Hospital General Universitario de Alicante

Diagnosing and treating skin diseases require advanced visual skills across domains and the ability to synthesize information from multiple imaging modalities. While current deep learning models excel at specific tasks such as skin cancer diagnosis from dermoscopic images, they struggle to meet the complex, multimodal requirements of clinical practice. Here we introduce PanDerm, a multimodal dermatology foundation model pretrained through self-supervised learning on over 2 million real-world skin disease images from 11 clinical institutions across 4 imaging modalities. We evaluated PanDerm on 28 diverse benchmarks, including skin cancer screening, risk stratification, differential diagnosis of common and rare skin conditions, lesion segmentation, longitudinal monitoring, and metastasis prediction and prognosis. PanDerm achieved state-of-the-art performance across all evaluated tasks, often outperforming existing models when using only 10% of labeled data. We conducted three reader studies to assess PanDerm’s potential clinical utility. PanDerm outperformed clinicians by 10.2% in early-stage melanoma detection through longitudinal analysis, improved clinicians’ skin cancer diagnostic accuracy by 11% on dermoscopy images and enhanced nondermatologist healthcare providers’ differential diagnosis by 16.5% across 128 skin conditions on clinical photographs. These results show PanDerm’s potential to improve patient care across diverse clinical scenarios and serve as a model for developing multimodal foundation models in other medical specialties, potentially accelerating the integration of artificial intelligence support in healthcare.

Perioperative chemoimmunotherapy has significantly improved survival rates for non-small cell lung cancer (NSCLC). However, current tissue biomarkers remain inadequate, underscoring the need for more sensitive and accessible alternatives to monitor relapse risk. Intratumoral B-cells are increasingly recognized for their role in enhancing immunotherapy outcomes, yet the contribution of peripheral B-cells to immune surveillance remains unexplored. Peripheral B-cell immunophenotypes were analyzed from blood samples (at diagnosis, post-neoadjuvant, and at 6- and 12-months of adjuvant treatment) in 41 stage IIIA NSCLC patients treated with perioperative nivolumab plus chemotherapy, included in the NADIM clinical trial (NCT03081689). Results were correlated with 5-year survival outcomes and validated through unsupervised clustering. An increase in the percentage of total B-cells (CD19⁺CD20⁺) and naïve B-cells (CD19⁺CD20⁺CD24⁺CD38⁺CD27⁻CD10⁻), along with a reduction in CD20 expression on total B-cells, a decrease in the proportion of memory B-cells (CD19⁺CD20⁺CD24⁺CD38−/lowCD27⁺) and transitional B-cells (CD19⁺CD20⁺CD24⁺⁺CD38⁺⁺CD10⁺), was observed during the time encompassed between the end of neoadjuvant treatment and the posterior 6 months of adjuvant treatment. Higher levels of CD20 expression on total B-cells, along with an increased percentage of memory B-cells, or activated B-cells (CD19⁺CD20⁺CD25⁺), at 6- and 12-months of adjuvant treatment, were associated with increased survival. Conversely, higher levels of a newly described circulating population of CD19⁺CD20lowCD25lowCD27low B-cells during adjuvant treatment were linked to disease progression. Perioperative nivolumab plus chemotherapy in resectable NSCLC patients induces significant changes in peripheral B-cells. The persistence of circulating memory B-cells during adjuvant treatment might play a crucial role in survival.

Background and objectives The PAN-PROMISE symptom score is the first patient-reported outcome (PRO) in acute pancreatitis (AP), and it was developed and validated in a prospective cohort of patients to be used as an endpoint in research. The aim of this study was to assess the performance of the score in a large randomized controlled trial (RCT) and its association with well-established AP endpoints. Methods This is an ancillary study of the WATERFALL trial, where PAN-PROMISE was evaluated at baseline, 24, 48 and 72 hours. The study examined the association between PAN-PROMISE with stablished endpoints in AP: severity, pancreatic and/or peripancreatic fat necrosis (necrosis), infected necrosis, intensive care unit (ICU) admission, persistent organ failure (POF), prolonged hospital stay and mortality. Areas under the ROC curve (AUC) were calculated and used to compare baseline PAN-PROMISE and baseline Bedside Index for Severity in AP (BISAP) for the prediction of these endpoints. Results 248 patients from the WATERFALL trial were included. A statistically significant association was found between PAN-PROMISE and severity, necrosis, POF, ICU admission, and prolonged hospital stay at all checkpoints (p<0.05). Higher scores were also significantly associated with infected pancreatic necrosis at 24, 48, and 72h and death at baseline and 24 hours. PAN-PROMISE baseline score had a slightly higher AUC than BISAP for severity and necrosis, but results were not statistically significant. Conclusions In the context of a RCT, the PAN-PROMISE score, a patient-centered measure, has been validated with established AP outcomes and as an endpoint for future clinical trials.

