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Cancer Research and Treatment May 2024Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology,...
PURPOSE
Novel clinical trial designs are conducted in the precision medicine era. This study aimed to evaluate biomarker-driven, adaptive phase II trials in precision oncology, focusing on infrastructure, efficacy, and safety.
MATERIALS AND METHODS
We systematically reviewed and analyzed the target studies. EMBASE and PubMed searches from 2015 to 2023 generated 29 eligible trials. Data extraction included infrastructure, biomarker screening methodologies, efficacy, and safety profiles.
RESULTS
Government agencies, cancer hospitals, and academic societies with accumulated experiences led investigator-initiated precision oncology clinical trials (IIPOCTs), which later guided sponsor-initiated precision oncology clinical trials (SIPOCTs). Most SIPOCTs were international studies with basket design. IIPOCTs primarily used the central laboratory for biomarker screening, but SIPOCTs used both central and local laboratories. Most of the studies adapted next-generation sequencing and/or immunohistochemistry for biomarker screening. Fifteen studies included an independent central review committee for outcome investigation. Efficacy assessments predominantly featured objective response rate as the primary endpoint, with varying results. Nine eligible studies contributed to the United States Food and Drug Administration's marketing authorization. Safety monitoring was rigorous, but reporting formats lacked uniformity. Health-related quality of life and patient-reported outcomes were described in some protocols but rarely reported.
CONCLUSION
Our results reveal that precision oncology trials with adaptive design rapidly and efficiently evaluate anticancer drugs' efficacy and safety, particularly in specified biomarker-driven cohorts. The evolution from IIPOCT to SIPOCT has facilitated fast regulatory approval, providing valuable insights into the precision oncology landscape.
PubMed: 38726510
DOI: 10.4143/crt.2024.128 -
Oral Diseases May 2024To perform a systematic review with meta-analysis to assess recent scientific evidence on the association between periodontitis and systemic parameters/conditions in... (Review)
Review
OBJECTIVE
To perform a systematic review with meta-analysis to assess recent scientific evidence on the association between periodontitis and systemic parameters/conditions in individuals with chronic kidney disease (CKD).
MATERIALS AND METHODS
The search for studies was performed in MedLine/PubMed, Scopus, Web of Science, and BIREME databases. Reference lists of selected articles were also searched. Studies with different epidemiological designs evaluating the influence of exposure to periodontitis on serum markers and mortality in individuals with CKD were eligible for inclusion. Three independent reviewers performed the article selection and data extraction. The assessment of methodological quality used the adapted Newcastle Ottawa Scale. Random effects meta-analysis was performed to calculate association measurements and 95% confidence intervals.
RESULTS
In total, 3053 records were identified in the database search, with only 25 studies meeting the eligibility criteria and, of these, 10 studies contributed data for meta-analysis. Using a random-effects model, periodontitis was associated with hypoalbuminemia (PR = 2.47; 95%CI:1.43-4.26), with high levels of C-reactive protein (PR = 1.35; 95%CI%:1.12-1.64), death from cardiovascular disease (RR = 2.29; 95%CI:1.67-3.15) and death from all causes (RR = 1.73; 95%CI:1.32-2.27).
CONCLUSIONS
The findings of this review validated a positive association between periodontitis and serum markers and mortality data in individuals with CKD.
PubMed: 38720642
DOI: 10.1111/odi.14981 -
Nutrition Reviews May 2024Riboflavin (vitamin B2) is a water-soluble micronutrient considered to be a precursor of the nucleotides flavin adenine dinucleotide and flavin mononucleotide. This...
CONTEXT
Riboflavin (vitamin B2) is a water-soluble micronutrient considered to be a precursor of the nucleotides flavin adenine dinucleotide and flavin mononucleotide. This vitamin makes up mitochondrial complexes and participates as an enzymatic cofactor in several mechanisms associated with energy metabolism.
OBJECTIVE
This systematic review collected and discussed the most relevant results on the role of riboflavin in the energy metabolism of lipids, proteins, and carbohydrates.
DATA SOURCES
A systematic search was carried out in the PubMed-Medline, Scopus, Embase, and Web of Science databases using the PICOS (Population, Intervention, Comparison, Outcome, Study design) strategy.
DATA EXTRACTION
The screening of studies went through 2 stages following predefined eligibility criteria. The information extracted covered reference details, study design, population characteristics, experimental model, treatment parameters and dosage, route of administration, duration of treatment, and results found.
DATA ANALYSIS
The risk of bias was assessed using the SYRCLE Risk of Bias (RoB) tool for in vivo studies and the QUIN tool adapted for in vitro studies, utilizing 10 domains, including selection bias, performance bias, detection bias, attrition bias, reporting bias, and other biases, to evaluate the methodological quality of the included studies.
