Logistical Considerations Research Articles

The history of cryotechnologies in reproductive medicine: From randomness to stability

The article provides an overview of the historical milestones in cryobiology, a scientific field that has found widespread practical application in reproductive medicine. Cryotechnologies have revolutionized assisted reproductive technologies, offering invaluable tools for the storage, protection, and management of reproductive cells such as sperm, oocytes, and embryos. The technology began with the first successful attempts at sperm cryopreservation, which not only demonstrated the possibility of preserving male gametes but also inspired a wave of research aimed at developing cryopreservation protocols for more sensitive and complex biological entities, including oocytes and preimplantation embryos. Cryopreservation has become a crucial component of fertility preservation, offering new opportunities for individuals and couples facing medical treatments that could compromise their reproductive potential, as well as providing options for delaying parenthood. Given the critical role of cryotechnologies in modern reproductive medicine, this article delves into the historical context of these developments, exploring the key breakthroughs that have shaped this field. The authors conducted an in-depth analysis of existing literature, drawing on a wide range of scientific databases to highlight the global impact of cryobiology on the current successes in reproductive medicine. Furthermore, the article presents the results of the authors' own research and practical experience in the field of reproductive cryobiology, with a particular focus on the application of these technologies in Ukraine. The review underscores the challenges and opportunities that have emerged throughout the history of cryopreservation, as well as ongoing efforts to improve and optimize these methods to further enhance infertility treatment outcomes. The discussion also addresses ethical and logistical considerations related to cryopreservation, particularly in the context of long-term storage and future use of cryopreserved materials. As cryobiology continues to evolve, its integration into reproductive medicine will undoubtedly lead to further innovations, making it a cornerstone of infertility treatment and reproductive health worldwide.

Polygenic Risk Score Implementation into Clinical Practice for Primary Prevention of Cardiometabolic Disease

Background: Cardiovascular disease is a leading cause of mortality globally and a major contributor to disability. Traditional risk factors, as initially established in the FRAMINGHAM study, have helped to stratify populations and identify patients for early intervention. Incorporating genetic factors enhances risk stratification tools, enabling the earlier identification of individuals at increased risk and facilitating more targeted and effective risk factor modifications. While monogenic risk variants are present in a minority of the population, polygenic risk scores (PRS) are collections of multiple single-nucleotide variants that collectively provide summative risk and capture a more accurate risk score for a greater number of people. PRS have demonstrated clear utility in cardiometabolic diseases by predicting onset, progression, and therapeutic response. Methods: A structured and exploratory hybrid search strategy was employed, combining keyword-based database searches and supplementary techniques to comprehensively synthesize the literature on PRS implementation in clinical practice. Discussion: A comprehensive overview of PRS in cardiometabolic diseases and their potential avenues for integration into primary care is discussed. First, we examine the implementation of genetic screening, risk communication, and intervention strategies through the lens of the American Heart Association’s implementation criteria, focusing on their efficacy, minimization of harm, and logistical considerations. Then, we explores how the varied perceptions of patients and practitioners towards PRS can influence both adoption and utilization. Lastly, we addresses the need for the development of clear guidelines and regulations to support this process, ensuring PRS integration is both scientifically sound and ethically responsible. Future directions: Initiatives aimed at advancing personalized approaches to disease prevention will enhance health outcomes. Developing guidelines for the responsible use of PRS by establishing benefits, while mitigating risk, will a key factor in implementation for clinical utility. Conclusions: For integration into clinical practice, we must address both patient and provider concerns and experience. Standardized guidelines and training will help to effectively implement PRS into clinical practice. Developing these resources will be essential for PRS to fulfill its potential in personalized, patient-centered care.

