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ABSTRACT BACKGROUND Due to a shortage of studies focusing on older adults, clinicians and policy makers frequently rely on clinical trials of the general population to provide supportive evidence for treating complex, older patients. OBJECTIVES To examine the inclusion and analysis of complex, older adults in randomized controlled trials. REVIEW METHODS A PubMed search identified phase III or IV randomized controlled trials published in 2007 in JAMA, NEJM, Lancet, Circulation, and BMJ. Therapeutic interventions that assessed major morbidity or mortality in adults were included. For each study, age eligibility, average age of study population, primary and secondary outcomes, exclusion criteria, and the frequency, characteristics, and methodology of age-specific subgroup analyses were reviewed. RESULTS Of the 109 clinical trials reviewed in full, 22 (20.2%) excluded patients above a specified age. Almost half (45.6%) of the remaining trials excluded individuals using criteria that could disproportionately impact older adults. Only one in four trials (26.6%) examined outcomes that are considered highly relevant to older adults, such as health status or quality of life. Of the 42 (38.5%) trials that performed an age-specific subgroup analysis, fewer than half examined potential confounders of differential treatment effects by age, such as comorbidities or risk of primary outcome. Trials with age-specific subgroup analyses were more likely than those without to be multicenter trials (97.6% vs. 79.1%, p < 0.01) and funded by industry (83.3% vs. 62.7%, p < 0.05). Differential benefit by age was found in seven trials (16.7%). CONCLUSION Clinical trial evidence guiding treatment of complex, older adults could be improved by eliminating upper age limits for study inclusion, by reducing the use of eligibility criteria that disproportionately affect multimorbid older patients, by evaluating outcomes that are highly relevant to older individuals, and by encouraging adherence to recommended analytic methods for evaluating differential treatment effects by age.

The exploitation of renewable energy resources is an effective option to respond to climate change challenges. Wind energy can be exploited more efficiently and effectively than any other renewable energy source. By switching from onshore wind energy projects to offshore, the positive aspects of onshore wind energy remain and, at the same time, no valuable onshore area is occupied, while their efficiency (e.g., capacity factor) is increased. Greece has a rich wind potential and the maritime region of Thrace is one of Greece’s maritime regions with the greatest potential for the development of offshore wind energy. The aim of the present paper is to identify the most appropriate sites for the deployment of offshore wind farms in the region of Thrace. The methodology includes (i) the delineation of the study area and the definition of the support structure of the wind turbine, (ii) the identification of seven (7) exclusion and fifteen (15) assessment criteria, (iii) the suitability analysis under five different zoning scenarios (equal weight, environmental, social, techno-economic, and researchers’ subjective), and (iv) the micro siting and qualitative assessment of the most suitable sites based on energy, environmental, social, and economic criteria. The methodology is based on the combined use of Geographical Information Systems (GISs), specifically ArcGIS Desktop version 10.8.1, wind assessment software tools (WaSPs), specifically WaSP version 12.8, and multi-criteria decision-making methods. The results of the paper illustrate that the optimal suitability area that is proposed for offshore wind farm deployment is located at the easternmost end of the Greek part of the Thracian Sea. The planning and the deployment of offshore wind farm projects should follow a holistic and environmentally driven approach to ensure the integrity of all habitats and species affected.

