Category: Statistics

Biom J. 2023 Jun 25:e2200229. doi: 10.1002/bimj.202200229. Online ahead of print.

ABSTRACT

The reference interval is the most widely used medical decision-making, constituting a central tool in determining whether an individual is healthy or not. When the results of several continuous diagnostic tests are available for the same patient, their clinical interpretation is more reliable if a multivariate reference region (MVR) is available rather than multiple univariate reference intervals. MVRs, defined as regions containing 95% of the results of healthy subjects, extend the concept of the reference interval to the multivariate setting. However, they are rarely used in clinical practice owing to difficulties associated with their interpretability and the restrictions inherent to the assumption of a Gaussian distribution. Further statistical research is thus needed to make MVRs more applicable and easier for physicians to interpret. Since the joint distribution of diagnostic test results may well change with patient characteristics independent of disease status, MVRs adjusted for covariates are desirable. The present work introduces a novel formulation for MVRs based on multivariate conditional transformation models (MCTMs). Additionally, we take into account the estimation uncertainty of such MVRs by means of tolerance regions. These conditional MVRs imply no parametric restriction on the response, and potentially nonlinear continuous covariate effects can be estimated. MCTMs allow the estimation of the effects of covariates on the joint distribution of multivariate response variables and on these variables’ marginal distributions, via the use of most likely transformation estimation. Our contributions proved reliable when tested with simulated data and for a real data application with two glycemic markers.

PMID:37357560 | DOI:10.1002/bimj.202200229

Clin Transl Allergy. 2023 Jun;13(6):e12270. doi: 10.1002/clt2.12270.

ABSTRACT

BACKGROUND: Atopic dermatitis and food allergy are two frequently concomitant manifestations of the presence of atopy. A substantial number of studies have been published on the association of birth order and sibship size (number of siblings) with atopic dermatitis, food allergy, and atopy. The present work is the first systematic synthesis of the existing literature on this topic.

METHODS: Fifteen databases were searched. Screening, data extraction, and quality assessment were performed by independent pairs. Comparable numerical data were statistically synthesized using random-effects robust variance estimation.

RESULTS: In total, 114 studies were included out of 8819 papers obtained from database searches. Birth order ≥2 versus 1 was associated with lower risk of ever atopic dermatitis (pooled risk ratio [RR] 0.91, 95% CI 0.84-0.98), current food allergy (RR 0.77, 95% CI 0.66-0.90), and positive skin prick test (SPT) to common aeroallergens (RR 0.86, 95% CI 0.77-0.97). Sibship size ≥2 versus 1 was associated with decreased risk of current atopic dermatitis (RR 0.90, 95% CI 0.83-0.98), ever atopic dermatitis (RR 0.92, 95% CI 0.86-0.97), and positive SPT to common aeroallergens (RR 0.88, 95% CI 0.83-0.92). No putative associations were seen regarding atopy assessed through allergen-specific immunoglobulin E with common allergens.

CONCLUSION: The presence of siblings and being second-born or later may decrease the lifetime risk of atopic dermatitis and food allergy, albeit marginally. Similar association was seen with SPT sensitization. However, significant protection was not found for IgE sensitization.

PMID:37357553 | DOI:10.1002/clt2.12270

J Magn Reson Imaging. 2023 Jun 25. doi: 10.1002/jmri.28880. Online ahead of print.

ABSTRACT

BACKGROUND: Little is known about the association between stroke and imaging and clinical features in conservatively treated patients with moyamoya disease (MMD).

PURPOSE: To investigate independent risk factors for stroke in conservatively treated patients with MMD during a long-term follow-up.

STUDY TYPE: Prospective study.

SUBJECTS: One hundred sixty conservatively managed patients with MMD (median age 46 years, 89 male).

FIELD STRENGTH/SEQUENCE: Time of flight, turbo inversion recovery magnitude T1WI, turbo spin echo (TSE) T2WI, echo-planar imaging DWI, T2-fluid attenuated inversion recovery, dynamic susceptibility contrast-magnetic resonance imaging, and pre- and post-contrast 3D TSE T1WI sequences at 3.0 Tesla.

