Allergic contact dermatitis in adults with and without atopic dermatitis: Evaluation of the Spanish Contact Dermatitis Registry (REIDAC).

BACKGROUND: Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are inflammatory skin conditions whose association is not clearly defined. OBJECTIVES: To identify differences in ACD profile between patients with and without AD among those referred for patch testing. Additionally, to determine the prevalence of sensitisation to standard Spanish contact allergens in both groups. METHODS: We analysed two groups (AD and non-AD) within the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy (REIDAC). Contact allergy, clinical relevance and epidemiological data were compared between them. RESULTS: A total of 5055 patients were included. Among them, 23% (1168) had a history or final diagnosis of AD. At least one positive reaction was seen in 468 (40%) of AD patients and 1864 (48%) of non-AD patients. In both groups, the most common positive reactions were to nickel sulphate, methylchloroisothiazolinone/methylisothiazolinone and cobalt chloride. Age-adjusted OR for sensitisation to nickel sulphate was 0.72 (95% CI: 0.61-0.86), indicating a decreased likelihood of sensitisation in AD patients compared to non-AD individuals. CONCLUSIONS: We did not find an increased presence of ACD in patients with AD referred for patch testing, exhibiting similar profiles to non-AD population, except for a negative relationship between AD and sensitisation to nickel sulphate.

Utilization of abdominal radiography in the emergency department: Appropriateness, interpretation, radiation protection and costs.

INTRODUCTION: The use of abdominal radiography (AXR) apparently continues to be widespread despite its limited indications, the potential radiation and unnecessary costs associated. In addition, the interpretation and its report seem variable and not always performed by a radiologist. Our objective is to analyze the use, adequacy and usefulness of AXR in the emergency of a tertiary referral hospital. MATERIAL AND METHODS: We retrospectively reviewed all the AXR performed in January 2020 in the emergency of our centre, as well as the patient's demographics and medical records, technical quality of the radiographs, indications according to the SERAM (Spanish Society of Radiology) Appropriateness Guidelines, presence of a formal radiology report, and impact on the clinical management of the patient. Of all non-appropriated AXR we calculated the radiation received by the patients and its extra costs. RESULTS: In January 2020, 429 AXR (9.1% of all radiographies) were performed in the emergency of our centre. The most frequent indication was abdominal pain (40%, n = 176), followed by low back pain (21.4%, n = 92). 12.4% of AXR requested did not include any clinical information. Most of the AXR (79.6%) had sufficient technical quality. 61.3% (n = 263) of the AXR performed were not indicated, assuming an average unjustified radiation dose per patient of 0.50 ±â€¯0.33 mSv, and a total additional cost of 6575;. Only 6% of the inadequate AXRs led to a change in the clinical management of the patient, compared to 29% of the adequate AXR (p < 0.001). Only 3% of the AXR had a formal radiology report. CONCLUSIONS: AXR is still common in the emergency setting, although most of them might be inadequate according to the SERAM Appropriateness Guidelines. Its use should be optimized to avoid unnecessary radiation and costs. Radiologists must have a more active participation in the management of AXR.

Evolution of Salmonella spp. isolated compared to those of Campylobacter spp. in faecal samples for 12 years.

OBJECTIVE: The Autonomous Community of Galicia has adopted DECREE 216/2011 on health standards for poultry production, in addition to the Spanish national programs. However, no program has yet been implemented to eradicate campylobacteriosis, which shares the same reservoir. The aim of this study was to compare the evolution of Salmonella spp. isolates with respect to those of Campylobacter spp. in faecal samples received by the Microbiology Department. METHODS: A retrospective descriptive comparative study was conducted through the Laboratory Information System (SIL) of Salmonella spp. isolated against Campylobacter spp. in faeces between 2011 and 2022 at the Lucus Augusti University Hospital (HULA), Lugo, Spain. RESULTS: A total of 35,704 stool samples were analysed, of which 3,045 were positive. 751 Salmonella spp. were isolated. Statistical differences were observed in the annual distribution (p<0.01), with a clear turning point in 2018. Five hundred and five patients required hospital care, especially in 2014 with 72 patients (69%). On the other hand, 1,587 Campylobacter spp. were isolated. Required hospital care 1,002 patients during the study, with a peak in 2019 with 111 cases (62%). CONCLUSIONS: The reduction of salmonellosis cases and the maintenance of campylobacteriosis cases are directly related to the implementation of DECREE 216/2011. This, in turn, has reduced the pressure on hospitals in the HULA health area. Therefore, we believe that the ONE Health concept is being strengthened in the area studied.

