Treprostinil is a relatively new tricyclic prostacyclin analog with a stable str-ucture,extended half-life and improved potency.Currently,treprostinil is indicated by the Food and Drug Administration in the United Sta...Treprostinil is a relatively new tricyclic prostacyclin analog with a stable str-ucture,extended half-life and improved potency.Currently,treprostinil is indicated by the Food and Drug Administration in the United States for the treatment of pulmonary arterial hypertension(group 1 in the pulmonary hy-pertension classification of the World Health Organization).It has a potent vasodilating effect along with the inhibition of platelet aggregation and the attenuation of the inflammatory response in pulmonary and systemic circulation.It is available in the following formulations:Subcutaneous,intravenous,inhaled and oral.Although unknown to many clinicians,several encouraging reports of off-label treprostinil use in the adult population suggest its potential effectiveness in other clinical conditions.Currently under investigation are digital ischemia secondary to systemic sclerosis,chronic limb ischemia,hepatic ischemia-reper-fusion injury and group 3 and 4 pulmonary hypertension.Based on review and analysis of the available literature,this article provides a thorough update on the off-label use of treprostinil in adult patients.展开更多
High-quality scientific research is very important in attempting to effectively control the coronavirus disease 2019(COVID-19)pandemic and ensure people’s health and safety.Chloroquine(CQ)and hydroxychloroquine(HCQ)h...High-quality scientific research is very important in attempting to effectively control the coronavirus disease 2019(COVID-19)pandemic and ensure people’s health and safety.Chloroquine(CQ)and hydroxychloroquine(HCQ)have received much attention.This article comprehensively investigates the ethical review of off-label CQ and HCQ research during the COVID-19 pandemic with regard to strictly abiding by review standards,improving review efficiency,ensuring the rights and interests of subjects and that ethics committees conduct independent reviews,and achieving full ethics supervision of research conducted during an emergency.Research must be both rigorous and prudent to ensure the best outcome,with the maximization of benefits as the core principle.Standardization of the application,implementation and ethical review processes are needed to prevent unnecessary risk.展开更多
Aim: To analyse antibiotic prescriptions in a cohort of extremely low birth weight neonates admitted to Italian level III Neonatal intensive Care Units. Methods: An online questionnaire was used to collect detailed in...Aim: To analyse antibiotic prescriptions in a cohort of extremely low birth weight neonates admitted to Italian level III Neonatal intensive Care Units. Methods: An online questionnaire was used to collect detailed information for each newborn. Antibiotic prescriptions were classified about their license status and compared with British National Formulary for Children (BNFC) and with a practical guide prepared by the Italian Society of Neonatology (ISN). Results: During the study period (May-July 2014) among 93 neonates admitted to 30 Italian Neonatal intensive Care Units, 56 (60%) received at least an antibiotic (92 prescriptions in total). Ampicillin, gentamicin and vancomycin were the antibiotics most commonly used for the prevention/treatment of bacterial infections. 56/92 antibiotic prescriptions (61%) resulted off-label mainly as regards dosing frequency, while 13 prescriptions (14%) regarded antibiotics used in absence of specific indication for newborns (meropenem, imipenem, piperacillin/tazobactam, clindamycin, clarithromycin). 50/56 neonates (89.3%) received at least one off-label antibiotic prescription. Differences have been observed in dosing regimens between current study and recommendations contained in BNFC, while prescriptions adhered more frequently to ISN indications. Conclusions: Our results confirm the high prevalence of off-label antibiotic use in ELBW neonates and underline a better adherence to indications based on clinical practice.展开更多
