Journal of Clinical Medicine

Editorial

6 pages, 237 KiB

Open AccessEditorial

Pharmacovigilance and Pharmacoepidemiology as a Guarantee of Patient Safety: The Role of the Clinical Pharmacologist

by Giada Crescioli, Roberto Bonaiuti, Renato Corradetti, Guido Mannaioni, Alfredo Vannacci and Niccolò Lombardi

J. Clin. Med. 2022, 11(12), 3552; https://doi.org/10.3390/jcm11123552 - 20 Jun 2022

Cited by 7 | Viewed by 2209

Abstract

Recent years, particularly the COVID-19 pandemic, can be considered a turning point for pharmacovigilance and pharmacoepidemiology in terms of their role in drug safety and drug utilisation monitoring in clinical practice [...] Full article

(This article belongs to the Special Issue Medication Safety and Pharmacovigilance in Clinical: From the Researcher Bench to the Patient Bedside)

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10 pages, 698 KiB

Open AccessArticle

Three Doses of COVID-19 Vaccines: A Retrospective Study Evaluating the Safety and the Immune Response in Patients with Multiple Sclerosis

by Giorgia Teresa Maniscalco, Daniele Di Giulio Cesare, Valerio Liguori, Valentino Manzo, Elio Prestipino, Simona Salvatore, Maria Elena Di Battista, Ornella Moreggia, Antonio Rosario Ziello, Vincenzo Andreone, Cristina Scavone and Annalisa Capuano

J. Clin. Med. 2023, 12(13), 4236; https://doi.org/10.3390/jcm12134236 - 23 Jun 2023

Viewed by 1260

Abstract

Since the beginning of the mass immunization of patients with multiple sclerosis (MS), many data on the efficacy and safety of COVID-19 vaccines have been produced. Considering that MS is an autoimmune disease and that some disease-modifying therapies (DMTs) could decrease the antibody [...] Read more.

Since the beginning of the mass immunization of patients with multiple sclerosis (MS), many data on the efficacy and safety of COVID-19 vaccines have been produced. Considering that MS is an autoimmune disease and that some disease-modifying therapies (DMTs) could decrease the antibody response against COVID-19 vaccines, we carried out this retrospective study with the aim to evaluate the safety of these vaccines in terms of AEFI occurrence and the antibody response after MS patients had received the third dose. Two hundred and ten patients (64.8% female; mean age: 46 years) received the third dose of the mRNA-based COVID-19 vaccine and were included in the study. Third doses were administered from October 2021 to January 2022. The majority of patients (n = 193) were diagnosed with RRMS and EDSS values were ≤3.0 in 72.4% of them. DMTs most commonly used by included patients were interferon Beta 1-a, dimethyl fumarate, natalizumab and fingolimod. Overall, 160 patients (68.8% female) experienced 294 AEFIs, of which about 90% were classified as short-term, while 9.2% were classified as long-term. The most commonly reported following the booster dose were pain at the injection site, flu-like symptoms, headache, fever and fatigue. Regarding the immune response, consistently with literature data, we found that patients receiving ocrelizumab and fingolimod had lower IgG titer than patients receiving other DMTs. Full article

(This article belongs to the Special Issue Medication Safety and Pharmacovigilance in Clinical: From the Researcher Bench to the Patient Bedside)

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13 pages, 969 KiB

Open AccessArticle

The Interplay of Perceived Risks and Benefits in Deciding to Become Vaccinated against COVID-19 While Pregnant or Breastfeeding: A Cross-Sectional Study in Italy

by Teresa Gavaruzzi, Marta Caserotti, Roberto Bonaiuti, Paolo Bonanni, Giada Crescioli, Mariarosaria Di Tommaso, Niccolò Lombardi, Lorella Lotto, Claudia Ravaldi, Enrico Rubaltelli, Alessandra Tasso, Alfredo Vannacci and Paolo Girardi

J. Clin. Med. 2023, 12(10), 3469; https://doi.org/10.3390/jcm12103469 - 15 May 2023

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Abstract

The present study examined the role of the perception of risks and benefits for the mother and her babies in deciding about the COVID-19 vaccination. In this cross-sectional study, five hypotheses were tested using data from a convenience sample of Italian pregnant and/or [...] Read more.

