Calcineurin Inhibitor in NEuRoloGically deceased donors to decrease kidney delayed graft function study: study protocol of the CINERGY Pilot randomised controlled trial.

INTRODUCTION: Most solid organ transplants originate from donors meeting criteria for death by neurological criteria (DNC). Within the organ donor, physiological responses to brain death increase the risk of ischaemia reperfusion injury and delayed graft function. Donor preconditioning with calcineurin inhibition may reduce this risk. METHODS AND ANALYSIS: We designed a multicentre placebo-controlled pilot randomised trial involving nine organ donation hospitals and all 28 transplant programmes in the Canadian provinces of Ontario and Québec. We planned to enrol 90 DNC donors and their approximately 324 organ recipients, totalling 414 participants. Donors receive an intravenous infusion of either tacrolimus 0.02 mg/kg over 4 hours prior to organ retrieval, or a matching placebo, while monitored in an intensive care unit for any haemodynamic changes during the infusion. Among all study organ recipients, we record measures of graft function for the first 7 days in hospital and we will record graft survival after 1 year. We examine the feasibility of this trial with respect to the proportion of all eligible donors enrolled and the proportion of all eligible transplant recipients consenting to receive a CINERGY organ transplant and to allow the use of their health data for study purposes. We will report these feasibility outcomes as proportions with 95% CIs. We also record any barriers encountered in the launch and in the implementation of this trial with detailed source documentation. ETHICS AND DISSEMINATION: We will disseminate trial results through publications and presentations at participating sites and conferences. This study has been approved by Health Canada (HC6-24-c241083) and by the Research Ethics Boards of all participating sites and in Québec (MP-31-2020-3348) and Clinical Trials Ontario (Project #3309). TRIAL REGISTRATION NUMBER: NCT05148715.

Episodic disability questionnaire (EDQ) measurement properties among adults living with HIV in Canada, Ireland, United Kingdom, and United States.

BACKGROUND: The Episodic Disability Questionnaire (EDQ) is a generic 35-item patient-reported outcome measure of presence, severity and episodic nature of disability. We assessed the measurement properties of the Episodic Disability Questionnaire (EDQ) with adults living with HIV. METHODS: We conducted a measurement study with adults living with HIV in eight clinical settings in Canada, Ireland, United Kingdom, and United States. We electronically administered the EDQ followed by three reference measures (World Health Organization Disability Assessment Schedule; Patient Health Questionnaire; Social Support Scale) and a demographic questionnaire. We administered the EDQ only 1 week later. We assessed the internal consistency reliability (Cronbach's alpha; > 0.7 acceptable), and test-retest reliability (Intra Class Correlation Coefficient; > 0.7 acceptable). We estimated required change in EDQ domain scores to be 95% certain that a change was not due to measurement error (Minimum Detectable Change (MDC95%)). We evaluated construct validity by assessing 36 primary hypotheses of relationships between EDQ scores and scores on the reference measures (> 75% hypotheses confirmed indicated validity). RESULTS: Three hundred fifty nine participants completed the questionnaires at time point 1, of which 321 (89%) completed the EDQ approximately 1 week later. Cronbach's alpha for internal consistency ranged from 0.84 (social domain) to 0.91 (day domain) for the EDQ severity scale, and 0.72 (uncertainty domain) to 0.88 (day domain) for the EDQ presence scale, and 0.87 (physical, cognitive, mental-emotional domains) to 0.89 (uncertainty domain) for the EDQ episodic scale. ICCs for test-retest reliability ranged from 0.79 (physical domain) to 0.88 (day domain) for the EDQ severity scale and from 0.71 (uncertainty domain) to 0.85 (day domain) for the EDQ presence scale. Highest precision was demonstrated in the severity scale for each domain (MDC95% range: 19-25 out of 100), followed by the presence (MDC95% range: 37-54) and episodic scales (MDC95% range:44-76). Twenty-nine of 36 (81%) construct validity hypotheses were confirmed. CONCLUSIONS: The EDQ possesses internal consistency reliability, construct validity, and test-retest reliability, with limited precision when administered electronically with adults living with HIV across in clinical settings in four countries. Given the measurement properties, the EDQ can be used for group level comparisons for research and program evaluation in adults living with HIV.

