Likelihood Ratio Research Articles

Urinary Free Glycosaminoglycans Identify Adults at High Risk of Developing Early-stage High-grade Bladder Cancer

Background and objectiveScreening for bladder cancer (BCa) could reduce mortality via early detection of early-stage high-grade (Ta/T1 N0 M0 grade 2–3) disease. Noninvasive biomarkers could aid in screening, but current markers lack the specificity required. The urinary free glycosaminoglycan profile (GAGome) is a promising biomarker for early detection of BCa metabolism. MethodsIn a prospective case-control development study, we included patients with BCa or no evidence of disease (NED) and measured the urinary GAGome. We then developed a score to predict the probability of BCa using GAGome features that correlated with BCa versus NED according to Bayesian regression. Next, in a retrospective, population-based, case-control study, we included adults from the Lifelines Cohort Study who were presumed healthy at baseline. All cases with BCa confirmed in the cancer registry by the 2-yr or 6-yr study visit were matched to randomly selected control subjects. We developed a reference logistic regression model using age and sex to predict BCa at 7 yr after baseline. We then added the GAGome score to the model and assessed model improvement using the likelihood ratio test. We dichotomized outputs for the reference model and saturated model (reference + GAGome score) into high-risk versus low-risk categories using a 99% specificity cutoff and estimated the sensitivity for association with BCa at 7 yr. Key findings and limitationsWe prospectively included 51 individuals with BCa and 38 with NED and observed alterations in three GAGome features compatible with BCa. We developed a score that discriminated BCa with an area under the receiver operating characteristic curve of 0.77 (95% confidence interval [CI] 0.67–0.87). We retrospectively selected a cohort of 1088 presumed healthy adults (median age 48 yr, 56% females), of whom 48 had developed BCa by 7 yr after baseline (median time to diagnosis 1.4 yr). The GAGome score was an independent predictor of BCa at 7 yr when added to the reference model (p < 0.001). The sensitivity for BCa at 7 yr for high-risk subjects was 31% (95% CI 20–43%) using the saturated model and 17% (95% CI 4.7–29%) using the reference model at 99% specificity (95% CI 98–99%). Conclusions and clinical implicationsThe urinary free GAGome is specifically altered in BCa and can be used for noninvasive identification of adults at high risk of developing BCa, independent of age and sex. This information could be useful for the design of risk-stratified targeted screening programs for BCa. Patient summaryWe tested whether measurement of a class of sugars called glycosaminoglycans (GAGs) in urine could be used for early detection of bladder cancer. Our results show that GAG levels in urine can distinguish people at high risk of developing bladder cancer within 7 years, even if they are healthy at the time of the urine sampling.

Additional predictors of stroke and transient ischaemic attack in BEFAST positive patients in out-of-hours emergency primary care

Introduction In patients suspected of stroke or transient ischemic attack (TIA), rapid triaging is imperative to improve clinical outcomes. For this purpose, balance-eye-face-arm-speech-time (BEFAST) items are used in out-of-hours primary care (OHS-PC). We explored the risk of stroke and TIA among BEFAST positive patients calling to the OHS-PC, and assessed whether additional predictors could improve risk stratification. Methods This is a cross-sectional study of retrospectively gathered routine care data from telephone triage tape-recordings of patients calling the OHS-PC with neurological deficit symptoms, classified as BEFAST positive. Four models–with the predictors age, sex, a history of cardiovascular or cerebrovascular disease, and cardiovascular risk factors–were fitted using logistic regression to predict the outcome stroke or TIA. Likelihood ratio testing was used to select the best model, which was subsequently internally validated. Results The risk of stroke or TIA diagnosis was 52% among 1,289 BEFAST positive patients, median age 72 years, 56% female sex. Of patients with the outcome stroke/TIA, 24% received a low urgency allocation, while 92% had signs or symptoms when calling. Only the addition of age and sex improved predicting stroke or TIA (internally validated c-statistic 0.72, 95%CI 0.69–0.75). The predicted risk of stroke or TIA remained below 20% in those aged below 40. Females aged 70 or over and males aged 55 or over, had a predicted risk above 50%. Discussion Urgency allocation appears to be suboptimal in BEFAST positive patients calling the OHS-PC. Risk stratification could be improved in this setting by adding age and sex.

