Evidence-based Considerations Research Articles

Contemporary Dental Pharmacology: Evidence-Based Considerations.

Contemporary Dental Pharmacology: Evidence-Based Considerations.

Management of Select Adverse Events Following Delandistrogene Moxeparvovec Gene Therapy for Patients With Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a rare, degenerative, recessive X-linked neuromuscular disease. Mutations in the gene encoding dystrophin lead to the absence of functional dystrophin protein. Individuals living with DMD exhibit progressive muscle weakness resulting in loss of ambulation and limb function, respiratory insufficiency, and cardiomyopathy, with multiorgan involvement. Adeno-associated virus vector-mediated gene therapy designed to enable production of functional dystrophin protein is a new therapeutic strategy. Delandistrogene moxeparvovec (Sarepta Therapeutics, Cambridge, MA) is indicated for treatment of ambulatory pediatric patients aged 4 through 5 years with DMD who have an indicated mutation in the DMD gene. Evidence-based considerations for management of potential adverse events following gene therapy treatment for DMD are lacking in clinical literature. Our goal was to provide interdisciplinary consensus considerations for selected treatment-related adverse events (TRAEs) (vomiting, acute liver injury, myocarditis, and immune-mediated myositis) that may arise following gene therapy dosing with delandistrogene moxeparvovec. An interdisciplinary panel of 12 specialists utilized a modified Delphi process to develop consensus considerations for the evaluation and management of TRAEs reported in delandistrogene moxeparvovec clinical studies. Panelists completed 2 Questionnaires prior to gathering for an in-person discussion. Consensus was defined as a majority (≥58% ; 7/12) of panelists either agreeing or disagreeing. Panelists agreed that the choice of baseline assessments should be informed by individual clinical indications, the treating provider's judgment, and prescribing information. Corticosteroid dosing for treatment of TRAEs should be optimized by considering individual risk versus benefit for each indication. In all cases involving patients with a confirmed TRAE, consultations with appropriate specialists were suggested. The Delphi Panel established consensus considerations for the evaluation and management of potential TRAEs for patients receiving delandistrogene moxeparvovec, including vomiting, acute liver injury, myocarditis, and immune-mediated myositis.

Bridging the humanitarian-development divide in a protracted crisis: a case study of the use of a central plant to supply oxygen for COVID-19 case management in South Sudan.

The rising demand for medicinal oxygen due to the COVID-19 pandemic exacerbated an underlying chronic shortage of the commodity in Africa. This situation is particularly dire in protracted crises where insecurity, dysfunctional health facilities, poor infrastructure and prohibitive costs hinder equitable access to the commodity. Against this backdrop, the Ministry of Health of South Sudan, with the guidance of its partners, procured and installed a pressure swing adsorption central oxygen supply plant to address the shortfall. The plant aimed to ensure a more sustainable and technologically appropriate medicinal oxygen supply system for the country and to bridge the humanitarian and development divide, which had always been challenging. This article discusses the key issues, challenges and lessons associated with the procurement and installation of this plant. The major challenges encountered during the procurement and installation of the plant were the time it took to procure and install in the face of urgent needs for medicinal oxygen and its short and long-term sustainability. Lessons learnt include the need for exhaustive and evidence-based considerations in deciding on which source of medicinal oxygen to deploy in protracted crisis settings. The successful installation and operationalization of the plant demonstrated that it is possible to bridge the humanitarian-development divide amidst the complexities of a protracted crisis and an ongoing pandemic. The Ministries of Health, with the support of its partners, should assess and document the impact of this and other similar central oxygen production plants in protracted crisis settings regarding their sustainability, cost, and effectiveness on medicinal oxygen supply. The Ministry of Health of South Sudan should expedite the finalization and operationalization of the longer-term public-private partnership and continue to monitor the quality of oxygen produced by this plant.

Internal and external load during on-field training drills with an aim of improving the physical performance of players in professional soccer: a retrospective observational study.