EEG for good outcome prediction after cardiac arrest: A multicentre cohort study.

AIM: Assess the prognostic ability of a non-highly malignant and reactive EEG to predict good outcome after cardiac arrest (CA). METHODS: Prospective observational multicentre substudy of the "Targeted Hypothermia versus Targeted Normothermia after Out-of-hospital Cardiac Arrest Trial", also known as the TTM2-trial. Presence or absence of highly malignant EEG patterns and EEG reactivity to external stimuli were prospectively assessed and reported by the trial sites. Highly malignant patterns were defined as burst-suppression or suppression with or without superimposed periodic discharges. Multimodal prognostication was performed 96 h after CA. Good outcome at 6 months was defined as a modified Rankin Scale score of 0-3. RESULTS: 873 comatose patients at 59 sites had an EEG assessment during the hospital stay. Of these, 283 (32%) had good outcome. EEG was recorded at a median of 69 h (IQR 47-91) after CA. Absence of highly malignant EEG patterns was seen in 543 patients of whom 255 (29% of the cohort) had preserved EEG reactivity. A non-highly malignant and reactive EEG had 56% (CI 50-61) sensitivity and 83% (CI 80-86) specificity to predict good outcome. Presence of EEG reactivity contributed (p < 0.001) to the specificity of EEG to predict good outcome compared to only assessing background pattern without taking reactivity into account. CONCLUSION: Nearly one-third of comatose patients resuscitated after CA had a non-highly malignant and reactive EEG that was associated with a good long-term outcome. Reactivity testing should be routinely performed since preserved EEG reactivity contributed to prognostic performance.

Resultados de cirugía resectiva colorrectal por Endometriosis Infiltrante Profunda: 6 años de experiencia

Objetivo: Describir los resultados tempranos de la cirugía resectiva colorrectal por Endometriosis Infiltrante Profunda (EIP) en mujeres intervenidas en centro clínico privado, durante los últimos 6 años. Material y Método Estudio transversal que muestra la evolución clínica de pacientes intervenidas quirúrgicamente con resecciones colorrectales por diagnóstico de (EIP), entre los años 2016-2022 en Clínica Indisa. Se agruparon en resecciones discoidales (Grupo I) y segmentarias (Grupo II) Resultados: De los pacientes operados por (EIP) entre los años 2016 al 2022, 160 pacientes fueron sometidas a resecciones colorrectales, 56 en el Grupo I y 104 en el grupo II. Las características demográficas de ambos grupos fueron similares, con excepción del hábito tabáquico que mostró un predominio en el Grupo II. El análisis de las variables quirúrgicas (tipo de abordaje, tasa de conversión, altura de la anastomosis y ostomía de protección) mostró una distribución similar en ambos grupos. En relación a la evolución postoperatoria, el Grupo I presentó una disminución significativa en el tiempo de realimentación con sólidos de 2 vs 3 días (p = 0,001). El inicio del tránsito intestinal, días de hospitalización y presencia de complicaciones Clavien-Dindo > = 3, no presentó diferencias significativas entre ambos grupos. Discusión: La endometriosis afecta, significativamente, a mujeres en todo el mundo, existiendo escasa evidencia que reporte los resultados de las cirugías colorrectales que comparen ambas técnicas, demostrando que el manejo en centros especializados tiene mejores resultados. Conclusión: Al comparar estas dos técnicas de resección colorrectal en DIE, concluimos que los pacientes operados por resección discoidal tienen una realimentación más temprana sin diferencias significativas en el resto de las variables estudiadas.

Objective: To describe the early outcomes of resective colorectal surgery for Deep Infiltrating Endometriosis (DIE) in women treated at private center over the past 6 years. Materials and Methods: This cross-sectional study presents the clinical evolution of surgically treated patients with colorectal resections for DIE diagnosis between 2016 and 2022 at Clínica INDISA. They were grouped into discoid resections (Group I) and segmental resections (Group II). Results: Of patients operated for DIE between 2016 and 2022, 160 underwent colorectal resections, with 56 in Group I and 104 in Group II. The demographic characteristics of both groups were similar, except for smoking habits, which showed a predominance in Group II. The analysis of surgical variables (approach type, conversion rate, anastomotic height, and protective ostomy) showed a similar distribution in both groups. Regarding postoperative outcomes, Group I showed a significant decrease in solid food resumption time, 2 vs 3 days (p = 0.001). The initiation of intestinal transit, hospitalization days, and presence of Clavien-Dindo complications >= 3 did not present significant differences between both groups. Discussion: Endometriosis significantly affects women worldwide, with limited evidence reporting colorectal surgery outcomes comparing both techniques, demonstrating that management in specialized centers yields better results. Conclusion: When comparing these two techniques of colorectal resection in DIE, we conclude that patients undergoing discoid resection have an earlier resumption of solid food intake without significant differences in the remaining studied variables.

