Aims: The aim of this study was to explore the suspected adverse drug reaction (ADR) data of five licensed statins in the UK: atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin. A secondary aim was to determine if there are any associations between the polypharmacological properties of the statins and their associated muscle-related side effects. Methods: The chemical database of bioactive molecules with drug-like properties, European Molecular Biology Laboratory (ChEMBL), was used to obtain data on the pharmacological interactions of statins with human proteins. The Medicines and Healthcare Products Regulatory Agency’s (MHRA) Yellow Card scheme was used to obtain reports of suspected ADRs from 2018 to 2022. The OpenPrescribing database was used to obtain the prescribing rates for statistical interpretation. Results: The study found no significant difference between the statins association with suspected ADRs across all organ classes (X2, p > 0.05). Fluvastatin was found to have a higher incidence of ADRs/100,000 Rx across multiple system organ classes. Conclusions: No significant difference was found between the suspected ADR incidence of the statins across all system organ classes.
{"title":"Associations between Suspected Adverse Drug Reactions of HMG-CoA Reductase Inhibitors and Polypharmacology Using a National Registry Approach","authors":"Hasan Yousaf, A. M. Jones","doi":"10.3390/pharma3030016","DOIUrl":"https://doi.org/10.3390/pharma3030016","url":null,"abstract":"Aims: The aim of this study was to explore the suspected adverse drug reaction (ADR) data of five licensed statins in the UK: atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin. A secondary aim was to determine if there are any associations between the polypharmacological properties of the statins and their associated muscle-related side effects. Methods: The chemical database of bioactive molecules with drug-like properties, European Molecular Biology Laboratory (ChEMBL), was used to obtain data on the pharmacological interactions of statins with human proteins. The Medicines and Healthcare Products Regulatory Agency’s (MHRA) Yellow Card scheme was used to obtain reports of suspected ADRs from 2018 to 2022. The OpenPrescribing database was used to obtain the prescribing rates for statistical interpretation. Results: The study found no significant difference between the statins association with suspected ADRs across all organ classes (X2, p > 0.05). Fluvastatin was found to have a higher incidence of ADRs/100,000 Rx across multiple system organ classes. Conclusions: No significant difference was found between the suspected ADR incidence of the statins across all system organ classes.","PeriodicalId":74431,"journal":{"name":"Pharmacoepidemiology","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141682269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
H. Johannesmeyer, Luiza Baloyan, Kristica Kolyouthapong
Clostridioides difficile infection (CDI) is the leading cause of nosocomial diarrhea in the United States. Tigecycline has been proposed as a potential treatment for CDI, though limited clinical data exist to support this practice. The objective of this study was to determine if the provision of tigecycline provides a clinically meaningful benefit to inpatients with CDI. This study was a retrospective chart review enrolling inpatients receiving treatment for CDI. Patients were divided into cohorts depending on whether they received a standard antibiotic therapy regimen for CDI or an antibiotic treatment regimen that included tigecycline. The primary outcome was clinical recovery at the time of hospital discharge. A total of 39 and 22 patients were included in the standard antibiotic therapy and tigecycline groups, respectively. ATLAS (Age, Treatment, Leukocyte, Albumin, Serum creatinine) scores at the time of CDI diagnosis were similar between the two groups, though patients in the tigecycline groups were more likely to represent a recurrent episode of CDI. There was no difference in the rate of clinical recovery at the time of hospital discharge between the standard antibiotic therapy and tigecycline groups (38.5% vs. 36.4%, p = 0.8710). These data do not support the routine use of tigecycline for the treatment of CDI, though interpretation is limited due to baseline differences between groups and the retrospective, observational nature of this study.
