BACKGROUND Cytomegalovirus(CMV)prophylaxis with valganciclovir and ganciclovir is associated with elevated neutropenia and leukopenia risk in kidney transplant recipients,although the impact of these events on healthc...BACKGROUND Cytomegalovirus(CMV)prophylaxis with valganciclovir and ganciclovir is associated with elevated neutropenia and leukopenia risk in kidney transplant recipients,although the impact of these events on healthcare resource utilization(HCRU)and clinical outcomes is unclear.AIM To quantify clinical events and HCRU associated with neutropenia and leukope-nia among adults receiving valganciclovir and/or ganciclovir post-kidney trans-plantation.METHODS Adult kidney transplant recipients receiving valganciclovir and/or ganciclovir prophylaxis were identified in the TriNetX database from 2012 to 2021.Patient characteristics were evaluated in the 1-year period pre-first transplant.HCRU and adjusted event rates per person-year were evaluated in follow-up year 1 and years 2-5 after first kidney transplantation among cohorts with vs without neutropenia and/or leukopenia.RESULTS Of 15398 identified patients,the average age was 52.39 years and 58.70%were male.Patients with neutropenia and/or leukopenia had greater risk of clinical events for CMV-related events,opportunistic infections,use of granulocyte colony stimulating factor,and hospitalizations(relative risk>1 in year 1 and years 2-5).Patients with vs without neutropenia and/or leukopenia had higher HCRU in year 1 and years 2-5 post kidney transplantation,including the mean number of inpatient admissions(year 1:3.47 vs 2.76;years 2-5:2.70 vs 2.29)and outpatient visits(48.97 vs 34.42;31.73 vs 15.59,respectively),as well as the mean number of labs(1654.55 vs 1182.27;622.37 vs 327.89).CONCLUSION Adults receiving valganciclovir and/or ganciclovir prophylaxis post-kidney transplantation had greater risk of neutropenia and/or leukopenia,which were associated with higher clinical event rates and HCRU up to 5 years post-transplantation.These findings suggest the need for alternative prophylaxis options with lower myelosup-pressive effects to improve patient outcomes.展开更多
BACKGROUND Sodium-glucose cotransporter 2(SGLT2)inhibitors are widely used for the tr-eatment of type 2 diabetes(T2D).AIM To evaluate the influence of SGLT2 inhibitors on homeostasis model assessment of insulin resist...BACKGROUND Sodium-glucose cotransporter 2(SGLT2)inhibitors are widely used for the tr-eatment of type 2 diabetes(T2D).AIM To evaluate the influence of SGLT2 inhibitors on homeostasis model assessment of insulin resistance(HOMA-IR)andβ-cell function(HOMA-β)in patients with T2D in a meta-analysis.METHODS Randomized controlled trials(RCTs)comparing SGLT2 inhibitors to placebo in T2D patients,with a minimum treatment duration of 12 weeks,were searched using the PubMed,EMBASE,and Cochrane Library databases.Risk of bias was assessed using the Cochrane Risk of Bias Tool,and the certainty of evidence was evaluated using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)system.Changes in HOMA-IR and HOMA-βwere the outcomes analyzed.Meta-analyses were performed using a random-effects model by incorporating the potential influences of heterogeneity.RESULTS Of 1388 articles identified,24 RCTs met the inclusion criteria.23 of the included studies were double-blind RCTs with low risk of bias.Pooled results including 2272 patients showed that SGLT2 inhibitors significantly reduced HOMA-IR compared to placebo[mean difference(MD)=-0.81,95%confidence interval(CI):-1.11 to-0.52,P<0.001;I2=82%],indicating reduced insulin resistance.Addi-tionally,meta-analysis with 2845 patients suggested that SGLT2 inhibitors significantly increased HOMA-β(MD=7.90,95%CI:5.44-10.37,P<0.001;I2=74%)compared to placebo in patients with T2D,indicating improvedβ-cell function.Based on GRADE assessment,the certainty of evidence was rated moderate for both outcomes due to heterogeneity.Subgroup analyses showed that HOMA-βincreased more substantially in non-Asian studies than in Asian studies(P for subgroup difference<0.01).Subgroup analyses according to the individual medications of SGLT2 inhibitors all showed significant improvement of HOMA-IR and HOMA-β(P all<0.05).No significant publication bias was detected(P for Egger’s test all>0.05).CONCLUSION SGLT2 inhibitors are associated with improvements in insulin resistance andβ-cell function in patients with T2D,although the certainty of evidence is moderate due to heterogeneity.展开更多
