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Objectives: To characterise the exposure to valproate within a cohort of pregnant women using electronic health records (EHRs) from Catalonia (System for the Development of Research in Primary Care, SIDIAP)., Design: Drug-utilisation cohort study covering the period from January 2011 to June 2020. The study included pregnancy episodes of women from Catalonia identified by the algorithm., Setting: Data were sourced from SIDIAP, a comprehensive EHR repository that includes information from various data sources: recorded prescriptions (both hospital and primary care), diagnoses and sociodemographic characteristics identified by primary care physicians, and sexual and reproductive health data from ASSIR (used by gynaecologists and midwives)., Participants: Women aged 12-50 with at least one pregnancy episode occurred during January 2011-June 2020 and at least a prescription of valproate during pregnancy., Primary and Secondary Outcomes: Primary outcomes included valproate exposure, measured through prevalence and cumulative incidence in pregnancy episodes and by trimester. The impact of regulatory measures (risk mitigation measures, RMMs) was assessed, and prescriptions over time were analysed using interrupted time series analysis. Secondary outcomes included health issues, pregnancy outcomes, smoking habits and socioeconomic characteristics., Results: A total of 99 605 pregnancies were identified, with at least 3.03‰ (95% CI 2.69‰ to 3.39‰) exposed to valproate at some point (302 pregnancies, 276 women). The median pregnancy duration was 38.30 weeks (IQR 12.6-40.1), and the median age at pregnancy was 32.37 years (IQR 27.20-36.56). Epilepsy was the most frequent health issue. The prevalence and cumulative incidence of valproate prescriptions decreased during pregnancy and increased postpregnancy. The RMMs implemented in 2014 led to a reduction in monthly valproate prescriptions during pregnancy in this cohort., Conclusions: The study highlights the decline in valproate prescriptions during pregnancy due to RMMs and underscores the need for standardised methodologies in future studies to ensure the safety of pregnant patients and optimise scientific evidence., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objectives: To determine whether income was associated with unexpected in-hospital mortality in older patients treated in Spanish public health system hospital emergency departments., Material and Methods: Fifty-one public health system hospital emergency departments in Spain voluntarily participated in the study. Together the hospitals covered 25% of the population aged 65 years or older included in all patient registers during a week in the pre-pandemic period (April 1-7, 2019) and a week during the COVID-19 pandemic (March 30 to April 5, 2020). We estimated a patient's gross income as the amount published for the postal code of the patient's address. We then calculated the standardized gross income (SGI) by dividing the patient's estimated income by the mean for the corresponding territory (Spanish autonomous community). The existence and strength of an association between the SGI and in-hospital mortality was evaluated by means of restricted cubic spline (RCS) curves adjusted for 10 patient characteristics at baseline. Odds ratios (ORs) for each income level were expressed in relation to a reference SGI of 1 (the mean income for the corresponding autonomous community). We compared the COVID-19 and pre-pandemic periods by means of first-order interactions., Results: Of the 35 280 patients attended in the 2 periods, gross income could be ascertained for 21 180 (60%), 15437 in the pre-pandemic period and 5746 during the COVID-19 period. SGIs were slightly higher for patients included before the pandemic (1.006 vs 0.994; P = .012). In-hospital mortality was 5.6% overall and higher during the pandemic (2.8% pre-pandemic vs 13.1% during COVID-19; P .001). The adjusted RCS curves showed that associations between income and mortality differed between the 2 periods (interaction P = .004). Whereas there were no significant income-influenced differences in mortality before the pandemic, mortality increased during the pandemic in the lowest-income population (SGI 0.5 OR, 1.82; 95% CI, 1.32-3.37) and in higher-income populations (SGI 1.5 OR, 1.32; 95% CI, 1.04-1.68, and SGI 2 OR, 1.92; 95% CI, 1.14-3.23). We found no significant differences between patients with COVID-19 and those with other diagnoses (interaction P = .667)., Conclusion: The gross income of patients attended in Spanish public health system hospital emergency departments, estimated according to a patient's address and postal code, was associated with in-hospital mortality, which was higher for patients with the lowest and 2 higher income levels. The reasons for these associations might be different for each income level and should be investigated in the future.