Exploring different models of pain phenotypes and their association with pain worsening in people with early knee osteoarthritis: The MOST cohort study.

OBJECTIVE: To determine i) pain phenotypes (PP) in people with early-stage knee osteoarthritis (EKOA); ii) the longitudinal association between the phenotypes and pain worsening at two years. DESIGN: We studied participants with EKOA from the Multicenter Osteoarthritis Study defined as pain intensity ≤3/10, Kellgren and Lawrence grade ≤2, intermittent pain none to sometimes, and no constant pain. Two models of PP were explored. Model A included pressure pain thresholds, temporal summation, conditioned pain modulation, pain catastrophizing, sleep quality, depression, and widespread pain (WSP). In Model B, gait characteristics, quadriceps strength, comorbidities, and magnetic resonance imaging features were added to Model A. Latent Class Analysis was used to create phenotypes, and logistic regression was used to determine their association with pain worsening. RESULTS: 750 individuals (60% females), mean age [standard deviation (SD)]: 60.3 (9.4) were included in Model A and 333 individuals (60% females), mean age (SD): 59.4 (8.1) in Model B. 3-class and 4-class solutions were chosen for Model A and Model B. In Model A, the most "severe" phenotype was dominated by psychosocial factors, WSP, and measures of nervous system sensitization. Similarly in Model B, the Model A phenotype plus gait variables, quadriceps strength, and comorbidities were dominant. Surprisingly, none of the phenotypes in either model had a significant relationship with pain worsening. CONCLUSION: Phenotypes based upon various factors thought to be important for the pain experience were identified in those with EKOA but were not significantly related to pain worsening. These phenotypes require validation with clinically relevant endpoints.

"Outcomes of the Use of Fresh Frozen Costal Cartilage in Rhinoplasty".

BACKGROUND: Rhinoplasty is made more challenging when there is insufficient septal cartilage for use as graft material. Several autologous and homologous graft options have been used in the past, though each comes with its own set of challenges. Fresh frozen costal cartilage (FFCC) is an increasingly popular alternative that yields the benefits of homologous tissue while having a lower theoretical risk profile. Given the relatively novel nature of this option, this study aims to analyze the complication rates of MTF (Musculoskeletal Transplant Foundation) FFCC. METHODS: A retrospective chart review of the use of FFCC in rhinoplasty in the senior author's practice was conducted between March 2018 to December 2021. 282 cases were reviewed and analyzed for rates of infection, warping, and resorption. The inclusion criteria were cases with a minimum of 12 months of follow-up. RESULTS: The mean age of our study group was 35.8 years old, with 27 males and 255 females. 40 cases were primary rhinoplasties while the remaining 242 were revisions. Mean follow-up period was 20.3 months. Six patients (2.1%) required empiric antibiotics postoperatively, zero patients had clinical signs of warping, resorption, or displacement, and six patients (2.1%) required operative revision unrelated to the FFCC. CONCLUSIONS: This study provides long-term follow up data on the complication profile of FFCC in rhinoplasty. Acute infection, warping, and resorption rates were found to be no greater than rhinoplasty complication rates when autologous or homologous tissue are used. FFCC is a safe, convenient, and patient-centered option for graft tissue in rhinoplasty.

Calcineurin Inhibition in Deceased Organ Donors: A Systematic Review and Meta-analysis of Preclinical Studies.

