Publications by authors named "Patrick Smith"

453 Publications

Depressive symptoms at 1 year after surgery increase the risk of cardiac allograft vasculopathy and mortality in heart transplant recipients: A prospective cohort study.

Gen Hosp Psychiatry 2021 Mar 26;71:20-26. Epub 2021 Mar 26.

Academic Centre for Nursing and Midwifery, Department of Public Health and Primary Care, KU Leuven - University of Leuven, Belgium; Institute of Nursing Science, Department Public Health, University of Basel, Switzerland. Electronic address:

Objective: To investigate the impact of depressive symptoms at 1-year post-heart transplant (HTx) on cardiac allograft vasculopathy (CAV) and mortality.

Methods: We performed a single-center prospective cohort study of patients 1-year post-HTx consecutively enrolled between January 2001 and September 2015, and followed-up until November 2020. Kaplan-Meier and uni- and multivariate cox proportional hazards models were used to investigate the impact of depressive symptoms (Beck Depression Inventory) on all-cause mortality and clustered CAV events, i.e. time to angiographically detected CAV, revascularizations, retransplantation/CAV-mortality.

Results: 23.7% (45/190) (median age 53.5 [IQR 19.3], 77% men) had mild to severe depressive symptoms (BDI 10-63). Forty-four patients (23.2%) died during a 10.4 years median follow-up. Depressive symptoms (BDI ≥ 10) increased all-cause mortality risk (HR = 2.52 [1.35-4.71], p = .004), even after adjusting for confounders (HR = 2.95 [1.50-5.80], p = .002). CAV data were available for 156 patients. During a 9.9 years median follow-up, 51 patients (32.7%) developed CAV or revascularization of which 8 received at least a second revascularization, 3 were re-transplanted, and 9 died from CAV-related causes. Analysis showed a significant increased CAV-risk among depressed patients (HR = 2.27 [1.10-4.69], p = .026), even in adjusted models (HR = 2.25 [1.01-4.98, p = .047).

Conclusion: Depressive symptoms at 1-year post-HTx unfavorably impact mortality and CAV, highlighting the need for interventions.
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http://dx.doi.org/10.1016/j.genhosppsych.2021.03.008DOI Listing
March 2021

3D-Printed Bioplastics with Shape-Memory Behavior Based on Native Bovine Serum Albumin.

ACS Appl Mater Interfaces 2021 Apr 19;13(16):19193-19199. Epub 2021 Apr 19.

Department of Chemistry, University of Washington, Seattle, Washington 98195, United States.

Bio-based plastics that can supplant petroleum-derived materials are necessary to meet the future demands of sustainability in the life cycle of plastic materials. While there are significant efforts to develop protein-based plastic materials for commercial use, their application is limited by poor processability and limitations in mechanical performance. Here, we present a bovine serum albumin (BSA)-based resin for stereolithographic apparatus (SLA) 3D printing that affords bioplastic objects with shape-memory behavior. We demonstrate that the native conformation of these globular proteins is largely retained in the 3D-printed constructs and that each protein molecule possesses a "stored length" that could be revealed during mechanical deformation (extension or compression) of the 3D bioplastic objects. While the plastically deformed objects could retain this state for an indefinite period of time, heating the object or submerging in water allowed it to return to its original 3D-printed shape.
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http://dx.doi.org/10.1021/acsami.0c22377DOI Listing
April 2021

Blueprint for pandemic response: Focus on translational medicine, clinical pharmacology and pharmacometrics.

Br J Clin Pharmacol 2021 Apr 14. Epub 2021 Apr 14.

Certara, Princeton, NJ, USA.

Perhaps the most important lesson learned from the COVID-19 pandemic is that of preparedness. Enhanced surveillance systems for early threat detection will be crucial to maximizing response time for implementation of public health measures and mobilization of resources in containing an emerging pandemic. Recent outbreaks have been dominated by viral pathogens, with RNA respiratory viruses being the most likely to have pandemic potential. These should therefore be a preparedness priority. Tools in the areas of virology, drug discovery, clinical pharmacology, translational medicine and pharmacometrics should be considered key components in the rapid identification and development of existing and novel interventions for a pandemic response. Prioritization of therapeutics should be based on in vitro activity, likelihood of achieving effective drug concentrations at the site of action, and safety profile at the doses that will be required for clinical efficacy. Deployment strategies must be tailored to the epidemiology of the disease, and the adequacy of the response should be re-evaluated in view of evolving epidemiological factors. An interdisciplinary framework integrating drug pharmacology, viral kinetics, epidemiology and health economics could help optimize the deployment strategy by improving decision-making around who to treat, when to treat, and with what type of intervention for optimal outcomes. Lastly, while an effective vaccine will ultimately end a pandemic, antiviral drug intervention guided by clinical pharmacology principles will continue to play a critical role in any pandemic response.
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http://dx.doi.org/10.1111/bcp.14859DOI Listing
April 2021

Editorial Commentary: Repair the Anterior Cruciate Ligament When You Can: Add Suture Tape Augmentation and Dress for Success.

