Category: Statistics

J Appl Lab Med. 2025 Jan 3;10(1):48-58. doi: 10.1093/jalm/jfae123.

ABSTRACT

BACKGROUND: In prolactinoma diagnosis, current guidelines recommend prolactin (PRL) assessment, considering values exceeding 200 ng/mL highly suggestive of prolactinoma. However, subtler hyperprolactinemia is more common, and to rule out potential prolactinomas, pituitary resonance magnetic imaging (MRI) studies are necessary. These present limitations in terms of availability, costs, and delays in diagnosis. We aimed to evaluate the screening utility of the metoclopramide (MCP) test in identifying patients with moderate hyperprolactinemia for whom MRI studies might be unnecessary.

METHODS: We retrospectively selected patients with moderate hyperprolactinemia, with an MCP test and a pituitary MRI within the same assistance, and with no interfering pharmacological treatment. Increases in PRL (ΔPRLMax) and thyrotropin (ΔTSHMax) after MCP infusion were compared according to MRI findings: patients with microadenoma (<10 mm; n = 23), with macroadenoma (≥10 mm; n = 5), or without adenoma (n = 39).

RESULTS: ΔPRLMax exceeds baseline PRL capability to identify patients with an adenoma (area under the curve = 0.872 vs 0.776). ΔPRLMax below 220% identifies 100% of these patients with 71% of specificity. This screening would have avoided 42% of MRI, resulting in a cost savings of 34%. Analysis of ΔTSHMax only slightly increased specificity when considered as a secondary criterion. Test duration can be shortened to 30 min without compromising its screening capability.

CONCLUSIONS: A short MCP test is a useful and cost-effective screening tool to avoid unnecessary MRI. Its simplicity allows its performance in almost any clinical facility to easily rule out prolactinoma in an important percentage of patients, something of upmost importance especially in regions where MRI facilities or their access are limited.

PMID:39749449 | DOI:10.1093/jalm/jfae123

J Appl Lab Med. 2025 Jan 3;10(1):148-161. doi: 10.1093/jalm/jfae135.

ABSTRACT

BACKGROUND: As clinical laboratories struggle to maintain their financial footing and as patients face mounting out-of-pocket expenses for diagnostic testing, being able to perform financial analysis of laboratory stewardship efforts has become an increasingly important skill.

CONTENT: Understanding the revenue cycle as it relates to diagnostic testing is fundamental to selecting, designing, implementing, and evaluating laboratory stewardship interventions for maximum financial return. Leveraging the data and processes driving the revenue cycle can inform informatics-based interventions (such as clinical decision support) and allow deliberate financial analyses of stewardship-focused projects. For labs striving not only to ensure their own financial health but also to help their patients avoid financial toxicity, the most effective strategies often depend on developing productive partnerships with key players along the revenue cycle.

SUMMARY: Financial laboratory analytics is an emerging skill set that can power laboratory stewardship efforts and whose benefits accrue to patients, clinicians, laboratories, and health systems.

PMID:39749448 | DOI:10.1093/jalm/jfae135

J Appl Lab Med. 2025 Jan 3;10(1):184-191. doi: 10.1093/jalm/jfae126.

ABSTRACT

BACKGROUND: Laboratory stewardship programs are increasingly adopted to enhance test utilization and improve patient care. Despite their potential, implementation within complex healthcare systems remains challenging. Benchmarking metrics helps institutions compare their performance against peers or best practices. However, the application in laboratory stewardship is underrepresented in the literature.

METHODS: The PLUGS (Patient-centered Laboratory Utiliazation Guidance Services) Informatics Working Group developed guidelines to address common test utilization issues. Metrics were based on data that are easily retrievable and calculable. Three key benchmarks were chosen for a pilot study: the ratio of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D test orders, the ratio of thyroid-stimulating hormone (TSH) to free thyroxine (FT4) test orders, and the percentage of iron workup orders after an initial low mean corpuscular volume (MCV). Institutions analyzed their own data and we established optimal benchmarks through inter-laboratory comparisons.