New reference nomograms for the study of ventricular size in preterm infants.

INTRODUCTION: Transfontanellar brain ultrasound is an essential tool for monitoring the size of the ventricles in preterm neonates and has many advantages over other alternative diagnostic techniques, including its accessibility and non-use of ionizing radiation. When considering the normal ventricular size, it is essential to have reference measurements based on age-matched populations. The objective of this article is to present our reference measures, based on a sample of preterm infants that we have studied. METHODS: A retrospective observational study was conducted. Measurements of the Levene index, frontal horn thickness, and Evans index were obtained in preterm neonates from 25 to 45 weeks, over a period of 5 years, between January 2016 and December 2020. After applying the exclusion criteria, a sample of 199 patients and 350 ultrasound scans were obtained. The independent samples t-test and the Mann-Whitney test were used for the comparison of samples. RESULTS: The distribution of the right and left Levene indices was normal (Shapiro-Wilk test with p = 0.16 and 0.05, respectively), unlike the thickness distribution of the frontal horns (p < 0.05 on both sides). No significant differences were detected between the sexes (p = 0.08). A linear correlation was found between the biparietal diameter and the Levene index. CONCLUSION: From the results obtained in our study, we present reference tables for ventricular size, with the 3rd, 25th, 50th, 75th, and 97th, being the first ones made in our country.

Protocol of a clinical trial on the effectiveness of pudendal nerve block with and without neurostimulation in reducing posthemorroidectomy pain.

INTRODUCTION: Hemorrhoidal pathology is the most frequent proctological problem with a prevalence of 44% of the adult population. The most effective treatment is surgery but it also has the highest postoperative pain rate with moderate to severe pain rates of 30-40% during the first 24-48 hours. Here lies the importance of seeking measures to improve this situation, such as the pudendal nerve block with local anesthetic. However, the variability of the pudendal nerve sometimes makes its blockade ineffective and for this reason nerve location methods are sought to achieve a higher rate of success. The main aim of the study is to compare pain in the immediate postoperative period (24 h) after hemorrhoidectomy in patients with pudendal nerve block guided by anatomical references and guided by neurostimulation. METHODS: The present project proposes the performance of a single-center, triple-blind, randomized clinical trial of efficacy, carried out under conditions of routine clinical practice. Patients over 18 years old with hemorrhoids refractory to medical treatment, symptomatic grade III-IV and grade II hemorrhoids that do not respond to conservative procedures in a third level hospital in Spain and that are subsidiaries of surgery in major ambulatory surgery will be included. Demographic variables, variables on hemorrhoidal pathology, details of surgery, verbal numeric pain scale in the preoperative period and surgical complications will be collected. RESULTS: Not avaliable until the end of the study. CONCLUSIONS: The pudendal nerve block guided by anatomical landmarks has been shown to be useful in postoperative pain control after hemorrhoidectomy although the use of the neurostimulator has not been well studied and we believe it may improve outcom.

Genomic analysis of inbreeding level, kinship and breed relationships in Creole cattle from South America.

The conservation of animal genetic resources refers to measures taken to prevent the loss of genetic diversity in livestock populations, including the protection of breeds from extinction. Creole cattle populations have suffered a drastic reduction in recent decades owing to absorbent crosses or replacement with commercial breeds of European or Indian origin. Genetic characterization can serve as a source of information for conservation strategies to maintain genetic variation. The objective of this work was to evaluate the levels of inbreeding and kinship through the use of genomic information. A total of 903 DNAs from 13 cattle populations from Argentina, Bolivia and Uruguay were genotyped using an SNP panel of 48 K. Also, a dataset of 76 K SNPs from Peruvian Creole was included. Two inbreeding indices (FROH and Fhat2) and kinship relationships were calculated. In addition, effective population size (Ne), linkage disequilibrium, population composition and phylogenetic relationships were estimated. In Creole cattle, FROH ranged from 0.14 to 0.03, and Fhat2 was close to zero. The inferred Ne trends exhibited a decline toward the present for all populations, whereas Creole cattle presented a lower magnitude of Ne than foreign breeds. Cluster analysis clearly differentiated the taurine and Zebu components (K2) and showed that Bolivian Creole cattle presented Zebu gene introgression. Despite the population reduction, Creole populations did not present extreme values of consanguinity and kinship and maintain high levels of genetic diversity. The information obtained in this work may be useful for planning conservation programmes for these valuable local animal genetic resources.

