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Biometrics Mar 2024Randomization-based inference using the Fisher randomization test allows for the computation of Fisher-exact P-values, making it an attractive option for the analysis of...
Randomization-based inference using the Fisher randomization test allows for the computation of Fisher-exact P-values, making it an attractive option for the analysis of small, randomized experiments with non-normal outcomes. Two common test statistics used to perform Fisher randomization tests are the difference-in-means between the treatment and control groups and the covariate-adjusted version of the difference-in-means using analysis of covariance. Modern computing allows for fast computation of the Fisher-exact P-value, but confidence intervals have typically been obtained by inverting the Fisher randomization test over a range of possible effect sizes. The test inversion procedure is computationally expensive, limiting the usage of randomization-based inference in applied work. A recent paper by Zhu and Liu developed a closed form expression for the randomization-based confidence interval using the difference-in-means statistic. We develop an important extension of Zhu and Liu to obtain a closed form expression for the randomization-based covariate-adjusted confidence interval and give practitioners a sufficiency condition that can be checked using observed data and that guarantees that these confidence intervals have correct coverage. Simulations show that our procedure generates randomization-based covariate-adjusted confidence intervals that are robust to non-normality and that can be calculated in nearly the same time as it takes to calculate the Fisher-exact P-value, thus removing the computational barrier to performing randomization-based inference when adjusting for covariates. We also demonstrate our method on a re-analysis of phase I clinical trial data.
Topics: Confidence Intervals; Computer Simulation; Humans; Biometry; Models, Statistical; Data Interpretation, Statistical; Random Allocation; Randomized Controlled Trials as Topic
PubMed: 38837900
DOI: 10.1093/biomtc/ujae051 -
The Journal of Adhesive Dentistry Jul 2023This randomized controlled trial aimed to evaluate the 14-year clinical performance of a HEMA-free 1-step self-etch adhesive (1SEa) compared with that of a 3-step... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
This randomized controlled trial aimed to evaluate the 14-year clinical performance of a HEMA-free 1-step self-etch adhesive (1SEa) compared with that of a 3-step etch-and-rinse adhesive (3E&Ra).
MATERIALS AND METHODS
267 non-carious cervical lesions in 52 patients were restored with the microhybrid composite Gradia Direct (GC), bonded in random order either with the HEMA-free 1SEa G-Bond (GB; GC) or the 3E&Ra Optibond FL (OFL; Kerr), which is considered the gold-standard E&Ra (control). The restorations were followed over 14 years for retention, marginal adaptation and discoloration, and caries occurrence. Statistical analysis involved a logistic regression model with generalized estimating equations (2-way GEE model).
RESULTS
The patient recall rate at 14 years was 63%. In total, 79 restorations (39 GB, 40 OFL) failed because of retention loss (GB: 19.4%, OFL: 19.6%), severe marginal defects, discoloration and/or caries (GB: 21.7%; OFL: 22.5%). The overall clinical success rate was 58.9% and 57.9% for GB and OFL, respectively. The number of restorations with an unacceptable marginal defect (GB: 14.5%; OFL: 19.2%) and deep marginal discoloration (GB: 18.2%; OFL: 13.2%) increased during the last 5 years. No significant difference in overall clinical performance was recorded between the two adhesives (p > 0.05). Changes in the medical health of some patients and recurrence of abrasion/erosion/abfraction increased the failure rate and retention rate.
CONCLUSION
After 14 years, restorations bonded with the HEMA-free 1SEa performed as well as those bonded with the 3E&Ra gold standard. Unacceptable marginal deterioration was the main reason for failure, followed by loss of retention.
Topics: Humans; Dental Caries; Research Design
PubMed: 37435814
DOI: 10.3290/j.jad.b4208859 -
BMJ Open Jul 2023Treatment strategies for primary aldosteronism (PA) include unilateral adrenalectomy and medical treatment with mineralocorticoid receptor (MR) antagonists. Whether...
INTRODUCTION
Treatment strategies for primary aldosteronism (PA) include unilateral adrenalectomy and medical treatment with mineralocorticoid receptor (MR) antagonists. Whether these two different treatment strategies are comparable in mitigating the detrimental effect of PA on outcomes is still debated.
OBJECTIVES
The primary aim of this systematic review is to identify, appraise and synthesise existing literature comparing clinical outcomes after treatment in patients with PA.
METHODS AND ANALYSIS
A systematic and comprehensive search will be performed using PubMed, Web of Science and EMBASE, for studies published until December 2022. Observational and interventional studies will be eligible for inclusion. The quality of observational studies will be assessed using the Newcastle-Ottawa Scale, while interventional studies will be assessed using the Cochrane Effective Practice Organization of Care tool. The collected evidence will be narratively synthesised. We will perform meta-analysis to pool estimates from studies considered to be homogeneous. Reporting of the systematic review and meta-analysis will be in accordance with the Meta-analysis of Observational Studies in Epidemiology Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines.