The present study examined the role of the perception of risks and benefits for the mother and her babies in deciding about the COVID-19 vaccination. In this cross-sectional study, five hypotheses were tested using data from a convenience sample of Italian pregnant and/or breastfeeding women (N = 1104, July–September 2021). A logistic regression model estimated the influence of the predictors on the reported behavior, and a beta regression model was used to evaluate which factors influenced the willingness to become vaccinated among unvaccinated women. The COVID-19 vaccination overall risks/benefits tradeoff was highly predictive of both behavior and intention. Ceteris paribus, an increase in the perception of risks for the baby weighed more against vaccination than a similar increase in the perception of risks for the mother. Additionally, pregnant women resulted in being less likely (or willing) to be vaccinated in their status than breastfeeding women, but they were equally accepting of vaccination if they were not pregnant. COVID-19 risk perception predicted intention to become vaccinated, but not behavior. In conclusion, the overall risks/benefits tradeoff is key in predicting vaccination behavior and intention, but the concerns for the baby weigh more than those for the mother in the decision, shedding light on this previously neglected aspect. Full article

(This article belongs to the Special Issue Medication Safety and Pharmacovigilance in Clinical: From the Researcher Bench to the Patient Bedside)

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12 pages, 892 KiB

Open AccessArticle

Exposures and Suspected Intoxications to Pharmacological and Non-Pharmacological Agents in Children Aged 0–14 Years: Real-World Data from an Italian Reference Poison Control Centre

by Valentina Brilli, Giada Crescioli, Andrea Missanelli, Cecilia Lanzi, Massimo Trombini, Alessandra Ieri, Francesco Gambassi, Alfredo Vannacci, Guido Mannaioni and Niccolò Lombardi

J. Clin. Med. 2023, 12(1), 352; https://doi.org/10.3390/jcm12010352 - 02 Jan 2023

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Abstract

This study describes the exposures and suspected intoxications in children (0–14 years) managed by an Italian reference poison control center (PCC). A seven-year observational retrospective study was performed on the medical records of the Toxicology Unit and PCC, Careggi University Hospital, Florence (Italy). [...] Read more.

This study describes the exposures and suspected intoxications in children (0–14 years) managed by an Italian reference poison control center (PCC). A seven-year observational retrospective study was performed on the medical records of the Toxicology Unit and PCC, Careggi University Hospital, Florence (Italy). During the study period (2015–2021), a total of 27,212 phone call consultations were managed by the PCC, of which 11,996 (44%) involved subjects aged 0–14 years. Most cases occurred in males (54%) aged 1–5 years (73.8%), mainly at home (97.4%), and with an oral route of intoxication (93%). Cases mainly occurred involuntarily. Consultations were generally requested by caregivers; however, in the age group 12–14 years, 70% were requested by healthcare professionals due to voluntary intoxications. Cleaners (19.44%) and household products (10.90%) were the most represented suspected agents. Pharmacological agents accounted for 28.80% of exposures. Covariates associated with a higher risk of emergency department visit or hospitalization were voluntary intoxication (OR 29.18 [11.76–72.38]), inhalation route (OR 1.87 [1.09–3.23]), and pharmacological agents (OR 1.34 [1.23–1.46]), particularly central nervous system medications. Overall, consultations do not burden national and regional healthcare facilities, revealing the activity of PCCs as having a strategic role in reducing public health spending, even during the COVID-19 pandemic. Full article

(This article belongs to the Special Issue Medication Safety and Pharmacovigilance in Clinical: From the Researcher Bench to the Patient Bedside)

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11 pages, 769 KiB

Open AccessArticle

Medication Adherence in Medicare-Enrolled Older Adults with Chronic Obstructive Pulmonary Disease before and during the COVID-19 Pandemic

by Ligang Liu, Armando Silva Almodóvar and Milap C. Nahata

J. Clin. Med. 2022, 11(23), 6985; https://doi.org/10.3390/jcm11236985 - 26 Nov 2022

Cited by 3 | Viewed by 1691

Abstract

Medication adherence to controller inhalers was unknown in older Medicare patients with chronic obstructive pulmonary disease (COPD) before and during the pandemic. This study evaluated changes in medication adherence to controller medications and factors associated with high adherence. This retrospective cohort study included [...] Read more.

