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Purpose: Emerging literature suggests caregiver self-efficacy is an important factor related to caregivers' shared reading practices with their children. Reduced shared reading has been documented among families of caregiver(s) with language-based learning disabilities (LBLD). Yet, it remains unclear whether caregivers' history of language and reading difficulties is associated with caregiver self-efficacy. The purpose of this study was to examine whether self-efficacy in language- and reading-related caregiver activities related to caregiver history of language and reading difficulties and shared reading practices. Method: One hundred seventy-six caregivers of children aged 18-60 months completed a custom self-efficacy in language- and reading-related caregiver activities questionnaire, as well as demographic, history of language and reading difficulties (used both as a continuous measure and to dichotomize caregivers with and without LBLD history), and shared reading measures in a one-time survey. Results: Caregivers with a history of LBLD reported an overall lower self-efficacy and a reduced amount of time reading with their children per week than caregivers without LBLD history. Examining caregiver history of language and reading difficulties continuously across the whole group, self-efficacy mediated the relationship between caregiver difficulties and shared reading practices, even when caregiver education was incorporated as an additional mediator in models. Conclusions: Findings indicate that self-efficacy and caregiver education mediate the relationship between caregiver history of language and reading difficulties and shared reading practices. Consideration of self-efficacy by clinicians and educators is warranted when promoting shared reading practices to caregivers of young children. There is a need for future research to examine relationships between self-efficacy and shared reading among caregivers with LBLD of culturally and linguistically diverse backgrounds.

Background: Peripheral nerve blocks (PNBs) may be utilized for postoperative pain control following total hip arthroplasty (THA). The purpose of this study was to evaluate the association between PNBs and postoperative complication rates, healthcare utilization, and opioid consumption following elective THA. Methods: Opioid-naive patients who received PNBs on the same day as undergoing THA for degenerative etiologies were identified from a large national database and matched 1:5 to a control cohort using propensity scoring. Rates of medical complications, inpatient readmissions, and emergency department presentations occurring within 90 days of THA and surgery-related complications occurring within 1 year of THA were compared using odds ratios. Total cost and perioperative opioid consumption in morphine milligram equivalents (MMEs) per day were also evaluated and compared between groups. Results: Propensity score matching resulted in 4748 PNB patients matched to 23,740 control patients. THA patients who received PNBs had lower incidences of deep vein thrombosis (odds ratio [OR] 0.67, P = .004), urinary tract infection (OR 0.76, P < .001), and dislocation (OR 0.51, P < .001). PNBs were also associated with decreased perioperative opioid consumption (38.6 MME/day vs 55.3 MME/day, P < .001). Regarding healthcare utilization, there were no differences between cohorts in rates of inpatient readmission, emergency department presentation, or total cost. Conclusions: PNBs are associated with decreased risk of deep vein thrombosis, urinary tract infection, and dislocation and decreased perioperative opioid consumption following THA. Level of evidence: III, Retrospective review.

Background: Juvenile idiopathic arthritis (JIA) is an inflammatory arthropathy that classically affects children but can cause long-term deformity to the femoral head and hip joint, which may require an arthroplasty procedure. There is a paucity of data surrounding the medical and surgical outcomes of total hip arthroplasty (THA) in patients with JIA compared to a control cohort. Methods: Patients with JIA who underwent THA from 2010 to 2019 were identified in a large national insurance database. A propensity score matching algorithm was used to obtain a control cohort who did not have JIA based upon age, sex, and Elixhauser Comorbidity Index in a 1:10 ratio. Seven hundred sixty-three patients with JIA and 7434 patients without JIA were identified who underwent THA. Ninety-day medical outcomes, 1-year surgical outcomes, and 90-day return to the emergency department and readmission were calculated. Results: Patients with JIA were at increased risk of 90-day transfusion (odds ratio [OR] 1.79; P < .001), pneumonia (OR 2.68; P < .001), urinary tract infection (OR 2.64; P < .001), and wound disruption (OR 2.72; P < .001), as well as 1-year risk of revision THA (OR 2.27; P < .001), periprosthetic joint infection (OR 2.98; P < .001), periprosthetic fracture (OR 2.93; P < .001), aseptic loosening (OR 3.92; P < .001), dislocation (OR 2.61; P = .001), and debridement, antibiotics, and implant retention procedure (OR 2.71; P < .001). Patients with JIA were also at increased risk of 90-day emergency department visit (OR 2.54; P < .001) and readmission (OR 2.59; P < .001). Conclusions: Patients with JIA were at increased risk of early medical and surgical complications following THA. These findings are imperative for surgeons to consider and may warrant tailored perioperative decision-making to avoid the aforementioned medical and surgical complications.