Factors Influencing School‐Based Mental Health Program Selection: Insights From Educational Stakeholders

ABSTRACTSchool mental health programs are an important component of the national response to the current student mental health crisis. However, evidence‐based programs often face numerous barriers to their selection, scale‐up, and sustainability in real‐world settings. In this study, we interviewed 15 educational stakeholders to examine what influences their selection of school‐based mental health programs. Interviews focused on factors influencing the selection and sustainability of mental health programs in schools. We coded transcribed interview data using a hybrid, iterative process, and generated themes from these codes. We identified five categories of themes related to key decision‐making criteria: program fit with student and school needs, evidence of program effectiveness, stakeholder buy‐in, logistical considerations for staff delivering programs, and cost and resource requirements. Findings have implications for researchers who wish to improve dissemination strategies for school‐based mental health prevention programs and for policymakers who wish to shape funding priorities to support greater diversity in program availability. Findings are also useful to practitioners who may use these insights to reflect on their own program selection practices or may see their own experiences reflected and normalized through the lens of the key themes presented here.

On Optimization of Factory Space Configuration

In factories, spatial configuration plays an important role in order to improve workers’ comfort which will result in maximising the productivity and at last will contribute to economy generation. With the goal of identifying the major variables influencing shoe factories' spatial layout choices, this study explores the spatial arrangement and organization of shoe factories. By analyzing a cluster of shoe manufacturing plants located in Agra in India through site visit and international case studies in Bangladesh, this study examines how factors such as workflow process, machinery placement, storage areas and logistical considerations impact the spatial arrangement of factories. With the help of workers and factory officials interviews in shoe factories, site visits, and spatial analysis techniques this research provides insights into the actual indoor environment of the factories in terms of spatial arrangement. This actual indoor environment is further comparatively analysed by existing standards for industrial buildings which helped to find out the potential areas for improvement. The findings of this research work aim at identifying the potential areas and best practices for improvement in spatial configuration of shoe factories which will contribute to workers’ comfort.

Human Spaceflight: Technological Advances, Health Implications, and the Path to Interplanetary Travel

Human spaceflight has advanced from brief orbital missions to sustained international cooperation on the International Space Station (ISS). As humanity looks toward more ambitious goals, such as lunar bases and Mars exploration, understanding the challenges and opportunities of human space travel is critical. This paper provides a comprehensive analysis of the current state of human spaceflight, focusing on technological advancements, health and safety concerns, and future mission planning. It reviews the physical, psychological, and environmental factors affecting astronauts, technological innovations supporting deep-space missions, and emerging ethical and logistical considerations. This research concludes with an evaluation of potential pathways for human settlement on Mars, the Moon, and beyond.

Sample Size and Statistical Power Calculation in Multivariable Analyses: Development and Implementation of "SampleSizeMulti" Packages in R

This paper presents advanced methodological approaches and practical tools for sample size calculation in epidemiological studies involving multivariable analyses. Traditional sample size calculation methods often fail to account for the complexity of modern statistical analyses, particularly regarding the correlation between covariates in multivariable models. We introduce a series of R packages (SampleSizeMulti) designed to address these limitations. These packages offer two distinct calculation approaches: one based on the multiple correlation coefficient between covariates (rho-based method) and another utilizing standard errors from previous studies (SE-based method). These complementary approaches provide comprehensive solutions for different association measures commonly used in epidemiological research: prevalence ratios, odds ratios, risk ratios, and hazard ratios. The rho-based method innovatively incorporates the explicit consideration of the multiple correlation coefficient between covariates, significantly impacting required sample sizes in multivariable analyses. The SE-based method leverages information from previous studies through their confidence intervals, offering an alternative when correlation estimates are unavailable but published results exist. Furthermore, both approaches integrate crucial logistical considerations, including rejection rates, eligibility criteria, and expected losses to follow-up, providing researchers with realistic estimates of recruitment requirements and timelines. Seven detailed case studies covering various epidemiological study designs and analytical scenarios demonstrate the practical application of these methods. These examples illustrate how correlation values, standard errors, and logistical factors influence sample size calculations and study planning. The implementation in R ensures accessibility and reproducibility, while the incorporation of logistical planning tools bridges the gap between theoretical calculations and practical research requirements. These methods represent a significant advancement in study design methodology, potentially improving the quality and efficiency of epidemiological research by ensuring adequate statistical power while optimizing resource utilization.

