Population-average mediation analysis for zero-inflated count outcomes.

Mediation analysis is an increasingly popular statistical method for explaining causal pathways to inform intervention. While methods have increased, there is still a dearth of robust mediation methods for count outcomes with excess zeroes. Current mediation methods addressing this issue are computationally intensive, biased, or challenging to interpret. To overcome these limitations, we propose a new mediation methodology for zero-inflated count outcomes using the marginalized zero-inflated Poisson (MZIP) model and the counterfactual approach to mediation. This novel work gives population-average mediation effects whose variance can be estimated rapidly via delta method. This methodology is extended to cases with exposure-mediator interactions. We apply this novel methodology to explore if diabetes diagnosis can explain BMI differences in healthcare utilization and test model performance via simulations comparing the proposed MZIP method to existing zero-inflated and Poisson methods. We find that our proposed method minimizes bias and computation time compared to alternative approaches while allowing for straight-forward interpretations.

Retrospective, multicenter analysis of the safety and effectiveness of direct oral anticoagulants for the treatment of venous thromboembolism in obesity.

BACKGROUND: Direct oral anticoagulants (DOACs) are the preferred treatment for venous thromboembolism (VTE). However, DOAC use in patients with a BMI greater than 40 kg/m2 has not been well studied despite the growing prevalence of obesity, and current literature is often underpowered. METHODS: This multicenter, retrospective, observational study evaluated patients 18 years and older who received DOACs for acute VTE treatment. Patients receiving DOACs for recurrent VTE or for failure of another agent were excluded. The primary efficacy outcome was recurrent VTE and the primary safety outcome was major bleeding within 12 months (or one month after stopping anticoagulation therapy). A propensity score analysis was performed to balance patient characteristics and evaluate the primary endpoints by BMI group. Time-to-event outcomes were analyzed using weighted Kaplan-Meier curves. RESULTS: There were 165 patients with a BMI of at least 40 kg/m2 and 320 patients with a BMI less than 40 kg/m2. The majority received apixaban (373, 77%). Recurrent VTE occurred in 5 (3.0%) and 13 (4.1%) of patients in the higher and lower BMI groups, respectively (adjusted OR: 0.66; 95% CI: 0.16-2.69). Major bleeding occurred in 5 (3.0%) and 15 (4.7%) of patients in the higher and lower BMI groups, respectively (adjusted OR: 1.19; 95% CI: 0.36-3.92). CONCLUSION: There was no significant difference in VTE recurrence or major bleeding related to BMI among patients treated with DOACs. This study showed that DOACs may be a safe and effective VTE treatment option in patients with obesity.

Causal decomposition maps: An exploratory tool for designing area-level interventions aimed at reducing health disparities.

Methods for decomposition analyses have been developed to partition between-group differences into explained and unexplained portions. In this paper, we introduce the concept of causal decomposition maps, which allow researchers to test the effect of area-level interventions on disease maps before implementation. These maps quantify the impact of interventions that aim to reduce differences in health outcomes between groups and illustrate how the disease map might change under different interventions. We adapt a new causal decomposition analysis method for the disease mapping context. Through the specification of a Bayesian hierarchical outcome model, we obtain counterfactual small area estimates of age-adjusted rates and reliable estimates of decomposition quantities. We present two formulations of the outcome model, with the second allowing for spatial interference of the intervention. Our method is utilized to determine whether the addition of gyms in different sets of rural ZIP codes could reduce any of the rural-urban difference in age-adjusted colorectal cancer incidence rates in Iowa ZIP codes.

Efficacy of Hybrid Plasma Scalpel in Reducing Blood Loss and Transfusions in Direct Anterior Total Hip Arthroplasty.