An effective and small sample-size valid confidence interval for isotonic dose-response curves by inverting a partial likelihood ratio test

A dose-response curve is essential for determining the safe dosage of a drug and is widely used in bioassay and in phase 1 clinical trials. It is generally accepted that the probability of death or the probability of dose-limiting toxicity is a non-decreasing function of the dose. This paper proposes and develops an effective point-wise confidence interval for an isotonic dose-response curve, a problem without a satisfactory solution so far. We show that one subset of the observations informs the lower limit while the other subset informs the upper limit. A partial likelihood ratio test using these subsets of observations is fully investigated. The resulting confidence interval is compared to three existing methods (Morris, Meyer, and Oron) in an extensive simulation study. The new method produces tight intervals while maintaining coverage. It is therefore preferred when maintaining an actual coverage probability is crucial as often in a regulatory environment. The new method extends to one-way ANOVA of a continuous response variable in a straightforward way. An R function is provided.

Measles—Clinical and Biological Manifestations in Adult Patients, Including a Focus on the Hepatic Involvement: Results from a Single-Center Observational Cohort Study from Romania

Background: Hepatic involvement in measles, particularly among adolescents and adults, has been recognized since 1960. This involvement typically manifests during the eruptive phase of the disease and is primarily characterized by hepatocellular dysfunction, with jaundice being a less common occurrence. Studies have reported hepatic involvement in 80–86% of measles cases among young adults associated with severe forms of the disease with intra-infectious hepatitis. Recent data from Romania indicated 20,035 confirmed measles cases between January and June 2024, including 17 fatalities and significant hepatic alterations. These findings underscore the need for the further investigation of the hepatic manifestations of measles. The primary objective of our study was to evaluate the clinical and baseline characteristics of the enrolled patients with a brief assessment of liver impairment. Methods: In light of these observations, we conducted a retrospective analysis between 1 November 2023 and 15 June 2024 in patients aged &gt;16 years who were confirmed, by the detection of measles IgM in serum samples, to have acute measles infection and hospitalization. Results: During the study period, 71 hospitalized patients were diagnosed with measles, of whom 37 were female (52.1%), with ages ranging from 16 to 64 years (mean age 34.21 years). Most cases (77.5%) exhibited moderate clinical forms of measles, while 22.5% had severe forms. Respiratory failure requiring oxygen therapy was uncommon (25.4% of severe pneumonia cases). Although a Pearson chi-square test indicated no significant association between the presence of pneumonia and clinical form (p = 0.066), the likelihood ratio test suggested a potential link (p = 0.018). Hepatic involvement was common with elevated AST (87.3%) and ALT (76%) levels. Jaundice was observed in 12.7% of patients. GGT changes were noted in 35.2% of cases, with significant correlations between GGT levels and disease severity (p = 0.001). Analysis of various symptoms revealed significant associations between nausea, dyspnea, and severe clinical forms. Anorexia, diarrhea, and nausea were the most frequently reported symptoms. Thrombocytopenia was observed in 11 patients, with no significant correlation with disease severity. Comorbidities, such as COPD, were significantly associated with disease severity (p = 0.010). Conclusions: Our findings highlight that, while cytolytic hepatic damage is a typical response to measles infection, cholestatic involvement may serve as an indicator of more severe disease progression.

Quantitative cervicovaginal fluid fetal fibronectin: A liquid biopsy for intra-amniotic inflammation.

Intra-amniotic inflammation is causally linked to spontaneous preterm labor. The gold standard for the diagnosis of intra-amniotic inflammation is the determination of an amniotic fluid profile obtained from transabdominal amniocentesis, which is invasive. Cervicovaginal fluid fetal fibronectin (fFN) is a widely-used predictive biomarker for spontaneous preterm labor. The aims of this study are to determine (1) whether a quantitative cervicovaginal fluid fFN test can be used to identify the presence of intra-amniotic inflammation; and (2) an appropriate cut-off value of a cervicovaginal fluid fFN concentration for the identification of intra-amniotic inflammation. This prospective cohort study included 78 patients with preterm labor and intact membranes who had a sample collected for quantitative cervicovaginal fluid fFN measurement and underwent transabdominal amniocentesis. Intra-amniotic inflammation was defined as an amniotic fluid interleukin-6 concentration ≥2.6 ng/mL. Clinicians were masked from the results of cervicovaginal fluid fFN and amniotic fluid interleukin-6 concentrations. Logistic regression analysis was used to determine which factors were significant predictors of intra-amniotic inflammation. The diagnostic indices of the cervicovaginal fluid fFN test for the identification of intra-amniotic inflammation were calculated. (1) Frequency of intra-amniotic inflammation was 26.9% (21/78); (2) the higher the cervicovaginal fluid fFN concentration, the greater the risk of intra-amniotic inflammation (p < 0.001); (3) cervicovaginal fluid fFN concentration ≥125 ng/mL had an area under the curve of 0.91 (95% confidence interval: 0.83-0.96) for the identification of intra-amniotic inflammation with 100% sensitivity, 100% negative predictive value, 82.46% specificity and a positive likelihood ratio of 5.7; and (4) cervicovaginal fluid fFN cut-off of 125 ng/mL had a significant higher predictive performance than the traditional cut-off (50 ng/mL) for the identification of intra-amniotic inflammation. Quantitative cervicovaginal fluid fFN with a cut-off of 125 ng/mL had a high sensitivity and a negative predictive value as well as a positive likelihood ratio for the identification of intra-amniotic inflammation. Its high sensitivity and negative predictive value can be used to decrease an index of suspicion of intra-amniotic inflammation. This test may be useful as an initial assessment test to select appropriate patients for amniocentesis to determine intra-amniotic inflammation.

