Journal of Clinical Medicine

2024

Jump to: 2023, 2022, 2021

16 pages, 699 KiB

Open AccessArticle

Comparative Analysis of Verapamil Pharmacokinetics: Evaluating the Impact of Simple Suspension and Crushing Administration Methods

by Sumito Kumagai, Takehiko Sambe, Keita Shibata, Takuya Mizukami, Hokuto Morohoshi, Kakei Ryu, Taigi Yamazaki, Sachiko Takenoshita, Shunsuke Matsukawa, Saki Goibuchi, Naoki Uchida, Naomi Kurata and Noriko Hida

J. Clin. Med. 2024, 13(19), 5969; https://doi.org/10.3390/jcm13195969 - 8 Oct 2024

Viewed by 643

Abstract

Background/Objective: It is not uncommon for elderly patients to experience difficulties with feeding and swallowing. In the simple suspension method, tablets are dissolved and suspended in warm water without prior crushing or decapsulation, and then administered via a tube. Despite the prevalence of [...] Read more.

Background/Objective: It is not uncommon for elderly patients to experience difficulties with feeding and swallowing. In the simple suspension method, tablets are dissolved and suspended in warm water without prior crushing or decapsulation, and then administered via a tube. Despite the prevalence of this method, the pharmacokinetics of suspended tablet dosage forms remain poorly understood. Methods: Verapamil was employed in dissolution tests following both the simple suspension and crushing methods. A pharmacokinetics study was conducted on healthy adult males. Results: The resultant dissolution profiles from the two methods exhibited notable dissimilarities. Drug release from the crushed product commenced earlier than that from the simple suspension and intact tablet. Furthermore, the area under the curve for verapamil during the initial 24 h period was 1.7 and 1.3 times greater in the crushed and simple suspension groups, respectively, than in the tablet group. Conclusions: The crushing and simple suspension methods are safe techniques for administering medications to patients with dysphagia, thereby preventing aspiration. Nevertheless, the processing of medications may result in an increased frequency of adverse effects. It is recommended that the processing of medicines prior to administration be avoided. Full article

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9 pages, 236 KiB

Open AccessArticle

Early Access for Medicines in ITALY: The Case of Ruxolitinib for Patients with Graft-Versus-Host Disease

by Lucia Gozzo, Salvatore Leotta, Giovanni Luca Romano, Calogero Vetro, Andrea Duminuco, Giuseppe Milone, Alessandra Cupri, Fanny Erika Palumbo, Serena Brancati, Rosy Ruscica, Laura Longo, Daniela Cristina Vitale, Giorgia Fiorenza, Giovanni Enrico Lombardo, Antonio Lazzara, Francesco Di Raimondo, Giuseppe Alberto Palumbo and Filippo Drago

J. Clin. Med. 2024, 13(14), 4273; https://doi.org/10.3390/jcm13144273 - 22 Jul 2024

Viewed by 976

Abstract

After European Medicines Agency (EMA) approval, national pricing and reimbursement procedures are necessary to guarantee access to drugs, based on the willingness to pay and the recognition of therapeutic value. These can result in delays in drug availability for patients, even for those [...] Read more.

After European Medicines Agency (EMA) approval, national pricing and reimbursement procedures are necessary to guarantee access to drugs, based on the willingness to pay and the recognition of therapeutic value. These can result in delays in drug availability for patients, even for those with important unfmet needs for whom it may be necessary and ethical to ensure access. The objective of this study was to evaluate the use of ruxolitinib for patients with graft-versus-host disease (GvHD) after EMA approval at the University Hospital of Catania. We analysed data about the use of ruxolitinib in patients with GvHD, describing their basic characteristics, their outcomes and the cost of the treatment. In the reference period, 24 ruxolitinib treatments were started according to the Summary of Product Characteristic. The average treatment duration was 10 months. Twenty patients showed a response, maintained over time, with no adverse reactions. The total expenditure amounts to EUR 963,424. The use of ruxolitinib in a real population confirms its role in an important therapeutic need. The quantification of costs requires a reflection on the sustainability of early access to medicines authorised by the EMA for serious diseases and in the absence of therapeutic alternatives. Full article

13 pages, 567 KiB

Open AccessArticle

by Mimi Truong, Wubshet Tesfaye, Kamal Sud, Connie Van, Shrey Seth, Nerida Croker and Ronald Lynel Castelino

J. Clin. Med. 2024, 13(2), 343; https://doi.org/10.3390/jcm13020343 - 7 Jan 2024

Cited by 2 | Viewed by 1752

Abstract

Background: Medication use during acute illness increases the risk of experiencing drug related problems (DRPs), including acute kidney injuries. It is recommended that potentially nephrotoxic medications are withheld during acute illness, including sulfonylureas, angiotensin converting enzyme inhibitors, diuretics, metformin, angiotensin receptor blockers, non-steroidal [...] Read more.

Background: Medication use during acute illness increases the risk of experiencing drug related problems (DRPs), including acute kidney injuries. It is recommended that potentially nephrotoxic medications are withheld during acute illness, including sulfonylureas, angiotensin converting enzyme inhibitors, diuretics, metformin, angiotensin receptor blockers, non-steroidal anti-inflammatories and sodium glucose co-transporter 2 inhibitors (SADMANS). It is unknown if Australian pharmacists currently provide sick day medication management advice regarding SADMANS medications. Hence, we aimed to identify current DRPs and the recommendations made during residential medication management reviews (RMMRs), especially with SADMANS medications. Methods: A retrospective review of 408 RMMRs was conducted. DRPs and pharmacist recommendations were classified according to a modified DOCUMENT system. General practitioners’ (GP) recommendations were also categorised. Results: Over 97% of residents experienced at least one DRP. Common problems for non-SADMANS medications were “toxicity or adverse drug reaction”, “drug selection” and “over/underdosing” and those for SADMANS medications included “toxicity or adverse drug reaction”, “monitoring” and “drug selection”. GPs agreed with pharmacist recommendations approximately 40% of the time. No pharmacists provided sick day medication management advice for SADMANS medications. Conclusion: DRPs remain highly prevalent in aged care facilities. Medication reviews effectively identify and resolve DRPs approximately 40% of the time, but do not currently minimise the risk associated with using SADMANS medications during sick days, which is a potential area of improvement. Full article

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2023

Jump to: 2024, 2022, 2021

23 pages, 807 KiB

Open AccessFeature PaperReview

Drug–Drug Interactions Involving Dexamethasone in Clinical Practice: Myth or Reality?

by Venceslas Bourdin, William Bigot, Anthony Vanjak, Ruxandra Burlacu, Amanda Lopes, Karine Champion, Audrey Depond, Blanca Amador-Borrero, Damien Sene, Chloe Comarmond and Stéphane Mouly

J. Clin. Med. 2023, 12(22), 7120; https://doi.org/10.3390/jcm12227120 - 15 Nov 2023

Cited by 5 | Viewed by 3530

Abstract

Concomitant administration of multiple drugs frequently causes severe pharmacokinetic or pharmacodynamic drug–drug interactions (DDIs) resulting in the possibility of enhanced toxicity and/or treatment failure. The activity of cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp), a drug efflux pump sharing localization and substrate affinities [...] Read more.

