Tag: statistics

Pediatr Infect Dis J. 2025 Mar 7. doi: 10.1097/INF.0000000000004788. Online ahead of print.

ABSTRACT

BACKGROUND: Congenital cytomegalovirus is the leading cause of nongenetic sensorineural hearing loss. Treatment with (val)ganciclovir improves audiologic outcomes. Neutropenia is a common adverse event, but correlates that predict who will develop neutropenia have not been identified.

METHODS: Data from 3 National Institutes of Health-funded studies of intravenous ganciclovir or oral valganciclovir were evaluated. Baseline absolute neutrophil count (ANC) was defined as high (ANC >1000 cells/mm3) or low (ANC ≤1000 cells/mm3), and neutropenia was defined as ANC <800 cells/mm3. Mean 12-hour area under the curve (AUC12) ganciclovir values were analyzed as a function of degree of neutropenia using analysis of variance. AUC12 values ≥40 mgxhr/L were defined as high drug exposure and <40 mgxhr/L as low drug exposure.

RESULTS: Of 134 subjects who had AUC12 values obtained during the first week of treatment, 61 (46%) developed neutropenia <800 cells/mm3. Infants with high drug exposure developed neutropenia more rapidly than subjects with low drug exposure (median of 28 vs. 216 days; P < 0.008). Although not significant, infants with a baseline ANC ≤1000 cells/mm3 were observed to develop neutropenia more rapidly compared with those with a high baseline ANC (estimated median of 69 vs. 216 days; P = 0.22) and in greater proportions, although not statistically significant [55.6% vs. 39.3%; P = 0.21; odds ratio, 1.9 (95% CI, 0.71-5.20)].

CONCLUSIONS: High AUC12 correlated with the development of neutropenia in infants treated for symptomatic congenital cytomegalovirus disease. Low baseline ANC also may contribute to the development of neutropenia.

PMID:40073375 | DOI:10.1097/INF.0000000000004788

Am J Public Health. 2025 Apr;115(4):519-527. doi: 10.2105/AJPH.2024.307925.

ABSTRACT

Objectives. To test the association between directly observed school masking behaviors and the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in school wastewater. Methods. We randomly sampled a subset of schools participating in a translational study on the effectiveness of passive wastewater surveillance in nonresidential K‒12 settings in San Diego County. Trained observers conducted biweekly systematic observations of masking behaviors between March 2 and May 27, 2022. Results. The proportion of individuals observed masking was a significant predictor of detecting SARS-CoV-2 in school wastewater (adjusted odds ratio = 0.91; 95% confidence interval = 0.85, 0.99; P = .034). For every 10% increase in the percentage of observed individuals who were fully masked, the odds of detecting SARS-CoV-2 in school wastewater decreased by nearly 10%. Conclusions. Masking does not need to be perfect to be effective. Mask mandates are unlikely to be reimplemented in US schools, but interventions that encourage moderate increases in masking may have an important role to play in improving children’s health and decreasing the spread of COVID-19 and other respiratory diseases. (Am J Public Health. 2025;115(4):519-527. https://doi.org/10.2105/AJPH.2024.307925).

PMID:40073362 | DOI:10.2105/AJPH.2024.307925

Am J Public Health. 2025 Apr;115(4):596-604. doi: 10.2105/AJPH.2024.307940.

ABSTRACT

Dual-harm, the co-occurrence of self- and other-harm, recognizes the overlap between these outcomes of aggressive behavior and their potential shared causes. Little progress has been made in preventing and responding to dual-harm in the broader population, and it remains understudied in public health research. We posit that the scientific investigation of dual-harm would greatly benefit from the application of public health principles and methods. In this essay, we operationalize dual-harm as a public health problem and identify gaps in knowledge, addressing its conceptual and definitional issues, prevalence estimates, methodological considerations, theoretical foundations, risk factors, and prevention strategies. We also offer a series of recommendations to advance dual-harm study and challenge the notion of conflating nonfatal dual-harm with homicide-suicide as part of a continuum, arguing that they are distinct phenomena. We identify the need for epidemiological studies to characterize those engaging in dual-harm and better understand their mechanisms and outcomes, focusing on adolescence as a critical developmental period. Future studies should develop, implement, and evaluate targeted intervention and preventive efforts for individuals involved in or at risk for dual-harm. (Am J Public Health. 2025;115(4):596-604. https://doi.org/10.2105/AJPH.2024.307940).

