1.Four intravenous iron formulations in the treatment of iron deficiency anemia:a rapid health technology assessment
Zhicong XING ; Fudong SUN ; Qingxia XUE ; Bei ZHANG ; Shengjun MU ; Quan ZHAO
Chinese Journal of Pharmacoepidemiology 2024;33(9):1030-1043
Objective To evaluate the efficacy,safety,and economy of 4 intravenous iron formulations in the treatment of iron deficiency anemia(IDA)by rapid health technology assessment,and to provide evidence for clinical decision-making.Methods PubMed,Embase,the Cochrane Library,CNKI,WanFang,SinoMed,and official websites of international health technology assessment agencies were electronically searched to collect health technology assessment reports,systematic reviews/Meta-analysis,and pharmacoeconomic studies concerning the treatment of IDA with iron sucrose(IS),iron dextran(ID),ferric carboxymaltose(FCM),and iron isomaltoside(IIM)from the inception to August 15,2024.Two researchers independently screened the studies,extracted data and assessed the quality of included studies.The results were then qualitatively described and analyzed.Results A total of 32 studies were included,including one health technology assessment report,16 systematic reviews/Meta-analysis,and 15 pharmacoeconomic evaluations.In terms of effectiveness,FCM had a higher response rate than that of IS(P<0.05),FCM and IIM had no statistical difference(P>0.05).Regarding hemoglobin level change,patients treated with FCM had higher hemoglobin levels than those treated with IS(P<0.05);the improvement in hemoglobin levels between IIM and FCM was inconclusive.In terms of ferritin level change,FCM might be superior to the other three intravenous iron formulations.In terms of safety,the adverse event rates for FCM,IS,ID and IIM were 12.0%,15.3%,12.0%and 17.0%,respectively;IIM was significantly associated with a lower rate of cardiovascular adverse events compared to FCM and IS(P<0.05);FCM had the highest rate of hypophosphatemia among the four formulations(P<0.05),and there was no significant difference among IIM,IS and ID(P>0.05);IIM had a lower risk of severe or serious hypersensitivity reactions compared to FCM and IS.In terms of economy,FCM and IIM had an economic advantage compared to IS.The economic efficiency ranking among IS,ID,and FCM was in the order of FCM,ID,and IS,the economic comparison between FCM and IIM remains inconclusive and needs to be further demonstrated.Conclusion FCM and IIM have good efficacy,safety and economy in the treatment of IDA,but most of the included economy studies based on foreign populations,and domestic economic studies need to be further demonstrated.
2.Influencing factors of genotypic drug resistance in people living with human immunodeficiency virus/acquired immunodeficiency syndrome who failed anti-retroviral therapy in Henan Province from 2018 to 2022
Yan SUN ; Zhaoyun CHEN ; Yuqi HUO ; Mengyao FENG ; Jinjin LIU ; Xuan YANG ; Qingxia ZHAO ; Xiaohua ZHANG ; Shuxian ZHAO ; Xue ZHANG ; Yan WANG
Chinese Journal of Infectious Diseases 2024;42(4):219-224
Objective:To analyze the influencing factors of genotypic drug resistance mutations in people living with human immunodeficiency virus and acquired immunodeficiency syndrome(PLWHA) who failed anti-retroviral therapy (ART) in Henan Province, in order to provide a basis for adjusting ART regimens and reducing drug resistance.Methods:PLWHA with virological failure (human immunodeficiency virus (HIV) RNA≥500 copies/mL) after receiving ART for more than 24 weeks were included in Henan Province from January 2018 to December 2022. Baseline CD4 + T lymphocyte counts, ART regimens and other clinical data were collected. HIV-1 gene subtypes and their drug resistance sequence mutations were detected in the Sixth People′s Hospital of Zhengzhou, and the sequences were submitted to the HIV Drug Resistance Interpretation System of Stanford University for comparison of test results. Genotypic drug resistance to nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI) and integrase inhibitors (INSTI) was determined. Multivariate logistic regression was used to analyze the influencing factors of drug resistance in patients with ART failure. Results:Among 982 PLWHA, the sequences of 899 cases were successfully amplified, and drug resistance was detected in 737 cases, with the drug resistance rate of 81.98%(737/899). The rates of resistance to NRTIs, NNRTIs, PIs and INSTIs were 71.97%(647/899), 79.31%(713/899), 5.23%(47/899) and 2.72%(20/734), respectively.The largest number of those who developed concomitant resistance to two classes of drugs was 588 cases (79.78%), mainly NRTI and NNRTI concomitant resistance in 583 cases (79.10%). There were 99 cases (13.43%) who developed resistance to only one class of drugs, and those who developed concurrent resistance to three classes of drugs were 48 cases (6.51%), and two cases (0.27%) were found to be resistant to all four classes of drugs mentioned above. A total of 10 HIV genotypes were detected, among which subtype B accounted for the most (59.73%(537/899)), followed by circulating recombinant form (CRF)01_AE subtype (21.91%(197/899)) and CRF07_BC subtype (9.45%(85/899)). The risk factors affecting the development of drug resistance were baseline CD4 + T lymphocyte counts, ART regimens and HIV-1 genotypes. The risk of drug resistance in patients with baseline CD4 + T lymphocyte counts <100/μL was 4.55 times (95% confidence interval ( CI) 2.69 to 7.70) higher than patients with CD4 + T lymphocyte counts≥250/μL, the risk of drug resistance in patients using 2NRTIs+ NNRTI regimen was 4.51 times (95% CI 1.75 to 11.63) higer than those using 2NRTIs+ INSTI regimen, and patients infected with B and CRF01_AE subtype was 2.18 times (95% CI 1.10 to 4.29) and 2.70 times (95% CI 1.26 to 5.78) higer than those with CRF07_BC subtype, respectively. Conclusions:The incidence of genotypic drug resistance in PLWHA with ART failure in Henan Province is high. Low baseline CD4 + T lymphocyte counts, 2NRTIs+ NNRTI regimens, and genotype B and CRF01_AE are risk factors for drug resistance in PLWHA.
3.Clinical and genetic analysis of a patient with short stature due to variant of RPL13 gene
Hanying WEN ; Ke WU ; Qingqing SHU ; Xin HE ; Qingxia XUE
Chinese Journal of Medical Genetics 2024;41(5):586-590
Objective:To analyze the clinical phenotype and genetic characteristics of a patient with Isidor-Toutain spinal epiphyseal dysplasia (SEMD) due to variant of RPL13 gene. Methods:A pregnant woman at 18 weeks of gestation who had presented at Quzhou Maternal and Child Health Care Hospital on January 14, 2023 was selected as the study subject. Whole exome sequencing (WES) was carried out for the patient, and candidate variant was validated by Sanger sequencing and bioinformatic analysis.Results:The woman was 37 years old with extremely short stature (135 cm) and "O" shaped legs. WES revealed that she has harbored a c. 548G>C (p.Arg183Pro) missense variant of the RPL13 gene (NM_000977.4). The same variant was not found in her fetus. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be likely pathogenic (PS4+ PM2_Supporting+ PP3+ PP4). Conclusion:Isidor-Toutain type SEMD due to variants of the RPL13 gene may have variable expressivity and diverse clinical phenotypes. Above finding has facilitated the differential diagnosis and genetic counseling for this family.
4.Characteristics of drug resistance in HIV/AIDS patients with antiretroviral treatment failure in Henan Province
Xuan YANG ; Yan SUN ; Yuqi HUO ; Jinjin LIU ; Xiaohua ZHANG ; Shuxian ZHAO ; Qingxia ZHAO ; Xue ZHANG ; Yan WANG ; Zhaoyun CHEN
Chinese Journal of Epidemiology 2023;44(11):1795-1801
Objective:To analyze the drug resistance characteristics of HIV/AIDS patients in Henan Province with antiretroviral treatment (ART) failure through the genotypic drug resistance detection.Methods:Blood samples were collected from HIV/AIDS patients who received ART for more than 6 months with viral loads ≥1 000 copies/ml in 18 cities of Henan from January 2018 to May 2021. The genotypic drug resistance detection was conducted by using an In-house drug resistance detection method. The drug resistance mutation (DRM) and antiretroviral susceptibility were analyzed by submitting the determined sequences to the Stanford HIV-1 drug resistance database. The information about patients' demographic characteristics and antiviral treatment data were collected.Results:A total of 887 HIV/AIDS patients with ART failure, 812 sequences were successfully amplified with the success rate of 91.54%. In the 812 patients, 676 were drug resistant (83.25%, 676/812). The drug resistance ratesto nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) were 73.40% (596/812), 80.54% (654/812), 5.54% (45/812), and 2.56% (17/663), respectively. There were significant differences in drug resistance rates among four types of drugs ( χ2=1 686.34, P<0.001). The drug resistance rate to two drugs was 66.38% (539/812), and the drug resistance rate to three drugs was 5.79% (47/812). A total of 9 subtypes of HIV-1were detected, in which subtype B accounted for 59.61%(484/812), followed by subtype CRF01_AE (22.17%, 180/812) and subtype CRF07_BC (9.48%, 77/812). There