Tag: statistics

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

Oral Radiol. 2023 Apr 21. doi: 10.1007/s11282-023-00686-7. Online ahead of print.

ABSTRACT

OBJECTIVE: There is no known preoperative marker that can effectively predict the risk of delayed neck metastasis (DNM), which is an important factor that determines the prognosis of early-stage oral cancer. In this study, we examined whether 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)/computed tomography (CT) uptake parameters of primary cancer can predict the risk of DNM in early-stage oral squamous cell carcinoma (OSCC).

METHODS: Data from patients with stage I-II OSCC who underwent surgical resection of the primary tumor without elective neck dissection between January 2009 and December 2016 were retrospectively reviewed. Patient characteristics, histopathological factors, and PET/CT parameters (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) were evaluated for their association with DNM. DNM rates were calculated, and the parameters that were statistically significant in the univariate analysis were used as explanatory variables. Independent factors associated with DNM were identified using multivariate analysis. For all statistical analyses, p-values < 0.05 were considered statistically significant.

RESULTS: Data from 71 patients were analyzed in the study. The overall DNM rate among all patients was 21.8%. The univariate analysis showed that the T classification, depth of invasion, pattern of invasion, lymphovascular invasion, SUVmax, MTV, and TLG were significant predictors of DNM. However, the multivariate analysis revealed that only the depth of invasion, MTV, and TLG were independent predictors of DNM.

CONCLUSION: This study suggests that, in addition to conventional predictors, volume-based PET parameters are useful predictors of DNM in those with early-stage OSCC.

PMID:37081306 | DOI:10.1007/s11282-023-00686-7

Clin Drug Investig. 2023 Apr 21. doi: 10.1007/s40261-023-01263-w. Online ahead of print.

ABSTRACT

Evidence-based medicine favours randomised controlled trials to limit bias and establish the effects of a treatment with statistical rigour. However, the controlled conditions and careful patient selection of randomised trials may produce results that cannot be generalised to a more diverse patient population in clinical practice. Therefore, there is growing recognition of the importance of supplementing randomised trial data with real-world evidence. Micronised purified flavonoid fraction has been investigated in several large-scale real-world studies, including the RELIEF and DECIDE studies, each of which included more than 1000 patients with chronic venous disease. These studies demonstrated a significant reduction in the prevalence and severity of chronic venous disease symptoms, and an improvement in quality of life. The chronic VEnous dIsorders maNagement and treatment effectivenesS evaluaTion in chronic vEnous disease, an international Program (VEINSTEP) study (NCT04574375), is currently underway in more than 6000 patients with chronic venous disease in nine countries. Preliminary data from one country (Morocco) indicate that chronic venous disease drug treatment, which was micronised purified flavonoid fraction in 75.7% of patients, was associated with a statistically significantly reduction in symptoms and improved quality of life. The overall results are awaited with interest. International chronic venous disease guidelines grade the evidence for micronised purified flavonoid fraction highly, as the benefits of micronised purified flavonoid fraction have been proven in randomised clinical trials and meta-analyses. Real-world studies demonstrate that the randomised evidence for micronised purified flavonoid fraction is generalisable to a clinical practice setting. Treatment decisions in chronic venous disease should consider evidence-based recommendations, including real-world data, as well as patient goals of symptom relief, functional improvement and/or better quality of life.

PMID:37081278 | DOI:10.1007/s40261-023-01263-w

Clin Transl Oncol. 2023 Apr 21. doi: 10.1007/s12094-023-03166-w. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the value of red blood cell parameters in Myelodysplastic syndrome (MDS) diagnosis and their relations to MDS subtypes and risk groups.

METHODS: The red blood cell parameter [mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width (RDW)] levels [203 MDS, 99 aplastic anemia (AA), 145 megaloblastic anemia (MA)] were collected from a single-center retrospective cohort. The cut-off values, area under the receiver operating characteristic curve (ROC) curve (AUC), sensitivity and specificity of the four parameters were calculated from the ROC. Furthermore, Kruskal-Wallis test and Dunn’s Test were performed to determine erythrocyte parameters in different subtypes and prognostic risks MDS.