PMID:40073361 | DOI:10.2105/AJPH.2024.307940

Am J Public Health. 2025 Apr;115(4):579-587. doi: 10.2105/AJPH.2024.307916.

ABSTRACT

Objectives. To evaluate the impact of the COVID-19 pandemic on HIV mortality rates with a focus on demographic predictors and Medicaid access. Methods. Using Wide-Ranging Online Data for Epidemiologic Research, we conducted a descriptive study comparing HIV mortality in the United States 2 years before the COVID-19 pandemic (2018-2019) and the initial 2 years of the pandemic (2020-2021), and identifying HIV mortality factors during the pandemic. Results. During the first 2 years of the pandemic, crude HIV death rates increased and then decreased marginally. COVID-19 and HIV together contributed to 11% of the HIV death rate. While African Americans had a higher HIV mortality rate, there was a slight decrease during the pandemic. Nonelderly adults in Medicaid expansion states had lower HIV mortality than those in nonexpansion states. Conclusions. Contrary to initial concerns, we found no substantial increase in HIV mortality. A slight decrease was observed with persisting racial disparities in mortality and lower mortality in states that expanded Medicaid. Public Health Implications. The study findings can inform the development of policies to address demographic disparities in HIV mortality through targeted system-level interventions for vulnerable populations, such as Medicaid expansion and Ryan White Program services. (Am J Public Health. 2025;115(4):579-587. https://doi.org/10.2105/AJPH.2024.307916).

PMID:40073359 | DOI:10.2105/AJPH.2024.307916

Health Syst Reform. 2025 Dec 31;11(1):2477941. doi: 10.1080/23288604.2025.2477941. Epub 2025 Mar 12.

ABSTRACT

Diabetes mellitus, once a rare diagnosis in precolonial and early post-colonial Nigeria, now has the highest prevalence and fatality rates in sub-Saharan Africa. This increased prevalence is attributed to rising population affluence characterized by sedentary lifestyles and higher consumption of processed and ultra-processed foods. The burden is further exacerbated by a poorly responsive healthcare system. Currently, less than 50% of affected individuals are aware of their condition. Factors such as misconceptions about the disease, a preference for unproven traditional herbal treatments, and the high cost of treatment hinder effective secondary responses. Health system challenges in diabetes management in Nigeria include inadequate implementation of existing policies and guidelines, high out-of-pocket payments, poor quality of healthcare, and limited public education about the disease. To address these issues, we recommend a policy focus on: 1) Implementing actionable policies and guidelines for diabetes prevention and care; 2) Improving the pre-paid care system to reduce out-of-pocket payments; 3) Enhancing the quality of services at all healthcare levels, with the establishment of centers of excellence for specialized diabetes management; 4) Continuing the training, retraining, motivation, and expansion of the workforce responsible for diabetes care; and 5) Health promotion and health awareness aimed at the public to address inaccurate beliefs and practices about diabetes. Addressing these multifaceted factors will help to reduce the rising incidence of diabetes in Nigeria.

PMID:40073328 | DOI:10.1080/23288604.2025.2477941

N Engl J Med. 2025 Mar 13;392(11):1089-1099. doi: 10.1056/NEJMoa2408645.

ABSTRACT

BACKGROUND: Hospital studies suggest that scrub typhus is a leading cause of severe undifferentiated fever in regions across Asia where the disease is endemic, but the population-based incidence of infection and illness has been little studied.

METHODS: We conducted a population-based cohort study to assess epidemiologic and clinical characteristics of scrub typhus in 37 villages in Tamil Nadu, India, where the disease is highly endemic. Study participants were visited every 6 to 8 weeks over a period of 2 years; a venous blood sample was obtained from those who had had fever since the last visit. A subcohort of participants underwent blood sampling to estimate the incidence of serologically confirmed Orientia tsutsugamushi infection.

