for 52 weeks (1 year). Secondary objectives include evaluating clinical (neurological and neuropsychological questionnaires) and biological (imaging and biochemical biomarkers) parameters. DISCUSSION: NPC is still an unmet medical need. Although different therapeutic approaches are under study, this is the first clinical trial (to the best of our knowledge) studying the effects of Efavirenz in adult- and late-juvenile-onset NPC. Despite the small sample size and the single-arm design, we expect the results to show Efavirenz's capacity of activating the CYP46 enzyme to compensate for NPC1 deficiency and correct synaptic changes, therefore compensating cognitive and psychiatric changes in these patients. This study may provide direct benefit to enrolled patients in terms of slowing down the disease progression.

Artritis psoriásica / Psoriatic arthritis

Psoriatic arthritis (PsA) is a type of inflammatory arthritis that is included within the spondyloarthritis, a group of rheumatological diseases characterized by different clinical manifestations and associated comorbidities, that can compromise the quality of life of patients. The diagnosis of PsA is sometimes difficult due to an enormous clinical and radiological variability, including six different domains of involvement: peripheral joint, axial skeleton, skin psoriasis, nail psoriasis, enthesitis and dactylitis. Currently, there are no biomarkers that allow the detection of PsA in patients with psoriasis, so a high level of suspicion is important, mainly by dermatologists, but also by other specialists, such as family doctors. Advances in the knowledge of new immunological mechanisms and joint management by rheumatologists and dermatologists have made it possible to improve the therapeutic approach in patients with PsA. (AU)

La artritis psoriásica (APs) es un tipo de artritis inflamatoria que se incluye dentro de las espondiloartritis, un grupo de enfermedades reumatológicas caracterizadas por diferentes manifestaciones clínicas y comorbilidades asociadas, que pueden comprometer significativamente la calidad de vida de los pacientes. Su enorme variabilidad clínica y radiológica dificulta la sospecha diagnóstica y justifica su abordaje según seis dominios de afectación: articular periférica, esqueleto axial, psoriasis cutánea, psoriasis ungueal, entesitis y dactilitis. En la actualidad no existen biomarcadores que permitan la detección de APs en pacientes con psoriasis, por lo que es importante un alto nivel de sospecha, fundamentalmente por los dermatólogos, pero también por otros especialistas, como son los médicos de familia. El avance en el conocimiento de nuevos mecanismos inmunológicos y el manejo conjunto por parte de reumatólogos y dermatólogos ha permitido mejorar el abordaje terapéutico en los pacientes con APs. (AU)

Psoriatic arthritis. / Artritis psoriásica.

Psoriatic arthritis (PsA) is a type of inflammatory arthritis that is included within the spondyloarthritis, a group of rheumatological diseases characterized by different clinical manifestations and associated comorbidities, that can compromise the quality of life of patients. The diagnosis of PsA is sometimes difficult due to an enormous clinical and radiological variability, including six different domains of involvement: peripheral joint, axial skeleton, skin psoriasis, nail psoriasis, enthesitis and dactylitis. Currently, there are no biomarkers that allow the detection of PsA in patients with psoriasis, so a high level of suspicion is important, mainly by dermatologists, but also by other specialists, such as family doctors. Advances in the knowledge of new immunological mechanisms and joint management by rheumatologists and dermatologists have made it possible to improve the therapeutic approach in patients with PsA.

A cohort study of guselkumab in the treatment of psoriasis refractory to previous biologic therapies: effectiveness, safety and adherence.