The effectiveness of autonomous public transport systems in densely populated urban areas

This paper presents an in-depth analysis and comparison of technologies for autonomous transport systems, focusing on logistical considerations, economic factors, and overall outcomes. The study evaluates various scenarios, including manned and autonomous ground vehicles, as well as infrastructure solutions, to provide insights into their operational efficiency and economic viability.In the logistical comparison, findings indicate that autonomous and manned ground vehicles operate within similar logistical frameworks but offer different operational flexibilities. Autonomous systems demonstrate potential advantages in adaptability to changing passenger needs and risk reduction through sensor-based navigation. Additionally, deploying autonomous infrastructure solutions shows promising results in reducing cycle time (-43 % to ground manned/autonomous vehicles) and increasing technical speed (+57 % to ground manned/autonomous vehicles), especially in strained infrastructure environments.The economic comparison reveals challenges in assessing the cost-effectiveness of autonomous solutions due to a lack of pricing data. While the automation of public transport vehicles incurs higher capital (e.g. 33 % increase for autonomous buses vs manned) and operational expenditures (e.g. 60 % increase for autonomous buses vs manned), autonomous systems offer benefits such as continuous operation and reduced idle time. Investments in infrastructure solutions present opportunities to diversify traffic flow and enhance the overall transportation system.In conclusion, the autonomous transport system market requires increased transparency in pricing structures and technical maturity. Successful deployment depends on thorough demand studies and compatibility analyses with existing infrastructure. Innovative approaches like autonomous monorails or suspended Light Rail Transit (LRT) offer scalability, efficiency, and reduced environmental impact. Integrating predictive maintenance systems and advanced fleet management enhances reliability and service quality. Fostering transparency, embracing innovation, and implementing robust management systems are crucial for the successful integration of autonomous transport systems into urban environments.

Application and development of wastewater epidemiology in public health current status and future trends

Abstract. Wastewater epidemiology has emerged as a powerful tool for public health surveillance, enabling the monitoring of infectious diseases at the community level. This paper provides an overview of wastewater epidemiology, including its methodology, applications, current status, and future trends. The challenges and ethical considerations associated with its implementation are also discussed. The methodology section explores the various techniques used in wastewater epidemiology, such as analyzing viral RNA and biomarkers in wastewater samples. These methods offer valuable insights into disease prevalence, transmission patterns, and trends in a population. The applications section highlights the wide range of public health applications for wastewater epidemiology. It discusses how this approach can contribute to disease surveillance, early detection of outbreaks, and monitoring the effectiveness of interventions. The current status section examines the progress made in wastewater epidemiology. It discusses the standardization of methodologies and the need for research collaboration to ensure reliable and comparable results. The future trends and developments section explores potential advancements in wastewater epidemiology. It discusses emerging technologies, such as next-generation sequencing and advanced data analysis techniques, that could enhance the capabilities of this approach. The challenges and ethical considerations section addresses the hurdles in implementing wastewater epidemiology. It emphasizes the importance of standardization, logistical considerations, privacy protection, transparent reporting, and equitable distribution of benefits. In conclusion, wastewater epidemiology holds great promise for public health surveillance. However, addressing the challenges and ethical considerations is crucial for its responsible and effective implementation. By proactively overcoming these obstacles and upholding ethical principles, wastewater epidemiology can continue to evolve as a valuable tool for improving public health outcomes.