Authors:
Patrick A Smith

Arthroscopy 2021 04;37(4):1242-1244

University of Missouri and Columbia Orthopaedic Group.

Preserving the native anterior cruciate ligament (ACL) through primary repair has seen a resurgence over the past few years-rightfully so-given the inherent advantages of repairing the ACL over reconstruction. The issue is how best to repair the ACL and protect it to optimize healing. Suture tape augmentation techniques have shown promising low failure rates, and recent biomechanical studies have demonstrated benefits of the suture tape and optimal fixation methods for ACL repair. So, I believe it is time for orthopaedic surgeons to strongly consider routine suture tape augmentation use for improved outcomes with primary ACL repair.
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http://dx.doi.org/10.1016/j.arthro.2020.12.218DOI Listing
April 2021

The association of post-operative delirium with patient-reported outcomes and mortality after lung transplantation.

Clin Transplant 2021 Mar 7:e14275. Epub 2021 Mar 7.

Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

Post-operative delirium after lung transplantation is common. Its associations with health-related quality of life (HRQL), depression, and mortality remains unknown. In 236 lung transplant recipients, HRQL and depressive symptoms were assessed as part of a structured survey battery before and after transplantation. Surveys included the Geriatric Depressive Scale (GDS) and Short Form 12 (SF12). Delirium was assessed throughout the post-operative intensive care unit (ICU) stay with Confusion Assessment Method for ICU. Delirium and mortality data were extracted from electronic medical records. We examined associations between delirium and changes in depressive symptoms and HRQL using linear mixed effects models and association between delirium and mortality with Cox-proportional hazard models. Post-operative delirium occurred in 34 participants (14%). Delirium was associated with attenuated improvements in SF12-PCS (difference ₋4.0; 95%CI: -7.4, -0.7) but not SF12-MCS (difference 2.2; 95%CI: -0.7,5.7) or GDS (difference ₋0.4; 95%CI: -1.5,0.7). Thirty-two participants died during the study period. Delirium was associated with increased adjusted hazard risk of mortality (HR 17.9, 95%CI: 4.4,72.5). Delirium after lung transplantation identifies a group at increased risk for poorer HRQL and death within the first post-operative year. Further studies should investigate potential causal links between delirium, and poorer HRQL and mortality risk after lung transplantation.
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http://dx.doi.org/10.1111/ctr.14275DOI Listing
March 2021

Structural Racism and Oral Health Inequities of Black vs. non-Hispanic White Adults in the U.S.

J Health Care Poor Underserved 2021 ;32(1):50-63

Structural racism negatively affects the health of Black populations in the U.S. Black populations experience a higher burden of oral diseases, such as tooth decay, periodontal disease, and oral and pharyngeal cancers than other racial groups experience. Oral health literature refers to racial inequities in the context of social disadvantage. However, structural racism perpetuates those contributory social disadvantages, such as inadequate access to affordable housing, education, and employment. In addition, in states where nearly 50% of U.S. Black populations reside, there is an inequitable distribution of adult Medicaid dental benefits as well as an inequitable availability of both Black and non-Black oral health care providers. Addressing structural racism in oral health should involve commitment among stakeholders to establish awareness and equity through community-building, policy, oral health workforce development, and research.
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http://dx.doi.org/10.1353/hpu.2021.0007DOI Listing
January 2021

Dental students' comfort discussing nutrition and obesity prevention with parents and caregivers.

J Dent Educ 2021 Feb 23. Epub 2021 Feb 23.

Division of Prevention and Public Health Sciences, Department of Pediatric Dentistry, University of Illinois Chicago College of Dentistry, Chicago, Illinois, IL, USA.

Purpose: Dentists can address childhood obesity by educating patients about mediating factors, such as nutrition and dietary habits, facilitating behavioral interventions, and participating in interprofessional collaborations. Dental schools are encouraged to prepare future dentists to address childhood obesity. The aim of this study was to assess dental students' attitudes, comfort, and perceived barriers discussing nutrition and obesity prevention with parents and caregivers of children aged 0-5, after a one-time service-learning experience in a pediatric primary care setting to promote oral health.

Methods: Following conversations with parents and caregivers, students completed an 11-item survey via Qualtrics.

Results: Of 144 second-year dental students that participated in the service-learning experience over 2 years, 101 participated in the survey for a response rate of 70.1%. Most students agreed that dentists' roles include discussing nutrition (98.0%) and obesity prevention (83.2%). During the service-learning experience, 78.2 percent of students discussed nutrition, and 5.0% discussed obesity prevention, with 3.0% and 22.8% of students reporting some level of discomfort with each topic, respectively. The most reported barriers for discussing both nutrition and obesity prevention were concern for "appearing judgmental" and "fear of offending clients." Mean comfort scores among students who reported barriers of "appearing judgmental" (p = < 0.0001) and "fear of offending clients" (p = 0.017) for nutrition discussions, and a "lack of parental acceptance of guidance" as a barrier for discussing obesity prevention (p = 0.016), suggest that those barriers were associated with less comfort.