{"title":"A Retrospective Analysis of the Clinical Effectiveness of Tigecycline in the Treatment of Clostridioides difficile-Associated Diarrhea","authors":"H. Johannesmeyer, Luiza Baloyan, Kristica Kolyouthapong","doi":"10.3390/pharma3020015","DOIUrl":"https://doi.org/10.3390/pharma3020015","url":null,"abstract":"Clostridioides difficile infection (CDI) is the leading cause of nosocomial diarrhea in the United States. Tigecycline has been proposed as a potential treatment for CDI, though limited clinical data exist to support this practice. The objective of this study was to determine if the provision of tigecycline provides a clinically meaningful benefit to inpatients with CDI. This study was a retrospective chart review enrolling inpatients receiving treatment for CDI. Patients were divided into cohorts depending on whether they received a standard antibiotic therapy regimen for CDI or an antibiotic treatment regimen that included tigecycline. The primary outcome was clinical recovery at the time of hospital discharge. A total of 39 and 22 patients were included in the standard antibiotic therapy and tigecycline groups, respectively. ATLAS (Age, Treatment, Leukocyte, Albumin, Serum creatinine) scores at the time of CDI diagnosis were similar between the two groups, though patients in the tigecycline groups were more likely to represent a recurrent episode of CDI. There was no difference in the rate of clinical recovery at the time of hospital discharge between the standard antibiotic therapy and tigecycline groups (38.5% vs. 36.4%, p = 0.8710). These data do not support the routine use of tigecycline for the treatment of CDI, though interpretation is limited due to baseline differences between groups and the retrospective, observational nature of this study.","PeriodicalId":74431,"journal":{"name":"Pharmacoepidemiology","volume":"58 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141349171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Taylor N. Hallet, David T. Zhu, Hannah Shadowen, Lillia Thumma, Madison M. Marcus, Amy Salisbury, Caitlin E. Martin
Buprenorphine is a safe and effective medication to treat opioid use disorder (OUD) in pregnant patients and is intended to be continued throughout pregnancy, delivery, and at least the one-year postpartum period. However, delivery often involves the need for acute pain management with opioid medications, such as after a cesarean section. For patients receiving buprenorphine, the provision of prescription opioids may negatively impact OUD treatment outcomes; however, not optimally managing acute pain may also impede OUD treatment benefit. Evidence is needed to disentangle the impacts of opioid prescription provision and methods of pain management in the immediate postpartum period on OUD treatment trajectories, ultimately to inform clinical guidelines tailored to the unique needs of pregnant and postpartum people receiving buprenorphine. Accordingly, this study took an initial step towards this goal to conduct a secondary analysis of a retrospective cohort of pregnant patients taking buprenorphine for OUD at the time of delivery (n = 142) to determine whether receipt of an opioid prescription at birth hospitalization discharge was associated with the time of buprenorphine discontinuation within the 12 months following delivery. Among the sample, 26% (n = 37) were prescribed an opioid at the time of birth hospitalization discharge. The number of weeks post-delivery until buprenorphine discontinuation occurred was shorter amongst patients who were prescribed an opioid (median 11 weeks) compared to patients who were not prescribed an opioid (median 39 weeks; p < 0.001 by Mann–Whitney U test). However, a Cox regression model reported that receipt of an opioid prescription following delivery did not significantly increase the hazard ratio for buprenorphine discontinuation. In other words, OUD patients not prescribed an opioid at birth hospitalization discharge continued their buprenorphine for a longer median duration after delivery compared to their counterparts who received prescription opioids; yet, this finding did not reach statistical significance when taking into account additional clinical variables. The findings indicate how further research is warranted to inform evidence-based post-delivery pain practices for postpartum OUD treatment patients.
