Search Results (26)

In recent years, an increasing number of case reports have mentioned the presence of illicit nootropics, smart drugs or mind doping products on the market. To better understand the extent of the problem, a market surveillance study was organised by the General European Official Medicines Control Laboratory Network and associated member Australia to detect substandard, falsified or illegal medicines or dietary supplements containing unauthorised nootropic molecules of natural or synthetic origin. From January 2020 to September 2024, 159 different samples were documented, which yielded a comprehensive dataset of 166 molecular identification entries. Within this dataset, 34 distinct molecules were identified. Most samples were sold or presented as dietary supplements (49%) or medicines (32%). The vast majority (69%) were collected from the illegal market. Prescription drugs and non-authorised drugs only available on prescription in Russia were found in pharmacological quantities; some of the latter (noopept, phenylpiracetam and phenibut) were intercepted as large bulk quantities of raw material. Unauthorised novel foods, prescription or higher amounts of melatonin, and clinically uncharacterised research molecules were also reported. This study highlights the need for more active monitoring and screening of such products, as consumption of some of the reported samples could have detrimental health effects. Furthermore, as a large number of the samples were presented as dietary supplements, consumers may not be aware of the possible dangers and side-effects of these products. Full article

Background/Objectives: Fluoropyrimidine derivatives, 5-fluorouracil (5-FU) and its prodrugs (capecitabine and tegafur), are widely used in patients suffering from colorectal cancer. The enzyme responsible for their metabolization, dihydropyrimidine dehydrogenase (DPD), is encoded by the DPYD gene, which is highly polymorphic and may contain polymorphisms which could severely compromise its function. This article aims to describe the prevalence of the four main DPYD polymorphisms in the Galician population (Spain) and to compare these frequencies with data obtained from European cohorts in genetic databases and a Spanish study. Methods: Galician data frequencies for the four main DPYD polymorphisms recommended by the European Medicine Agency (EMA) and the Spanish Agency for Medicines and Health Products (AEMPS) (rs3918290 (c.1905+1G>A), rs55886062 (c.1679T>G), rs56038477 (c.1236G>A) and rs67376798 (c.2846A>T)) were collected, as well as data from the genomic databases 1000 Genomes and gnomAD. Additionally, the results from a Spanish DPYD study were included. Results: Significant differences in DPYD variant allele frequencies were observed in the Galician population compared to the frequencies reported in the European population, as well as in the Spanish PhotoDPYD study. Specifically, the rs56038477-T variant (most prevalent) along with the rs3918290-T variant, exhibited significantly lower frequencies than anticipated in the Galician cohort, with a high degree of statistical significance. Conclusions: Observed allele frequencies for the four DPYD variants suggest that Europeans and Spanish frequencies may not be fully applicable to the Galician population. These results emphasize the emerging need for incorporating the genetic information of populations that might be underrepresented into populational databases available worldwide. Full article

On 4 September 2024, the Reagan-Udall Foundation for the FDA (FDA Foundation) in collaboration with the Food and Drug Administration (FDA) and the Gates Foundation hosted a workshop titled “Scientific Advancements in Gene Therapies: Opportunities for Global Regulatory Convergence”. The event brought together a diverse group of experts, including international regulatory bodies, regulated industries, healthcare professionals, patients, academic researchers and global health advocates, to discuss the rapid advancements in gene therapy and the pressing need for equitable access in low-and middle-income countries (LMICs), with sickle cell disease (SCD) serving as the model disorder for the discussions. Although there has been significant progress in gene therapy, such as breakthroughs in clustered regularly interspaced short palindromic repeats (CRISPR)-based technologies and FDA-approved therapies, access to these therapies remain limited in underresourced regions. The workshop addressed critical challenges, including the high cost of therapies, regulatory gaps and barriers and ethical concerns regarding informed consent and public engagement in LMICs. This paper highlights the critical discussion points from the workshop with a focus on exploring strategies for global regulatory convergence, the role of international collaborations and the potential pathways to making gene therapies affordable and accessible to all. Full article

Pseudomonas aeruginosa is an opportunistic pathogen with a multidrug-resistant profile that has become a critical threat to global public health. It is one of the main causes of severe nosocomial infections, including ventilator-associated pneumonia, chronic infections in patients with cystic fibrosis, and bloodstream infections in immunosuppressed individuals. Development of vaccines against P. aeruginosa is a major challenge owing to the high capacity of this bacterium to form biofilms, its wide arsenal of virulence factors (including secretion systems, lipopolysaccharides, and outer membrane proteins), and its ability to evade the host immune system. This review provides a comprehensive historical overview of vaccine development efforts targeting this pathogen, ranging from early attempts in the 1970s to recent advancements, including vaccines based on novel proteins and emerging technologies such as nanoparticles and synthetic conjugates. Despite numerous promising preclinical developments, very few candidates have progressed to clinical trials, and none have achieved final approval. This panorama highlights the significant scientific efforts undertaken and the inherent complexity of successfully developing an effective vaccine against P. aeruginosa. Full article