Background: Dry needling (DN) is often used for the treatment of muscle pain among physiotherapists. However, little is known about the mechanisms of action by which its effects are generated. The aim of this randomized controlled trial was to determine if the use of DN in healthy subjects activates the sympathetic nervous system, thus resulting in a decrease in pain caused by stress., Methods: Sixty-five healthy volunteer subjects were recruited from the University of Alcala, Madrid, Spain, with an age of 27.78 (SD = 8.41) years. The participants were randomly assigned to participate in a group with deep DN in the adductor pollicis muscle or a placebo needling group. The autonomic nervous system was evaluated, in addition to local and remote mechanical hyperalgesia., Results: In a comparison of the moment at which the needling intervention was carried out with the baseline, the heart rate of the dry needling group significantly increased by 20.60% (SE = 2.88), whereas that of the placebo group increased by 5.33% (SE = 2.32) ( p = 0.001, d = 1.02). The pressure pain threshold showed significant differences between both groups, being significantly higher in the needling group (adductor muscle p = 0.001; d = 0.85; anterior tibialis muscle p = 0.022, d = 0.58)., Conclusions: This work appears to indicate that dry needling produces an immediate activation in the sympathetic nervous system, improving local and distant mechanical hyperalgesia.

Objectives: To describe the process of implementing the Spanish Triage System (SET, in its Spanish abbreviation) in nonspecialist hospital emergency departments (EDs) in the public health service., Material and Methods: Multicenter cross-sectional study at 4 time cut-points (6 months before implementation and at the end of 1, 2 and 3 semesters afterwards). The study was carried out in 29 public hospital EDs in Andalusia. We recorded the following data: type of hospital, proportion of cases in which the SET was applied, priority classifications assigned on triage, wait time before triage, and duration of the triage process. We also recorded the following proportions: patients waiting less than 10 minutes for the assigned priority, cases with a triage processing time less than 5 minutes, ED revisits within 72 hours, ED deaths, and patients leaving before discharge., Results: We saw SET use increase progressively over the 3 semesters. The mean wait time decreased, and the proportion of patients waiting less than 10 minutes increased. The mean triage processing time tended to decrease nonsignificantly as the proportion of cases triaged in less than 5 minutes rose. The proportion of patients leaving before discharge increased with time; in overall and by hospital type. The proportion of ED deaths did not change significantly, and revisits within 72 hours increased only in more complex hospitals (P = .019)., Conclusion: Implementing a structured triage approach like SET is a gradual process. Quality indicators must be followed over time so that the impact of a triage system on ED care processes can be assessed.