Asymptotic Confidence Interval, Sample Size Formulas and Comparison Test for the Agreement Intra-Class Correlation Coefficient in Inter-Rater Reliability Studies.

The agreement intra-class correlation coefficient (ICCa) is a suitable statistical index for inter-rater reliability studies. With balanced Gaussian data, we prove the explicit form of ICCa asymptotic normality (ASN), valid both with analysis of variance (ANOVA), maximum likelihood (ML), or restricted ML (REML) estimates. An asymptotic confidence interval is then derived and its performances are examined by simulation compared to the most commonly used methods, under small, moderate and large sample size designs. Then, we deduce sample size calculation formulas, for the number of subjects and observers needed, to achieve a desired confidence interval width or an acceptable ICCa value test power and give concrete examples of their use. Finally, we propose a likelihood ratio test (LRT) to compare two ICCa's from two distinct subpopulations of patients (or raters) and study by simulation its first order risk and power properties. These methods are illustrated using data from two inter-rater reliability studies, one in physiotherapy with 42 patients and 10 raters and the second in neonatology with 80 subjects and 14 raters. In conclusion, we made recommendations to employ the proposed confidence interval for medium to large samples combined with the quantification of the minimal required sample size at the planning step, or the posterior-power at the analysis step, using simple dedicated formulas. Furthermore, with sufficient sizes, the proposed LRT seems suitable to compare inter-rater reliability between two patient subpopulations. Used wisely, this proposed methods toolbox can remedy common current issues in inter-rater reliability studies.

274 Evaluation of recombinant Capripoxvirus antigens in the development of indirect enzyme linked immunosorbent assays

Abstract Capripoxvirus is a genus of DNA viruses that includes sheep pox virus, goat pox virus and lumpy skin disease virus (LSDV). These viruses are considered high consequence viruses due to the severe clinical disease leading to economic losses to production and impact on trade. The recent spread of LSDV in Europe and Asia has demonstrated the transboundary nature of LSDV. The vaccines used to control Capripoxvirus infections currently do not have the ability to differentiate infected from vaccinated animals (DIVA) and the enzyme linked immunosorbent assays (ELISA) available for detection of antibodies to Capripoxvirus infections are not ideal. Previous research has been done to evaluate different Capripoxvirus antigens using E. coli expressed antigens; however, there has been no prior evaluation of baculovirus expressed Capripoxvirus antigens for use in ELISA. The objective of the current research was to produce 6 recombinant Capripoxvirus antigens using a baculovirus expression vector system (BEVS) and to evaluate these antigens in ELISAs to test bovine, sheep, and goat serum. The sequences used to produce the recombinant antigens were based on a consensus obtained using reference genomes consisting of all three viruses within the genus. All six antigens were produced and purified in-house using BEVS followed by benchtop or FPLC purification (Figure 1). To date, the antigens have been fully validated for performance in indirect ELISA using sheep sera (Figure 2) and partially using cattle sera, with goat sera validation to follow. The ELISAs were developed and optimized using known reference sera as controls. The performance of the ELISAs developed was assessed in comparison with the only commercially available Capripoxvirus serological test. The results demonstrate that some of the antigens used for the ELISAs completely outperformed the commercial test. Several antigens were found to be useful for ELISAs to detect responses in sheep and cattle sera. The sensitivities and specificities of the different ELISAs for sheep sera ranged from 99.54% to 53.57% sensitivity and 99.54 to 94.95% specificity with likelihood ratios above 10 using receiver operating characteristic curve analysis, while the commercial kit had a 42.85% sensitivity using the same positive sheep serum panel evaluated. The development of these serological assays allows for the simultaneous evaluation of immunogenicity of Capripoxvirus antigens through the testing of serum from experimentally infected animals. This study demonstrates the proof of principle, that sensitive and specific ELISAs can be developed for Capripoxviruses.