Background Guselkumab is indicated for moderate-to-severe plaque psoriasis. Data from real-life clinical practice regarding its use are scarce, especially concerning patients who relapse after previous biologic therapies. Aim This study aimed to evaluate the effectiveness, safety, and adherence to guselkumab in psoriasis refractory to biologic therapies. Method This real-life, retrospective study included patients who initiated guselkumab between February 2019 and October 2020. The main objective was to assess effectiveness, expressed as the psoriasis area and severity index (PASI) ≤5, ≤2 and 0, at the first follow-up medical visit. As secondary effectiveness outcomes, we assessed the body surface area (BSA) and dermatology life quality index (DLQI). We also evaluated adverse events and adherence (using the medication possession ratio [MPR]). Results The study included 35 patients who had previously received a median of two biologic drugs. The median basal PASI score (IQR) was 11 (7.3-15.9), decreasing to 0 (0-1.4) at first follow-up medical visit. At this point, 32 patients (94.1%) reached PASI ≤5, 28 (82.4%) PASI ≤2 and 19 (55.9%) PASI 0. We also found statistically significant improvements in PASI, BSA and DLQI at first follow-up (p<0.001). Three patients developed adverse events. Most patients (N=29, 85.3%) had an MPR ≥90%. The MPR was not associated with PASI score at first follow-up. Conclusion Our study supports evidence that guselkumab is an effective and safe drug in psoriasis refractory to biologic therapies. Adherence to treatment is not related to effectiveness, suggesting that, in some cases, the interval between doses could be increased.

Effectiveness and safety of guselkumab for the treatment of psoriasis in real-world settings at 24 weeks: A retrospective, observational, multicentre study by the Spanish Psoriasis Group.

Data on the effectiveness and safety of a drug in real-world clinical practice complement the evidence from clinical trials, which are carried out in a different setting. Little has been published on the effectiveness and safety of guselkumab in the treatment of psoriasis in clinical practice. The ojective of this study was to assess the effectiveness and safety of guselkumab at 24 weeks in patients with moderate to severe plaque psoriasis in routine clinical practice. A retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis treated with guselkumab for at least 24 weeks was carried out in Spain. We studied 343 patients, 249 of whom were followed for 24 weeks. By week 24, the mean (SD) psoriasis area severity index (PASI) had decreased from 11.1 (7.3) to 1.7 (2.8) (-9.3; [-10.2;-8.4]), 85.9% of the patients had achieved PASI score of 4 or less and 77.9% a PASI score of 2 or less. In terms of relative PASI response, 59.4% of the patients achieved a PASI-90 response and 49.0% a PASI-100 response. On multivariate analysis, two factors reduced the probability of a PASI of 2 or less at 24 weeks: a BMI ≥30 (OR, 0.44; 95% CI, 0.22-0.88) and a greater previous exposure to biologic therapy (OR, 0.69; 95% CI, [0.56-0.84]). Adverse events were rare (9.9%) and led to withdrawal from treatment in only nine patients (2.6%) by the end of the follow-up period. The results of this study confirm the high efficacy and safety of guselkumab indicated by the clinical trial data. In clinical practice, the absolute PASI score appears to be a better marker of response to treatment than the relative value.

Daptomycin Plus Fosfomycin Versus Daptomycin Alone for Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis: A Randomized Clinical Trial.

BACKGROUND: We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis. METHODS: A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy. RESULTS: Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93-1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018). CONCLUSIONS: Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events. CLINICAL TRIALS REGISTRATION: NCT01898338.

The impact of frailty in aortic valve surgery.

BACKGROUND: Frailty is a geriatric syndrome that diminishes potential functional recovery after any surgical procedure. Preoperative surgical risk assessment is crucial to calibrate the risk and benefit of cardiac surgery. The aim of this study was to test usefulness of FRAIL Scale and other surgical-risk-scales and individual features of frailty in cardiac aortic valve surgery. METHODS: Prospective study. From May-2014 to February-2016, we collected 200 patients who underwent aortic valve replacement, either surgically or transcatheter. At 1-year follow-up, quality of life measurements were recorded using the EQ-5D (EuroQol). Univariate and multivariate analyses correlated preoperative condition, features of frailty and predicted risk scores with mortality, morbidity and quality of life at 1 year of follow-up. RESULTS: Mean age 78.2y, 56%male. Mean-preoperative-scores: FRAIL scale 1.5(SD 1.02), STS 2.9(SD 1.13), BI 93.8(SD 7.3), ESlog I 12.8(SD 8.5) and GS 7.3 s (SD 1.9). Morbidity at discharge, 6 m and 1 year was 51, 14 and 28%. Mortality 4%. Survival at 6 m/ 1-y was 97% / 88%. Complication-rate was higher in TAVI group due to-vascular complications. Renal dysfunction, anemia, social dependence and GS slower than 7 s were associated with morbidity. On multivariate analysis adjusted STS, BI and GS speed were statistically significant. Quality of life at 1-year follow-up adjusted for age and prosthesis type showed a significant association with STS and FRAIL scale scores. CONCLUSIONS: Frailty increases surgical risk and is associated with higher morbidity. Preoperative GS slower 7 s, and STS and FRAIL scale scores seem to be reliable predictors of quality of life at 1-year follow-up.