Extensive research has led to evidence-based methodological recommendations for appropriate prescription and implementation of different training drills to improve the physical performance of professional soccer players, while also pointing out limitations of drills. Less is known about the current methods used in an ecological context and the extent to which evidence-based considerations are applied. Knowledge of current practices might also enable to identify pitfalls in successful implementation and/or deficiencies in the communication of scientific knowledge. Thus, the aim of this study was to quantify and compare the load that players experience in an ecological context during drills that are frequently used, and in which there is an intention to improve the players' physical capacities. Therefore, a retrospective observational cohort study was conducted over a 14-month period, analyzing 9 load measures during training drills of 39 players of a team competing in the highest Swiss league. The load experienced by players was statistically significant different between the assessed drill categories for each load measure (all p < .001). This indicates different drills provide different stimuli. HIIT drills proved to be a more powerful tool of getting players to cover distances at high-speed and to spend time at an intensity ≥90% HRmax compared to sided games. The sprint distance of players was very low in all sided games and in most cases also in HIIT drills, in the latter the players also hardly performed any deceleration. In small goal-oriented sided games, players covered a greater distance per minute when outside floaters were present. Particularly regarding an improvement of the players' aerobic capacity, the present data emphasize the relevance for coaches to ensure an appropriate exposure. In general, the importance of individual load management in professional soccer is highlighted.

H - 67 Socially Responsible Neuropsychology (SRN) in Action: Considering Culture, Brain Structure, and Function Longitudinally in an Atypical Pituitary Adenoma Case.

Research on the neuropsychological profile associated with pituitary adenoma (PA) in diverse populations is limited. Clinically, PAs are categorized by size (micro-vs-macro) and hormone secretion levels (functional/secreting-vs-nonfunctional/non-secreting [NFPA]). Macro-NFPA are associated with visual-spatial, memory, and executive functioning declines, likely due to mass effects. No previous reports of cognitive declines in micro-NFPA were found in the literature. We present a clinical case illustrating the application of an SRN model in a 75-year-old, Spanish-English bilingual male, with cognitive declines, diagnosed with micro-NFPA. An SRN model was applied to promote equitable care through evidence-based consideration of neuropsychological syndromes in bilinguals, neurodiagnostics, and complex psychosocial factors. The patient underwent longitudinal language-congruent neuropsychological assessment and structural/functional neuroimaging. Educational background, linguistic proficiencies, acculturation level, social/behavioral comportment, and limitations in available neuropsychological tools/norms were integrated to reflect the complexity in conducting a reliable bilingual assessment and formulating differential diagnoses. The SRN model guided complex clinical decision-making. Neuropsychological profile (frontal-subcortical-vs-cortical-involvement) varied across language and time-point. Within/between variable performances in memory, executive functioning, processing speed, and verbal fluency were inconsistent with structural neuroimaging at assessment points, increasing diagnostic ambiguity. Advocated-for functional neuroimaging revealed pituitary hypometabolism. To our knowledge, this is the first reported case of neurocognitive impairment in micro-NFPA, and the first reported neuropsychological profile of a bilingual individual with PA. The findings suggest the need for further research on neurocognitive declines in NFPA in diverse populations. It also highlights the importance of assessing in all relevant languages when conducting longitudinal assessments to boost sensitivity and specificity in differential diagnoses.

A comparative cradle-to-grave life cycle approach for addressing construction design choices: An applicative case study for a residential tower in Aalborg, Denmark

Energy demand reduction targets and sustainable design paradigms are fueling the search for more and more effective design solutions in the building sector, and new technologies and construction systems are being presented. However, each design solution has its own consequences for the environmental impact of the building. The use of Building Information Modelling (BIM) and Life Cycle Assessment (LCA) can be profitably adopted for supporting the decision-making process. This paper reports a comparative methodology developed to analyse the impacts of alternative structural solutions for timber-based high-rise structures. Embodied, operational, and end-of-life environmental impacts based on two structural frame types, a reinforced concrete (RC) structure and cross-laminated timber (CLT) are explored. Two main inputs are used for performing a comprehensive cradle-to-grave LCA for the whole building: the bill of quantities from a Revit BIM model and the energy demand from DesignStudio. Then, an LCA is performed using the One Click LCA tool for a service life of 50 years and 12 impact categories. The environmental impacts of building materials are based on Environmental Product Declarations (EPDs) directly embedded in the tool. The method is then applied to a case study in Aalborg, Denmark. Results indicate that the total emissions for the considered case study are 9.6 kg- CO2 eq./m2/y for the CLT structure against 10.8 kg- CO2 eq./m2/y for the RC structure. The production stage of building materials, including building systems and installations, accounts for around 55% of the total emissions, while energy use (B6 phase) during the in-use stage of the building recorded a lower environmental impact (45%). The outcomes confirm the opportunity to base the discussion on alternative design options on more objective and data-based elements to support the different positions which already involve a wide range of architectural, functional and financial criteria. This is of great relevance in achieving balanced and informed decisions which do not simply follow green-labelled ideas but are grounded on evidence-based considerations.