Medication adherence to controller inhalers was unknown in older Medicare patients with chronic obstructive pulmonary disease (COPD) before and during the pandemic. This study evaluated changes in medication adherence to controller medications and factors associated with high adherence. This retrospective cohort study included older Medicare patients with COPD. The proportion of days covered (PDC) reflected changes in medication adherence from January to July in 2019 and in 2020. Paired t-test evaluated changes in adherence. Logistic regression determined the association of patient characteristics with high adherence (PDC ≥ 80%). Mean adherence decreased (p < 0.001) for long-acting beta-agonists, long-acting muscarinic antagonists, and inhaled corticosteroids in 2020. The percentage of patients with high adherence dropped from 74.4% to 58.1% (p < 0.001). The number of controllers, having ≥3 albuterol fills, and a 90-day supply were associated with high adherence in 2019 and 2020 (p < 0.001). The COVID-19 pandemic may negatively impact medication adherence. Patients with evidence of more severe diseases and a 90-day supply were more likely to adhere to therapy. Healthcare professionals should prioritize prescribing 90-day supplies of medications and monitor drug-related problems as components of pharmacovigilance to enhance adherence to therapies and the desired clinical outcomes among patients with COPD. Full article

(This article belongs to the Special Issue Medication Safety and Pharmacovigilance in Clinical: From the Researcher Bench to the Patient Bedside)

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11 pages, 874 KiB

Open AccessArticle

The Safety Profile of COVID-19 Vaccines in Patients Diagnosed with Multiple Sclerosis: A Retrospective Observational Study

by Giorgia Teresa Maniscalco, Cristina Scavone, Annamaria Mascolo, Valentino Manzo, Elio Prestipino, Gaspare Guglielmi, Maria Luisa Aiezza, Santolo Cozzolino, Adele Bracco, Ornella Moreggia, Daniele Di Giulio Cesare, Antonio Rosario Ziello, Angela Falco, Marida Massa, Massimo Majolo, Eliana Raiola, Roberto Soprano, Giuseppe Russo, Giuseppe Longo, Vincenzo Andreone and Annalisa Capuano Show full author list Hide full author list

J. Clin. Med. 2022, 11(22), 6855; https://doi.org/10.3390/jcm11226855 - 21 Nov 2022

Cited by 8 | Viewed by 2835

Abstract

In the current COVID-19 pandemic, patients diagnosed with multiple sclerosis (MS) are considered to be one of the highest priority categories, being recognized as extremely vulnerable people. For this reason, mRNA-based COVID-19 vaccines are strongly recommended for these patients. Despite encouraging results on [...] Read more.

In the current COVID-19 pandemic, patients diagnosed with multiple sclerosis (MS) are considered to be one of the highest priority categories, being recognized as extremely vulnerable people. For this reason, mRNA-based COVID-19 vaccines are strongly recommended for these patients. Despite encouraging results on the efficacy and safety profile of mRNA-based COVID-19 vaccines, to date, in frail populations, including patients diagnosed with MS, this information is rather limited. We carried out a retrospective observational study with the aim to evaluate the safety profile of mRNA-based COVID-19 vaccines by retrieving real-life data of MS patients who were treated and vaccinated at the Multiple Sclerosis Center of the Hospital A.O.R.N. A. Cardarelli. Three-hundred and ten medical records of MS patients who received the first dose of the mRNA-based COVID-19 vaccine were retrieved (63% female; mean age: 45.9 years). Of these patients, 288 also received the second dose. All patients received the Pfizer-BioNTech vaccine. Relapsing-Remitting Multiple Sclerosis (RRSM) was the most common form of MS. The Expanded Disability Status Scale (EDSS) values were <3.0 in 70% of patients. The majority of patients received a Disease Modifying Therapy (DMT) during the study period, mainly interferon beta 1-a, dimethyl fumarate, and natalizumab and fingolimod. Overall, 913 AEFIs were identified, of which 539 were after the first dose of the vaccine and 374 after the second dose. The majority of these AEFIs were classified as short-term since they occurred within the first 72 h. The most common identified adverse events were pain at injection site, flu-like symptoms, and headache. Fever was reported more frequently after the second dose than after the first dose. SARS-CoV-2 infection occurred in 3 patients after the first dose. Using historical data of previous years (2017–2020), the relapses’ rate during 2021 was found to be lower. Lastly, the results of the multivariable analysis that assessed factors associated with the occurrence of AEFIs revealed a statistical significance for age, sex, and therapy with ocrelizumab (p < 0.05). In conclusion, our results indicated that Pfizer-BioNTech vaccine was safe for MS patients, being associated with AEFIs already detected in the general population. Larger observational studies with longer follow-up and epidemiological studies are strongly needed. Full article