EXTH-51. ENHANCING GLIOBLASTOMA TREATMENT: ALLOGENEIC CAR-T CELLS OVERCOMES FUNCTIONAL DEFICITS OF PATIENT-DERIVED AUTOLOGOUS PRODUCTS

Abstract Glioblastoma (GBM) is the most common primary brain malignancy in adults, with a dismal prognosis despite an intensive standard of care. Recently, chimeric antigen receptor T-cell (CAR-T) therapy has shown promising outcomes in treating liquid malignancies. However, clinical trials targeting various tumor antigens in GBM failed to show durable clinical benefit. Though this may stem from various tumor-intrinsic immune evasion strategies typical of GBM, there has been little work investigating whether the problem lies in the quality of the CAR-T products treatment itself. Currently, CAR-T cells for clinical studies are produced in an autologous setting, where T-cells are extracted from patients, engineered ex-vivo, and then re-infused. However, peripheral T-cells taken from GBM patients have shown qualitative and functional deficits, which may contribute to suboptimal treatment outcomes. Thus, we aimed to explore whether CAR-Ts generated from GBM patients had any functional deficits in comparison to healthy donors, utilizing our previously validated CD133 CAR-T. In this study, we show pre-treatment exhaustion, poor tumor control, and reduced survival advantage in autologous, patient-derived CD133-targeting CAR-T cell products using an orthotopic xenograft model of human GBM. To address the functional and logistical considerations of autologous therapy, we also sought to generate an “off-the-shelf” allogeneic CD133 CAR-T. Using CRISPR gene editing technology, we generated TCR-knockout CAR-T cells with comparable pre-clinical efficacy to our healthy donor derived autologous models. Ultimately, this work highlights the need to reevaluate autologous CAR-T therapy for GBM and consider allogeneic approaches as biologically-informed therapeutic alternatives.

A systematic review of virtual elective programmes for medical students.

Clinical electives are a compulsory part of many medical courses, enabling students to gain exposure to foreign health systems. The COVID-19 pandemic led to a surge in the development in virtual elective programmes, for which there had been a sparse evidence base. This is the first systematic review assessing the implementation, advantages and disadvantages of virtual elective programmes for medical students. The systematic review was conducted in accordance with PRISMA guidelines. Databases were searched, capturing results from the past 10 years for original evaluations of electives where medical students engaged in a fully virtual programme with another institution, with no restrictions on location. Descriptive, quantitative and qualitative data were extracted by two independent reviewers. Fourteen articles were included for review. All the articles were published between 2020 and 2023. All studies were conducted in the United States of America. The average length of the virtual electives in the studies was 3 weeks, and a variety of teaching formats including virtual clinics, seminars and one-on-one meetings were implemented. Logistical considerations and challenges in delivering virtual electives included the variability in students' learning styles, reduction in patient interactions and technological challenges. Most included studies derived that these virtual electives would play a role in the future, possibly replacing in-person electives. Positive attributes of virtual electives included increasing diversity of social backgrounds, high student satisfaction and interest and reducing harms to the environment. However, further research is required to thoroughly evaluate the efficacy of virtual electives in medical education.

Accentuated Eccentric Loading and Alternative Set Structures: A Narrative Review for Potential Synergies in Resistance Training.

Chae, S, McDowell, KW, Baur, ML, Long, SA, Tufano, JJ, and Stone, MH. Accentuated eccentric loading and alternative set structures: A narrative review for potential synergies in resistance training. J Strength Cond Res 38(11): 1987-2000, 2024-As athletes become adapted to training over time, it becomes more difficult to develop their strength and power. In a conventional resistance training strategy, volume or load may be increased to provide novel stimuli to break through a plateau. However, physiological stress markers increase with increased volume or load, which is an innate shortcoming. In that case, practitioners strive to develop unconventional strategies that could increase training stimuli while adjusting fatigue. Two programming tactics, accentuated eccentric loading (AEL) using eccentric overload and alternative set structures (AS) using intraset rests, have been reported to increase training stimuli and alleviate fatigue, respectively. Importantly, when merging AEL and AS in various contexts, the 2 benefits could be accomplished together. Because AEL and AS cause different outcomes, it is important to deal with when and how they may be integrated into periodization. Moreover, prescribing eccentric overload and intraset rests requires logistical considerations that need to be addressed. This review discusses the scientific and practical aspects of AEL and AS to further optimize strength and power adaptations. This review discusses (a) scientific evidence as to which tactic is effective for a certain block, (b) potential practical applications, and (c) related discussions and future research directions.