Conclusion: Dental students' perceived barriers to discussing nutrition and obesity prevention with parents and caregivers may negatively influence dental students' comfort.
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http://dx.doi.org/10.1002/jdd.12575DOI Listing
February 2021

Structural mechanism of DNA recognition by the p204 HIN domain.

Nucleic Acids Res 2021 03;49(5):2959-2972

Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, P.R. China.

The interferon gamma-inducible protein 16 (IFI16) and its murine homologous protein p204 function in non-sequence specific dsDNA sensing; however, the exact dsDNA recognition mechanisms of IFI16/p204, which harbour two HIN domains, remain unclear. In the present study, we determined crystal structures of p204 HINa and HINb domains, which are highly similar to those of other PYHIN family proteins. Moreover, we obtained the crystal structure of p204 HINab domain in complex with dsDNA and provided insights into the dsDNA binding mode. p204 HINab binds dsDNA mainly through α2 helix of HINa and HINb, and the linker between them, revealing a similar HIN:DNA binding mode. Both HINa and HINb are vital for HINab recognition of dsDNA, as confirmed by fluorescence polarization assays. Furthermore, a HINa dimerization interface was observed in structures of p204 HINa and HINab:dsDNA complex, which is involved in binding dsDNA. The linker between HINa and HINb reveals dynamic flexibility in solution and changes its direction at ∼90° angle in comparison with crystal structure of HINab:dsDNA complex. These structural information provide insights into the mechanism of DNA recognition by different HIN domains, and shed light on the unique roles of two HIN domains in activating the IFI16/p204 signaling pathway.
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http://dx.doi.org/10.1093/nar/gkab076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969034PMC
March 2021

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials.

Lancet 2021 03 19;397(10277):881-891. Epub 2021 Feb 19.

Department of Infection, Guy's and St Thomas' NHS Foundation Trust, St Thomas' Hospital, London, UK; MRC Clinical Trials Unit, University College London, London, UK.

Background: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered.

Methods: We present data from three single-blind randomised controlled trials-one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)-and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 10 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 10 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005).

Findings: Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4-74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3-85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59-0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3-91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0-69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18-55 years (GMR 2·32 [2·01-2·68]).

Interpretation: The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose.

Funding: UK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.
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http://dx.doi.org/10.1016/S0140-6736(21)00432-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894131PMC
March 2021

Psychosocial considerations in the assessment of hand transplant candidates: A single-center experience and brief literature review.

Clin Transplant 2021 Apr 17;35(4):e14268. Epub 2021 Mar 17.

Department of Surgery, Duke University Medical Center, Durham, NC, USA.

Vascularized composite allograft, including hand transplantation (HT), has gained wider usage as a reconstructive treatment over the past 30 years. HT recipients face unique psychosocial challenges compared to their solid organ and/or bone marrow transplant counterparts. Accordingly, the psychosocial evaluation among HT candidates continues to evolve, leaving a lack of consensus as to the critical psychosocial domains and psychometric testing instruments to help evaluate individuals considering HT. The present manuscript describes the psychosocial evaluation process within the Duke HT program, which been contacted by 80 potential candidates since 2014. The Duke HT evaluation process incorporates a comprehensive psychosocial assessment within domains including personality, cognitive function, mood, behavioral adherence, social support, and substance use history, among others. Our experience underscores the potential utility of collecting thorough psychosocial evaluations, supplemented by psychometric test data, to comprehensively assess potential HT candidates.
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http://dx.doi.org/10.1111/ctr.14268DOI Listing
April 2021

The relationship between marijuana use and psychosocial variables in living kidney donor candidates.

Clin Transplant 2021 Feb 8:e14248. Epub 2021 Feb 8.

Department of Psychiatry and Behavioral Sciences, Division of Behavioral Medicine, Duke University Medical Center, Durham, NC, USA.

Background: We investigate whether marijuana use in living kidney donor candidates is associated with psychosocial risk factors that place donors at higher risk for adverse outcomes and the unique associations between marijuana use and donor candidacy.

Methods: Medical records of 757 living kidney donor candidates were reviewed. Patients were grouped into marijuana users/abstainers; demographic, psychiatric, and substance use variables were compared. Multivariate logistic regression assessed the independent association of marijuana use on committee approval for donation.

Results: Marijuana use was associated with lack of health insurance, legal history, lower education level, active and history of substance use disorder, active psychiatric disorder, history of multiple psychiatric diagnoses, and history of suicidality. Marijuana users were also more likely to be young, male, unmarried, and less likely to be approved for donation by the multidisciplinary selection committee. This latter association persisted in multivariate models.

Conclusions: This is the first study to show that marijuana use is associated with psychosocial factors that could impact behavioral adherence following kidney donation, while reducing chances of committee approval for kidney donation. Special attention to potential overlay between psychosocial risk factors and marijuana use should be considered when evaluating kidney donors, particularly in context of increasingly legal use.
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http://dx.doi.org/10.1111/ctr.14248DOI Listing
February 2021

Model-Informed Drug Development for Anti-Infectives: State of the Art and Future.

Clin Pharmacol Ther 2021 Apr 9;109(4):867-891. Epub 2021 Mar 9.

