Category: Statistics

Int Forum Allergy Rhinol. 2023 Apr 21. doi: 10.1002/alr.23171. Online ahead of print.

ABSTRACT

BACKGROUND: Quality-of-life (QOL) for individuals with sinonasal malignancy (SNM) is significantly understudied yet critical for counseling and may impact treatment. This study evaluated the how patient, treatment, and disease factors impact sinonasal-specific and generalized QOL using validated metrics in a large cohort over a 5-year post-treatment timeframe.

METHODS: Patients with SNM who underwent definitive treatment with curative intent were enrolled into a prospective, multi-site, longitudinal observational study. QOL was assessed using the Sinonasal Outcome Test-22 (SNOT-22) and University of Washington Quality of Life Questionnaire (UWQOL) instruments at pre-treatment baseline and multiple follow-ups through 5 years post-treatment. Multivariable modelling was used to determine demographic, disease, and treatment factors associated with disease-specific and generalized physical and social/emotional function QOL.

RESULTS: 194 patients with SNM were analyzed. All QOL indices were impaired at pre-treatment baseline and improved post-treatment. SNOT-22 scores improved 3 months and UWQOL scores improved 6-9 months post-treatment. Patients who underwent open compared to endoscopic tumor resection had worse generalized QOL (p<0.001), adjusted for factors including T stage. Pterygopalatine fossa (PPF) involvement was associated with worse QOL (SNOT-22, p<0.001; UWQOL-Physical, p = 0.02). Adjuvant radiation was associated with worse disease-specific QOL (p = 0.03). Neck dissection was associated with worse generalized physical function QOL (p = 0.01). Positive margins were associated with worse generalized social/emotional function QOL (p = 0.01).

CONCLUSIONS: Disease-specific and generalized QOL is impaired at baseline in patients with SNM and improves following treatment. Endoscopic resection is associated with better QOL. PPF involvement, adjuvant radiation, neck dissection, and positive margins were associated with worse QOL post-treatment. This article is protected by copyright. All rights reserved.

PMID:37082883 | DOI:10.1002/alr.23171

Andrology. 2023 Apr 21. doi: 10.1111/andr.13443. Online ahead of print.

ABSTRACT

BACKGROUND: The causal relationship between obesity-related anthropometric indicators/body composition and erectile dysfunction (ED) has not been established in previous observational studies.

METHOD: We screened single nucleotide polymorphisms significantly associated with exposure from genome-wide association studies (GWAS) as instrumental variables (IVs) (P < 5.0 × 10^-8 ). The summary statistics for ED were collected from a GWAS with a sample size of 223,805. Exposure and outcome populations included are of European ancestry. We used univariate and multivariate Mendelian randomization (MR) (i) to investigate the causal relationship between genetically predicted obesity-related anthropometric indicators/body composition and ED (ii) to examine the mediating role of coronary artery disease (CAD). MR analysis was conducted using an inverse variance weighted method. A series of sensitivity analyses validated the results of the MR analysis. Causal estimates are expressed as odds ratios (OR) with 95% confidence intervals (CI).