Influence of male targeted short message service on knowledge, nature of attitude and male involvement on uptake of family planning among spouses in Marsabit County, Kenya

Background: Family planning services helps the individuals or couples to regulate the number and determine healthy spacing and timing of pregnancies. Globally, contraceptive prevalence stands at 49.0%, Sub-Saharan Africa at 29.0%, Kenya at 56.9% and Marsabit County at 5.6%. Some of the reasons given for low uptake include low knowledge level, negative attitude and lack of male involvement on family planning matters. This study aimed at establishing the influence of male targeted short message service on knowledge, nature of attitude and male involvement on uptake of family planning among spouses in Marsabit County. Methods: A pre-test and post-test quasi experimental study design was adopted involving randomly selected 220 couples from Laisamis (control group) and Moyale (intervention group) sub-counties. Intervention of male targeted short message service was offered weekly to male spouses from Moyale sub-county. A questionnaire was used to collect data. Data analysis was done using SPSS. All the required ethical and logistical considerations were adhered to accordingly. Results: Male targeted short message service increased level of knowledge significantly (OR 4.173, p=0.001), changed nature of attitude (OR 2.7335, p=0.004) and male involvement in family planning (OR 4.4306, p=0.001). Conclusions: The study concluded male targeted SMS intervention increased level of knowledge, attitude changed and males were involved. The County government of Marsabit should engage opinion leaders in family planning to help in educating and changing the attitude of the men towards family planning.

Influence of male targeted short message service on uptake of family planning among spouses in Marsabit County, Kenya

Background: Family planning helps in regulating the number of children and determine healthy spacing and timing of births between pregnancies. The global contraceptive prevalence stands at 49.0%, Sub-Saharan Africa at 29.0%, Kenya at 56.9% while in Marsabit County at 5.6%. Male spouse involvement on matters of family planning deserves attention. This study aimed at establishing the influence of male targeted short message service on uptake of family planning among female spouses in Marsabit County, Kenya. Methods: A pre-test and post-test quasi experimental study design was adopted involving randomly selected 220 couples from Laisamis and Moyale sub-counties. Intervention of male targeted short message service was offered to male spouses from Moyale sub-county for a period of 4 months. A questionnaire was used to collect data. Quantitative data analysis was done using SPSS. All the required ethical and logistical considerations followed. Results: At baseline level of uptake was overall 14.3%, control 13.2% and intervention 15.4% while at endline overall 30.2%, control 20.4% and intervention 39.5%. Further results revealed that uptake of family planning was increased by use of short message service. Conclusions: The study concluded that the level of uptake was low but with SMS intervention uptake significantly increased. The Ministry of Health should consider integrating male targeted short message service intervention in provision of family planning services to increase uptake.

Carbon Carriers Driving the Net-Zero Future: The Role of Torrefied Biomass Pellets in Power-To-X

The latest Intergovernmental Panel on Climate Change Sixth Assessment Report urgently calls for sweeping action to mitigate the unprecedented impacts of climate change. The path to a carbon-neutral future is intricate, necessitating a multi-faceted approach that integrates decarbonization, defossilization, and energy/resource efficiency. Power-to-X (PtX) stands as a technological linchpin, converting renewable electricity into a range of sustainable products, from fuels to chemicals. However, its full potential is intrinsically tied to the availability of sustainable carbon sources. This paper evaluates the various avenues for carbon sourcing for PtX: direct air capture (DAC), biogenic carbon, and Long-cycle Industrial Carbon. DAC, although promising for the long term, has limitations in scalability and land requirements. Industrial long-cycle carbon capture technology is improving but requires a thorough Life Cycle Assessment for evaluating its sustainability. This study examines the environmental impacts, scalability, and logistical considerations of each carbon source. Biogenic carbon offers a near-term solution, and its various forms could simplify transportation logistics. An analysis of gasification processes, syngas cleaning, and hydrogen integration was conducted to assess the technical viability of these carbon sources in PtX applications. The results show that torrefied biomass pellets, after a thorough technical assessment, present a globally feasible and sustainable carbon carrier, setting the stage for industry standardization and easier global transportation. Syngas produced through the gasification of the pellets complemented by green hydrogen can be utilized in Fischer–Tropsch, methanol synthesis, and methanation, allowing PtX to synthesize practically any type of organic compounds in a hybrid Biomass–PtX (HBPtX) process. This study provides key insights for industries and policymakers by demonstrating the technical feasibility and sustainability of torrefied biomass as a carbon carrier, thereby supporting the development of comprehensive climate mitigation strategies.