ASSESSMENT: Patients were assessed at baseline and followed yearly. Ischemic and hemorrhagic stroke incidence rates were determined. Multiple demographic, clinical (modified Rankin score [mRS]), and cerebral imaging (cerebral blood volume [CBV] and concentric enhancement of arterial wall) factors at baseline were considered as potential predictors of stroke during the follow-up period.

STATISTICAL TESTS: Univariable and multivariable Cox proportional hazards models to calculate the hazard ratios (HRs) and corresponding 95% confidence interval (CI) for stroke. Cumulative risk of stroke was estimated by the Kaplan-Meier product-limit method. A P value <0.05 was considered statistically significant.

RESULTS: The median follow-up duration was 47 months. During the follow-up period, 18 (11.25%) patients experienced stroke events (13 [8.13%] ischemic, 5 [3.12%] hemorrhagic). Univariable analysis showed that 11 factors were significantly associated with stroke. After adjustment for clinical characteristics, multivariable analysis showed that mRS score ≥3 (HR, 1.99; 95% CI, 1.26-3.14), decreased CBV (HR, 5.31; 95% CI, 2.32-12.13), and concentric enhancement of the arterial wall (HR, 4.16; 95% CI, 1.55-11.15) were significantly associated with stroke.

DATA CONCLUSION: Decreased CBV, mRS score ≥ 3, and concentric enhancement of the arterial wall were significantly associated with increased incidence of stroke in conservatively treated MMD.

EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 4.

PMID:37357525 | DOI:10.1002/jmri.28880

Curr Mol Med. 2023 Jun 23. doi: 10.2174/1566524023666230623155659. Online ahead of print.

ABSTRACT

BACKGROUND: The role of deficiency of vitamin D in a wide range of human cancer, including breast cancer, has been proven, but its role in benign breast diseases remains unknown. This study aimed to determine the prevalence of vitamin D deficiency in patients with fibrocystic breast (FB) disease.

METHODS: First, the hospital prevalence of fibrocystic breast was determined by a cross-sectional study. Then, patients were divided into two groups by a case-control study; women with confirmed fibrocystic breasts based on breast pain, physical examination, and ultrasonography were included as a case group (N=48) and age-matched women without fibrocystic breasts were also included as a control group (N=48). After recording the demographic and gynecological characteristics and exposure to the sun, gynecological records, and family history of fibrocystic breast, the blood sample was taken to determine vitamin D. Data were analyzed by Stata software.

RESULTS: The result indicated that the studied groups had significant differences in regards to weight, breast pain, the severity of breast pain, breast heaviness, family history of fibrocystic breast, history of breast disease, caffeine consumption, and exposure to sunlight (p <0.05), but did not show significant differences based on age, occupation, education, gynecological history, diabetes mellitus, hypertension, obesity and hypothyroidism, vegetable, fast food, and dairy products consumption. The frequency of vitamin D deficiency in the case group was 45.8%, and in the control group, it was 20.8%, and there was a statistically significant difference (p <0.05).

CONCLUSION: Vitamin D deficiency is more common in women with fibrocystic breast disease and may play a role in the development of the disease.

PMID:37357512 | DOI:10.2174/1566524023666230623155659

Psychogeriatrics. 2023 Jun 25. doi: 10.1111/psyg.12993. Online ahead of print.

ABSTRACT

BACKGROUND: The real-world status of satisfaction with medication for dementia with Lewy bodies (DLB) has not been elucidated. We assessed the satisfaction of patients with DLB, their caregivers, and their attending physicians (trios) with medication according to the clinical symptom domains of DLB.