Certara, Princeton, New Jersey, USA.

Model-informed drug development (MIDD) has a long and rich history in infectious diseases. This review describes foundational principles of translational anti-infective pharmacology, including choice of appropriate measures of exposure and pharmacodynamic (PD) measures, patient subpopulations, and drug-drug interactions. Examples are presented for state-of-the-art, empiric, mechanistic, interdisciplinary, and real-world evidence MIDD applications in the development of antibacterials (review of minimum inhibitory concentration-based models, mechanism-based pharmacokinetic/PD (PK/PD) models, PK/PD models of resistance, and immune response), antifungals, antivirals, drugs for the treatment of global health infectious diseases, and medical countermeasures. The degree of adoption of MIDD practices across the infectious diseases field is also summarized. The future application of MIDD in infectious diseases will progress along two planes; "depth" and "breadth" of MIDD methods. "MIDD depth" refers to deeper incorporation of the specific pathogen biology and intrinsic and acquired-resistance mechanisms; host factors, such as immunologic response and infection site, to enable deeper interrogation of pharmacological impact on pathogen clearance; clinical outcome and emergence of resistance from a pathogen; and patient and population perspective. In particular, improved early assessment of the emergence of resistance potential will become a greater focus in MIDD, as this is poorly mitigated by current development approaches. "MIDD breadth" refers to greater adoption of model-centered approaches to anti-infective development. Specifically, this means how various MIDD approaches and translational tools can be integrated or connected in a systematic way that supports decision making by key stakeholders (sponsors, regulators, and payers) across the entire development pathway.
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http://dx.doi.org/10.1002/cpt.2198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014105PMC
April 2021

Arthroscopic Centralization of the Extruded Medial Meniscus.

Arthrosc Tech 2021 Jan 19;10(1):e43-e48. Epub 2020 Dec 19.

Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota, U.S.A.

Tears of the posterior medial meniscus root commonly result in extrusion of the meniscus and disruption of tibiofemoral contact mechanics. Transtibial pull-through repair of the root often results in healing of the tear, but postoperative extrusion may persist. In this scenario, the meniscus is unlikely to be chondroprotective. Therefore, an additional centralization procedure is necessary to improve the extrusion. Biomechanical studies have demonstrated that centralization can improve meniscus mechanics and potentially reduce the risk of osteoarthritis. This Technical Note describes an arthroscopic technique for medial meniscus posterior root repair that combines transtibial pullout and centralization sutures.
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http://dx.doi.org/10.1016/j.eats.2020.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823061PMC
January 2021

Mobile health technology to improve emergent frailty after lung transplantation.

Clin Transplant 2021 Apr 5;35(4):e14236. Epub 2021 Feb 5.

Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California San Francisco, San Francisco, CA, USA.

We evaluated the feasibility, safety, and efficacy of a mHealth-supported physical rehabilitation intervention to treat frailty in a pilot study of 18 lung transplant recipients. Frail recipients were defined by a short physical performance battery (SPPB score ≤7). The primary intervention modality was Aidcube, a customizable rehabilitation mHealth platform. Our primary aims included tolerability, feasibility, and acceptability of use of the platform, and secondary outcomes were changes in SPPB and in scores of physical activity, and disability measured using the Duke Activity Status Index (DASI) and Lung Transplant-Value Life Activities (LT-VLA). Notably, no adverse events were reported. Subjects reported the app was easy to use, usability improved over time, and the app enhanced motivation to engage in rehabilitation. Comments highlighted the complexities of immediate post-transplant rehabilitation, including functional decline, pain, tremor, and fatigue. At the end of the intervention, SPPB scores improved a median of 5 points from a baseline of 4. Physical activity and patient-reported disability also improved. The DASI improved from 4.5 to 19.8 and LT-VLA score improved from 2 to 0.59 at closeout. Overall, utilization of a mHealth rehabilitation platform was safe and well received. Remote rehabilitation was associated with improvements in frailty, physical activity and disability. Future studies should evaluate mHealth treatment modalities in larger-scale randomized trials of lung transplant recipients.
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http://dx.doi.org/10.1111/ctr.14236DOI Listing
April 2021

Editorial Commentary: Independent Femoral Tunnel Drilling Avoids Anterior Cruciate Ligament Graft Malpositioning: Advice From a Transtibial Convert.

Authors:
Patrick A Smith

Arthroscopy 2021 01;37(1):338-339

University of Missouri.

Optimal femoral anterior cruciate ligament graft placement has been extensively studied. The champions of transtibial reconstruction debate the backers of anteromedial portal and outside-in drilling. The holy grail is footprint restoration and how we best to get there. To me, creating the femur independently provides the best chance of finding that footprint by being unconstrained by the tibia. Anterior cruciate ligament surgery is challenging enough; decrease intraoperative stress and increase your likelihood of femoral footprint restoration by drilling it though the anteromedial portal.
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http://dx.doi.org/10.1016/j.arthro.2020.10.026DOI Listing
January 2021

Knotless Primary Anterior Cruciate Ligament Repair with Adjustable Loop Device and Internal Brace Augmentation.