The interpretation of radiological images for head and neck tumors often lacks standardized protocols, increasing the risk of diagnostic inconsistencies. This study introduces a computerized radiological checklist designed to enhance diagnostic accuracy and standardize the evaluation of oropharyngeal squamous cell carcinoma (OPSCC) imaging among otolaryngologists (ENTs). A radiological checklist was developed based on a comprehensive literature review and digitized into an intuitive interface. A concordance study involving 15 ENTs was conducted, assessing 90 OPSCC cases in two phases: before and after using the checklist. Diagnostic agreement with radiologists was measured using Cohen’s kappa coefficient, and a mixed-effects linear model evaluated accuracy improvements, accounting for patient sex, age, stage, and HPV status. The checklist significantly improved diagnostic concordance, increasing Cohen’s kappa from 0.28 (95% CI: 0.09–0.46) without it to 0.66 (95% CI: 0.55–0.77) with it (p < 0.01). The mixed-effects model showed a mean improvement of 2.66 correct responses in the checklist group (SE 0.31, p < 0.001). This study supports the effectiveness of this checklist in improving the diagnostic consistency and accuracy of OPSCC imaging. This method shows promise as a practical tool to reduce errors and enhance clinical practice among ENT specialists. Supplementary Information The online version contains supplementary material available at 10.1038/s41598-025-03895-8.

Importance Understanding the risk factors for symptom development will allow clinicians to stratify people with radiologically isolated syndrome (pwRIS) more effectively and tailor their management strategies accordingly. Objective To identify prognostic factors at radiologically isolated syndrome (RIS) diagnosis associated with the development of multiple sclerosis (MS) symptoms. Design, Setting, and Participants This cohort study was performed in samples collected between July 2004 and September 2022 and included 33 MS centers. All pwRIS who meet the 2017 McDonald criteria for dissemination in space with a sample collected near the diagnostic magnetic resonance imaging were included. No patients who met eligibility criteria were excluded. The data were analyzed from July 2024 to November 2024. Exposure Body fluid biomarkers and environmental factors in pwRIS. Main outcomes and measures The main outcome was the development of MS symptoms. Analyses involved univariable and multivariable Cox proportional hazards models, including age, sex, and treatment following RIS diagnosis, as additional independent variables. Results The study included 273 pwRIS (mean age, 38.6 [SD 11.6] years; 207 women [75.8%] and 66 men [24.2%]) with a median follow-up of 5.0 [IQR, 2.5-7.7] years. A total of 101 pwRIS developed MS symptoms (37.0%). The presence of immunoglobulin G oligoclonal bands (OBs) (hazard ratio [HR], 5.09; 95% CI, 2.36-10.97; P < .001), immunoglobulin M OBs (HR, 2.58; 95% CI, 1.61-4.14; P < .001), and a κ free light chain index of 6.1 or more (HR, 2.79; 95% CI, 1.37-5.67; P = .005) were associated with MS symptoms. High cerebrospinal fluid neurofilament light chain (NfL) levels (HR, 1.31; 95% CI, 1.18-1.45; P < .001) and high serum NfL z scores (HR, 1.42; 95% CI, 1.16-1.72; P = .005) were also associated with an increased risk of MS symptoms. In contrast, high anti-cytomegalovirus titers (HR, 0.59; 95% CI, 0.38-0.93; P = .02) and high ultraviolet radiation exposure in the year before (HR, 0.52; 95% CI, 0.37-0.74; P < .001) and the year after (HR, 0.54, 95% CI, 0.38-0.75; P < .001) diagnosis reduced the risk of MS symptoms. For all these prognostic factors, the multivariable analysis yielded similar results. The combination of high serum NfL z scores and positive immunoglobulin G OBs conferred a 5-year risk of clinical symptoms of 58.3% (95% CI, 45.9-67.9). This risk increased to 81.6% (95% CI, 60.9-91.4) in pwRIS who were younger and positive for immunoglobulin M OBs. Conclusions and Relevance The study elucidates the prognostic factors that significantly impact the risk of developing MS symptoms in pwRIS at diagnosis, thereby, enhancing the potential for tailored clinical interventions.

