FARMACIA HOSPITALARIA最新文献

Objective: The individualization of treatments through pharmacokinetic monitoring is a therapeutic strategy aimed at improving both the effectiveness and safety of drug therapy. For tumor necrosis factor inhibitors used in Crohn's disease, a robust correlation has been demonstrated between drug exposure and clinical response. However, evidence regarding ustekinumab concentrations and their relationship with treatment effectiveness remains limited. The objective of this study was to analyze ustekinumab concentrations at week 8 of treatment for Crohn's disease and to evaluate their association with biochemical remission at week 24 and treatment persistence.

Methods: This prospective study included patients with Crohn's disease who initiated ustekinumab between 2020 and 2023. Ustekinumab trough plasma concentrations were measured at week 8. Quartile analysis and binary logistic regression were performed to assess the relationship between ustekinumab concentrations and biochemical remission rates at week 24. Treatment persistence across concentration quartiles was evaluated using Kaplan-Meier analysis.

Results: A total of 36 patients were included. Individuals achieving biochemical remission at week 24 had higher ustekinumab concentrations at week 8 compared with non-responders (10.64 vs. 5.83 μg/mL; p = 0.016). Patients within the quartile-4 (>13.29 μg/mL) at week 8 showed significantly higher biochemical remission rates at week 24 compared with the remaining quartiles (100% vs. 57.1%; p = 0.023); Odds Ratio = 1.20; 95%-Confidence Interval [1.02-1.42]; p = 0.027. The 2-year treatment persistence rate was significantly greater among patients in quartiles 3-4 (100%) compared with those in quartile-1 (55.6%) and quartile 2 (50%) (p = 0.014).

Conclusion: This study confirms the association between ustekinumab concentrations at week 8 and treatment effectiveness in Crohn's disease. A concentration >13.29 μg/mL at week 8 was identified as a predictive marker of biochemical remission at week 24, which could serve as a basis for future therapeutic decision-making algorithms.

Introduction: Inhaled antibiotics are used in the treatment of various respiratory diseases, including cystic fibrosis (CF), non-CF bronchiectasis, and ventilator-associated pneumonia. While some of these drugs are marketed as ready-to-use formulations, others require prior manipulation, such as dilution or reconstitution procedures that are often not standardized. Furthermore, certain antibiotics are only approved for intravenous administration, making it necessary to develop specific protocols for their preparation and use via the inhaled route. Their biochemical properties may also compromise patient safety and tolerability. The aim of this study was to assess how frequently preparation methods and biochemical parameters of inhaled antibiotic solutions are described in the scientific literature. Additionally, we explored their prevalence of use in our country and evaluated their biochemical characteristics to assess tolerability.

Methods: A literature review was conducted using the MEDLINE database to identify studies describing the dilutions used for the administration of inhaled antibiotics. In addition, a nationwide survey was carried out to assess the dilutions currently used in hospital clinical practice. Biochemical analyses were performed in parallel to determine the pH, osmolality, and sodium and chloride ion concentrations of the solutions employed. Excipients present in each formulation were recorded based on information from the product's summary of characteristics.

Results: The literature review identified 533 full-text publications describing 737 different inhaled antibiotic mixtures. Of these, 476 were not standardized. Only 190 mixtures included precise dilution instructions, while just 31 provided data on pH and 28 on osmolality. The national survey revealed a high prevalence of inhaled antibiotic use among participating hospitals, with 22 centres (64.7%) reporting the use of intravenous formulations administered via inhalation. Laboratory analyses showed that some of the evaluated dilutions fell outside the acceptable tolerability range, particularly those involving reconstitution of dry powders or dilution of concentrated intravenous solutions.

Conclusion: There is limited information in the scientific literature regarding preparation methods and the biochemical characteristics of inhaled antibiotic solutions. Off-label use of intravenous formulations for inhalation is widespread, and some of the dilutions used exhibit biochemical parameters outside the recommended tolerability range, which may compromise both the safety and effectiveness of treatment.

