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BMC Medical Research Methodology Nov 2021The natural indirect effect (NIE) and mediation proportion (MP) are two measures of primary interest in mediation analysis. The standard approach for mediation analysis...
BACKGROUND
The natural indirect effect (NIE) and mediation proportion (MP) are two measures of primary interest in mediation analysis. The standard approach for mediation analysis is through the product method, which involves a model for the outcome conditional on the mediator and exposure and another model describing the exposure-mediator relationship. The purpose of this article is to comprehensively develop and investigate the finite-sample performance of NIE and MP estimators via the product method.
METHODS
With four common data types with a continuous/binary outcome and a continuous/binary mediator, we propose closed-form interval estimators for NIE and MP via the theory of multivariate delta method, and evaluate its empirical performance relative to the bootstrap approach. In addition, we have observed that the rare outcome assumption is frequently invoked to approximate the NIE and MP with a binary outcome, although this approximation may lead to non-negligible bias when the outcome is common. We therefore introduce the exact expressions for NIE and MP with a binary outcome without the rare outcome assumption and compare its performance with the approximate estimators.
RESULTS
Simulation studies suggest that the proposed interval estimator provides satisfactory coverage when the sample size ≥500 for the scenarios with a continuous outcome and sample size ≥20,000 and number of cases ≥500 for the scenarios with a binary outcome. In the binary outcome scenarios, the approximate estimators based on the rare outcome assumption worked well when outcome prevalence less than 5% but could lead to substantial bias when the outcome is common; in contrast, the exact estimators always perform well under all outcome prevalences considered.
CONCLUSIONS
Under samples sizes commonly encountered in epidemiology and public health research, the proposed interval estimator is valid for constructing confidence interval. For a binary outcome, the exact estimator without the rare outcome assumption is more robust and stable to estimate NIE and MP. An R package mediateP is developed to implement the methods for point and variance estimation discussed in this paper.
Topics: Bias; Computer Simulation; Humans; Models, Statistical; Research Design; Sample Size
PubMed: 34800985
DOI: 10.1186/s12874-021-01425-4 -
BMJ Open Oct 2023Exposure of pregnant women and newborns to secondhand smoke (SHS) can lead to adverse maternal and neonatal health outcomes. Among expectant and new fathers, who are the...
INTRODUCTION
Exposure of pregnant women and newborns to secondhand smoke (SHS) can lead to adverse maternal and neonatal health outcomes. Among expectant and new fathers, who are the main source of SHS exposure for pregnant women, new mothers and babies, smoking rates remain high. A partner's pregnancy potentially constitutes a critical period where expectant and new fathers are motivated to quit smoking. However, there is no consensus on the optimal form and delivery of smoking cessation and relapse-prevention interventions. We present a systematic review and network meta-analysis protocol that aims to synthesise and evaluate the effectiveness of smoking cessation and relapse-prevention interventions tailored for this population.
METHODS AND ANALYSIS
To identify relevant studies, we will conduct a comprehensive search, in English and Chinese, of 10 electronic databases. The review will include randomised and quasi-randomised controlled trials that compare behavioural interventions (tailored and non-tailored) with/without the addition of pharmacotherapy with usual care, a minimal or placebo control for assisting expectant and new fathers to quit smoking and prevent smoking relapse. The primary outcome of interest is the self-reported and/or biochemically verified smoking abstinence at ≥1-month follow-up. Two reviewers will independently screen, select and extract relevant studies, and perform a quality assessment. Disagreements will be resolved by a consensus or third-party adjudication. The Cochrane Risk of Bias tool V.2 will be used to assess the risk of bias in the included studies. We will obtain the results of the systematic review through pooled quantitative analyses using a network meta-analysis. Sensitivity and subgroup analyses will be performed.
ETHICS AND DISSEMINATION
Ethical approval is not required for this systematic review of published data. The findings will be disseminated via peer-reviewed publication.
PROSPERO REGISTRATION NUMBER
CRD42022340617.
Topics: Humans; Female; Infant, Newborn; Pregnancy; Male; Smoking Cessation; Network Meta-Analysis; Systematic Reviews as Topic; Pregnant Women; Fathers; Meta-Analysis as Topic
PubMed: 37802607
DOI: 10.1136/bmjopen-2023-071745 -
Current Opinion in Organ Transplantation Apr 2023Combined heart and liver transplantation (CHLT) is an uncommon but increasingly performed procedure with rising need as the population who has undergone Fontan... (Review)
Review
PURPOSE OF REVIEW
Combined heart and liver transplantation (CHLT) is an uncommon but increasingly performed procedure with rising need as the population who has undergone Fontan palliation for single ventricle physiology grows. This article reviews the current literature to summarize what is known about patient selection and outcomes and highlights the questions that remain.