Background Prurigo nodularis/chronic nodular prurigo (PN/CNP) is a subtype of chronic prurigo characterized by pruritic nodules on the limbs and trunk. It predominantly affects older adults and women. The multifactorial etiology of PN/CNP complicates its diagnosis and treatment. This study aims to evaluate the clinical characteristics, diagnostic approaches, and patient burden of PN/CNP in Spain. Methods This observational, cross‐sectional, multicenter study was conducted across 12 Spanish hospitals and involved adult patients with PN/CNP. Data were collected from clinical records, patient interviews, and self‐administered questionnaires. The study assessed clinical characteristics, diagnostic methods, treatments, and the burden of the disease. Descriptive statistics were used for analysis. Results A total of 97 patients with PN/CNP were included, 65% of whom were female. The cohort had a mean age of 53 years. Most patients were White (87.5%) with Fitzpatrick phototype III (60.9%). Common comorbidities included dyslipidemia (36.1%), atopic dermatitis (33%), and anxiety/depression (30.9%). Topical treatments were used by 67% of patients, while systemic treatments were used by 63.9%. The average time to diagnosis was 4.5 years, and most patients reported mild to moderate pruritus and pain. Key therapeutic goals included reducing itch intensity (76.3%) and lesion count (37.1%). Overall, 66% of patients were satisfied with their treatment. Conclusion This study provides a comprehensive profile of patients with PN/CNP in Spain, highlighting complex clinical characteristics and diverse treatment patterns. The findings emphasize the need for innovative, multidisciplinary approaches to the management of PN/CNP to improve patient care and guide future research.

Guselkumab, a selective interleukin-23 (IL-23) inhibitor, has emerged as a promising biologic therapy for the management of patients with moderate-to-severe Crohn’s disease (CD) and has been recently approved for its treatment. Unlike conventional therapies, guselkumab offers a different mechanism of action by selectively inhibiting IL-23, a key cytokine implicated in the pathogenesis of CD. IL-23 drives intestinal inflammation through activation of the Th17 cell pathway and other immune processes, positioning IL-23 inhibition as a critical therapeutic approach. In randomized Phase III clinical trials, guselkumab proved to be effective in inducing clinical and endoscopic remission both in patients naive to biologics and in patients already exposed to advanced therapies. Furthermore, no safety issues were found, supporting the well-characterized safety in other indications and its use in clinical practice also in IBD. Moreover, guselkumab has been approved for other immunomediated inflammatory disease moderate to severe plaque psoriasis, psoriatic arthritis and ulcerative colitis. This review summarizes the available evidence on efficacy and safety of guselkumab in patients with moderate to severe CD, focusing on its positioning in the treatment algorithm.

Relapse is the main cause of treatment failure in T‐cell acute lymphoblastic leukemia (T‐ALL). Despite this, data from adult T‐ALL patients treated with specific chemotherapeutic regimens that examine predictive markers and describe relapse mechanisms are scarce. In this study, we studied 74 paired diagnosis‐relapse samples from 37 patients homogeneously treated with three consecutive measurable residual disease‐oriented trials to identify genetic determinants involved in relapse in adult T‐ALL. Analysis of single‐nucleotide variants and copy number alterations consistently found N/KRAS mutations (20% relapsed cases) at diagnosis and at relapse (resistance profile). N/KRASmut patients frequently relapse early during consolidation treatment. Relapse‐specific mutations in NT5C2, NR3C1, SMARCA4, and TP53 (40% relapse cases) were not detected at diagnosis by conventional molecular techniques (relapse profile). However, single‐cell‐based analysis revealed a very minor clone containing the NT5C2(p.R367Q) variant at diagnosis. Patients with the NT5C2(p.R367Q) variant mostly relapse later during maintenance treatment. Tracking the NT5C2 variant by digital PCR confirm the expansion of the NT5C2 clone at maintenance treatment. Overall, our exploratory analysis suggests a role for these genetic events, most of which have already been described in pediatric cases, driving resistance associated to specific chemotherapeutic agents, contributing to the relapse of a high proportion of adult T‐ALL patients (60%).