(This article belongs to the Special Issue Medication Safety and Pharmacovigilance in Clinical: From the Researcher Bench to the Patient Bedside)

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14 pages, 1305 KiB

Open AccessArticle

Safety Surveillance of Mass Praziquantel and Albendazole Co-Administration in School Children from Southern Ethiopia: An Active Cohort Event Monitoring

by Tigist Dires Gebreyesus, Eyasu Makonnen, Tafesse Tadele, Habtamu Gashaw, Workagegnew Degefe, Heran Gerba, Birkneh Tilahun Tadesse, Parthasarathi Gurumurthy and Eleni Aklillu

J. Clin. Med. 2022, 11(21), 6300; https://doi.org/10.3390/jcm11216300 - 26 Oct 2022

Cited by 4 | Viewed by 1152

Abstract

Preventive chemotherapy (PC) with praziquantel and albendazole co-administration to all at-risk populations is the global intervention strategy to eliminate schistosomiasis and soil-transmitted helminth (STH) from being public health problems. Due to weak pharmacovigilance systems, safety monitoring during a mass drug administration (MDA) is [...] Read more.

Preventive chemotherapy (PC) with praziquantel and albendazole co-administration to all at-risk populations is the global intervention strategy to eliminate schistosomiasis and soil-transmitted helminth (STH) from being public health problems. Due to weak pharmacovigilance systems, safety monitoring during a mass drug administration (MDA) is lacking, especially in sub-Saharan Africa. We conducted large-scale active safety surveillance to identify the incidence, types, severity, and associated risk factors of adverse events (AEs) following praziquantel and albendazole MDA in 5848 school children (5–15 years old). Before MDA, 1484 (25.4%) children were prescreened for S. mansoni and STH infections, of whom 71.8% were infected with at least one parasite; 34.5% (512/1484) had S. mansoni and 853 (57.5%) had an STH infection. After collecting the baseline socio-demographic, clinical, and medical data, including any pre-existing clinical symptoms, participants received single dose praziquantel and albendazole MDA. Treatment-associated AEs were actively monitored on days 1 and 7 of the MDA. The events reported before and after the MDA were cross-checked and verified to identify MDA-associated AEs. The cumulative incidence of experiencing at least one type of MDA-associated AE was 13.3% (95% CI = 12.5–14.2%); 85.5%, 12.4%, and 1.8% of reported AEs were mild, moderate, and severe, respectively. The proportion of experiencing one, two, or ≥ three types of AEs was 57.7%, 34.1%, and 8.2%, respectively. The cumulative incidence of AEs in S. mansoni- and (17.0%) and STH (14.1%)-infected children was significantly higher (p < 0.001, χ² = 15.0) than in non-infected children (8.4%). Headache, abdominal pain, vomiting, dizziness, and nausea were the most common AEs. Being female, older age, having S. mansoni or STH infection were significant predictors of MDA-associated AEs. In summary, praziquantel and albendazole co-administration is generally safe and tolerable. MDA-associated AEs are mostly mild-to-moderately severe and transient. The finding of few severe AEs and significantly high rates of AEs in helminth-infected children underscores the need to integrate pharmacovigilance in MDA programs, especially in high schistosomiasis and STH endemic areas. Full article

(This article belongs to the Special Issue Medication Safety and Pharmacovigilance in Clinical: From the Researcher Bench to the Patient Bedside)

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21 pages, 2345 KiB

Open AccessArticle

COVID-19 Vaccines Adverse Reactions Reported to the Pharmacovigilance Unit of Beira Interior in Portugal

by Carina Amaro, Cristina Monteiro and Ana Paula Duarte

J. Clin. Med. 2022, 11(19), 5591; https://doi.org/10.3390/jcm11195591 - 23 Sep 2022

Cited by 3 | Viewed by 2022

Abstract

Coronavirus disease 2019 is an acute respiratory disease caused by the severe acute respiratory syndrome coronavirus 2. As the virus spreads rapidly, it has become a major public health emergency, which has led to rapid vaccines development. However, vaccines can present harmful and [...] Read more.