Background: Although extensor mechanism failure following total knee arthroplasty (TKA) is a devastating complication and has been heavily studied in the literature, the impact of extensor mechanism rupture and concomitant repair prior to TKA has not previously been evaluated. The purpose of this investigation was to evaluate how quadriceps and/or patellar tendon repairs prior to TKA would impact medical and surgery-related complications following TKA. Methods: The PearlDiver database was retrospectively reviewed to identify all primary TKA patients from 2010 to 2019. Patients who underwent quadriceps or patellar tendon repair prior to TKA were matched using a propensity score algorithm to a control cohort. We compared medical and surgical complication rates, emergency room visits, readmissions, and 90-day cost of care between the groups. Results: A total of 1197 patients underwent extensor mechanism repair prior to TKA and were matched to 11,970 patients who did not undergo repair prior to TKA. Patients who underwent extensor mechanism repair had higher rates of 90-day medical complications, as well as 1-year surgery-related complications including revision TKA (odds ratio [OR] 6.06; P < .001), lysis of adhesions (OR 2.18; P = .026), aseptic loosening (OR 2.21; P = .018), infection (OR 7.58; P < .001), and fracture (OR 8.53; P < .001). Patients with prior extensor mechanism repair were more likely to return to the emergency department (OR 1.66; P < .001) and become readmitted (OR 4.15; P < .001) within 90 days. Conclusions: Patients with previous extensor mechanism repair exhibited higher medical and surgery-related complications, including lysis of adhesions, following TKA than a control cohort. These findings may suggest that patients may require additional surveillance in the early postoperative period to avoid these disastrous complications following primary TKA.

Self-amplifying mRNA vaccines offer the benefit of driving potent immune responses at low doses, as the mRNA replicates intracellularly. Here, the authors report the preclinical evaluation of a self-amplifying mRNA SARS-CoV-2 vaccine in non-human primates.

Background: Statistical fragility is a quantitative measure of the robustness of the statistical conclusions drawn in a study. Although statistical fragility has been comprehensively evaluated in the arthroplasty literature, the statistical fragility of large-scale randomized trials evaluating venous thromboembolism (VTE) prophylaxis has not been evaluated. The purpose of this study was to determine the utility of applying the fragility index (FI) and the fragility quotient (FQ) analysis to randomized controlled trials (RCTs) evaluating VTE prophylaxis following total joint arthroplasty. Methods: A systematic review was performed by searching multiple databases to identify RCTs that evaluated VTE prophylaxis following total joint arthroplasty from 2000 to 2020. The FI was determined by manipulating each reported dichotomous outcome event until a reversal of significance was appreciated with 2 × 2 contingency tables. The associated FQ was determined by dividing the FI by the sample size. Results: Thirty-two RCTs were ultimately included for analysis. The overall FI incorporating all 32 RCTs was only 7 (interquartile range 3-9), suggesting that the reversal of only 7 events is required to change study significance. The associated FQ was determined to be 0.01. Of the RCTs that reported lost-to-follow-up data, the majority of studies had lost-to-follow-up numbers greater than 7. Conclusions: Our findings suggest that RCTs evaluating VTE prophylaxis following total hip arthroplasty and total knee arthroplasty may lack statistical stability as few outcome events are required to reverse the significance of outcomes. Future randomized trials should consider reporting FI and FQ along with the P value analysis to provide better context to the integrity of statistical stability.

