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Standardising management of consent withdrawal and other clinical trial participation changes: The UKCRC Registered Clinical Trials Unit Network’s PeRSEVERE project

Clin Trials. 2025 Jul 4:17407745251344524. doi: 10.1177/17407745251344524. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: Existing regulatory and ethical guidance does not address real-life complexities in how clinical trial participants’ level of participation may change. If these complexities are inappropriately managed, there may be negative consequences for trial participants and the integrity of trials they participate in. These concerns have been highlighted over many years, but there remains no single, comprehensive guidance for managing participation changes in ways that address real-life complexities while maximally promoting participant interests and trial integrity. Motivated by the lack of agreed standards, and observed variability in practice, representatives from academic clinical trials units and linked organisations in the United Kingdom initiated the PeRSEVERE project (PRincipleS for handling end-of-participation EVEnts in clinical trials REsearch) to agree on guiding principles and explore how these principles should be implemented.

METHODS: We developed the PeRSEVERE principles through discussion and debate within a large, multidisciplinary collaboration, including research professionals and public contributors. We took an inclusive approach to drafting the principles, incorporating new ideas if they were within project scope. Our draft principles were scrutinised through an international consultation survey which focussed on the principles’ clarity, feasibility, novelty and acceptability. Survey responses were analysed descriptively (for category questions) and using a combination of deductive and inductive analysis (for open questions). We used predefined rules to guide feedback handling. After finalising the principles, we developed accompanying implementation guidance from several sources.

RESULTS: In total, 280 people from 9 countries took part in the consultation survey. Feedback showed strong support for the principles with 96% of respondents agreeing with the principles’ key messages. Based on our predefined rules, it was not necessary to amend our draft principles, but comments were nonetheless used to enhance the final project outputs. Our 17 finalised principles comprise 7 fundamental, ‘overarching’ principles, 6 about trial design and setup, 2 covering data collection and monitoring, and 2 on trial analysis and reporting.

CONCLUSION: We devised a comprehensive set of guiding principles, with detailed practical recommendations, to aid the management of clinical trial participation changes, building on existing ethical and regulatory texts. Our outputs reflect the contributions of a substantial number of individuals, including public contributors and research professionals with various specialisms. This lends weight to our recommendations, which have implications for everyone who designs, funds, conducts, oversees or participates in trials. We suggest our principles could lead to improved standards in clinical trials and better experiences for participants. We encourage others to build on our work to explore the application of these ideas in other settings and to generate empirical evidence to support best practice in this area.

PMID:40613224 | DOI:10.1177/17407745251344524

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Genetic Modifiers of HbF in HbAA and HbAS Women From São Tomé e Príncipe: An Association Study of Common Genetic Variants in BCL11A, MYB, HBG2, and BGLT3

Front Biosci (Schol Ed). 2025 Jun 25;17(2):38388. doi: 10.31083/FBS38388.

ABSTRACT

BACKGROUND: While an increase in fetal hemoglobin (HbF) has no consequences in healthy adults, clinical benefits can be promoted in sickle cell disease (SCD) and β-thalassemia patients. Single-nucleotide polymorphisms (SNPs) in three genomic regions: the HBB gene cluster, the BCL11A gene, and the HBS1L-MYB (HMIP) intergenic region, have been associated with HbF regulation. Therefore, the present study aimed to examine the potential association of SNPs in BCL11A (rs11886868 and rs1427407), HMIP (rs66650371 and rs4895441), HBG2 (rs7482144), and BGLT3 (rs7924684) with HbF levels in an adult population sample from São Tomé e Príncipe (Central Africa).

METHODS: A total of 145 women aged 18 to 49 years were involved in this study, comprising 98 women with the normal hemoglobin (Hb) genotype (HbAA) and 47 with sickle cell trait (HbAS). From the HbAA individuals, we selected a control group of 60 subjects with normal HbF levels, ranging from 0.2% to 1.4% (mean: 0.75%), and a case group of 38 subjects with elevated HbF levels, ranging from 1.8% to 3.7% (mean: 2.35%). In the group of HbAS individuals, the HbF levels ranged from 0.4% to 3.7% (mean: 1.56%). SNP genotyping was conducted using standard molecular methods.

RESULTS: Logistic regression, in the additive model, revealed significant associations with increased levels of HbF for the minor alleles of the two BCL11A SNPs, rs11886868 [C] and rs1427407 [T], in HbAA women (p = 0.00018 and p = 0.00076, respectively). When comparisons of HbF levels were conducted among genotypes in the HbAA women, significant differences were observed for BCL11A SNPs rs11886868 and rs1427407, as well as for the HBG2 rs7482144 and BGLT3 rs7924684 variants. We found no association between HbF levels and the two HMIP variants rs66650371 and rs4895441 in the HbAA women. Among the HbAS women, no statistically significant associations were observed between the six analyzed polymorphisms and HbF levels (p > 0.05).