Background Severe asthma is frequently associated with psychological comorbidities that negatively affect disease control and quality of life. Despite clinical guideline recommendations, psychological care remains limited in multidisciplinary asthma units. Objective To evaluate the effectiveness of an online group psychological intervention in improving emotional well-being and disease control in patients with severe asthma. Methods A longitudinal study was conducted between 2021 and 2024 in a specialized severe asthma unit. The intervention consisted of eight weekly online sessions combining cognitive-behavioral techniques and emotional regulation strategies. Psychological and quality-of-life variables were assessed at baseline, post-intervention, and at 6 and 12 months of follow-up. Results A total of 41 patients completed the program. Significant and sustained improvements were observed in anxiety, depression, hyperventilation, and asthma-related quality of life up to 12 months after the intervention. No changes were found in alexithymia, perceived social support, or family functioning. Conclusion An online group psychological intervention is a feasible and effective approach to improving emotional health and quality of life in patients with severe asthma. Its integration into asthma care units may contribute to a more comprehensive and patient-centered management strategy.

Purpose Patients with non-severe hemophilia A (PwnSHA) may be at risk for joint damage (JD), yet data remain scarce. Our aim was to evaluate the joint condition in PwnSHA in a real-world setting. Patients and Methods A nationwide, multicenter, cross-sectional study was conducted. To mitigate the impact of discrepancies between factor VIII (FVIII) assays, baseline FVIII levels were determined using chromogenic and one-step clotting assays. Mutation in F8 gene, baseline FVIII levels, thrombin generation and age were assessed. The joint condition was described using the HEAD-US score by trained specialists at each participating hospital. Results One hundred and twenty-four patients were recruited, 84 of them with an available HEAD-US evaluation, who were finally included in our analysis. The median age was 38.4 years (18.3–48.5). Twenty percent (16/84) had moderate hemophilia (MoH) with FVIII levels of 4.0 IU/dL (2.6–4.6), and 80% (68/84) had mild hemophilia (MiH) with FVIII levels of 14.8 IU/dL (10.4–19.9), (p< 0.001). JD (HEAD-US>0) was observed in 50% (8/16) of MoH patients (HEAD-US= 6.5 [5.5–8.5]) and in 40% (27/68) of those with MiH (HEAD-US= 3.0 [2.0–6.5]), p=0.198. In the moderate group, JD was primarily observed in ankles (44%), while in the MiH group, knees were the most affected (31%). MoH patients reported a hypocoagulable thrombin generation profile compared to MiH patients (p<0.05). Conclusion Near half of PwnSHA had JD. A worse joint health and a lower thrombin generation was observed in MoH population. These patients can benefit from an early prophylaxis and prevent further joint deterioration. Future research should explore additional variables that might influence joint condition.

Background Registry studies are needed to provide comprehensive and updated assessments of the long‐term safety profiles of systemic drugs in psoriasis. Objective To analyse the safety of biologic drugs and new oral molecules used for the treatment of moderate‐to‐severe psoriasis in patients included in the Spanish Registry of Adverse Events of Biological Therapy (BIOBADADERM), compared to that of adalimumab. Methods Prospective, multicentre cohort of patients with psoriasis. The safety profiles of biologic agents (etanercept, infliximab, adalimumab, certolizumab, ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab and tildrakizumab), apremilast and dimethyl fumarate were studied. The incidence rate ratio (IRR) and adjusted IRR of specific adverse events were assessed for each drug, using adalimumab as a reference. Propensity scores were used to adjust for selection bias. Results Our study included 4212 patients (7590 treatment cycles; 17,284 patient‐years of follow‐up). Adalimumab had an incidence rate for all adverse events of 614 per 1000 patient‐years (95% confidence interval [CI] (591; 637)). The risk of all adverse events was significantly lower for guselkumab (adjusted IRR [aIRR] 0.56, 95% CI (0.47; 0.67)), risankizumab (aIRR 0.59, 95% CI (0.48; 0.71)), tildrakizumab [aIRR 0.6, 95% CI (0.46; 0.8)], ixekizumab (aIRR 0.65, 95% CI (0.56; 0.76)) and ustekinumab (aIRR 0.73 95% CI (0.65; 0.82)) compared to adalimumab ( p ≤ 0.002), as well as the risk for some specific organ‐based groups of adverse events. Conversely, the risk for all adverse events was significantly higher for dimethyl fumarate (aIRR 3.67, 95% CI (2.71; 4.97)), infliximab (aIRR 1.88, 95% CI (1.45; 2.43)) ( p ≤ 0.002) and apremilast (aIRR 1.27, 95% CI (1.05; 1.53)) ( p 0.012). The risk of malignant neoplasms was significantly reduced in the group treated with ixekizumab (aIRR 0.14 95% CI (0.04; 0.47)). Conclusion Our data support that, overall, the new biologic treatments have a superior safety profile in real‐world practice compared to adalimumab and its biosimilars.