Off-label use is defined by the prescription of a marketed drug outside the conditions described in the summary of product characteristics.In oncology,off-label prescribing of targeted therapies may occur in patients ...Off-label use is defined by the prescription of a marketed drug outside the conditions described in the summary of product characteristics.In oncology,off-label prescribing of targeted therapies may occur in patients with other tumor types expressing the same target.Agents associated to phenotypic approaches such as therapies against the tumoral vasculature(anti-angiogenic drugs) and new immunotherapies(checkpoint inhibitors) also carry the potential of alternative indications or combinations.Off-label use of targeted therapies is little documented and appears to be in the same range than that regarding older drugs with wide variations among agents.When compared with older agents,off-label use of targeted therapies is probably more rational through tumoral genotyping but is faced with a limited clinical support,reimbursement challenges related to the very high pricing and the cost of genotyping or molecular profiling,when applicable.展开更多
Background Off-label use of psychotropic prescriptions for pediatric patients has been increasing in Japan.This study sought to clarify pediatric patients' off-label use of psychotropics approved only for adults i...Background Off-label use of psychotropic prescriptions for pediatric patients has been increasing in Japan.This study sought to clarify pediatric patients' off-label use of psychotropics approved only for adults in Japan.Methods This retrospective study on psychotropic utilization employed a pharmaceutical health insurance claims database supplied by a pharmacy for the fiscal year 2016.Seven psychotropic drugs were examined.For each drug,we calculated the proportion of patients aged < 16 years or who were under the approved age limit set in the United States out of all patients.The maximum daily dose of each drug within the study period was plotted by age.Results Data of 45,715 patients (female:26,799,male:18,916) with 331,920 prescriptions were examined in this study.For each drug,the proportion of pediatric patients aged < 16 years ranged from 0.15 to 1.1%,while the proportion of those under the approved age limit in the United States ranged from 0 to 0.27%.Olanzapine had the highest reported proportion.No drugs other than olanzapine were taken under the approved age limit in the United States.Conclusions We identified the pediatric off-label use of psychotropics that were limited to adult use in Japan.The results indicated the possibility of referring to international guidelines or evidence in clinical practice,but these factors do not discount the existing problems with off-label use.More clinical trials within the pediatric population in Japan are needed to address the issue of off-label use and obtain useful and reliable information in the package inserts for rational use in future pediatric patients.展开更多
Background Off-label and unlicensed prescriptions pose a severe safety concern among the pediatric population.We aimed to summarize the up-to-date evidence on the extent,reasons,and consequences of off-label and unlic...Background Off-label and unlicensed prescriptions pose a severe safety concern among the pediatric population.We aimed to summarize the up-to-date evidence on the extent,reasons,and consequences of off-label and unlicensed drugs in hospitalized pediatric patients.Methods We systematically searched PubMed,EMBASE,SCOPUS,Web of Science and Google Scholar between 1990 and 2020 in which the last search was conducted on 12 February 2021.We included studies with the following inclusion criteria:(1)observational studies in design;(2)target population was hospitalized pediatric patients whether admitted in the intensive care unit or in the general ward;(3)study reporting the prevalence of off-label,unlicensed prescriptions or both;and(4)published in English.Results A total of 47 studies were eligible for inclusion.The proportion of off-label and unlicensed prescriptions ranged from 7.4%to 99.5%and 0.1%to 74.4%,respectively.The most frequent category of off-label prescriptions was prescription outside the age range,with the most commonly reported reason for off-label prescriptions being the lack of information specifically for pediatrics on the drug information leaflets.The consequences of off-label and unlicensed prescriptions ranged from minor and bearable skin reactions to debilitating renal failure,risking deaths.Conclusions Off-label and unlicensed prescriptions are extensive and require progressively meditative interventions.However,the pediatric population is currently a“therapeutic orphan”.Unless adequate pediatric clinical trials and licensed drugs become available,off-label and unlicensed drug prescription should not entirely be banned but rather promoted in an organized manner.展开更多