CONCLUSIONS: We successfully replicated the association between the two well-known BCL11A SNPs, rs11886868 and rs1427407, with HbF levels in women with the normal HbAA genotype from São Tomé e Príncipe. Other signals of association with HbF levels were identified for the SNPs HBG2 (rs7482144) and BGLT3 (rs7924684).

PMID:40613211 | DOI:10.31083/FBS38388

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Analysis of ABO System Hemolytic Disease of the Newborn in 283 Cases at Yunnan Province

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Jun;33(3):881-885. doi: 10.19746/j.cnki.issn.1009-2137.2025.03.039.

ABSTRACT

OBJECTIVE: To analyze the laboratory detection results of hemolytic disease of the fetus and newborn(HDFN).

METHODS: Related test results of 283 newborns and their mothers’ blood samples from Kunming Maternal and Child Health Hospital from August 2023 to May 2024 were collected, including mother and child ABO blood group, RhD blood group, as well as 3 tests of HDFN, total bilirubin (TBil) and indirect bilirubin (IBil).

RESULTS: 283 were ABO incompatibility, among which 187 were HDFN positive, with a positive rate of 66.08%; the positive rate of HDFN in neonates with antigen-A incompatibility was 74.12%(126/170), the positive rate of HDFN in neonates with antigen-B incompatibility was 53.57%(60/112), which was the highest in neonates with O/A incompatibility [75.45%(126/167)], followed by O/B incompatibility[54.55%(60/110)]. Group by age, the positive rates of HDFN in the ≤1 d group, 2 d group, 3 d group, 4 d group, 5 d group and ≥6 d group were 76.03%(111/146), 67.86%(38/56), 57.14%(24/42), 38.46%(5/13), 46.15%(6/13) and 23.08%(3/13), respectively. With the increase of age, the positive rates of HDFN gradually decreased, there was a statistically significant difference between the ≤3 day age group and >3 day age group ( P <0.05). There was no statistically significant difference in TBil and IBil levels between the “direct antibody+indirect antibody+release+” group and the HDFN negative group in newborns. HDFN infants exhibited a rapid increase in bilirubin levels within the first day after birth, with significantly higher TBil and IBil values compared to Non ABO-HDFN infants in the ≤1 day group ( P <0.01). However, the difference of bilirubin levels between the two groups gradually narrowed from 2-6 days after birth, and the difference was not statistically significant (P >0.05). The peak value of TBil and IBil occurred on the 4th day after birth in HDFN infants.

CONCLUSION: ABO-HDFN is most commonly seen in newborns whose mothers are type-O, and the positive rate was the highest in newborns with O/A incompatibility. The detection rate of HDFN is affected by the age of the newborns, and the two were correlated inversely. ABO-HDFN group developed more rapidly with a higher peak. Therefore, HDFN tests should be carried out as soon as possible for mothers and newborns with incompatible blood types, and appropriate treatment should be provided to prevent complications.

PMID:40613186 | DOI:10.19746/j.cnki.issn.1009-2137.2025.03.039

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Investigation of Infection in HBV-Reactive Blood Donors in Wuhan

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Jun;33(3):875-880. doi: 10.19746/j.cnki.issn.1009-2137.2025.03.038.

ABSTRACT

OBJECTIVE: To investigate the pattern of hepatitis B virus (HBV) infection and the prevalence of hepatitis D virus (HDV) infection among voluntary blood donors who tested reactive for HBV in Wuhan, and to provide data support for the prevention and treatment of HBV and HDV infections.

METHODS: Electrochemiluminescence (ECL) method was used to detect hepatitis B serological markers in the samples with HBsAg and/or HBV DNA reactivity, and the HBV infection in different groups was statistically analyzed. The HDV IgM and IgG antibodies were screened by ELISA, and the prevalence of HDV infection in the retained samples was analyzed.

