bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adherence to Sedation Targets With Weight-Based Propofol and Dexmedetomidine in Patients With Morbid Obesity
Authors: Hayes Emily , Esteves Alyson 
Published: July 2022

Background: Propofol and dexmedetomidine are routinely used in intensive care units (ICUs). Both are lipophilic, potentially leading to accumulation in adipose tissue. Limited evidence exists on what body weight to utilize in patients with morbid obesity. Objective: The purpose of this research was to evaluate the safety and efficacy of weight-based sedation with propofol and dexmedetomidine in ICU patients with morbid obesity. Methods: Retrospective review of ICU patients admitted from January 2018 to January 2020 who were sedated for ≥48 hours was performed. The primary outcome was the percentage of time within target sedation during the first 48 hours, stratified by body mass index (BMI) <40 or ≥40 kg/m2. Additional outcomes included adverse events and the infusion rate to achieve target sedation. Data were evaluated using descriptive statistics. Results: A total of 80 patients were analyzed. Patients on propofol with a BMI <40 kg/m2 were in their target Richmond Agitation-Sedation Scale (RASS) 11.7% versus 16.1% with a BMI ≥40 kg/m2 ( P = .580). Patients with a BMI <40 kg/m2 on dexmedetomidine were in their target RASS 27.6% versus 10.7% with a BMI ≥40 kg/m2 ( P = .053). Conclusion and Relevance: Body mass index did not significantly alter propofol target sedation attainment. However, patients with morbid obesity on dexmedetomidine demonstrated significantly less time in target sedation. An actual body weight dosing strategy of these drugs did not achieve desired target sedation for those with a BMI ≥40 versus BMI <40 kg/m2. These findings support future research on the optimal sedation dosing strategy in this patient population.
Efficacy of Postoperative Oral Antibiotics in Foot and Ankle Surgery
Authors: Frederick Robert M. , Burnette Hannah , Joyce Myles , Kumar Padam , McGee Trevor , Chiu Chi-Yang , Bettin Clayton C. , Grear Benjamin J. , Murphy G. Andrew , Richardson David R. 
Published: July 2022

Background: Preoperative oral antibiotic use in patients undergoing foot and ankle surgery is standard practice, but no consensus has been reached regarding the efficacy of postoperative oral antibiotics. The purpose of this study was to determine whether postoperative oral antibiotics reduce the rate of surgical site infections (SSIs) in patients, with and without comorbidities, undergoing foot and ankle surgery. Methods: A retrospective chart review was conducted identifying patients who underwent foot and ankle surgery by 4 fellowship-trained, foot and ankle orthopaedic surgeons between January 1, 2015, and January 1, 2019. Patients were divided into 2 groups: those who received postoperative oral antibiotics (group 1) and those who did not (group 2). Two surgeons routinely prescribed postoperative oral antibiotics, and 2 did not. Demographics, comorbidities, and procedure complexity based on surgical site and Current Procedural Terminology code were recorded from the charts. The primary outcome was postoperative infection (superficial or deep) within 6 months after surgery. Patients with antibiotic use prior to surgery, preoperative infection, or lack of follow-up >6 weeks were excluded. Multivariate logistic regression modeling was used to analyze differences in infection rate and severity. Results: Chart review identified 3631 patients, 1227 of whom did not receive postoperative oral antibiotics whereas 2394 patients did. Routine postoperative oral antibiotic use did not significantly affect postoperative infection rates or severity. However, all covariates studied (diabetes, hypertension, obesity, tobacco use, alcohol use, rheumatoid conditions, and age) influenced postoperative infection rates and severity. Conclusion: The results of this study indicate that postoperative oral antibiotics are not associated with differences in infection rates or severity. We do not recommend routine use in foot and ankle surgery.
Engagement of patient and family advisors in health system redesign in Canada
Authors: Sibbald Shannon L , Kokorelias Kristina M , Embuldeniya Gayathri , Wodchis Walter P 
Published: July 2022