RECENT FINDINGS
Congenital heart disease (CHD) with Fontan-associated liver disease (FALD) has surpassed noncongenital heart disease as the most common indication for CHLT. In patients with failing Fontan physiology, accurate assessment of recoverability of liver injury remains challenging and requires multifaceted evaluation to determine who would benefit from isolated versus dual organ transplantation. Patient survival has improved over time without significant differences between those with and without a diagnosis of CHD. En bloc surgical technique and best use of intraoperative mechanical circulatory support are topics of interest as the field continues to evolve.
SUMMARY
A more refined understanding of appropriate patient selection and indication-specific outcomes will develop as we gain more experience with this complex operation and perform prospective, randomized studies.
Topics: Humans; Liver Transplantation; Patient Selection; Prospective Studies; Heart Transplantation; Heart Defects, Congenital; Retrospective Studies
PubMed: 36454232
DOI: 10.1097/MOT.0000000000001041 -
Journal of the American College of... Dec 2020Emergency physicians must maintain procedural skills, but clinical opportunities may be insufficient. We sought to determine how often practicing emergency physicians in...
BACKGROUND
Emergency physicians must maintain procedural skills, but clinical opportunities may be insufficient. We sought to determine how often practicing emergency physicians in academic, community and freestanding emergency departments (EDs) perform 4 procedures: central venous catheterization (CVC), tube thoracostomy, tracheal intubation, and lumbar puncture (LP).
METHODS
This was a retrospective study evaluating emergency physician procedural performance over a 12-month period. We collected data from the electronic records of 18 EDs in one healthcare system. The study EDs included higher and lower volume, academic, community and freestanding, and trauma and non-trauma centers. The main outcome measures were median number of procedures performed. We examined differences in procedural performance by physician years in practice, facility type, and trauma status.
RESULTS
Over 12 months, 182 emergency physicians performed 1582 of 2805 procedures (56%) and supervised (resident, nurse practitioner or physician assistant) an additional 1223 of the procedures they did not perform (43%). Median (interquartile range) physician performance for each procedure was CVC 0 [0, 2], tube thoracostomy 0 [0, 0], tracheal intubation 3 [0.25, 8], and LP 0 [0, 2]. The percentage of emergency physicians who did not perform at least one of each procedure during the 1-year time frame ranged from 25.3% (tracheal intubation) to 76.4% (tube thoracostomy). Physicians who work at high-volume EDs (>50,000 visits per year) performed nearly twice as many tracheal intubations, CVCs, and LPs than those at low-volume EDs or freestanding EDs when normalized per 1000 visits. Years out of training were inversely related to total number of procedures performed. Emergency physicians at trauma centers performed almost 3 times as many tracheal intubations and almost 4 times as many CVCs compared to non-trauma centers.
CONCLUSION
In a large healthcare system, regardless of ED type, emergency physicians infrequently performed the 4 procedures studied. Physicians in high-volume EDs, trauma centers, and recent graduates performed more procedures. Our study adds to a growing body of research that suggests clinical frequency alone may be insufficient for all emergency physicians to maintain competency.
PubMed: 33392575
DOI: 10.1002/emp2.12238 -
PloS One 2023Various methods are available to determine optimal cutpoints for diagnostic measures. Unfortunately, many authors fail to report the precision at which these optimal...
Various methods are available to determine optimal cutpoints for diagnostic measures. Unfortunately, many authors fail to report the precision at which these optimal cutpoints are being estimated and use sample sizes that are not suitable to achieve an adequate precision. The aim of the present study is to evaluate methods to estimate the variance of cutpoint estimations based on published descriptive statistics ('post-hoc') and to discuss sample size planning for estimating cutpoints. We performed a simulation study using widely-used methods to optimize the Youden index (empirical, normal, and transformed normal method) and three methods to determine confidence intervals (the delta method, the parametric bootstrap, and the nonparametric bootstrap). We found that both the delta method and the parametric bootstrap are suitable for post-hoc calculation of confidence intervals, depending on the sample size, the distribution of marker values, and the correctness of model assumptions. On average, the parametric bootstrap in combination with normal-theory-based cutpoint estimation has the best coverage. The delta method performs very well for normally distributed data, except in small samples, and is computationally more efficient. Obviously, not every combination of distributions, cutpoint optimization methods, and optimized metrics can be simulated and a lot of the literature is concerned specifically with cutpoints and confidence intervals for the Youden index. This complicates sample size planning for studies that estimate optimal cutpoints. As a practical tool, we introduce a web-application that allows for running simulations of width and coverage of confidence intervals using the percentile bootstrap with various distributions and cutpoint optimization methods.