RESULTS: In 351 ELISA and/or nucleic acid test (NAT) reactive samples, the serological tests for hepatitis B revealed that 4 cases (1.1%) were positive for HBsAg, HBeAg, and anti-HBc, 182 cases (51.9%) were positive for HBsAg, anti-HBe, and anti-HBc, and 55 cases (15.7%) were negative for HBsAg but positive for anti-HBc. Among them, the HBsAg ELISA dual reagent reactive group (HBsAg R&R group) and the HBsAg ELISA single reagent reactive/HBV DNA reactive group (HBsAg R&NR/HBV DNA R group) had the highest rates of HBsAg(+), anti-HBe(+), and anti-HBc(+), accounting for more than 90% and 65%, respectively, followed by low activity of HBV acute infection or chronic carriers, accounting for about 5% and 20%, respectively. In the HBsAg R&NR/HBV DNA NR group, the combined proportion of individuals with anti-HBs single positive and all hepatitis B serological markers negative accounted for 78%, and those who were HBsAg negative but anti-HBc positive accounted for approximately 20%. In the HBsAg NR&NR/HBV DNA R group, there was nearly 9% of HBsAg(+), anti-HBe(+), and anti-HBc(+), the remaining were all HBsAg negative but anti-HBc positive, with a 100% anti-HBc positivity rate in this group. No HDV IgM or IgG antibodies were detected in the retained samples.

CONCLUSION: Blood donors with HBV-reactive results in blood screening exhibit multiple patterns of infection indicators. The prevalence rate of HDV infection among blood donors in Wuhan is extremely low. However, the risk of asymptomatic occult hepatitis B infection (OBI) blood donors being co-infected with HDV should not be overlooked in areas with high prevalence of HBV.

PMID:40613185 | DOI:10.19746/j.cnki.issn.1009-2137.2025.03.038

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The Efficacy of Combination of Avatrombopag and rhIL-11 in Adult Patients of Acute Myeloid Leukemia with Cancer Treatment-Induced Thrombocytopenia

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Jun;33(3):848-852. doi: 10.19746/j.cnki.issn.1009-2137.2025.03.033.

ABSTRACT

OBJECTIVE: To investigate the safety and efficacy of avatrombopag(AVA) combined with rhIL-11 in treating thrombocytopenia induced by chemotherapy in acute myeloid leukemia.

METHODS: The clinical information of 8 patients in the real world who received avatrombopag combined with rhIL-11 in cancer treatment-induced thrombocytopenia(CTIT) after AML chemotherapy were retrospectively analyzed, and at the same time, 8 patients who received rhIL-11 only in CTIT after AML chemotherapy served as the control group, A preliminary observation was to summarize and compare the therapeutic efficacy and adverse effects between the two groups.

RESULTS: D3 and D7 platelet counts were not significantly different between the observation group and the control group after treatment. The platelet counts in the observation group was significantly higher than those of the control group on the 10th day after treatment (P < 0.01). The adverse reactions, such as weakness, abdominal pain, fatigue, nausea and edema after treatment were mild in the observation group and the control group. Except for one patient in the observation group who had a history of cerebral infarction before the onset of the disease and was routinely taking antiplatelet drugs, no thrombosis events occurred in the patients in the observation and control groups during the period of administration of the drug, and the total incidence rate of adverse reactions was not significantly different between the two groups.

CONCLUSION: The combination of AVA and rhIL-11 can enhance platelet recovery in CTIT of AML patients after chemotherapy. Compared with the rhIL-11 alone group, the platelet recovery time in AVA+rhIL-11 group was significantly shorter, the platelet count on the 10th day after drug administration was significantly higher. No statistically significant difference in the total incidence rate of adverse reactions was observed between rhIL-11 alone group and AVA+rhIL-11 group.

PMID:40613180 | DOI:10.19746/j.cnki.issn.1009-2137.2025.03.033

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Relationship between Peripheral Blood TIM-3 and Iron Overload in Patients with Myelodysplastic Syndrome Undergoing Red Blood Cell Transfusion

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Jun;33(3):841-847. doi: 10.19746/j.cnki.issn.1009-2137.2025.03.032.

ABSTRACT

OBJECTIVE: To investigate the relationship between peripheral blood T-cell immunoglobulin mucin-3 (TIM-3) and iron overload in patients with myelodysplastic syndrome (MDS) undergoing red blood cell transfusion.

METHODS: 120 MDS patients who received treatment at Wuhan Third Hospital from June 2020 to May 2022 were included and analyzed as research subjects, all of whom met the indications for red blood cell transfusion. Blood routine and biochemical indicators were tested before transfusion, and general clinical data of the patients were statistically analyzed. The iron metabolism status of the patients were evaluated. The clinical characteristics of patients with iron overload and the factors affecting iron overload were analyzed. And a correlation analysis was conducted between TIM-3 and other factors affecting iron overload.