Concomitant administration of multiple drugs frequently causes severe pharmacokinetic or pharmacodynamic drug–drug interactions (DDIs) resulting in the possibility of enhanced toxicity and/or treatment failure. The activity of cytochrome P450 (CYP) 3A4 and P-glycoprotein (P-gp), a drug efflux pump sharing localization and substrate affinities with CYP3A4, is a critical determinant of drug clearance, interindividual variability in drug disposition and clinical efficacy, and appears to be involved in the mechanism of numerous clinically relevant DDIs, including those involving dexamethasone. The recent increase in the use of high doses of dexamethasone during the COVID-19 pandemic have emphasized the need for better knowledge of the clinical significance of drug–drug interactions involving dexamethasone in the clinical setting. We therefore aimed to review the already published evidence for various DDIs involving dexamethasone in vitro in cell culture systems and in vivo in animal models and humans. Full article

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17 pages, 2086 KiB

Open AccessArticle

Bradyphrenia and Tachyphrenia in Idiopathic Parkinsonism Appear, in Part, Iatrogenic: An Observational Study with Systematic Review Background

by Wenjing Wang, Kieran Baker, Chianna Umamahesan, Steven Gilmour, André Charlett, David Taylor, Allan H. Young, R. John Dobbs and Sylvia M. Dobbs

J. Clin. Med. 2023, 12(20), 6499; https://doi.org/10.3390/jcm12206499 - 12 Oct 2023

Viewed by 2840

Abstract

We question whether bradyphrenia, slowing of cognitive processing not explained by depression or a global cognitive assessment, is a nosological entity in idiopathic parkinsonism (IP). The time taken to break contact of an index finger with a touch-sensitive plate was measured, with and [...] Read more.

We question whether bradyphrenia, slowing of cognitive processing not explained by depression or a global cognitive assessment, is a nosological entity in idiopathic parkinsonism (IP). The time taken to break contact of an index finger with a touch-sensitive plate was measured, with and without a warning in the alerting signal as to which side the imperative would indicate, in 77 people diagnosed with IP and in 124 people without an IP diagnosis. The ability to utilise a warning, measured by the difference between log_e-transformed reaction times (unwarned minus warned), was termed ‘cognitive efficiency’. It was approximately normally distributed. A questionnaire on self- and partner perception of proband’s bradyphrenia was applied. A multivariable model showed that those prescribed levodopa were less cognitively efficient (mean −5.2 (CI −9.5, −1.0)% per 300 mg/day, p = 0.02), but those prescribed the anti-muscarinic trihexyphenidyl were more efficient (14.7 (0.2, 31.3)% per 4 mg/day, p < 0.05) and those prescribed monoamine oxidase-B inhibitor (MAOBI) tended to be more efficient (8.3 (0.0, 17.4)%, p = 0.07). The variance in efficiency was greater within IP (F-test, p = 0.01 adjusted for any demographic covariates: coefficient of variation, with and without IP, 0.68 and 0.46, respectively), but not so after adjustment for anti-parkinsonian medication (p = 0.13: coefficient of variation 0.62). The within-participant follow-up time, a median of 4.8 (interquartile range 3.1, 5.5) years (101 participants), did not influence efficiency, irrespective of IP status. Perception of bradyphrenia did not usefully predict efficiency. We conclude that both bradyphrenia and ‘tachyphrenia’ in IP appear to have iatrogenic components, of clinically important size, related to the dose of antiparkinsonian medication. Levodopa is the most commonly prescribed first-line medication: co-prescribing a MAOBI may circumvent its associated bradyphrenia. The previously reported greater efficiency associated with (low-dose) anti-muscarinic was confirmed. Full article

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15 pages, 1165 KiB

Open AccessReview

Surgical Pharmacy for Optimizing Medication Therapy Management Services within Enhanced Recovery after Surgery (ERAS^®) Programs

by Jingwen Xie, Xiaoyan Huang, Min Gao, Li Wei, Ruolun Wang, Jisheng Chen, Yingtong Zeng, Bo Ji, Tao Liu, Jinghao Wang, Hongwei Wu, Yong Wang, Li Qin, Yiting Wang, Zhuoling Zheng, Jing Xue, Junyan Wu, Xiao Chen, Zhihua Zheng and Xiaoyan Li

J. Clin. Med. 2023, 12(2), 631; https://doi.org/10.3390/jcm12020631 - 12 Jan 2023

Cited by 9 | Viewed by 5428

Abstract

Drug-related problems (DRPs) are common among surgical patients, especially older patients with polypharmacy and underlying diseases. DRPs can potentially lead to morbidity, mortality, and increased treatment costs. The enhanced recovery after surgery (ERAS) system has shown great advantages in managing surgical patients. Medication [...] Read more.

Drug-related problems (DRPs) are common among surgical patients, especially older patients with polypharmacy and underlying diseases. DRPs can potentially lead to morbidity, mortality, and increased treatment costs. The enhanced recovery after surgery (ERAS) system has shown great advantages in managing surgical patients. Medication therapy management for surgical patients (established as “surgical pharmacy” by Guangdong Province Pharmaceutical Association (GDPA)) is an important part of the ERAS system. Improper medication therapy management can lead to serious consequences and even death. In order to reduce DRPs further, and promote the rapid recovery of surgical patients, the need for pharmacists in the ERAS program is even more pressing. However, the medication therapy management services of surgical pharmacy and how surgical pharmacists should participate in ERAS programs are still unclear worldwide. Therefore, this article reviews the main perioperative medical management strategies and precautions from several aspects, including antimicrobial agents, antithrombotic agents, pain medication, nutritional therapy, blood glucose monitoring, blood pressure treatment, fluid management, treatment of nausea and vomiting, and management of postoperative delirium. Additionally, the way surgical pharmacists participate in perioperative medication management, and the relevant medication pathways are explored for optimizing medication therapy management services within the ERAS programs. This study will greatly assist surgical pharmacists’ work, contributing to surgeons accepting that pharmacists have an important role in the multidisciplinary team, benefitting medical workers in treating, counseling, and advocating for their patients, and further improving the effectiveness, safety and economy of medication therapy for patients and promoting patient recovery. Full article

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2022

Jump to: 2024, 2023, 2021

20 pages, 398 KiB

Open AccessPerspective

Positive Patient Postoperative Outcomes with Pharmacotherapy: A Narrative Review including Perioperative-Specialty Pharmacist Interviews

by Richard H. Parrish II, Heather Monk Bodenstab, Dustin Carneal, Ryan M. Cassity, William E. Dager, Sara J. Hyland, Jenna K. Lovely, Alyssa Pollock, Tracy M. Sparkes and Siu-Fun Wong

J. Clin. Med. 2022, 11(19), 5628; https://doi.org/10.3390/jcm11195628 - 24 Sep 2022

Cited by 4 | Viewed by 3354

Abstract

The influence of pharmacotherapy regimens on surgical patient outcomes is increasingly appreciated in the era of enhanced recovery protocols and institutional focus on reducing postoperative complications. Specifics related to medication selection, dosing, frequency of administration, and duration of therapy are evolving to optimize [...] Read more.