ETHICS AND DISSEMINATION
As this study is based solely on the published literature, no ethics approval is required. This review will aim to provide some estimates on outcomes, including survival, rates of clinical and biochemical control, cardiovascular and cerebrovascular events, as well as data on quality of life and renal function, in patients with PA treated surgically or with MR antagonists. The study findings will be presented at scientific meetings and will be published in an international peer-reviewed scientific journal.
PROSPERO REGISTRATION NUMBER
CRD42022362506.
Topics: Humans; Quality of Life; Systematic Reviews as Topic; Meta-Analysis as Topic; Treatment Outcome; Hyperaldosteronism; Research Design; Review Literature as Topic
PubMed: 37518075
DOI: 10.1136/bmjopen-2023-072585 -
The Journal of Continuing Education in... Sep 2023The purpose of this program evaluation was to investigate the efficacy of simulation-based primary care procedural skills training to increase participant confidence,...
INTRODUCTION
The purpose of this program evaluation was to investigate the efficacy of simulation-based primary care procedural skills training to increase participant confidence, knowledge, and skill in performing the procedures included in the training and to evaluate the cost-effectiveness of the training.
METHODS
A retrospective, within-subjects analysis of the change in perceived confidence, skill, and knowledge in procedure performance after the simulation-based primary care procedural skills training program measured by pretraining and post-training Likert scale surveys and change in clinical procedure performance frequency for abscess incision and drainage and laceration repair up to 6 months before and 6 months after the training in the outpatient setting was performed.
RESULTS
Participants self-reported higher median confidence, perceived skill, and perceived knowledge of all procedures included in the training course, with statistically significant increases for all procedures. A mean increase in laceration repairs in the clinical setting of 10% after training was found. Higher median performance of abscess incision and drainage after training (median = 20.00%, n = 25) compared with before training (median = 0.00%, n = 25) and a mean increase in performance of abscess incision and drainage in the clinical setting of 6% after training was found, but increases were not statistically significant.
DISCUSSION
Participation in a 2-day simulation-based primary care procedural skills training program was an effective method to increase confidence, perceived skill, and knowledge of outpatient procedures among practicing providers. Further evaluation to establish return on investment is needed, because statistically significant increases in clinical procedure performance were unable to be demonstrated.
PubMed: 37713161
DOI: 10.1097/CEH.0000000000000530 -
Nature Protocols Jan 2024Fluidic channels at atomic scales regulate cellular trafficking and molecular filtration across membranes, and thus play crucial roles in the functioning of living... (Review)
Review
Fluidic channels at atomic scales regulate cellular trafficking and molecular filtration across membranes, and thus play crucial roles in the functioning of living systems. However, constructing synthetic channels experimentally at these scales has been a significant challenge due to the limitations in nanofabrication techniques and the surface roughness of the commonly used materials. Angstrom (Å)-scale slit-like channels overcome such challenges as these are made with precise control over their dimensions and can be used to study the fluidic properties of gases, ions and water at unprecedented scales. Here we provide a detailed fabrication method of the two-dimensional Å-scale channel devices that can be assembled to contain a desired number of channels, a single channel or up to hundreds of channels, made with atomic-scale precision using layered crystals. The procedure includes the fabrication of the substrate, flake, spacer layer, flake transfers, van der Waals assembly and postprocessing. We further explain how to perform molecular transport measurements with the Å-channels to directly probe the intriguing and anomalous phenomena that help shed light on the physics governing ultra-confined transport. The procedure requires a total of 1-2 weeks for the fabrication of the two-dimensional channel device and is suitable for users with prior experience in clean room working environments and nanofabrication.
Topics: Feces; Filtration; Research Design; Water
PubMed: 38012396
DOI: 10.1038/s41596-023-00911-x -
Methods in Molecular Biology (Clifton,... 2024Proteins usually do not function as monomers but rather perform their functions by interacting with themselves or other proteins. Co-immunoprecipitation is an essential...
Proteins usually do not function as monomers but rather perform their functions by interacting with themselves or other proteins. Co-immunoprecipitation is an essential assay for detecting protein interactions in vivo. In this chapter, we describe how to use co-immunoprecipitation to detect protein interactions in Arabidopsis protoplasts, seedlings, and Nicotiana benthamiana leaves. When using co-immunoprecipitation assays to detect protein interactions, it is necessary to pay attention to the design of the experimental and control groups.
Topics: Arabidopsis; Biological Assay; Control Groups; Immunoprecipitation; Plant Leaves
PubMed: 37987909
DOI: 10.1007/978-1-0716-3485-1_16 -
Periodontology 2000 Oct 2023Lateral ridge augmentation is a standard surgical procedure that can be performed prior to (staged) or simultaneously with implant placement. The decision between a... (Review)
Review
Lateral ridge augmentation is a standard surgical procedure that can be performed prior to (staged) or simultaneously with implant placement. The decision between a simultaneous or staged approach involves considering multiple variables. This paper proposed a decision-making process that serves as a guideline for choosing the best treatment choice based on the available evidence and the author's clinical experience.