Beyond the conventional view of bipolarity: methodological considerations for examining the relationship between well-being and ill-being

ABSTRACT One of the controversies central to the study of positive psychology is whether well-being is the bipolar opposite of, or independent of, ill-being. In a recent study , we utilized a data-driven approach and found that well-being and ill-being represent opposite ends of a bipolar continuum. In response to our work, a recent commentary in the Journal of Positive Psychology argued that positive psychology is better served by a bivariate rather than a bipolar conceptualization. In this article, we clarify that our position is driven by evidence-based considerations rather than theoretical ideology and call attention to refining the methodological understanding of bipolarity. We point out that the evidence supporting bipolarity can be confounded by measurement artifacts, and that well-being and ill-being co-endorsements and functional independence present insufficient justification for shifting the investigation away from bipolarity. We welcome more rigorous investigations to foster open and humble constructive dialogue.

Clinical management of mosaic results from preimplantation genetic testing for aneuploidy of blastocysts: a committee opinion

This revised document incorporates a growing number of published studies about mosaic embryo transfer and provides current evidence-based considerations for the clinical management of embryos with mosaic results on preimplantation genetic testing for aneuploidy. This document replaces the document titled "Clinical management of mosaic results from preimplantation genetic testing for aneuploidy (PGT-A) of blastocysts: a committee opinion," published in 2020 (Fertil Steril 2020;114:246-54).

Effective collaborative learning for early childhood teachers: structural, motivational and sustainable features

ABSTRACT Research on teachers’ professional learning and development (PLD) has investigated the nature and design of such learning initiatives, itemising characteristics that promote high-quality PLD and outcomes for individual teachers. However, much learning for teachers happens as they work together to consider and discuss their ability to implement their new learning. Features that create teacher collaboration have not been as explicitly pinpointed within the existing literature. We report a content analysis of literature aimed at identifying and grouping features of what we term ‘teachers’ collaborative learning’ (TCL), specifically for early childhood teachers. Three interdependent themes that promote collaboration were identified. First, structural features reflect how effective TCL is organised. Second, motivational features promote the depth and quality of teachers’ learning experience. The third set of features are those that promote sustainability of both changes and improvements in teaching and learning arising from TCL. We argue that an understanding of effective TCL for early childhood teachers is enhanced when many of these features function together cohesively. We conclude with evidence-based considerations for designing PLD. We highlight the need to address power differences in PLD, respond to cultural issues affecting knowledge building, and understand challenges faced in teachers sustaining collaborative learning.

'Drug decriminalization' in Canada: a plea for a nuanced, evidence-informed, and realistic approach towards improved health outcomes.

Canada has been home to an exceptional public health crisis of illicit (mainly synthetic opioid but increasingly other) drug deaths for numerous years. Despite extensive health-oriented interventions, this crisis remains acute and devastating. Earlier this year, the federal and British Columbia governments implemented the 'drug decriminalization initiative' (DDI) which exempts drug users from criminal enforcement of small amounts of personal drug possession; this has been promoted as a 'solution' for the drug-death crisis. This commentary examines and discusses that while decriminalization of drug use is fundamentally required to align drug policy with principles of health, evidence-based consideration of the drug death crisis' essential dynamics as well as enforcement realities substantially curtail the DDI's plausible prospects to significantly reduce the drug-fatality toll. Decriminalization efforts elsewhere ('Portugal model') are set in distinct ecologies and parameters, and not readily transferable to Canadian contexts. While the DDI has symbolic value for policy reform, for decriminalization to provide tangible benefits for drug users and public health, its scope and design require fundamental reconsideration and improvement. Meanwhile, given the principally causal role of toxic drug supply for the current drug-death epidemic, more effective health and life-saving measures-specifically involving 'safer supply'-need to be urgently implemented to alleviate this crisis.