The influence of pharmacotherapy regimens on surgical patient outcomes is increasingly appreciated in the era of enhanced recovery protocols and institutional focus on reducing postoperative complications. Specifics related to medication selection, dosing, frequency of administration, and duration of therapy are evolving to optimize pharmacotherapeutic regimens for many enhanced recovery protocolized elements. This review provides a summary of recent pharmacotherapeutic strategies, including those configured within electronic health record (EHR) applications and functionalities, that are associated with the minimization of the frequency and severity of postoperative complications (POCs), shortened hospital length of stay (LOS), reduced readmission rates, and cost or revenue impacts. Further, it will highlight preventive pharmacotherapy regimens that are correlated with improved patient preparation, especially those related to surgical site infection (SSI), venous thromboembolism (VTE), nausea and vomiting (PONV), postoperative ileus (POI), and emergence delirium (PoD) as well as less commonly encountered POCs such as acute kidney injury (AKI) and atrial fibrillation (AF). The importance of interprofessional collaboration in all periprocedural phases, focusing on medication management through shared responsibilities for drug therapy outcomes, will be emphasized. Finally, examples of collaborative care through shared mental models of drug stewardship and non-medical practice agreements to improve operative throughput, reduce operative stress, and increase patient satisfaction are illustrated. Full article

13 pages, 1220 KiB

Open AccessArticle

Acute Poisoning Readmissions to an Emergency Department of a Tertiary Hospital: Evaluation through an Active Toxicovigilance Program

by Raúl Muñoz Romo, Alberto M. Borobia Pérez, Rosa Mayayo Alvira, Mikel Urroz, Amelia Rodríguez Mariblanca, Francisco J. Guijarro Eguinoa, Lucia Diaz García, Julio Cobo Mora, Angelica Rivera, Rosario Torres and Antonio J. Carcas Sansuán

J. Clin. Med. 2022, 11(15), 4508; https://doi.org/10.3390/jcm11154508 - 2 Aug 2022

Cited by 1 | Viewed by 1756

Abstract

The aim of this study is to investigate hospital readmissions during 1 year after acute poisoning cases (APC), analyze the temporal behavior of early readmissions (ER) (in the month after the index episode) and predict possible ER. A descriptive analysis of the patients [...] Read more.

The aim of this study is to investigate hospital readmissions during 1 year after acute poisoning cases (APC), analyze the temporal behavior of early readmissions (ER) (in the month after the index episode) and predict possible ER. A descriptive analysis of the patients with APC assisted between 2011 and 2016 in the Emergency Department of Hospital La Paz is presented, and various methods of inferential statistics were applied and confirmed by Bayesian analysis in order to evaluate factors associated with total and early readmissions. Out of the 4693 cases of APC included, 968 (20.6%) presented, at least one readmission and 476 (10.1%) of them were ER. The mean age of APC with readmission was 41 years (12.7 SD), 78.9% had previous psychiatric pathology and 44.7% had a clinical history of alcohol addiction. Accidental poisoning has been a protective factor for readmission (OR 0.50; 0.26–0.96). Type of toxin (“drug of abuse” OR 8.88; 1.17–67.25), history of addiction (OR 1.93; 1.18–3.10) and psychiatric history (OR 3.30; 2.53–4.30) are risk factors for readmissions during the first year. Women showed three or more readmissions in a year. The results of the study allow for identification of the predictors for the different numbers of readmissions in the year after the index APC, as well as for ERs. Full article

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16 pages, 2906 KiB

Open AccessProtocol

Assessment of Antibiotic Pharmacokinetics, Molecular Biomarkers and Clinical Status in Critically Ill Adults Diagnosed with Community-Acquired Pneumonia and Receiving Intravenous Piperacillin/Tazobactam and Hydrocortisone over the First Five Days of Intensive Care: An Observational Study (STROBE Compliant)

by István Vincze, Rita Czermann, Zsuzsanna Nagy, Mária Kovács, Michael Neely, Róbert Farkas, Ibolya Kocsis, Gellért Balázs Karvaly and Csaba Kopitkó

J. Clin. Med. 2022, 11(14), 4140; https://doi.org/10.3390/jcm11144140 - 16 Jul 2022

Cited by 2 | Viewed by 2689

Abstract

Severe community-acquired pneumonia (CAP) is a condition that frequently requires intensive care and, eventually, can cause to death. Piperacillin/tazobactam antibiotic therapy is employed as an empiric intravenous regimen, in many cases supplemented with intravenous bolus hydrocortisone treatment. The individual and condition-dependent pharmacokinetic properties [...] Read more.

Severe community-acquired pneumonia (CAP) is a condition that frequently requires intensive care and, eventually, can cause to death. Piperacillin/tazobactam antibiotic therapy is employed as an empiric intravenous regimen, in many cases supplemented with intravenous bolus hydrocortisone treatment. The individual and condition-dependent pharmacokinetic properties of these drugs may lead to therapeutic failure. The impact of systemic inflammation, as well as of hydrocortisone on the altered pharmacokinetics of piperacillin is largely unknown. The protocol of a clinical study aimed at the characterization of the pharmacokinetics of piperacillin and tazobactam and its association with the concentrations of inflammatory markers and adrenal steroids during CAP therapy will be investigated in up to 40 critically ill patients. The serum concentrations of piperacillin and tazobactam, cortisol, cortisone, corticosterone and 11-deoxycortisol and interleukin-6 levels, as well as routine clinical chemistry and hematology parameters will be monitored from the beginning of treatment for up to five days. Nonparametric population pharmacokinetic modeling and Monte-Carlo simulations will be performed to make estimates of the pharmacokinetics of piperacillin and tazobactam and the probability of pharmacokinetic-pharmacodynamic target attainment. The observed individual characteristics and changes will be correlated with clinical and laboratory findings. The protocol of the observational study will be designed following the STROBE guideline. Full article

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16 pages, 769 KiB

Open AccessArticle

Evaluation of Cough Medication Use Patterns in Ambulatory Care Settings in the United States: 2003–2018

by Seonkyeong Yang, Juan M. Hincapie-Castillo, Xuehua Ke, Jonathan Schelfhout, Helen Ding, Mandel R. Sher, Lili Zhou, Ching-Yuan Chang, Debbie L. Wilson and Wei-Hsuan Lo-Ciganic

J. Clin. Med. 2022, 11(13), 3671; https://doi.org/10.3390/jcm11133671 - 25 Jun 2022

Cited by 7 | Viewed by 3361

Abstract

Using 2003–2018 National Ambulatory Medical Care Survey data for office-based visits and 2003–2018 National Hospital Ambulatory Medical Care Survey data for emergency department (ED) visits, we conducted cross-sectional analyses to examine cough medication (CM) use trends in the United States (US) ambulatory care [...] Read more.

Using 2003–2018 National Ambulatory Medical Care Survey data for office-based visits and 2003–2018 National Hospital Ambulatory Medical Care Survey data for emergency department (ED) visits, we conducted cross-sectional analyses to examine cough medication (CM) use trends in the United States (US) ambulatory care settings. We included adult (≥18 years) patient visits with respiratory-infection-related or non-infection-related cough as reason-for-visit or diagnosis without malignant cancer or benign respiratory tumor diagnoses. Using multivariable logistic regressions, we examined opioid antitussive, benzonatate, dextromethorphan-containing antitussive, and gabapentinoid use trends. From 2003–2005 to 2015–2018, opioid antitussive use decreased in office-based visits (8.8% to 6.4%, P_trend = 0.03) but remained stable in ED visits (6.3% to 5.9%, P_trend = 0.99). In both settings, hydrocodone-containing antitussive use declined over 50%. Benzonatate use more than tripled (office-based:1.6% to 4.8%; ED:1.5% to 8.0%; both P_trend < 0.001). Dextromethorphan-containing antitussive use increased in ED visits (1.8% to 2.6%, P_trend = 0.003) but stayed unchanged in office-based visits (3.8% to 2.7%; P_trend = 0.60). Gabapentinoid use doubled in office-based visits (1.1% in 2006–2008 to 2.4% in 2015–2018, P_trend < 0.001) but was negligible in ED visits. In US office-based and ED ambulatory care settings, hydrocodone-containing antitussive use substantially declined from 2003 to 2018, while benzonatate use more than tripled, and dextromethorphan-containing antitussive and gabapentinoid use remained low (<3%). Full article