Topics: Humans; Dental Implantation, Endosseous; Alveolar Ridge Augmentation; Bone Transplantation; Guided Tissue Regeneration, Periodontal; Patient Selection; Dental Implants
PubMed: 37529966
DOI: 10.1111/prd.12512 -
Journal of Dairy Science Dec 2023Allowing the dam to rear her calf is an alternative practice in the dairy industry where cow and calf may gain welfare benefits from performing natural and highly...
Allowing the dam to rear her calf is an alternative practice in the dairy industry where cow and calf may gain welfare benefits from performing natural and highly motivated behaviors. However, this system has been linked to an increased separation and weaning response. Reducing the daily dam-calf contact time may be a way to prepare the calf for weaning and separation. The first aim of the present study was to investigate the effect of 8 wk of half-day dam-calf contact on calf response to weaning and separation, compared with calves reared with whole-day dam-calf contact and an artificially reared, group-housed control with unrestricted access to milk for 20 min twice daily. Weaning off milk and separation from the dam can be viewed as 2 independent stressors. By introducing each stressor separately, it may be possible to reduce the overall behavioral response. The second aim of the present study was to investigate the effect of 1-wk fence-line weaning before permanent separation. The study was conducted with a 3 × 2 factorial design with dam contact treatments (whole-day, half-day, and control) and weaning treatments (simultaneous, and stepwise). Whole-day calves were separated twice daily from their dams during milking, whereas half-day calves were separated daily from the afternoon milking and until next morning milking. Simultaneous weaning and separation were done in wk 9, and stepwise weaning and separation started in wk 8 with calves being fence-line weaned before permanent separation in wk 9. Data were collected on 69 dairy calves in wk 8 and wk 9, and data were summarized over the 2 weeks for analysis. Stepwise weaning and separation reduced the number of high-pitched vocalizations and activity of dam-reared dairy calves but had little effect on control calves. There was no difference between whole-day and half-day calves in their response to separation, but as expected, dam-reared calves reacted more strongly than the control group. This was also reflected in the average daily BW gain the week after weaning, with control calves having higher average daily gains than whole-day, while half-day calves were intermediate. However, the behavioral response did not fully wane within the observation period (0-48 h of interventions). In conclusion, 1-wk fence-line weaning reduced the summed weaning and separation response in dam-reared calves. However, no difference between half-day dam-calf contact and whole-day dam contact was detected in the behavioral response to weaning and separation.
Topics: Female; Animals; Cattle; Weaning; Behavior, Animal; Milk; Research Design; Dairying; Animal Feed
PubMed: 37641322
DOI: 10.3168/jds.2023-23393 -
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 -
BMJ Open Aug 2023High-performing primary care is recognised as the foundation of an effective and efficient healthcare system. Many medical graduates report they are not prepared for...
INTRODUCTION
High-performing primary care is recognised as the foundation of an effective and efficient healthcare system. Many medical graduates report they are not prepared for independent practice. To date, no research has been conducted to identify the key capabilities and competencies of high-performing family medicine graduates in Canada. This pilot project aims to identify the capabilities and competencies of high-performing early-career family physicians in Ontario, Canada, and explore opportunities for enhancing learning, teaching and assessment within family medicine residency programmes.
METHODS AND ANALYSIS
Employing a mixed-methods explanatory sequential study design, this research will use a theory-driven Professional Capability Framework, previously validated in studies across nine professions, to guide the investigation. The first (quantitative) phase involves surveying ~50 high-performing early-career family physicians identified as high performing by educators, colleagues and leaders. The objective of the survey is to identify the key competencies and personal, interpersonal and cognitive capabilities of high-performing family physicians. The second (qualitative) phase involves conducting workshops with stakeholders, including educators, professional associations, regulators and colleges, to test the veracity of the results. Quantitative data will be analysed using descriptive statistics, and qualitative data will be analysed using Braun and Clarke's thematic analysis. The first and second phases will identify the key capabilities and competencies required to confidently adapt to the independent practice of comprehensive family medicine and inform fit-for-purpose educational strategies for teaching, learning and assessment.
ETHICS AND DISSEMINATION
The study is approved by the University of Toronto's Health Sciences Research Ethics Board (#41799). Research findings will be discussed with professional bodies, educators responsible for family medicine curricula and universities. Study findings will also be disseminated through academic conferences and academic publications in peer-reviewed journals. Project summaries and infographics will be developed and disseminated to key stakeholders.
Topics: Humans; Physicians, Family; Pilot Projects; Family Practice; Research Design; Ontario
PubMed: 37591643
DOI: 10.1136/bmjopen-2023-072266