RESULTS: Obesity-related anthropometric indicators/body composition were associated with an increased risk of ED in univariate MR analyses. For the 1-SD increase in BMI, the OR was 1.841 (95% CI: 1.049-1.355, P = 0.006). For the 1-SD increase in waist circumference and hip circumference, the ORs were 1.275 (95% CI: 1.101-1.478, P = 0.001) and 1.156 (95% CI: 1.015-1.317, P = 0.009), respectively. The OR for the 1-SD increase in whole body fat mass was 1.221 (95% CI: 1.047-1.388, P = 0.002). For the 1-SD increase in leg fat percentage (left & right), the ORs were 1.256 (95% CI: 1.006-1.567, P = 0.044) and 1.285 (95% CI: 1.027-1.608, P = 0.028), respectively. For the 1-SD increase in leg fat mass (left & right), the ORs were 1.308 (95% CI: 1.108-1.544, P = 0.001) and 1.290 (95% CI: 1.091-1.524, P = 0.003), respectively. For the 1-SD increase in arm fat mass (left & right), the ORs were 1.269 (95% CI: 1.113-1.447, P < 0.001) and 1.254, respectively. Multivariate MR analysis showed that after adjusting for CAD, some genetic predispositions to obesity-related anthropometric indicators and body composition were still associated with an increased risk of ED. Significant associations were found for waist circumference-ED (OR: 1.218, 95% CI: 1.036-1.432), leg fat percentage (left)-ED (OR: 1.245, 95% CI: 1.035-1.497), leg fat mass (left)-ED (OR: 1.264, 95% CI: 1.051-1.521), arm fat mass (right)-ED (OR: 1.186, 95% CI: 1.024-1.373), and arm fat mass (left)-ED (OR: 1.17, 95% CI: 1.018-1.360). Meanwhile, CAD mediated the effects of fat on ED, and the proportion of CAD-mediated cases ranged from 10% to 22%.

CONCLUSION: There is a potential causal relationship between obesity-related anthropometric indicators/body composition and ED. Higher waist circumference, leg fat percentage, and arm fat mass may increase the risk of ED, and CAD partly mediates this overall effect. Understanding the causal relationship between obesity and ED and the mediating role of CAD may provide more information for ED intervention and prevention strategies. This article is protected by copyright. All rights reserved.

PMID:37082877 | DOI:10.1111/andr.13443

J Cosmet Dermatol. 2023 Apr 21. doi: 10.1111/jocd.15776. Online ahead of print.

ABSTRACT

BACKGROUND: Acne vulgaris is a common skin disease that is more common in young population and it can be associated with some sequels after resolving the lesions. Post-inflammatory erythema is one of these complications that can be disturbing for patients and does not have any definite treatment. This study was aimed to evaluate the efficacy and safety of tranexamic acid (TA) as mesotherapy in treatment of post-acne erythema (PAE) treatment.

METHOD: This clinical trial study was performed in the dermatology clinic on 17 patients with persistent PAE (3 months after acne recovery). Two sessions of treatment were performed by a physician with 2-week intervals; TA was injected as mesotherapy into the right side of each patient’s face as the case group, while the opposite side was used as the control group. A Visioface device was used to compare before and after treatment photographs of each side of the face in color mode with quantitative measures such as lesions count, area, and area percent.

RESULTS: Finally, 15 patients completed treatment sessions. There were statistically significant differences in right side lesions before and after treatment with p-values of 0.047, 0.002, and 0.035 for count, area, and area percent, respectively. There was no significant difference before and after treatment in terms of count, area. and area-percent on the left side.

CONCLUSION: According to the results of this study, TA injection as mesotherapy for resolving PAE can be effective. However, due to small sample size, further studies are needed.

PMID:37082869 | DOI:10.1111/jocd.15776

Eur J Haematol. 2023 Apr 21. doi: 10.1111/ejh.13981. Online ahead of print.

ABSTRACT

BACKGROUND: No adequate data exist on the impact of multiple myeloma (MM) with extramedullary disease (EMD) after autograft and maintenance therapy.

METHODS: We identified 808 patients with newly diagnosed MM who received first autograft, of whom 107 had EMD (83 paraskeletal and 24 organ involvement), and who had been reported to the EBMT registry December 2018. Distribution according to type of involvement was similar between the treatment groups (p = .69). For EMD, 46 (40%) received thalidomide, 59 (51%) lenalidomide, and 11 (10%) bortezomib.

RESULTS: The median follow-up from maintenance start was 44 months. Three-year progression-free survival (PFS) was 52% (48%-57%) for no EMD, 56% (44%-69%) for paraskeletal involvement, and 45% (22%-68%) for organ involvement (p = .146). Early PFS (within first year) appeared to be significantly worse for organ involvement (hazard ratio, 3.40), while no significant influence was found after first year from maintenance start. Three-year overall survival (OS) was 81% (77%-84%), 88% (80%-96%), and 68% (47%-89%; p = .064), respectively. With thalidomide as reference, lenalidomide was significantly associated with better PFS and OS, whereas bortezomib appeared to improve outcome specifically in EMD.