Osteogenesis imperfecta (OI) is an inherited disorder that causes low mineral density and bone fragility. Previous studies have shown the efficacy of bisphosphonates to increase bone mineral density (BMD). This study assessed changes over time in BMD and biochemical markers of bone metabolism in adult patients with osteogenesis imperfecta treated with intravenous zoledronic acid and the safety of this treatment., Patients and Methods: A prospective, observational study in patients with OI, osteoporosis or osteopenia (T score <-2) who were administered zoledronic acid infusions (4mg IV) every 6 months for three years and annually thereafter. Densitometry was performed annually. Acute changes in complete blood count and calcium, phosphate, and creatinine levels, as well as side effects of the infusion, were recorded 24 and 48h after treatment. Calcium, phosphate, parathyroid hormone (iPTH), 25OH-vitamin D and bone turnover markers (bone alkaline phosphatase, ß-crosslaps and urinary deoxypyridinoline) were measured at baseline and every 12 months. Adverse events and new fractures were recorded., Results: Twenty patients (6 men and 14 women) were treated. Median follow-up time was five years. Calcium levels and platelet counts significantly decreased 24 and 48hours after the first infusion, and the red blood cell count decreased at 24hours. These changes were not clinically relevant. Seven patients experienced a flu-like episode after the first dose. Treatment induced significant increases in BMD in the lumbar spine (6.7%) after 12 months of follow-up (0.791±0.178 vs. 0.791±0.140g/cm 2 , p=.003) and at three (5.7%) and five years (9%) of follow-up. Femoral neck BMD significantly increased after 3 years (11.1%): 0.648±0.148 vs. 0.720±0.138g/cm 2 ; p=.01. In total hip, increase in BMD (10.1%) was significant after three years of treatment (0.706±0.118 vs. 0.720±0.138, p=.01). There were no significant differences in calcium and 25OH-vitamin D levels during follow-up, phosphorus significantly decreased after one year, and iPTH increased at three years. ß-crosslaps decreased after one year of treatment. Only one patient sustained new fractures., Conclusions: Zoledronic acid is a convenient, safe, and effective treatment that increases BMD in adult patients with OI., (Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background and Aims: The early onset of cardio-metabolic abnormalities, known as metabolically unhealthy (MU) status, is highly associated with obesity and cardiovascular disease (CVD), as well as with increased morbidity and mortality later in life. Given the lack of a consensus MU classification for prepubertal children, we aimed to compare available MU definitions in terms of their association with CVD risk biomarkers., Methods and Results: A total of 930 prepubertal children (622 with overweight/obesity, 462 males) aged 5-10.9 years were recruited, anthropometric measures were taken and biomarkers were analyzed. Children were classified using eight MU definitions based on different cut-offs for blood pressure, triacylglycerides, high-density lipoprotein cholesterol, glucose and homeostasis model assessment for insulin resistance (HOMA-IR). MU prevalence in children with overweight/obesity ranged between 30% and 60% across definitions. Plasma concentrations of resistin, leptin, myeloperoxidase (MPO) and total plasminogen activator inhibitor 1 (tPAI-1) were higher, and those of adiponectin were lower, in MU compared to MH children with overweight/obesity. Linear regression analyses confirmed the contribution of MPO and tPAI-1 concentrations to MU status, with most significant results derived from definitions that use age and sex-specific criteria and that account for HOMA-IR., Conclusion: Plasma concentrations of MPO and tPAI-1 are increased in prepubertal MU children irrespective of having normal-weight or overweight/obesity. Inclusion of age and sex-specific cut-offs for cardio-metabolic components as well as insulin resistance criteria increases the quality of MU definitions as seen by their stronger association with CVD biomarkers concentrations., (Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

In a previous study, we have shown the added value of (1) H MRS for the neuroradiological characterisation of adult human brain tumours. In that study, several methods of MRS analysis were used, and a software program, the International Network for Pattern Recognition of Tumours Using Magnetic Resonance Decision Support System 1.0 (INTERPRET DSS 1.0), with a short-TE classifier, provided the best results. Since then, the DSS evolved into a version 2.0 that contains an additional long-TE classifier. This study has two objectives. First, to determine whether clinicians with no experience of spectroscopy are comparable with spectroscopists in the use of the system, when only minimum training in the use of the system was given. Second, to assess whether or not a version with another TE is better than the initial version. We undertook a second study with the same cases and nine evaluators to assess whether the diagnostic accuracy of DSS 2.0 was comparable with the values obtained with DSS 1.0. In the second study, the analysis protocol was flexible in comparison with the first one to mimic a clinical environment. In the present study, on average, each case required 5.4 min by neuroradiologists and 9 min by spectroscopists for evaluation. Most classes and superclasses of tumours gave the same results as with DSS 1.0, except for astrocytomas of World Health Organization (WHO) grade III, in which performance measured as the area under the curve (AUC) decreased: AUC = 0.87 (0.72-1.02) with DSS 1.0 and AUC = 0.62 (0.55-0.70) with DSS 2.0. When analysing the performance of radiologists and spectroscopists with respect to DSS 1.0, the results were the same for most classes. Having data with two TEs instead of one did not affect the results of the evaluation., (Copyright © 2014 John Wiley & Sons, Ltd.)