Arthrosc Tech 2020 Dec 21;9(12):e1967-e1975. Epub 2020 Dec 21.

Department of Orthopaedic Surgery, University of Missouri, Columbia, Missouri, U.S.A.

With the recent resurgence of primary anterior cruciate ligament repair, it is important to strive for optimal patient outcomes. This knotless primary repair procedure takes advantage of the use of an adjustable loop device, which allows for intraoperative retensioning by the surgeon. This technical advancement combined with augmentation with an internal brace could potentially minimize gap formation at the repair site, thereby increasing repair stability and ultimate outcome.
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http://dx.doi.org/10.1016/j.eats.2020.08.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768549PMC
December 2020

Relationship Between Depression/Anxiety and Cognitive Function Before and 6 Weeks After Major Non-Cardiac Surgery in Older Adults.

J Geriatr Psychiatry Neurol 2020 Dec 30:891988720978791. Epub 2020 Dec 30.

Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.

Objective: To determine the relationship between affective measures and cognition before and after non-cardiac surgery in older adults.

Methods: Observational prospective cohort study in 103 surgical patients age ≥ 60 years old All participants underwent cognitive testing, Center for Epidemiologic Studies-Depression, and State Anxiety Inventory screening before and 6 weeks after surgery. Cognitive test scores were combined by factor analysis into 4 cognitive domains, whose mean was defined as the continuous cognitive index (CCI). Postoperative global cognitive change was defined by CCI change from before to after surgery, with negative CCI change indicating worsened postoperative global cognition and vice versa.

Results: Lower global cognition before surgery was associated with greater baseline depression severity (Spearman's r = -0.30, p = 0.002) and baseline anxiety severity (Spearman's r = -0.25, p = 0.010), and these associations were similar following surgery (r = -0.36, p < 0.001; r = -0.26, p = 0.008, respectively). Neither baseline depression or anxiety severity, nor postoperative changes in depression or anxiety severity, were associated with pre- to postoperative global cognitive change.

Conclusions: Greater depression and anxiety severity were each associated with poorer cognitive performance both before and after surgery in older adults. Yet, neither baseline depression or anxiety symptoms, nor postoperative change in these symptoms, were associated with postoperative cognitive change.
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http://dx.doi.org/10.1177/0891988720978791DOI Listing
December 2020

Using in silico viral kinetic models to guide therapeutic strategies during a pandemic: An example in SARS-CoV-2.

Br J Clin Pharmacol 2020 Dec 29. Epub 2020 Dec 29.

Certara, Princeton, NJ, USA.

Aims: We propose the use of in silico mathematical models to provide insights that optimize therapeutic interventions designed to effectively treat respiratory infection during a pandemic. A modelling and simulation framework is provided using SARS-CoV-2 as an example, considering applications for both treatment and prophylaxis.

Methods: A target cell-limited model was used to quantify the viral infection dynamics of SARS-CoV-2 in a pooled population of 105 infected patients. Parameter estimates from the resulting model were used to simulate and compare the impact of various interventions against meaningful viral load endpoints.

Results: Robust parameter estimates were obtained for the basic reproduction number, viral release rate and infected-cell mortality from the infection model. These estimates were informed by the largest dataset currently available for SARS-CoV-2 viral time course. The utility of this model was demonstrated using simulations, which hypothetically introduced inhibitory or stimulatory drug mechanisms at various target sites within the viral life-cycle. We show that early intervention is crucial to achieving therapeutic benefit when monotherapy is administered. In contrast, combination regimens of two or three drugs may provide improved outcomes if treatment is initiated late. The latter is relevant to SARS-CoV-2, where the period between infection and symptom onset is relatively long.

Conclusions: The use of in silico models can provide viral load predictions that can rationalize therapeutic strategies against an emerging viral pathogen.
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http://dx.doi.org/10.1111/bcp.14718DOI Listing
December 2020

T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial.

Nat Med 2021 02 17;27(2):270-278. Epub 2020 Dec 17.

The Jenner Institute, University of Oxford, Oxford, UK.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses and might reduce the potential for disease enhancement. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection. Studies of patients infected with SARS-CoV-2 have suggested a protective role for both humoral and cell-mediated immune responses in recovery from COVID-19 (refs. ). ChAdOx1 nCoV-19 (AZD1222) is a candidate SARS-CoV-2 vaccine comprising a replication-deficient simian adenovirus expressing full-length SARS-CoV-2 spike protein. We recently reported preliminary safety and immunogenicity data from a phase 1/2 trial of the ChAdOx1 nCoV-19 vaccine (NCT04400838) given as either a one- or two-dose regimen. The vaccine was tolerated, with induction of neutralizing antibodies and antigen-specific T cells against the SARS-CoV-2 spike protein. Here we describe, in detail, exploratory analyses of the immune responses in adults, aged 18-55 years, up to 8 weeks after vaccination with a single dose of ChAdOx1 nCoV-19 in this trial, demonstrating an induction of a Th1-biased response characterized by interferon-γ and tumor necrosis factor-α cytokine secretion by CD4 T cells and antibody production predominantly of IgG1 and IgG3 subclasses. CD8 T cells, of monofunctional, polyfunctional and cytotoxic phenotypes, were also induced. Taken together, these results suggest a favorable immune profile induced by ChAdOx1 nCoV-19 vaccine, supporting the progression of this vaccine candidate to ongoing phase 2/3 trials to assess vaccine efficacy.
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http://dx.doi.org/10.1038/s41591-020-01194-5DOI Listing
February 2021

Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses.