Impact of hypochloremia as a prognostic factor in patients with heart failure, a retrospective cohort study.

BACKGROUND: some studies suggest that hypochloremia is a risk factor in the prognosis of heart failure (HF) in patients with recent decompensation. MATERIALS AND METHODS: retrospective cohort study of patients discharged due to HF decompensation who began follow-up in a specialized clinic. Two groups are defined: patients with hypochloremia (chloride < 98 mmol/L) and normochloremic patients (chloride > 98 mmol/L) in the initial assessment within the first month after discharge. The rate of intravenous diuretic rescue, emergency department visits, readmission for HF and cardiovascular (CV) death are compared using a Cox proportional hazards model. RESULTS: 165 patients were included (59% women, mean age 85 years), with 60 (36%) having hypochloremia. Both groups were comparable in terms of baseline characteristics, except for female sex, presence of peripheral artery disease, moderate-to-severe liver disease (more prevalent in the hypochloremia group), PROFUND index, and baseline furosemide dose (higher in patients with hypochloremia). The incidence of the primary event was higher in subjects with hypochloremia than in normochloremic subjects (HR: 1.59, 95% CI 0.97-2.62), mainly due to the need for intravenous diuretic rescue (HR: 1.86, 95% CI 1.07-3.24). CONCLUSIONS: hypochloremia following admission for HF decompensation is associated with a greater need for intravenous diuretic rescue therapy and probably worse overall prognosis across the spectrum of the disease, regardless of left ventricular ejection fraction (LVEF).

Clinical validation of a capnodynamic method for measuring end-expiratory lung volume in critically ill patients.

RATIONALE: End-expiratory lung volume (EELV) is reduced in mechanically ventilated patients, especially in pathologic conditions. The resulting heterogeneous distribution of ventilation increases the risk for ventilation induced lung injury. Clinical measurement of EELV however, remains difficult. OBJECTIVE: Validation of a novel continuous capnodynamic method based on expired carbon dioxide (CO2) kinetics for measuring EELV in mechanically ventilated critically-ill patients. METHODS: Prospective study of mechanically ventilated patients scheduled for a diagnostic computed tomography exploration. Comparisons were made between absolute and corrected EELVCO2 values, the latter accounting for the amount of CO2 dissolved in lung tissue, with the reference EELV measured by computed tomography (EELVCT). Uncorrected and corrected EELVCO2 was compared with total CT volume (density compartments between - 1000 and 0 Hounsfield units (HU) and functional CT volume, including density compartments of - 1000 to - 200HU eliminating regions of increased shunt. We used comparative statistics including correlations and measurement of accuracy and precision by the Bland Altman method. MEASUREMENTS AND MAIN RESULTS: Of the 46 patients included in the final analysis, 25 had a diagnosis of ARDS (24 of which COVID-19). Both EELVCT and EELVCO2 were significantly reduced (39 and 40% respectively) when compared with theoretical values of functional residual capacity (p < 0.0001). Uncorrected EELVCO2 tended to overestimate EELVCT with a correlation r2 0.58; Bias - 285 and limits of agreement (LoA) (+ 513 to - 1083; 95% CI) ml. Agreement improved for the corrected EELVCO2 to a Bias of - 23 and LoA of (+ 763 to - 716; 95% CI) ml. The best agreement of the method was obtained by comparison of corrected EELVCO2 with functional EELVCT with a r2 of 0.59; Bias - 2.75 (+ 755 to - 761; 95% CI) ml. We did not observe major differences in the performance of the method between ARDS (most of them COVID related) and non-ARDS patients. CONCLUSION: In this first validation in critically ill patients, the capnodynamic method provided good estimates of both total and functional EELV. Bias improved after correcting EELVCO2 for extra-alveolar CO2 content when compared with CT estimated volume. If confirmed in further validations EELVCO2 may become an attractive monitoring option for continuously monitor EELV in critically ill mechanically ventilated patients. TRIAL REGISTRATION: clinicaltrials.gov (NCT04045262).

Severe pulmonary hypertension and circulatory failure associated with Congenital syphilis. Case report.