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10 pages, 1585 KiB

Open AccessArticle

Temporal Trends and Geographic Variability in the Prescription of Antiretroviral Treatments in People Living with HIV in Spain, 2004–2020

by Marta Ruiz-Algueró, Victoria Hernando, María Riero, José Ramón Blanco Ramos, Miguel Alberto de Zarraga Fernández, Pepa Galindo, Alexandre Pérez-González, Asunción Díaz, Inés Suárez-García, Inma Jarrín and CoRIS cohort

J. Clin. Med. 2022, 11(7), 1896; https://doi.org/10.3390/jcm11071896 - 29 Mar 2022

Cited by 5 | Viewed by 2176

Abstract

Background: The purpose of this study was to describe temporal trends in the use of antiretroviral therapy (ART) among people living with HIV (PLWHIV) from the cohort of the Spanish HIV/AIDS research network (CoRIS), 2004–2020. Methods: We described the yearly evolution of the [...] Read more.

Background: The purpose of this study was to describe temporal trends in the use of antiretroviral therapy (ART) among people living with HIV (PLWHIV) from the cohort of the Spanish HIV/AIDS research network (CoRIS), 2004–2020. Methods: We described the yearly evolution of the proportion of patients receiving ART and the most frequently prescribed antiretroviral drugs among newly recruited treatment-naïve patients and among all patients with active follow-up. Results: Of 15,539 patients included, 14,618 (94.1%) started ART during their follow-up. Regarding initial regimens, the use of 2NRTI plus 1NNRTI (which were the most frequently prescribed until 2014) and 2NRTI plus 1bPI decreased after 2014, being gradually replaced by INI-based triple therapies. Since 2019, other regimens started to be prescribed, mainly dual therapies. TDF/FTC/EFV was the single-tablet regimen (STR) most frequently prescribed as initial ART until 2012, decreasing thereafter as TDF/FTC/RPV, TDF/FTC/EVG/COBI, and ABC/3TC/DTG became available. TAF/FTC/BIC accounted for 53.6% of initial prescriptions in 2020, followed by DTG/3TC (24%). The percentage of patients on ART increased from 45.7% in 2004 to 98.2% in 2020. Among all patients receiving ART, regimens based on 2NRTI plus 1INI increased from 0.1% in 2007 to 53.3% in 2020. During 2007–2015, most patients were receiving TDF/FTC/EFV, which was replaced after 2017 by ABC/3TC/DTG. In 2020, 13.0% of patients were receiving dual therapies. Conclusions: Robust real-world data on ART use in PLWHIV over more than 15 years show historical trends in prescriptions with an unprecedented visualization of the contemporary treatment patterns. Full article

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17 pages, 6354 KiB

Open AccessArticle

Statins and Colorectal Cancer Risk: A Population-Based Case-Control Study and Synthesis of the Epidemiological Evidence

by Antonio Rodríguez-Miguel, Encarnación Fernández-Antón, Diana Barreira-Hernández, Luis A. García-Rodríguez, Miguel Gil, Alberto García-Lledó and Francisco J. De Abajo

J. Clin. Med. 2022, 11(6), 1528; https://doi.org/10.3390/jcm11061528 - 10 Mar 2022

Cited by 6 | Viewed by 3734

Abstract

(1) Background: The pleiotropic effects of statins may explain a chemoprotective action against colorectal cancer (CRC). Many studies have tested this hypothesis, but results have been inconsistent so far. Moreover, few have examined statins individually which is important for determining whether there is [...] Read more.

(1) Background: The pleiotropic effects of statins may explain a chemoprotective action against colorectal cancer (CRC). Many studies have tested this hypothesis, but results have been inconsistent so far. Moreover, few have examined statins individually which is important for determining whether there is a class effect and if lipophilicity and intensity may play a role. (2) Methods: From 2001–2014, we carried out a study comprised of 15,491 incident CRC cases and 60,000 matched controls extracted from the primary healthcare database BIFAP. We fit a logistic regression model to compute the adjusted-odds ratios (AOR) with their 95% confidence intervals (CIs). Additionally, we carried out a systematic review and meta-analysis. (3) Results: Current use of statins showed a reduced risk of CRC (AOR = 0.87; 95% CI: 0.83–0.91) not sustained after discontinuation. The association was time-dependent, starting early (AOR_{6months–1year} = 0.85; 95% CI: 0.76–0.96) but weakened beyond 3-years. A class effect was suggested, although only significant for simvastatin and rosuvastatin. The risk reduction was more marked among individuals aged 70 or younger, and among moderate-high intensity users. Forty-eight studies were included in the meta-analysis (pooled-effect-size = 0.90; 95% CI: 0.86–0.93). (4) Conclusions: Results from the case-control study and the pooled evidence support a moderate chemoprotective effect of statins on CRC risk, modified by duration, intensity, and age. Full article

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16 pages, 430 KiB

Open AccessArticle

Trends in the Management of Headache Disorders in US Emergency Departments: Analysis of 2007–2018 National Hospital Ambulatory Medical Care Survey Data

by Seonkyeong Yang, Yulia Orlova, Abigale Lipe, Macy Boren, Juan M. Hincapie-Castillo, Haesuk Park, Ching-Yuan Chang, Debbie L. Wilson, Lauren Adkins and Wei-Hsuan Lo-Ciganic

J. Clin. Med. 2022, 11(5), 1401; https://doi.org/10.3390/jcm11051401 - 3 Mar 2022

Cited by 9 | Viewed by 5049

Abstract

We examined trends in management of headache disorders in United States (US) emergency department (ED) visits. We conducted a cross-sectional study using 2007–2018 National Hospital Ambulatory Medical Care Survey data. We included adult patient visits (≥18 years) with a primary ED discharge diagnosis [...] Read more.

We examined trends in management of headache disorders in United States (US) emergency department (ED) visits. We conducted a cross-sectional study using 2007–2018 National Hospital Ambulatory Medical Care Survey data. We included adult patient visits (≥18 years) with a primary ED discharge diagnosis of headache. We classified headache medications by pharmacological group: opioids, butalbital, ergot alkaloids/triptans, acetaminophen/nonsteroidal anti-inflammatory drugs (NSAIDs), antiemetics, diphenhydramine, corticosteroids, and intravenous fluids. To obtain reliable estimates, we aggregated data into three time periods: 2007–2010, 2011–2014, and 2015–2018. Using multivariable logistic regression, we examined medication, neuroimaging, and outpatient referral trends, separately. Among headache-related ED visits, opioid use decreased from 54.1% in 2007–2010 to 28.3% in 2015–2018 (P_trend < 0.001). There were statistically significant increasing trends in acetaminophen/NSAIDs, diphenhydramine, and corticosteroids use (all P_trend < 0.001). Changes in butalbital (6.4%), ergot alkaloid/triptan (4.7%), antiemetic (59.2% in 2015–2018), and neuroimaging (37.3%) use over time were insignificant. Headache-related ED visits with outpatient referral for follow-up increased slightly from 73.3% in 2007–2010 to 79.7% in 2015–2018 (P_trend = 0.02). Reflecting evidence-based guideline recommendations for headache management, opioid use substantially decreased from 2007 to 2018 among US headache-related ED visits. Future studies are warranted to identify strategies to promote evidence-based treatment for headaches (e.g., sumatriptan, dexamethasone) and appropriate outpatient referral and reduce unnecessary neuroimaging orders in EDs. Full article

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14 pages, 1065 KiB

Open AccessArticle

Early Access to Medicines: Use of Multicriteria Decision Analysis (MCDA) as a Decision Tool in Catalonia (Spain)

by Montse Gasol, Noelia Paco, Laura Guarga, Josep Àngel Bosch, Caridad Pontes and Mercè Obach

J. Clin. Med. 2022, 11(5), 1353; https://doi.org/10.3390/jcm11051353 - 1 Mar 2022

Cited by 6 | Viewed by 3948

Abstract

Early access to medicines allows the prescription of a medicine before it is available in the public formulary to patients with severe or rare diseases with high unmet needs who have no authorised therapeutic alternatives available. In this context, consistent decision making is [...] Read more.