Acetaminophen is one of the most widely used drugs in clinical practice due to its analgesic and antipyretic properties. However, overdose is one of the leading causes of severe acute liver failure. N-acetylcysteine, introduced as an antidote in 1974, has revolutionized the management of this intoxication by reducing hepatotoxicity and mortality associated with acetaminophen toxicity. At the end of the 19th century, acetaminophen was identified as the main active metabolite of phenacetin and acetanilide. Its therapeutic use began to gain popularity in the 1950s and later became one of the main drugs involved in suicide attempts, particularly among adolescents and young adults. Acetaminophen-induced hepatotoxicity was first described in 1966, establishing that an overdose could lead to fulminant hepatic necrosis. In 1975, Rumack and Matthew published a nomogram that allowed stratification of hepatic toxicity risk based on plasma drug levels. The mechanism of hepatotoxicity was elucidated in the early 1970s when it was discovered that acetaminophen is metabolized by cytochrome P450 into a highly reactive intermediate, N-acetyl-p-benzoquinoneimine, which is normally neutralized by hepatic glutathione. In overdose situations, glutathione depletion leads to hepatic necrosis. Based on these findings, sulfhydryl-containing agents such as cysteamine and methionine were introduced as antidotes, but N-acetylcysteine ultimately proved to be the most effective treatment. Since its introduction, N-acetylcysteine administration protocols have evolved to optimize efficacy and minimize adverse effects. Protocols such as the Scottish and Newcastle Acetylcysteine Protocol and the Two Bags regimen have simplified dosing and reduced the incidence of anaphylactoid reactions. Over the past 50 years, N-acetylcysteine has saved thousands of lives and remains the gold-standard antidotal treatment for acetaminophen poisoning.

Objective: To compare radiographic progression-free survival in metastatic prostate cancer patients treated with low-dose abiraterone versus standard-dose abiraterone acetate (Abi-SD), and to evaluate prostate-specific antigen progression-free survival.

Methods: Retrospective cohort study of patients with metastatic prostate cancer, castration-sensitive or castration-resistant, treated with low or standard-dose abiraterone. All patients were followed until radiographic or prostate-specific antigen progression. Cox proportional hazards regression was used to assess radiographic progression-free survival and prostate-specific antigen progression-free survival according to abiraterone dose (low vs. standard-dose). The model was adjusted for Charlson Comorbidity Index, castration resistance status, disease volume based on CHAARTED criteria, and presence of de novo metastases.

Results: A total of 144 patients with metastatic prostate cancer were included in the study, with 28.4% (n = 41) receiving low-dose abiraterone. The median age was 79 years (IQR: 75-85) in the low-dose group and 75 years (IQR: 70-81) in the standard-dose group. For radiographic progression-free survival, the crude hazard ratio for the low-dose group compared with the standard-dose group was 0.49 (95% CI: 0.23-1.07). After adjusting for clinical variables, the adjusted hazard ratio was 0.65 (95% CI: 0.29-1.45). For prostate-specific antigen progression-free survival, the crude hazard ratio was 0.48 (95% CI: 0.24-0.90), and the adjusted hazard ratio was 0.58 (95% CI: 0.29-1.14).

Conclusion: This study provides evidence supporting the use of low-dose abiraterone in patients with metastatic prostate cancer, showing survival and progression outcomes comparable to those of the standard-dose. This approach may improve access to treatment; however, larger studies are needed to validate these findings.

Background: On 11 March 2020, World Health Organisation declared COVID-19 a pandemic. During the early stages, treatments lacking scientific evidence, such as hydroxychloroquine and later remdesivir, were used; meanwhile, clinical trials were being conducted in Spain to evaluate new therapies with greater scientific rigor. This article analyses the study profile, publication rate and completion of studies during the COVID-19 pandemic in Spain.

Methods: Meta-epidemiological, analytical, and retrospective study analyzed the characteristics and rate of completion of clinical trials with SARS-CoV-2-related drugs authorized in Spain between March 2020 and March 2021, focusing on treatment and prophylaxis. 179 clinical trials were reviewed using sources such as Registro Español de Estudios Clínicos, ClinicalTrials.gov, PubMed, Embase and TESEO. Statistical analysis was performed with SPSS v.26.

Results: 67.0% of the trials were national and 71.0% multicentre, with non-commercial sponsors (64.8%) and phase II (44.7%) and phase III (48.0%) studies being the most common. The majority employed a comparative design (93.9%), preferentially focused on treatment (91.1%) versus prophylaxis of SARS-CoV-2 disease, with a predominance of therapeutic repositioning (72.1%). Notably, studies initiated during the first wave of the pandemic (March-June 2020) were mostly non-international, non-commercial, non-placebo-controlled and aimed at drug repositioning. Some 21.2% of the clinical trials closed prematurely, mainly due to recruitment problems, Involuntary discontinuation or Failure to achieve expected efficacy. By the end of the study, 41.1% of the clinical trials had a final report and 31.3% published their results, most of them (71.9%) in first quartile journals. Statistically significant associations were found between the publication of results and variables such as multicentre, not having closed prematurely, having a final report, and phase III trials. The fact that a large number of clinical trials were not published (68.7%) represents a missed opportunity in terms of knowledge.