Objectives Globally, there has been a shift towards integrated care delivery and patient-centredness in the design of health services. Such a transformation is underway in Ontario, which is progressively using an interprofessional team-based approach known as Ontario Health Teams (OHTs) to deliver care. During their initial development, OHTs were required to integrate patient and families’ preferences, experiences and opinions in the form of consultation and partnership with patient and family advisors (PFAs). This study aimed to understand how PFAs were involved in the early stages of planning for health system change and the perceived benefits of including PFAs in system reform. Methods This study used a qualitative descriptive design. Semi-structured interviews were conducted with 126 participants at 12 OHTs, including PFA ( n = 16) and non-PFA ( n = 110) members (e.g. clinicians). Data were analysed thematically. Results We identified four themes; mechanisms of engagement, motivations to engage, challenges to PFA engagement and PFAs’ impact and added value. Overall, participants viewed PFA engagement positively and PFAs felt valued and empowered. There remain logistical challenges around PFA compensation, and the amount of time and training expected of PFAs. However, all participants believed that developing an understanding of the patient, caregiver and family experience will strengthen the engagement of PFAs in OHT planning, decisions and policies. Conclusions Diverse approaches to and stages of PFA engagement fostered meaningful and highly valued contributions to OHT development. These were considered critical to successfully achieving the mandate of patient-centred care reform.
Clinician factors related to the delivery of psychotherapy for autistic youth and youth with attention-deficit hyperactivity disorder
Authors: Roudbarani Flora , Tablon Modica Paula , Maddox Brenna B , Bohr Yvonne , Weiss Jonathan A 
Published: July 2022

Autistic children and adolescents are more likely than non-autistic youth to experience mental health problems, such as anxiety or depression, but less likely to receive psychotherapy to address these concerns. Recent research indicates that clinician factors, such as knowledge, attitudes, confidence and beliefs, can impact their decisions to provide care, though this work has primarily focused on adults or within the context of one kind of treatment (cognitive behaviour therapy). The current study examined psychological predictors (e.g. attitudes and confidence) of clinicians’ intention to deliver psychotherapy to autistic youth and those with attention-deficit hyperactivity disorder. Participants included 611 clinicians across publicly funded agencies in Ontario, Canada. Multiple mediation analyses revealed that clinician knowledge on mental health-related topics (e.g. core symptoms, developing treatment plans and identifying progress towards treatment goals) was associated with intention to treat autistic clients or clients with attention-deficit hyperactivity disorder, and normative pressures and attitudes partially mediated this association. Clinicians felt less likely to treat autistic clients than clients with attention-deficit hyperactivity disorder, partly because of differences in attitudes, normative pressures and knowledge. This research suggests that targeted training around autism and mental health care may be a useful initiative for agency staff. Lay abstract Autistic children and youth often experience mental health problems, such as anxiety, depression and behavioural challenges. Although there are therapy programmes that have been found helpful in reducing these issues, such as cognitive behaviour therapy, autistic children often struggle to receive adequate mental health care. Clinicians’ knowledge, attitudes, confidence and beliefs about treating mental health problems in autistic people may be related to their choices in providing psychotherapy. Across Ontario, Canada, 611 mental health clinicians, working in publicly funded agencies, completed an online survey about their experiences and opinions on delivering therapy for autistic clients compared to those with attention-deficit hyperactivity disorder. Clinician knowledge was associated with their intention to treat autistic clients or clients with attention-deficit hyperactivity disorder, partly because of their attitudes and the social pressures or values they felt. Clinicians reported feeling less intent on providing therapy to autistic youth compared to youth with attention-deficit hyperactivity disorder because of differences in their attitudes, social pressures and knowledge. This research can inform the training and educational initiatives for mental health practitioners.
Clinical Implications of Diabetic Peripheral Neuropathy in Primary Infrapopliteal Angioplasty Approach for Neuro-Ischemic Foot Wounds
Authors: Alexandrescu Vlad Adrian , Van Overmeire Lionel , Makrygiannis Georgios , Azdad Khalid , Popitiu Mircea , Paquet Séverine , Poppe Laura , Nodit Mihaela 
Published: July 2022