Early access to medicines allows the prescription of a medicine before it is available in the public formulary to patients with severe or rare diseases with high unmet needs who have no authorised therapeutic alternatives available. In this context, consistent decision making is difficult, and a systematic assessment procedure could be useful to tackle complex situations and guarantee the equity of medicines’ access. A multidisciplinary panel (MP) conducted four workshops to develop an early access framework based on a reflective multiple criteria decision analysis (MCDA). A set of 12 criteria was agreed: eight quantitative (severity of disease, urgency, efficacy, safety, internal and external validity, therapeutic benefit and plausibility) and four qualitative (therapeutic alternative, existence of precedents, management impact and costs). Quantitative criteria were weighted using a five-point scale. The relative importance of quantitative criteria had mean weights from 4.7 to 3.6, showing its relevance in the decisions. The framework was tested using two case studies, and reliability was assessed by re-test. The re-test revealed no statistical differences, indicating the consistency and replicability of the framework developed. MCDA may help to structure discussions for heterogeneous treatment requests, providing predictability and robustness in decision making involving sensitive and complex situations. Full article

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17 pages, 673 KiB

Open AccessReview

Role and Impact of Cerebrolysin for Ischemic Stroke Care

by Dafin F. Mureșanu, Livia Livinț Popa, Diana Chira, Victor Dăbală, Elian Hapca, Irina Vlad, Vitalie Văcăraș, Bogdan Ovidiu Popescu, Răzvan Cherecheș, Ștefan Strilciuc and Michael Brainin

J. Clin. Med. 2022, 11(5), 1273; https://doi.org/10.3390/jcm11051273 - 25 Feb 2022

Cited by 15 | Viewed by 9136

Abstract

Stroke is still a significant health problem that affects millions of people worldwide, as it is the second-leading cause of death and the third-leading cause of disability. Many changes have occurred in the treatment of acute ischemic stroke. Although the innovative concepts of [...] Read more.

Stroke is still a significant health problem that affects millions of people worldwide, as it is the second-leading cause of death and the third-leading cause of disability. Many changes have occurred in the treatment of acute ischemic stroke. Although the innovative concepts of neuroprotection and neurorecovery have been vigorously investigated in a substantial number of clinical studies in the past, only a few trials managed to increase the number of promising outcomes with regard to the multidimensional construct of brain protection and rehabilitation. In terms of pharmacological therapies with proven benefits in the post-ischemic process, drugs with neurorestorative properties are thought to be effective in both the acute and chronic phases of stroke. One significant example is Cerebrolysin, a combination of amino acids and peptides that mimic the biological functions of neurotrophic factors, which has been shown to improve outcomes after ischemic stroke, while preserving a promising safety profile. The purpose of this paper is to offer an overview on the role and impact of Cerebrolysin for ischemic stroke care, by touching on various aspects, from its complex, multimodal and pleiotropic mechanism of action, to its efficacy and safety, as well as cost effectiveness. Full article

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15 pages, 15161 KiB

Open AccessArticle

Carisoprodol Single and Multiple Dose PK-PD. Part II: Pharmacodynamics Evaluation Method for Central Muscle Relaxants. Double-Blind Placebo-Controlled Clinical Trial in Healthy Volunteers

by Aitana Calvo, Mercedes González-Hidalgo, Ana Terleira, Nieves Fernández and Antonio Portolés

J. Clin. Med. 2022, 11(4), 1141; https://doi.org/10.3390/jcm11041141 - 21 Feb 2022

Cited by 1 | Viewed by 2431

Abstract

Centrally acting skeletal muscle relaxants (CMR) such as carisoprodol are used to treat acute, painful musculoskeletal conditions, though its precise mode of action has not been characterized. A double-blinded, placebo-controlled, randomized clinical trial was designed to evaluate the pharmacokinetics–pharmacodynamics (PKPD) of CMR after [...] Read more.

Centrally acting skeletal muscle relaxants (CMR) such as carisoprodol are used to treat acute, painful musculoskeletal conditions, though its precise mode of action has not been characterized. A double-blinded, placebo-controlled, randomized clinical trial was designed to evaluate the pharmacokinetics–pharmacodynamics (PKPD) of CMR after single (350 mg), double (700 mg), and multiple doses (up to 350 mg/8 h, 14 days) of carisoprodol. Muscular (Electromyogram–EMG, muscular strength dynamometry), central (sedation), and tolerability (psychomotor activity test, adverse events) parameters, as well as withdrawal symptoms, were evaluated. Thirteen healthy volunteers were enrolled. No evidence of direct muscle relaxation was evidenced, but some differences on sedation were evidenced throughout the study, suggesting that CMRs act, at least partly, through sedation. Most significant differences were detected at 1.5 h after dosing. The effect on psychomotor impairment was variable, most prominently after 1.5 h, too, suggesting that it is produced by carisoprodol rather than by meprobamate. No withdrawal symptoms were detected, so the risk of dependence following maximum doses and duration of treatment recommended, and under medical supervision, should be low. Full article

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10 pages, 717 KiB

Open AccessArticle

Melatonin in the Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers (MeCOVID): A Randomised Clinical Trial

by Irene García-García, Enrique Seco-Meseguer, Pilar Ruiz-Seco, Gema Navarro-Jimenez, Raúl Martínez-Porqueras, María Espinosa-Díaz, Juan José Ortega-Albás, Iñigo Sagastagoitia, María Teresa García-Morales, María Jiménez-González, Lucía Martínez de Soto, Ana Isabel Bajo-Martínez, María del Palacio-Tamarit, Raquel López-García, Lucía Díaz-García, Javier Queiruga-Parada, Christine Giesen, Ana Pérez-Villena, Marta de Castro-Martínez, Juan J. González-García, Miguel Rodriguez-Rubio, Pedro de la Oliva, José R. Arribas, Antonio J. Carcas and Alberto M. Borobia Show full author list Hide full author list

J. Clin. Med. 2022, 11(4), 1139; https://doi.org/10.3390/jcm11041139 - 21 Feb 2022

Cited by 7 | Viewed by 4537

Abstract

We evaluated in this randomised, double-blind clinical trial the efficacy of melatonin as a prophylactic treatment for prevention of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Healthcare workers fulfilling inclusion criteria were recruited in five hospitals in Spain and [...] Read more.