Background: Preconditioning deceased organ donors with calcineurin inhibitors (CNIs) may reduce ischemia-reperfusion injury to improve transplant outcomes. Methods: We searched MEDLINE, EMBASE, Cochrane Library, and conference proceedings for animal models of organ donation and transplantation, comparing donor treatment with CNIs with either placebo or no intervention, and evaluating outcomes for organ transplantation. Reviewers independently screened and selected studies, abstracted data, and assessed the risk of bias and clinical relevance of included studies. Where possible, we pooled results using meta-analysis; otherwise, we summarized findings descriptively. Results: Eighteen studies used various animals and a range of CNI agents and doses and evaluated their effects on a variety of transplant outcomes. The risk of bias and clinical applicability were poorly reported. Pooled analyses suggested benefit of CNI treatment on early graft function in renal transplants (3 studies; serum creatinine: ratio of means [RoM] 0.54; 95% confidence interval [CI], 0.34-0.86) but not for liver transplants (2 studies; serum alanine transaminase: RoM 0.61; 95% CI, 0.30-1.26; and serum aspartate aminotransferase: RoM 0.58; 95% CI, 0.26-1.31). We found no reduction in graft loss at 7 d (2 studies; risk ratio 0.54; 95% CI, 0.08-3.42). CNI treatment was associated with reduced transplant recipient levels of interleukin-6 (4 studies; RoM 0.36; 95% CI, 0.19-0.70), tumor necrosis factor-alpha (5 studies; RoM 0.36; 95% CI, 0.12-1.03), and cellular apoptosis (4 studies; RoM 0.30; 95% CI, 0.19-0.47). Conclusions: Although this compendium of animal experiments suggests that donor preconditioning with CNIs may improve early kidney graft function, the limited ability to reproduce a true clinical environment in animal experiments and to assess for risk of bias in these experiments is a serious weakness that precludes current clinical application.

Complications Following Facelift and Neck Lift: Implementation and Assessment of Large Language Model and Artificial Intelligence (ChatGPT) Performance Across 16 Simulated Patient Presentations.

INTRODUCTION: ChatGPT represents a potential resource for patient guidance and education, with the possibility for quality improvement in healthcare delivery. The present study evaluates the role of ChatGPT as an interactive patient resource, and assesses its performance in identifying, triaging, and guiding patients with concerns of postoperative complications following facelift and neck lift surgery. METHODS: Sixteen patient profiles were generated to simulate postoperative patient presentations, with complications of varying acuity and severity. ChatGPT was assessed for its accuracy in generating a differential diagnosis, soliciting a history, providing the most-likely diagnosis, the appropriate disposition, treatments/interventions to begin from home, and red-flag symptoms necessitating an urgent presentation to the emergency department. RESULTS: Overall accuracy in providing a complete differential diagnosis in response to simulated presentations was 85%, with an accuracy of 88% in identifying the most-likely diagnosis after history-taking. However, appropriate patient dispositions were suggested in only 56% of cases. Relevant home treatments/interventions were suggested with an 82% accuracy, and red-flag symptoms with a 73% accuracy. A detailed analysis, stratified according to latency of postoperative presentation (<48 h, 48 h-1 week, or >1 week), and according to acuity of complications, is presented herein. CONCLUSIONS: ChatGPT overestimated the urgency of indicated patient dispositions in 44% of cases, concerning for potential unnecessary increase in healthcare resource utilization. Imperfect performance, and the tool's tendency for overinclusion in its responses, risk increasing patient anxiety and straining physician-patient relationships. While artificial intelligence has great potential in triaging postoperative patient concerns, and improving efficiency and resource utilization, ChatGPT's performance, in its current form, demonstrates a need for further refinement before its safe and effective implementation in facial aesthetic surgical practice. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Mechanisms hypothesized for pain-relieving effects of exercise in fibromyalgia: a scoping review.