Background: To assess the clinical effects of diabetic peripheral neuropathy (DPN) in patients with chronic limb-threatening ischemia (CLTI) treated by primary infrapopliteal angioplasty for neuro-ischemic Rutherford 5, foot wounds. Materials and methods: Over a 10-year period (2009–2019), a series of 304 diabetic ischemic limbs adding or not evincible neuropathic affectation were treated by primary infrapopliteal angioplasty and their files were retrospectively reviewed. Mean length of treated arterial lesions was 6.1 cm (range 1–22 cm). Inferior limb vibration perception threshold diagnostic was performed for comparing and scoring detectable DPN in all studied diabetic patients (classed from 0 to 10 points). There were 19% limbs with normal (0–1 points) perception (group 1), 55% others with “mild” and “moderate” (2–6 points) neuropathic impairment (group 2), and 26% limbs showing “severe” (7–10 points) DPN (group 3). Results: Primary infrapopliteal angioplasty succeeded in 89% cases in group 1, in 82% in group 2, and in 68% of limbs in group 3. This latest group assembled the heaviest neuropathic affectation and arterial calcifications and proved the lowest clinical benefit at 36 months: 35% (95% confidence interval [CI]=22% to 48%) of primary patency, 36% (95% CI=22% to 50%) wound healing, and 54% (95% CI=39% to 69%) limb preservation rates. A comparison between groups 1 vs 3 and 2 vs 3 of primary patency (p=0.014 and p=0.043), tissue healing (p=0.049 and p=0.01), and limb salvage (p=0.006 and p=0.023) proved significant, yet without statistical weight for group 1 vs 2 (p>0.05). Overall survival was not significantly affected between groups (p=0.34). Conclusion: The presence of severe DPN may jeopardize the results of infrapopliteal angioplasty in terms of patency, tissue cicatrization, and limb preservation, yet without significance on survival of these patients. When present, DPN requires appropriate stratification as specific indicator in CLTI treatment.
Suprarenal Aortic Occlusion Due to Coral Reef Calcification: Successful Endovascular Management Assisted by Intravascular Lithotripsy and Visceral Protection
Authors: Sekar Natarajan , Manoj Sivaramakrishnan , Jagan Jithin 
Published: July 2022

Purpose: Suprarenal aortic occlusion due to coral reef calcification has been considered not suitable for endovascular therapy because of visceral artery involvement. Unfortunately, open surgical treatment also carries high morbidity and mortality. We describe here successful endovascular management of a case of suprarenal aortic occlusion due to coral reef calcification with the use of intravascular lithotripsy (IVL) and visceral protection. Case Report: A 72-year-old women presented with uncontrolled hypertension, heart failure, and intermittent claudication. She was found to have occlusion of suprarenal aorta due to coral reef calcification at the level of the celiac artery. Celiac, superior mesenteric, and left renal arteries had stenosis. Right renal artery was normal. Intravascular lithotripsy–assisted balloon angioplasty and stenting of the aorta was done. Distal embolic protection of right renal artery and superior mesenteric artery was done during this procedure. Post procedure, there was no pressure gradient across the aortic stenosis, and all visceral arterial flow was maintained. Her cardiac function improved and hypertension could be managed with a single drug. Her pedal pulses became palpable Conclusion: Coral reef calcification of suprarenal aorta can be safely managed by endovascular therapy using IVL and distal embolic protection of the visceral arteries.
Landscape of coronavirus disease 2019 clinical trials: New frontiers and challenges
Authors: Halabi Susan , Zhou Jinyi , He Yijie , Bressler Linda R , Hernandez Adrian F , Turner Nicholas A , Hong Hwanhee 
Published: July 2022

Background/AimThe number of coronavirus disease 2019 deaths and cases continues to increase globally. Novel therapies are urgently needed to treat patients with coronavirus disease 2019. We sought to provide a critical review of trials designed during the coronavirus disease 2019 pandemic. Our primary goal was to provide a critical review of the landscape of clinical trials designed to address the coronavirus disease 2019 pandemic. Specifically, we were interested in assessing the design of phase II/III and phase III interventional trials.MethodsWe utilized the ClinicalTrials.gov database to include trials registered between 1 December 2019 and 11 April 2021 to survey the current landscape of clinical trials for coronavirus disease 2019. Variables extracted included: National Clinical Trial number, title, location, sponsor, study type, start date, completion date, gender group, age group, primary outcome, secondary outcome, overall status, and associated references.ResultsAbout 57% of studies were interventional, 14.5% were phase III trials, and the majority of the therapeutic trials included hospitalized patients. There were 52 primary composite outcomes and 285 unique interventions spanning 10 drug classes. The outcomes, disease severity, and comparators varied substantially across trials, and the trials were often too small to be definitive.ConclusionThese findings are relevant as we strongly advocate for global coordination of efforts through the use of common platforms that enable harmonizing of endpoints, collection of common key variables and clear definition of disease severity to have clinically meaningful results from clinical trials.
An adaptive clinical trial design to identify the target dose of tenecteplase for treatment of acute pulmonary embolism
Authors: Yeatts Sharon D , Foster Lydia D , Barsan William G , Berry Nicholas S , Callaway Clifton W , Lewis Roger J , Saville Benjamin R , Silbergleit Robert , Kline Jeffrey A 
Published: July 2022