RESULTS: Nine laboratories evaluated vitamin D testing, with 2 implementing stewardship interventions beforehand. A benchmark of 50:1 was established, where a higher ratio indicates intentional ordering of 1,25-dihydroxyvitamin D. Nine laboratories evaluated thyroid testing, with 3 implementing interventions. The benchmark of 3.5:1 was established, with a higher ratio suggesting judicious TSH ordering. Seven laboratories evaluated iron workups, proposing a benchmark of 50% as a starting metric. Intervention guidelines were provided for laboratories below the benchmarks to promote improvement.

CONCLUSIONS: Benchmarking metrics provide a standardized framework for assessing and enhancing test utilization practices across multiple laboratories. Continued collaboration and refinement of benchmarking methodologies is essential in maximizing the impact of laboratory stewardship programs on patient safety and resource utilization.

PMID:39749447 | DOI:10.1093/jalm/jfae126

J Appl Lab Med. 2025 Jan 3;10(1):73-78. doi: 10.1093/jalm/jfae097.

ABSTRACT

BACKGROUND: Diagnostic stewardship is the science of improving diagnostic test use. Whether electronic health record (EHR) design influences clinician diagnostic testing behavior and electronic medical record interventions can improve diagnostic stewardship outcomes are key questions. We leveraged the natural experiment of a recent change in EHR platforms to investigate if changing how 2 commonly misused tests, blood cultures for acid-fast bacilli (AFB) and fungi, are displayed affected their use.

METHODS: We performed a retrospective chart review of all AFB and fungal blood cultures at 4 hospitals with a shared EHR. The preintervention and postintervention periods were 52 and 26 weeks, respectively. The culture rate was standardized per 1000 patient-days and segmented into 2-week periods. Pre- and postintervention median rates were compared with the Wilcoxon rank sum test and further analyzed with an interrupted time series (ITS) analysis using a quasi-Poisson regression model.

RESULTS: The biweekly median AFB blood culture rate decreased by 41.6% in the postintervention period (0.46/1000 patient-days vs 0.79/1000 patient-days, P < 0.001). The median rate of fungal blood cultures decreased by 54.3% in the postintervention period (0.42/1000 patient-days vs 0.92/1000 patient-days, P < 0.001). In ITS analysis, the EHR change was associated with a level change in AFB (-31.8%, 95% CI: -54.6% to +2.6%) and fungal (-44.6%, 95% CI: -59.3% to -24.7%) blood culture use.

CONCLUSIONS: An electronic medical record design change resulted in decreased use of 2 commonly misused diagnostic tests. This highlights the impact of EHR design on clinician behavior and diagnostic stewardship programs’ potential to reduce waste.

PMID:39749440 | DOI:10.1093/jalm/jfae097

Child Care Health Dev. 2025 Jan;51(1):e70029. doi: 10.1111/cch.70029.

ABSTRACT

BACKGROUND: Malaria remains a major cause of preventable deaths among children worldwide, despite the availability of several interventions for controlling and eliminating the disease. The WHO recommended the first malaria vaccine, RTS, S/AS01 in October 2021 to immunize children in sub-Saharan Africa. In this study, we set out to evaluate the knowledge, awareness and acceptability of the malaria vaccine among mothers of under 5 in south-west Nigeria before the vaccine’s rollout in Nigeria.

METHODS: We employed a hospital-based cross-sectional study for this study. A pretested semistructured, interviewer-administered questionnaire was used to elicit information from the study participants. Data obtained were analysed using the Statistical Package for Social Sciences (SPSS version 20.0).

RESULTS: A total of 797 respondents participated in the study. Only 26.0% of the respondents were aware of the new vaccine. However, the majority (90.0%) were willing to accept the malaria vaccination and to pay for it (82.1%). The crude odds ratio reveals that the odds of awareness of the malaria vaccine were more than 5 times higher among those who have tertiary education (OR = 5.470, CI = 1.224-24.444) compared with those with primary education.

CONCLUSION: The level of awareness of the malarial vaccine is low among the caregivers of under 5 children living in south-western Nigeria. However, the willingness to accept the vaccine is high. Recruiting, training and retraining of healthcare providers and other stakeholders with the designated role of providing health education on malaria prevention and vaccines are key in ensuring the success of malaria vaccination.