Background: The 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme catalyses the regeneration of active cortisol from inert cortisone and plays a critical role in tissue-specific corticosteroid reactions; therefore, 11β-HSD1 is a key molecule associated with the development of obesity. Despite evidence for its role in obesity, no genetic polymorphisms have been significantly associated with the disease per se., Objective: The aim of this study was to evaluate whether HSD11B1 gene variants, which have never been studied before, are associated with obesity and its related traits, as well as its relation to biomarkers of inflammation, liver damage and cardiovascular disease in a cohort of Spanish children., Design: We performed a prospective case-control study., Subjects: A total of 534 children were examined and classified as being obese (n=292) or normal weight (n=242). Anthropometric and biochemical measurements related to obesity, including inflammation, liver damage and cardiovascular disease, were determined. Genomic DNA was extracted and 10 HSD11B1 gene single-nucleotide polymorphisms (SNPs) were genotyped., Results: A novel SNP, rs3753519, was strongly associated with obesity and this SNP was the only statistically significant HSD11B1 gene SNP remaining after a Bonferroni correction (odds ratio=1.97 for allelic effect, 95% confidence interval 1.23-3.16; P=0.004 and Bonferroni corrected P=0.046). In addition, this SNP was significantly and positively associated with increased body mass index (BMI), BMI z-score, weight, waist circumference, plasma γ-glutamyl transpeptidase and plasma active plasminogen activator inhibitor 1. The SNP was negatively associated with plasma adiponectin and cortisol after adjusting for sex and age. None of the inflammation biomarkers tested were associated with the risk allele., Conclusion: These data, which link an HSD11B1 genotype with both disease prevalence and its related phenotypes, strongly support a role for the rs3753519 polymorphism in the pathogenesis of pediatric-onset obesity.

Background and Purpose: There is a large range of survival times in patients with HGA that can only be partially explained by histologic grade and clinical aspects. This study aims to retrospectively assess the predictive value of single-voxel (1)H-MRS regarding survival in HGA., Materials and Methods: Pretreatment (1)H-MRS in 187 patients with HGA produced 180 spectra at STE (30 ms) and 182 at LTE (136 ms). Patients were dichotomized into 2 groups according to survival better or worse than the median. The spectra of the 2 groups were compared using the Mann-Whitney U test. The points on the spectrum with the most significant differences were selected for discriminating patients with good and poor prognosis. Thresholds were defined with ROC curves, and survival was analyzed by using the Kaplan-Meier method and the Cox proportional hazards model., Results: Four points on the spectrum showed the most significant differences: 0.98 and 3.67 ppm at STE; and 0.98 and 1.25 ppm at LTE (P between <.001 and .011). These points were useful for stratifying 2 prognostic groups (P between <.001 and .003, Kaplan-Meier). The Cox forward stepwise model selected 3 spectroscopic variables: the intensity values of the points 3.67 ppm at STE (hazard ratio, 2.132; 95% CI, 1.504-3.023), 0.98 ppm at LTE (hazard ratio, 0.499; 95% CI, 0.339-0.736), and 1.25 ppm at LTE (hazard ratio, 0.574; 95% CI, 0.368-0.897)., Conclusions: (1)H-MRS is of value in predicting the length of survival in patients with HGA and could be used to stratify prognostic groups.

Objectives: A continuous intervention based on healthcare management agreements was associated in our hospital with an increase in the absolute number of spontaneous reporting of adverse drug reactions (ADRs), and also with an increase in the number of reports of serious or unexpected ADRs and ADRs associated with new drugs. The objective was to analyse the effect of this intervention on the features of ADRs spontaneously reported in a hospital, the drugs involved and the number of signals identified., Methods: A longitudinal study with two periods, the 1st period without intervention from 1998 to 2002 and the 2nd period with intervention from 2003 to 2005, was carried out in a tertiary teaching hospital. Changes between the two periods with regard to the following variables were analysed: the patients' characteristics, such as gender and age; the reported ADRs, and the medical assistance required; the suspected drugs involved in the ADRs; the main signals identified., Results: Gender and age distribution of patients described in the spontaneous reports were no different in the two periods. During the second period, spontaneously reported cases requiring hospital admission and those occurring in hospital increased (236 from 2 in the first period and 277 from 99 in the first period respectively) and cases from outpatient hospital consultations began to be reported (13.9% of reports). The spontaneous reporting on all kinds of ADRs and drugs increased during the second period. Cutaneous reactions were the most frequently spontaneously reported ADRs in both periods followed by cardiovascular and neurological reactions in the first period, and haematological and gastrointestinal reactions in the second one. However, during the second period the higher increase was for endocrinological, urinary and hepatic reactions. Systemic antibiotics, anti-thrombotics and cardiac therapy drugs were the most common therapeutic subgroups reported to be suspected drugs in both periods, but in the second period the proportion of immunostimulants, beta blocking agents, immunosuppressants and psychoanaleptics increased. No signals were recognised during the first period; however, two signals and one additional safety concern were identified during the second., Conclusion: An intervention based on healthcare management agreements, was associated with an important increase in spontaneous reporting of ADRs by hospital physicians and also with a change in terms of the type of ADRs identified affecting different organs or systems, and the therapeutic groups of drugs involved. Future studies should analyse the effect of different types of intervention on the spontaneous reporting of ADRs in hospitals.