Artificial intelligence as an initial reader for double reading in breast cancer screening: a prospective initial study of 32,822 mammograms of the Egyptian population

BackgroundAlthough artificial intelligence (AI) has potential in the field of screening of breast cancer, there are still issues. It is vital to make sure AI does not overlook cancer or cause needless recalls. The aim of this work was to investigate the effectiveness of indulging AI in combination with one radiologist in the routine double reading of mammography for breast cancer screening. The study prospectively analyzed 32,822 screening mammograms. Reading was performed in a blind-paired style by (i) two radiologists and (ii) one radiologist paired with AI. A heatmap and abnormality scoring percentage were provided by AI for abnormalities detected on mammograms. Negative mammograms and benign-looking lesions that were not biopsied were confirmed by a 2-year follow-up.ResultsDouble reading by the radiologist and AI detected 1324 cancers (6.4%); on the other side, reading by two radiologists revealed 1293 cancers (6.2%) and presented a relative proportion of 1·02 (p < 0·0001). At the recall stage, suspicion and biopsy recommendation were more presented by the AI plus one radiologist combination than by the two radiologists. The interpretation of the mammogram by AI plus only one radiologist showed a sensitivity of 94.03%, a specificity of 99.75%, a positive predictive value of 96.571%, a negative predictive value of 99.567%, and an accuracy of 99.369% (from 99.252 to 99.472%). The positive likelihood ratio was 387.260, negative likelihood ratio was 0.060, and AUC “area under the curve” was 0.969 (0.967–0.971).ConclusionsAI could be used as an initial reader for the evaluation of screening mammography in routine workflow. Implementation of AI enhanced the opportunity to reduce false negative cases and supported the decision to recall or biopsy.

Subarachnoid haemorrhage in the emergency department (SHED): a prospective, observational, multicentre cohort study

BackgroundPeople presenting to the ED with acute severe headache often undergo investigation to exclude subarachnoid haemorrhage (SAH). International guidelines propose that brain imaging within 6 hours of headache onset can...

Accuracy and reliability of the Ipswich touch test in identifying loss of protective sensation among diabetic patients

ObjectiveTo evaluate the accuracy of the Ipswich touch test compared to the 10-g monofilament test for identifying of loss of protective sensation in Thai patients with diabetes mellitus. MethodsA cross-sectional observational study was conducted on Thai patients with diabetes mellitus who attended routine annual foot check-ups in an outpatient diabetes clinic. The loss of protective sensation was assessed by the Ipswich touch test and compared with the Semmes-Weinstein 10-g monofilament test. Sensitivity, specificity, predictive values and likelihood ratios were calculated to measure the accuracy of the Ipswich touch test against 10-g monofilament as a reference standard. The interrater reliability of the Ipswich touch test was assessed by two raters. ResultsIn a study of 283 diabetic patients, 10-g monofilament detected a 25 % prevalence of loss protective sensation. The Ipswich touch test demonstrated a good diagnostic accuracy, with a sensitivity of 70.8 %, specificity of 98.6 %, and an area under the curve of 0.85 when compared to 10-g monofilament. Positive and negative predictive values were 94.4 % and 90.8 % respectively. The positive likelihood ratio was 49.82, and the negative likelihood ratio was 0.30. Interrater reliability, assessed with two raters in a subset of 93 participants, yielded a kappa of 0.88, indicating almost perfect agreement. ConclusionsThe Ipswich Touch Test demonstrated good accuracy and interrater reliability compared to the standard 10-g monofilament, thus establishing its effectiveness as a valuable diagnostic tool for identifying loss of protective sensation among diabetic patients. However, its relatively low sensitivity suggests it should be used with caution as a screening tool.