RESULTS: There are significant statistic differences in RDW (P < 0.001), MCH (P = 0.036) and MCHC (P < 0.001) (MDS vs AA); RDW (P = 0.009), MCV (P < 0.001), MCH (P < 0.001) and MCHC (P = 0.001) (MDS vs MA); MCV (P = 0.011) and MCH (P = 0.008) (higher-risk MDS vs lower-risk MDS). Between MDS and MA, the area under the receiver operating characteristic curve (ROC) curve (AUC) values of MCV, MCH, MCHC, RDW were 0.846, 0.855, 0.617, and 0.593. Between MDS and AA, the AUC values of MCH, MCHC, RDW were 0.609, 0.671, and 0.662, respectively.

CONCLUSIONS: The red blood cell parameters contribute to the differential diagnosis of MDS, AA and MA and are related to MDS subtypes and risk groups.

PMID:37081223 | DOI:10.1007/s12094-023-03166-w

Int J Colorectal Dis. 2023 Apr 21;38(1):107. doi: 10.1007/s00384-023-04399-5.

ABSTRACT

PURPOSE: If could be a potential pathophysiological connection between colonic diverticula and colonic superficial neoplastic lesions, beyond the shared risk factors, has been a subject of debate in the last years. This study tries to evaluate the association between diverticulosis and colonic neoplastic lesions.

METHODS: This is a cross-sectional study including asymptomatic patients who underwent a screening colonoscopy (patients with a positive fecal occult blood test under the regional program of colorectal cancer (CRC) screening), surveillance after polypectomy resection, or familiarity (first-degree relatives) between 2020 and 2021 to evaluate the association between diverticula and colonic polyps. A multivariate analysis with multiple logistic regression and odds ratio (OR) to study the independent association between adenomas and adenocarcinomas was performed.

RESULTS: One thousand five hundred one patients were included. A statistically significant association between adenomas or CRC alone and colonic diverticula was found (p = 0.045). On a multivariate analysis of demographic (age, gender) and clinical parameters (familiarity for diverticula and adenoma/CRC), only age was significantly associated with the development of colorectal adenomas or cancer (OR 1.05, 95% CI 1.03-1.07, p < 0.0001).

CONCLUSIONS: This study showed a statistically significant association between diverticula and colonic adenomas. However, it is impossible to establish a cause-effect relationship due to the intrinsic characteristics of this study design. A study with a prospective design including both patients with diverticulosis and without colonic diverticula aimed at establishing the incidence of adenoma and CRC could help to answer this relevant clinical question, since a potential association could indicate the need for closer endoscopic surveillance.

PMID:37081187 | DOI:10.1007/s00384-023-04399-5

Adv Rheumatol. 2023 Apr 20;63(1):16. doi: 10.1186/s42358-023-00302-6.

ABSTRACT

BACKGROUND: The prevalence of HLA-B27 gene positivity in healthy Caucasian communities varies between 8 and 14%. However, there is a lack of information in countries with a high rate of miscegenation, such as Brazil.

AIM: To estimate the frequency of HLA-B27 in the Brazilian general population using a large national registry database.

METHODS: This is a cross-sectional ecological study using the Brazilian Registry of Volunteer Bone Marrow Donors (REDOME) database on HLA-B27 allelic frequency and proportion of positives of healthy donors (18-60 years old). Data were analyzed according to sex, age, race (by self-reported skin color recommended by the Brazilian Institute of Geography and Statistics – IBGE), and geographic region of residence.

RESULTS: From 1994 to 2022, a total of 5,389,143 healthy bone marrow donors were included. The overall positivity for HLA-B27 was 4.35% (CI 95% 4.32-4.37%), regardless of sex and age (57.2% were women, mean age was 41.7yo). However, there was a difference between races: 4.85% in Whites; 2.92% in Blacks; 3.76% in Pardos (Browns i.e. mixed races); 3.95% in Amarelos (Yellows i.e. Asian Brazilians); and 3.18% in Indigenous. There was also a difference regarding geographic region of residence (North: 3.62%; Northeast: 3.63%; Southeast: 4.29%; Midwest: 4.5% and 5.25% in South). The homozygosity rate for the HLA-B27 was 1.32% of all the positives and only 0.06% in the general population.