Coronavirus disease 2019 is an acute respiratory disease caused by the severe acute respiratory syndrome coronavirus 2. As the virus spreads rapidly, it has become a major public health emergency, which has led to rapid vaccines development. However, vaccines can present harmful and unintended responses, which must be notified to the National Pharmacovigilance System. The aim of this study is to characterize the adverse drug reactions (ADRs) of these vaccines notified in the region covered by the Regional Pharmacovigilance Unit (RPU) of Beira Interior, in Portugal, between 1 and 31 December 2020. During this period, 4 vaccines were administered: Comirnaty^®, Spikevax^®, Vaxzevria^® and Jcovden^®. The RPU of Beira Interior received 2134 notifications corresponding to 5685 ADRs, of which 20.34% (n = 434) of the notifications were considered serious reactions. Of these, 9.52% (n = 42) resulted in hospitalization and 0.45% (n = 2) resulted in death. Among the ADRs notified, reactions at or around the injection site, myalgia, headaches and pyrexia were the most commonly notified. Most ADRs were resolved within a few hours or days without sequelae. These ADRs are in accordance with clinical trials, the summary of product characteristics (SmPC) of each vaccine and ADR notifications from other countries. However, further studies are needed to confirm these results. Full article

(This article belongs to the Special Issue Medication Safety and Pharmacovigilance in Clinical: From the Researcher Bench to the Patient Bedside)

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13 pages, 1056 KiB

Open AccessArticle

Did the COVID-19 Pandemic Affect Contrast Media-Induced Adverse Drug Reaction’s Reporting? A Pharmacovigilance Study in Southern Italy

by Claudia Rossi, Rosanna Ruggiero, Liberata Sportiello, Ciro Pentella, Mario Gaio, Antonio Pinto and Concetta Rafaniello

J. Clin. Med. 2022, 11(17), 5104; https://doi.org/10.3390/jcm11175104 - 30 Aug 2022

Cited by 6 | Viewed by 1362

Abstract

Medical imaging is required for a complete clinical evaluation to identify lung involvement or pulmonary embolism during SARS-CoV-2 infection or pulmonary and cardiovascular sequelae. Contrast media (CM) have undoubtedly been useful in clinical practice due to their ability to improve medical imaging in [...] Read more.

Medical imaging is required for a complete clinical evaluation to identify lung involvement or pulmonary embolism during SARS-CoV-2 infection or pulmonary and cardiovascular sequelae. Contrast media (CM) have undoubtedly been useful in clinical practice due to their ability to improve medical imaging in COVID-19 patients. Considering their important use, especially in hospitalized COVID-19 patients, and that increased use of a medical tool could also be associated with its deeper knowledge, we chose to explore if new information emerged regarding CM safety profiles. We analyzed all Individual Case Safety Reports (ICSRs) validated by Campania Pharmacovigilance Regional Centre from 1 January 2018 to 31 December 2021 and reported a CM (ATC code V08) as a suspected drug. We compared CM-related reporting between 2 years before (period 1) and 2 years during (period 2) the COVID-19 pandemic. From our analysis, it emerged that, during the COVID-19 pandemic, CM-related ADR reporting decreased, but a significant increase in reporting of serious cases emerged. Serious ADRs were mainly related to iodinated CM (V08A ATC) compared to magnetic resonance imaging CM (V08C ATC). Cutaneous and respiratory disorders were the most frequently reported in both periods. No new or unknown ADRs were reported in the overall study period. Full article

(This article belongs to the Special Issue Medication Safety and Pharmacovigilance in Clinical: From the Researcher Bench to the Patient Bedside)

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10 pages, 2004 KiB

Open AccessArticle

Effect of Dipeptidyl Peptidase-4 Inhibitors vs. Metformin on Major Cardiovascular Events Using Spontaneous Reporting System and Real-World Database Study

by Yoshihiro Noguchi, Shunsuke Yoshizawa, Tomoya Tachi and Hitomi Teramachi

J. Clin. Med. 2022, 11(17), 4988; https://doi.org/10.3390/jcm11174988 - 25 Aug 2022

Cited by 3 | Viewed by 1476

Abstract

Background: Metformin had been recommended as the first-line treatment for type 2 diabetes since 2006 because of its low cost, high efficacy, and potential to reduce cardiovascular events, and thus death. However, dipeptidyl peptidase-4 (DPP-4) inhibitors are the most commonly prescribed first-line agents [...] Read more.