Objectives: Chronic kidney disease-associated pruritus (CKD-aP) is underdiagnosed and not fully understood by healthcare professionals, which leads to poor patient management and impacts patients’ quality of life (QoL). The aim of this study was to analyse unmet needs in CKD-aP management and explore the attributes/characteristics that the ideal CKD-aP treatment should have from the perspective of a group of nephrologists, hospital pharmacists, nurses, patient representatives, and regional health authorities in Spain. Methods: A descriptive, cross-sectional study was conducted using an e-survey including ad hoc questions (6-point Likert scale) related to unmet needs in CKD-aP and best–worst scaling (BWS) to prioritise the attributes/characteristics of the ideal CKD-aP treatment. The survey was developed from a literature review, a patient focus group, and a multidisciplinary expert committee. Results: A total of 21 people participated, and it was considered, among other aspects, that CKD-aP had a significant impact on patient QoL (4.29/5), but the diagnosis rate and knowledge level of agents involved, as well as current treatment efficacy and safety, were low (1.71/5, 2.19/5, 1.91/5, and 2.67/5, respectively). The attributes “improves overall QoL (physical and mental)”, “reduces itch with statistical significance”, and “treatment is supported by clinical development/high evidence and has AEMPS (Spanish Agency for Medicines and Medical Devices)-approved indication for pruritus” were selected as the most valued attributes. There was a positive balance between best–worst scores (86-5, 71-2, and 78-13 points, respectively). Conclusions: The results show the need to undertake actions to drive relevant changes in current clinical practice to improve CKD-aP diagnosis and management. Full article

Background: Tolerance and dependence stand out as the most relevant risks observed during benzodiazepine (BZD) treatments. Objectives: To evaluate the degree of dependence of patients on BZD treatments using the Tyrer test; to define a profile of patients at risk of developing BZD dependence; and to discuss the role of the pharmaceutical care offered by the community pharmacy during dispensing. Methods: Prospective cross-sectional descriptive observational study (August 2020–February 2021) involving 127 patients using BZD. They voluntarily answered a questionnaire during the dispensing pharmaceutical care service. The study was evaluated and codified (code: DAA-CLO-2020-01) by the Spanish Agency for Drugs and Health Products (AEMPS), and statistical analysis was performed with SPSS 25.0. Results: 19.05% of patients using BZD were suspected of suffering from BZD tolerance, and 77.88% of all patients were identified as being at a high risk of BZD dependence. The Tyrer test for dependence indicated a mean score of 5.59 out of 13 points. An 18-fold increased risk of developing dependence was detected in the case of coexistence of high anxiety or depression. Conclusions: The community pharmacy, through protocolized care practices and supported by tools such as the Tyrer test, can play a decisive role in the detection, prevention, and resolution of the risks associated with BZD treatments. Full article

Antithrombotics have been widely used to treat and prevent COVID-19-related thrombosis; however, studies on their use at population levels are limited. We aimed to describe antithrombotic use patterns during the pandemic in Spanish primary care and hospital-admitted patients with COVID-19. Methods: A real-world data study was performed. Data were obtained from BIFAP’s electronic health records. We investigated the antithrombotic prescriptions made within ±14 days after diagnosis between March 2020 and February 2022, divided their use into prior and new/naive groups, and reported their post-discharge use. Results: We included 882,540 individuals (53.4% women), of whom 78,499 were hospitalized. The median age was 44.7 (IQR 39–59). Antithrombotics were prescribed in 37,183 (4.6%) primary care subjects and 42,041 (53.6%) hospital-admitted patients, of whom 7505 (20.2%) and 20,300 (48.3%), respectively, were naive users. Prior users were older and had more comorbidities than new users. Enoxaparin was the most prescribed antithrombotic in hospitals, with higher prescription rates in new than prior users (2348.2, IQR 2390–3123.1 vs. 1378, IQR 1162–1751.6 prescriptions per 10,000 cases, p = 0.002). In primary care, acetylsalicylic acid was the most used antithrombotic, with higher use rates in prior than in naïve users. Post-discharge use occurred in 6686 (15.9%) subjects (median use = 10 days, IQR 9-30). Conclusions: Our study identified a consensus on prescribing antithrombotics in COVID-19 patients, but with low use rates in hospitals. Full article

