Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical trials site recruitment optimisation: Guidance from Clinical Trials: Impact and Quality

Background/Aims: Participants are integral to the success of any clinical research study, yet participant recruitment into clinical trials poses ongoing and complex challenges. It is widely accepted and recognised that clinical trial sites often find it difficult to meet recruitment goals, both in terms of accrual targets and timelines. This can impact the validity of trials or cause major delays for research. There are very few frameworks available to clinical trial sites to improve recruitment. The GREET project (Guidance to Recruitment: Examining Experiences at clinical Trial sites) sought to identify barriers to recruitment and produce formal guidance to optimise recruitment outcomes. Methods: Clinical Trials: Impact and Quality, a collaborative of sector stakeholders, convened a project team with comprehensive knowledge of the Australian clinical trials sector to undertake the GREET project. The project scope included exploration of recruitment issues at a site level across all phases of clinical trials and all types of trial sites. The scope excluded upstream issues such as protocol design and general public clinical trial awareness, participant retention and elements of recruitment outside a site’s capacity to directly influence or control. The project team’s extensive knowledge and experience conducting clinical trials in Australia was used to collaboratively identify a list of 24 key barriers and 12 enablers to site recruitment which formed the basis of the project. Key stakeholder groups were surveyed to challenge project team assumptions. A national and international environmental scan and literature review was conducted to identify best-practice recruitment solutions. Results: A total of 343 people responded to a survey sent to sites, sponsors, and contract research organisations, and 162 people responded to a survey sent to consumers via consumer networks. The key barriers and enablers initially identified by the project team aligned with the key outcomes of the surveys, which in turn assisted in the development of best-practice recommendations in the form of a Clinical Trial Site Recruitment Guide. Recommendations were grouped into four key themes; conducting accurate study feasibility; proactive planning during start-up; selecting optimal recruitment methods; and participant involvement. Early intervention was identified as a key facilitator in maximising improved recruitment outcomes. The GREET Clinical Trial Site Recruitment Guide is publicly accessible on the Clinical Trials: Impact and Quality website. Conclusion: Participant recruitment challenges experienced at a site level are widespread and varied, and there is no universal recruitment solution. However, this project identified that there are interventions and assessments that can be proactively implemented and selectively applied to facilitate improved recruitment outcomes.
The timing of amputation of mangled lower extremities does not predict post-injury outcomes and mortality: A retrospective analysis from the ACS TQIP database

Supplemental digital content is available in the text. BACKGROUND While limb salvage does not result in improved functional outcomes among patients with a mangled lower extremity, the impact of attempted limb salvage on mortality and complications is poorly understood. The objective of this study was to evaluate the relationship between attempted limb salvage and in-hospital outcomes among patients with a mangled lower extremity. METHODS We performed a retrospective cohort study of adults, 16 years or older, with a mangled lower extremity. Data were derived from the American College of Surgeons’ Trauma Quality Improvement Program (2012–2017). We compared mortality, complications (severe sepsis, acute kidney injury [AKI], decubitus ulcers) and length of stay between patients managed with the intention of limb salvage (amputation beyond 24 hours or no amputation) and those who underwent early amputation (within 24 hours of presentation). Instrumental variable analysis was used to evaluate the relationship between management strategy and outcomes. RESULTS We identified 5,527 patients with a mangled lower extremity, of which 901 (16.3%) underwent early amputation. Among those managed with attempted limb salvage, 42.5% underwent amputation prior to discharge. After adjusting for patient and hospital characteristics, there was no association between initial management strategy and mortality (odds ratio, 1.20; 95% confidence interval [CI], 0.83–1.74 early amputation vs. attempted limb salvage). Early amputation was associated with lower odds of AKI (OR, 0.59; 95% CI, 0.39–0.88) and a trend toward shorter length of stay (relative risk, 0.77; 95% CI, 0.52–1.14). CONCLUSION Over half of patients who sustain a mangled lower extremity undergo amputation during their initial hospital course. While a limb salvage strategy is associated with an elevated risk of AKI, there is no association between attempted limb preservation and mortality. These findings suggest that in patients in which there is no clear indication for early amputation, attempts at limb salvage do not come at the cost of increased mortality. LEVEL OF EVIDENCE Therapeutic study, level IV.
Estrogen and estrogen mimics contamination in water and the role of sewage treatment