{"title":"Association of Receipt of Opioid Prescription for Acute Post-Delivery Pain Management with Buprenorphine Discontinuation among Postpartum People with Opioid Use Disorder","authors":"Taylor N. Hallet, David T. Zhu, Hannah Shadowen, Lillia Thumma, Madison M. Marcus, Amy Salisbury, Caitlin E. Martin","doi":"10.3390/pharma3020012","DOIUrl":"https://doi.org/10.3390/pharma3020012","url":null,"abstract":"Buprenorphine is a safe and effective medication to treat opioid use disorder (OUD) in pregnant patients and is intended to be continued throughout pregnancy, delivery, and at least the one-year postpartum period. However, delivery often involves the need for acute pain management with opioid medications, such as after a cesarean section. For patients receiving buprenorphine, the provision of prescription opioids may negatively impact OUD treatment outcomes; however, not optimally managing acute pain may also impede OUD treatment benefit. Evidence is needed to disentangle the impacts of opioid prescription provision and methods of pain management in the immediate postpartum period on OUD treatment trajectories, ultimately to inform clinical guidelines tailored to the unique needs of pregnant and postpartum people receiving buprenorphine. Accordingly, this study took an initial step towards this goal to conduct a secondary analysis of a retrospective cohort of pregnant patients taking buprenorphine for OUD at the time of delivery (n = 142) to determine whether receipt of an opioid prescription at birth hospitalization discharge was associated with the time of buprenorphine discontinuation within the 12 months following delivery. Among the sample, 26% (n = 37) were prescribed an opioid at the time of birth hospitalization discharge. The number of weeks post-delivery until buprenorphine discontinuation occurred was shorter amongst patients who were prescribed an opioid (median 11 weeks) compared to patients who were not prescribed an opioid (median 39 weeks; p < 0.001 by Mann–Whitney U test). However, a Cox regression model reported that receipt of an opioid prescription following delivery did not significantly increase the hazard ratio for buprenorphine discontinuation. In other words, OUD patients not prescribed an opioid at birth hospitalization discharge continued their buprenorphine for a longer median duration after delivery compared to their counterparts who received prescription opioids; yet, this finding did not reach statistical significance when taking into account additional clinical variables. The findings indicate how further research is warranted to inform evidence-based post-delivery pain practices for postpartum OUD treatment patients.","PeriodicalId":74431,"journal":{"name":"Pharmacoepidemiology","volume":"9 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140696530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing Wei Neo, Qihuang Xie, Pei San Ang, Hui Xing Tan, Belinda Foo, Yen Ling Koon, A. Ng, S. Tan, D. Teo, Mun Yee Tham, A. Yap, N. Ng, C. Loke, Li Fung Peck, Huilin Huang, S. Dorajoo
Background: Hypertension is frequently studied in epidemiological studies that have been conducted using retrospective observational data, either as an outcome or a variable. However, there are few validation studies investigating the accuracy of hypertension phenotyping algorithms in aggregated electronic health record (EHR) data. Methods: Utilizing a centralized repository of inpatient EHR data from Singapore for the period of 2019–2020, a new algorithm that incorporates both diagnostic codes and medication details (Diag+Med) was devised. This algorithm was intended to supplement and improve the diagnostic code-only model (Diag-Only) for the classification of hypertension. We computed various metrics (sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)) to assess the algorithm’s effectiveness in identifying hypertension on 2813 chart-reviewed records. This pool was composed of two patient cohorts: a random sampling of all inpatient admissions (Random Cohort) and a targeted group with atrial fibrillation diagnoses (AF Cohort). Results: The Diag+Med algorithm was more sensitive at detecting hypertension patients in both cohorts compared to the Diag-Only algorithm (83.8 and 87.6% vs. 68.2 and 66.5% in the Random and AF Cohorts, respectively). These improvements in sensitivity came at minimal costs in terms of PPV reductions (88.2 and 90.3% vs. 91.4 and 94.2%, respectively). Conclusion: The combined use of diagnosis codes and specific antihypertension medication exposure patterns facilitates a more accurate capture of patients with hypertension in a database of aggregated EHRs from diverse healthcare institutions in Singapore. The results presented here allow for the bias correction of risk estimates derived from observational studies involving hypertension.
{"title":"Pioneering Arterial Hypertension Phenotyping on Nationally Aggregated Electronic Health Records","authors":"Jing Wei Neo, Qihuang Xie, Pei San Ang, Hui Xing Tan, Belinda Foo, Yen Ling Koon, A. Ng, S. Tan, D. Teo, Mun Yee Tham, A. Yap, N. Ng, C. Loke, Li Fung Peck, Huilin Huang, S. Dorajoo","doi":"10.3390/pharma3010010","DOIUrl":"https://doi.org/10.3390/pharma3010010","url":null,"abstract":"Background: Hypertension is frequently studied in epidemiological studies that have been conducted using retrospective observational data, either as an outcome or a variable. However, there are few validation studies investigating the accuracy of hypertension phenotyping algorithms in aggregated electronic health record (EHR) data. Methods: Utilizing a centralized repository of inpatient EHR data from Singapore for the period of 2019–2020, a new algorithm that incorporates both diagnostic codes and medication details (Diag+Med) was devised. This algorithm was intended to supplement and improve the diagnostic code-only model (Diag-Only) for the classification