CONCLUSION: Lenalidomide maintenance is standard of care for MM without EMD, whereas extramedullary organ involvement remains a significant risk factor for worse outcome, especially for early events after maintenance start.

PMID:37082839 | DOI:10.1111/ejh.13981

J Matern Fetal Neonatal Med. 2023 Dec;36(1):2203797. doi: 10.1080/14767058.2023.2203797.

ABSTRACT

OBJECTIVE: To explore the appropriate application of glycemic qualification rate (GQR) calculated by fingerstick blood glucose (BG) monitoring for patients with gestational diabetes mellitus (GDM) by analyzing the relationship between BG control and adverse pregnancy outcomes.

METHODS: Fingerstick Blood Glucose data during the second and third trimester of singleton pregnant women diagnosed with GDM were collected. GQR which is defined as the percentage of fingerstick BG values reaching the targets of BG control in a period of time was calculated. Patients were divided into three groups according to tertiles (tertile 1, GQR <56.25%; tertile 2, GQR 56.25-75%; and tertile 3, GQR ≥75%). Pregnant outcomes were compared among the three groups. Univariate analysis and logistic regression were performed to analyze the potential relationship between GQR and pregnancy outcomes. Receiver operating characteristic (ROC) curves were calculated to determine the cutoff values. We also explored that whether twice or three times monitoring per day would be adequate for GQR calculation, so we brought in two or three glucose measuring times per day to explore the relationship between new GQR and adverse outcomes.

RESULTS: A total of 311 patients diagnosed with GDM were analyzed. In univariate analysis, the incidences of cesarean section of tertile 1-3 groups were 61.4%, 58.7%, and 44.9%, respectively (p < .05). The incidences of neonatal hypoglycemia of tertiles 1-3 groups were 19.8%, 18.6%, and 8.7% (p < .05). The difference of composite outcomes was statistically significant (p = .001). After adjustment, the patients with worse BG control (lower GQR) had higher risk of cesarean section (tertile 1 – aOR = 2.029, 1.128-3.648), neonatal hypoglycemia (tertile 1: aOR = 2.498, 1.082-5.766) as well as composite outcomes. The ROC curve of GQR indicated the predictive value for neonatal hypoglycemia (area under the ROC curve (AUC) 0.612 (0.532-0.692)) and neonatal composite outcomes (AUC 0.593 (0.528-0.657)) with optimal cutoff values of 81.1% and 73.5%, respectively. We also explored that whether twice or three times monitoring per day would be adequate for GQR calculation. The result showed that GQR only calculated by FBG + 2hPG after lunch (2h AL) per day also had well relationship with cesarean section (tertile 1: OR = 2.412, 1.322-4.398), neonatal hypoglycemia (tertile 1: aOR = 4.497, 1.607-12.586), and neonatal composite outcomes (tertile 1: aOR = 1.959, 95% confidence interval (CI): 1.114-3.444, p = .020).

CONCLUSIONS: The GQR calculated by the easily applicable fingerstick BG is related to occurrence of cesarean section and neonatal hypoglycemia in GDM women. GQR ≥ 80% is recommended for better pregnancy outcomes. As for the number of points monitoring per day, GQR calculated by FBG + 2h AL was an optimal option for better pregnancy outcomes if mothers needed to simplify the process of monitoring.

PMID:37080918 | DOI:10.1080/14767058.2023.2203797

J Matern Fetal Neonatal Med. 2023 Dec;36(1):2183083. doi: 10.1080/14767058.2023.2183083.

ABSTRACT

OBJECTIVE: The primary objective of this study was to explore whether antisense oligonucleotides (ASOs) that reduce LncNR_040117 expression in patients with antiphospholipid antibody syndrome (APS)-induced recurrent pregnancy loss (RPL), and further decrease apoptosis and improve trophoblasts invasion through mitogen-activated protein kinase (MAPK) pathways. This paper aimed to provide a new strategy to treat APS-induced RPL.