CONCLUSION
This review concludes that riboflavin regulates energy metabolism by activating primary metabolic pathways and is involved in energy balance homeostasis.
PubMed: 38719205
DOI: 10.1093/nutrit/nuae041 -
BMC Pregnancy and Childbirth May 2024Climate change, particularly global warming, is amongst the greatest threats to human health. While short-term effects of heat exposure in pregnancy, such as preterm...
BACKGROUND
Climate change, particularly global warming, is amongst the greatest threats to human health. While short-term effects of heat exposure in pregnancy, such as preterm birth, are well documented, long-term effects have received less attention. This review aims to systematically assess evidence on the long-term impacts on the foetus of heat exposure in utero.
METHODS
A search was conducted in August 2019 and updated in April 2023 in MEDLINE(PubMed). We included studies on the relationship of environmental heat exposure during pregnancy and any long-term outcomes. Risk of bias was assessed using tools developed by the Joanna-Briggs Institute, and the evidence was appraised using the GRADE approach. Synthesis without Meta-Analysis (SWiM) guidelines were used.
RESULTS
Eighteen thousand six hundred twenty one records were screened, with 29 studies included across six outcome groups. Studies were mostly conducted in high-income countries (n = 16/25), in cooler climates. All studies were observational, with 17 cohort, 5 case-control and 8 cross-sectional studies. The timeline of the data is from 1913 to 2019, and individuals ranged in age from neonates to adults, and the elderly. Increasing heat exposure during pregnancy was associated with decreased earnings and lower educational attainment (n = 4/6), as well as worsened cardiovascular (n = 3/6), respiratory (n = 3/3), psychiatric (n = 7/12) and anthropometric (n = 2/2) outcomes, possibly culminating in increased overall mortality (n = 2/3). The effect on female infants was greater than on males in 8 of 9 studies differentiating by sex. The quality of evidence was low in respiratory and longevity outcome groups to very low in all others.
CONCLUSIONS
Increasing heat exposure was associated with a multitude of detrimental outcomes across diverse body systems. The biological pathways involved are yet to be elucidated, but could include epigenetic and developmental perturbations, through interactions with the placenta and inflammation. This highlights the need for further research into the long-term effects of heat exposure, biological pathways, and possible adaptation strategies in studies, particularly in neglected regions. Heat exposure in-utero has the potential to compound existing health and social inequalities. Poor study design of the included studies constrains the conclusions of this review, with heterogenous exposure measures and outcomes rendering comparisons across contexts/studies difficult.
TRIAL REGISTRATION
PROSPERO CRD 42019140136.
Topics: Humans; Female; Pregnancy; Hot Temperature; Prenatal Exposure Delayed Effects; Climate Change; Infant, Newborn; Adult
PubMed: 38704541
DOI: 10.1186/s12884-024-06512-0 -
Nurse Education Today Aug 2024This study assesses changes and challenges within the nursing curriculum in the Brazilian context, focusing on addressing contemporary professional and societal demands. (Review)
Review
OBJECTIVE
This study assesses changes and challenges within the nursing curriculum in the Brazilian context, focusing on addressing contemporary professional and societal demands.
DESIGN
A systematic literature review (SLR) was conducted to identify and analyze the changes in Brazil's nursing curricula over time.
DATA SOURCES
Articles published between 1987 and 2023 were selected from Scopus and Web of Science databases for the systematic review.
REVIEW METHODS
A hybrid review approach was employed, integrating Systematic Literature Review (SLR), Bibliometrics, and metanarrative. The study adhered to the SPAR-4-SLR (Scientific Procedures and Rationale for Systematic Literature Reviews) protocol, involving three main stages: (i) aggregation, (ii) organization, and (iii) evaluation. The analysis primarily focused on identifying emerging trends and evaluating curricular changes over the specified timeframe.
RESULTS
Analysis of the selected literature identified four principal thematic groups that emerged during the review period: (i) longitudinal curriculum assessment, (ii) biological and health sciences, (iii) human and social sciences, and (iv) nursing sciences. Noteworthy trends included the integration of emerging topics like mental health and care for victims of violence, coupled with a notable increase in emphasis on transformative and competency-based education. Nevertheless, significant gaps were observed in the existing literature, particularly concerning the absence of perspectives from students and recent graduates and limited research on vulnerabilities within the curriculum structure.
CONCLUSIONS
This study underscores the imperative for flexible and adaptable nursing curricula that effectively address Brazil's diverse regional and social realities. It emphasizes the significance of adopting a holistic and inclusive approach to nursing education, preparing professionals to confront contemporary health challenges in a nation characterized by extensive cultural diversity and vast geographical dimensions. Further research and input from students and recent graduates are indispensable to rectify the gaps and ensure the continuous evolution of nursing education in Brazil.