Effectiveness and safety of ustekinumab 90 mg in patients weighing 100 kg or less: a retrospective, observational, multicenter study.

Background: Scant information from clinical practice is available on the effectiveness and safety of ustekinumab (UST) 90 mg in patients with psoriasis weighing 100 kg or less.Objectives: To assess the effectiveness and safety at weeks 16 and 24 of UST 90 mg in patients with psoriasis weighing ≤100 kg, and to study the impact on clinical outcomes of body mass index (BMI) and prior exposure to UST 45 mg.Methods: A retrospective, observational, and multicenter study of 74 adult patients who were treated with UST 90 mg at least 24 weeks.Results: Mean (standard deviation [SD]) score on psoriasis area and severity index (PASI) was 7.9 (4.8) at baseline, 3.3 (3.5) at week 16, and 2.2 (2.4) at week 24, when 69.7% of the patients had a PASI under 3. Overweight and obese patients achieved a mean PASI of 2.2 by week 24 (p= .995). In patients who had previously been treated with UST 45 mg (52/74) with insufficient response, mean (SD) absolute PASI score was 2.7 (2.6) at week 24. No serious adverse events were reported.Conclusions: In patients who weigh 100 kg or less but are overweight or obese and do not present an adequate response with UST 45 mg, increasing the dose to UST 90 mg could be an alternative option.

Predictive factors for Enterococcus faecalis in complicated community-acquired urinary tract infections in older patients.

AIM: Risk factors for complicated community acquired Enterococcus faecalis urinary tract infection (UTI) in older patients are not well known. METHODS: We identified the predictive factors for E. faecalis on a cohort of 659 older patients admitted to hospital with complicated UTI. We also examined the adequacy of empirical antimicrobial therapy and outcomes in E. faecalis UTI. Multivariable logistic regression was used to identify predictors of E. faecalis UTI. RESULTS: A total of 87 (13.2%) patients had E. faecalis UTI; of these 63.2% were men, their mean age was 82.3 years and they had a great number of comorbidities. Severe sepsis or septic shock was present in 50.5%, and bacteremia was present in 26%. Indwelling urinary catheter and previous urinary instrumentation were risk factors for E. faecalis UTI by multivariate analysis (OR 2.05; 95% CI 1.15-3.65 and OR 2.16; 95% CI 1.08-4.34, respectively). Inadequate empirical antimicrobial therapy was higher in E. faecalis UTI than in UTI caused by Gram-negative microorganisms (66.6% vs 19%, P < 0.001). No significant differences in length of hospital stay or mortality were noted between E. faecalis and Gram-negative UTI. CONCLUSIONS: In older patients admitted to hospital with complicated community-acquired UTI, E. faecalis should be considered for empirical treatment if the patient has a urinary catheter or previous urinary tract instrumentation in order to avoid inadequate empirical antibiotic therapy. Geriatr Gerontol Int 2019; ••: ••-••.

Biosimilars for the treatment of psoriasis.

Introduction: Biosimilars are biological products that are very similar to their originators, with no meaningful differences in terms of efficacy, safety, and purity. Since the patents of some of the biologics used to treat patients with psoriasis have expired, uptake of biosimilars provides a good opportunity to reduce the cost of treatment. Areas covered: In this review we summarize the stages in development of a biosimilar product, the main differences with the originator biologic, and their potential implications. We have also reviewed clinical trials of biosimilars approved for the treatment of psoriasis. Expert opinion: Because of efficacy and convenience of administration, adalimumab biosimilars will be used to greater extent than etanercept or infliximab to treat patients with moderate-to-severe psoriasis. The pharmacokinetics, efficacy, safety and immunogenicity of approved biosimilars are equivalent to those of their reference products in clinical trials, and multiple-switch studies are intended to provide evidence in support of FDA-required interchangeability. Non-medical switching is expected to become frequent, and the nocebo effect will be relevant. Traceability of biologics is an essential requirement to gather relevant information on their long-term efficacy and safety, especially when multiple switches occur.