Background/Aims Fibrinolytic therapy with tenecteplase has been proposed for patients with pulmonary embolism but the optimal dose is unknown. Higher-than-necessary dosing is likely to cause excess bleeding. We designed an adaptive clinical trial to identify the minimum and assumed safest dose of tenecteplase that maintains efficacy. Methods We propose a Bayesian adaptive, placebo-controlled, group-sequential dose-finding trial using response-adaptive randomization to preferentially allocate subjects to the most promising doses, dual analyses strategies (continuous and dichotomized) using a gatekeeping approach to maximize clinical impact, and interim stopping rules to efficiently address competing trial objectives. The operating characteristics of the proposed design were evaluated using Monte Carlo simulation across multiple hypothetical efficacy scenarios. Results Simulation demonstrated response-adaptive randomization can preferentially allocate subjects to doses which appear to be performing well based on interim data. Interim decision-making, including the interim evaluation of both analysis strategies with gatekeeping, allows the trial to continue enrollment when success with the dichotomized analysis strategy appears sufficiently likely and to stop enrollment and declare superiority based on the continuous analysis strategy when there is little chance of ultimately declaring superiority with the dichotomized analysis. Conclusion The proposed design allows evaluation of a greater number of dose levels than would be possible with a non-adaptive design and avoids the need to choose either the continuous or the dichotomized analysis strategy for the primary endpoint.
Association between Social Activity and Development of Dementia in Hearing Impairment: A Cohort Study in Japan from Japan Gerontological Evaluation Study
Authors: Kojima Kaori , Okada Eisaku , Ojima Toshiyuki , Aida Jun , Hiratsuka Yoshimune , Kondo Katsunori 
Published: July 2022

We aimed to clarify the association between social activity and the development of dementia in older adults by hearing-impaired (HI) status. We applied a community-based prospective cohort study over 6 years as part of the Japan Gerontological Evaluation Study. The study included 53,549 participants aged 65 years and older who did not require long-term care. A baseline questionnaire survey was conducted; explanatory variables included physical and social activities, and the objective variable was dementia onset assessed by standardized protocol. Cox regression models were used to calculate hazard ratios (HRs) for dementia stratified by HI status. During the follow-up period, 6013 (11.2%) participants developed dementia. Analyses revealed increased dementia risk for participants with HI who participated in the following activities less than once a month: sport groups (HR 2.17, 95% CI 1.53-3.08), hobby groups (HR 1.70, 95% CI 1.34-2.17), going out (HR 2.19, 95% CI 1.51-3.17), and meeting with friends (HR 1.27, 95% CI 1.06-1.53). HI and lack of social activity increase the risk of dementia. The study results indicate that there is an association between low social activity and the development of dementia in people with HI; the strongest associations were found for low participation in sports and hobby groups.
The Methylation Inhibitor 5-Aza-2′-Deoxycytidine Induces Genome-Wide Hypomethylation in Rice
Authors: Liu Shuo , Bao Yu , Deng Hui , Liu Guanqing , Han Yangshuo , Wu Yuechao , Zhang Tao , Chen Chen 
Published: July 2022