Background: The information about the use of off-labeldrugs in pediatric nephrology is still lacking, which leadsto increased adverse reactions and medical disputes. Weretrospectively analyzed the use of off-label dru...Background: The information about the use of off-labeldrugs in pediatric nephrology is still lacking, which leadsto increased adverse reactions and medical disputes. Weretrospectively analyzed the use of off-label drugs in thein-patient ward of the nephrology department of NanjingChildren's Hospital, China in order to provide morecomplete information about the use of drugs for children.Methods: Proportional stratified random samplingwas applied to select patients with renal diseases aged 1month to 18 years, who were admitted to the hospital fromOctober 1, 2012 to September 30, 2013. All nephrologyrelateddrugs prescribed in the hospitalization period andtake-home drugs prescribed on discharge were recordedand evaluated as off-label drugs or not from threedifferent perspectives: person-time, prescription, anddrug category.Results: From 385 person-times of patients with 1424prescriptions, according to the ratio between off-labeldrugs and person-times, drug prescriptions, and drugproducts, the rates of off-label drugs were 40.78%, 16.64%,and 31.43%, respectively. Low-molecular-weight heparin,alfacalcidol and diltiazem were the most commonly usedoff-label drugs. Infants and younger children were thehigh-risk population of off-label drug use. The high rateoff-label nephrology-related drug use in children wasmainly related to lacking clinical research into drugs inchildren and the pace of drug label's revision, which cannotfollow the development of medical science.Conclusions: Approximaely half of pediatric patientswith renal diseases are usually prescribed with off-labelnephrology-related drugs. Analyzing the off-label conditionsfrom different perspectives may lead to various results.More clinical research into drugs for infants and youngerchildren is needed so as to update drug descriptions.展开更多
This study sought to investigate adverse drug event(ADE)signals associated with eltrombopag use in pediatric patients aged 0–18 years,utilizing data from the U.S.Food and Drug Administration Adverse Event Reporting S...This study sought to investigate adverse drug event(ADE)signals associated with eltrombopag use in pediatric patients aged 0–18 years,utilizing data from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS).By analyzing this extensive pharmacovigilance database,the study aimed to offer meaningful insights for improving the clinical safety of eltrombopag in children.Data covering eltrombopag-related ADEs from Q12004 to Q42023 were extracted from FAERS,and signal detection was conducted using both the reporting odds ratio(ROR)and proportional reporting ratio(PRR)methods.ADEs were categorized based on the System Organ Class(SOC)classification in MedDRA version 25.0.A total of 582 reports involving pediatric patients receiving eltrombopag were identified,encompassing 21 SOC categories.The analysis revealed that,in addition to the known ADEs listed in the drug label,clinicians should remain vigilant for potential off-label ADE signals.These included abnormal platelet counts,thrombocytosis,antiphospholipid syndrome,myelofibrosis,reduced serum iron levels,myelodysplastic syndrome,hepatic infections,and other related conditions.Given these findings,it is strongly recommended that serum iron and ferritin levels should be routinely monitored in pediatric patients undergoing eltrombopag therapy,particularly during long-term treatment.Such proactive surveillance may help prevent the onset of iron deficiency anemia and enhance overall treatment safety.展开更多
文摘Treprostinil is a relatively new tricyclic prostacyclin analog with a stable str-ucture,extended half-life and improved potency.Currently,treprostinil is indicated by the Food and Drug Administration in the United States for the treatment of pulmonary arterial hypertension(group 1 in the pulmonary hy-pertension classification of the World Health Organization).It has a potent vasodilating effect along with the inhibition of platelet aggregation and the attenuation of the inflammatory response in pulmonary and systemic circulation.It is available in the following formulations:Subcutaneous,intravenous,inhaled and oral.Although unknown to many clinicians,several encouraging reports of off-label treprostinil use in the adult population suggest its potential effectiveness in other clinical conditions.Currently under investigation are digital ischemia secondary to systemic sclerosis,chronic limb ischemia,hepatic ischemia-reper-fusion injury and group 3 and 4 pulmonary hypertension.Based on review and analysis of the available literature,this article provides a thorough update on the off-label use of treprostinil in adult patients.
基金Supported by National Natural Science Foundation of China,No.81900641Peking University Health Center for Combating the Pandemic Programs,No.BMU 2021MX020,and No.BMU 2022MX008.