Escherichia coli isolates that are resistant to cefixime and amoxicillin/clavulanic acid, but apparently susceptible to cefuroxime, with no ESBL identified, were initially detected in Madrid from urine samples in 2019. Throughout 2020 and 2021, all cases of community UTI by E. coli from six health areas in Madrid were studied. A representative sample of 23 cases was selected for further studies. The broth microdilution method and the agar diffusion method were performed to determine the antibiotic susceptibility. WGS was carried out for phylogeny, resistome and virulome analysis. Community consumption of third-generation oral cephalosporins in Madrid (2017–2021) was analyzed. A total of 582 (1.3%) E. coli isolates had the mentioned resistance profile. The mutation at position –32 (T > A) of the AmpC promoter was found in 21 isolates. No plasmid AmpC- or ESBL-encoding genes were detected. A cluster of 20 ST12 isolates was detected by cgMLST. A 6.2% increase in the consumption of third-generation oral cephalosporins, especially cefixime, was observed in Madrid. Chromosomal AmpC-hyperproducing ST12 E. coli isolates could be implicated in the increase in community UTI cases by cefixime-resistant isolates, which correlates with an increasing trend of cefixime consumption. Full article

Although pregnant women were considered a risk population for COVID-19, little is known of their drug use during the pandemic. We aimed to investigate COVID-19 distribution, drug use patterns and COVID-19 medication. We conducted a retrospective cohort of validated pregnancies aged 15–49 years, from January 2020 to December 2022, using the BIFAP database. An identified cohort of pregnant women with COVID-19 was matched by age, gestational age, length of pregnancy and outcome to a cohort free of COVID-19 (8413 vs. 24,975). We performed a descriptive analysis on COVID-19 cases, estimated the drug use patterns and assessed COVID-19-specific drugs within the week prior/after diagnosis, stratified by pandemic wave and gestational week. The results showed that 72% of pregnant women with COVID-19 received at least one prescription vs. 66.6% of those free of COVID-19, with analgesics, antibiotics and thyroid hormones being the most prescribed drugs in both groups. In the COVID-19 group, they were antithrombotics (40 prescriptions per 100 women), analgesic/NSAIDs (19.64/6.29) and antibiotics (6.95). COVID-19 cases gradually increased, peaking at the fifth and second waves. Prescription rates were similar when compared to pre-pandemic studies. The use of drugs compatible with COVID-19 treatments was in line with recommendations. Full article

Background: electronic health records (EHRs) are helpful tools in epidemiology despite not being primarily collected for research. In Spain, primary care physicians play a central role and manage patients even in specialized care. All of this introduces variability that may lead to diagnostic inconsistencies. Therefore, data validation studies are crucial, so we aimed to develop and validate case-finding algorithms for digestive cancer in the primary care database BIFAP. Methods: from 2001 to 2019, subjects aged 40–89 without a cancer history were included. Case-finding algorithms using diagnostic codes and text-mining were built. We randomly sampled, clustered, and manually reviewed 816 EHRs. Then, positive predictive values (PPVs) and 95% confidence intervals (95% CIs) for each cancer were computed. Age and sex standardized incidence rates (SIRs) were compared with those reported by the National Cancer Registry (REDECAN). Results: we identified 95,672 potential cases. After validation, the PPV (95% CI) for hepato-biliary cancer was 87.6% (81.8–93.4), for esophageal cancer, it was 96.2% (93.1–99.2), for pancreatic cancer, it was 89.4% (84.5–94.3), for gastric cancer, it was 92.5% (88.3–96.6), and for colorectal cancer, it was 95.2% (92.1–98.4). The SIRs were comparable to those reported by the REDECAN. Conclusions: the case-finding algorithms demonstrated high performance, supporting BIFAP as a suitable source of information to conduct epidemiologic studies of digestive cancer. Full article

Chronic wounds, especially those that are hard-to-heal, constitute a serious public-health problem. Although progress has been made in the development of wound dressings for healing, there is little high-quality evidence of their efficacy, with no evidence of superiority in the use of one hydrogel over another. To evaluate the superiority of a hydrogel (EHO-85), containing Olea europaea leaf extract (OELE), over a standard hydrogel (SH), the promotion and/or improvement of healing of difficult-to-heal wounds was compared in a prospective, parallel-group multicenter, randomized, observer-blinded, controlled trial (“MACAON”). Non-hospitalized patients with pressure, venous or diabetic foot-ulcers difficult-to-heal were recruited and treated with standard care, and EHO-85 (n = 35) or VariHesive (n = 34) as SH. Wound-area reduction (WAR; percentage) and healing rate (HR; mm²/day) were measured. EHO-85 showed a statistically significant superior effect over VariHesive. At the end of the follow-up period, the relative WAR decreased by 51.6% vs. 18.9% (p < 0.001), with a HR mean of 10.5 ± 5.7 vs. 1.0 ± 7.5 mm²/day (p = 0.036). EHO-85 superiority is probably based on its optimal ability to balance the ulcer bed, by modulating pH and oxidative stress. That complements the wetting and barrier functions, characteristics of conventional hydrogels. These results support the use of EHO-85 dressing, for treatment of hard-to-heal ulcers. Trial Registration AEMPS:PS/CR623/17/CE. Full article