of hypertension. We computed various metrics (sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)) to assess the algorithm’s effectiveness in identifying hypertension on 2813 chart-reviewed records. This pool was composed of two patient cohorts: a random sampling of all inpatient admissions (Random Cohort) and a targeted group with atrial fibrillation diagnoses (AF Cohort). Results: The Diag+Med algorithm was more sensitive at detecting hypertension patients in both cohorts compared to the Diag-Only algorithm (83.8 and 87.6% vs. 68.2 and 66.5% in the Random and AF Cohorts, respectively). These improvements in sensitivity came at minimal costs in terms of PPV reductions (88.2 and 90.3% vs. 91.4 and 94.2%, respectively). Conclusion: The combined use of diagnosis codes and specific antihypertension medication exposure patterns facilitates a more accurate capture of patients with hypertension in a database of aggregated EHRs from diverse healthcare institutions in Singapore. The results presented here allow for the bias correction of risk estimates derived from observational studies involving hypertension.","PeriodicalId":74431,"journal":{"name":"Pharmacoepidemiology","volume":"40 S18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140250875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this cross-sectional descriptive study conducted in the Ratnapura district, Sri Lanka, we assessed the affordability of oral pediatric anti-infective medicines (OPAIMs). Using a modified WHO/HAI medicinal price methodology, we examined the availability, median price ratios (MPRs), mean percentage difference, and affordability of the standard treatment of the originator brand (OB) and lowest-priced generic (LPG) OPAIMs in 30 private and 2 state-owned pharmacies. The study revealed disparities in availability, with only 50% of private pharmacies offering all 11 medicinal drugs in their generic form. The MPRs of OPAIMs for OB and LPG varied, with three drugs exceeding the financially acceptable MPR of 2 (albendazole, amoxicillin, and erythromycin). The standard treatment with LPGs costs between 0.17 and 0.85 and between 0.06 and 0.28 days’ wages for the lowest daily salary of the private sector and unskilled public employees, respectively. We identified erythromycin and albendazole as having less than 50% availability in their generic form in private pharmacies. To address these findings, we recommend frequent pricing revisions based on exchange rates and associated costs, coupled with the establishment of a transparent scientific criterion to subsidize essential medicines deemed “unaffordable.” Failure to implement such measures amidst economic crises may adversely impact financial access to essential medications.
{"title":"Affordability of Paediatric Oral Anti-Infective Medicines in a Selected District, Sri Lanka","authors":"Malith Kumarasinghe, M. Weerasinghe","doi":"10.3390/pharma3010011","DOIUrl":"https://doi.org/10.3390/pharma3010011","url":null,"abstract":"In this cross-sectional descriptive study conducted in the Ratnapura district, Sri Lanka, we assessed the affordability of oral pediatric anti-infective medicines (OPAIMs). Using a modified WHO/HAI medicinal price methodology, we examined the availability, median price ratios (MPRs), mean percentage difference, and affordability of the standard treatment of the originator brand (OB) and lowest-priced generic (LPG) OPAIMs in 30 private and 2 state-owned pharmacies. The study revealed disparities in availability, with only 50% of private pharmacies offering all 11 medicinal drugs in their generic form. The MPRs of OPAIMs for OB and LPG varied, with three drugs exceeding the financially acceptable MPR of 2 (albendazole, amoxicillin, and erythromycin). The standard treatment with LPGs costs between 0.17 and 0.85 and between 0.06 and 0.28 days’ wages for the lowest daily salary of the private sector and unskilled public employees, respectively. We identified erythromycin and albendazole as having less than 50% availability in their generic form in private pharmacies. To address these findings, we recommend frequent pricing revisions based on exchange rates and associated costs, coupled with the establishment of a transparent scientific criterion to subsidize essential medicines deemed “unaffordable.” Failure to implement such measures amidst economic crises may adversely impact financial access to essential medications.","PeriodicalId":74431,"journal":{"name":"Pharmacoepidemiology","volume":"58 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140251054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Teimur Kayani, Bachar Ahmad, Rachel Chang, Frank Qian, M. Sahinoz, Muhammad Rehan, Antonio Giaimo, Erica Spatz, Jiun-Ruey Hu
Although statins have served as the cornerstone for pharmacological lowering of lipid levels in atherosclerotic cardiovascular disease (ASCVD) risk reduction, many patients are unable to achieve target doses of statin medication due to side effects or target levels of cholesterol reduction on statin monotherapy. The landscape of lipid-lowering strategies has expanded in recent years, with the emergence of therapies that make use of small interfering RNA (siRNA) and antisense oligonucleotides, in addition to traditional small-molecule agents. Non-statin therapies that have shown promising results in randomized controlled trials include adenosine triphosphate-citrate lyase inhibitors, proprotein convertase subtilisin/kexin 9 (PCSK9)-inhibiting antibodies and siRNA, omega-3 polyunsaturated fatty acids, and lipoprotein(a) gene-inhibiting siRNA and ASOs, in addition to older therapies such as ezetimibe. In contrast, cholesteryl ester transfer protein (CETP) inhibitors have shown less promising results in randomized trials. The purpose of this narrative review is to summarize the evidence for these medications, with a focus on phase III randomized trials.
