Comparison of the Kinematics Following Gait Perturbation in Individuals Who Did or Did Not Undergo Total Knee Replacement

We aimed to compare the spatiotemporal parameters and joint kinematics during unperturbed and perturbed gait between individuals with osteoarthritis (OA) who did or did not undergo total knee replacement (TKR) one year post a baseline evaluation. OA subjects scheduled for TKR (TKR group; n = 14) and not scheduled for TKR (NTKR group; n = 17) were age-matched. Outcome measures included: joint range of motion, timed up and go, joint pain levels, Oxford score, and the Activities-specific Balance Confidence Scale. In addition, spatiotemporal gait parameters and joint kinematics were recorded during perturbed and unperturbed gait. After one year, most of the TKR group (71%), but only 41% of the NTKR group, increased their gait velocity by more than 0.1m/sec, which is the meaningful clinical important difference for gait velocity. After perturbation of the contralateral limb, the TKR group showed a greater decrease in the maximal extension of the OA hip compared to the NTKR group (p = 0.031). After perturbation of the OA limb, more subjects decreased their OA knee flexion–extension range in the NTKR group compared to the TKR group (p = 0.011) and more subjects decreased their maximal ankle plantar flexion in the TKR group (p = 0.049). Although the surgery was successful in terms of pain reduction and increased functionality, individuals following TKR exhibited unique compensatory strategies in response to the perturbation of both limbs. These findings might suggest that balance deficits remain in individuals following TKR and therefore are associated with a risk of falls

Effect of FAmily CEntered (FACE®) Advance Care Planning on Longitudinal Congruence in End-of-Life Treatment Preferences: A Randomized Clinical Trial

© 2020, Springer Science+Business Media, LLC, part of Springer Nature. Trial tested effect of advance care planning on family/surrogates’ understanding of patients’ end-of-life treatment preferences longitudinally. A multisite, assessor-blinded, intent-to-treat, parallel-group, randomized controlled clinical trial in five hospital-based HIV clinics enrolled 449 participants aged 22 to 77 years during October 2013-March 2017. Patients living with HIV/family dyads were randomized at 2:1 ratio to 2 weekly ~ 60-min sessions either ACP (n = 155 dyads)—(1) ACP facilitated conversation, (2) Advance directive completion; or Control (n = 68 dyads)—(1) Developmental/relationship history, (2) Nutrition/exercise tips. ACP families/surrogates were more likely to accurately report patients’ treatment preferences at Time 1 (T1) and 12 months post-intervention (T2) compared to controls, experiencing high congruence longitudinally (high→high transition), [63·6% vs 37·7% (difference = 25·9%, 95% CI: 11·3%, 40·4%, χ2 = 11·52, p = 0·01)], even as patients’ preferences changed over time. ACP families/surrogates had eight times the odds of controls of having an excellent understanding of patients’ treatment preferences (Adjusted Odds Ratio 7.91, 95%CI: 3.08, 20.3). Conversations matter

Advance Care Planning—Complex and Working: Longitudinal Trajectory of Congruence in End-of-Life Treatment Preferences: An RCT

© The Author(s) 2021. Context: The effect of advance care planning (ACP) interventions on the trajectory of end-of-life treatment preference congruence between patients and surrogate decision-makers is unstudied. Objective: To identify unobserved distinctive patterns of congruence trajectories and examine how the typology of outcome development differed between ACP and controls. Methods: Multisite, assessor-blinded, intent-to-treat, randomized clinical trial enrolled participants between October 2013 to March 2017 from 5 hospital-based HIV clinics. Persons living with HIV(PLWH)/surrogate dyads were randomized to 2 weekly 60-minute sessions: ACP (1) ACP facilitated conversation, (2) advance directive completion; or Control (1) Developmental/relationship history, (2) Nutrition/Exercise. Growth Mixed Modeling was used for 18-month post-intervention analysis. Findings: 223 dyads (N = 449 participants) were enrolled. PLWH were 56% male, aged 22 to 77 years, and 86% African American. Surrogates were 56% female, aged 18 to 82 years, and 84% African American. Two latent classes (High vs. Low) of congruence growth trajectory were identified. ACP influenced the trajectory of outcome growth (congruence in all 5 AIDS related situations) by latent class. ACP dyads had a significantly higher probability of being in the High Congruence latent class compared to controls (52%, 75/144 dyads versus 27%, 17/62 dyads, p = 0.001). The probabilities of perfect congruence diminished at 3-months post-intervention but was then sustained. ACP had a significant effect (β = 1.92, p = 0.006, OR = 7.10, 95%C.I.: 1.729, 26.897) on the odds of being in the High Congruence class. Conclusion: ACP had a significant effect on the trajectory of congruence growth over time. ACP dyads had 7 times the odds of congruence, compared to controls. Three-months post-intervention is optimal for booster sessions