METHODS: This was a subanalysis of a cross-sectional, questionnaire-based, survey study of trios. The subanalysis set comprised analysis populations for cognitive impairment, parkinsonism, psychiatric symptoms, sleep-related disorders, and autonomic dysfunction (orthostatic hypotension, constipation, and dysuria). These analysis populations included trios of patients who had any symptom domain and took medication for each symptom domain, and for which all trio data on satisfaction with medication for the symptom domain were available. The degrees of satisfaction with medication were classified as ‘satisfied’, ‘neutral’, or ‘dissatisfied’.

RESULTS: The analysis set for this study included 110 trios for cognitive impairment, 62 for parkinsonism, 47 for psychiatric symptoms, 29 for sleep-related disorders, none for orthostatic hypotension, 11 for constipation, and seven for dysuria. There were no statistically significant differences in the degree of satisfaction with medication for symptom domains other than parkinsonism and dysuria between patients-caregivers, patients-physicians, and caregivers-physicians. Regarding satisfaction with medication for parkinsonism, significantly more physicians than patients answered ‘satisfied’ (75.8% vs. 51.6%), and significantly more patients than physicians answered ‘neutral’ (35.5% vs. 14.5%) (P = 0.013). Regarding satisfaction with medication for dysuria, significantly more caregivers than physicians answered ‘satisfied’ (100% vs. 28.6%, P = 0.038).

CONCLUSIONS: Satisfaction with medication for symptom domains other than parkinsonism and dysuria was similar among trios. Our results suggest that physicians should pay more attention to patients’ satisfaction with medication for parkinsonism, and to caregivers’ satisfaction with medication for dysuria to help prevent undermedication.

PMID:37357011 | DOI:10.1111/psyg.12993

Zhonghua Xue Ye Xue Za Zhi. 2023 Apr 14;44(4):284-288. doi: 10.3760/cma.j.issn.0253-2727.2023.04.004.

ABSTRACT

Objective: To determine the optimal cutoff value of Epstein-Barr virus (EBV) DNA load that can assist in the diagnosis of post-transplant lymphoproliferative disease (PTLD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: The data of patients with EBV infection after haplo-HSCT from January to December 2016 were retrospectively analyzed. Through constructing the receiver operating characteristic (ROC) curve and calculating the Youden index to determine the cutoff value of EBV-DNA load and its duration of diagnostic significance for PTLD. Results: A total of 94 patients were included, of whom 20 (21.3% ) developed PTLD, with a median onset time of 56 (40-309) d after transplantation. The median EBV value at the time of diagnosis of PTLD was 70,400 (1,710-1,370,000) copies/ml, and the median duration of EBV viremia was 23.5 (4-490) d. Binary logistic regression was used to analyze the peak EBV-DNA load (the EBV-DNA load at the time of diagnosis in the PTLD group) and duration of EBV viremia between the PTLD and non-PTLD groups. The results showed that the difference between the two groups was statistically significant (P=0.018 and P=0.001) . The ROC curve was constructed to calculate the Youden index, and it was concluded that the EBV-DNA load ≥ 41 850 copies/ml after allogeneic hematopoietic stem cell transplantation had diagnostic significance for PTLD (AUC=0.847) , and the sensitivity and specificity were 0.611 and 0.932, respectively. The duration of EBV viremia of ≥20.5 d had diagnostic significance for PTLD (AUC=0.833) , with a sensitivity and specificity of 0.778 and 0.795, respectively. Conclusion: Dynamic monitoring of EBV load in high-risk patients with PTLD after haplo-HSCT and attention to its duration have important clinical significance, which can help clinically predict the occurrence of PTLD in advance and take early intervention measures.

PMID:37356996 | DOI:10.3760/cma.j.issn.0253-2727.2023.04.004

Zhonghua Xue Ye Xue Za Zhi. 2023 Mar 14;44(3):222-229. doi: 10.3760/cma.j.issn.0253-2727.2023.03.008.