Exploring the influencing factors of scrub typhus in Gannan region, China, based on spatial regression modelling and geographical detector

Scrub typhus is a significant public health issue with a wide distribution and is influenced by various determinants. However, in order to effectively eradicate scrub typhus, it is crucial to identify the specific factors that contribute to its incidence at a detailed level. Therefore, the objective of our study is to identify these influencing factors, examine the spatial variations in incidence, and analyze the interplay of two factors on scrub typhus incidence, so as to provide valuable experience for the prevention and treatment of scrub typhus in Gannan and to alleviate the economic burden of the local population.This study employed spatial autocorrelation analyses to examine the dependent variable and ordinary least squares model residuals. Additionally, spatial regression modelling and geographical detector were used to analyze the factors influencing the annual mean 14-year incidence of scrub typhus in the streets/townships of Gannan region from 2008 to 2021. The results of spatial1 autocorrelation analyses indicated the presence of spatial correlation. Among the global spatial regression models, the spatial lag model was found to be the best fitting model (log likelihood ratio = −319.3029, AIC = 666.6059). The results from the SLM analysis indicated that DEM, mean temperature, and mean wind speed were the primary factors influencing the occurrence of scrub typhus. For the local spatial regression models, the multiscale geographically weighted regression was determined to be the best fitting model (adjusted R2 = 0.443, AICc = 726.489). Further analysis using the MGWR model revealed that DEM had a greater impact in Xinfeng and Longnan, while the southern region was found to be more susceptible to scrub typhus due to mean wind speed. The geographical detector results revealed that the incidence of scrub typhus was primarily influenced by annual average normalized difference vegetation index. Additionally, the interaction between GDP and the percentage of grassland area had a significant impact on the incidence of scrub typhus (q = 0.357). This study illustrated the individual and interactive effects of natural environmental factors and socio-economic factors on the incidence of scrub typhus; and elucidated the specific factors affecting the incidence of scrub typhus in various streets/townships. The findings of this study can be used to develop effective interventions for the prevention and control of scrub typhus.

Evaluation of MRI proton density fat fraction in hepatic steatosis: a systematic review and meta-analysis.

Amidst the global rise of metabolic dysfunction-associated steatotic liver disease (MASLD), driven by increasing obesity rates, there is a pressing need for precise, non-invasive diagnostic tools. Our research aims to validate MRI Proton Density Fat Fraction (MRI-PDFF) utility, compared to liver biopsy, in grading hepatic steatosis in MASLD. A systematic search was conducted across Embase, PubMed/Medline, Scopus, and Web of Science until January 13, 2024, selecting studies that compare MRI-PDFF with liver biopsy for hepatic steatosis grading, defined as grades 0 (< 5% steatosis), 1 (5-33% steatosis), 2 (34-66% steatosis), and 3 (> 66% steatosis). Twenty-two studies with 2844 patients were included. The analysis showed high accuracy of MRI-PDFF with AUCs of 0.97 (95% CI = 0.96-0.98) for grade 0 vs ≥ 1, 0.91 (95% CI = 0.88-0.93) for ≤ 1 vs ≥ 2, and 0.91 (95% CI = 0.88-0.93) for ≤ 2 vs 3, diagnostic odds ratio (DOR) from 98.74 (95% CI = 58.61-166.33) to 23.36 (95% CI = 13.76-39.68), sensitivity and specificity from 0.93 (95% CI = 0.88-0.96) to 0.76 (95% CI = 0.63-0.85) and 0.93 (95% CI = 0.88-0.96) to 0.89 (95% CI = 0.84-0.93), respectively. Likelihood ratio (LR) + ranged from 13.3 (95% CI = 7.4-24.0) to 7.2 (95% CI = 4.9-10.5), and LR - from 0.08 (95% CI = 0.05-0.13) to 0.27 (95% CI = 0.17-0.42). The proposed MRI-PDFF threshold of 5.7% for liver fat content emerges as a potential cut-off for the discrimination between grade 0 vs ≥ 1 (p = 0.075). MRI-PDFF is a precise non-invasive technique for diagnosing and grading hepatic steatosis, warranting further studies to establish its diagnostic thresholds. This study underscores the high diagnostic accuracy of MRI-PDFF for distinguishing between various grades of hepatic steatosis for early detection and management of MASLD, though further research is necessary for broader application. MRI-PDFF offers precision in diagnosing and monitoring hepatic steatosis. The diagnostic accuracy of MRI-PDFF decreases as the grade of hepatic steatosis advances. A 5.7% MRI-PDFF threshold differentiates steatotic from non-steatotic livers.