文摘High-quality scientific research is very important in attempting to effectively control the coronavirus disease 2019(COVID-19)pandemic and ensure people’s health and safety.Chloroquine(CQ)and hydroxychloroquine(HCQ)have received much attention.This article comprehensively investigates the ethical review of off-label CQ and HCQ research during the COVID-19 pandemic with regard to strictly abiding by review standards,improving review efficiency,ensuring the rights and interests of subjects and that ethics committees conduct independent reviews,and achieving full ethics supervision of research conducted during an emergency.Research must be both rigorous and prudent to ensure the best outcome,with the maximization of benefits as the core principle.Standardization of the application,implementation and ethical review processes are needed to prevent unnecessary risk.
文摘Aim: To analyse antibiotic prescriptions in a cohort of extremely low birth weight neonates admitted to Italian level III Neonatal intensive Care Units. Methods: An online questionnaire was used to collect detailed information for each newborn. Antibiotic prescriptions were classified about their license status and compared with British National Formulary for Children (BNFC) and with a practical guide prepared by the Italian Society of Neonatology (ISN). Results: During the study period (May-July 2014) among 93 neonates admitted to 30 Italian Neonatal intensive Care Units, 56 (60%) received at least an antibiotic (92 prescriptions in total). Ampicillin, gentamicin and vancomycin were the antibiotics most commonly used for the prevention/treatment of bacterial infections. 56/92 antibiotic prescriptions (61%) resulted off-label mainly as regards dosing frequency, while 13 prescriptions (14%) regarded antibiotics used in absence of specific indication for newborns (meropenem, imipenem, piperacillin/tazobactam, clindamycin, clarithromycin). 50/56 neonates (89.3%) received at least one off-label antibiotic prescription. Differences have been observed in dosing regimens between current study and recommendations contained in BNFC, while prescriptions adhered more frequently to ISN indications. Conclusions: Our results confirm the high prevalence of off-label antibiotic use in ELBW neonates and underline a better adherence to indications based on clinical practice.
文摘Off-label use is defined by the prescription of a marketed drug outside the conditions described in the summary of product characteristics.In oncology,off-label prescribing of targeted therapies may occur in patients with other tumor types expressing the same target.Agents associated to phenotypic approaches such as therapies against the tumoral vasculature(anti-angiogenic drugs) and new immunotherapies(checkpoint inhibitors) also carry the potential of alternative indications or combinations.Off-label use of targeted therapies is little documented and appears to be in the same range than that regarding older drugs with wide variations among agents.When compared with older agents,off-label use of targeted therapies is probably more rational through tumoral genotyping but is faced with a limited clinical support,reimbursement challenges related to the very high pricing and the cost of genotyping or molecular profiling,when applicable.
文摘Background Off-label use of psychotropic prescriptions for pediatric patients has been increasing in Japan.This study sought to clarify pediatric patients' off-label use of psychotropics approved only for adults in Japan.Methods This retrospective study on psychotropic utilization employed a pharmaceutical health insurance claims database supplied by a pharmacy for the fiscal year 2016.Seven psychotropic drugs were examined.For each drug,we calculated the proportion of patients aged < 16 years or who were under the approved age limit set in the United States out of all patients.The maximum daily dose of each drug within the study period was plotted by age.Results Data of 45,715 patients (female:26,799,male:18,916) with 331,920 prescriptions were examined in this study.For each drug,the proportion of pediatric patients aged < 16 years ranged from 0.15 to 1.1%,while the proportion of those under the approved age limit in the United States ranged from 0 to 0.27%.Olanzapine had the highest reported proportion.No drugs other than olanzapine were taken under the approved age limit in the United States.Conclusions We identified the pediatric off-label use of psychotropics that were limited to adult use in Japan.The results indicated the possibility of referring to international guidelines or evidence in clinical practice,but these factors do not discount the existing problems with off-label use.More clinical trials within the pediatric population in Japan are needed to address the issue of off-label use and obtain useful and reliable information in the package inserts for rational use in future pediatric patients.