A mathematical model for potash supply chain management with a strategic logistics perspective

Abstract Accepted by: M. Zied Babai This paper introduces a novel Integer Linear Programming model designed to enhance the efficiency and sustainability of the potash supply chain, a crucial element supporting global agriculture. The developed mathematical optimization model focuses on fleet selection (private/outsource) and incorporates the concept of ‘inter-warehouse collaboration’, which addresses key logistics considerations. Integrating mining, processing, storage and transportation, the model encompasses decision variables like extracted carnallite amount, production, storage levels and shipped potash amount. Illustrated through a case study on the Arab Potash Company in Jordan, the results showcase the model’s proficiency in meeting local and international market demands. The model ensures resilient and sustainable supply chain performance by emphasizing logistics optimization, particularly in fleet selection. The study attains the highest ‘warehouse-to-warehouse’ support for Standard and Granular potash types in the international demand scenario, contributing to efficient production planning and fleet management. In conclusion, the presented mathematical model is a valuable tool for potash industry stakeholders, offering insights for strategic decision-makers involved in production planning and fleet management.

Immersive Virtual Reality (IVR) Systems for Comprehensive Fire Safety Education in Primary School

In the evolving landscape of educational technology, immersive virtual reality (IVR) has emerged as a promising tool to enhance safety education for primary school students. Traditional fire safety methods, while foundational, face challenges in engaging young learners actively. This study aims to comprehensively investigate the intricate dynamics of integrating IVR technology into fire safety education for primary school students. By examining students' perceptions, assessing engagement levels, and evaluating learning outcomes, the research seeks to offer nuanced insights into the potential benefits and challenges associated with VR-based safety education. Conducted as a qualitative study, 25 semi-structured interviews were performed with primary school students (Grades 4-6 in China), employing a three-step thematic analysis. The research explores students' experiences with IVR fire safety simulations, comparing them with traditional methods, and addressing practical considerations for integration. Preliminary findings suggest positive perceptions, heightened engagement, and improved learning outcomes among students exposed to VR simulations. Practical challenges, including logistical considerations, were identified. The comparison with traditional methods illuminated strengths and weaknesses, guiding educators and policymakers. This research contributes to the intersection of education and technology by offering novel insights into the potential of IVR simulations in fire safety education. The study's significance lies in informing pedagogical practices, addressing practical challenges, and promoting safety awareness among primary school students, guiding future educational technology initiatives.

Deterministic Model For Blood Bank Inventory Control With Increasing Demand And Logistic Considerations Using Multi-Objective Optimization

Deterministic Model For Blood Bank Inventory Control With Increasing Demand And Logistic Considerations Using Multi-Objective Optimization

Pushing Scuba to New Heights: Approach, Decompression, and Logistical Considerations for High-Altitude Diving.

There is interest among technical, expedition, commercial, and military divers in expanding diving operations to high altitude. However, altitude diving presents unique challenges including acclimatization, increased decompression sickness (DCS) risk, and logistical and equipment considerations. Divers must plan altitude acclimatization strategies conservatively to reduce risk of acute mountain sickness and dehydration before diving. Several methods of augmenting sea level diving tables to be used at altitude have been theorized and tested both in simulated dives and high-altitude expeditions. With proper acclimatization, augmentation of standard diving tables, equipment, and safety planning, diving at high altitude may be performed in many contexts safely while minimizing risk of DCS or injury.