ABSTRACT

Objective: TP53-abnormal MDS/acute myeloid leukemia (AML) patients’ allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment’s effectiveness and influencing factors should be studied. Methods: 42 patients with TP53 gene status change MDS/AML who underwent allo-HSCT from 2014.8.1 to 2021.7.31 at the Hematology Hospital of the Chinese Academy of Medical Sciences were the subject of a retrospective analysis. The 42 patients were divided into three groups: the TP53 deletion group (group A) , TP53 mono-alle mutation group (group B) , and TP53 multi-hit group (group C) . The differences in clinical features and prognostic factors after transplantation were analyzed. Results: There were 42 MDS/AML patients, including 21 patients with MDS, and 21 patients with AML. The median follow-up period was 34.0 (7.5-75.0) months and the median patient age at the time of transplantation was 41.5 (18-63) years old. The total OS was 66.3% (95% CI 53.4%-82.4%) in 3 years after transplantation, and EFS was 61.0% (95% CI 47.7%-78.0%) in 3 years. For 3 years after receiving hematopoietic stem cell transplantation, there were no statistically significant differences in 3-year OS and EFS in groups A, B, and C (P≥0.05) . The 3 years OS was 82.5% (95% CI 63.1%-100.0%) in group A, 60.6% (95% CI 43.5%-84.4%) in group B, and 57.1% (95% CI 30.1%-100.0%) in group C. Univariate analysis revealed that the number of co-mutant genes, pre-HSCT treatment, and disease type did not affect prognosis, while age, karyotype, co-mutation, positive blast cell before transplantation, and positive blast cell after transplantation were common prognostic factors for OS and EFS (P<0.1) . MRD levels before transplantation were found to be independent risk factors for OS (P=0.037, HR=33.40, 95% CI 1.24-901.17) in a multivariate analysis. Conclusion: Patients with MDS/AML who have TP53 mutations can benefit from allo-HSCT, but patients with complex karyotypes have a worse prognosis. Meanwhile, the final flow cytometry (FCM) monitoring blast cell test before HSCT has a certain guiding significance for prognostic assessment.

PMID:37356984 | DOI:10.3760/cma.j.issn.0253-2727.2023.03.008

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Jun;31(3):889-895. doi: 10.19746/j.cnki.issn.1009-2137.2023.03.040.

ABSTRACT

OBJECTIVE: To investigate the expression and clinical significance of soluble Fas (sFas) and sFasL in patients with secondary hemophagocytic lymphohistiocytosis (sHLH).

METHODS: From September 2015 to December 2020, 86 sHLH patients who met the HLH2004 diagnostic criteria were collected. They were divided into 55 cases in the MAHLH group and 31 cases in the NonMAHLH group according to the etiology. Thirty healthy persons were chosen as the normal control group, and 20 patients with systemic lupus erythematosus (SLE) were chosen as the disease control group. The expression levels of sFas and sFasL in the serum of patients with each group were detected by ELISA, and the clinical data were collected for statistical analysis. The significance of sFas and sFasL in sHLH was analyzed by ROC curve.

RESULTS: Serum levels of sFas and sFasL in patients with newly diagnosed sHLH were significantly higher than those in disease control group and normal control group (P<0.01). The levels of sFas and sFasL in MAHLH group were significantly higher than those in nonMAHLH (infection related HLH and autoimmune disease related HLH) group (P<0.01). The serum levels of sFas and sFasL in 17 newly treated patients with sHLH (17/86) after treatment were significantly lower than those before treatment (P<0.01). The serum sFas level in newly diagnosed sHLH patients was positively correlated with SF(r=0.35), sCD25(r=0.79) and sFasL(r=0.73). The serum sFasL level was positively correlated with SF(r=0.39), sCD25(r=0.64) and sFas(r=0.73). Compared with the NonMAHLH group, the area under the ROC curve was 0.707 (95% CI: 0.593-0.821) (P=0.0015). The optimal critical value for diagnosing MAHLH by sFas level was 12 743 pg/ml, and the sensitivity and specificity were 70.9% and 71% respectively. Compared with the NonMAHLH group, the area under the ROC curve was 0.765(95% CI: 0.659-0.87)(P<0.01). The median OS time of sFas high expression group (≥16798.5 pg/ml) and sFasL high expression group (≥4 785 pg/ml) was significantly shorter than that of the low expression group (P<0.001).