Background: Exercise is one of the most recommended management strategies by treatment guidelines for fibromyalgia (FM); however, the mechanism through which exercise improves pain in FM is still unknown. Objective: We aimed to summarize the hypothesized theoretical mechanisms for the pain-relieving effects of exercise in people with FM. Eligibility Criteria: Randomized controlled trials (RCTs) in English reporting mechanisms for pain-relieving effects of exercise in the 'Introduction' and 'Discussion' sections and significant within- group or between-group effects of exercise interventions were included. Sources of Evidence: We searched the databases Ovid MEDLINE(R), EMBASE, CINAHL, COCHRANE, Sports Discuss, and AMED with the keywords: exercise and fibromyalgia until December 2021. Charting Methods: Two authors independently performed title/abstract, full-text review, and data abstraction using a data abstraction form. The hypothesized mechanisms from individual studies were grouped into three categories. Results: The literature search resulted in 2147 studies, out of which 220 studies were considered for full-text review. A total of 50 RCTs proposing 29 unique mechanisms for the pain-relieving effects of exercise were included. These mechanisms were divided into three categories: physical, neuro-physiological, and psychological. The neuro-physiological category was further subdivided into exercise-induced hypoalgesia (EIH), pain sensitization, the autonomic system, the immune system, the endocrine system, and miscellaneous categories. The most frequently hypothesized mechanisms were EIH (n = 15), autonomic modulation (n = 7), improved sleep (n = 6), muscle oxygenation (n = 6), self-efficacy (n = 5), mental health (n = 4), and benefits of the aquatic environment (n = 12). While all exercise interventions involved FM patients, most of the supporting evidence for these mechanisms was cited from previous studies conducted on healthy samples. No studies performed analyses to demonstrate causal associations between the mechanisms and outcomes. Conclusion: Multiple mechanisms were hypothesized for the positive influence of exercise in people with FM. Future studies using causal analyses, such as mediation analysis, are recommended to validate these mechanisms.

Episodic Disability Questionnaire (EDQ) measurement properties among adults living with HIV in Canada, Ireland, United Kingdom, and United States.

Background: The Episodic Disability Questionnaire (EDQ) is a generic 35-item patient-reported outcome measure of presence, severity and episodic nature of disability. We assessed the measurement properties of the Episodic Disability Questionnaire (EDQ) with adults living with HIV. Methods: We conducted a measurement study with adults living with HIV in eight clinical settings in Canada, Ireland, United Kingdom, and United States. We electronically administered the EDQ followed by three reference measures (World Health Organization Disability Assessment Schedule; Patient Health Questionnaire; Social Support Scale) and a demographic questionnaire. We administered the EDQ only 1 week later. We assessed the internal consistency reliability (Cronbach's alpha; >0.7 acceptable), and test-retest reliability (Intra Class Correlation Coefficient; >0.7 acceptable). We estimated required change in EDQ domain scores to be 95% certain that a change was not due to measurement error (Minimum Detectable Change (MDC95%)). We evaluated construct validity by assessing 36 primary hypotheses of relationships between EDQ scores and scores on the reference measures (> 75% hypotheses confirmed indicated validity). Results: 359 participants completed the questionnaires at time point 1, of which 321 (89%) completed the EDQ approximately 1 week later. Cronbach's alpha for internal consistency ranged from 0.84 (social domain) to 0.91 (day domain) for the EDQ severity scale, and 0.72 (uncertainty domain) to 0.88 (day domain) for the EDQ presence scale, and 0.87 (physical, cognitive, mental-emotional domains) to 0.89 (uncertainty domain) for the EDQ episodic scale. ICCs for test-retest reliability ranged from 0.79 (physical domain) to 0.88 (day domain) for the EDQ severity scale and from 0.71 (uncertainty domain) to 0.85 (day domain) for the EDQ presence scale. Highest precision was demonstrated in the severity scale for each domain (MDC95% range: 19-25 out of 100), followed by the presence (MDC95% range: 37-54) and episodic scales (MDC95% range:44-76). Twenty-nine of 36 (81%) construct validity hypotheses were confirmed. Conclusions: The EDQ possesses internal consistency reliability, construct validity, and test-retest reliability, with limited precision when administered electronically with adults living with HIV across in clinical settings in four countries. Given the measurement properties, the EDQ can be used for group level comparisons for research and program evaluation in adults living with HIV.

Catalytic deconstruction of waste polyethylene with ethylene to form propylene.