BACKGROUND: Allogeneic blood transfusions have inherent risk and direct cost in total hip arthroplasty. Anterior total hip arthroplasty has grown in popularity with increased utilization. This approach may offer an enhanced recovery but has been associated with increased blood loss. Several technologies have been developed including the Canady Hybrid Plasma Scalpel (CHPS) and Aquamantys Bipolar Sealer (BS) to decrease blood loss. METHODS: Two hundred forty-four consecutive patients undergoing anterior supine intermuscular total hip arthroplasty were separated by intraoperative cautery device (CHPS vs BS). Exclusion criteria included blood dyscrasias and contraindication to tranexamic acid. Demographic data, blood loss, transfusion requirements, and Harris Hip Scores were obtained. Differences between groups were evaluated using the Student t-test or Wilcoxon rank-sum test for continuous variables and chi-square test for categorical variables. RESULTS: There were no differences in demographic data between the groups. Patients in the CHPS group had a significantly smaller decrease in postoperative hemoglobin (-2.3 mg/dL vs -2.7 mg/dL, P < .05), estimated blood loss (240.3 mL vs 384.4 mL, P < .001), and calculated actual blood loss (1.11 L vs 2.47 L, P < .001). There were 12 transfusions in the BS group and none in CHPS group (P < .001). CONCLUSION: The use of the hybrid plasma scalpel resulted in significantly less blood loss and transfusions than the BS. Additionally, patients treated with the hybrid plasma scalpel had significantly shorter operative times and reduced hospital length of stay. The hybrid scalpel shows promise in reducing blood loss in anterior total hip arthroplasty and is a valuable tool in the multimodal approach to avoiding transfusions.

The association of manganese overexposure and neurobehavioral function is moderated by arsenic: A metal mixture analysis of children living near coal ash storage sites.

Manganese is an essential element but can be neurotoxic if overexposed. Our previous study found that a higher level of manganese in nail biomarkers from children living near coal ash storage sites was associated with poorer neurobehavioral function. Children living near this type of pollution may be exposed to other metal neurotoxicants and a better understanding of manganese in the context of multiple exposures is needed. Mixture analyses were completed using nail samples from 251 children aged 6-14 years old. These biomarkers containing metals known to impact brain functioning were investigated to test our hypothesis that a mixture of metals including manganese impacts the development of children living near coal ash sites. Nails collected from children were analyzed using ICP-MS for manganese, arsenic, cadmium, lead, and zinc based on previous research on neurotoxicity. Bayesian kernel machine regression (BKMR) was used while adjusting for age, sex, and maternal education as potential covariates. Children also completed the Behavioral Assessment Research System (BARS) to provide neurobehavioral measures of attention and processing speed as outcomes for mixture analyses. Metal mixture analyses indicated that the relationship of manganese concentration and attention and processing speed was moderated by arsenic.,. When nail biomarkers for arsenic were highest (90th percentile), manganese was associated with poorer neurobehavioral performance on the BARS, measured by CPT hit latency. At low levels of arsenic (10th percentile), there was no evidence of harmful effects from overexposure to manganese on CPT hit latency based on BKMR analysis. Previously reported effects of manganese on neurobehavioral function may be moderated by arsenic exposure. Metal exposures and behavior outcomes can be studied with mixture analyses such as BKMR to evaluate effects of simultaneous exposures on children exposed to pollution.

Application of marginalized zero-inflated models when mediators have excess zeroes.

Mediation analysis has become increasingly popular over the last decade as researchers are interested in assessing mechanistic pathways for intervention. Although available methods have increased, there are still limited options for mediation analysis with zero-inflated count variables where the distribution of response has a "cluster" of data at the zero value (i.e. distribution of number of cigarettes smoked per day, where nonsmokers cluster at zero cigarettes). The currently available methods do not obtain unbiased population average effects of mediation effects. In this paper, we propose an extension of the counterfactual approach to mediation with direct and indirect effects to scenarios where the mediator is a count variable with excess zeroes by utilizing the Marginalized Zero-Inflated Poisson Model (MZIP) for the mediator model. We derive direct and indirect effects for continuous, binary, and count outcomes, as well as adapt to allow mediator-exposure interactions. Our proposed work allows straightforward calculation of direct and indirect effects for the overall population mean values of the mediator, for scenarios in which researchers are interested in generalizing direct and indirect effects to the population. We apply this novel methodology to an application observing how alcohol consumption may explain sex differences in cholesterol and assess model performance via a simulation study comparing the proposed MZIP mediator framework to existing methods for marginal mediator effects.