Nat Med 2021 02 17;27(2):279-288. Epub 2020 Dec 17.

The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.

More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we reported early immunogenicity and safety outcomes of a viral vector coronavirus vaccine, ChAdOx1 nCoV-19 (AZD1222), in a single-blinded phase 1/2 randomized controlled trial of healthy adults aged 18-55 years ( NCT04324606 ). Now we describe safety and exploratory humoral and cellular immunogenicity of the vaccine, from subgroups of volunteers in that trial, who were subsequently allocated to receive a homologous full-dose (SD/SD D56; n = 20) or half-dose (SD/LD D56; n = 32) ChAdOx1 booster vaccine 56 d following prime vaccination. Previously reported immunogenicity data from the open-label 28-d interval prime-boost group (SD/SD D28; n = 10) are also presented to facilitate comparison. Additionally, we describe volunteers boosted with the comparator vaccine (MenACWY; n = 10). In this interim report, we demonstrate that a booster dose of ChAdOx1 nCoV-19 is safe and better tolerated than priming doses. Using a systems serology approach we also demonstrate that anti-spike neutralizing antibody titers, as well as Fc-mediated functional antibody responses, including antibody-dependent neutrophil/monocyte phagocytosis, complement activation and natural killer cell activation, are substantially enhanced by a booster dose of vaccine. A booster dose of vaccine induced stronger antibody responses than a dose-sparing half-dose boost, although the magnitude of T cell responses did not increase with either boost dose. These data support the two-dose vaccine regime that is now being evaluated in phase 3 clinical trials.
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http://dx.doi.org/10.1038/s41591-020-01179-4DOI Listing
February 2021

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

Lancet 2021 01 8;397(10269):99-111. Epub 2020 Dec 8.

St George's Vaccine Institute, St George's, University of London, London, UK.

Background: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials.

Methods: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 10 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674.

Findings: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; p=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation.

Interpretation: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials.

Funding: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.
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http://dx.doi.org/10.1016/S0140-6736(20)32661-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723445PMC
January 2021

ACT with CF: A telehealth and in-person feasibility study to address anxiety and depressive symptoms among people with cystic fibrosis.

J Cyst Fibros 2021 Jan 2;20(1):133-139. Epub 2020 Dec 2.

Thomas Jefferson University Hospital, Department of Pulmonology, 834 Walnut St, Philadelphia, PA 19107.

Background: Anxiety and depressive symptoms are common among individuals with cystic fibrosis (CF) and are associated with decreased lung function [3], quality of life [4], and treatment adherence [2]. However, CF-specific targeted psychotherapeutic interventions are lacking. This study examined whether Acceptance and Commitment Therapy (ACT) [7], delivered via telehealth, would address this need and improve clinical symptoms. Telehealth is ideal for CF patients, given exposure precautions and frequent hospitalization. ACT emphasizes acceptance, thereby reducing avoidance of anxiety and depressive symptoms associated with CF. It was hypothesized that our ACT with CF protocol [11] would also improve lung function among people with CF.

Methods: Participants were 28 adults with CF and elevated clinical symptoms who completed 6 ACT with CF sessions. They completed measures of depression, anxiety, and cognitive fusion at baseline, post-intervention, and at a 3-month follow-up. Lung function was calculated 3 months pre- and 3 months post-treatment.

Results: The majority of participants selected treatment via telehealth (n = 22; 79%). 96% of participants (n=27) completed all 6 sessions, with 93% (n=26) voicing a strong desire to continue treatment with ACT. 79% of the sample (n=22) indicated, after just 1 session of ACT with CF, that treatment seemed logical and feeling confident that it would reduce symptoms of anxiety and depression. ACT with CF was associated with a statistically significant reduction in a composite score of psychological distress from pre to post treatment, corresponding to a large standardized effect size, that was not sustained at 3 months. Telehealth-delivered ACT with CF was as effective as in-person. Reductions in cognitive fusion were strongly related to improvements in psychosocial functioning. This is particularly promising as it reflects the proposed mechanism of action of ACT. ACT with CF was also associated with increased FEV/FVC ratio at post-treatment follow-up.

Conclusions: ACT with CF delivered via telehealth or in-person is a feasible and potentially effective treatment for improving anxiety and depressive symptoms, and increasing psychological flexibility via reductions in cognitive fusion. Due to the effect size associated with reduction in psychosocial distress, we are cautiously optimistic that ACT with CF will prove an effective treatment. Larger randomized controlled trials are needed to confirm the observed findings and further delineate the potential effects of ACT with CF on clinical outcomes among individuals with CF.
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http://dx.doi.org/10.1016/j.jcf.2020.11.013DOI Listing
January 2021

The Role of Exercise in Management of Mental Health Disorders: An Integrative Review.

