Objective:To elucidate the characteristics,management strategies,risk factors,and clinical impacts associated with adverse drug reactions(ADRs)induced by first-line antitubercular drugs to enhance tuberculosis(TB)mana...Objective:To elucidate the characteristics,management strategies,risk factors,and clinical impacts associated with adverse drug reactions(ADRs)induced by first-line antitubercular drugs to enhance tuberculosis(TB)management.Methods:A retrospective cohort study was conducted by retrieving drug-susceptible TB records among adult patients who received TB treatment from 2018 to 2021 at 10 public health clinics in Sarawak,Malaysia.Only the initial TB treatment and occurrence of specific ADRs within the study period were considered.Regression analysis was performed to identify the risk factors associated with both overall ADRs and individual types of ADRs.Results:Among 2953 cases,705(23.9%)developed ADRs.Cutaneous reactions were the most prevalent(47.1%),followed by hepatotoxicity(32.8%)and gastrointestinal disturbances(29.8%).Six out of seven types of ADRs investigated occurred within the intensive phase,mostly manifesting at approximately 2 weeks of initiation.Hepatotoxicity resulted in the majority(85.3%)of treatment discontinuations,while vision problems led to treatment modifications in half of the cases.Risk factors for all ADRs included age≥60 years,females,illicit drug use,and comorbidities such as HIV-positive,diabetes,and chronic liver disease.Alcohol consumption was independently associated with hepatotoxicity.ADRs caused around one-third of interruptions exceeding 2 weeks(33.0%)and subsequently necessitated treatment restarts(34.5%).Conclusions:Understanding these various aspects contributes to improving the overall management of ADRs in TB treatment.Close ADR monitoring and reporting are essential to strengthen ADR management.展开更多
The majority of patients who experience cutaneous adverse drug reactions(cADRs)concurrently receive multiple medications,meaning that the causative drug remains unidentified.We explored the association between human l...The majority of patients who experience cutaneous adverse drug reactions(cADRs)concurrently receive multiple medications,meaning that the causative drug remains unidentified.We explored the association between human leukocyte antigen(HLA)alleles and cADRs,regardless of the allergenic drug,to investigate whether different drug-induced cADRs were associated with the same or similar risk alleles in a Han Chinese population.We genotyped a sample of 146 cADR patients and 230 population controls from the same hospital and systematically analyzed the association between HLA Class I genes and cADRs.The carrier frequency of HLAB∗46:01 in cADR patients was found to be significantly higher than that in population controls(P=.0021,odds ratio[OR]=2.18,95%confidence interval[CI]:1.33-2.58).Subgroup analysis showed that HLA-B∗46:01 was significantly associated with urticaria and erythema multiforme(P=.0077,OR=2.53,95%CI:1.30-4.91;and P=.0049,OR=2.77,95%CI:1.39-5.50,respectively).Furthermore,a significant association was also detected between HLA-A∗02:01 and erythema multiforme(P=.0038,OR=2.65,95%CI:1.31-5.33).This study is the first to demonstrate that HLA-B∗46:01 is a risk allele for cADRs in a Han Chinese population,indicating that screening for HLA-B∗46:01 prior to the administration of medication may predict the risk of developing cADRs.展开更多
文摘Objective:To elucidate the characteristics,management strategies,risk factors,and clinical impacts associated with adverse drug reactions(ADRs)induced by first-line antitubercular drugs to enhance tuberculosis(TB)management.Methods:A retrospective cohort study was conducted by retrieving drug-susceptible TB records among adult patients who received TB treatment from 2018 to 2021 at 10 public health clinics in Sarawak,Malaysia.Only the initial TB treatment and occurrence of specific ADRs within the study period were considered.Regression analysis was performed to identify the risk factors associated with both overall ADRs and individual types of ADRs.Results:Among 2953 cases,705(23.9%)developed ADRs.Cutaneous reactions were the most prevalent(47.1%),followed by hepatotoxicity(32.8%)and gastrointestinal disturbances(29.8%).Six out of seven types of ADRs investigated occurred within the intensive phase,mostly manifesting at approximately 2 weeks of initiation.Hepatotoxicity resulted in the majority(85.3%)of treatment discontinuations,while vision problems led to treatment modifications in half of the cases.Risk factors for all ADRs included age≥60 years,females,illicit drug use,and comorbidities such as HIV-positive,diabetes,and chronic liver disease.Alcohol consumption was independently associated with hepatotoxicity.ADRs caused around one-third of interruptions exceeding 2 weeks(33.0%)and subsequently necessitated treatment restarts(34.5%).Conclusions:Understanding these various aspects contributes to improving the overall management of ADRs in TB treatment.Close ADR monitoring and reporting are essential to strengthen ADR management.
基金This study was supported in part by grants from the National Natural Science Foundation of China(No.81071287 and No.31371274)the National Key Research and Development Program(No.2016 YFC0905001)+1 种基金the Scientific and Technological Research in Open Collaborative Projects of Henan Province(No.152106000044)the Shanghai Municipal Commission of Science and Technology Program(No.14DJ1400100).
文摘The majority of patients who experience cutaneous adverse drug reactions(cADRs)concurrently receive multiple medications,meaning that the causative drug remains unidentified.We explored the association between human leukocyte antigen(HLA)alleles and cADRs,regardless of the allergenic drug,to investigate whether different drug-induced cADRs were associated with the same or similar risk alleles in a Han Chinese population.We genotyped a sample of 146 cADR patients and 230 population controls from the same hospital and systematically analyzed the association between HLA Class I genes and cADRs.The carrier frequency of HLAB∗46:01 in cADR patients was found to be significantly higher than that in population controls(P=.0021,odds ratio[OR]=2.18,95%confidence interval[CI]:1.33-2.58).Subgroup analysis showed that HLA-B∗46:01 was significantly associated with urticaria and erythema multiforme(P=.0077,OR=2.53,95%CI:1.30-4.91;and P=.0049,OR=2.77,95%CI:1.39-5.50,respectively).Furthermore,a significant association was also detected between HLA-A∗02:01 and erythema multiforme(P=.0038,OR=2.65,95%CI:1.31-5.33).This study is the first to demonstrate that HLA-B∗46:01 is a risk allele for cADRs in a Han Chinese population,indicating that screening for HLA-B∗46:01 prior to the administration of medication may predict the risk of developing cADRs.