We evaluated in this randomised, double-blind clinical trial the efficacy of melatonin as a prophylactic treatment for prevention of SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Healthcare workers fulfilling inclusion criteria were recruited in five hospitals in Spain and were randomised 1:1 to receive melatonin 2 mg administered orally for 12 weeks or placebo. The main outcome was the number of SARS-CoV-2 infections. A total of 344 volunteers were screened, and 314 were randomised: 151 to placebo and 163 to melatonin; 308 received the study treatment (148 placebo; 160 melatonin). We detected 13 SARS-CoV-2 infections, 2.6% in the placebo arm and 5.5% in the melatonin arm (p = 0.200). A total of 294 adverse events were detected in 127 participants (139 in placebo; 155 in melatonin). We found a statistically significant difference in the incidence of adverse events related to treatment: 43 in the placebo arm and 67 in the melatonin arm (p = 0.040), and in the number of participants suffering from somnolence related to treatment: 8.8% (n = 14) in the melatonin versus 1.4% (n = 2) in the placebo arm (p = 0.008). No severe adverse events related to treatment were reported. We cannot confirm our hypothesis that administration of melatonin prevents the development of SARS-CoV-2 infection in healthcare workers. Full article

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19 pages, 765 KiB

Open AccessReview

Abuse Potential of Cathinones in Humans: A Systematic Review

by Lourdes Poyatos, Adrián Torres, Esther Papaseit, Clara Pérez-Mañá, Olga Hladun, Melani Núñez-Montero, Georgina de la Rosa, Marta Torrens, Daniel Fuster, Robert Muga and Magí Farré

J. Clin. Med. 2022, 11(4), 1004; https://doi.org/10.3390/jcm11041004 - 15 Feb 2022

Cited by 13 | Viewed by 4073

Abstract

Introduction and objective: Assessing the abuse potential of new substances with central nervous system activity is essential for preventing possible risks of misuse and addiction. The same methodology is recommended for the evaluation of the abuse potential of recreational drugs. This systematic [...] Read more.

Introduction and objective: Assessing the abuse potential of new substances with central nervous system activity is essential for preventing possible risks of misuse and addiction. The same methodology is recommended for the evaluation of the abuse potential of recreational drugs. This systematic review aims to assess the pharmacological effects related to the abuse potential and pharmacokinetics of cathinones, which are evaluated in both experimental and prospective observational studies in humans. Materials and Methods: A systematic search of the published literature was conducted to retrieve studies that had administered cathinone, mephedrone, methylone, and diethylpropion to evaluate their acute pharmacological effects related to abuse potential. Results: The search yielded 583 results, 18 of which were included to assess the abuse potential of cathinone (n = 5), mephedrone (n = 7), methylone (n = 1), and diethylpropion (n = 5). All four substances induce stimulant and euphorigenic effects that resemble those of amphetamines and MDMA, and their different intensities may be associated with varying levels of abuse potential. Conclusions: Cathinone, mephedrone, methylone, and diethylpropion induce a range of desirable and reinforcing effects that may, to some extent, result in abuse potential. Further investigation is needed to minimize and prevent their impact on society and public health. Full article

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11 pages, 5423 KiB

Open AccessArticle

Single and Multiple Dose PK–PD Characterization for Carisoprodol. Part I: Pharmacokinetics, Metabolites, and 2C19 Phenotype Influence. Double-Blind, Placebo-Controlled Clinical Trial in Healthy Volunteers

by Aitana Calvo, Saioa Alonso, Esther Prieto, Ana Ascaso-del-Rio, Jordi Ortuño, Nieves Fernandez and Antonio Portolés

J. Clin. Med. 2022, 11(3), 858; https://doi.org/10.3390/jcm11030858 - 6 Feb 2022

Cited by 2 | Viewed by 2677

Abstract

Carisoprodol was authorised in 1959 without a full pharmacokinetic–pharmacodynamic (PK–PD) characterisation. We designed a crossover, double-blind, placebo-controlled, randomized clinical trial to characterize the PKs of carisoprodol and its main active metabolite, meprobamate, after single (350 mg), multiple (350 mg/8 h, 14 days), and [...] Read more.

Carisoprodol was authorised in 1959 without a full pharmacokinetic–pharmacodynamic (PK–PD) characterisation. We designed a crossover, double-blind, placebo-controlled, randomized clinical trial to characterize the PKs of carisoprodol and its main active metabolite, meprobamate, after single (350 mg), multiple (350 mg/8 h, 14 days), and double (700 mg) doses of carisoprodol. Thirteen healthy volunteers were enrolled. After a single (350 mg) dose, the main carisoprodol parameters were (mean ± SD) Cmax: 2580 ± 1214 ng/mL, AUC_0–∞: 8072 ± 6303 h·ng/mL, and half-life (T_1/2): 2 ± 0.8 h. For meprobamate, the parameters were Cmax: 2181 ± 605 ng/mL and 34,529 ± 7747 h·ng/mL y 9 ± 1.9 h. Different profiles were found for extensive and poor 2C19 metabolizers. After 14 days of treatment (350 mg/8 h) the results for carisoprodol were (mean ± SD) Cmax: 2504 ± 730 ng/mL, AUC_0–∞: 7451 ± 3615 h·ng/mL, and T_1/2: 2 ± 0.7 h. For meprobamate (a steady state was reached), the parameters were Cmax: 5758 ± 1255 ng/mL and 79,699 ± 17,978 h·ng/mL y 8.7 ± 1.4 h. The study allowed for the full characterization of the pharmacokinetic profile of carisoprodol and meprobamate. Accumulation of meprobamate but not of carisoprodol was evident after 14 days of treatment. Full article

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2021

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12 pages, 712 KiB

Open AccessArticle

The Effect of Statins in Cancer Risk Reduction in Patients on Dialysis: A Population-Based Case-Control Study

by Po-Huang Chen, Hong-Jie Jhou, Chi-Hsiang Chung, Cho-Hao Lee, Yi-Ying Wu, Wei-Chou Chang, Wu-Chien Chien and Ping-Ying Chang

J. Clin. Med. 2021, 10(23), 5602; https://doi.org/10.3390/jcm10235602 - 28 Nov 2021

Cited by 2 | Viewed by 2221

Abstract

Background: To realize whether statins reduce the risk of cancer in susceptible dialysis populations, this study analyzed the relationship between statin use and cancer risk in patients on dialysis. Methods: Patients having a history of chronic kidney disease with hemodialysis or peritoneal dialysis [...] Read more.

Background: To realize whether statins reduce the risk of cancer in susceptible dialysis populations, this study analyzed the relationship between statin use and cancer risk in patients on dialysis. Methods: Patients having a history of chronic kidney disease with hemodialysis or peritoneal dialysis and receiving statin prescriptions or not were enrolled. The main outcome was cancer diagnosis. This study used univariate and multivariate Cox regression analyses. Results: In total, 4236 individuals in the statin group and 8472 individuals in the statin nonuser group were included in the study. Multivariate Cox regression analysis revealed that statin users are significantly less likely to develop cancer than statin nonusers (adjusted hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.78–0.90). Subgroup analyses revealed that statin cumulative defined daily doses >365 were associated with a significantly decreased risk of cancer incidence (adjusted HR 0.59, 95% CI 0.45–0.87), and statin users have a reduced risk of respiratory, soft tissue and connective tissue, breast, gynecological, prostate, central nervous system, and lymphatic and hematopoietic cancer than nonusers. Conclusions: Our population-based cohort study provides an association that statins reduce the risk of malignancy in patients on dialysis, especially with a longer treatment duration, and certain types of cancer. Full article

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15 pages, 324 KiB

Open AccessArticle

Spontaneous Reporting of Adverse Drug Reactions in a Pediatric Population in a Tertiary Hospital

by Laura López-Valverde, Èlia Domènech, Marc Roguera, Ignasi Gich, Magí Farré, Carlos Rodrigo and Eva Montané

J. Clin. Med. 2021, 10(23), 5531; https://doi.org/10.3390/jcm10235531 - 26 Nov 2021

Cited by 2 | Viewed by 3358

Abstract

The pediatric population is a vulnerable group for adverse drug reactions (ADRs), and data on spontaneous reporting of ADRs in the hospital setting are scarce. We conducted a retrospective analysis of ADRs in pediatric patients spontaneously reported by health care professionals to a [...] Read more.