Annu Rev Med 2021 01 30;72:45-62. Epub 2020 Nov 30.

Department of Psychiatry and Behavioral Sciences.

A large and growing body of evidence suggests that physical activity (PA) may hold therapeutic promise in the management of mental health disorders. Most evidence linking PA to mental health outcomes has focused on the effects of aerobic exercise training on depression, although a growing body of work supports the efficacy of both aerobic and resistance exercise paradigms in the treatment of anxiety and post-traumatic stress disorder. Despite abundant evidence linking PA and mental health, use of exercise training as a mental health treatment remains limited due to three important sources of uncertainty: () large individual differences in response to exercise treatment within multiple mental health domains; () the critical importance of sustained PA engagement, not always achieved, for therapeutic benefit; and () disagreement regarding the relative importance of putative therapeutic mechanisms. Our review of treatment data on exercise interventions and mental health outcomes focuses primarily on depression and anxiety within a health neuroscience framework. Within this conceptual framework, neurobiological and behavioral mechanisms may have additiveor synergistic influences on key cognitive and behavioral processes that influence mental health outcomes. We therefore highlight sources of treatment heterogeneity by integrating the critical influences of () neurobiological mechanisms enhancing neuroplasticity and () behavioral learning of self-regulatory skills. Understanding the interrelationships between dynamic neurobiological and behavioral mechanisms may help inform personalized mental health treatments and clarify why, and for whom, exercise improves mental health outcomes. The review concludes with recommendations for future studies leveraging individual differences to refine treatment approaches to optimize mental health benefits.
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http://dx.doi.org/10.1146/annurev-med-060619-022943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020774PMC
January 2021

Efficient and selective alkene hydrosilation promoted by weak, double Si-H activation at an iron center.

Chem Sci 2020 Jul 18;11(27):7070-7075. Epub 2020 Jun 18.

Department of Chemistry , University of California, Berkeley , Berkeley , California 94720-1460 , USA . Email:

Cationic iron complexes [Cp*(PrMeP)FeHSiHR], generated and characterized in solution, are very efficient catalysts for the hydrosilation of terminal alkenes and internal alkynes by primary silanes at low catalyst loading (0.1 mol%) and ambient temperature. These reactions yield only the corresponding secondary silane product, even with SiH as the substrate. Mechanistic experiments and DFT calculations indicate that the high rate of hydrosilation is associated with an inherently low barrier for dissociative silane exchange (product release).
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http://dx.doi.org/10.1039/d0sc01749cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690220PMC
July 2020

Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial.

Lancet 2021 12 19;396(10267):1979-1993. Epub 2020 Nov 19.

The Jenner Institute, University of Oxford, Oxford, UK.

Background: Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19 (AZD1222), in young adults, and now describe the safety and immunogenicity of this vaccine in a wider range of participants, including adults aged 70 years and older.

Methods: In this report of the phase 2 component of a single-blind, randomised, controlled, phase 2/3 trial (COV002), healthy adults aged 18 years and older were enrolled at two UK clinical research facilities, in an age-escalation manner, into 18-55 years, 56-69 years, and 70 years and older immunogenicity subgroups. Participants were eligible if they did not have severe or uncontrolled medical comorbidities or a high frailty score (if aged ≥65 years). First, participants were recruited to a low-dose cohort, and within each age group, participants were randomly assigned to receive either intramuscular ChAdOx1 nCoV-19 (2·2 × 10 virus particles) or a control vaccine, MenACWY, using block randomisation and stratified by age and dose group and study site, using the following ratios: in the 18-55 years group, 1:1 to either two doses of ChAdOx1 nCoV-19 or two doses of MenACWY; in the 56-69 years group, 3:1:3:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY; and in the 70 years and older, 5:1:5:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY. Prime-booster regimens were given 28 days apart. Participants were then recruited to the standard-dose cohort (3·5-6·5 × 10 virus particles of ChAdOx1 nCoV-19) and the same randomisation procedures were followed, except the 18-55 years group was assigned in a 5:1 ratio to two doses of ChAdOx1 nCoV-19 or two doses of MenACWY. Participants and investigators, but not staff administering the vaccine, were masked to vaccine allocation. The specific objectives of this report were to assess the safety and humoral and cellular immunogenicity of a single-dose and two-dose schedule in adults older than 55 years. Humoral responses at baseline and after each vaccination until 1 year after the booster were assessed using an in-house standardised ELISA, a multiplex immunoassay, and a live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) microneutralisation assay (MNA). Cellular responses were assessed using an ex-vivo IFN-γ enzyme-linked immunospot assay. The coprimary outcomes of the trial were efficacy, as measured by the number of cases of symptomatic, virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were by group allocation in participants who received the vaccine. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. This study is ongoing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137.