METHODS: In this study, we used quantitative reverse transcription-polymerase chain reaction (RT-qPCR) to analyze the expression level of LncNR 040117 in HTR-8/SVneo cells following transfection with ASOs. Then we utilized Western blotting to test the expression levels of interleukin-1β (IL-1β), intracellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and key molecules of MAPK pathways, including the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinases (JNK) and p38. In addition, we examined the HTR-8/SVneo cells apoptosis by cell apoptosis assay, and migration and invasion by transwell antibody assay. Each experiment was repeated three times. The data are presented as the means ± SDs, and statistical comparisons were performed using Student’s t-test. p < 0.05 was considered significant.

RESULT: Transfected with ASOs, LncNR_040117 was downregulated in trophoblasts compared with APS-induced RPL patients. And LncNR_040117 low expression induced IL-1β and downstream adhesion molecules ICAM-1 and VCAM-1expression level decreased, as well as MAPK pathways downregulation, including the ERK pathway, JNK pathway and p38/MAPK pathway. Furthermore, all these changes resulted in decreased apoptosis and increased migration and invasion of trophoblasts.

CONCLUSION: This study indicated that ASOs that decrease LncNR_040117 expression can reduce apoptosis and enhance the invasion and migration of trophoblasts by regulating the MAPK pathway.

PMID:37080915 | DOI:10.1080/14767058.2023.2183083

Ann Lab Med. 2023 Sep 1;43(5):425-433. doi: 10.3343/alm.2023.43.5.425.

ABSTRACT

BACKGROUND: To ensure valid results of big data research in the medical field, the input laboratory results need to be of high quality. We aimed to establish a strategy for evaluating the quality of laboratory results suitable for big data research.

METHODS: We used Korean Association of External Quality Assessment Service (KEQAS) data to retrospectively review multicenter data. Seven measurands were analyzed using commutable materials: HbA1c, creatinine (Cr), total cholesterol (TC), triglyceride (TG), alpha-fetoprotein (AFP), prostate-specific antigen (PSA), and cardiac troponin I (cTnI). These were classified into three groups based on their standardization or harmonization status. HbA1c, Cr, TC, TG, and AFP were analyzed with respect to peer group values. PSA and cTnI were analyzed in separate peer groups according to the calibrator type and manufacturer, respectively. The acceptance rate and absolute percentage bias at the medical decision level were calculated based on biological variation criteria.

RESULTS: The acceptance rate (22.5%-100%) varied greatly among the test items, and the mean percentage biases were 0.6%-5.6%, 1.0%-9.6%, and 1.6%-11.3% for all items that satisfied optimum, desirable, and minimum criteria, respectively.

CONCLUSIONS: The acceptance rate of participants and their external quality assessment (EQA) results exhibited statistically significant differences according to the quality grade for each criterion. Even when they passed the EQA standards, the test results did not guarantee the quality requirements for big data. We suggest that the KEQAS classification can serve as a guide for building big data.

PMID:37080743 | DOI:10.3343/alm.2023.43.5.425

Ann Lab Med. 2023 Sep 1;43(5):408-417. doi: 10.3343/alm.2023.43.5.408.

ABSTRACT

Functional reference limits describe key changes in the physiological relationship between a pair of physiologically related components. Statistically, this can be represented by a significant change in the curvature of a mathematical function or curve (e.g., an observed plateau). The point at which the statistical relationship changes significantly is the point of curvature inflection and can be mathematically modeled from the relationship between the interrelated biomarkers. Conceptually, they reside between reference intervals, which describe the statistical boundaries of a single biomarker within the reference population, and clinical decision limits that are often linked to the risk of morbidity or mortality and set as thresholds. Functional reference limits provide important physiological and pathophysiological insights that can aid laboratory result interpretation. Laboratory professionals are in a unique position to harness data from laboratory information systems to derive clinically relevant values. Increasing research on and reporting of functional reference limits in the literature will enhance their contribution to laboratory medicine and widen the evidence base used in clinical decision limits, which are currently almost exclusively contributed to by clinical trials. Their inclusion in laboratory reports will enhance the intellectual value of laboratory professionals in clinical care beyond the statistical boundaries of a healthy reference population and pave the way to them being considered in shaping clinical decision limits. This review provides an overview of the concepts related to functional reference limits, clinical examples of their use, and the impetus to include them in laboratory reports.