尽管他汀类药物一直是降低动脉粥样硬化性心血管疾病（ASCVD）风险的药物降脂基石，但由于副作用或他汀类药物单药治疗的胆固醇降幅达不到目标水平，许多患者无法达到他汀类药物的目标剂量。近年来，除传统的小分子药物外，还出现了利用小干扰 RNA（siRNA）和反义寡核苷酸的疗法，降脂策略的范围不断扩大。在随机对照试验中显示出良好疗效的非他汀类疗法包括三磷酸腺苷柠檬酸裂解酶抑制剂、蛋白转换酶亚基酶/kexin 9（PCSK9）抑制抗体和 siRNA、ω-3 多不饱和脂肪酸、脂蛋白（a）基因抑制 siRNA 和 ASO，以及依折麦布等老式疗法。相比之下，胆固醇酯转移蛋白（CETP）抑制剂在随机试验中显示出的效果并不乐观。本综述旨在总结这些药物的证据，重点关注 III 期随机试验。
{"title":"Beyond Statins: Novel Lipid-Lowering Agents for Reducing Risk of Atherosclerotic Cardiovascular Disease","authors":"Teimur Kayani, Bachar Ahmad, Rachel Chang, Frank Qian, M. Sahinoz, Muhammad Rehan, Antonio Giaimo, Erica Spatz, Jiun-Ruey Hu","doi":"10.3390/pharma3010009","DOIUrl":"https://doi.org/10.3390/pharma3010009","url":null,"abstract":"Although statins have served as the cornerstone for pharmacological lowering of lipid levels in atherosclerotic cardiovascular disease (ASCVD) risk reduction, many patients are unable to achieve target doses of statin medication due to side effects or target levels of cholesterol reduction on statin monotherapy. The landscape of lipid-lowering strategies has expanded in recent years, with the emergence of therapies that make use of small interfering RNA (siRNA) and antisense oligonucleotides, in addition to traditional small-molecule agents. Non-statin therapies that have shown promising results in randomized controlled trials include adenosine triphosphate-citrate lyase inhibitors, proprotein convertase subtilisin/kexin 9 (PCSK9)-inhibiting antibodies and siRNA, omega-3 polyunsaturated fatty acids, and lipoprotein(a) gene-inhibiting siRNA and ASOs, in addition to older therapies such as ezetimibe. In contrast, cholesteryl ester transfer protein (CETP) inhibitors have shown less promising results in randomized trials. The purpose of this narrative review is to summarize the evidence for these medications, with a focus on phase III randomized trials.","PeriodicalId":74431,"journal":{"name":"Pharmacoepidemiology","volume":"18 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140264016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Severe acute respiratory syndrome coronavirus 2 has infected millions of people, but about 20% of infected individuals do not develop symptoms. COVID-19 is an inflammatory disease that affects a portion of individuals infected with the virus and it is associated with liver injury and other complications, leading to hospitalization, critical illness, and death. Remdesivir is an antiviral agent used for the treatment of hospitalized patients with COVID-19 to improve the time to recovery, reduce the duration of mechanical ventilation, decrease the need for supplemental oxygen, and decrease the risk of mortality. Remdesivir-associated hepatotoxicity has been observed as increased transaminases more than five times the upper limit of normal in hospitalized patients with COVID-19, but causality has not been proven. It is generally difficult to distinguish between remdesivir-associated hepatotoxicity and COVID-19-induced hepatotoxicity. The purpose of this review is to evaluate the evidence for remdesivir-associated hepatotoxicity. Current evidence suggests that elevated liver enzymes in hospitalized COVID-19 patients are more likely to be due to the infection than remdesivir, and a 5-day course of remdesivir seems to be safe in regard to hepatotoxicity.