Key questions for the evaluation of anti-amyloid immunotherapies for Alzheimer's disease.

The clinical benefit associated with anti-amyloid immunotherapies, a new class of drugs for the treatment of Alzheimer's disease, is predicated on their ability to modify disease course by lowering brain amyloid levels. At the time of writing, two amyloid-lowering antibodies, aducanumab and lecanemab, have obtained United States Food and Drug Administration accelerated approval, with further agents of this class in the Alzheimer's disease treatment pipeline. Based on limited published clinical trial data to date, regulators, payors and physicians will need to assess their efficacy, clinical effectiveness and safety, as well as cost and accessibility. We propose that attention to three important questions related to treatment efficacy, clinical effectiveness and safety should guide evidence-based consideration of this important class of drugs. These are: (1) Were trial statistical analyses appropriate and did they convincingly support claims of efficacy? (2) Do reported treatment effects outweigh safety concerns and are they generalizable to a representative clinical population of people with Alzheimer's disease? and (3) Do the data convincingly demonstrate disease course modification, suggesting that increasing clinical benefits beyond the duration of the trials are likely? We suggest specific approaches to interpreting trial results for these drugs and highlight important areas of uncertainty where additional data and a cautious interpretation of existing results is warranted. Safe, effective and accessible treatments for Alzheimer's disease are eagerly awaited by millions of patients and their caregivers worldwide. While amyloid-targeting immunotherapies may be promising disease-modifying Alzheimer's disease treatments, rigorous and unbiased assessment of clinical trial data is critical to regulatory decision-making and subsequently determining their provision and utility in routine clinical practice. Our recommendations provide a framework for evidence-based appraisal of these drugs by regulators, payors, physicians and patients.

Evidence-based Considerations on Donor Nerve Selection and Ideal Muscle Weight in Long-standing Facial Paralysis – The Freiburg Algorithm

Introduction: Free functional muscle transfer (FMT) is the standard for smile reconstruction in long-standing facial paralysis. Using the contralateral NVII for innervation of the transferred muscle frequently produces satisfying results. However, axon counts of facial nerve branches used as donor nerves for cross-face nerve grafts (CFNG) generally decrease with age resulting in insufficient muscle contraction. Also, the volume of the transferred muscle segment necessary for symmetric oral excursion depends on the donor nerve. This study presents our algorithm for donor nerve selection and ideal muscle weight in long-standing facial paralysis. Materials and Methods: In a prospective cohort study, we evaluated facial palsy patients scheduled for dynamic smile reanimation preoperatively via EMG for involuntary masseter muscle activation upon smiling. Six months after noting the first muscle contraction, we assessed smile synchronicity and correlated the results with the EMG results. Furthermore, we correlated oral commissure amplitude with the weight of the muscle segment and the donor nerve used. Results: We recruited 30 patients for the prospective study and included 22 patients in the retrospective analysis. Postoperatively, all patients demonstrated a voluntary smile. The preoperative coactivation of the masseter muscle predicted the outcome regarding synchronicity of the smile with high sensitivity and specificity. Also, we observed a significant increase in oral commissure excursion with increasing muscle weight when using the NV. Conclusion: The lack of masseter coactivation upon smiling predicts the absence of a synchronous, involuntary smile after FMT using the masseteric nerve. The ideal muscle weight depends on the donor nerve and should be smaller for the NV.

How to Effectively Promote Eco-Friendly Behaviors: Insights from Contextual Behavioral Science

The rapidly increasing rate of climate change is a major threat of our time. Human behaviors contribute to climate change. These behaviors are malleable. To change human behavior in significant and sustainable ways, we need a scientific understanding of motivation and behavior change. One area in psychological science that provides precision, scope, and depth to our understanding of human behavior and motivation is contextual behavioral science (CBS). The current article provides an account of how CBS can provide real-world solutions to promoting positive behavior change to reduce human-induced climate issues. Specifically, we will outline six evidence-based considerations for organizations aiming to promote pro-environmental behaviors through messaging, advertising, and social marketing. Practical examples are provided across all six considerations to promote behavior change to reduce the rapidly increasing rate of climate change.