were significant differences in drug resistance rate among different subtypes ( χ2=21.33, P=0.001). Among NRTIs related mutation sites, the DRM rate of M184V/I was highest (63.42%, 515/812), followed by K65R (27.46%, 223/812). The top three DRM rates were detected for K103N/S (34.98%, 284/812), G190A/S (26.11%, 212/812) and V106M/I (24.63%, 200/812) among NNRTIs related mutation sites, and M46I (4.31%, 35/812), V82A/F (3.82%, 31/812), and I54V/MV (3.69%, 30/812) among PIs related mutation sites. While among INSTIs related mutation sites, E157Q/EQ had the highest DRM rate (3.47%, 23/663), followed by R263K (0.75%, 5/663) and G140A (0.75%, 5/663). The resistance to lamivudine and emtricitabine of NRTIs was at high-level (65.52%, 532/812), and the resistance to nevirapine (77.46%, 629/812) and efavirenz (71.18%, 578/812) of NNRTIs was also at high-level. The medium/high-level resistance to lopinavir/ritonavir of PIs was only 4.19% (34/812), the medium/high-level resistance to elvitegravir and raltegravir of INSTIs was 1.66% (11/663) and 1.21% (8/663), respectively, and no high-level resistance to bictegravir or dolutegravir was found. Conclusions:The drug resistance in HIV/AIDS patients with ART failure was high in Henan, characterized by high drug resistance rates to NRTIs and NNRTIs, and diverse and complex resistance mutations. So high resistance barrier ART-regimens were recommended, and the viral load monitoring and drug resistance testing after ART should be strengthened.
5.Application of noninvasive prenatal DNA screening combined with nuchal translucency thickness measurement in the diagnosis of fetal chromosomal aneuploidy
Yin WU ; Xiaoling HU ; Xin HE ; Qingxia XUE
Chinese Journal of Primary Medicine and Pharmacy 2022;29(11):1639-1643
Objective:To investigate the application value of noninvasive prenatal DNA screening combined with nuchal translucency thickness measurement in the diagnosis of fetal chromosome aneuploidy.Methods:A total of 5 730 pregnant women who were screened for fetal chromosomal diseases in the Quzhou Maternal and Child Health Hospital from January 2017 to March 2019 were included in this study. All of them underwent noninvasive prenatal DNA screening and nuchal translucency thickness measurement. The results of amniocentesis were used as the gold standard to evaluate the diagnostic efficacy of noninvasive prenatal DNA screening, nuchal translucency thickness measurement and their combination.Results:Noninvasive prenatal DNA screening revealed that 64 (1.12%) women out of 5 730 pregnant women had high risk of developing chromosomal abnormalities. Ultrasound examination results showed that nuchal translucency was thickened in 140 (2.44%) women. The outcome of adverse pregnancy increased with the increase of nuchal translucency thickness. Among the 68 pregnant women who underwent amniocentesis, 51 women developed chromosomal abnormalities, with trisomy 21 syndrome being the majority (23/51,45.10%). The diagnostic efficacy of noninvasive prenatal DNA screening combined with nuchal translucency thickness measurement in the diagnosis of fetal chromosomal aneuploidy reached the ideal level.Conclusion:Noninvasive prenatal DNA screening combined with nuchal translucency thickness measurement has a high clinical application value. The combined method can be used as the main prenatal DNA screening method for pregnant women and it can effectively avoid the birth of children with chromosomal abnormalities.
6.Research Progress of PNI and CONUT in Breast Cancer
XiaoFei XU ; Yang LI ; Lingyun CHEN ; Heyang DAI ; Jiaojiao XUE ; Qingxia LI
Cancer Research on Prevention and Treatment 2022;49(9):961-964
Breast cancer has overtaken lung cancer as the most common malignancy in women. Although the early diagnostic rate has continuously improved, recurrence and metastasis remain a problem to be solved. Therefore, scientists should search for effective prognostic markers for breast cancer patients and adopt individualized programs for different patients. Studies have shown that cancer prognosis, to a certain extent, is related to the nutrition inflammation index. Preoperative prognostic nutritional index (PNI) and controlled nutritional status (CONUT) are indicators that comprehensively reflect the nutritional level and inflammatory state of patients, respectively. Different from other cancers, the incidence of breast cancer is related to nutritional status, and an extremely high or low score is not conducive to the prognosis of breast cancer patients. This paper reviews the research progress of PNI and CONUT in breast cancer.