The rationale for intraperitoneal chemotherapy after complete macroscopic cytoreduction (CC-0) is well-established for peritoneal surface malignancies. This study aimed to analyze prognostic factors for disease-free survival (DFS) of patients with high-grade serous ovarian cancer (HGSOC) undergoing interval CC-0 cytoreductive surgery (iCRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This retrospective multicenter study included 293 HGSOC patients treated between January 2010 and May 2023. All the patients received neoadjuvant platinum-based chemotherapy followed by CC-0 iCRS and HIPEC with cisplatin or paclitaxel. Prognostic factors for DFS were analyzed using Kaplan–Meier curves, log-rank tests, and Cox proportional hazards regression. The median DFS was 23 months, with 3- and 5-year survival rates of 39 % and 29 %, respectively. The patients with a peritoneal carcinomatosis index (PCI) of 15 or lower had significantly better DFS than those with a PCI greater than 15 (24 vs 15 months; p < 0.05). Paclitaxel-based HIPEC was associated with superior DFS compared with cisplatin (25 vs 16 months; p < 0.05). Multivariate analysis showed a PCI greater than 15 related to a lower DFS (hazard ratio [HR], 1.539; p = 0.048) and paclitaxel-based HIPEC as a factor associated with better DFS (HR, 0.663; p = 0.016). The patients treated with HIPEC-paclitaxel and with a PCI of 15 or lower demonstrated the best outcomes (median DFS, 33 months). In HGSOC, the PCI is the most significant determinant of DFS after CC-0 iCRS and HIPEC. Paclitaxel-based HIPEC showed better outcomes than cisplatin, particularly for patients with a PCI of 15 or lower. Further prospective studies are needed to confirm the role of paclitaxel and to evaluate BRCA mutation and homologous recombination deficiency status in treatment efficacy.

Our aim was to evaluate long-term health-related quality of life (HRQoL) in 253 people living with HIV (PLH) from the CoRIS cohort presenting to care with advanced HIV disease (AIDS or CD4 ≤ 100 cells/µL) and who had survived ≥ 5 years. Participants completed the WHOQOL-HIV-BREF and EQ-5D-5 L questionnaires. Clinical and immunological data were provided by the CoRIS at enrollment and on questionnaire completion. Linear repeated measures analyses assessed the evolution of immunological markers. Partial least squares structural equation modeling showed the longitudinal impact of baseline immunological markers on HRQoL. High baseline CD4 counts predicted higher WHOQOL-HIV-BREF independence scores (p = 0.021) and a marginally higher EQ-5D-5 L index value (p = 0.058), which was also associated with CD8 (p = 0.015). A higher CD4/CD8 ratio predicted lower scores on the WHOQOL-HIV-BREF ‘spirituality, religion and personal belief’ dimension (p = 0.006). Currently, PLH who present with advanced HIV disease achieve a moderate long-term HRQoL, with room for improvement.

BACKGROUND The “textbook outcome” (TO) is defined as a composite indicator that signifies the ideal postoperative course following surgical intervention. To date, TO in hernias has not been studied deeply. This study aims to determine TO in W3 incisional hernia repair using data from the Spanish national EVEREG registry and analyze the variables associated with achieving TO. STUDY DESIGN A retrospective observational study of W3 incisional hernia repair from the EVEREG registry was performed between January 2012 and December 2022. TO for W3 incisional hernia was defined as: hospital stay <8 days, no major postoperative complications (Clavien-Dindo ≥IIIa), and no mortality or readmission within 30 days of surgery. Characteristics between TO group and versus non-TO group were compared using both univariable and multivariable logistic regressions. RESULTS A total of 2763 patients were included in the study. TO was achieved in 2099 patients (75.97%), a prolonged hospital stay was the main factor related to nonachievement. There were multiple variables statistically associated with textbook outcome achievement. Also, eventration through an umbilical trocar, clean surgery, laparoscopic approach, the use of non-biological mesh, elective surgery or high-risk patients parameters were identified as a statistically significant predictor of textbook outcome achievement. CONCLUSIONS We propose novel TO criteria for W3 incisional hernia repair. In this database, the rate of TO was 76%. TO is a composite measure that can be used to carry out healthcare quality improvement programs and compare results between hospitals.