Background: Spontaneous reporting of adverse drug reactions (ADRs) in hospitals is scarce and several obstacles to such reporting have been identified previously., Objective: To assess the effectiveness of a multifaceted intervention based on healthcare management agreements for improving spontaneous reporting of ADRs by physicians in a hospital setting., Methods: In 2003, the spontaneous reporting of ADRs was included as one of the objectives of hospital physicians at the Vall d'Hebron Hospital, Barcelona, Spain, within the context of management agreements between clinical services and hospital managers. A continuous intervention related to these management agreements, including periodic educational meetings and economic incentives, was then initiated. We carried out an ecological time series analysis and assessed the change in the total number of spontaneous reports of ADRs, and the number of serious ADRs, unexpected ADRs, and ADRs associated with new drugs between a period previous to the intervention (from 1998 to 2002) and the period during the intervention (from 2003 to 2005). A time series analysis with ARIMA (Auto-Regressive Integrated Moving Average) models was performed., Results: The median number of reported ADRs per year increased from 40 (range 23-55) in the first period to 224 (range 98-248) in the second period. In the first period, the monthly number of reported ADRs was stable (3.47 per month; 95% CI 1.90, 5.03), but in the second period the number increased progressively (increase of 0.74 per month; 95% CI 0.62, 0.86). In the second period, the proportion of reported serious ADRs increased nearly 2-fold (63.1% vs 32.5% in the first period). The absolute number of previously unknown or poorly known ADRs increased 4-fold in the second period (54 vs 13 in the first period). There was also an increase in the absolute number of suspected pharmacological exposures to new drugs (97 vs 28) and in the number of different new drugs suspected of causing ADRs (50 vs 19)., Conclusion: A continuous intervention based on healthcare management agreements with economic incentives and educational activities is associated with a quantitative and qualitative improvement of spontaneous reporting of ADRs by hospital physicians.

Aim: To describe the opinions of hospital physicians concerning problems regarding the spontaneous reporting of adverse drug reactions (ADRs) and ways to solve them., Methods: A qualitative study was carried out. Fifteen focus groups were conducted among physicians working in a tertiary teaching hospital. A total of 208 physicians from different medical specialities participated. The focus group discussions were recorded by three different observers and the transcripts of each session were analysed for issues and themes emerging from the text., Results: Four types of obstacles to spontaneous reporting were considered particularly important: (i) problems with the ADR(S) diagnosis; (ii) problems with the usual workload and lack of time; (iii) problems related to the organization and activities of the pharmacovigilance system; (iv) and problems related to potential conflicts. The potential solutions suggested for improving spontaneous reporting were to define the kind of ADR(S) which should be reported, to facilitate an easy contact and quick access to the hospital pharmacovigilance system, to facilitate information and support for reporting and feedback of pharmacovigilance activities., Conclusions: The perception of the different obstacles by the hospital physicians is an important factor in determining the causes of the underreporting of ADRs and addressing these obstacles could lead to an improvement in spontaneous reporting. A closer relationship between the doctors and the pharmacovigilance centre is suggested as a means of solving these problems. More information is needed to improve the spontaneous reporting of ADR(S) in specialized healthcare.