Diagnostic Accuracy of Magnetic Resonance Imaging in the Diagnosis of Placenta Accreta Spectrum: A Systematic Review and Meta-analysis

Abstract Objective To evaluate the diagnostic accuracy of magnetic resonance imaging (MRI) in diagnosing placenta accreta spectrum (PAS). Methods We conducted a comprehensive literature search from database inception to November 2023 using terms such as placenta creta, increta, percreta, PAS, MRI, and their respective Medical Subject Headings terms. All prospective and retrospective cohort, case-control, and cross-sectional studies involving prenatal magnetic resonance imaging diagnosis of PAS with subsequent pathological confirmation were included. Results A total of 40 studies encompassing 3664 women met the inclusion criteria, with 1894 cases confirmed pathologically as PAS. The overall sensitivity of MRI was 0.867 (95% confidence interval, 0.807–0.910), and the specificity was 0.860 (95% confidence interval, 0.799–0.905), with a correlation of 0.693 between sensitivity and specificity. The estimated odds ratio was 28.693 (95% confidence interval (CI): 14.463–56.924), the negative likelihood ratio was 0.178 (95% CI: 0.122–0.258), and the positive likelihood ratio was 4.316 (95% CI: 3.186–5.846). Analysis of individual MRI criteria revealed estimates of sensitivity, specificity, odds ratio, negative likelihood ratio, and positive likelihood ratio for abnormal placental bed vascularization as 0.500, 0.740, 2.788, 0.571, and 1.645 respectively; 0.384, 0.985, 6.270, 0.471, and 2.720 for bladder wall interruption; 0.766, 0.818, 13.638, 0.262, and 3.375 for the presence of dark intraplacental bands; 0.691, 0.913, 10.828, 0.352, and 3.361 for heterogeneous placenta; 0.688, 0.984, 34.886, 0.254, and 7.164 for indistinctive myometrium; 0.757, 0.864, 8.496, 0.362, and 2.778 for loss of retroplacental dark zone; 0.828, 0.593, 5.829, 0.329, and 1.766 for myometrial thinning; and 0.518, 0.916, 9.473, 0.411, and 3.526 for placental bulge, respectively. Conclusion MRI demonstrates significant utility in diagnosing PAS and its severity. It is recommended for use in all cases with inconclusive ultrasonographic findings. Registration Registration number CRD42021267501

On-Demand Meal Delivery: A Markov Model for Circulating Couriers

On-demand meal delivery has become a feature of most cities around the world as a result of platforms and apps that facilitate it as well as the pandemic, which for a period, closed restaurants. Meals are delivered by couriers, typically on bikes, e-bikes, or scooters, who circulate collecting meals from kitchens and delivering them to customers, who usually order online. A Markov model for circulating couriers with n + 1 parameters, where [Formula: see text] is the number of kitchens plus customers, is derived by entropy maximization. There is one parameter for each kitchen and customer representing the demand for a courier, and there is one parameter representing the urgency of delivery. It is shown how the mean and variance of delivery time can be calculated once the parameters are known. The Markov model is irreducible. Two procedures are presented for calibrating model parameters on a data set of orders. Both procedures match known order frequencies with fitted visit probabilities; the first inputs an urgency parameter value and outputs mean delivery time, whereas the second inputs mean delivery time and outputs the corresponding urgency parameter value. Model calibration is demonstrated on a publicly available data set of meal orders from Grubhub. Grubhub data are also used to validate the calibrated model using a likelihood ratio. By changing the location of one kitchen, it is shown how the calibrated model can estimate the resulting change in demand for its meals and the corresponding mean delivery time. The Markov model could also be used for the assignment of courier trips to a street network. History: This paper has been accepted for the Transportation Science Special Issue on ISTTT Conference.

Recalibrating the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) Environmental Risk Score for Use in US Veterans.

Risk for colorectal cancer (CRC) may accumulate through multiple environmental factors. Understanding their effects, along with genetics, age and family history, could allow improvements in clinical decisions for screening protocols. We aimed to extend previous work by recalibrating an environmental risk score (e-Score) for CRC among a sample of US Veteran participants of the Million Veteran Program (MVP). Demographic, lifestyle, and CRC data from 2011-2022 were abstracted from survey responses and health records of 227,504 male MVP participants. Weighting for each environmental factor's effect size was recalculated using VA training data to create a recalibrated e-Score. This recalibrated score was compared with the original weighted e-Score in a validation sample of 113,752 (n cases=590). Nested multiple logistic regression models tested associations between quintiles for recalibrated and original e-Scores. Likelihood Ratio Tests were used to compare model performance. Age (p<0.0001), education (p<0.0001), diabetes (p<0.0001), physical activity (p<0.0001), smoking (p<0.0001), NSAID use (p<0.0001), calcium (p=0.015), folate (p=0.020), and fruit consumption (p=0.019) were significantly different between CRC case and control groups. In the validation sample, the recalibrated e-Score model significantly improved the base model performance (p<0.001), but the original e-Score model did not (p=0.07). The recalibrated e-Score model quintile 5 was associated with significantly higher odds for CRC compared with quintile 1 (Q5 vs Q1: 1.79, 95% CI: 1.38-2.33). Multiple environmental factors, and the recalibrated e-Score quintiles were significantly associated with CRC cases. A recalibrated, Veteran-specific e-Score could be used to help personalize CRC screening and prevention strategies.