Background Breast cancer (BC) is the most common cancer type in women. The purpose of this study was to assess the eligibility criteria in recent clinical trials in BC, especially those that can limit the enrollment of older patients as well as those with comorbidities and poor performance status. Methods Data on clinical trials in BC were extracted from ClinicalTrials.gov. Co-primary outcomes were proportions of trials with different types of the eligibility criteria. Associations between trial characteristics and the presence of certain types of these criteria (binary variable) were determined with univariate and multivariate logistic regression. Results Our analysis included 522 trials of systemic anticancer treatments started between 2020 and 2022. Upper age limits, strict exclusion criteria pertaining to comorbidities, and those referring to inadequate performance status of the patient were used in 204 (39%), 404 (77%), and 360 (69%) trials, respectively. Overall, 493 trials (94%) had at least one of these criteria. The odds of the presence of each type of the exclusion criteria were significantly associated with investigational site location and trial phase. We also showed that the odds of the upper age limits and the exclusion criteria involving the performance status were significantly higher in the cohort of recent trials compared with cohort of 309 trials started between 2010 and 2012 (39% vs 19% and 69% vs 46%, respectively; p  < 0.001 for univariate and multivariate analysis in both comparisons). The proportion of trials with strict exclusion criteria was comparable between the two cohorts ( p  > 0.05). Only three of recent trials (1%) enrolled solely patients aged 65 or 70 and older. Conclusions Many recent clinical trials in BC exclude large groups of patients, especially older adults, individuals with different comorbidities, and those with poor performance status. Careful modification of some of the eligibility criteria in these trials should be considered to allow investigators to assess the benefits and harms of investigational treatments in participants with characteristics typically encountered in clinical practice.

Background: Antidepressants are amongst the most frequently prescribed medications. More than a decade ago, our clinical research group applied a prototypic set of inclusion/exclusion criteria used in an antidepressant efficacy trial (AET) to patients presenting for treatment in our outpatient practice and found that most patients would not qualify for the trial. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we apply the psychiatric inclusion/exclusion criteria used in 158 placebo-controlled studies to a large sample of depressed patients who presented for outpatient treatment to determine the range and extent of the representativeness of samples treated in AETs and whether this has changed over time. Method: We applied the inclusion and exclusion criteria used in 158 AETs to 1,271 patients presenting to an outpatient practice who received a principal diagnosis of major depressive disorder. The patients underwent a thorough diagnostic evaluation. Results: Across all 158 studies, the percentage of patients that would have been excluded ranged from 44.4 to 99.8% (mean = 86.1%). The percentage of patients that would have been excluded was significantly higher in the studies published in 2010 through 2014 compared to the studies published from 1995 to 2009 (91.4 vs. 83.8%, t(156) = 3.74, p < 0.001). Conclusions: Only a minority of depressed patients seen in clinical practice are likely to be eligible for most AETs. The generalizability of AETs has decreased over time. It is unclear how generalizable the results of AETs are to patients treated in real-world clinical practice.

The purpose of this paper is to systematically sort out and analyze the cutting-edge research on the eligibility criteria of clinical trials. Eligibility criteria are important prerequisites for the success of clinical trials. It directly affects the final results of the clinical trials. Inappropriate eligibility criteria will lead to insufficient recruitment, which is an important reason for the eventual failure of many clinical trials. We have investigated the research status of eligibility criteria for clinical trials on academic platforms such as arXiv and NIH. We have classified and sorted out all the papers we found, so that readers can understand the frontier research in this field. Eligibility criteria are the most important part of a clinical trial study. The ultimate goal of research in this field is to formulate more scientific and reasonable eligibility criteria and speed up the clinical trial process. The global research on the eligibility criteria of clinical trials is mainly divided into four main aspects: natural language processing, patient pre-screening, standard evaluation, and clinical trial query. Compared with the past, people are now using new technologies to study eligibility criteria from a new perspective (big data). In the research process, complex disease concepts, how to choose a suitable dataset, how to prove the validity and scientific of the research results, are challenges faced by researchers (especially for computer-related researchers). Future research will focus on the selection and improvement of artificial intelligence algorithms related to clinical trials and related practical applications such as databases, knowledge graphs, and dictionaries.