CONCLUSION: Serum levels of sFas and sFasL can be used for the early diagnosis and differential diagnosis of sHLH disease, and are the factor related to the poor prognosis of sHLH.

PMID:37356956 | DOI:10.19746/j.cnki.issn.1009-2137.2023.03.040

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Jun;31(3):866-870. doi: 10.19746/j.cnki.issn.1009-2137.2023.03.037.

ABSTRACT

OBJECTIVE: To investigate the risk factors of oral ulcers and bloodstream infection in patients with hematopoietic stem cell transplantation.

METHODS: The clinical data of 401 hematopoietic stem cell transplant patients in the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021 were retrospective analyzed, and the risk factors of oral ulcers and bloodstream infection statistical and analyzed.

RESULTS: Among the 401 patients, the incidence of oral ulcers was 61.3% (246/401), and the incidence of bloodstream infection was 9.0% (36/401). A total of 40 strains of pathogenic bacteria were isolated from 36 patients, including 26 strains of Gram negative strains (65%), 13 strains of Gram positive strains (32.5%), and 1 strain of fungi (2.5%). Single-factor analysis showed that oral hygiene was associated with the occurrence of bloodstream infection, and the Multi-factor analysis showed that age ≥14 years old, disease diagnosis of leukemia, and allogeneic hematopoietic stem cell transplantation were risk factors for oral ulcers.

CONCLUSION: The incidence of oral ulcers in patients with hematopoietic stem cell transplantation is high. The age ≥14 years, disease diagnosis of leukemia, and allogeneic hematopoietic stem cell transplantation were risk factors for oral ulcers in patients, and oral hygiene was associated with the occurrence of bloodstream infection.

PMID:37356953 | DOI:10.19746/j.cnki.issn.1009-2137.2023.03.037

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2023 Jun;31(3):860-865. doi: 10.19746/j.cnki.issn.1009-2137.2023.03.036.

ABSTRACT

AbstractObjective: To analysis the clinical data of patients after single-center hematopoietic stem cell transplantation (HSCT) and construct a predictive model for metabolic syndrome (MS) diagnosis.

METHODS: Ninety-three hematology patients who underwent HSCT at the First Hospital of Lanzhou University from July 2015 to September 2022 were selected to collect basic data, transplantation status and postoperative data, the clinical characteristics of patients with and without MS after transplantation were compared and analyzed. Logistic regression model was used to analyze the influence fators of MS after transplantation, and a predictive model of HSCT-MS diagnosis was constructed under the influence of independent influence factors. The model was evaluated using the ceceiver operating characteristic curve (ROC curve).

RESULTS: Metabolic syndrome occurred in 36 of 93 HSCT patients and did not occur in 57. Compared with non-HSCT-MS group, HSCT-MS had significantly higher fasting blood glucose (FBG) levels before transplantation, shorter course before transplantation, and higher bilirubin levels after transplantation (P<0.05). The statistically significant clinical indicators were subjected to multi-factor logistic regression analysis, and the results showed that pre-transplant high FBG, pre-transplant short disease course and post-transplant high bilirubin were independent influence factors for HSCT-MS. The standard error of predicting the occurrence of HSCT-MS based on the clinical model was 0.048, the area under the curve AUC=0.776, 95% CI :0.683-0.869, the optimal threshold was 0.58 based on the Jorden index at maximum, the sensitivity was 0.694, and the specificity was 0.772, which has certain accuracy.

CONCLUSION: A clinical prediction model for HSCT-MS based on logistic regression analysis is constructed through the analysis of clinical data, which has certain clinical value.

PMID:37356952 | DOI:10.19746/j.cnki.issn.1009-2137.2023.03.036