Measuring the impact of an empiric antibiotic algorithm for pulmonary exacerbation in children and young adults with cystic fibrosis

BACKGROUND: Antimicrobial stewardship is a systematic effort to change prescribing attitudes that can provide benefit in the provision of care to persons with cystic fibrosis (CF). Our objective was to decrease the unwarranted use of broad-spectrum antibiotics and assess the impact of an empiric antibiotic algorithm using quality improvement methodology. METHODS: We assembled a multidisciplinary team with expertise in CF. We assessed baseline antibiotic use for treatment of pulmonary exacerbation (PEx) and developed an algorithm to guide empiric antibiotic therapy. We included persons with CF admitted to Children\u27s National Hospital for treatment of PEx between January 2017 and March 2020. Our primary outcome measure was reducing unnecessary broad-spectrum antibiotic use, measured by use consistent with the empiric antibiotic algorithm. The primary intervention was the initiation of the algorithm. Secondary outcomes included documentation of justification for broad-spectrum antibiotic use and use of infectious disease (ID) consult. RESULTS: Data were collected from 56 persons with CF who had a total of 226 PEx events. The mean age at first PEx was 12 (SD 6.7) years; 55% were female, 80% were white, and 29% were Hispanic. After initiation of the algorithm, the proportion of PEx with antibiotic use consistent with the algorithm increased from 46.2% to 79.5%. Documentation of justification for broad-spectrum antibiotics increased from 56% to 85%. Use of ID consults increased from 17% to 54%. CONCLUSION: Antimicrobial stewardship initiatives are beneficial in standardizing care and fostering positive working relationships between CF pulmonologists, ID physicians, and pharmacists

FAmily-CEntered (FACE) Advance Care Planning Among African-American and Non-African-American Adults Living With HIV in Washington, DC: A Randomized Controlled Trial to Increase Documentation and Health Equity

© 2018 American Academy of Hospice and Palliative Medicine Context: No prospective studies address disease-specific advance care planning (ACP) for adults living with HIV/AIDS. Objective: To examine the efficacy of FAmily-CEntered (FACE) ACP in increasing ACP and advance directive documentation in the medical record. Methods: Longitudinal, two-arm, randomized controlled trial with intent-to-treat design recruited from five hospital-based outpatient HIV clinics in Washington, DC. Adults living with HIV and their surrogate decision-makers (N = 233 dyads) were randomized to either an intensive facilitated two-session FACE ACP (Next Steps: Respecting Choices goals of care conversation and Five Wishes advance directive) or healthy living control (conversations about developmental/relationship history and nutrition). Results: Patients (n = 223) mean age: 51 years, 56% male, 86% African-American. One hundred ninety-nine dyads participated in the intervention. At baseline, only 13% of patients had an advance directive. Three months after intervention, this increased to 59% for the FACE ACP group versus 17% in the control group (P \u3c 0.0001). Controlling for race, the odds of having an advance directive in the medical record in the FACE ACP group was approximately seven times greater than controls (adjusted odds ratio = 6.58, 95% CI: 3.21–13.51, P \u3c 0.0001). Among African-Americans randomized to FACE, 58% had completed/documented advance directives versus 20% of controls (P \u3c 0.0001). Conclusions: The FACE ACP intervention significantly improved ACP completion and advance directive documentation in the medical record among both African-American and non-African-American adults living with HIV in Washington, DC, providing health equity in ACP, which can inform best practices

Nuclear Acetyl-CoA Production by ACLY Promotes Homologous Recombination

While maintaining the integrity of the genome and sustaining bioenergetics are both fundamental functions of the cell, potential crosstalk between metabolic and DNA repair pathways is poorly understood. Since histone acetylation plays important roles in DNA repair and is sensitive to the availability of acetyl coenzyme A (acetyl-CoA), we investigated a role for metabolic regulation of histone acetylation during the DNA damage response. In this study, we report that nuclear ATP-citrate lyase (ACLY) is phosphorylated at S455 downstream of ataxia telangiectasia mutated (ATM) and AKT following DNA damage. ACLY facilitates histone acetylation at double-strand break (DSB) sites, impairing 53BP1 localization and enabling BRCA1 recruitment and DNA repair by homologous recombination. ACLY phosphorylation and nuclear localization are necessary for its role in promoting BRCA1 recruitment. Upon PARP inhibition, ACLY silencing promotes genomic instability and cell death. Thus, the spatial and temporal control of acetyl-CoA production by ACLY participates in the mechanism of DNA repair pathway choice