Identifying homelessness using health administrative data in Ontario, Canada: how coding policies impact case validity

Conducting longitudinal research about the health of people experiencing homelessness poses unique challenges. In Canada, we previously demonstrated that identification through health administrative databases permits population-level studies, despite relatively low sensitivity. Since then, coding of homelessness became mandatory in hospitals nationally. As a result, case validity since 2018 is unknown. We re-validated case definitions for identifying homelessness in health administrative databases between 2018 and 2022 against the longitudinally collected housing history of a representative sample of people experiencing homelessness (n=640) and randomly selected, housed people (n=128,000) in Toronto, Canada. We calculated sensitivity, specificity, positive and negative predictive values, and positive likelihood ratios for 42 unique case definitions. We compared the resulting true positives against false positives and false negatives to identify potential causes of misclassification. The optimal case (best sensitivity/scalability beyond Ontario) definition included any indicator during a hospital-based encounter within 180 days of a period of homelessness (sensitivity=52.9%; specificity=99.5%). Among periods of homelessness with ≥1 hospital-based encounter, the optimal case definition had good sensitivity (75.1%) with minimal reduction in specificity (98.5%). Review of false positives suggests homeless status is sometimes improperly carried forward in healthcare encounters occurring after transitioning out of homelessness. Case definitions to identify homelessness using health administrative data exhibit moderate sensitivity and excellent specificity, with two-fold increases in sensitivity since the implementation of mandatory coding in Canada. Mandatory collection of social determinants of health information within administrative data present invaluable opportunities for advancing research on the health and healthcare needs of people experiencing homelessness.

Gender differences in the relationship between the triglyceride-glucose index and serum Klotho concentrations among the middle-aged and elderly: a cross-sectional analysis

BackgroundThe triglyceride-glucose (TyG) index is recognized as a robust indicator for evaluating insulin resistance (IR). Despite the well-documented anti-aging biological functions of Klotho protein, its correlation with the TyG index remains unexplored.MethodsA cross-sectional analysis was conducted involving participants from the National Health and Nutrition Examination Surveys (NHANES) 2007–2016. The TyG index was computed using laboratory data, while serum Klotho concentrations was determined using ELISA kit. After adjusting potential confounding variables, multivariate regression models were employed to evaluate the association between the TyG index and Klotho protein levels among middle-aged and elderly females and males separately. Additionally, smooth curve fitting and segmented regression model were applied to investigate potential threshold effects and identify the inflection point.ResultsA total of 6,573 adults qualified for inclusion, comprising 3,147 (47.88%) males and 3,426 (52.12%) females. Multivariate regression analysis revealed that females with a higher TyG index exhibited significantly lower serum Klotho concentrations (β=-83.41, 95% CI: -124.23 to -42.60, P < 0.0001). This association was not statistically significant in males (β = 15.40, 95% CI: -19.16 to 49.95, P = 0.3827). Subgroup analyses revealed a significant interaction effect by diabetes status in females (P-interaction = 0.0121), where non-diabetic females showed a stronger negative association between TyG index and serum Klotho levels compared to diabetic females. In the female group, when TyG index was divided into quartiles, individuals in the highest quartile of TyG index exhibited reduced levels of Klotho protein (Q4: -88.77 pg/ml) compared to those in the lowest quartile (Q1) after full adjustment (P = 0.0041). Segmented regression analysis indicated a turning point value of 9.4 in females. Notably, a 1-unit increase in TyG index was significantly associated with a decrease in Klotho levels by -111.43 pg/ml (95% CI: -157.34 to -65.52, P < 0.0001) when TyG index was below 9.4, while above this threshold, the association was not significant (Log likelihood ratio test: 0.009).ConclusionsThe findings highlight a non-linear correlation between the TyG index and serum Klotho concentrations among females, indicative of a saturation effect. This relationship was particularly pronounced in non-diabetic women. In contrast, no statistically significant association was observed in male participants.