Findings: Between May 30 and Aug 8, 2020, 560 participants were enrolled: 160 aged 18-55 years (100 assigned to ChAdOx1 nCoV-19, 60 assigned to MenACWY), 160 aged 56-69 years (120 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY), and 240 aged 70 years and older (200 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY). Seven participants did not receive the boost dose of their assigned two-dose regimen, one participant received the incorrect vaccine, and three were excluded from immunogenicity analyses due to incorrectly labelled samples. 280 (50%) of 552 analysable participants were female. Local and systemic reactions were more common in participants given ChAdOx1 nCoV-19 than in those given the control vaccine, and similar in nature to those previously reported (injection-site pain, feeling feverish, muscle ache, headache), but were less common in older adults (aged ≥56 years) than younger adults. In those receiving two standard doses of ChAdOx1 nCoV-19, after the prime vaccination local reactions were reported in 43 (88%) of 49 participants in the 18-55 years group, 22 (73%) of 30 in the 56-69 years group, and 30 (61%) of 49 in the 70 years and older group, and systemic reactions in 42 (86%) participants in the 18-55 years group, 23 (77%) in the 56-69 years group, and 32 (65%) in the 70 years and older group. As of Oct 26, 2020, 13 serious adverse events occurred during the study period, none of which were considered to be related to either study vaccine. In participants who received two doses of vaccine, median anti-spike SARS-CoV-2 IgG responses 28 days after the boost dose were similar across the three age cohorts (standard-dose groups: 18-55 years, 20 713 arbitrary units [AU]/mL [IQR 13 898-33 550], n=39; 56-69 years, 16 170 AU/mL [10 233-40 353], n=26; and ≥70 years 17 561 AU/mL [9705-37 796], n=47; p=0·68). Neutralising antibody titres after a boost dose were similar across all age groups (median MNA at day 42 in the standard-dose groups: 18-55 years, 193 [IQR 113-238], n=39; 56-69 years, 144 [119-347], n=20; and ≥70 years, 161 [73-323], n=47; p=0·40). By 14 days after the boost dose, 208 (>99%) of 209 boosted participants had neutralising antibody responses. T-cell responses peaked at day 14 after a single standard dose of ChAdOx1 nCoV-19 (18-55 years: median 1187 spot-forming cells [SFCs] per million peripheral blood mononuclear cells [IQR 841-2428], n=24; 56-69 years: 797 SFCs [383-1817], n=29; and ≥70 years: 977 SFCs [458-1914], n=48).

Interpretation: ChAdOx1 nCoV-19 appears to be better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose. Further assessment of the efficacy of this vaccine is warranted in all age groups and individuals with comorbidities.

Funding: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.
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http://dx.doi.org/10.1016/S0140-6736(20)32466-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674972PMC
December 2021

Initial clinical outcomes comparing frozen versus fresh meniscus allograft transplants.

Knee 2020 Dec 13;27(6):1811-1820. Epub 2020 Nov 13.

Department of Orthopaedic Surgery, University of Missouri, Columbia, MO, USA; Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Department of Orthopaedic Surgery, Columbia, MO, USA; Mizzou BioJoint Center, University of Missouri Department of Orthopaedic Surgery, Columbia, MO, USA. Electronic address:

Background: To evaluate initial clinical outcomes using fresh meniscal allografts with high cell viability at transplantation time and meniscotibial ligament (MTL) reconstruction (Fresh) in comparison to standard fresh-frozen (Frozen) meniscus allograft transplantation (MAT).

Methods: Patients treated for medial and/or lateral meniscal deficiency using either Fresh or Frozen MAT with minimum of 1-year follow-up were identified from a prospective registry. Patient demographics, prior surgeries, MAT surgery data, complications, revisions, and failures were documented. Functional outcome scores were collected preoperatively, and 6 months and yearly after surgery and radiographic joint space measurements were performed. Treatment cohorts were compared for statistically significant (P < 0.005) differences using t-Tests and Fisher's exact tests.

Results: Twenty-seven patients (14 Fresh, 13 Frozen) met inclusion criteria and showed comparable characteristics. For Fresh MAT + MTL, 10 medial, two lateral, and two medial + lateral MAT were performed. For Frozen MAT, nine medial, and four lateral MAT were performed. There was significantly more improvement in the Fresh cohort compared to the Frozen cohort for VAS pain (P = 0.014), PROMIS Physical Function (P = 0.036) and Single Assessment Numeric Evaluation (P = 0.033) from preoperatively to 2 years postoperatively. Tegner Activity Scale and PROMIS Mobility score showed no significant differences. The International Knee Documentation Committee score revealed a clinically meaningful change for the Fresh group. Radiographic measurements showed no significant differences between groups. There were two Fresh MAT + MTL revisions and one conversion to TKA in each cohort.

Conclusions: Fresh MAT + MTL is safe and associated with potential advantages with respect to initial pain relief and function compared to standard frozen MAT.
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http://dx.doi.org/10.1016/j.knee.2020.09.015DOI Listing
December 2020

"'There's No Harm in Talking'…True…But It Depends on and What We Then Do".

Authors:
Patrick T Smith

Am J Bioeth 2020 12;20(12):32-34

Duke University Divinity School.

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http://dx.doi.org/10.1080/15265161.2020.1832619DOI Listing
December 2020