The recruitment of participants for clinical trials has traditionally been a passive and challenging process, leading to difficulties in acquiring a sufficient number of qualified participants in a timely manner. This issue has impeded advancements in medical research. However, recent years have seen the evolution of knowledge graphs and the introduction of large language models (LLMs), providing innovative approaches for the pre-screening and recruitment phases of clinical trials. These developments promise enhanced recruitment efficiency and increased participant involvement. To ensure the safety and efficacy of clinical trials, it is crucial to establish precise inclusion and exclusion criteria for participant selection. This paper introduces a method to optimize the pre-recruitment stage by utilizing these criteria in conjunction with the cutting-edge capabilities of knowledge graphs and LLMs. The enhanced strategy includes the automated generation of questionnaires, algorithmic evaluation of eligibility, supplemental query-response functions, and a broader participant screening reach. The application of this framework yielded a detailed clinical trial recruitment questionnaire that accurately encompasses all necessary criteria. Its JSON output is noteworthy for its precision and reliability, achieving an impressive 90% accuracy rate in summarizing patient responses. Additionally, the questionnaire’s ancillary question-and-answer feature complies with stringent legal and ethical standards, meeting the requirements for practical deployment. This study validates the practicality and technological soundness of the presented approach. Utilizing this framework is expected to enhance the efficiency of trial recruitment and the level of patient participation.

Background Low back pain is a common health complaint resulting in substantial economic burden. Each year, upwards of 20 randomised controlled trials (RCTs) evaluating interventions for non-specific low back pain are published. Use of the term non-specific low back pain has been criticised on the grounds of encouraging heterogeneity and hampering interpretation of findings due to possible heterogeneous causes, challenging meta-analyses. We explored selection criteria used in trials of treatments for nsLBP. Methods A systematic review of English-language reports of RCTs in nsLBP population samples, published between 2006 and 2012, identified from MEDLINE, EMBASE, and the Cochrane Library databases, using a mixed-methods approach to analysis. Study inclusion and exclusion criteria were extracted, thematically categorised, and then descriptive statistics were used to summarise the prevalence by emerging category. Results We included 168 studies. Two inclusion themes (anatomical area, and symptoms and signs) were identified. Anatomical area was most reported as between costal margins and gluteal folds ( n  = 8, 5%), while low back pain ( n  = 150, 89%) with or without referred leg pain ( n  = 27, 16%) was the most reported symptom. Exclusion criteria comprised 21 themes. Previous or scheduled surgery ( n  = 84, 50%), pregnancy ( n  = 81, 48%), malignancy ( n  = 78, 46%), trauma ( n  = 63, 37%) and psychological conditions ( n  = 58, 34%) were the most common. Sub-themes of exclusion criteria mostly related to neurological signs and symptoms: nerve root compromise ( n  = 44, 26%), neurological signs ( n  = 34, 20%) or disc herniation ( n  = 30, 18%). Specific conditions that were most often exclusion criteria were spondylolisthesis ( n  = 35, 21%), spinal stenosis ( n  = 31, 18%) or osteoporosis ( n  = 27, 16%). Conclusion RCTs of interventions for non-specific low back pain have incorporated diverse inclusion and exclusion criteria. Guidance on standardisation of inclusion and exclusion criteria for nsLBP trials will increase clinical homogeneity, facilitating greater interpretation of between-trial comparisons and meta-analyses. We propose a template for reporting inclusion and exclusion criteria.

PurposeA multidisciplinary approach is recommended for patients with complex chronic pain (CP). Many multidisciplinary pain treatment facilities (MTPFs) use patient exclusion criteria but little is known about their characteristics. The objective of this study was to describe the frequency and characteristics of exclusion criteria in public Canadian MTPFs.MethodsWe conducted a cross-sectional study in which we defined an MPTF as a clinic staffed with professionals from three disciplines or more (including at least one medical specialty) and whose services were integrated within the facility. We disseminated a web-based questionnaire in 2017–2018 to the administrative leads of MPTFs across the country. They were invited to complete the questionnaire about the characteristics of their facilities. Data were analyzed using descriptive statistics and correlation measures.ResultsA total of 87 MTPFs were included in the analyses. Half of them (52%) reported using three exclusion criteria or more. There was no significant association between the number of exclusion criteria and wait time for a first appointment or number of new consultations in the past year. Fibromyalgia and migraine were the most frequently excluded pain syndromes (10% and 7% of MPTFs, respectively). More than one MPTF out of four excluded patients with mental health disorders (30%) and/or substance use disorders (29%), including MPTFs with specialists in their staff.ConclusionsMultidisciplinary pain treatment facility exclusion criteria are most likely to affect CP patients living with complex pain issues and psychosocial vulnerabilities. Policy efforts are needed to support Canadian MPTFs in contributing to equitable access to pain management.