CONCLUSIONS: Our findings provide the first Brazilian national prevalence for HLA-B27 in 4.35%. There is a gradient gene positivity from North to South, suggesting that the genetic background related to the miscegenation due to colonization, slavery, and some later waves of immigration together with internal migratory flows, could explain our findings.

PMID:37081582 | DOI:10.1186/s42358-023-00302-6

Microbiome. 2023 Apr 20;11(1):80. doi: 10.1186/s40168-023-01530-0.

ABSTRACT

BACKGROUND: Understanding human genetic influences on the gut microbiota helps elucidate the mechanisms by which genetics may influence health outcomes. Typical microbiome genome-wide association studies (GWAS) marginally assess the association between individual genetic variants and individual microbial taxa. We propose a novel approach, the covariate-adjusted kernel RV (KRV) framework, to map genetic variants associated with microbiome beta-diversity, which focuses on overall shifts in the microbiota. The KRV framework evaluates the association between genetics and microbes by comparing similarity in genetic profiles, based on groups of variants at the gene level, to similarity in microbiome profiles, based on the overall microbiome composition, across all pairs of individuals. By reducing the multiple-testing burden and capturing intrinsic structure within the genetic and microbiome data, the KRV framework has the potential of improving statistical power in microbiome GWAS.

RESULTS: We apply the covariate-adjusted KRV to the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) in a two-stage (first gene-level, then variant-level) genome-wide association analysis for gut microbiome beta-diversity. We have identified an immunity-related gene, IL23R, reported in a previous microbiome genetic association study and discovered 3 other novel genes, 2 of which are involved in immune functions or autoimmune disorders. In addition, simulation studies show that the covariate-adjusted KRV has a greater power than other microbiome GWAS methods that rely on univariate microbiome phenotypes across a range of scenarios.

CONCLUSIONS: Our findings highlight the value of the covariate-adjusted KRV as a powerful microbiome GWAS approach and support an important role of immunity-related genes in shaping the gut microbiome composition. Video Abstract.

PMID:37081571 | DOI:10.1186/s40168-023-01530-0

Int J Behav Nutr Phys Act. 2023 Apr 20;20(1):46. doi: 10.1186/s12966-023-01442-0.

ABSTRACT

BACKGROUND: Policy interventions to increase physical activity in early childhood education and care (ECEC) services are effective in increasing physical activity among young children. However, a large proportion of ECEC services do not have nor implement a physical activity policy. Play Active is an evidence-informed physical activity policy intervention with implementation support strategies to enable ECEC services to successfully implement their policy. This study examined the effectiveness, implementation, and process outcomes of Play Active.

METHODS: A pragmatic cluster randomised trial in 81 ECEC services in Perth, Western Australia was conducted in 2021. Services implemented their physical activity policy over a minimum of three months. The effectiveness outcomes were changes in educator practices related to daily time provided for total physical activity and energetic play. Implementation outcomes included changes in director- and educator-reported uptake of policy practices and director-reported uptake of high impact and low effort policy practices. Process evaluation outcomes included awareness, fidelity, reach, and acceptability of the intervention and implementation strategies. Analysis involved descriptive statistics and generalised linear mixed effects models.

RESULTS: There was a significant increase in the uptake of director-reported policy practices (p = 0.034), but no change in the uptake of the subset of high impact and low effort policy practices. Intervention group educators reported high awareness of the Play Active policy recommendations (90%). Play Active acceptability was high among educators (83%) and directors (78%). Fidelity and reach were high for most implementation support strategies (> 75%). There were no significant changes in the amount of physical activity or energetic play educators provided to children or in the proportion of educators providing the policy recommended ≥ 180 min of physical activity/day or ≥ 30 min of energetic play/day for intervention compared to wait-listed comparison services.

CONCLUSIONS: Play Active resulted in significantly higher uptake of physical activity practices. However, there was no change in the amount of physical activity provided to children, which may be explained by the relatively short policy implementation period. Importantly, Play Active had high awareness, fidelity, reach, and acceptability. Future research should investigate the effectiveness of Play Active over longer implementation periods and its scalability potential.

TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (reference number 12620001206910, registered 13/11/2020, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378304&isReview=true ).

PMID:37081560 | DOI:10.1186/s12966-023-01442-0