Meta-analysis of the diagnostic value of functional magnetic resonance imaging for distinguishing unresponsive wakefulness syndrome/vegetative state and minimally conscious state

ObjectiveUnresponsive wakefulness syndrome/vegetative state (UWS/VS) and minimally conscious state (MCS) are considered different clinical entities, but their differential diagnosis remains challenging. As a potential clinical tool, functional magnetic resonance imaging (fMRI) could detect residual awareness without the need for the patients’ actual motor responses. This study aimed to investigate the diagnostic value of fMRI for distinguishing between UWS/VS and MCS through a meta-analysis of the existing studies.MethodsWe conducted a comprehensive search (from the database creation date to November. 2023) for relevant English articles on fMRI for the differential diagnosis of UWS/VS and MCS. The pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR−), summary receiver operating characteristic (SROC) curve, and area under the curve (AUC) were calculated to assess the diagnostic value of fMRI in distinguishing between UWS/VS and MCS. The statistical I2 test was used to assess heterogeneity, and the source of heterogeneity was investigated by performing a meta-regression analysis. Publication bias was assessed using the Deeks funnel plot asymmetry test.ResultsTen studies were included in the meta-analysis. The pooled sensitivity and specificity were 0.71 (95% CI 0.62–0.79) and 0.71 (95% CI 0.54–0.84), respectively. The fMRI for the differential diagnosis of UWS/VS and MCS has a moderate positive likelihood ratio (2.5) and a relatively low negative likelihood ratio (0.40). Additionally, SROC curves showed that the AUC was 0.76 (95% CI 0.72–0.80).ConclusionFunctional magnetic resonance imaging has a good performance in the differential diagnosis of UWS/VS and MCS, and may provide a potential tool for evaluating the prognosis and guiding the rehabilitation therapy in patients with disorders of consciousness.

The diagnostic performance of the one-step nucleic acid amplification assay for the detection of sentinel lymph node metastases in cytokeratin 19-positive breast cancer: a PRISMA-compliant meta-analysis

BackgroundThe status of the sentinel lymph nodes (SLNs) is an important prognostic factor for many different types of cancer. The one-step nucleic acid amplification (OSNA) assay has emerged as a rapid intraoperative molecular diagnostic tool for LN metastasis detection. We aimed to evaluate and summarize the value of the OSNA assay for the diagnosis of SLN metastasis in cytokeratin 19 (CK19)-positive breast cancer.MethodsTo evaluate the diagnostic value, the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled. The threshold effect, followed by subgroup analysis, was performed to explore the source of heterogeneity. A sensitivity analysis was performed to assess the stability of this meta-analysis model. Fagan plots and likelihood ratio scattergrams were used to explore the potential clinical significance.ResultsA total of 29 eligible studies, which consisted of 5,331 patients with 10,343 SLNs, were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.86 (95% CI: 0.85–0.88), 0.94 (95% CI, 0.94–0.95), 18.00 (95% CI, 13.54–23.92), 0.13 (95% CI, 0.10–0.17), and 138.99 (95% CI, 86.66–222.92), respectively. The AUC was 0.97 (95% CI, 0.95–0.98). Sensitivity analysis showed that four studies had an impact on the pooled results and mainly contributed to the heterogeneity. Fagan's nomogram revealed that the prior probability was 50%, the post-probability positive was 95%, and the post-probability negative was 11%.DiscussionOur results suggested that OSNA can predict the occurrence of SLN metastasis in CK19-positive breast cancer. However, more well-designed and multicenter diagnostic tests are needed to validate our results.

Sequential analysis of variance: Increasing efficiency of hypothesis testing.

Researchers commonly use analysis of variance (ANOVA) to statistically test results of factorial designs. Performing an a priori power analysis is crucial to ensure that the ANOVA is sufficiently powered, however, it often poses a challenge and can result in large sample sizes, especially if the expected effect size is small. Due to the high prevalence of small effect sizes in psychology, studies are frequently underpowered as it is often economically unfeasible to gather the necessary sample size for adequate Type-II error control. Here, we present a more efficient alternative to the fixed ANOVA, the so-called sequential ANOVA that we implemented in the R package "sprtt." The sequential ANOVA is based on the sequential probability ratio test (SPRT) that uses a likelihood ratio as a test statistic and controls for long-term error rates. SPRTs gather evidence for both the null and the alternative hypothesis and conclude this process when a sufficient amount of evidence has been gathered to accept one of the two hypotheses. Through simulations, we show that the sequential ANOVA is more efficient than the fixed ANOVA and reliably controls long-term error rates. Additionally, robustness analyses revealed that the sequential and fixed ANOVAs exhibit analogous properties when their underlying assumptions are violated. Taken together, our results demonstrate that the sequential ANOVA is an efficient alternative to fixed sample designs for hypothesis testing. (PsycInfo Database Record (c) 2024 APA, all rights reserved).