Background: Metformin had been recommended as the first-line treatment for type 2 diabetes since 2006 because of its low cost, high efficacy, and potential to reduce cardiovascular events, and thus death. However, dipeptidyl peptidase-4 (DPP-4) inhibitors are the most commonly prescribed first-line agents for patients with type 2 diabetes in Japan. Therefore, it is necessary to clarify the effect of DPP-4 inhibitors on preventing cardiovascular events, taking into consideration the actual prescription of antidiabetic drugs in Japan. Methods: This study examined the effect of DPP-4 inhibitors on preventing cardiovascular events. The Japanese Adverse Drug Event Report (JADER) database, a spontaneous reporting system in Japan, and the Japanese Medical Data Center (JMDC) Claims Database, a Japanese health insurance claims and medical checkup database, were used for the analysis. Metformin was used as the DPP-4 inhibitor comparator. Major cardiovascular events were set as the primary endpoint. Results: In the analysis using the JADER database, a signal of major cardiovascular events was detected with DPP-4 inhibitors (IC: 0.22, 95% confidence interval: 0.03–0.40) but not with metformin. In the analysis using the JMDC Claims Database, the hazard ratio of major cardiovascular events for DPP-4 inhibitors versus metformin was 1.01 (95% CI: 0.84–1.20). Conclusions: A comprehensive analysis using two different databases in Japan, the JADER and the JMDC Claims Database, showed that DPP-4 inhibitors, which are widely used in Japan, have a non-inferior risk of cardiovascular events compared to metformin, which is used as the first-line drug in the United States and Europe. Full article

(This article belongs to the Special Issue Medication Safety and Pharmacovigilance in Clinical: From the Researcher Bench to the Patient Bedside)

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13 pages, 1106 KiB

Open AccessArticle

Efficacy and Safety of Empagliflozin in Type 2 Diabetes Mellitus Saudi Patients as Add-On to Antidiabetic Therapy: A Prospective, Open-Label, Observational Study

by Fahad M. Althobaiti, Safaa M. Alsanosi, Alaa H. Falemban, Abdullah R. Alzahrani, Salma A. Fataha, Sara O. Salih, Ali M. Alrumaih, Khalid N. Alotaibi, Hazim M. Althobaiti, Saeed S. Al-Ghamdi and Nahla Ayoub

J. Clin. Med. 2022, 11(16), 4769; https://doi.org/10.3390/jcm11164769 - 16 Aug 2022

Cited by 4 | Viewed by 2299

Abstract

The Saudi Food and Drug Authority (SFDA) approved sodium-glucose cotransporter-2 (SGLT2) inhibitors in 2018. The efficacy and safety of empagliflozin (EMPA) have been confirmed in the U.S., Europe, and Japan for patients with type 2 diabetes mellitus (T2DM); however, analogous evidence is lacking [...] Read more.

The Saudi Food and Drug Authority (SFDA) approved sodium-glucose cotransporter-2 (SGLT2) inhibitors in 2018. The efficacy and safety of empagliflozin (EMPA) have been confirmed in the U.S., Europe, and Japan for patients with type 2 diabetes mellitus (T2DM); however, analogous evidence is lacking for Saudi T2DM patients. Therefore, the current study aimed to assess the efficacy and safety of EMPA in Saudi patients (n = 256) with T2DM. This is a 12-week prospective, open-label, observational study. Adult Saudi patients with T2DM who had not been treated with EMPA before enrolment were eligible. The exclusion criteria included T2DM patients less than 18 years of age, adults with type one diabetes, pregnant women, paediatric population. The results related to efficacy included a significant decrease in haemoglobin A1c (HbA1c) (adjusted mean difference −0.93% [95% confidence interval (CI) −0.32, −1.54]), significant improvements in fasting plasma glucose (FPG) (−2.28 mmol/L [95% CI −2.81, −1.75]), and a reduction in body weight (−0.874 kg [95% CI −4.36, −6.10]) following the administration of 25 mg of EMPA once daily as an add-on to ongoing antidiabetic therapy after 12 weeks. The primary safety endpoints were the change in the mean blood pressure (BP) values, which indicated significantly reduced systolic and diastolic BP (−3.85 mmHg [95% CI −6.81, −0.88] and −0.06 mmHg [95% CI −0.81, −0.88], respectively) and pulse rate (−1.18 [95% CI −0.79, −3.15]). In addition, kidney function was improved, with a significant reduction in the urine albumin/creatinine ratio (UACR) (−1.76 mg/g [95% CI −1.07, −34.25]) and a significant increase in the estimated glomerular filtration rate (eGFR) (3.54 mL/min/1.73 m² [95% CI 2.78, 9.87]). Furthermore, EMPA reduced aminotransferases (ALT) in a pattern (reduction in ALT > AST). The adjusted mean difference in the change in ALT was −2.36 U/L [95% CI −1.031, −3.69], while it was −1.26 U/L [95% CI −0.3811, −2.357] for AST and −1.98 U/L [95% CI −0.44, −3.49] for GGT. Moreover, in the EMPA group, serum high-density lipoprotein (HDL) significantly increased (0.29 mmol/L [95% CI 0.74, 0.15]), whereas a nonsignificant increase was seen in low-density lipoprotein (LDL) (0.01 mmol/L [95% CI 0.19, 0.18]) along with a significant reduction in plasma triglyceride (TG) levels (−0.43 mmol/L [95% CI −0.31, −1.17]). Empagliflozin once daily is an efficacious and tolerable strategy for treating Saudi patients with insufficiently controlled T2DM as an add-on to ongoing antidiabetic therapy. Full article