The focus of this meeting was to discuss the suitability of using bacteriophages as alternative antimicrobials in the agrifood sector. Following a One Health approach, the workshop explored the possibilities of implementing phage application strategies in the agriculture, animal husbandry, aquaculture, and food production sectors. Therefore, the meeting had gathered phage researchers, representatives of the agrifood industry, and policymakers to debate the advantages and potential shortcomings of using bacteriophages as alternatives to traditional antimicrobials and chemical pesticides. Industry delegates showed the latest objectives and demands from consumers. Representatives of regulatory agencies (European Medicines Agency (EMA) and Spanish Agency of Medicines and Health Products (AEMPS)) presented an update of new regulatory aspects that will impact and support the approval and implementation of phage application strategies across the different sectors. Full article

This paper explores the impact of investment and employment on Egypt’s agricultural growth during the period 1991 to 2021 using annual time series data. We use the ARDL approach to examine the long-run and short-run relationships among agricultural investment, agricultural employment and agricultural GDP. The results reveal that the variables of interest are bound together in the long run. The long-run relationship and the error correction model are estimated. The accompanying equilibrium correction proves that long-run linkages exist in a meaningful way. Results show that agricultural investment and agricultural employment are major short- and long-run determinants of the agricultural GDP. In the long run, every 1% increase in agricultural employment (AEMP) results in an increase in the agricultural GDP (AGDP) of 3.73%, while every 1% increase in agricultural investment (AINV) improves the AGDP by 0.43%. In the short run, 26% of all disequilibrium-causing motions are adjusted for in a single session. Therefore, it takes 3.85 years for the Egyptian agricultural GDP to achieve the transition from a short-term disequilibrium situation to a long-term equilibrium. Thus, decision makers should increase the rates of investment in the agricultural sector, in parallel to the development of the agricultural labor force in Egypt. Moreover, the increased allocation of public investments and the injection of private investments are highly recommended. In addition, the Egyptian agricultural sector needs improvements regarding human capital development and agricultural training. Finally, the government must initiate comprehensive farmer support services, bolstered farm/non-farm links and the promotion of rural SMEs to serve as the foundation for agricultural and rural development. Full article

Conflicting results about the association of calcium supplements (CS) with ischemic stroke (IS) have been reported. We tested this hypothesis by differentiating between CS alone (CaM) and CS with vitamin D (CaD) and between cardioembolic and non-cardioembolic IS. We examined the potential interaction with oral bisphosphonates (oBs). A nested case-control study was carried out. We identified incident IS cases aged 40–90 and randomly sampled five controls per case matched by age, sex, and index date. Current users were compared to non-users. An adjusted odds ratios (AOR) and 95% CI were computed through conditional logistic regression. Only new users were considered. We included 13,267 cases (4400 cardioembolic, 8867 non-cardioembolic) and 61,378 controls (20,147 and 41,231, respectively). CaM use was associated with an increased risk of cardioembolic IS (AOR = 1.88; 95% CI: 1.21–2.90) in a duration-dependent manner, while it showed no association with non-cardioembolic IS (AOR = 1.05; 95% CI: 0.74–1.50); its combination with oBs increased the risk of cardioembolic IS considerably (AOR = 2.54; 95% CI: 1.28–5.04), showing no effect on non-cardioembolic. CaD use was not associated with either cardioembolic (AOR = 1.08; 95% CI: 0.88–1.31) or non-cardioembolic IS (AOR = 0.98; 95% CI: 0.84–1.13) but showed a small association with cardioembolic IS when combined with oBs (AOR = 1.35; 95% CI: 1.03–1.76). The results support the hypothesis that CS increases the risk of cardioembolic IS, primarily when used concomitantly with oBs. Full article

Background: Botulism is a low incidence but potentially fatal infectious disease caused by neurotoxins produced mainly by Clostridium botulinum. There are different routes of acquisition, food-borne and infant/intestinal being the most frequent presentation, and antitoxin is the treatment of choice in all cases. In Spain, botulism is under surveillance, and case reporting is mandatory. Methods: This retrospective study attempts to provide a more complete picture of the epidemiology of botulism in Spain from 1997 to 2019 and an assessment of the treatment, including the relationship between a delay in antitoxin administration and the length of hospitalization using the Cox proportional hazards test and Kruskal–Wallis test, and an approach to the frequency of adverse events, issues for which no previous national data have been published. Results: Eight of the 44 outbreaks were associated with contaminated commercial foods involving ≤7 cases/outbreak; preserved vegetables were the main source of infection, followed by fish products; early antitoxin administration significantly reduces the hospital stay, and adverse reactions to the antitoxin affect around 3% of treated cases. Full article