文摘Background Off-label and unlicensed prescriptions pose a severe safety concern among the pediatric population.We aimed to summarize the up-to-date evidence on the extent,reasons,and consequences of off-label and unlicensed drugs in hospitalized pediatric patients.Methods We systematically searched PubMed,EMBASE,SCOPUS,Web of Science and Google Scholar between 1990 and 2020 in which the last search was conducted on 12 February 2021.We included studies with the following inclusion criteria:(1)observational studies in design;(2)target population was hospitalized pediatric patients whether admitted in the intensive care unit or in the general ward;(3)study reporting the prevalence of off-label,unlicensed prescriptions or both;and(4)published in English.Results A total of 47 studies were eligible for inclusion.The proportion of off-label and unlicensed prescriptions ranged from 7.4%to 99.5%and 0.1%to 74.4%,respectively.The most frequent category of off-label prescriptions was prescription outside the age range,with the most commonly reported reason for off-label prescriptions being the lack of information specifically for pediatrics on the drug information leaflets.The consequences of off-label and unlicensed prescriptions ranged from minor and bearable skin reactions to debilitating renal failure,risking deaths.Conclusions Off-label and unlicensed prescriptions are extensive and require progressively meditative interventions.However,the pediatric population is currently a“therapeutic orphan”.Unless adequate pediatric clinical trials and licensed drugs become available,off-label and unlicensed drug prescription should not entirely be banned but rather promoted in an organized manner.
基金supported by a grant from the Jiangsu Provincial Special Program of Medical Science(BL2014007).
文摘Background: The information about the use of off-labeldrugs in pediatric nephrology is still lacking, which leadsto increased adverse reactions and medical disputes. Weretrospectively analyzed the use of off-label drugs in thein-patient ward of the nephrology department of NanjingChildren's Hospital, China in order to provide morecomplete information about the use of drugs for children.Methods: Proportional stratified random samplingwas applied to select patients with renal diseases aged 1month to 18 years, who were admitted to the hospital fromOctober 1, 2012 to September 30, 2013. All nephrologyrelateddrugs prescribed in the hospitalization period andtake-home drugs prescribed on discharge were recordedand evaluated as off-label drugs or not from threedifferent perspectives: person-time, prescription, anddrug category.Results: From 385 person-times of patients with 1424prescriptions, according to the ratio between off-labeldrugs and person-times, drug prescriptions, and drugproducts, the rates of off-label drugs were 40.78%, 16.64%,and 31.43%, respectively. Low-molecular-weight heparin,alfacalcidol and diltiazem were the most commonly usedoff-label drugs. Infants and younger children were thehigh-risk population of off-label drug use. The high rateoff-label nephrology-related drug use in children wasmainly related to lacking clinical research into drugs inchildren and the pace of drug label's revision, which cannotfollow the development of medical science.Conclusions: Approximaely half of pediatric patientswith renal diseases are usually prescribed with off-labelnephrology-related drugs. Analyzing the off-label conditionsfrom different perspectives may lead to various results.More clinical research into drugs for infants and youngerchildren is needed so as to update drug descriptions.
文摘This study sought to investigate adverse drug event(ADE)signals associated with eltrombopag use in pediatric patients aged 0–18 years,utilizing data from the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS).By analyzing this extensive pharmacovigilance database,the study aimed to offer meaningful insights for improving the clinical safety of eltrombopag in children.Data covering eltrombopag-related ADEs from Q12004 to Q42023 were extracted from FAERS,and signal detection was conducted using both the reporting odds ratio(ROR)and proportional reporting ratio(PRR)methods.ADEs were categorized based on the System Organ Class(SOC)classification in MedDRA version 25.0.A total of 582 reports involving pediatric patients receiving eltrombopag were identified,encompassing 21 SOC categories.The analysis revealed that,in addition to the known ADEs listed in the drug label,clinicians should remain vigilant for potential off-label ADE signals.These included abnormal platelet counts,thrombocytosis,antiphospholipid syndrome,myelofibrosis,reduced serum iron levels,myelodysplastic syndrome,hepatic infections,and other related conditions.Given these findings,it is strongly recommended that serum iron and ferritin levels should be routinely monitored in pediatric patients undergoing eltrombopag therapy,particularly during long-term treatment.Such proactive surveillance may help prevent the onset of iron deficiency anemia and enhance overall treatment safety.