BACKGROUND: Congenital syphilis is a vertical infection caused by Treponema pallidum. Despite the implementation of preventive strategies during pregnancy, its incidence is increasing, and it constitutes an important public health problem. Most patients with congenital syphilis are asymptomatic; however, a small group may develop severe disease at birth with the need of advanced resuscitation in the delivery room, acute hypoxemic respiratory failure, and hemodynamic instability. Therefore, awareness is needed. METHODS AND RESULTS: This series describes the clinical course of two late preterm infants with congenital syphilis who developed acute hypoxemic respiratory failure, pulmonary hypertension, and circulatory collapse early after birth. Integrated hemodynamic evaluation with neonatologist-performed echocardiography (NPE) and therapeutic management is provided. CONCLUSIONS: A comprehensive hemodynamic evaluation including early and serial functional echocardiography in these patients is needed to address the underlying complex pathophysiology and to help to establish accurate treatment.

Standard and Expanded Series Patch Testing Update by the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC). / Actualización de la batería estándar y batería ampliada de pruebas alérgicas de contacto por el Grupo Español de Investigación en Dermatitis de Contacto y Alergia Cutánea (GEIDAC).

After the meeting held by the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) back in October 2021, changes were suggested to the Spanish standard series patch testing. Hydroxyethyl methacrylate (2% pet.), textile dye mixt (6.6% pet.), linalool hydroperoxide (1% pet.), and limonene hydroperoxide (0.3% pet.) were, then, added to the series that agreed upon in 2016. Ethyldiamine and phenoxyethanol were excluded. Methyldibromoglutaronitrile, the mixture of sesquiterpene lactones, and hydroxyisohexyl 3-cyclohexene (Lyral) were alo added to the extended Spanish series of 2022.

Congenital stromal corneal dystrophy in a Spanish family: Clinical, genetic and histological analysis.

PURPOSE: To present the clinical, genetic, and histopathological features of the ninth family affected by congenital stromal corneal dystrophy (CSCD) to date. METHODS: Twelve cases of a Spanish family affected by CSCD were analyzed regarding history, visual acuity (VA, decimal scale), an ophthalmologic exam and specular microscopy. Five eyes were treated by deep anterior lamellar keratoplasty (DALK), and thirteen eyes by penetrating keratoplasty (PK). In the two last generations, a genetic study was performed. RESULTS: Most of the patients affected were born with opaque corneas except for three, whose corneas were clear at birth. Biomicroscopy showed a whitish diffuse stromal opacity with an unaltered epithelium, causing poor VA (from hand motions to 0.4). Patients treated with PK presented mean postoperative VA of 0.19±0.20 over a follow-up time of 235.3±101.4months with 38% recurrences. Patients who underwent DALK experienced VA improvement to 0.17±0.11 over a follow-up time of 10.8±2.6months without signs of recurrence. In the latter, the big bubble technique was not achieved, so a manual technique was performed. The genetic study showed heterozygosis for a 1-bp deletion at nucleotide 962 in exon 8 of the decorin gene. CONCLUSIONS: CSCD is a rare entity, which should be treated by DALK whenever possible, obtaining better results than PK. Close monitoring of children of affected individuals is important, because CSCD can progress during the early years of life.

Epidemiological, Clinical, and Allergic Profile of Psoriatic Patients. Evaluation of the Spanish Registry of Contact Dermatitis and Cutaneous Allergy (REIDAC). / Perfil epidemiológico, clínico y alérgico en pacientes con psoriasis. Evaluación del Registro Español de Dermatitis de Contacto (REIDAC).

BACKGROUND: Psoriasis is a chronic inflammatory dermatosis whose clinical and topographic distribution requires differential diagnosis, or the possible association with allergic contact dermatitis (ACD), requiring patch testing (PT) as part of the diagnostic procedure. OBJECTIVES: To describe the epidemiological, clinical, and allergic profile of patients with a primary or secondary diagnosis of psoriasis undergoing PT and compare them with patients with a diagnosis of ACD at the end of the diagnostic process. METHODS: Cross-sectional study with data from REIDAC from 2018 through 2023 of selected patients with a diagnosis of psoriasis and/or ACD. RESULTS: A total of 11 502 patients were included, 513 of whom had been diagnosed with primary or secondary psoriasis, 3640 with ACD, and 108 with both diseases. Men were more predominant in the groups of patients with psoriasis, psoriasis+ACD, and lesions were more predominantly seen in the hands with little association with atopic factors vs the ACD group. The rate of positivity in PT to the 2022 Spanish battery of allergens was lower in the group with psoriasis only in 27% of the patients. The most common allergens found in the psoriasis group were also the most common ones found in the overall ACD population. CONCLUSIONS: Overall, 36.2% of psoriatic patients tested positive in PT to the 2022 Spanish battery of allergens, which proved that this association is not uncommon. Overall, psoriatic patients had a higher mean age, were more predominantly men, and showed more hand involvement.