RESULTS: We systematically assessed 32,279 participants from 7619 households for acute febrile illness. During 54,588 person-years of follow-up, we observed 6175 episodes of fever. A blood sample was obtained in 4474 episodes (72.5%), of which 328 (7.3%) met the clinical case definition of scrub typhus (detection of IgM against O. tsutsugamushi on enzyme-linked immunosorbent assay [ELISA] or detection of O. tsutsugamushi on polymerase-chain-reaction assay). The incidence of clinical infection was 6.0 cases per 1000 person-years (95% confidence interval [CI], 4.8 to 7.5). A total of 71 clinical cases (21.6%) resulted in hospitalization (incidence, 1.3 events per 1000 person-years; 95% CI, 1.0 to 1.7). A total of 29 clinical cases (8.8%) were severe, as indicated by the presence of organ dysfunction or adverse pregnancy outcomes (incidence, 0.5 cases per 1000 person-years; 95% CI, 0.4 to 0.8). Among 2128 participants in the subcohort who provided samples at the beginning and end of a study year, the incidence of seroconversion independent of any symptoms was 81.2 events per 1000 person-years (95% CI, 70.8 to 91.6). The incidence of clinical infection was higher in older age groups than in younger age groups and higher among female participants than among male participants. By contrast, the age-adjusted rate of severe infection was similar among male and female participants. Among 5602 participants assessed at the start of the first year of the study, the seroprevalence of IgG as assessed with ELISA was 42.8% (95% CI, 35.8 to 50.2). IgG seropositivity at the beginning of years 1 or 2 did not protect against clinical illness during the subsequent year but was associated with less severe disease than IgG seronegativity.

CONCLUSIONS: We describe the burden of scrub typhus, including the incidence of asymptomatic infection, in a region of Asia where the disease is endemic. (Funded by the U.K. Medical Research Council; ClinicalTrials.gov number, NCT04506944.).

PMID:40073309 | DOI:10.1056/NEJMoa2408645

Neurology. 2025 Apr 8;104(7):e213374. doi: 10.1212/WNL.0000000000213374. Epub 2025 Mar 12.

ABSTRACT

BACKGROUND AND OBJECTIVES: Medical clearance for return to play (RTP) after sports-related concussion is based on clinical assessment. It is unknown whether brain physiology has entirely returned to preinjury baseline at the time of clearance. In this longitudinal study, we assessed whether concussed individuals show functional and structural MRI brain changes relative to preinjury levels that persist beyond medical clearance. Secondary objectives were to test whether postconcussion changes exceed uninjured brain variability and to correlate MRI findings with clinical recovery time.

METHODS: For this prospective observational study, healthy athletes without a history of psychiatric, neurologic, or sensory-motor conditions were recruited from a single university sport medicine clinic. Clinical and MRI data were collected at preseason baseline, and those who were later concussed were reassessed at 1-7 days after injury, RTP, 1-3 months after RTP, and 1 year after RTP. A demographically matched control cohort of uninjured athletes was also reassessed at their subsequent preseason baseline. Primary outcomes were postconcussion changes in MRI measures of cerebral blood flow (CBF), white matter mean diffusivity (MD), and fractional anisotropy (FA), evaluated using mixed models. Secondary outcomes were group differences in MRI change scores and correlations of change scores with days to RTP.

RESULTS: Of the 187 athletes enrolled in the study, 25 had concussion with follow-up imaging (20.3 ± 1.5 years, 56% male, 44% female) and were compared with 27 controls (19.7 ± 1.8 years, 44% male, 56% female). Concussed athletes showed statistically significant changes from baseline, including decreased frontoinsular CBF (mean and 95% CI -8.97 [-12.80, -5.01] mL/100 g/minute, z = -4.53), along with increased MD (1.94 × 10^-5 [1.26, 2.69] × 10^-5, z = 5.48) and reduced FA (-7.30 × 10^-3 [-9.80, -5.05] × 10^-3, z = -6.07) in the corona radiata and internal capsule. Effects persisted beyond RTP, although only CBF changes exceeded longitudinal variability in controls. For participants with longer recovery periods, significantly greater changes in medial temporal CBF were also seen (ρ = 0.64 [0.44, 0.81], z = 6.80).

DISCUSSION: This study provides direct evidence of persistent postconcussion changes in CBF and white matter at RTP and up to 1 year later. These results support incomplete recovery of brain physiology at medical clearance, with secondary analyses emphasizing the sensitivity of CBF to clinical recovery.

PMID:40073308 | DOI:10.1212/WNL.0000000000213374

Dentomaxillofac Radiol. 2025 Mar 12:twaf015. doi: 10.1093/dmfr/twaf015. Online ahead of print.

ABSTRACT

OBJECTIVE: To quantitatively and qualitatively compare directly two types of cisternography images for diagnosing trigeminal neuralgia (TN) using 3-T magnetic resonance imaging.