Topics: Sample Size; Confidence Intervals; Computer Simulation; Software
PubMed: 36595525
DOI: 10.1371/journal.pone.0279693 -
Cureus Dec 2022Background Knowing the predicting factors for difficult neuraxial blocks might help better plan the procedure. This study aimed to determine the predictors of failed...
Background Knowing the predicting factors for difficult neuraxial blocks might help better plan the procedure. This study aimed to determine the predictors of failed spinal arachnoid puncture procedures using artificial neural network (ANN) analysis. Methodology With approvals, prospectively collected data from 300 spinal arachnoid punctures in the operation theater of an academic institute having postgraduate anesthesia training were retrospectively evaluated. Fifteen variables from anthropo-demographic, spinal surface anatomy, procedure, and performers' experiences were fed as input for the ANN. A failed spinal arachnoid puncture procedure was defined as the requirement of more than three punctures, with three punctures but more than six passes, or if the performer handed over the procedure to another, considering it difficult after the second puncture. STATCRAFT v.2 software (Predictive Analytics Solutions Pvt. Ltd., Bengaluru, India) was used for ANN model generation. Considering the overfitting tendency of the ANN, Pr(>||) < 0.01 in the ANN was considered significant. The area under the receiver operating characteristic (AuROC) curve of the ANN model and its sensitivity and specificity were also assessed. Significant factors with multiple gradings were also evaluated for their statistical significance across the grades or classes using INSTAT software (Graphpad Prism, La Jolla, CA, USA); a two-tailed -value of <0.05 was considered significant. Results Interspinous process-based spine grade, performers' experience, and positioning difficulty were significant determinants of failed spinal arachnoid puncture procedures in the ANN model. The ANN model had an AuROC of 0.907, specificity of 0.976, and sensitivity of 0.385. The interclass comparison showed that increasing spinal grades and decreasing experiences were associated with increased pass and puncture. Conclusions The ANN model found the determinants of the failed spinal arachnoid puncture procedure well with good AuROC and specificity but poor sensitivity.
PubMed: 36699768
DOI: 10.7759/cureus.32891 -
ALTEX 2024Many laboratory procedures generate data on properties of chemicals, but they cannot be equated with toxicological "test methods". This apparent discrepancy is not...
Many laboratory procedures generate data on properties of chemicals, but they cannot be equated with toxicological "test methods". This apparent discrepancy is not limited to in vitro testing, using animal-free new approach methods (NAM), but also applies to animal-based testing approaches. Here, we give a brief overview of the differences between data generation and the setup or use of a complete test method. While there is excellent literature available on this topic for specialists (GIVIMP guidance; ToxTemp overview), a brief overview and easily-accessible entry point may be useful for a broader community. We provide a single figure to summarize all test method elements and processes required in the development (setup and adaptation) of a test method. The exposure scheme, the endpoint, and the test system are briefly outlined as fundamental elements of any test method. A rationale is provided, why they are not sufficient. We then explain the importance and role of purpose definition (including some information on what is modelled) and the prediction model, aka data interpretation procedure, which depends on the purpose definition, as further essential elements. This connection exemplifies that all fundamental elements are interdependent, and none can be omitted. Finally, discussion is provided on validation as a measure to provide confidence in the reliability, performance, and relevance of a test method. In this sense, validation may be considered a sixth fundamental element for practical use of test methods.
Topics: Animals; Humans; Reproducibility of Results; Research Design; Biological Science Disciplines
PubMed: 38207287
DOI: 10.14573/altex.2401041 -
BMJ Open Jul 2022The optimal dose and treatment modality of neoadjuvant radiotherapy applied for treating borderline resectable and locally advanced pancreatic ductal adenocarcinoma...
Comparative efficacy and safety of neoadjuvant radiotherapy for patients with borderline resectable, and locally advanced pancreatic ductal adenocarcinoma: a systematic review and network meta-analysis protocol.
INTRODUCTION
The optimal dose and treatment modality of neoadjuvant radiotherapy applied for treating borderline resectable and locally advanced pancreatic ductal adenocarcinoma (PDAC) have been debated topics in oncology. The objective of the present network meta-analysis (NMA) is to study and compare the efficacy and safety of neoadjuvant radiotherapy comprehensively using different doses in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC).
METHODS AND ANALYSIS
Four electronic databases, including PubMed, EMBASE, Cochrane library and Web of science, will be searched thoroughly to identify relevant studies published from 2006 to October 2020. Electronic searching by titles using neoadjuvant treatments for PDAC will be performed in the annual meetings of European Society of Medical Oncology and American Society of Clinical Oncology (2018-2020).