The conversion of polyolefins to monomers would create a valuable carbon feedstock from the largest fraction of waste plastic. However, breakdown of the main chains in these polymers requires the cleavage of carbon-carbon bonds that tend to resist selective chemical transformations. Here, we report the production of propylene by partial dehydrogenation of polyethylene and tandem isomerizing ethenolysis of the desaturated chain. Dehydrogenation of high-density polyethylene with either an iridium-pincer complex or platinum/zinc supported on silica as catalysts yielded dehydrogenated material containing up to 3.2% internal olefins; the combination of a second-generation Hoveyda-Grubbs metathesis catalyst and [PdP(tBu)3(µ-Br)]2 as an isomerization catalyst selectively degraded this unsaturated polymer to propylene in yields exceeding 80%. These results show promise for the application of mild catalysis to deconstruct otherwise stable polyolefins.

Assessing the sensibility and utility of a short-form version of the HIV Disability Questionnaire in clinical practice settings in Canada, Ireland and the USA: a mixed methods study.

OBJECTIVES: The Short-Form HIV Disability Questionnaire (SF-HDQ) was developed to measure the presence, severity and episodic nature of health challenges across six domains. Our aim was to assess the sensibility, utility and implementation of the SF-HDQ in clinical practice. DESIGN: Mixed methods study design involving semistructured interviews and questionnaire administration. PARTICIPANTS: We recruited adults living with HIV and HIV clinicians in Canada, Ireland and the USA. METHODS: We electronically administered the SF-HDQ followed by a Sensibility Questionnaire (face and content validity, ease of usage, format) and conducted semistructured interviews to explore the utility and implementation of the SF-HDQ in clinical practice. The threshold for sensibility was a median score of >5/7 (adults living with HIV) and>4/7 (HIV clinicians) for ≥80% of items. Qualitative interview data were analysed using directed content analysis. RESULTS: Median sensibility scores were >5 (adults living with HIV; n=29) and >4 (HIV clinicians; n=16) for 18/19 (95%) items. Interview data indicated that the SF-HDQ represents the health-related challenges of living with HIV and other concurrent health conditions; captures the daily episodic nature of HIV; and is easy to use. Clinical utility included measuring health challenges and change over time, guiding referral to specialists and services, setting goals, facilitating communication and fostering a multidisciplinary approach to care. Considerations for implementation included flexible, person-centred approaches to administration, and communicating scores based on personal preferences. CONCLUSIONS: The SF-HDQ possesses sensibility and utility for use in clinical settings with adults living with HIV and HIV clinicians in three countries.

Contra-thermodynamic Olefin Isomerization by Chain-Walking Hydroboration and Dehydroboration.

We report a dehydroboration process that can be coupled with chain-walking hydroboration to create a one-pot, contra-thermodynamic, short- or long-range isomerization of internal olefins to terminal olefins. This dehydroboration occurs by a sequence comprising activation with a nucleophile, iodination, and base-promoted elimination. The isomerization proceeds at room temperature without the need for a fluoride base, and the substrate scope of this isomerization is expanded over those of previous isomerizations we have reported with silanes.

Transport and dispersion of tracers simulating COVID-19 aerosols in passenger aircraft.

Many laboratory experiments and model development activities have been underway to better estimate the risk of a person indoors becoming infected with COVID-19. The current paper focusses on the near-field (distances < about 5 m) transport and dispersion (T&D) of the virons, treating them as inert tracers. The premise is that the T&D process follows widely used basic analytical near-field formulations such as a slab model, a Gaussian plume model, or a diffusivity (K) model. A slab or Gaussian model is more appropriate for cloud sizes less than the distance scale of the turbulence, while a K model is more appropriate for cloud sizes larger than the distance scale. The proposed slab model is evaluated with observations from the TRANSCOM tracer experiment in Boeing 767 and 777 airplanes, which involved multiple release scenarios. Release rates of 1-µm plastic bead inert tracers were constant over 60 s from a mannequin's mouth and samplers were placed at about 40 nearby seat locations. A simple basic science near-field slab model is shown to agree with observations of maximum concentration and dose within a factor of two or three.

Disability and self-care living strategies among adults living with HIV during the COVID-19 pandemic.