The yeast estrogen screen was applied to sewage treatment process waters to identify the presence of estrogenic activity and to investigate the fate and behavior of estrogenic substances through treatment. Hydrophobic fractions in the water phase were extracted and concentrated using C18 cartridges for the effective extraction of 17β-estradiol (E2) and other estrogen mimics. Clear dose-dependent elevation in the synthesis of β-galactosidase in the yeast screen was observed with all the samples tested, demonstrating that these samples were estrogenic. However, estrogenic activity tended to reduce during the treatment, especiallyiin the biological process. Quantification results of the yeast estrogen screen in terms of E2 equivalent were compared with actual E2 concentrations measured by an ELISA. E2 occupied 34% of the whole estrogenicity in the raw sewage, while almost 100% in the final effluent. The analyses of the sewage treatment process waters revealed that human estrogens are major causative substances in terms of estrogenic activity in sewage and its treated effluent. Although findings of possible correlation of environmental estrogens with the real impact on human health and the ecosystem are still the focus of scientific debate and investigation, proper management should be established in the sewage treatment process which receives various environmental contaminants.
Effects of Iron Oxide Nanoparticles on Structural Organization of Hepatocyte Chromatin: Gray Level Co-occurrence Matrix Analysis

Abstract Gray level co-occurrence matrix (GLCM) analysis is a contemporary and innovative computer-based algorithm that can be used for the quantification of subtle changes in a cellular structure. In this work, we use this method for the detection of discrete alterations in hepatocyte chromatin distribution after in vivo exposure to iron oxide nanoparticles (IONPs). The study was performed on 40 male, healthy C57BL/6 mice divided into four groups: three experimental groups that received different doses of IONPs and 1 control group. We describe the dose-dependent reduction of chromatin textural uniformity measured as GLCM angular second moment. Similar changes were detected for chromatin textural uniformity expressed as the value of inverse difference moment. To the best of our knowledge, this is the first study to investigate the impact of iron-based nanomaterials on hepatocyte GLCM parameters. Also, this is the first study to apply discrete wavelet transform analysis, as a supplementary method to GLCM, for the assessment of hepatocyte chromatin structure in these conditions. The results may present the useful basis for future research on the application of GLCM and DWT methods in pathology and other medical research areas.
Macular Cone Abnormalities in Behçet's Disease Detected by Adaptive Optics Scanning Light Ophthalmoscope.

BACKGROUND AND OBJECTIVE Investigations of morphological changes in photoreceptors in Behçet's disease (BD) using adaptive optics scanning light ophthalmoscope (AOSLO) are lacking. The authors aimed to evaluate macular cone density and regularity in BD patients with or without a history of uveitis with good visual acuity (VA). PATIENTS AND METHODS The authors included 16 patients (29 eyes) with BD and 12 healthy volunteers (12 eyes) as controls. All subjects had VA of 20/20 or higher. Subjects underwent AOSLO to evaluate the photoreceptor status including cone density (numbers/mm2) and proportion of hexagonal Voronoi domains. RESULTS Hyporeflective patches that were not detected in color fundus photograph or optical coherence tomography were observed by AOSLO in BD patients both with and without past uveitis history; these were not detected in the control group. Cone density was significantly reduced in BD patients with a history of uveitis compared to controls (P = .002). The proportion of hexagonal Voronoi domains was significantly reduced in BD eyes both with and without history of uveitis relative to controls (P < .001). CONCLUSION Macular photoreceptor damage was observed in BD patients with and without a history of uveitis. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:218-225. ].
The adjunct of transcranial direct current stimulation to Robot-assisted therapy in upper limb post-stroke treatment

