AIM:To analyze sex differences in adverse drug reactions(ADR) to the immune suppressive medication in inflammatory bowel disease(IBD) patients.METHODS:All IBD patients attending the IBD outpatient clinic of a referral...AIM:To analyze sex differences in adverse drug reactions(ADR) to the immune suppressive medication in inflammatory bowel disease(IBD) patients.METHODS:All IBD patients attending the IBD outpatient clinic of a referral hospital were identified through the electronic diagnosis registration system.The electronic medical records of IBD patients were reviewed and the files of those patients who have used immune suppressive therapy for IBD,i.e.,thiopurines,methotrexate,cyclosporine,tacrolimus and anti-tumor necrosis factor agents(anti-TNF);infliximab(IFX),adalimumab(ADA) and/or certolizumab,were further analyzed.The reported ADR to immune suppressive drugs were noted.The general definition of ADR used in clinical practice comprised the occurrence of the ADR in the temporal relationship with its disappearance upon discontinuation of the medication.Patients for whom the required information on drug use and ADR was not available in the electronic medical record and patients with only one registered contact and no further followup at the outpatient clinic were excluded.The difference in the incidence and type of ADR between male and female IBD patients were analyzed statistically by χ 2 test.RESULTS:In total,1009 IBD patients were identified in the electronic diagnosis registration system.Out of these 1009 patients,843 patients were eligible for further analysis.There were 386 males(46%),mean age 42 years(range:16-87 years) with a mean duration of the disease of 14 years(range:0-54 years);578 patients with Crohn's disease,244 with ulcerative colitis and 21 with unclassified colitis.Seventy percent(586 pts) of patients used any kind of immune suppressive agents at a certain point of the disease course,the majority of the patients(546 pts,65%) used thiopurines,176 pts(21%) methotrexate,46 pts(5%) cyclosporine and one patient tacrolimus.One third(240 pts,28%) of patients were treated with anti-TNF,the majority of patients(227 pts,27%) used IFX,99(12%) used ADA and five patients certolizumab.There were no differences between male and female patients in the use of immune suppressive agents.With regards to ADR,no differences between males and females were observed in the incidence of ADR to thiopurines,methotrexate and cyclosporine.Among 77 pts who developed ADR to one or more anti-TNF agents,significantly more females(54 pts,39% of all anti-TNF treated women) than males(23 pts,23% of all antiTNF treated men) experienced ADR to an anti-TNF agent [P = 0.011;odds ratio(OR) 2.2,95%CI 1.2-3.8].The most frequent ADR to both anti-TNF agents,IFX and ADA,were allergic reactions(15% of all IFX users and 7% of all patients treated with ADA) and for both agents a significantly higher rate of allergic reactions in females compared with males was observed.As a result of ADR,36 patients(15% of all patients using anti-TNF) stopped the treatment,with significantly higher stopping rate among females(27 females,19% vs 9 males,9%,P = 0.024).CONCLUSION:Treatment with anti-TNF antibodies is accompanied by sexual dimorphic profile of ADR with female patients being more at risk for allergic reactions and subsequent discontinuation of the treatment.展开更多
Background:Problems with emotional processing are widely reported in individuals with attentiondeficit/hyperactivity disorder(ADHD).Although methylphenidate(MPH)effectively alleviates inattention and hyperactivity sym...Background:Problems with emotional processing are widely reported in individuals with attentiondeficit/hyperactivity disorder(ADHD).Although methylphenidate(MPH)effectively alleviates inattention and hyperactivity symptoms in ADHD,its effects on emotional processing and internalizing symptoms have remained elusive.While we previously found that acute MPH administration modulated neural mechanisms underlying emotional processing in an age-dependent manner,the effects of prolonged administration remained unknown.Objectives:Therefore,we investigated:(i)whether prolonged MPH treatment influences neural substrates(amygdala reactivity and connectivity)of emotional processing,and(ii)whether these effects are modulated by age.Methods:The“effects of Psychotropic drugs On Developing brain-MPH”(“ePOD-MPH”)randomized controlled trial was a 16-week double-blind,placebo-controlled,multi-center trial with MPH in 50 boys(10–12 years of age)and 49 men(23–40 years of age),all stimulant treatment-naive and diagnosed with ADHD.Participants performed an emotional face-matching task during functional magnetic resonance imaging.We assessed their symptoms of ADHD and internalizing symptoms at baseline,during the trial(8 weeks),and 1 week after the trial end(17 weeks).Results and Conclusions:We did not find effects of prolonged MPH treatment on emotional processing,as measured by amygdala reactivity and connectivity and internalizing symptoms in this trial with stimulant treatment-naive participants.This differs from our findings on emotional processing following acute MPH administration and the effects of prolonged MPH treatment on the dopamine system,which were both modulated by age.Interestingly,prolonged MPH treatment did improve ADHD symptoms,although depressive and anxiety symptoms showed a medication-independent decrease.Furthermore,our data indicate that baseline internalizing symptoms may be used to predict MPH treatment effects on ADHD symptoms,particularly in(male)adults with ADHD.展开更多