{"title":"Remdesivir and the Liver: A Concise Narrative Review of Remdesivir-Associated Hepatotoxicity in Patients Hospitalized Due to COVID-19","authors":"Alireza FakhriRavari, M. Malakouti","doi":"10.3390/pharma3010005","DOIUrl":"https://doi.org/10.3390/pharma3010005","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 has infected millions of people, but about 20% of infected individuals do not develop symptoms. COVID-19 is an inflammatory disease that affects a portion of individuals infected with the virus and it is associated with liver injury and other complications, leading to hospitalization, critical illness, and death. Remdesivir is an antiviral agent used for the treatment of hospitalized patients with COVID-19 to improve the time to recovery, reduce the duration of mechanical ventilation, decrease the need for supplemental oxygen, and decrease the risk of mortality. Remdesivir-associated hepatotoxicity has been observed as increased transaminases more than five times the upper limit of normal in hospitalized patients with COVID-19, but causality has not been proven. It is generally difficult to distinguish between remdesivir-associated hepatotoxicity and COVID-19-induced hepatotoxicity. The purpose of this review is to evaluate the evidence for remdesivir-associated hepatotoxicity. Current evidence suggests that elevated liver enzymes in hospitalized COVID-19 patients are more likely to be due to the infection than remdesivir, and a 5-day course of remdesivir seems to be safe in regard to hepatotoxicity.","PeriodicalId":74431,"journal":{"name":"Pharmacoepidemiology","volume":"16 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139779638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Severe acute respiratory syndrome coronavirus 2 has infected millions of people, but about 20% of infected individuals do not develop symptoms. COVID-19 is an inflammatory disease that affects a portion of individuals infected with the virus and it is associated with liver injury and other complications, leading to hospitalization, critical illness, and death. Remdesivir is an antiviral agent used for the treatment of hospitalized patients with COVID-19 to improve the time to recovery, reduce the duration of mechanical ventilation, decrease the need for supplemental oxygen, and decrease the risk of mortality. Remdesivir-associated hepatotoxicity has been observed as increased transaminases more than five times the upper limit of normal in hospitalized patients with COVID-19, but causality has not been proven. It is generally difficult to distinguish between remdesivir-associated hepatotoxicity and COVID-19-induced hepatotoxicity. The purpose of this review is to evaluate the evidence for remdesivir-associated hepatotoxicity. Current evidence suggests that elevated liver enzymes in hospitalized COVID-19 patients are more likely to be due to the infection than remdesivir, and a 5-day course of remdesivir seems to be safe in regard to hepatotoxicity.
{"title":"Remdesivir and the Liver: A Concise Narrative Review of Remdesivir-Associated Hepatotoxicity in Patients Hospitalized Due to COVID-19","authors":"Alireza FakhriRavari, M. Malakouti","doi":"10.3390/pharma3010005","DOIUrl":"https://doi.org/10.3390/pharma3010005","url":null,"abstract":"Severe acute respiratory syndrome coronavirus 2 has infected millions of people, but about 20% of infected individuals do not develop symptoms. COVID-19 is an inflammatory disease that affects a portion of individuals infected with the virus and it is associated with liver injury and other complications, leading to hospitalization, critical illness, and death. Remdesivir is an antiviral agent used for the treatment of hospitalized patients with COVID-19 to improve the time to recovery, reduce the duration of mechanical ventilation, decrease the need for supplemental oxygen, and decrease the risk of mortality. Remdesivir-associated hepatotoxicity has been observed as increased transaminases more than five times the upper limit of normal in hospitalized patients with COVID-19, but causality has not been proven. It is generally difficult to distinguish between remdesivir-associated hepatotoxicity and COVID-19-induced hepatotoxicity. The purpose of this review is to evaluate the evidence for remdesivir-associated hepatotoxicity. Current evidence suggests that elevated liver enzymes in hospitalized COVID-19 patients are more likely to be due to the infection than remdesivir, and a 5-day course of remdesivir seems to be safe in regard to hepatotoxicity.","PeriodicalId":74431,"journal":{"name":"Pharmacoepidemiology","volume":"91 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139839487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elena Baybulatova, Mikhail Chenkurov, Elina Korovyakova, S. Zyryanov, L. Ziganshina