Background: The primary treatment of schizophrenia is pharmacotherapy with antipsychotic agents, such as risperidone and paliperidone. Population pharmacokinetic (PopPK) modelling plays a crucial role in optimising therapy by predicting of plasma concentrations, therapeutic efficacy, and the risk of adverse effects using model informed precision dosing. Objectives: This systematic review examined the PopPK models of risperidone and paliperidone in patients diagnosed with schizophrenia based on the available scientific evidence. Methods: A systematic review of the health science databases was conducted. The inclusion criteria were original articles published in peer-reviewed journals, studies focusing on the development of original PopPK models of risperidone and paliperidone, and clinical studies. The exclusion criteria were full-text articles that could not be retrieved; studies not including subjects diagnosed with schizophrenia or schizoaffective disorders; and studies that did not investigate risperidone or paliperidone. Results: A total of 19 studies developing PopPK models were analysed, including one- or two-compartment PopPK model structures. Interindividual variability in the pharmacokinetic parameters was shown to be influenced by factors such as CYP2D6 activity, renal function, body mass index, and sex. Parameter estimation revealed high variability in clearance and volume of distribution. Conclusion: Numerous PopPK models for risperidone and paliperidone have been published with a detailed characterisation of absorption, metabolism, and elimination. Therefore, future research should focus on the external validation of these models to facilitate their integration into clinical practice and optimise individualised dosing, ultimately improving treatment efficacy and safety across diverse patient populations.

Background The emergence and spread of third-generation cephalosporins (3GC) and carbapenem-resistant Klebsiella pneumoniae pose a global critical challenge. Understanding the transmission dynamics within and between hospital environments is crucial to develop effective control strategies. Methods From 2017 to 2019, we conducted a genomic surveillance program in eight hospitals of the Comunitat Valenciana, Spain, collecting and sequencing 1,768 3GC- and carbapenem-resistant isolates. We quantified the overall transmission using core genomes and assessed the contribution of national and global isolates to the spread of AMR in the region by including 11,967 database genomes in the analysis. Results The local collection was highly diverse, involving 188 lineages, including global high-risk clones such as ST307 and ST11, and 3GC and carbapenem resistance determinants. Half of the isolates were involved in transmission, with 70.5% occurring within hospitals. Conclusions Different transmission patterns characterized the spread of 3GC- and carbapenem resistance in the region. While inter-hospital transmission played a significant role in the spread of 3GC-resistance, this was only sporadic for carbapenem resistance. Moreover, the factors behind inter-hospital spread for each type of resistance differed: while 3GC-resistance likely disseminated between hospitals through intermediate steps, carbapenem resistance was driven by more direct transmission routes. The burden of national and global cases on the ongoing regional AMR dissemination was low. Moreover, we revealed the rapid expansion in the region and globally of lineage ST307 carrying the blaCTX-M-15 gene, a main driver of local transmissions, providing a deeper understanding of the successful spread of this high-risk clone.

Purpose Telepharmacy must be monitored within a quality management system in order to guarantee the efficiency, safety and quality of the activities it encompasses. The Spanish Society of Hospital Pharmacy has proposed the first scorecard of quality and activity indicators for Telepharmacy (TIS). The objective of this project is to validate this TIS for its implementation in hospital pharmacy services. Material and Methods The project was developed in 4 phases: elaboration of the validation questionnaire/validation criteria; selection of hospitals where the study will be carried out; completion of the validation questionnaire by the selected hospitals; analysis of the results, a proposal of conclusions, and preparation of the final document. The validation criteria were performed using the RAND/UCLA methodology for each of the 5 TIS characteristics: holistic, practical, quantitative, usability, and continuous improvement. Characteristics were considered validated when the median was found to be within the score range 5–9 and at least 2/3 (66.66%) of the respondents scored in the range containing the median. Results Forty-four hospitals were included and the responses related to TIS characteristics were: holistic=8.2 and 98.5% of responses >5; practical=7.9 and 98.9% of responses >5; quantitative=7.9 and 98.6% of responses >5; usability=6.9 and 87.37% of responses >5; continuous improvement= 7.9 and 100% of responses >5. Discussion TIS has been validated for use in hospital pharmacy services and its tools and supporting documents are very useful and comprehensive. Hospital informatics systems are needed to allow efficient extraction of the data necessary to obtain the TIS indices.