文摘BACKGROUND Cytomegalovirus(CMV)prophylaxis with valganciclovir and ganciclovir is associated with elevated neutropenia and leukopenia risk in kidney transplant recipients,although the impact of these events on healthcare resource utilization(HCRU)and clinical outcomes is unclear.AIM To quantify clinical events and HCRU associated with neutropenia and leukope-nia among adults receiving valganciclovir and/or ganciclovir post-kidney trans-plantation.METHODS Adult kidney transplant recipients receiving valganciclovir and/or ganciclovir prophylaxis were identified in the TriNetX database from 2012 to 2021.Patient characteristics were evaluated in the 1-year period pre-first transplant.HCRU and adjusted event rates per person-year were evaluated in follow-up year 1 and years 2-5 after first kidney transplantation among cohorts with vs without neutropenia and/or leukopenia.RESULTS Of 15398 identified patients,the average age was 52.39 years and 58.70%were male.Patients with neutropenia and/or leukopenia had greater risk of clinical events for CMV-related events,opportunistic infections,use of granulocyte colony stimulating factor,and hospitalizations(relative risk>1 in year 1 and years 2-5).Patients with vs without neutropenia and/or leukopenia had higher HCRU in year 1 and years 2-5 post kidney transplantation,including the mean number of inpatient admissions(year 1:3.47 vs 2.76;years 2-5:2.70 vs 2.29)and outpatient visits(48.97 vs 34.42;31.73 vs 15.59,respectively),as well as the mean number of labs(1654.55 vs 1182.27;622.37 vs 327.89).CONCLUSION Adults receiving valganciclovir and/or ganciclovir prophylaxis post-kidney transplantation had greater risk of neutropenia and/or leukopenia,which were associated with higher clinical event rates and HCRU up to 5 years post-transplantation.These findings suggest the need for alternative prophylaxis options with lower myelosup-pressive effects to improve patient outcomes.
文摘BACKGROUND Sodium-glucose cotransporter 2(SGLT2)inhibitors are widely used for the tr-eatment of type 2 diabetes(T2D).AIM To evaluate the influence of SGLT2 inhibitors on homeostasis model assessment of insulin resistance(HOMA-IR)andβ-cell function(HOMA-β)in patients with T2D in a meta-analysis.METHODS Randomized controlled trials(RCTs)comparing SGLT2 inhibitors to placebo in T2D patients,with a minimum treatment duration of 12 weeks,were searched using the PubMed,EMBASE,and Cochrane Library databases.Risk of bias was assessed using the Cochrane Risk of Bias Tool,and the certainty of evidence was evaluated using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)system.Changes in HOMA-IR and HOMA-βwere the outcomes analyzed.Meta-analyses were performed using a random-effects model by incorporating the potential influences of heterogeneity.RESULTS Of 1388 articles identified,24 RCTs met the inclusion criteria.23 of the included studies were double-blind RCTs with low risk of bias.Pooled results including 2272 patients showed that SGLT2 inhibitors significantly reduced HOMA-IR compared to placebo[mean difference(MD)=-0.81,95%confidence interval(CI):-1.11 to-0.52,P<0.001;I2=82%],indicating reduced insulin resistance.Addi-tionally,meta-analysis with 2845 patients suggested that SGLT2 inhibitors significantly increased HOMA-β(MD=7.90,95%CI:5.44-10.37,P<0.001;I2=74%)compared to placebo in patients with T2D,indicating improvedβ-cell function.Based on GRADE assessment,the certainty of evidence was rated moderate for both outcomes due to heterogeneity.Subgroup analyses showed that HOMA-βincreased more substantially in non-Asian studies than in Asian studies(P for subgroup difference<0.01).Subgroup analyses according to the individual medications of SGLT2 inhibitors all showed significant improvement of HOMA-IR and HOMA-β(P all<0.05).No significant publication bias was detected(P for Egger’s test all>0.05).CONCLUSION SGLT2 inhibitors are associated with improvements in insulin resistance andβ-cell function in patients with T2D,although the certainty of evidence is moderate due to heterogeneity.