AbstractDNA methylation is a conserved epigenetic modification which is vital for regulating gene expression and maintaining genome stability in both mammals and plants. Homozygous mutation of rice methyltransferase 1 (met1) gene can cause host death in rice, making it difficult to obtain plant material needed for hypomethylation research. To circumvent this challenge, the methylation inhibitor, 5-Aza-2′-deoxycytidine (AzaD), is used as a cytosine nucleoside analogue to reduce genome wide hypomethylation and is widely used in hypomethylation research. However, how AzaD affects plant methylation profiles at the genome scale is largely unknown. Here, we treated rice seedlings with AzaD and compared the AzaD treatment with osmet1-2 mutants, illustrating that there are similar CG hypomethylation and distribution throughout the whole genome. Along with global methylation loss class I transposable elements (TEs) which are farther from genes compared with class II TEs, were more significantly activated, and the RNA-directed DNA Methylation (RdDM) pathway was activated in specific genomic regions to compensate for severe CG loss. Overall, our results suggest that AzaD is an effective DNA methylation inhibitor that can influence genome wide methylation and cause a series of epigenetic variations.
OsPP65 Negatively Regulates Osmotic and Salt Stress Responses Through Regulating Phytohormone and Raffinose Family Oligosaccharide Metabolic Pathways in Rice
Authors: Liu Qing , Ding Jierong , Huang Wenjie , Yu Hang , Wu Shaowen , Li Wenyan , Mao Xingxue , Chen Wenfeng , Xing Junlian , Li Chen , Yan Shijuan 
Published: July 2022

AbstractAlthough type 2C protein phosphatases (PP2Cs) have been demonstrated to play important roles in regulating plant development and various stress responses, their specific roles in rice abiotic stress tolerance are still largely unknown. In this study, the functions of OsPP65 in rice osmotic and salt stress tolerance were investigated. Here, we report that OsPP65 is responsive to multiple stresses and is remarkably induced by osmotic and salt stress treatments. OsPP65 was highly expressed in rice seedlings and leaves and localized in the nucleus and cytoplasm. OsPP65 knockout rice plants showed enhanced tolerance to osmotic and salt stresses. Significantly higher induction of genes involved in jasmonic acid (JA) and abscisic acid (ABA) biosynthesis or signaling, as well as higher contents of endogenous JA and ABA, were observed in the OsPP65 knockout plants compared with the wild-type plants after osmotic stress treatment. Further analysis indicated that JA and ABA function independently in osmotic stress tolerance conferred by loss of OsPP65. Moreover, metabolomics analysis revealed higher endogenous levels of galactose and galactinol but a lower content of raffinose in the OsPP65 knockout plants than in the wild-type plants after osmotic stress treatment. These results together suggest that OsPP65 negatively regulates osmotic and salt stress tolerance through regulation of the JA and ABA signaling pathways and modulation of the raffinose family oligosaccharide metabolism pathway in rice. OsPP65 is a promising target for improvement of rice stress tolerance using gene editing.
Marine gregarine genomes reveal the breadth of apicomplexan diversity with a partially conserved glideosome machinery
Authors: Boisard Julie , Duvernois-Berthet Evelyne , Duval Linda , Schrével Joseph , Guillou Laure , Labat Amandine , Le Panse Sophie , Prensier Gérard , Ponger Loïc , Florent Isabelle 
Published: July 2022

AbstractOur current view of the evolutionary history, coding and adaptive capacities of Apicomplexa, protozoan parasites of a wide range of metazoan, is currently strongly biased toward species infecting humans, as data on early diverging apicomplexan lineages infecting invertebrates is extremely limited. Here, we characterized the genome of the marine eugregarinePorospora gigantea, intestinal parasite of Lobsters, remarkable for the macroscopic size of its vegetative feeding forms (trophozoites) and its gliding speed, the fastest so far recorded for Apicomplexa. Two highly syntenic genomes named A and B were assembled. Similar in size (~ 9 Mb) and coding capacity (~ 5300 genes), A and B genomes are 10.8% divergent at the nucleotide level, corresponding to 16–38 My in divergent time. Orthogroup analysis across 25 (proto)Apicomplexa species, includingGregarina niphandrodes, showed that A and B are highly divergent from all other known apicomplexan species, revealing an unexpected breadth of diversity. Phylogenetically these two species branch sisters to Cephaloidophoroidea, and thus expand the known crustacean gregarine superfamily. The genomes were mined for genes encoding proteins necessary for gliding, a key feature of apicomplexans parasites, currently studied through the molecular model called glideosome. Sequence analysis shows that actin-related proteins and regulatory factors are strongly conserved within apicomplexans. In contrast, the predicted protein sequences of core glideosome proteins and adhesion proteins are highly variable among apicomplexan lineages, especially in gregarines. These results confirm the importance of studying gregarines to widen our biological and evolutionary view of apicomplexan species diversity, and to deepen our understanding of the molecular bases of key functions such as gliding, well known to allow access to the intracellular parasitic lifestyle in Apicomplexa.