CLINICALTRIALS
gov will also be searched for grey literature. Two reviewers will perform search strategies and extract data independently. R0 resection rate and local control rate are defined as primary outcomes. Secondary outcomes include overall survival, disease-free survival and acute and late grade 3 and grade 4 toxicities. For randomised control trials, the risk of bias will be assessed using the Cochrane Risk of Bias Tool, while the risk of bias for non-randomised, observational studies will be evaluated using the Risk Of Bias In Non-randomised Studies-of Interventions. The quality of evidence will be evaluated using the version of Cochrane tool and Grades of Recommendation, Assessment, Development and Evaluation. Subgroup analysis and sensitivity analysis will be conducted in the present NMA.
ETHICS AND DISSEMINATION
This study will synthesise the evidence regarding dose schedule of neoadjuvant radiotherapy in patients with BRPC and LAPC. We hope the findings from this NMA will help clinicians and patients select the optimal modality and dose schedule of neoadjuvant radiotherapy with respect to patient-reported outcomes. As no primary data collection will be undertaken, no ethics approval is required. The results will be disseminated through peer-reviewed journal.
PROSPERO REGISTRATION NUMBER
CRD42020222408.
Topics: Carcinoma, Pancreatic Ductal; Humans; Meta-Analysis as Topic; Neoadjuvant Therapy; Network Meta-Analysis; Pancreatic Neoplasms; Systematic Reviews as Topic
PubMed: 35831044
DOI: 10.1136/bmjopen-2021-050558 -
Biometrics Dec 2022Biomedical research is increasingly data rich, with studies comprising ever growing numbers of features. The larger a study, the higher the likelihood that a substantial...
Biomedical research is increasingly data rich, with studies comprising ever growing numbers of features. The larger a study, the higher the likelihood that a substantial portion of the features may be redundant and/or contain contamination (outlying values). This poses serious challenges, which are exacerbated in cases where the sample sizes are relatively small. Effective and efficient approaches to perform sparse estimation in the presence of outliers are critical for these studies, and have received considerable attention in the last decade. We contribute to this area considering high-dimensional regressions contaminated by multiple mean-shift outliers affecting both the response and the design matrix. We develop a general framework and use mixed-integer programming to simultaneously perform feature selection and outlier detection with provably optimal guarantees. We prove theoretical properties for our approach, that is, a necessary and sufficient condition for the robustly strong oracle property, where the number of features can increase exponentially with the sample size; the optimal estimation of parameters; and the breakdown point of the resulting estimates. Moreover, we provide computationally efficient procedures to tune integer constraints and warm-start the algorithm. We show the superior performance of our proposal compared to existing heuristic methods through simulations and use it to study the relationships between childhood obesity and the human microbiome.
Topics: Child; Humans; Pediatric Obesity; Algorithms; Sample Size; Probability
PubMed: 34437713
DOI: 10.1111/biom.13553 -
Family Medicine Mar 2024Proficiency in procedural care achieved during residency is a major driver of family physician scope of practice. To date, no inventory exists of the advanced procedures...
BACKGROUND AND OBJECTIVES
Proficiency in procedural care achieved during residency is a major driver of family physician scope of practice. To date, no inventory exists of the advanced procedures and clinical skills performed by teaching family physicians. This study comprises the first such survey and assesses the attitude of respondents toward the importance of family physicians performing procedures.
METHODS
We sent a clinical skills inventory to a convenience sample of teaching family physicians employed at 18 medical school-affiliated, community, and military residency programs across the United States.
RESULTS
The overall response rate was 46% (N=337). Respondents performed a median of 12 advanced procedures and clinical skills (IQR: 8-18). Endorsed procedures ranged from skin biopsy (n=316, 93.8%) and joint injection (n=279, 82.8%) to colonoscopy (n=21, 6.2%) and cesarean delivery (n=23, 6.8%), and reported skills ranged from medication-assisted treatment (n=181, 53.7%) to highly active antiretrovial therapy (n=35, 10.4%). Gender and career stage were associated with statistically significant differences in endorsement of specific procedures. For example, fracture management was more likely to be performed by late- versus early-career faculty (54.1% vs 24.2%, P<.001) and by male versus female respondents (54.9% vs 24.2%, P<.001). Most respondents (84.3%) agreed that future family physicians should learn procedures and advanced clinical skills.
CONCLUSIONS
Family medicine teaching faculty perform a wide array of procedures and advanced skills. Apparent differences by career stage and gender identity in the performance of some of the procedural and skill areas may portend a shift in the procedural training of future family physicians.
Topics: Pregnancy; Humans; Male; Female; United States; Family Practice; Gender Identity; Physicians, Family; General Practitioners; Surveys and Questionnaires; Internship and Residency; Clinical Competence; Teaching
PubMed: 38241746
DOI: 10.22454/FamMed.2024.197714