The pediatric population is a vulnerable group for adverse drug reactions (ADRs), and data on spontaneous reporting of ADRs in the hospital setting are scarce. We conducted a retrospective analysis of ADRs in pediatric patients spontaneously reported by health care professionals to a Pharmacovigilance Program in a tertiary hospital between 2010 and 2020, and we compared characteristics of ADRs between pediatric age subgroups. From 1787 spontaneously reported ADRs in an 11-year period, 103 (5.85%) were pediatric ADRs. The median age of patients with ADRs was 8.4 years (range 1 day–17 years) and 57.3% were male. The most frequent ADRs reported were nervous system disorders (13.6%) and the most frequently involved drugs were antineoplastics and immunodulators (32.4%). A 59.2% of the ADRs were serious and 55.3% were classified as being type B reactions. Medication errors were involved in 7.8% of the ADRs and 11.9% of the suspected drugs were used off-label. Spontaneous reports of ADRs in newborns, infants, and toddlers were more serious and less often described in the product data sheet than in children and adolescents (p < 0.001 and p = 0.004 respectively). Medication errors were more frequent in patients under two years of age. These results should be interpreted with caution due to under-reporting and biases in spontaneous reporting of ADRs. Full article

13 pages, 423 KiB

Open AccessArticle

Off-Label Use of Rituximab in Patients with Different Types of Nephropathies in a Tertiary Hospital: A Retrospective Study

by Carla Sans-Pola, Antònia Agustí, Josep Àngel Bosch, Irene Agraz, Carmen Alerany and Immaculada Danés

J. Clin. Med. 2021, 10(21), 4941; https://doi.org/10.3390/jcm10214941 - 26 Oct 2021

Cited by 1 | Viewed by 2608

Abstract

Off-label use of rituximab is commonly requested for patients with resistant nephropathies. The outcomes and tolerability of rituximab in adult patients with nephropathy treated at our hospital (from 2013 to 2018) were described. Data were retrieved from electronic medical records. Response was classified [...] Read more.

Off-label use of rituximab is commonly requested for patients with resistant nephropathies. The outcomes and tolerability of rituximab in adult patients with nephropathy treated at our hospital (from 2013 to 2018) were described. Data were retrieved from electronic medical records. Response was classified as complete remission (CR), partial remission (PR), or no response (NR) according to the KDIGO criteria. A total of 89 requests were received for 61 patients. Median age was 58 years (45.9% female). Idiopathic membranous nephropathy (MN) (n = 30) was the most frequent indication, followed by minimal change disease (MCD) (n = 15) and secondary membranoproliferative glomerulonephritis (MPGN) (n = 12). Three patients with focal segmental glomerulosclerosis (FSGS) were included. After most treatment cycles in MN, a CR or PR was observed; median proteinuria levels significantly decreased for these patients (6000 mg/24h (IQR 3584–10,300) vs. 1468.8 (IQR 500–4604.25), p < 0.01). In MPGN, no response was documented after 46.7% of rituximab cycles. A CR or PR was described with the majority of rituximab cycles in MCD, with a significant decrease in proteinuria (6000 mg/24 h (IQR 4007–11,426) vs. 196.8 (IQR 100–1300), p = 0.013). No cycles produced a response in FSGS. Mean CD19+ B-cell decreased in all types of nephropathy (10.44% vs. 0.29%, p < 0.0001). Eleven patients presented infusion-related reactions, and 17 presented infectious complications. The majority of patients with MN and MCD had complete or partial responses; however, neither MPGN nor FSGS had encouraging results. Full article

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16 pages, 286 KiB

Open AccessArticle

by Ana Lucía Arellano, Pau Alcubilla, Magí Farré and Eva Montané

J. Clin. Med. 2021, 10(18), 4053; https://doi.org/10.3390/jcm10184053 - 8 Sep 2021

Cited by 3 | Viewed by 3029

Abstract

Drug-related deaths (DRDs) are a common cause of hospital death. Pharmacovigilance, either as spontaneous reporting or active surveillance, plays a key role in the detection and reporting of suspected adverse drug reactions (ADRs). We conducted a retrospective analysis of all DRDs spontaneously reported [...] Read more.

Drug-related deaths (DRDs) are a common cause of hospital death. Pharmacovigilance, either as spontaneous reporting or active surveillance, plays a key role in the detection and reporting of suspected adverse drug reactions (ADRs). We conducted a retrospective analysis of all DRDs spontaneously reported to a pharmacovigilance program of a tertiary hospital, by health care professionals. We compared these results to those of a previous retrospective study conducted in the same hospital from the hospital’s mortality registry. From 1460 spontaneous reported ADRs in a 10-year period, 73 (5%) were DRDs. The median age of DRD was 75 years (range 1 month–94) and 60.3% were men. The most frequent DRDs were hemorrhages (41.1%), followed by infections (17.8%). The most frequently involved drugs were anticoagulants and/or antithrombotic (30%), and antineoplastics (26.3%). When comparing both studies, spontaneous reporting detected more type B reactions (p < 0.001) and hospital-acquired DRD (p < 0.001); the number of concomitant drugs was higher (p = 0.0035); and the kind of ADR were different. The combination of several methods is mandatory to detect, assess, understand, and design strategies to prevent ADRs in a hospital setting, to ensure patient safety. Full article

16 pages, 1206 KiB

Open AccessReview

PriME-PGx: La Princesa University Hospital Multidisciplinary Initiative for the Implementation of Pharmacogenetics

by Pablo Zubiaur, Gina Mejía-Abril, Marcos Navares-Gómez, Gonzalo Villapalos-García, Paula Soria-Chacartegui, Miriam Saiz-Rodríguez, Dolores Ochoa and Francisco Abad-Santos

J. Clin. Med. 2021, 10(17), 3772; https://doi.org/10.3390/jcm10173772 - 24 Aug 2021

Cited by 21 | Viewed by 3011

Abstract

The implementation of clinical pharmacogenetics in daily practice is limited for various reasons. Today, however, it is a discipline in full expansion. Accordingly, in the recent times, several initiatives promoted its implementation, mainly in the United States but also in Europe. In this [...] Read more.