(This article belongs to the Special Issue Medication Safety and Pharmacovigilance in Clinical: From the Researcher Bench to the Patient Bedside)

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13 pages, 871 KiB

Open AccessArticle

Novel Method for Early Prediction of Clinically Significant Drug–Drug Interactions with a Machine Learning Algorithm Based on Risk Matrix Analysis in the NICU

by Nadir Yalçın, Merve Kaşıkcı, Hasan Tolga Çelik, Karel Allegaert, Kutay Demirkan, Şule Yiğit and Murat Yurdakök

J. Clin. Med. 2022, 11(16), 4715; https://doi.org/10.3390/jcm11164715 - 12 Aug 2022

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Abstract

Aims: Evidence for drug–drug interactions (DDIs) that may cause age-dependent differences in the incidence and severity of adverse drug reactions (ADRs) in newborns is sparse. We aimed to develop machine learning (ML) algorithms that predict DDI presence by integrating each DDI, which is [...] Read more.

Aims: Evidence for drug–drug interactions (DDIs) that may cause age-dependent differences in the incidence and severity of adverse drug reactions (ADRs) in newborns is sparse. We aimed to develop machine learning (ML) algorithms that predict DDI presence by integrating each DDI, which is objectively evaluated with the scales in a risk matrix (probability + severity). Methods: This double-center, prospective randomized cohort study included neonates admitted to the neonatal intensive care unit in a tertiary referral hospital during the 17-month study period. Drugs were classified by the Anatomical Therapeutic Chemical (ATC) classification and assessed for potential and clinically relevant DDIs to risk analyses with the Drug Interaction Probability Scale (DIPS, causal probability) and the Lexicomp^® DDI (severity) database. Results: A total of 412 neonates (median (interquartile range) gestational age of 37 (4) weeks) were included with 32,925 patient days, 131 different medications, and 11,908 medication orders. Overall, at least one potential DDI was observed in 125 (30.4%) of the patients (2.6 potential DDI/patient). A total of 38 of these 125 patients had clinically relevant DDIs causing adverse drug reactions (2.0 clinical DDI/patient). The vast majority of these DDIs (90.66%) were assessed to be at moderate risk. The performance of the ML algorithms that predicts of the presence of relevant DDI was as follows: accuracy 0.944 (95% CI 0.888–0.972), sensitivity 0.892 (95% CI 0.769–0.962), F1 score 0.904, and AUC 0.929 (95% CI 0.874–0.983). Conclusions: In clinical practice, it is expected that optimization in treatment can be achieved with the implementation of this high-performance web tool, created to predict DDIs before they occur with a newborn-centered approach. Full article

(This article belongs to the Special Issue Medication Safety and Pharmacovigilance in Clinical: From the Researcher Bench to the Patient Bedside)

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17 pages, 1322 KiB

Open AccessArticle

Evaluating the Medication Regimen Complexity Score as a Predictor of Clinical Outcomes in the Critically Ill

by Mohammad A. Al-Mamun, Jacob Strock, Yushuf Sharker, Khaled Shawwa, Rebecca Schmidt, Douglas Slain, Ankit Sakhuja and Todd N. Brothers

J. Clin. Med. 2022, 11(16), 4705; https://doi.org/10.3390/jcm11164705 - 11 Aug 2022

Cited by 2 | Viewed by 1987

Abstract

Background: Medication Regimen Complexity (MRC) refers to the combination of medication classes, dosages, and frequencies. The objective of this study was to examine the relationship between the scores of different MRC tools and the clinical outcomes. Methods: We conducted a retrospective cohort study [...] Read more.