METHODS: This prospective study recruited 64 patients with a clinical diagnosis or suspicion of TN. Patients were examined through the three-dimensional (3D) Constructive Interference in Steady State (CISS) and Sampling Perfection with Application-optimized Contrasts using different flip angle Evolutions (SPACE) sequences. Three radiologists quantitatively measured the signal intensity of the trigeminal nerve (cranial nerve V, CN5) (SICN5), cerebrospinal fluid (CSF) (SICSF), and contrast between CN5 and CSF (Cont.). Additionally, two radiologists qualitatively evaluated the basilar artery (BA), CN5, CSF, image artefacts, and overall image quality. Statistical analyses included paired-sample t-tests, non-parametric McNemar tests, and the Friedman test (significance set at p < 0.05).

RESULTS: Mean SICN5 (p < 0.001), SICSF (p = 0.679), and Cont. (p < 0.001) were as follows: 203.08 ± 26.68, 936.03 ± 91, and 3.68 ± 0.74 in CISS; 46.80 ± 16.88, 940.61 ± 71.39, and 23.19 ± 14.52 in SPACE. Low-to-moderate CN5 and BA visibility was observed in all cases in CISS, while it was noted in one case for CN5 and in none for BA in SPACE (p < 0.001). Homogenous CSF and minor artefacts were observed in 14 cases in CISS, while it was seen in 52 cases for CN5 and 59 for BA in SPACE (p < 0.001). The overall image quality was scored as four in 57 cases in SPACE, while no cases received this score in CISS (p < 0.001).

CONCLUSIONS: SPACE provided better images than CISS for evaluating CN5 and prepontine cistern vascularity, indicating a valuable sequence for TN diagnosis.

ADVANCES IN KNOWLEDGE: This study indicates that SPACE should be selected for TN diagnosis instead of CISS sequence.

PMID:40073237 | DOI:10.1093/dmfr/twaf015

Bioinformatics. 2025 Mar 12:btaf096. doi: 10.1093/bioinformatics/btaf096. Online ahead of print.

ABSTRACT

MOTIVATION: Inferring gene networks provides insights into biological pathways and functional relationships among genes. When gene expression samples exhibit heterogeneity, they may originate from unknown subtypes, prompting the utilization of mixture Gaussian graphical model for simultaneous subclassification and gene network inference. However, this method overlooks the heterogeneity of network relationships across subtypes and does not sufficiently emphasize shared relationships. Additionally, GGM assumes data follows a multivariate Gaussian distribution, which is often not the case with zero-inflated scRNA-seq data.

RESULTS: We propose an Adaptive Joint Graphical Model (AJGM) for estimating multiple gene networks from single-cell or bulk data with unknown heterogeneity. In AJGM, an overall network is introduced to capture relationships shared by all samples. The model establishes connections between the subtype networks and the overall network through adaptive weights, enabling it to focus more effectively on gene relationships shared across all networks, thereby enhancing the accuracy of network estimation. On synthetic data, the proposed approach outperforms existing methods in terms of sample classification and network inference, particularly excelling in the identification of shared relationships. Applying this method to gene expression data from triple-negative breast cancer confirms known gene pathways and hub genes, while also revealing novel biological insights.

AVAILABILITY AND IMPLEMENTATION: The Python code and demonstrations of the proposed approaches are available at https://github.com/yyytim/AJGM, and the software is archived in Zenodo with DOI: 10.5281/zenodo.14740972.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:40073230 | DOI:10.1093/bioinformatics/btaf096

Elife. 2025 Mar 12;13:RP95802. doi: 10.7554/eLife.95802.

ABSTRACT

Fiber photometry has become a popular technique to measure neural activity in vivo, but common analysis strategies can reduce the detection of effects because they condense within-trial signals into summary measures, and discard trial-level information by averaging across-trials. We propose a novel photometry statistical framework based on functional linear mixed modeling, which enables hypothesis testing of variable effects at every trial time-point, and uses trial-level signals without averaging. This makes it possible to compare the timing and magnitude of signals across conditions while accounting for between-animal differences. Our framework produces a series of plots that illustrate covariate effect estimates and statistical significance at each trial time-point. By exploiting signal autocorrelation, our methodology yields joint 95% confidence intervals that account for inspecting effects across the entire trial and improve the detection of event-related signal changes over common multiple comparisons correction strategies. We reanalyze data from a recent study proposing a theory for the role of mesolimbic dopamine in reward learning, and show the capability of our framework to reveal significant effects obscured by standard analysis approaches. For example, our method identifies two dopamine components with distinct temporal dynamics in response to reward delivery. In simulation experiments, our methodology yields improved statistical power over common analysis approaches. Finally, we provide an open-source package and analysis guide for applying our framework.

PMID:40073228 | DOI:10.7554/eLife.95802