Abstract Transcranial direct current stimulation (TDCS) and robot-assisted therapy (RAT) proved to be promising interventions in post-stroke rehabilitation. However, the effects of combining the two treatments are not significantly clear. To determine the effects of combined therapy using transcranial direct current stimulation (tDCS) with robot-assisted therapy (RAT) in the impairment of the upper limb in stroke rehabilitation. The Cochrane Library, MEDLINE, Embase, Google Scholar, and Trial Registries were systematically searched for randomised controlled trials in May 2020. As the outcome, the Fugl-Meyer Assessment score (FMS) was used. A pairwise and a network meta-analysis were performed. 5 RCTs with RAT versus RAT + tDCS groups and 21 RCTs with RAT versus the control group with 892 people were analysed. Of these studies, 10 RCTs evaluated acute-subacute (<8 weeks) people, while 16 chronic people. By analysing the FMS with a pair-wise meta-analysis, we demonstrate significant improvements only in the RAT alone compared to the control (acute-subacute, SMD:4.09 (1.31, 6.87) and chronic, SMD:2.22 (0.99, 3.45)). Instead, performing a network meta-analysis, through an analysis of the surface under the cumulative ranking curve (SUCRA) we report a ranking of the effectiveness of the interventions. We assess SUCRA in acute-subacute stroke: Control:0.23, RAT + tDCS:0.31, RAT:0.96 and in chronic stroke: Control:0.06, RAT + tDCS:0.62, RAT:0.82. RAT is, respectively, 96% and 82% likely to be the best-ranked treatment. Despite the limitations, this network meta-analysis appears to demonstrate through the rank of interventions that adding tDCS to RAT is not useful in upper-limb stroke rehabilitation.
Long-Term Outcomes of the Coarctation of the Aorta Stent Trials

Supplemental Digital Content is available in the text. Background: Long-term outcome data of stent-implantation for coarctation of the aorta are limited. We report up to 5 years of postimplant follow-up in patients enrolled into the COAST (Coarctation of the Aorta Stent Trial) and the COAST II trial (Covered Cheatham-Platinum Stents for Prevention or Treatment of Aortic Wall Injury Associated With Coarctation of the Aorta), evaluating the bare and Covered Cheatham-Platinum Stents for the treatment of coarctation of the aorta and associated aortic wall injury. Methods: Data was prospectively collected during the 2 multi-center studies, enrolling 248 patients (COAST: n=121, COAST II: n=127). Late follow-up data (48–60 month) was compared with immediate (1 month) and early (12 months) follow-up. Results: There was a notable decrease in the use of antihypertensive medication, from 53% at immediate, to 42% at early, and 29% at late follow-up. The cumulative incidence of stent fractures was 0% immediately, 2.9% at early, and 24.4% at late follow-up. Independent predictors for stent fractures at late follow-up were age <18 years, male sex, minimum stent diameter ≥12 mm, and use of bare metal stent. The cumulative incidence of reintervention was 1.6% at immediate, 5.1% at early, and 21.3% at late follow-up. Independent predictors for reinterventions at late follow-up were age <18 years, post implantation systolic arm-leg blood pressure gradient ≥10 mm Hg, minimum stent diameter at implantation <12 mm, and initial coarctation minimum diameter <6 mm. There were 13 patients with aortic aneurysms, with a cumulative incidence of 6.3% at late follow-up. Conclusions: Coarctation stenting is effective at maintaining obstruction relief up to 60 months postimplant with reduction in the number of patients requiring antihypertensive medication. However, an increase in-stent fractures and reinterventions were observed between medium and long-term follow-up. Covered stents appear to confer some protection from the development of stent fractures but do not provide complete protection from late aneurysm formation. Registration: URL: https://www.clinicaltrials. gov; Unique identifiers: NCT00552812 and NCT01278303.
Visual mechanisms for voice‐identity recognition flexibly adjust to auditory noise level