Background: Medication Regimen Complexity (MRC) refers to the combination of medication classes, dosages, and frequencies. The objective of this study was to examine the relationship between the scores of different MRC tools and the clinical outcomes. Methods: We conducted a retrospective cohort study at Roger William Medical Center, Providence, Rhode Island, which included 317 adult patients admitted to the intensive care unit (ICU) between 1 February 2020 and 30 August 2020. MRC was assessed using the MRC Index (MRCI) and MRC for the Intensive Care Unit (MRC-ICU). A multivariable logistic regression model was used to identify associations among MRC scores, clinical outcomes, and a logistic classifier to predict clinical outcomes. Results: Higher MRC scores were associated with increased mortality, a longer ICU length of stay (LOS), and the need for mechanical ventilation (MV). MRC-ICU scores at 24 h were significantly (p < 0.001) associated with increased ICU mortality, LOS, and MV, with ORs of 1.12 (95% CI: 1.06–1.19), 1.17 (1.1–1.24), and 1.21 (1.14–1.29), respectively. Mortality prediction was similar using both scoring tools (AUC: 0.88 [0.75–0.97] vs. 0.88 [0.76–0.97]. The model with 15 medication classes outperformed others in predicting the ICU LOS and the need for MV with AUCs of 0.82 (0.71–0.93) and 0.87 (0.77–0.96), respectively. Conclusion: Our results demonstrated that both MRC scores were associated with poorer clinical outcomes. The incorporation of MRC scores in real-time therapeutic decision making can aid clinicians to prescribe safer alternatives. Full article

(This article belongs to the Special Issue Medication Safety and Pharmacovigilance in Clinical: From the Researcher Bench to the Patient Bedside)

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by Silvia Pagani, Niccolò Lombardi, Giada Crescioli, Violetta Giuditta Vighi, Giulia Spada, Paola Andreetta, Annalisa Capuano, Alfredo Vannacci, Mauro Venegoni, Giuseppe Danilo Vighi and on behalf of the MEREAFaPS Study Group

J. Clin. Med. 2022, 11(10), 2811; https://doi.org/10.3390/jcm11102811 - 16 May 2022

Cited by 12 | Viewed by 2821

Abstract

The aim of the present study is to describe pharmacological characteristics of drug-related allergies and anaphylaxis leading to the emergency department (ED). An 8-year post hoc analysis on the MEREAFaPS Study database was performed (2012–2019). Subjects who experienced drug-related hypersensitivity leading to an [...] Read more.

The aim of the present study is to describe pharmacological characteristics of drug-related allergies and anaphylaxis leading to the emergency department (ED). An 8-year post hoc analysis on the MEREAFaPS Study database was performed (2012–2019). Subjects who experienced drug-related hypersensitivity leading to an ED visit were selected. Logistic regression analyses were used to estimate the reporting odds ratios (RORs) of drug-related allergies and anaphylaxis adjusting for sex, age classes, and ethnicity. In addition, a systematic review of observational studies evaluating drug-related hypersensitivity reactions leading to ED visits in outpatients was performed. Out of 94,073 ED visits, 14.4% cases were drug-related allergies and 0.6% were anaphylaxis. Females accounted for 56%. Multivariate logistic regression showed a higher risk of drug-related allergy among males and all age classes < 65 years, while a higher risk of anaphylaxis was observed for females (ROR 1.20 [1.01–1.42]) and adults (ROR 2.63 [2.21–3.14]). The systematic review included 37 studies. ED visits related to allergy and anaphylaxis ranged from 0.004% to 88%, and drug-related allergies and anaphylaxis ranged from 0.007% to 88%. Both in our analysis and in primary studies, antibacterials, analgesics, and radiocontrast agents were identified as the most common triggers of hypersensitivity. Full article

(This article belongs to the Special Issue Medication Safety and Pharmacovigilance in Clinical: From the Researcher Bench to the Patient Bedside)

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