PMID:37080741 | DOI:10.3343/alm.2023.43.5.408

Hepatology. 2023 Apr 24. doi: 10.1097/HEP.0000000000000417. Online ahead of print.

ABSTRACT

BACKGROUND AIMS: The presence of at-risk nonalcoholic steatohepatitis (NASH) is associated with an increased risk of cirrhosis and complications. Therefore, noninvasive identification of at-risk NASH with an accurate biomarker is a critical need for pharmacologic therapy. We aim to explore the performance of several magnetic resonance (MR)-based imaging parameters in diagnosing at-risk NASH.

APPROACH RESULTS: This prospective clinical trial (NCT02565446) includes 104 paired MR exams and liver biopsies performed in patients with suspected or diagnosed nonalcoholic fatty liver disease. MR Elastography (MRE)-assessed liver stiffness (LS), 6-point Dixon-derived proton density fat fraction (PDFF), single-point saturation-recovery acquisition-calculated T1 relaxation time were explored. Among all predictors, LS showed the significantly highest accuracy in diagnosing at-risk NASH (AUCLS: 0.89 [0.82, 0.95], AUCPDFF: 0.70 [0.58, 0.81], AUCT1: 0.72 [0.61, 0.82], z-score test z > 1.96 for LS vs. any of others). The optimal cut-off value of LS to identify at-risk NASH patients was 3.3kPa (sensitivity 79%, specificity 82%, NPV 91%), while the optimal cut-off value of T1 was 850ms (sensitivity 75%, specificity 63%, and NPV 87%). PDFF had the highest performance in diagnosing NASH with any fibrosis stage (AUCPDFF: 0.82 [0.72, 0.91], AUCLS: 0.73 [0.63, 0.84], AUCT1: 0.72 [0.61, 0.83], |z| < 1.96 for all).

CONCLUSIONS: MRE-assessed liver stiffness alone outperformed PDFF, and T1 in identifying patients with at-risk NASH for therapeutic trials.

PMID:37080558 | DOI:10.1097/HEP.0000000000000417

Microbiome. 2023 Apr 21;11(1):83. doi: 10.1186/s40168-023-01523-z.

ABSTRACT

BACKGROUND: Microbial interactions are fundamental for Earth’s ecosystem functioning and biogeochemical cycling. Nevertheless, they are challenging to identify and remain barely known. Omics-based censuses are helpful in predicting microbial interactions through the statistical inference of single (static) association networks. Yet, microbial interactions are dynamic and we have limited knowledge of how they change over time. Here, we investigate the dynamics of microbial associations in a 10-year marine time series in the Mediterranean Sea using an approach inferring a time-resolved (temporal) network from a single static network.

RESULTS: A single static network including microbial eukaryotes and bacteria was built using metabarcoding data derived from 120 monthly samples. For the decade, we aimed to identify persistent, seasonal, and temporary microbial associations by determining a temporal network that captures the interactome of each individual sample. We found that the temporal network appears to follow an annual cycle, collapsing, and reassembling when transiting between colder and warmer waters. We observed higher association repeatability in colder than in warmer months. Only 16 associations could be validated using observations reported in literature, underlining our knowledge gap in marine microbial ecological interactions.

CONCLUSIONS: Our results indicate that marine microbial associations follow recurrent temporal dynamics in temperate zones, which need to be accounted for to better understand the functioning of the ocean microbiome. The constructed marine temporal network may serve as a resource for testing season-specific microbial interaction hypotheses. The applied approach can be transferred to microbiome studies in other ecosystems. Video Abstract.

PMID:37081491 | DOI:10.1186/s40168-023-01523-z