Evidence-based considerations on bowel preparation for colonoscopy.

We recently read with interest the article, “Novel frontiers of agents for bowel cleansing for colonoscopy”. This is a practical narrative review, which could be of particular importance to clinicians in order to improve their current practice. Although we appreciate the venture of our colleagues, based on our in-depth analysis, we came across several minor issues in the article; hence, we present our comments in this letter. If the authors consider these comments further in their relevant research, we believe that their contribution would be of considerable importance for future studies.

Evidence-Based Considerations for the Design of an Open-Source Ventilator: A Systematic Review.

OBJECTIVE:To inform the design of open-source ventilators, we performed a systematic review of clinical practice guidelines (CPGs) to consolidate the evidence on mechanical ventilation strategies that result in improved patient-important outcomes for acute hypoxic respiratory failure.DATA SOURCES:We developed a search strategy to identify relevant CPGs from Ovid Medline, Ovid Medline In-Process & Other Non-Indexed Citations, Embase, the Cochrane Library, Mendeley, and Google scholar from 2010 to February 17, 2022.STUDY SELECTION:Using a two-step screening process with two independent reviewers, we included CPGs that made recommendations on mechanical ventilation strategies of interest. Guidelines that reported at least one recommendation about mechanical ventilation in ICU patients with acute hypoxic respiratory failure were included.DATA EXTRACTION:From the 13 eligible guidelines, we collected data on country, aim, patient population, impact on morbidity and mortality (effect size and CIs), recommendations, strength of Recommendation (as per Grading of Recommendations, Assessment, Development and Evaluations), and details of supporting evidence base.DATA SYNTHESIS:We identified three ventilation strategies that confer a mortality and morbidity benefit for ventilated patients with acute hypoxic respiratory failure: low-tidal volume ventilation, plateau pressures of less than 30 cm H2O, and higher positive end-expiratory pressure (PEEP). These moderate-to-strong recommendations were based on moderate-to-high certainty in evidence. We identified several other recommendations with no or minimal certainty in evidence.CONCLUSIONS:Our systematic review of international CPGs identified no recommendations favoring specific mode of ventilation and three ventilation strategies that confer mortality and morbidity benefits, backed by moderate-to-strong evidence. Ventilator design teams must include the ability to consistently provide and measure low-tidal volume ventilation, plateau pressures of less than 30 cm H2O, and higher PEEP into their designs. Based on our findings, we provide the first public framework for open-source ventilator design.

Integrating Immunotherapy in Early-Stage Triple-Negative Breast Cancer: Practical Evidence-Based Considerations.

The KEYNOTE-522 study is a practice-changing phase III randomized study that demonstrated that the addition of pembrolizumab to polychemotherapy improves outcomes in patients with high-risk early-stage triple-negative breast cancer (TNBC). This regimen is highly efficacious with unprecedented pathologic complete response (pCR) rates, and clinically meaningful improvements in event-free survival (EFS). However, the combination is also associated with significant high-grade treatment-related toxicity. The backbone regimen deviated from common practice, including the addition of carboplatin, lack of dose dense anthracyclines, and adjuvant capecitabine for residual disease, thus brining important questions regarding real-world translation of these results. This brief report practically addresses some of the most relevant questions physicians and patients face in optimizing care using the best available evidence.

Articulation of postsurgical patient discharges: coordinating care transitions from hospital to home.