Topics: Brazil; Curriculum; Humans; Education, Nursing
PubMed: 38696884
DOI: 10.1016/j.nedt.2024.106228 -
IEEE Transactions on Neural Systems and... 2024This review aims to provide a systematic analysis of the literature focused on the use of intelligent control systems in robotics for physical rehabilitation,...
This review aims to provide a systematic analysis of the literature focused on the use of intelligent control systems in robotics for physical rehabilitation, identifying trends in recent research and comparing the effectiveness of intelligence used in control, with the aim of determining important factors in robot-assisted rehabilitation and how intelligent controller design can improve them. Seven electronic research databases were searched for articles published in the years 2015 - 2022 with articles selected based on relevance to the subject area of intelligent control systems in rehabilitation robotics. It was found that the most common use of intelligent algorithms for control is improving traditional control strategies with optimization and learning techniques. Intelligent algorithms are also commonly used in sensor output mapping, model construction, and for various data learning purposes. Experimental results show that intelligent controllers consistently outperform non-intelligent controllers in terms of transparency, tracking accuracy, and adaptability. Active participation of the patients and lowered interaction forces are consistently mentioned as important factors in improving the rehabilitation outcome as well as the patient experience. However, there are limited examples of studies presenting experimental results with impaired participants suffering limited range of motion, so the effectiveness of therapy provided by these systems is often difficult to quantify. A lack of universal evaluation criteria also makes it difficult to compare control systems outside of articles which use their own comparison criteria.
Topics: Humans; Robotics; Algorithms; Artificial Intelligence; Rehabilitation; Treatment Outcome
PubMed: 38696295
DOI: 10.1109/TNSRE.2024.3396065 -
Brain Impairment : a Multidisciplinary... Jan 2024Background Stigma after Acquired Brain Injury (ABI) has been described as a significant obstacle for the recovery of survivors. Despite its theoretical and clinical...
Background Stigma after Acquired Brain Injury (ABI) has been described as a significant obstacle for the recovery of survivors. Despite its theoretical and clinical relevance, studies dedicated to stigma after ABI are just starting to emerge. The goal of this systematic review was to integrate the existing scientific evidence and develop a model of stigma after brain injury that can guide interventions at different levels. Method Three electronic databases were employed. A search strategy was adapted for each database. Articles that explored stigma in adult ABI populations were included. All articles used quantitative, qualitative or mixed method designs and were published in English, Spanish or Portuguese. Results A total of 21 articles were selected. They considered three types of stigma after ABI: (1) self-stigma, (2) stigma-by-association and (3) public stigma. It was also found that information can be processed at implicit and explicit levels across all three forms of stigma. Definitions of each type of stigma used with ABIs are provided as well as related concepts and theoretical frameworks employed. Evidence emerging from different forms of stigma after ABI is summarised. Conclusion Research on stigma after ABI is heterogeneous, and existing studies have explored its impact at individual, family and public levels. A model of stigma after ABI should consider all these levels as well as the interactions that can occur between them. Future studies should explore how to incorporate stigma management as part of neuropsychological rehabilitation programs.
Topics: Humans; Social Stigma; Brain Injuries
PubMed: 38683937
DOI: 10.1071/IB23076 -
Trials Apr 2024The fragility index is a statistical measure of the robustness or "stability" of a statistically significant result. It has been adapted to assess the robustness of...
Assessing fragility of statistically significant findings from randomized controlled trials assessing pharmacological therapies for opioid use disorders: a systematic review.
BACKGROUND
The fragility index is a statistical measure of the robustness or "stability" of a statistically significant result. It has been adapted to assess the robustness of statistically significant outcomes from randomized controlled trials. By hypothetically switching some non-responders to responders, for instance, this metric measures how many individuals would need to have responded for a statistically significant finding to become non-statistically significant. The purpose of this study is to assess the fragility index of randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder. This will provide an indication as to the robustness of trials in the field and the confidence that should be placed in the trials' outcomes, potentially identifying ways to improve clinical research in the field. This is especially important as opioid use disorder has become a global epidemic, and the incidence of opioid related fatalities have climbed 500% in the past two decades.
METHODS
Six databases were searched from inception to September 25, 2021, for randomized controlled trials evaluating opioid substitution and antagonist therapies for opioid use disorder, and meeting the necessary requirements for fragility index calculation. Specifically, we included all parallel arm or two-by-two factorial design RCTs that assessed the effectiveness of any opioid substitution and antagonist therapies using a binary primary outcome and reported a statistically significant result. The fragility index of each study was calculated using methods described by Walsh and colleagues. The risk of bias of included studies was assessed using the Revised Cochrane Risk of Bias tool for randomized trials.