FLAIR hyperintensity in the subarachnoid space: Main differentials.

The fluid-attenuated inversion recovery (FLAIR) sequence forms part of the vast majority of current diagnostic protocols for brain MRI. This sequence enables the suppression of the signal from cerebrospinal fluid, facilitating the detection of disease involving the subarachnoid space. The causes of hyperintensity in the arachnoid space in this sequence can be divided into two main categories: hyperintensity due to disease and hyperintensity due to artifacts. Hyperintensity due to tumors, inflammation, vascular disease, or hypercellularity of the cerebrospinal fluid or hematic contents is well known. However, numerous other non-pathological conditions, mainly due to artifacts, that are also associated with this finding are a potential source of diagnostic errors.

Advancing precision in histocompatibility and immunogenetics: a comprehensive review of the UCLA exchange program.

Precise typing of human leukocyte antigens (HLA) is crucial for clinical hematopoietic stem cell and solid organ transplantations, transfusion medicine, HLA-related disease association, and drug hypersensitivity analysis. The UCLA Cell Exchange program has played a vital role in providing educational and proficiency testing surveys to HLA laboratories worldwide for the past 5 decades. This article highlights the significant contribution of the UCLA Cell and DNA Exchange Programs in advancing HLA antibody testing, genotyping, crossmatches, and, more recently, virtual crossmatches. Additionally, we discuss future directions of the UCLA Cell Exchange program to support histocompatibility testing to adapt to the fast-evolving field of immunotherapy, tolerance and xenotransplantation.

[Translated article] Requirements for Accessing New Dermatology Drugs in Spain: Results of the EQUIDAD Study.

BACKGROUND: Although the Spanish Ministry of Health prepares national therapeutic positioning reports (TPRs) and drug reimbursement policies, each of the country's 17 autonomous communities (ACs) is responsible for health care services and prescription requirements in its territory. The aim of the EQUIDAD study was to describe and explore potential differences in prescription requirements for new dermatology drugs across the autonomous communities. MATERIAL AND METHODS: Cross-sectional study conducted in April and May, 2023. Two dermatologists with management responsibilities from each autonomous community reported on territorial and more local prescription requirements for drugs covered by national TPRs issued between 2016 and 2022. RESULTS: Thirty-three researchers from 17 autonomous communities participated. The data submitted revealed between-community inequities in access to new drugs. Overall, 64.7% of the regions imposed additional prescription requirements to those mentioned in the TPRs for psoriasis. This percentage was lower for atopic dermatitis (35.3%) and melanoma (11.8%). The most common requirement for accessing a new drug was a previous prescription for another drug. Differences and additional requirements were also detected at the local level (i.e., differences between hospitals within the same autonomous community). CONCLUSIONS: Spain's autonomous communities have multiple regional and local prescription requirements that are not aligned with national TPR recommendations. These differences result in inequitable access to new drugs for both patients and practitioners across Spain.

A dynamical measure of the black hole mass in a quasar 11 billion years ago.

Tight relationships exist in the local Universe between the central stellar properties of galaxies and the mass of their supermassive black hole (SMBH)1-3. These suggest that galaxies and black holes co-evolve, with the main regulation mechanism being energetic feedback from accretion onto the black hole during its quasar phase4-6. A crucial question is how the relationship between black holes and galaxies evolves with time; a key epoch to examine this relationship is at the peaks of star formation and black hole growth 8-12 billion years ago (redshifts 1-3)7. Here we report a dynamical measurement of the mass of the black hole in a luminous quasar at a redshift of 2, with a look back in time of 11 billion years, by spatially resolving the broad-line region (BLR). We detect a 40-µas (0.31-pc) spatial offset between the red and blue photocentres of the Hα line that traces the velocity gradient of a rotating BLR. The flux and differential phase spectra are well reproduced by a thick, moderately inclined disk of gas clouds within the sphere of influence of a central black hole with a mass of 3.2 × 108 solar masses. Molecular gas data reveal a dynamical mass for the host galaxy of 6 × 1011 solar masses, which indicates an undermassive black hole accreting at a super-Eddington rate. This suggests a host galaxy that grew faster than the SMBH, indicating a delay between galaxy and black hole formation for some systems.