Background: Many hip fracture patients have a poor nutritional status which may be one explanation for their increased mortality., Patients and Methods: We studied nutritional status and other mortality-related factors prospectively in 165 patients with hip fractures (85 women). We concentrated on differences between death rates and survival rates at 3 months and at 1 year, and between those patients who died within 3 months and those who died later., Results: In general, men had a poorer nutritional status and a larger number of comorbidities. Also, there were more smokers and alcohol abusers amongst the men. Of the patients who died during the first 3 months, most were men, and their initial nutritional status was poorer than that of women. Multivariate logistic regression analysis revealed a correlation between mortality and total serum protein, retinol binding protein and the number of comorbidities. Among patients who died after 3 months, mortality was associated with the number of comorbidities and smoking., Interpretation: The higher mortality rate in men than in women after hip fracture may in part be explained by the poor nutritional status in men.

A long-term epidemiological study of Cryptosporidium molnari in aquacultured European sea bass (ESB) and gilthead sea bream (GSB) was performed in different types of facilities on the Atlantic, Cantabric, and Mediterranean coasts. Four types of studies were carried out. In study A, fish raised from juveniles to marketable size (ongrowing stage) were periodically sampled in three different types of cultures. Studies B and C focused on hatchery and nursery facilities. In study D, occasional samplings were performed during mortality or morbidity outbreaks. As a general trend, C. molnari was more prevalent in GSB than in ESB. Data on the distribution pattern of C. molnari in total sampled GSB (studies A, B, and D) had a variance higher than the mean (overdispersion). In GSB (study A), the type of ongrowing system (sea cages, earth ponds, or indoor tanks) was found to have no significant effect. There was a significant relationship between the presence of the parasite and both fish weight and season. The highest infection values were recorded in spring. Prevalence and intensity had convex weight profiles, with a peak in 30- to 100-g fish. In study D, the prevalence of infection was higher in fish recently introduced in sea cages and in preongrowing systems. In studies B and C, fish were almost never infected before entering the postlarval and nursery facilities. The parasite seems to enter the host mainly through the water in production steps with less stringent water treatment. Recirculation systems and fish cannibalism could contribute to oocyst concentration and dispersion in aquaculture facilities.

Background: Analgesics can avoid postoperative pain. The aim of this study was to evaluate their prescription after abdominal surgery., Patients and Methods: Prospective study including patients who had undergone abdominal surgery in two hospitals in Barcelona, in 1993. Prescription and administration of analgesic drugs, and pain severity during the first 48 hours of the postoperative period were evaluated., Results: One hundred and sixty-four patients (83 men) were included. The most frequently prescribed drugs were metamizol (111; 68%), pethidine (83, 51%), and diclofenac (44; 27%). A high percentage of analgesic prescriptions on an "as needed" basis was recorded. Administered doses were lower than those recommended, and lower than those prescribed. Fifty-three percent of patients suffered significant pain during the first day., Conclusion: A too low proportion of analgesic drugs is prescribed in a predetermined schedule, in contrast to "as needed" prescription. Opiate derivatives are underused. All analgesic drugs are prescribed at inadequate dosage. This prescription pattern is associated with a high prevalence of postoperative pain.

Purpose: To assess the polymorphism of the platelet membrane glycoprotein in castilians and gypsy people and to confirm the genetic transmission of such glycoprotein by means of family studies., Material and Methods: Two-hundred castilians and 87 gypsy subjects were studied. Glycoprotein Ib was analysed by means of SDS polyacrylamide gel electrophoresis followed by Western-Blotting and labelling with glycoprotein-specific monoclonal antibodies and lectins. The different populations were compared by using the chi-square method (Fisher's test)., Results: Only three groups of glycoprotein Ib, namely, B, C and D, were found in both population groups, no differences being observed in the expression of the different phenotypic variants. Lesser polymorphism was present in the gypsy group. The family studies showed that glycoprotein Ib is genetically determined, the two alleles being co-dominantly expressed in each individual., Conclusions: The polymorphism of glycoprotein Ib is similar to that of caucasians, type A being not found. No differences seem to exist between castilians and gypsy people. The heredity pattern is autosomal co-dominant.