7.Analysis of drug resistance in patients with acquired immunodeficiency syndrome who failed antiviral therapy
Zhaoyun CHEN ; Yan SUN ; Chaofeng LI ; Chunli LIU ; Xuan YANG ; Xue ZHANG ; Yuanyuan CHEN ; Yan CAI ; Kun CAO ; Qingxia ZHAO
Chinese Journal of Infectious Diseases 2021;39(8):480-484
Objective:To investigate the drug resistance of patients with acquired immunodeficiency syndrome (AIDS) who failed antiviral therapy.Methods:A total of 156 AIDS patients with antiviral therapy failure at the Sixth People′s Hospital of Zhengzhou from October 2017 to December 2018 were selected. The human immunodeficiency virus (HIV)-1 ViroSeq? genotyping method was used for the detection of HIV resistance, and Stanford University HIV drug resistance database (http: ∥hivdb.stanford.edu/) was used for testing results comparison.Results:Among the 156 AIDS patients with antiviral therapy failure, 122(78.21%) developed drug resistance. One hundred and six (67.95%) cases were multi-resistant to nucleoside reverse transcriptase inhibitor (NRTI), among which, 104 (66.67%) were resistant to lamivudine, emtricitabine and abacavir. One hundred and eighteen (75.64%) were resistant to non-nucleoside reverse transcriptase inhibitor (NNRTI), and 118 (75.64%) were multi-resistant to efavirenz and nevirapine. And seven (4.49%) were resistant to protease inhibitor (PI). There were 16 resistant sites for NRTI, with 87 (71.31%) most frequent M184V/I mutations. There were 13 resistant sites for NNRTI, with 49 (40.16%) K103N/R mutations. There were 11 resistant sites for PI, with 49 (40.16%) A71V/T mutations. The antiviral drugs lamivudine and emtricitabine were moderately and highly resistant in 102 (83.61%) cases, efavirenz and nevirapine were moderately and highly resistant in 117 (95.90%) cases. Once drug resistance developed, these drugs were likely to be moderate or high resistance. There were 29 (23.77%), 48 (39.34%), and five (4.10%) cases were resistant to zidovudine, tenofovir and lopinavir/ritonavir, respectively. The resistance barrier of these drugs was relatively high.Conclusion:The incidence of drug resistance in patients with AIDS treatment failure is high, and multi-drug resistance is serious with various sites of drug resistance.
8.Analysis of AIDS epidemic and clinical features in some part regions of Henan province during 2006-2015
Yan SUN ; Zhaoyun CHEN ; Xuan YANG ; Xue ZHANG ; Chaofeng LI ; Qingxia ZHAO
Chinese Journal of Primary Medicine and Pharmacy 2018;25(21):2761-2764,后插1
Objective To discuss the epidemiology and clinical characteristics of AIDS in some part of Henan regions.Methods Retrospective analysis was conducted based on the clinical and epidemic information collected from AIDS patients who were treated in the Sixth People's Hospital of Zhengzhou between 2006 and 2015 in He'nan province.Results Between 2006 and 2015,the number of hospitalization increased every year.The average growth rate was 20.31%.The average age of patients was (43.91 ± 13.56) years old.The patients from 40 to 60 years old group occupied 54.06% of total patients,and 71.12% of patients were farmers.During 2006 to 2015,the propagation path changed a lot.Before 2008,blood transmission was the major propagation path (72.72%),but after 2013,the major propagation path was sexual activity (59.69%).40.41% of patients were infected by two or more opportunistic infections.The top five opportunistic infections were bacterial pneumonia (32.68%),tuberculosis (19.29%),fungal infection (18.65%),pneumocystis carinii pneumonia (12.96%),extra pulmonary tuberculosis (7.45%).The death rate was 5.79%.The number of CD4 cells in peripheral blood was closely related to the severity of illness.Conclusion Early anti-virus treatment and opportunistic infection control are key factors to relieve the severity of illness and reduce the death rate.