文摘AIM:To analyze sex differences in adverse drug reactions(ADR) to the immune suppressive medication in inflammatory bowel disease(IBD) patients.METHODS:All IBD patients attending the IBD outpatient clinic of a referral hospital were identified through the electronic diagnosis registration system.The electronic medical records of IBD patients were reviewed and the files of those patients who have used immune suppressive therapy for IBD,i.e.,thiopurines,methotrexate,cyclosporine,tacrolimus and anti-tumor necrosis factor agents(anti-TNF);infliximab(IFX),adalimumab(ADA) and/or certolizumab,were further analyzed.The reported ADR to immune suppressive drugs were noted.The general definition of ADR used in clinical practice comprised the occurrence of the ADR in the temporal relationship with its disappearance upon discontinuation of the medication.Patients for whom the required information on drug use and ADR was not available in the electronic medical record and patients with only one registered contact and no further followup at the outpatient clinic were excluded.The difference in the incidence and type of ADR between male and female IBD patients were analyzed statistically by χ 2 test.RESULTS:In total,1009 IBD patients were identified in the electronic diagnosis registration system.Out of these 1009 patients,843 patients were eligible for further analysis.There were 386 males(46%),mean age 42 years(range:16-87 years) with a mean duration of the disease of 14 years(range:0-54 years);578 patients with Crohn's disease,244 with ulcerative colitis and 21 with unclassified colitis.Seventy percent(586 pts) of patients used any kind of immune suppressive agents at a certain point of the disease course,the majority of the patients(546 pts,65%) used thiopurines,176 pts(21%) methotrexate,46 pts(5%) cyclosporine and one patient tacrolimus.One third(240 pts,28%) of patients were treated with anti-TNF,the majority of patients(227 pts,27%) used IFX,99(12%) used ADA and five patients certolizumab.There were no differences between male and female patients in the use of immune suppressive agents.With regards to ADR,no differences between males and females were observed in the incidence of ADR to thiopurines,methotrexate and cyclosporine.Among 77 pts who developed ADR to one or more anti-TNF agents,significantly more females(54 pts,39% of all anti-TNF treated women) than males(23 pts,23% of all antiTNF treated men) experienced ADR to an anti-TNF agent [P = 0.011;odds ratio(OR) 2.2,95%CI 1.2-3.8].The most frequent ADR to both anti-TNF agents,IFX and ADA,were allergic reactions(15% of all IFX users and 7% of all patients treated with ADA) and for both agents a significantly higher rate of allergic reactions in females compared with males was observed.As a result of ADR,36 patients(15% of all patients using anti-TNF) stopped the treatment,with significantly higher stopping rate among females(27 females,19% vs 9 males,9%,P = 0.024).CONCLUSION:Treatment with anti-TNF antibodies is accompanied by sexual dimorphic profile of ADR with female patients being more at risk for allergic reactions and subsequent discontinuation of the treatment.
基金This study was funded by a personal research grant awarded to L.R.by the Academic Medical Center,University of Amsterdam,and 11.32050.26 ERA-NET PRIOMEDCHILD FP 6(EU)and a grant from Amsterdam Brain and Cognition(ABC)Suffugium,a Dutch nonprofit organization,financially supported M.B.as well as A.K.A.K.and L.R.were financially supported by EUROSTARS(E!113351 DEPREDICT)+1 种基金A.S.was supported by an NWOVeni(016.196.153)A.S.and P.J.L.are supported by the Urban Mental Health program of the University of Amsterdam.
文摘Background:Problems with emotional processing are widely reported in individuals with attentiondeficit/hyperactivity disorder(ADHD).Although methylphenidate(MPH)effectively alleviates inattention and hyperactivity symptoms in ADHD,its effects on emotional processing and internalizing symptoms have remained elusive.While we previously found that acute MPH administration modulated neural mechanisms underlying emotional processing in an age-dependent manner,the effects of prolonged administration remained unknown.Objectives:Therefore,we investigated:(i)whether prolonged MPH treatment influences neural substrates(amygdala reactivity and connectivity)of emotional processing,and(ii)whether these effects are modulated by age.Methods:The“effects of Psychotropic drugs On Developing brain-MPH”(“ePOD-MPH”)randomized controlled trial was a 16-week double-blind,placebo-controlled,multi-center trial with MPH in 50 boys(10–12 years of age)and 49 men(23–40 years of age),all stimulant treatment-naive and diagnosed with ADHD.Participants performed an emotional face-matching task during functional magnetic resonance imaging.We assessed their symptoms of ADHD and internalizing symptoms at baseline,during the trial(8 weeks),and 1 week after the trial end(17 weeks).Results and Conclusions:We did not find effects of prolonged MPH treatment on emotional processing,as measured by amygdala reactivity and connectivity and internalizing symptoms in this trial with stimulant treatment-naive participants.This differs from our findings on emotional processing following acute MPH administration and the effects of prolonged MPH treatment on the dopamine system,which were both modulated by age.Interestingly,prolonged MPH treatment did improve ADHD symptoms,although depressive and anxiety symptoms showed a medication-independent decrease.Furthermore,our data indicate that baseline internalizing symptoms may be used to predict MPH treatment effects on ADHD symptoms,particularly in(male)adults with ADHD.