Cardiac surgery patients are at high risk for readmissions after hospital discharge- few of these readmissions are preventable by mitigating barriers underlying discharge care transitions. An in-depth evaluation of the nuances underpinning the discharge process and the use of tools to support the process, along with insights on patient and clinician experiences, can inform the design of evidence-based strategies to reduce preventable readmissions. The study objectives are 3-fold: elucidate perceived factors affecting the postsurgical discharge care transitions of cardiac surgery patients going home; highlight differences among clinician and patient perceptions of the postsurgical discharge experiences, and ascertain the impact of these transitions on patient recovery at home. We conducted a prospective multi-stakeholder study using mixed methods, including general observations, patient shadowing, chart reviews, clinician interviews, and follow-up telephone patient and caregiver surveys/interviews. We followed thematic and content analyses. Participants included 49 patients, 6 caregivers, and 27 clinicians. We identified interdependencies between the predischarge preparation, discharge education, and postdischarge follow-up care phases that must be coordinated for effective discharge care transitions. We identified several factors that could lead to fragmented discharges, including limited preoperative preparation, ill-defined discharge education, and postoperative plans. To address these, clinicians often performed behind-the-scenes work, including offering informal preoperative preparation, tailoring discharge education, and personalizing postdischarge follow-up plans. As a result, majority of patients reported high satisfaction with care transitions and their positive impact on their home recovery. Articulation work by clinicians (ie, behind the scenes work) is critical for ensuring safety, care continuity, and overall patient experience during care transitions. We discuss key evidence-based considerations for re-engineering postsurgical discharge workflows and re-designing discharge interventions.

For profit and progress: Rethinking the role of the private sector in humanitarian action

Key global frameworks and guiding strategies including the Sendai Framework for Disaster Risk Reduction 2015-2030 highlight the value of the private sector in the fields of humanitarian action and disaster risk management (DRM). Nonetheless, the fundamental ‘business case’ for commercial enterprises to be actively engaged in DRM and addressing humanitarian crises still requires further examination and evidence-based consideration to determine mutually beneficial value addition. This paper provides a conceptual overview of the shift in the private sector’s engagement in humanitarian action and DRM. It also considers how such engagement with the private sector has corresponded with a heightened recognition for commercial enterprises to safeguard their own business operations from disaster events while implementing development interventions that address the needs of populations affected by disasters.

The role of the neural stimulus in regulating skeletal muscle hypertrophy.

Resistance training is frequently performed with the goal of stimulating muscle hypertrophy. Due to the key roles motor unit recruitment and mechanical tension play to induce muscle growth, when programming, the manipulation of the training variables is oriented to provoke the correct stimulus. Although it is known that the nervous system is responsible for the control of motor units and active muscle force, muscle hypertrophy researchers and trainers tend to only focus on the adaptations of the musculotendinous unit and not in the nervous system behaviour. To better guide resistance exercise prescription for muscle hypertrophy and aiming to delve into the mechanisms that maximize this goal, this review provides evidence-based considerations for possible effects of neural behaviour on muscle growth when programming resistance training, and future neurophysiological measurement that should be tested when training to increase muscle mass. Combined information from the neural and muscular structures will allow to understand the exact adaptations of the muscle in response to a given input (neural drive to the muscle). Changes at different levels of the nervous system will affect the control of motor units and mechanical forces during resistance training, thus impacting the potential hypertrophic adaptations. Additionally, this article addresses how neural adaptations and fatigue accumulation that occur when resistance training may influence the hypertrophic response and propose neurophysiological assessments that may improve our understanding of resistance training variables that impact on muscular adaptations.

Position Paper on the Management of Pregnancy-Associated Superficial Venous Thrombosis. Balkan Working Group for Prevention and Treatment of Venous Thromboembolism.

Venous thromboembolism (VTE) is a multifactorial disease that can possibly affect any part of venous circulation. The risk of VTE increases by about 2 fold in pregnant women and VTE is one of the major causes of maternal morbidity and mortality. For decades superficial vein thrombosis (SVT) has been considered as benign, self-limiting condition, primarily local event consequently being out of scope of well conducted epidemiological and clinical studies. Recently, the approach on SVT has significantly changed considering that prevalence of lower limb SVT is twice higher than both deep vein thrombosis (DVT) and pulmonary embolism (PE). The clinical severity of SVT largely depends on the localization of thrombosis, when it concerns the major superficial vein vessels of the lower limb and particularly the great saphenous vein. If untreated or inadequately treated, SVT can potentially cause DVT or PE. The purpose of this review is to discuss the complex interconnection between SVT and risk factors in pregnancy and to provide evidence-based considerations, suggestions, and recommendations for the diagnosis and treatment of this precarious and delicate clinical entity.