Background: The coronavirus pandemic has led to the creation of clinical guidelines by a large number of professional medical communities. However, the quality and methodology of development of Russian clinical guidelines has been little studied. The continued relevance of studying the use of DOACs (Direct oral anticoagulants) in patients with COVID-19 was the basis for conducting this study. Aim: The objective of this study was to assess DOAC consumption and expenditure in the Russian Federation during the COVID-19 pandemic and to analyze whether it was supported by the domestic evidence base for the use of DOACs in COVID-19 patients through identifying all publicly available Russian-produced CPGs (Clinical practice guidelines) for the treatment of COVID-19 and assessing their quality as the source of recommendations for the use of oral anticoagulants for the prevention of thrombotic complications in COVID-19 patients. We searched Russian databases for CPGs, published between 2020 and 2023. We identified seven relevant documents that met our inclusion criteria. Three authors analyzed Russian clinical guidelines using an AGREE II questionnaire. We calculated DOAC DDD (defined daily dose) consumption according to Russian clinical guidelines and DDD consumption in patients with COVID-19 for the period 2020–2022. Results: Seven clinical CPGs were analyzed with the AGREE II tool. It was revealed that experts gave the highest scores for the sections on scope and purpose (from 62.98% to 100%), and clarity of presentation (from 96.30% to 100%). The lowest scores were given for the sections on stakeholder involvement (33.33% to 64.81%), rigour of development (from 0% to 49.31%), applicability (from 23.61% to 50%), and editorial independence (from 0% to 50%). When comparing the total score, it was found that two clinical guidelines received the highest scores—ROPNIZ (Livzan), and ROPNIZ (Drapkina). The minimum score was registered with the NIIOZMM (Khripun) clinical guideline. No guideline received a total score of more than 70%. According to clinical recommendations, the consumption of apixaban and rivaroxaban is 15 DDD (30-day course of therapy), or 22.5 DDD (45-day course of therapy). Consumption of apixaban in the Russian Federation in 2020 and 2021 corresponds to the indicators presented in clinical recommendations (in 2020—26.59 DDD per patient with COVID-19; in 2021—15.75 DDD per patient with COVID-19), and in 2022—10.67 DDD, which is below the recommended values. In 2020, consumption of rivaroxaban in the Russian Federation was 26.59 which corresponds to data from clinical recommendations; in 2021, consumption decreased to 7.87 DDD; in 2022 it decreased to 5.48 DDD, which is 2.74 times less than recommended. Conclusions: Analysis of seven clinical recommendations revealed that such sections of clinical recommendations as scope, purpose, and clarity of presentation had the highest degree of assessment in accordance with AGREE II. The lowest scores
{"title":"Direct Oral Anticoagulants’ Consumption and Expenditure in the COVID-19 Pandemic in Russia and Clinical Practice Guidelines for Their Use","authors":"Elena Baybulatova, Mikhail Chenkurov, Elina Korovyakova, S. Zyryanov, L. Ziganshina","doi":"10.3390/pharma3010001","DOIUrl":"https://doi.org/10.3390/pharma3010001","url":null,"abstract":"Background: The coronavirus pandemic has led to the creation of clinical guidelines by a large number of professional medical communities. However, the quality and methodology of development of Russian clinical guidelines has been little studied. The continued relevance of studying the use of DOACs (Direct oral anticoagulants) in patients with COVID-19 was the basis for conducting this study. Aim: The objective of this study was to assess DOAC consumption and expenditure in the Russian Federation during the COVID-19 pandemic and to analyze whether it was supported by the domestic evidence base for the use of DOACs in COVID-19 patients through identifying all publicly available Russian-produced CPGs (Clinical practice guidelines) for the treatment of COVID-19 and assessing their quality as the source of recommendations for the use of oral anticoagulants for the prevention of thrombotic complications in COVID-19 patients. We searched Russian databases for CPGs, published between 2020 and 2023. We identified seven relevant documents that met our inclusion criteria. Three authors analyzed Russian clinical guidelines using an AGREE II questionnaire. We calculated DOAC DDD (defined daily dose) consumption according to Russian clinical guidelines and DDD consumption in patients with COVID-19 for the period 2020–2022. Results: Seven clinical CPGs were analyzed with the AGREE II tool. It was revealed that experts gave the highest scores for the sections on scope and purpose (from 62.98% to 100%), and clarity of