BACKGROUND: Elevations of hepatic transaminase (serum alanine transaminase [ALT] and serumaspartate aminotransferase [AST]) levels in patients with acute coronary syndrome (ACS), althoughtransient, may result in exclusions from clinical efficacy trials due to suspected liver disease. The aimof this study was to evaluate the concentrations of serum transaminases in ACS and relate these to currentlyaccepted AST/ALT exclusion criteria from clinical trials. METHODS: One hundred consecutive patients with ACS were prospectively examined. Blood samplesfor AST, ALT, total bilirubin and troponin I concentration were obtained at the time of admission andafter 6, 12 and 24 hours. RESULTS: Eighty percent of patients had elevated AST, and 47% ALT; 43% of patients characterizedAST concentration > 3 × upper limit of normal (ULN) in at least one measurement, while 8% ofpatients presented ALT concentration > 3 × ULN. AST presented higher concentrations when comparedto ALT, resulting in a high De-Ritis ratio at every time point. No significant or high correlationswere found between the concentrations of serum transaminases, De-Ritis ratio and troponin I. Twodifferent cut-off values of troponin I were adopted to define the amount of infarcted myocardium thatdistinguished 28–31% of individuals with “large infarction”. Among these patients, approximately 93%presented AST concentrations > 3 × ULN. CONCLUSIONS: Hepatic transaminases are often elevated in ACS, with the majority of patients withmore extensive myocardial injury presenting high concentrations of AST. In the setting of ACS, currenttransaminase thresholds for liver dysfunction used in clinical trials may lead to excessive and inadequateexclusions of patients with larger infarcts from such trials.

Purpose 3–8% of US adults with cancer are enrolled in a clinical trial due to various barriers to enrollment. The purpose of this study is to evaluate the variability of eligibility criteria, which currently have no standard guidelines. Methods This descriptive analysis utilized all therapeutic breast protocols offered at the University of Alabama at Birmingham between 2004 and 2020. Exclusion criteria were abstracted using OnCore and ClinicalTrials.gov. Laboratory values included liver function tests and hematologic labs. Comorbid conditions included congestive heart failure, cardiovascular disease, central nervous system (CNS) metastases, and prior cancer history. Comorbid conditions were further analyzed by amount of time protocols required participants to be from diagnosis or exacerbation-free. Results 102 protocols were eligible. Among liver laboratory values, bilirubin (78%) was included in most protocols ranging from institutional upper limit of normal (ULN) (9%) to 3xULN (2%), with 1.5xULN (56%) being most common. Similar variability was observed in alanine transaminase and aspartate transaminase. Among hematological labs, 82% of protocols defined a lower limit of acceptable absolute neutrophil count ranging from 500 μL (1%) to 1800 μL (1%), with 1500 μL (64%) being most common. Of the comorbid conditions, exclusion criteria varied for congestive heart failure (49%), an acute exacerbation of cardiovascular disease (80%), CNS metastases (59%), and a prior cancer (66%). The allowable timeframe varied between protocols for cardiovascular disease and prior cancer. Conclusion Substantial heterogeneity was observed across laboratory values and comorbid variables among protocols. Future research should focus on defining standardized eligibility criteria while allowing for deviation based on drug specificity.