BACKGROUND: Events associated with the COVID-19 pandemic, such as physical distancing, closure of community services, postponement of health appointments, and loss of employment can lead to social isolation, financial uncertainty, and interruption of antiretroviral adherence, resulting in additional health-related challenges (disability) experienced among adults living with chronic illness such as HIV. 'Living strategies' is a concept derived from the perspectives of people living with HIV, defined as behaviors, attitudes and beliefs adopted by people living with HIV to help deal with disability associated with HIV and multi-morbidity. Our aim was to describe disability among adults living with HIV and self-care living strategies used during the COVID-19 pandemic. METHODS: Adults living with HIV in Toronto, Ontario, Canada, including some with pre-pandemic HIV Disability Questionnaire (HDQ) data, completed a cross-sectional web-based survey between June-August 2020. The survey included the HDQ and questions about self-care living strategy use during the pandemic. We compared disability (HDQ) scores prior to versus during the pandemic using paired t-tests. We reported the proportion of participants who engaged in various living strategies at least 'a few times a week' or 'everyday' during the pandemic. RESULTS: Of the 63 respondents, 84% were men, median age 57 years, and 62% lived alone. During the pandemic the greatest disability severity was in the uncertainty [median 30; Interquartile range (IQR): 16, 43] and mental-emotional (25; IQR: 14, 41) domains. Among the 51 participants with pre-pandemic data, HDQ severity scores were significantly greater (worse) during the pandemic (vs prior) in all domains. Greatest change from prior to during the pandemic was in the mental-emotional domain for presence (17.7; p < 0.001), severity (11.4; p < 0.001), and episodic nature (9.3; p < 0.05) of disability. Most participants (> 60%) reported engaging a 'few times a week' or 'everyday' in self-care strategies associated with maintaining sense of control and adopting positive attitudes and beliefs. CONCLUSIONS: People living with HIV reported high levels of uncertainty and mental-emotional health challenges during the pandemic. Disability increased across all HDQ dimensions, with the greatest worsening in the mental-emotional health domain. Results provide an understanding of disability and self-care strategy use during the COVID-19 pandemic.

Disability and Self-care Living Strategies Among Adults Living With HIV During the COVID-19 Pandemic.

BackgroundEvents associated with the COVID-19 pandemic, such as physical distancing, closure of community services, postponement of health appointments, and loss of employment can lead to social isolation, financial uncertainty, and interruption of antiretroviral adherence, resulting in additional health-related challenges (disability) experienced among adults living with chronic illness such as HIV. 'Living strategies' is a concept derived from the perspective of people living with HIV, defined as behaviors, attitudes and beliefs adopted by people living with HIV to help deal with disability associated with HIV and multi-morbidity. Our aim was to describe disability among adults living with HIV and self-care living strategies used during the COVID-19 pandemic. MethodsAdults living with HIV in Toronto, Ontario, Canada, including some with pre-pandemic HIV Disability Questionnaire (HDQ) data, completed a cross-sectional web-based survey between June-August 2020. The survey included the HDQ and questions about self-care living strategy use during the pandemic. We compared disability (HDQ) scores prior to versus during the pandemic using paired t-tests. We reported the proportion of participants who engaged in various living strategies at least 'a few times a week' or 'everyday' during the pandemic. ResultsOf the 63 respondents, 84% were men, median age 57 years, and 62% lived alone. During the pandemic the greatest disability severity was in the uncertainty (median 30; Interquartile range (IQR): 16, 43) and mental-emotional (25; IQR: 14, 41) domains. Among the 51 participants with pre-pandemic data, HDQ severity scores were significantly greater (worse) during the pandemic (vs prior) in all domains. Greatest change from prior to during the pandemic was in the mental-emotional domain for presence (17.7; p<0.001), severity (11.4; p<0.001), and episodic nature (9.3; p<0.05) of disability. Most participants (>60%) reported engaging a 'few times a week' or 'everyday' in self-care strategies associated with maintaining sense of control and adopting positive attitudes and beliefs. ConclusionsPeople living with HIV reported high levels of uncertainty and mental-emotional health challenges during the pandemic. Disability increased across all HDQ dimensions, with the greatest worsening in the mental-emotional health domain. Results provide an understanding of disability and self-care strategy use during the COVID-19 pandemic.