Background: Unicompartmental knee arthroplasty (UKA) is a common orthopedic procedure with overall good clinical outcomes; however, more recent literature has identified disparities in treatment access and outcomes based on sociodemographic factors. There is a paucity of literature examining whether payor type, including Medicare, Medicaid, and commercial insurance types, impacts early medical complications and rates of reoperation following a UKA. Methods: Patients with Medicare, Medicaid, or commercial payor type who underwent primary medial or lateral UKA between 2010 and 2019 were identified using a large national database. Ninety-day incidence of emergency department visit and 1-year incidence of revision, revision to arthroplasty, reimbursement, and cost of care were evaluated. Propensity score matching was used to control for patient demographic factors and comorbidities as covariates. Results: Medicaid insurance was associated with an increased risk of emergency room visit (odds ratio [OR] 2.77; P < .001), revision surgery (OR 1.85; P < .001), and conversion to total knee arthroplasty (OR 1.50; P = .0292) compared to commercially insured patients. Medicaid insurance was associated with an increased risk of emergency room visit (OR 3.58; P < .001), revision surgery (OR 1.97; P < .001), and conversion to total knee arthroplasty (OR 1.80; P = .003). Medicaid patients were associated with a higher overall cost of care and lower reimbursement than commercial and Medicare patients (P < .001 and P < .001, respectively). Conclusions: These findings demonstrate that payor type is associated with increased rates of reoperation and health-care utilization following UKA despite controlling for covariates. Additional work is required to understand the complex relationship between socioeconomic status and outcomes to ensure appropriate health-care access for all patients and pursue appropriate risk stratification. Level of Evidence: III, retrospective chart review.

Background: Obstructive sleep apnea (OSA) has been shown to increase the risk of complications following total knee arthroplasty (TKA) although prior studies were limited by their ability to stratify OSA patients by disease severity. The objective of this study was to determine the effect size of the use of continuous positive airway pressure (CPAP) on early medical and surgery-related complications following TKA among patients with OSA. Methods: Patients with OSA who underwent primary TKA were identified using the PearlDiver Mariner database. Ninety-day incidences of medical complications and 1-year incidences of surgery-related complications as well as hospital utilization were evaluated for OSA patients who had used CPAP prior to TKA compared to those who did not. Results: CPAP patients were at increased 90-day risk of emergency department presentation (odds ratio [OR] 1.61; P < .0001), hospital admission (OR 1.33; P < .001), ICU admission (OR 1.45, P < .0001), pulmonary embolism (OR 1.68, P < .0001), deep vein thrombosis (OR 1.31, P < .0001), transfusion (OR 1.89, P < .0001), pneumonia (OR 1.63, P < .0001), cerebrovascular accident (OR 1.92, P < .0001), myocardial infarction (OR 1.57, P = .0015), sepsis (OR 1.35, P = .0025), blood loss anemia (OR 1.67, P < .0001), acute kidney injury (OR 1.65, P < .0001), and urinary tract infection (OR 1.99, P < .0001), as well as increased 1-year risk of undergoing revision surgery (OR 1.14, P = .0028), compared to OSA patients not using CPAP. Conclusions: OSA patients on CPAP undergoing TKA have significantly increased complication rates compared to OSA patients not using CPAP. Level of Evidence: III, Retrospective review.

Abstract Purpose Hormone replacement therapy (HRT) causes a significant increase in the risk of venous thrombosis. The risk of medical and surgery‐related complications among women taking HRT following total hip arthroplasty (THA) is poorly understood, and there are currently no guidelines in place regarding venous thromboembolism prophylaxis in this patient population. The purpose of this study was to evaluate the frequency of early medical and surgery‐related complications following THA among women taking HRT. Methods Women aged > 40 years of age who underwent primary THA were identified from a retrospective database review. A control group of non‐HRT users was matched using propensity scoring to HRT users. Rates of 90‐day medical complications and 1‐year surgery‐related complications were compared between cohorts using odds ratios. Postoperative anticoagulation regimens were also compared. Results There were 3,936 patients in the HRT cohort who were matched to 39,360 patients not taking HRT. There were no significant differences in rates of DVT (OR 0.94, p = 0.6601) or PE (OR 0.80, p = 0.4102) between cohorts. Patients on HRT were more likely to sustain a dislocation (OR 1.35, p = 0.0269) or undergo revision surgery (OR 1.23, p = 0.0105). HRT patients were more likely to be prescribed warfarin (OR 1.21, p = 0.0001) or enoxaparin (OR 1.18, p = 0.0022) and less likely to be prescribed rivaroxaban (OR 0.62, p