Conclusion: We conclude that there is a need to improve transparency, record all results- including negative ones- and review key aspects of design and funding, as recommendations for future research, including in health emergencies.

Objective: The effectiveness of alemtuzumab in patients with relapsing-remitting multiple sclerosis (RRMS) have been demonstrated in clinical trials. The primary endpoint was to describe the annual effectiveness of alemtuzumab over a 4-year period, according to the different parameters of the NEDA-3 concept (no evidence of disease activity) in clinical practice.

Methods: A retrospective, observational multicentric open study of patients with RRMS treated with alemtuzumab between 2015 and 2024. Effectiveness was assessed according to different parameters of the NEDA-3 concept (absence of relapses, stability in disability status according to the EDSS scale, and absence of new lesions and/or contrast enhancement in brain magnetic resonance imaging) with annual follow-up for up to four years.

Results: A cohort of 32 patients (71.9% women, mean age 40.3 ± 11 years) were included. The proportion of patients achieving NEDA-3 was 51.7% (15/29) in the first year, 56.2% (12/26) in the second year, 47.4% (9/19) in the third year, and 47.1% (8/17) in the fourth year. At the end of the study, 82% of patients remained relapse-free, 59% had stable disability according to the EDSS scale, and over 47% were free of radiological activity.

Conclusions: Alemtuzumab has proven to be effective, over 4 years, in clinical practice in patients with RRMS according to the different parameters of the NEDA-3 concept.

Pomalidomide is a third-generation immunomodulatory drug that has been shown to be effective in the treatment of relapsed/refractory multiple myeloma. Although it is generally well tolerated, some patients may experience hypersensitivity reactions that limit its use. We present the case of an 85-year-old patient with refractory multiple myeloma who developed cutaneous hypersensitivity to pomalidomide. The drug was discontinued and desensitization to pomalidomide was scheduled, which consisted of administering increasing doses of pomalidomide orally in 10 steps, with 15-min intervals between each dose. The patient tolerated the procedure without experiencing adverse reactions, which allowed restarting treatment with pomalidomide. This case highlights the usefulness of desensitization to pomalidomide in patients with multiple myeloma who present hypersensitivity reactions, Further studies are needed to evaluate the efficacy and safety of this procedure with other drugs and in more severe forms of hypersensitivity.

Sepsis and septic shock are major global health issues, with significant morbidity and mortality. Early identification and appropriate management during the first few hours are crucial for improving clinical outcomes. Sepsis treatment focuses on infection control, restoration of perfusion, and the implementation of adjunctive therapies. A thorough understanding of these approaches is essential for the clinical pharmacist in the intensive care unit to provide optimal pharmacotherapeutic validation.

Introduction: Intensive Care Units (ICU) are recognized as high-risk settings for medication errors, primarily due to the complex pharmacological regimens and the critical condition of patients. It is estimated that the probability of errors occurring in these units is two to three times higher than in general hospital patients, with prescribing and administration being the stages most frequently associated with such incidents.

Objective: To evaluate the applicability and satisfaction with electronic prescribing systems in Intensive Care Units of hospitals in Spain.

Methods: A nationwide survey was conducted targeting pharmacists to assess the functionalities of the electronic prescribing systems used in these units. The evaluation covered hospital characteristics, features of the prescribing software, and healthcare professionals' satisfaction, with the aim of understanding the current situation and proposing improvement strategies to enhance medication safety through prescribing systems in the context of critically ill patients.

Results: A total of 64 surveys were completed across 55 different hospitals. In 50.8% of cases, a prescribing system different from that used in general hospital wards was employed. In 84.4% of cases, the system had been developed by a commercial vendor. In 65.1% of hospitals, the system enabled communication with the pharmacy, and in 57.7% it allowed for pharmaceutical validation. However, 50.8% of the systems were not capable of interfacing with automated dispensing or administration systems. In 71.9% of cases, the system allowed for direct data extraction. Pharmacists reported satisfactory overall perceptions in only 43.8% of cases, while 42.9% identified unmet needs requiring improvement.

Conclusions: Despite significant heterogeneity in the functionalities of electronic prescribing systems across Spanish ICUs, such systems are widely implemented nationwide and are regarded as a key element in ensuring medication safety within these units. Clinical pharmacists reported a generally acceptable level of satisfaction; however, there remains considerable scope for improvement.