Treatment of patients with plaque psoriasis with secukinumab in a real-life setting: a 52-week, multicenter, retrospective study in Spain.

Background: The efficacy and safety of secukinumab in patients with plaque psoriasis (PsO) have been demonstrated in randomized clinical trials (RCTs). However, data regarding its efficacy and safety in real-life settings are scarce. Objectives: To evaluate the efficacy and safety of secukinumab in clinical practice in patients with PsO attending 10 dermatology centers in Spain. Methods: Data from 136 patients consecutively treated with secukinumab for at least 52 weeks were collected in a retrospective observational study. Results: After 52 weeks of treatment, 69% and 46% of patients achieved a PASI-75, PASI-90, respectively. PASI-score ≤5 was achieved in 83% of patients, PASI-score ≤3 in 73% and PASI-score ≤1 in 47%. Response rates were found significantly lower in patients with obesity and non-naïve to biologics (p < .05). The most common adverse event (AE) was candidiasis (5/136). Thirty-six patients (26.5%) discontinued treatment by week 52 due to lack or loss of response (n = 29), AEs (n = 2) or other causes (n = 5). Conclusion: These findings complement the efficacy and safety profiles of secukinumab in PsO outlined in RCTs. The effectiveness in clinical practice may be lower in patients with a BMI ≥30 and those previously treated with other biologic agents.

PRBAM: a new tool to analyze the MHC class I and HLA-DR anchor motifs.

Major histocompatibility complex (MHC) genes are highly polymorphic, which makes each MHC molecule different regarding their peptide repertoire, so they can bind and present to T lymphocytes. The increasing importance of immunopeptidomics and its use in personalized medicine in different fields such as oncology or autoimmunity demand the correct analysis of the peptide repertoires bound to human leukocyte antigen type 1 (HLA-I) and HLA-II molecules. Purification of the peptide pool by affinity chromatography and individual peptide sequencing using mass spectrometry techniques is the standard protocol to define the binding motifs of the different MHC-I and MHC-II molecules. The identification of MHC-I binding motifs is relatively simple, but it is more complicated for MHC-II. There are some programs that identify the anchor motifs of MHC-II molecules. However, these programs do not identify the anchor motif correctly for some HLA-II molecules and some anchor motifs have been deduced using subjective interpretation of the data. Here, we present a new software, called PRBAM (Peptide Repertoire-Based Anchor Motif) that uses a new algorithm based on the peptide-MHC interactions and, using peptide lists obtained by mass spectrometry sequencing, identifies the binding motif of MHC-I and HLA-DR molecules. PRBAM has an easy-to-use interface, and the results are presented in graphics, tables and peptide lists. Finally, the fact that PRBAM uses a new algorithm makes it complementary to other existing programs.

Secukinumab is the most efficient treatment for achieving clear skin in psoriatic patients: a cost-consequence study from the Spanish National Health Service.

OBJECTIVE: To compare the cost consequence of biologic drugs for moderate-to-severe psoriasis from the perspective of the Spanish National Health System. METHODS: We built a decision tree with a two-year time horizon. Efficacy data for biologics (etanercept, infliximab, adalimumab, ustekinumab and secukinumab) were drawn from published meta-analyses: PASI75 for the induction phase and PASI90 for the rest of follow-up. Patients with PASI < 75 at week 10-16 were switched to another biologic agent. Efficacy at week 24 was considered the highest possible efficacy for each drug and assumed to remain constant throughout the two-year period. Only drug treatment costs were used. The number needed to treat (NNT), annual cost per patient, annual cost per patient with PASI90 (cost per responder) and cost of primary failure (PASI < 75 at first efficacy evaluation) were calculated. RESULTS: Secukinumab monotherapy was associated with the lowest cost per responder, followed by infliximab and ustekinumab. Treatment sequences starting with secukinumab were the most efficient, having the lowest NNT and cost per responder. Although the annual cost per treatment is similar for all drugs, there are huge differences in the cost per responder. CONCLUSIONS: Secukinumab as first-line biologic treatment is the most efficient treatment for moderate-to-severe plaque psoriasis in the short-to-medium term.