RESULTS: Among the 120 MDS patients included in this study, 82 cases (68.33%) were detected to have iron overload after red blood cell transfusion. The occurrence time of iron overload was 20-42 weeks, with an average time of 32.35±5.26 weeks, calculated from the first transfusion of red blood cells. The proportion of patients with high-risk and extremely high-risk according to the revised International Prognostic Scoring System (IPSS-R) and WHO classification-based Prognostic Scoring System (WPSS), the volume of blood transfusions, the proportion of transfusion-dependent patients, and the levels of serum hepcidin (Hepc), erythropoietin (EPO), and TIM-3 in patients with iron overload were higher than those in patients with normal iron metabolism, and the differences were statistically significant (P < 0.05). Logistic regression analysis showed that high-risk and extremely high-risk according to WPSS, blood transfusion volume, transfusion dependence, and upregulation of serum Hepc, EPO, and TIM-3 expression were factors affecting iron overload in MDS patients undergoing red blood cell transfusion (P < 0.05). Pearson correlation analysis showed that serum TIM-3 level in MDS patients were positively correlated with the other factors affecting iron overload (P < 0.05).

CONCLUSION: Serum TIM-3 is associated with iron overload in MDS patients undergoing red blood cell transfusion, and upregulation of serum TIM-3 expression increases the risk of iron overload after red blood cell transfusion.

PMID:40613179 | DOI:10.19746/j.cnki.issn.1009-2137.2025.03.032

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A Retrospective Clinical Analysis of Multiple Myeloma Patients with Cardiac Amyloidosis

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Jun;33(3):834-840. doi: 10.19746/j.cnki.issn.1009-2137.2025.03.031.

ABSTRACT

OBJECTIVE: To investigate the clinical characteristics, curative effect and prognostic factors of patients with multiple myeloma (MM) complicated with light chain myocardial amyloidosis (AL-CA).

METHODS: The data of 38 patients diagnosed with MM complicated with AL-CA in our hospital from January 2018 to December 2023 were retrospectively analyzed, and the data were comprehensively screened by multiple methods such as positive two-dimensional spot tracking echocardiography (2D-STE). Survival analysis was performed using the Kaplan-Meier method. Cox regression models were used to screen for independent prognostic factors.

RESULTS: Among the 38 MM patients with AL-CA, 23 were male and 15 were female, with a median age of 60(50,75) years. The 1-year survival rate was 71.05%. Patients who underwent transplantation had significantly better survival outcomes than those who did not (P < 0.01). Additionally, the median survival time of patients with all-negative FISH results at the first visit was statistically different compared to patients with other mutations (P < 0.05). Multivariate Cox regression analysis showed that all negative FISH results at the first visit and the absence of autologous hematopoietic stem cell transplantation (ASCT) were not independent risk factor for the prognosis of patients with MM and AL-CA (P >0.05).

CONCLUSION: ASCT may improve the prognosis of MM patients with AL-CA, and negative FISH results may indicate poor prognosis, but the results still need to be verified by larger samples.

PMID:40613178 | DOI:10.19746/j.cnki.issn.1009-2137.2025.03.031

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Correlation between Serum FGF-23, HPSE Levels and Early Renal Impairment in Patients with Multiple Myeloma

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Jun;33(3):822-827. doi: 10.19746/j.cnki.issn.1009-2137.2025.03.029.

ABSTRACT

OBJECTIVE: To investigate the relationship between serum levels of fibroblast growth factor-23 (FGF-23), heparanase (HPSE) and early renal impairment (RI) in patients with multiple myeloma (MM).

METHODS: A retrospective analysis was conducted on the clinical data of 125 MM patients who were initially diagnosed in the Department of Hematology of the First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology from June 2020 to June 2023. The patients were divided into RI group (>176.80 μmol/L) and non-RI group (≤176.80 μmol/L) based on their serum creatinine levels when diagnosed. The baseline data and laboratory indexes of the two groups were compared. The relationship between serum FGF-23, HPSE and early RI in MM patients was analyzed.

RESULTS: Among 125 newly diagnosed MM patients, 33 cases developed early RI, accounting for 26.40%. The proportion of light chain type, blood urea nitrogen (BUN), blood uric acid, lactate dehydrogenase, FGF-23, and HPSE levels in RI group were higher than those in non-RI group (all P <0.05). There was no statistical significant difference in other data between the two groups (P >0.05). Multivariate logistic regression analysis showed that BUN, FGF-23 and HPSE were associated with early RI in MM patients (all P <0.05). The serum FGF-23 level was divided into Q1-Q4 groups by quartile, and the serum HPSE level was divided into q1-q4 groups. The correlation analysis showed that with the increase of serum FGF-23 and HPSE levels, the incidence of early RI increased (r =0.668, 0.592). Furthermore, logistic regression analysis showed that after controlling for confounding factors, elevated levels of serum FGF-23 and HPSE were still influencing factors for early RI in MM patients (OR>1, P <0.05). According to Pearson’s linear correlation test, there was a positive correlation between serum FGF-23 level and HPSE level (r =0.373).