Recognising the identity of voices is a key ingredient of communication. Visual mechanisms support this ability: recognition is better for voices previously learned with their corresponding face (compared to a control condition). This so‐called ‘face‐benefit’ is supported by the fusiform face area (FFA), a region sensitive to facial form and identity. Behavioural findings indicate that the face‐benefit increases in noisy listening conditions. The neural mechanisms for this increase are unknown. Here, using functional magnetic resonance imaging, we examined responses in face‐sensitive regions while participants recognised the identity of auditory‐only speakers (previously learned by face) in high (SNR −4 dB) and low (SNR +4 dB) levels of auditory noise. We observed a face‐benefit in both noise levels, for most participants (16 of 21). In high‐noise, the recognition of face‐learned speakers engaged the right posterior superior temporal sulcus motion‐sensitive face area (pSTS‐mFA), a region implicated in the processing of dynamic facial cues. The face‐benefit in high‐noise also correlated positively with increased functional connectivity between this region and voice‐sensitive regions in the temporal lobe in the group of 16 participants with a behavioural face‐benefit. In low‐noise, the face‐benefit was robustly associated with increased responses in the FFA and to a lesser extent the right pSTS‐mFA. The findings highlight the remarkably adaptive nature of the visual network supporting voice‐identity recognition in auditory‐only listening conditions.
Aquaculture mediates global transmission of a viral pathogen to wild salmon

Molecular epidemiology reveals that aquaculture contributes to emergence of a fish virus at both global and local epidemic hierarchies. Global expansion of aquaculture and agriculture facilitates disease emergence and catalyzes transmission to sympatric wildlife populations. The health of wild salmon stocks critically concerns Indigenous peoples, commercial and recreational fishers, and the general public. Despite potential impact of viral pathogens such as Piscine orthoreovirus-1 (PRV-1) on endangered wild salmon populations, their epidemiology in wild fish populations remains obscure, as does the role of aquaculture in global and local spread. Our phylogeographic analyses of PRV-1 suggest that development of Atlantic salmon aquaculture facilitated spread from Europe to the North and South East Pacific. Phylogenetic analysis and reverse transcription polymerase chain reaction surveillance further illuminate the circumstances of emergence of PRV-1 in the North East Pacific and provide strong evidence for Atlantic salmon aquaculture as a source of infection in wild Pacific salmon. PRV-1 is now an important infectious agent in critically endangered wild Pacific salmon populations, fueled by aquacultural transmission.
Prevalence of adverse drug reactions in the primary care setting: A systematic review and meta-analysis

Background Adverse drug reactions (ADRs) represent a major cause of iatrogenic morbidity and mortality in patient care. While a substantial body of work has been undertaken to characterise ADRs in the hospital setting, the overall burden of ADRs in the primary care remains unclear. Objectives To investigate the prevalence of ADRs in the primary care setting and factors affecting the heterogeneity of the estimates. Methods Studies were identified through searching of Medline, Embase, CINAHL and IPA databases. We included observational studies that reported information on the prevalence of ADRs in patients receiving primary care. Disease and treatment specific studies were excluded. Quality of the included studies were assessed using Smyth ADRs adapted scale. A random-effects model was used to calculate the pooled estimate. Potential source of heterogeneity, including age groups, ADRs definitions, ADRs detection methods, study setting, quality of the studies, and sample size, were investigated using sub-group analysis and meta-regression. Results Thirty-three studies with a total study population of 1,568,164 individuals were included. The pooled prevalence of ADRs in the primary care setting was 8.32% (95% CI, 7.82, 8.83). The percentage of preventable ADRs ranged from 12.35–37.96%, with the pooled estimate of 22.96% (95% CI, 7.82, 38.09). Cardiovascular system drugs were the most commonly implicated medication class. Methods of ADRs detection, age group, setting, and sample size contributed significantly to the heterogeneity of the estimates. Conclusion ADRs constitute a significant health problem in the primary care setting. Further research should focus on examining whether ADRs affect subsequent clinical outcomes, particularly in high-risk therapeutic areas. This information may better inform strategies to reduce the burden of ADRs in the primary care setting.
Justice beliefs buffer against perceived barriers to colorectal cancer screening among African Americans