A review of current practice in the design and analysis of extremely small stepped-wedge cluster randomized trials.

Stepped-wedge cluster randomized trials tend to require fewer clusters than standard parallel-arm designs due to the switches between control and intervention conditions, but there are no recommendations for the minimum number of clusters. Trials randomizing an extremely small number of clusters are not uncommon, but the justification for small numbers of clusters is often unclear and appropriate analysis is often lacking. In addition, stepped-wedge cluster randomized trials are methodologically more complex due to their longitudinal correlation structure, and ignoring the distinct within- and between-period intracluster correlations can underestimate the sample size in small stepped-wedge cluster randomized trials. We conducted a review of published small stepped-wedge cluster randomized trials to understand how and why they are used, and to characterize approaches used in their design and analysis. Electronic searches were used to identify primary reports of full-scale stepped-wedge cluster randomized trials published during the period 2016-2022; the subset that randomized two to six clusters was identified. Two reviewers independently extracted information from each report and any available protocol. Disagreements were resolved through discussion. We identified 61 stepped-wedge cluster randomized trials that randomized two to six clusters: median sample size (Q1-Q3) 1426 (420-7553) participants. Twelve (19.7%) gave some indication that the evaluation was considered a "preliminary" evaluation and 16 (26.2%) recognized the small number of clusters as a limitation. Sixteen (26.2%) provided an explanation for the limited number of clusters: the need to minimize contamination (e.g. by merging adjacent units), limited availability of clusters, and logistical considerations were common explanations. Majority (51, 83.6%) presented sample size or power calculations, but only one assumed distinct within- and between-period intracluster correlations. Few (10, 16.4%) utilized restricted randomization methods; more than half (34, 55.7%) identified baseline imbalances. The most common statistical method for analysis was the generalized linear mixed model (44, 72.1%). Only four trials (6.6%) reported statistical analyses considering small numbers of clusters: one used generalized estimating equations with small-sample correction, two used generalized linear mixed model with small-sample correction, and one used Bayesian analysis. Another eight (13.1%) used fixed-effects regression, the performance of which requires further evaluation under stepped-wedge cluster randomized trials with small numbers of clusters. None used permutation tests or cluster-period level analysis. Methods appropriate for the design and analysis of small stepped-wedge cluster randomized trials have not been widely adopted in practice. Greater awareness is required that the use of standard sample size calculation methods can provide spuriously low numbers of required clusters. Methods such as generalized estimating equations or generalized linear mixed models with small-sample corrections, Bayesian approaches, and permutation tests may be more appropriate for the analysis of small stepped-wedge cluster randomized trials. Future research is needed to establish best practices for stepped-wedge cluster randomized trials with a small number of clusters.

Personalized management of aspirin-exacerbated respiratory disease: From clinical presentation to therapeutic strategies

Aspirin-exacerbated respiratory disease (AERD), defined as the triad of asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), and development of upper- and/or lower-respiratory symptoms after exposure to aspirin or other cyclooxygenase-1 inhibitors, has a prevalence of up to 30% for adults with asthma and with CRSwNP. The pathogenesis is likely due to a combination of abnormal genetic variants and environmental exposures, which results in types 1, 2, and/or 3 inflammation and dysregulation of arachidonic acid metabolism. Patients with AERD often fail to respond to conservative medical treatment, including all topical corticosteroids, antileukotrienes, and saline solution irrigation; furthermore, short courses of SCS generally provide only temporary improvement. Advanced therapeutic options include endoscopic sinus surgery; aspirin treatment after aspirin desensitization; and biologics, e.g., dupilumab, omalizumab, and mepolizumab. A successful and long-lasting clinical response often requires combination or sequential treatments with more than one of these therapeutic approaches. After a review of the efficacy, safety, and logistical considerations of each of these therapeutic options, an algorithmic approach for patient management is presented.