RESULTS
Ten studies with a median sample size of 82.5 (interquartile range (IQR) 58, 179, range 52-226) were eligible for inclusion. Overall risk of bias was deemed to be low in seven studies, have some concerns in two studies, and be high in one study. The median fragility index was 7.5 (IQR 4, 12, range 1-26).
CONCLUSIONS
Our results suggest that approximately eight participants are needed to overturn the conclusions of the majority of trials in opioid use disorder. Future work should focus on maximizing transparency in reporting of study results, by reporting confidence intervals, fragility indexes, and emphasizing the clinical relevance of findings.
TRIAL REGISTRATION
PROSPERO CRD42013006507. Registered on November 25, 2013.
Topics: Humans; Analgesics, Opioid; Data Interpretation, Statistical; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome
PubMed: 38678289
DOI: 10.1186/s13063-024-08104-x -
Sensors (Basel, Switzerland) Apr 2024Reinforcement learning (RL) has emerged as a dynamic and transformative paradigm in artificial intelligence, offering the promise of intelligent decision-making in... (Review)
Review
Reinforcement learning (RL) has emerged as a dynamic and transformative paradigm in artificial intelligence, offering the promise of intelligent decision-making in complex and dynamic environments. This unique feature enables RL to address sequential decision-making problems with simultaneous sampling, evaluation, and feedback. As a result, RL techniques have become suitable candidates for developing powerful solutions in various domains. In this study, we present a comprehensive and systematic review of RL algorithms and applications. This review commences with an exploration of the foundations of RL and proceeds to examine each algorithm in detail, concluding with a comparative analysis of RL algorithms based on several criteria. This review then extends to two key applications of RL: robotics and healthcare. In robotics manipulation, RL enhances precision and adaptability in tasks such as object grasping and autonomous learning. In healthcare, this review turns its focus to the realm of cell growth problems, clarifying how RL has provided a data-driven approach for optimizing the growth of cell cultures and the development of therapeutic solutions. This review offers a comprehensive overview, shedding light on the evolving landscape of RL and its potential in two diverse yet interconnected fields.
Topics: Robotics; Humans; Algorithms; Artificial Intelligence; Delivery of Health Care; Machine Learning
PubMed: 38676080
DOI: 10.3390/s24082461 -
Journal of the American Medical... Jul 2024Home-based primary care (HBPC) provides interdisciplinary, longitudinal, comprehensive care at home to homebound older adults. The prevalence of dementia among HBPC... (Review)
Review
OBJECTIVES
Home-based primary care (HBPC) provides interdisciplinary, longitudinal, comprehensive care at home to homebound older adults. The prevalence of dementia among HBPC recipients is approximately 50%. To date, little research has been performed to determine whether dementia-specific interventions have been conducted in HBPC or their efficacy. We performed a scoping review to assess the landscape of dementia interventions in HBPC.
DESIGN
Systematic scoping review.
SETTING AND PARTICIPANTS
Care delivery programs for patients or caregivers of patients with dementia for the purpose of improving the management of dementia in the setting of HBPC.
METHODS
The PRISMA-ScR protocol was followed. Literature searches were performed using PubMed, Embase, and Scopus for articles on dementia-focused interventions implemented in HBPC. Articles were excluded if they consisted of abstracts only, were not in English, or were not dementia interventions in HBPC.
RESULTS
A total of 1657 unique titles and abstracts were screened. Overall, 1584 titles and abstracts were excluded, resulting in 73 full-text studies to assess for eligibility. Of these 73 full-text studies, 1 study met criteria for inclusion, an observational study assessing the implementation of the Resources for Enhancing Alzheimer's Caregiver Health (REACH) intervention in Veterans Affairs HBPC. That study found the intervention to be effective in reducing caregiver burden, with a decrease of 2 hours on duty per day, trending toward significance. Among the excluded 72 full-text studies, some studies included potentially relevant interventions that could be translated into HBPC care, including dementia interventions that targeted long-term services and supports, office-based primary care and other nonhome settings such as nursing homes, and home-based palliative care.
CONCLUSIONS AND IMPLICATIONS
Despite high prevalence of dementia among homebound older adults receiving HBPC, there are a dearth of studies on HBPC-specific dementia interventions. Future studies should consider adapting and testing interventions found to be effective in other settings to HBPC.
Topics: Humans; Dementia; Home Care Services; Primary Health Care; Aged; Caregivers; Female; Male
PubMed: 38663452
DOI: 10.1016/j.jamda.2024.03.112