The implementation of clinical pharmacogenetics in daily practice is limited for various reasons. Today, however, it is a discipline in full expansion. Accordingly, in the recent times, several initiatives promoted its implementation, mainly in the United States but also in Europe. In this document, the genotyping results since the establishment of our Pharmacogenetics Unit in 2006 are described, as well as the historical implementation process that was carried out since then. Finally, this progress justified the constitution of La Princesa University Hospital Multidisciplinary Initiative for the Implementation of Pharmacogenetics (PriME-PGx), promoted by the Clinical Pharmacology Department of Hospital Universitario de La Princesa (Madrid, Spain). Here, we present the initiative along with the two first ongoing projects: the PROFILE project, which promotes modernization of pharmacogenetic reporting (i.e., from classic gene-drug pair reporting to complete pharmacogenetic reporting or the creation of pharmacogenetic profiles specific to the Hospital’s departments) and the GENOTRIAL project, which promotes the communication of relevant pharmacogenetic findings to any healthy volunteer participating in any bioequivalence clinical trial at the Clinical Trials Unit of Hospital Universitario de La Princesa (UECHUP). Full article

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10 pages, 254 KiB

Open AccessArticle

Spontaneously Reported Adverse Drug Reactions and Their Description in Hospital Discharge Reports: A Retrospective Study

by Cristina Aguilera, Antònia Agustí, Eulàlia Pérez, Rosa M. Gracia, Eduard Diogène and Immaculada Danés

J. Clin. Med. 2021, 10(15), 3293; https://doi.org/10.3390/jcm10153293 - 26 Jul 2021

Cited by 2 | Viewed by 2189

Abstract

The inclusion of spontaneously reported adverse drug reactions (ADRs) in hospital discharge reports was examined, in addition to the factors associated with their inclusion, the resulting therapeutic decisions, and any recommendations made upon patient discharge regarding the suspected offending drugs. ADRs that were [...] Read more.

The inclusion of spontaneously reported adverse drug reactions (ADRs) in hospital discharge reports was examined, in addition to the factors associated with their inclusion, the resulting therapeutic decisions, and any recommendations made upon patient discharge regarding the suspected offending drugs. ADRs that were spontaneously reported during 2017 and 2018 to the pharmacovigilance program were retrospectively analyzed. Information regarding patient characteristics, drug treatments, and ADRs was collected from the ADR notifications and from patient electronic medical records. The dependent variable was the mentioning of ADRs in the discharge reports, while characteristics of the ADRs, pharmacovigilance causality algorithms, and some of the suspected drugs themselves were the independent variables during bivariant analysis. A total of 286 reports of suspected ADRs from 271 patients (50.2% female; 77% adults) were included. Information regarding the ADRs was present in the discharge reports for 238 reports (83.2%); the ADR seriousness and the lack of potential alternative causes were the only associated factors. Withdrawal or withdrawal and substitution by an alternative drug were the most common therapeutic decisions, although often no recommendation was made. Overall, there is still room for improvement in terms of including information related to ADRs in hospital discharge reports. Full article

12 pages, 1073 KiB

Open AccessArticle

Acenocoumarol Pharmacogenetic Dosing Algorithm versus Usual Care in Patients with Venous Thromboembolism: A Randomised Clinical Trial

by Hoi Yan Tong, Alberto M. Borobia, Manuel Quintana-Díaz, Sara Fabra, Manuel González-Viñolis, Carmen Fernández-Capitán, María A. Rodriguez-Dávila, Alicia Lorenzo, Ana María López-Parra, Nuria Ruiz-Giménez, Francisco Abad-Santos, Carmen Suarez, Olga Madridano, Jorge Francisco Gómez-Cerezo, Pilar Llamas, Carlos Baeza-Richer, Eduardo Arroyo-Pardo, Antonio J. Carcas and The PGX-ACE Spanish Investigators Group

J. Clin. Med. 2021, 10(13), 2949; https://doi.org/10.3390/jcm10132949 - 30 Jun 2021

Cited by 4 | Viewed by 3675

Abstract

Patients with venous thromboembolism (VTE) require immediate treatment with anticoagulants such as acenocoumarol. This multicentre randomised clinical trial evaluated the effectiveness of a dosing pharmacogenetic algorithm versus a standard-of-care dose adjustment at the beginning of acenocoumarol treatment. We included 144 patients with VTE. [...] Read more.

Patients with venous thromboembolism (VTE) require immediate treatment with anticoagulants such as acenocoumarol. This multicentre randomised clinical trial evaluated the effectiveness of a dosing pharmacogenetic algorithm versus a standard-of-care dose adjustment at the beginning of acenocoumarol treatment. We included 144 patients with VTE. On the day of recruitment, a blood sample was obtained for genotyping (CYP2C9*2, CYP2C9*3, VKORC1, CYP4F2, APOE). Dose adjustment was performed on day 3 or 4 after the start of treatment according to the assigned group and the follow-up was at 12 weeks. The principal variable was the percentage of patients with an international normalised ratio (INR) within the therapeutic range on day 7. Thirty-four (47.2%) patients had an INR within the therapeutic range at day 7 after the start of treatment in the genotype-guided group compared with 14 (21.9%) in the control group (p = 0.0023). There were no significant differences in the time to achieve a stable INR, the number of INRs within the range in the first 6 weeks and at the end of study. Our results suggest the use of a pharmacogenetic algorithm for patients with VTE could be useful in achieving target INR control in the first days of treatment. Full article

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13 pages, 308 KiB

Open AccessArticle

Valproic Acid-Induced Liver Injury: A Case-Control Study from a Prospective Pharmacovigilance Program in a Tertiary Hospital

by Enrique S. Meseguer, Mikel U. Elizalde, Alberto M. Borobia and Elena Ramírez

J. Clin. Med. 2021, 10(6), 1153; https://doi.org/10.3390/jcm10061153 - 10 Mar 2021

Cited by 19 | Viewed by 5436

Abstract

Introduction: Valproic acid (VPA) is an antiepileptic drug extensively used for treating partial and generalised seizures, acute mania and as prophylaxis for bipolar disorder. Drug-induced liver injury (DILI) persists as a significant issue related to fatal outcomes by VPA. The aim of this [...] Read more.

Introduction: Valproic acid (VPA) is an antiepileptic drug extensively used for treating partial and generalised seizures, acute mania and as prophylaxis for bipolar disorder. Drug-induced liver injury (DILI) persists as a significant issue related to fatal outcomes by VPA. The aim of this study was to increase our knowledge about this condition and to better identify patients affected. Methods: We conducted an observational retrospective case-control study that identified cases of DILI by VPA from the Pharmacovigilance Programme from our Laboratory Signals at La Paz University Hospital from January 2007 to December 2019. From the Therapeutic VPA Monitoring program, two control groups were assigned, VPA-tolerant patients and the other with patients who developed mild VPA-related liver injury but who did not meet the DILI criteria, matched for date, age and sex. Results: A total of 60 patients were included in the study: 15 cases of DILI, 30 VPA-tolerant controls and 15 controls with mild liver injury. Mean age for the cases was 45.7 years, 4 (26.7%) were women and 5 (33.34%) were children under 18 years, of them 3 (20%) were fatal. Polytherapy with other antiepileptic drugs (p = 0.047) and alcohol consumption (p < 0.001) were associated with a greater risk of developing DILI by VPA. A diagnosis of epileptic seizure was more frequently related to DILI when compared with the VPA-tolerant controls (p < 0.001). The cases developed hepatocellular liver injury (p < 0.001), while the mild hepatic damage controls had a higher rate of cholestatic liver injury (p < 0.001). The laboratory lactate dehydrogenase values were statistically higher (even at baseline) in patients with DILI than in both control groups (p = 0.033 and p = 0.039). Conclusions: VPA hepatotoxicity remains a considerable problem. This study offers interesting findings for characterising VPA-induced liver injury and at-risk patients. Full article

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