presentation (from 96.30% to 100%). The lowest scores were given for the sections on stakeholder involvement (33.33% to 64.81%), rigour of development (from 0% to 49.31%), applicability (from 23.61% to 50%), and editorial independence (from 0% to 50%). When comparing the total score, it was found that two clinical guidelines received the highest scores—ROPNIZ (Livzan), and ROPNIZ (Drapkina). The minimum score was registered with the NIIOZMM (Khripun) clinical guideline. No guideline received a total score of more than 70%. According to clinical recommendations, the consumption of apixaban and rivaroxaban is 15 DDD (30-day course of therapy), or 22.5 DDD (45-day course of therapy). Consumption of apixaban in the Russian Federation in 2020 and 2021 corresponds to the indicators presented in clinical recommendations (in 2020—26.59 DDD per patient with COVID-19; in 2021—15.75 DDD per patient with COVID-19), and in 2022—10.67 DDD, which is below the recommended values. In 2020, consumption of rivaroxaban in the Russian Federation was 26.59 which corresponds to data from clinical recommendations; in 2021, consumption decreased to 7.87 DDD; in 2022 it decreased to 5.48 DDD, which is 2.74 times less than recommended. Conclusions: Analysis of seven clinical recommendations revealed that such sections of clinical recommendations as scope, purpose, and clarity of presentation had the highest degree of assessment in accordance with AGREE II. The lowest scores ","PeriodicalId":74431,"journal":{"name":"Pharmacoepidemiology","volume":"63 s242","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139146149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nina Z. Y. Smith, J. D. Thornton, Susan H. Fenton, Debora Simmons, Tiffany Champagne-Langabeer
Prescription drug misuse is a global problem, especially in the United States (US). Clinician involvement is necessary in this crisis, and prescription drug monitoring programs (PDMPs) are a recommended tool for the prevention, recognition, and management of prescription opioid misuse. However, because of the plethora of differences between different PDMPs, research on their effects is mixed. Yet, despite varied evidence, policy on PDMP use is trending stricter and more comprehensive. We aimed to identify patterns in the research to inform clinicians and policy. Through a systematic review of four literature databases (CINAHL, Cochrane Database, Embase, and Medline/OVID), we found 56 experimental and quasi-experimental studies published between 2016 and 2023 evaluating PDMP effects on clinician behavior. To address study heterogeneity, we categorized studies by type of intervention and study outcome. The review suggests that more comprehensive PDMP legislation is associated with decreases in the number of opioid prescriptions overall and the number of risky prescriptions prescribed or dispensed. However, this review shows that much is still unknown, encourages improvements to PDMPs and policies, and suggests further research.
{"title":"Helpful, Unnecessary, or Harmful: A Systematic Review of the Effects of Prescription Drug Monitoring Program Use on Opioid Prescriptions","authors":"Nina Z. Y. Smith, J. D. Thornton, Susan H. Fenton, Debora Simmons, Tiffany Champagne-Langabeer","doi":"10.3390/pharma2040030","DOIUrl":"https://doi.org/10.3390/pharma2040030","url":null,"abstract":"Prescription drug misuse is a global problem, especially in the United States (US). Clinician involvement is necessary in this crisis, and prescription drug monitoring programs (PDMPs) are a recommended tool for the prevention, recognition, and management of prescription opioid misuse. However, because of the plethora of differences between different PDMPs, research on their effects is mixed. Yet, despite varied evidence, policy on PDMP use is trending stricter and more comprehensive. We aimed to identify patterns in the research to inform clinicians and policy. Through a systematic review of four literature databases (CINAHL, Cochrane Database, Embase, and Medline/OVID), we found 56 experimental and quasi-experimental studies published between 2016 and 2023 evaluating PDMP effects on clinician behavior. To address study heterogeneity, we categorized studies by type of intervention and study outcome. The review suggests that more comprehensive PDMP legislation is associated with decreases in the number of opioid prescriptions overall and the number of risky prescriptions prescribed or dispensed. However, this review shows that much is still unknown, encourages improvements to PDMPs and policies, and suggests further research.","PeriodicalId":74431,"journal":{"name":"Pharmacoepidemiology","volume":"17 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138999916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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