PMID:39749414 | DOI:10.1111/cch.70029

Nat Genet. 2025 Jan 2. doi: 10.1038/s41588-024-01994-2. Online ahead of print.

ABSTRACT

Complex diseases often have distinct mechanisms spanning multiple tissues. We propose tissue-gene fine-mapping (TGFM), which infers the posterior inclusion probability (PIP) for each gene-tissue pair to mediate a disease locus by analyzing summary statistics and expression quantitative trait loci (eQTL) data; TGFM also assigns PIPs to non-mediated variants. TGFM accounts for co-regulation across genes and tissues and models uncertainty in cis-predicted expression models, enabling correct calibration. We applied TGFM to 45 UK Biobank diseases or traits using eQTL data from 38 Genotype-Tissue Expression (GTEx) tissues. TGFM identified an average of 147 PIP > 0.5 causal genetic elements per disease or trait, of which 11% were gene-tissue pairs. Causal gene-tissue pairs identified by TGFM reflected both known biology (for example, TPO-thyroid for hypothyroidism) and biologically plausible findings (for example, SLC20A2-artery aorta for diastolic blood pressure). Application of TGFM to single-cell eQTL data from nine cell types in peripheral blood mononuclear cells (PBMCs), analyzed jointly with GTEx tissues, identified 30 additional causal gene-PBMC cell type pairs.

PMID:39747598 | DOI:10.1038/s41588-024-01994-2

Nat Genet. 2025 Jan 2. doi: 10.1038/s41588-024-01997-z. Online ahead of print.

ABSTRACT

Profiling tumors with single-cell RNA sequencing has the potential to identify recurrent patterns of transcription variation related to cancer progression, and to produce therapeutically relevant insights. However, strong intertumor heterogeneity can obscure more subtle patterns that are shared across tumors. Here we introduce a statistical method, generalized binary covariance decomposition (GBCD), to address this problem. We show that GBCD can decompose transcriptional heterogeneity into interpretable components-including patient-specific, dataset-specific and shared components relevant to disease subtypes-and that, in the presence of strong intertumor heterogeneity, it can produce more interpretable results than existing methods. Applied to data on pancreatic ductal adenocarcinoma, GBCD produced a refined characterization of existing tumor subtypes, and identified a gene expression program prognostic of poor survival independent of tumor stage and subtype. The gene expression program is enriched for genes involved in stress responses, and suggests a role for the integrated stress response in pancreatic ductal adenocarcinoma.

PMID:39747597 | DOI:10.1038/s41588-024-01997-z

Nat Genet. 2025 Jan 2. doi: 10.1038/s41588-024-01982-6. Online ahead of print.

ABSTRACT

Complete characterization of the genetic effects on gene expression is needed to elucidate tissue biology and the etiology of complex traits. In the present study, we analyzed 2,344 subcutaneous adipose tissue samples and identified 34,774 conditionally distinct expression quantitative trait locus (eQTL) signals at 18,476 genes. Over half of eQTL genes exhibited at least two eQTL signals. Compared with primary eQTL signals, nonprimary eQTL signals had lower effect sizes, lower minor allele frequencies and less promoter enrichment; they corresponded to genes with higher heritability and higher tolerance for loss of function. Colocalization of eQTLs with genome-wide association study (GWAS) signals for 28 cardiometabolic traits identified 1,835 genes. Inclusion of nonprimary eQTL signals increased discovery of colocalized GWAS-eQTL signals by 46%. Furthermore, 21 genes with ≥2 colocalized GWAS-eQTL signals showed a mediating gene dosage effect on the GWAS trait. Thus, expanded eQTL identification reveals more mechanisms underlying complex traits and improves understanding of the complexity of gene expression regulation.

PMID:39747594 | DOI:10.1038/s41588-024-01982-6

Eur Radiol. 2025 Jan 2. doi: 10.1007/s00330-024-11325-y. Online ahead of print.

NO ABSTRACT

PMID:39747591 | DOI:10.1007/s00330-024-11325-y

Eur Radiol. 2025 Jan 2. doi: 10.1007/s00330-024-11298-y. Online ahead of print.

NO ABSTRACT

PMID:39747590 | DOI:10.1007/s00330-024-11298-y