9.Survival analysis and associated factors of acquired immune deficiency syndrome patients under antiretroviral therapy in He'nan Province during 2005 to 2015
Yan SUN ; Qingxia ZHAO ; Xuan YANG ; Chunli LIU ; Xue ZHANG ; Chaofeng LI ; Zhaoyun CHEN
Chinese Journal of Infectious Diseases 2018;36(2):74-77
Objective To study the survival status and the prognostic factors of aquired immune deficiency syndrome (AIDS) patients under the highly active antiretroviral therapy (HAART) in He'nan Province.Methods Survival data of AIDS patients were collected from the National HAART reporting system between 2005 and 2015,and analyzed using SPSS 23.0 software.Results A total of 38 143 AIDS cases were enrolled in this study.The cumulative survival rate of patients under antiretroviral therapy after 1-5 years were 95%,91%,89%,86% and 85%,respectively.The cumulative death cases were 5 704 and the total mortality was 3.68/100 person years (5 704/155 060 person years).A total of 1 975 cases died within a year with a percentage of 34.62%.Cox proportional hazard regression model analysis indicated that the hazard ratioc (HR [95%CI]) of death in patients with age of 40-49 years,50-59 yrears,60-69 yrears and ≥70 years groups compared to those with age <30 years group were 1.49 (1.22-1.80),1.88 (1.55-2.28),2.82 (2.32 3.42) and 4.60 (3.75-5.65),respectively.The HR (95% CI) of death in patients with CD4 T cell counts <50 cells/μL,50-199 cells/μL,200-349 cells/μL groups compared to those of ≥350 cells/μL group were 3.28 (2.98-3.61),2.30 (2.09-2.53) and 1.39 (1.25-1.54),respectively.Male (HR-1.35,95%CI:1.28-1.42) and not switching to second line therapy (HR=4.41,95%CI:4.12-4.73) were the risk factors of death.Compared to sex transmission,blood transmission was the risk factors of death in AIDS patients.Conclusions The initiation of early HAART and timely switching to second line therapy for AIDS patients are key to prolong the survival time and to reduce AIDS related death.
10.Evaluation of the virological and immune responses and their impact factors of Lopinavir/Ritonavir based second-line regimen in elderly acquired immunodeficiency syndrome patients who failed first line regimens
Xuan YANG ; Xin DENG ; Li WANG ; Chaofeng LI ; Xue ZHANG ; Yan SUN ; Qingxia ZHAO
Chinese Journal of Infectious Diseases 2017;35(2):65-69
Objective To evaluate the virological and immune responses of Lopinavir/Ritonavir (LPV/r) based second-line regimen in elderly acquired immunodeficiency syndrome (AIDS) patients who failed first line regimens.Methods This was a retrospective cohort study.Elderly patients (≥50 years) who switched to LPV/r-based second-line antiretroviral therapy with human immuno-deficiency virus (HIV) RNA >1 000 copies/mL after more than 1 year of first-line treatment were recruited from Zhengzhou No.6 People Hospital from January 2010 to December 2011.The virological and immunological data during 60-month treatment were collected.Multivariate logistic regression was used to explore the risk factors associated with virological failure or immunological failure of 60-month second-line therapy.Results Totally 256 patients were enrolled with 109 male and 147 female.89.5% were plasma donator.The median age at the time of switching to LPV/r based second-line regimen was 61 years old.Twelve out of the 256 cases were detected for genotypic drug resistance and ten of them were resistant to drugs.No resistance to protease inhibitor (PI) was found.After switching to LPV/r based second-line regimen, HIV viral suppression (HIV RNA≤400 copies/mL) rates at 12, 24, 36, 48, 60 months were 69.5%, 78.4%, 79.0%, 79.7%, and 83.2%, respectively.The CD4+ T cell counts were (313±135) /mL at 12 months, (377±151) /mL at 24 months, (396±155) /mL at 36 months, (389±163) /mL at 48 months and (412±147) /mL at 60 months, which were all significantly higher than that at the initiation of therapy ([243±146] /mL,t=19.092,18.598,12.843,8.516 and 12.980, respectively;all P<0.05).After switching to LPV/r based second-line regimen for 60 months, 43 patients occurred virological failure and 48 patients occurred immunological failure.Multivariate logistic regression showed that poor adherence (OR=48.5, 95% CI: 15.9-98.4, P<0.01) and ART drug toxicity (OR=4.5, 95% CI: 2.6-11.3, P<0.01) were the main factors associated with virological failure at 60 months.Poor adherence (OR=15.1,95% CI: 6.89-33.3, P<0.01), CD4≤100 /mL at the time of switching therapy (OR=10.5,95% CI: 5.1-21.7, P<0.01), concomitant medications (OR=3.6,95% CI:1.6-4.1,P<0.01) were main factors associated with immunological failure at 60 months.Conclusions Elderly patients (≥50 years) who failed first line regimen should switch to LPV/r contained regimen as early as possible.Adherence education should be strengthened, drug toxicity as well as complications of treatment should be managed in time and concomitant medications should be reduced.

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