Attitudes toward research and scholarly activities among medical laboratory science professionals in the United States.

BACKGROUND: Medical laboratory science (MLS) professionals play a crucial role in health care teams. However, research culture in the profession has not been well developed or studied. It is necessary to characterize attitudes toward research and scholarly activities among MLS professionals and identify ways to promote research in the profession. METHODS: A cross-sectional survey was administered through American Society for Clinical Laboratory Science channels. Survey responses were summarized using descriptive statistics, and linear regression models were constructed to identify characteristics that predicted 2 research attitudes: "valuing the role of research" and "perceived research environment" in the profession. RESULTS: Of the 116 MLS professionals in this study, 53% reported currently participating in research activities. Opinions toward research were generally positive, although many respondents were not currently conducting research. Individuals with education and research practice focuses tended to place greater value on research, and education level was a significant predictor of perceived research environment. Dedicated research time and mentorship were cited as effective ways for employers to promote research in MLS. CONCLUSION: Overall, respondents had favorable attitudes toward research in MLS, but approximately half of participants noted a lack of incentives to conduct research. This study highlights several initiatives that may be effective for promoting increased research activity among MLS professionals.

Associations between baseline cognitive status and motor outcomes after treadmill training in people with Parkinson's disease: a pilot study.

PURPOSE: To determine the effect of baseline cognition on gait outcomes after a treadmill training program for people with Parkinson's disease (PD). METHODS: This pilot clinical trial involved people with PD who were classified as having no cognitive impairment (PD-NCI) or mild cognitive impairment (PD-MCI). Baseline executive function and memory were assessed. The intervention was a 10-week gait training program (twice-weekly treadmill sessions), with structured speed and distance progression and verbal cues for gait quality. Response to intervention was assessed by gait speed measured after week 2 (short-term) and week 10 (long-term). RESULTS: Participants (n = 19; 12 PD-NCI, 7 PD-MCI) had a mean (standard deviation) age of 66.5 (6.3) years, disease duration of 8.8 (6.3) years, and MDS-UPDRS III score of 21.3 (10.7). Gait speed increased at short-term and long-term assessments. The response did not differ between PD-NCI and PD-MCI groups; however, better baseline memory performance and milder PD motor severity were independently associated with greater improvements in gait speed in unadjusted and adjusted models. CONCLUSIONS: These findings suggest that memory impairments and more severe motor involvement can influence the response to gait rehabilitation in PD and highlight the need for treatments optimized for people with greater cognitive and motor impairment.IMPLICATIONS FOR REHABILITATIONCognitive deficits in Parkinson's disease (PD) could impact motor learning and gait rehabilitation, yet little is known about the effects of cognitive impairments on the response to rehabilitation in people with PD.This study demonstrates that the response to gait rehabilitation did not differ between people with PD who had no cognitive impairment and those with mild cognitive impairment.Across all participants, better baseline memory was associated with greater improvements in gait speed.Rehabilitation professionals should be mindful of PD severity, as those with more substantial memory and motor impairments may require additional dosing or support to maximize gait training benefits.

Testing an anxiety process biomarker: Generalisation from an auditory to a visual stimulus.

We have previously reported an anxiolytic-sensitive human EEG biomarker, goal conflict specific rhythmicity (GCSR), using an auditory stop signal task (SST). Here we test if a visual SST could allow testing of GCSR in people with hearing impairments. The visual SST produced GCSR within the 4-12Hz band at the expected right frontal site, F8, but to a lesser extent than in previous auditory SSTs, possibly due to response instability. Positive GCSR appeared to be reduced by both buspirone (10mg), and triazolam (0.25mg), as previously; negative GCSR was increased. However, neuroticism, trait anxiety and Behavioural Inhibition System scores failed to show consistent positive correlations with GCSR, contrary to prediction. The visual SST generates anxiolytic-sensitive GCSR; but its limited extent and unexpected personality correlations suggest it needs further development to obtain quantitative equivalence with the auditory SST.