Abstract Purpose Despite benefits of total knee arthroplasty (TKA) on function and quality of life, obese patients have less improved functional outcomes following TKA compared to their normal weight counterparts. Furthermore, obesity is a risk factor for aseptic loosening and revision surgery following TKA. With known benefits of robotic‐assisted TKA (RaTKA) in precision and patient satisfaction, we aimed to evaluate the differences in patient reported outcome and early complication rates for patients undergoing RaTKA versus conventional TKA among patients of varying BMI groups. Methods This study was a retrospective cohort study of patients who underwent conventional versus RaTKA. Patients were grouped by BMI range ( 40 kg/m2). Patient‐reported outcomes were measured by Oxford Knee Scores and 12‐Item Short Form Survey scores preoperatively, 6‐month, 1‐year, and 2‐year postoperatively. Mixed‐effects linear models were built for each patient‐reported outcome to assess the interaction between type of surgery and BMI while adjusting for known confounders such as demographic variables. Results A total of 350 patients (n = 186 RaTKA, n = 164 conventional TKA) met inclusion criteria. SF‐12 physical scores were significantly higher at 2‐year follow‐up among non‐obese patients compared to obese and morbidly obese patients (p = 0.047). There was no statistically significant interaction between the type of surgery performed (RaTKA versus conventional TKA) and obesity regarding their effects on patient reported outcomes. Conclusions This study demonstrates no differences in functional outcomes among patients undergoing RaTKA compared to conventional TKA. Furthermore, obesity had no significant effect on this association. Level of evidence III.

Herpetic keratitis (HK) caused by herpes simplex virus 1 (HSV-1) is the major cause of infection-related blindness in developed countries. Current treatment is based on curative and preventive use of antiherpetic acyclic nucleoside analogues (ANAs), namely acyclovir (ACV) or other molecules with the same mechanism of action. The frequency of HK caused by acyclovir-resistant viruses is steadily increasing. Virological proof of resistance is obtained from an ocular sample sent to a specialized laboratory. Genotypic characterization by DNA sequencing of the viral enzymes targeted by antivirals allows adaptation of treatment according to the mutation identified. Mutations of the viral thymidine kinase (TK) are the most frequent and leave few viable alternatives for long-term prophylactic treatment among currently available drugs. Amenamevir (AMNV), a new drug targeting the viral helicase-primase (HP) enzyme complex, with proven efficacy for treatment of herpetic infections of other sites, has recently shown value in the management of ACV-resistant HK. Its TK-independent mechanism allows it to retain its antiviral activity even in cases of patient resistance to ACV., Competing Interests: Déclaration des liens d’intérêts Rafael Boucher, Sonia Burrel, Oscar Haigh, Emmanuel Barreau, Maya Benali et Sourou Meziou déclarent ne pas avoir de liens d’intérêts. David Boutolleau a consulté pour bioMérieux, Qiagen, DiaSorin Molecular et Roche Diagnostics à propos de sujets indépendants de cette étude. Marc Labetoulle a consulté au cours des 5 dernières années pour Alcon, Allergan, Bausch and Lomb, Dompe, Horus, GSK, MSD, Novartis, Santen, Shire et Thea à propos de sujets indépendants de cette étude. Antoine Rousseau a consulté pour Thea, Horus Pharma, Allergan, Alnylam, Glaukos, Bauch and Lomb à propos de sujets indépendants de cette étude., (Copyright © 2025 Elsevier Masson SAS. All rights reserved.)