Abstract Objectives African Americans develop and die from colorectal cancer (CRC) more than any other racial group in the United States. Perceived barriers to screening (e.g. embarrassment and financial costs) likely exacerbate these disparities. Identifying psychological factors that can reduce the impact of perceived barriers and encourage CRC screening is therefore critical. This study explored whether believing the world is fairer for oneself than in general (personal justice ascendancy) would moderate the impact that perceived barriers have on receptivity to CRC screening. Method Four-hundred fifty-seven screening eligible African Americans completed measures of beliefs about justice for self and others, as well as perceived barriers to CRC screening. Participants also completed theory of planned behaviour (TPB) measures of screening receptivity (attitudes, norms, perceived behavioural control and intentions). Results Perceived barriers and justice beliefs interacted to predict perceived behavioural control over screening. Perceived barriers were associated with less perceived behavioural control only when personal justice beliefs were low. In turn, perceived behavioural control predicted stronger intentions to obtain CRC screening. Conclusions Interactive effects with perceived barriers highlight that strong personal justice beliefs play an important role in CRC screening and could aid in addressing CRC screening disparities among African Americans.
Benefits of combination therapy of hydrocortisone, ascorbic acid and thiamine in sepsis and septic shock: A systematic review

Background: Sepsis and septic shock are severe medical conditions that can damage multiple organs with a higher risk of mortality. Recently, the combination of hydrocortisone, ascorbic acid and thiamine (HAT) was hypothesized to work synergistically to reverse septic shock and reduce mortality. Aim: To ascertain the efficacy of HAT therapy and compare whether HAT therapy is more beneficial compared to the standard of care in sepsis and septic shock patients. Methods: PubMed, Clinicaltrials.gov, Scopus, Web of Science, Cochrane and Embase are databases that were used to identify trials that conducted a study of the combination of HAT in sepsis or septic shock. Results: There were 134 articles identified through a database search and 16 from other sources, which were subsequently reduced to 11 trials (six randomized trials and five non-randomized trials) that were deemed appropriate for inclusion in this review. Most of the outcomes from these studies focused on mortality, the need for renal replacement therapy, duration of vasopressor use, changes in Sequential Organ Failure Assessment score, procalcitonin clearance and lengths of intensive care unit stay. Conclusion: Due to inconsistent results from clinical studies, the benefits of HAT therapy cannot be confirmed at this point in sepsis and septic shock. Currently, there are at least 20 randomized controlled trials testing HAT in various combinations and dosages in patients with severe sepsis and septic shock. The results of these studies are required before definitive conclusions can be made regarding the impact of this novel treatment strategy on the morbidity and mortality of patients with sepsis.
Association of the Geriatric 8 with treatment intensity and prognosis in older patients with diffuse large B‐cell lymphoma

Because of the heterogeneity among older patients with diffuse large B‐cell lymphoma (DLBCL), the establishment of an easy‐to‐use geriatric assessment tool is an unmet need. We verified the impact of the Geriatric 8 (G8) on treatment stratification and overall survival (OS). We conducted a retrospective, multicentre analysis of older patients (≥65 years) with DLBCL. The primary endpoint was OS. The total average relative dose intensity (tARDI) was defined as the average delivered dose intensity divided by the planned dose intensity through all cycles. A total of 451 patients were diagnosed with DLBCL from 2007 to 2017, and 388 patients received standard regimens. A multivariate Cox model confirmed that the G8 was a significant predictor of OS (hazard ratio 0·88, 95% confidence interval 0·828–0·935). A Cox model with restricted cubic spline showed a linear association between the G8 and the mortality risk. The G8 had a significant impact on OS in elderly patients with DLBCL. The upper limit of tARDI for standard regimens to improve OS might be appropriate at ≥80% for patients with high G8 scores and 60% for patients with low G8 scores. However, the standard regimens should be given to all patients regardless of the G8 score to improve OS.