CONCLUSION: There is a certain correlation between serum levels of FGF-23, HPSE and early RI in MM patients, and the incidence of early RI is higher in patients with abnormally high levels of both.

PMID:40613176 | DOI:10.19746/j.cnki.issn.1009-2137.2025.03.029

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Clinical Characteristics and Prognostic Analysis of Peripheral T-Cell Lymphoma, Not Otherwise Specified

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Jun;33(3):753-759. doi: 10.19746/j.cnki.issn.1009-2137.2025.03.019.

ABSTRACT

OBJECTIVE: To investigate the clinical characteristics and prognosis of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS).

METHODS: Clinical data of 10 patients with PTCL-NOS in Gansu Provincial Hospital from May 2016 to June 2023 were collected. The treatment outcomes were evaluated, and the factors affecting prognosis were analyzed.

RESULTS: The median age of onset for the 10 patients was 60.7 (47-75) years, with 7 males and 3 females. Nine cases received chemotherapy, while one case died suddenly after diagnosis, and the median course of chemotherapy was 6.9 (1-13) courses. Assessing the efficacy, 3 patients achieved complete remission (CR) while 7 patients showed progression. Age, sex, lactate dehydrogenase (LDH) level, Ki-67 and the presence of hemophagocytic lymphohistocytosis (HLH) were not statistically correlated with CR rate ( P >0.05). Patients with IPI score 3-5, and Ann Arbor stage III-IV had statistically lower CR rates (both P <0.05). Age, B symptoms, LDH level ,hemoglobin, Ki-67 index and PLR value were not statistically correlated with overall survival (OS) time ( P >0.05). Male, platelet <150×109/L, IPI score 3-5, Ann Arbor stage III-IV, presence of HLH, NLR≥4.05, and LMR <2.81 were statistically correlated with shorter OS (all P <0.05). Among the 10 patients, 3 cases have survived and are still in CR status, while 7 cases have died, with a median survival time of 7.5 (1-85) months.

CONCLUSIONS: Patients with IPI score 3-5 and Ann Arbor stage III-IV have low CR rate and poor prognosis. The OS of patients who are male, with platelet <150×109/L, IPI score 3-5, Ann Arbor stage III-IV, complication of HLH, NLR≥4.05, and LMR <2.81 is short, and prognosis is poor.

PMID:40613166 | DOI:10.19746/j.cnki.issn.1009-2137.2025.03.019

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Curative Efficacy Analysis of Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia with ASXL1 Mutation

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2025 Jun;33(3):720-725. doi: 10.19746/j.cnki.issn.1009-2137.2025.03.014.

ABSTRACT

OBJECTIVE: To explore the efficacy and apoptosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute myeloid leukemia (AML) with ASXL1 mutation.

METHODS: The clinical data of 80 AML patients with ASXL1 mutation treated in our hospital from January 2019 to December 2021 were retrospectively analyzed. The clinical characteristics of the patients were summarized, and the therapeutic effect and prognostic factors of allo-HSCT for the patients were analyzed.

RESULTS: Among the 80 patients, 38 were males and 42 were females, and the median age was 39(14-65) years. There were 17 patients in low-risk group, 25 patients in medium-risk group and 38 patients in high-risk group. ASXL1 mutation co-occurred with many other gene mutations, and the frequent mutated genes were TET2 (71.25%), NRAS (18.75%), DNMT3A (16.25%), NPM1 (15.00%), CEBPA (13.75%). Among medium and high-risk patients, 29 underwent allo-HSCT, while 34 received chemotherapy. The 2-year overall survival (OS) rate and disease-free survival (DFS) rate of the allo-HSCT group were 72.4% and 70.2%, while those of the chemotherapy group were 44.1% and 34.0%, respectively. The statistical analysis showed significant differences between the two groups (both P < 0.01). Multivariate analysis showed that age at transplantation >50- years and occurrence of acute graft-versus-host disease after transplantation were poor prognostic factors for OS and DFS in transplantation patients.

CONCLUSION: Allo-HSCT can improve the prognosis of AML patients with ASXL1 mutation.

PMID:40613161 | DOI:10.19746/j.cnki.issn.1009-2137.2025.03.014