Background: Sedentary behavior is highly prevalent and associated with morbidity and mortality in chronic kidney disease (CKD). A Sit Less, Interact and Move More (SLIMM) sedentary activity coaching intervention can reduce sedentary duration among persons with CKD, but preliminary data suggest that effects may not persist. Prior studies have suggested that moderate/vigorous intensity physical activities are not sustainable in persons with CKD. Therefore, we aimed to determine whether guided resistance training ± oral semaglutide co-intervention improves adherence and/or persistence of the SLIMM intervention., Method/design: The SLIMM-2 is a two-center study designed with a 3-month sedentary activity coaching (SLIMM) followed by a 9-month randomized controlled trial with three arms: SLIMM + standard of care resistance training + oral placebo, SLIMM + guided resistance training + oral placebo, or SLIMM + guided resistance training + oral semaglutide. The study is recruiting persons with CKD (eGFR 20 to ≤60 ml/min/1.73 m 2 ). ActivPAL, a wearable tri-axial accelerometer, is used to assess outcomes including sedentary duration (primary outcome), stepping duration and the average number of steps per day. Additional outcomes include 6-min walk distance and body fat percentage. Persons randomized to standard of care resistance training will be encouraged to maintain individualized physical activity goals; those randomized to guided resistance training will attend guided sessions per month and be prescribed daily independent exercises., Results: Enrollment, interventions, and follow-up are ongoing., Conclusions: Results from the SLIMM-2 study are expected to inform clinical practice, with the potential to enhance physical health and functioning among persons with CKD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: Myelofibrosis (MF) is a clonal haematopoietic disease, with median overall survival for patients with primary MF only 6.5 years. The most frequent gene mutation found in patients is JAK2 V617F , causing constitutive activation of the kinase and activation of downstream signalling. Fedratinib is an oral selective JAK2 inhibitor. It has shown activity in MF and is well-tolerated, but combination with other therapies is likely needed to achieve clonal remission. Combining a JAK2 inhibitor with an interferon may be synergistic, as haematopoietic cells are activated from quiescence (a typical kinase resistance mechanism) rendering them more sensitive to inhibition. Ropeginterferon alfa-2b is a next generation pegylated interferon-α-2b with high tolerability and clinical activity in patients with MF, however, evidence of tolerability and activity in combination with fedratinib is lacking in this setting. The aim of the FEDORA trial is to assess tolerability, safety, and activity of fedratinib with ropeginterferon alfa-2b in patients with MF who require treatment to justify further investigation in a phase III trial., Methods: FEDORA is a single arm, multicentre, open-label, Bayesian phase II trial to assess tolerability, safety, and activity of fedratinib with ropeginterferon alfa-2b aiming to recruit 30 patients. Patients with JAK2 V617F positive primary or secondary MF, who are aged ≥ 18 years, have intermediate-1 with palpable splenomegaly of > 5cm, intermediate-2, or high-risk disease according to the Dynamic International Prognostic Scoring System (DIPSS), and who require treatment are eligible. The primary outcome is tolerability, whereby the combination is deemed intolerable in a patient if drug-related toxicities in the first four months of treatment lead to: either drug being discontinued; delays in treatment exceeding 28 consecutive days; or death. FEDORA uses a within-patient dose escalation regimen to ensure each patient reaches a personalised dose combination that is acceptable., Discussion: FEDORA is using a Bayesian trial design and aims to provide evidence of the tolerability, safety, and activity of combining fedratinib with ropeginterferon alfa-2b upon which the decision as to whether a phase III trial is warranted will be based., Trial Registration: EudraCT number: 2021-004056-42., Isrctn: 88,102,629., Competing Interests: Declarations. Ethics approval and consent to participate: The trial is being performed in accordance with the recommendations guiding physicians in biomedical research involving human subjects, adopted by the 18th World Medical Association General Assembly, Helsinki, Finland, 1964, amended by the 48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996. The protocol (currently v4.0, dated 10-May-2023) was initially approved by the Yorkshire & The Humber—Leeds West Research Ethics Committee on 07-Jan-2022 (Ref. 21/YH/0300). Approval was also granted by the Medicines and Healthcare Products Regulatory Agency on 28-Jan-2022. The FEDORA Trial Office coordinates and communicates protocol modifications to all relevant parties. Consent for publication: Not applicable. Competing interests: MFM has participated in advisory boards for Novartis, BMS, Incyte and GSK, and has received speakers bureau from Novatis, AOP Health, and Incyte. All other authors declare no competing interests., (© 2025. The Author(s).)

Purpose: The purpose of this study was to describe the efficacy and tolerance of amenamevir (AMNV), an inhibitor of the viral helicase-primase, for the treatment of recalcitrant herpes simplex keratitis (HSK) caused by acyclovir-resistant (ACVR) herpes simplex virus 1 strains., Methods: In this retrospective case series, 6 consecutive patients with HSK caused by an ACVR herpes simplex virus 1 strain with a failure of conventional antiviral therapy were included after having been treated with AMNV (there was no control group of comparable patients for whom previous treatment would have been continued despite its inefficacy). Medical files were assessed for clinical data including reason(s) for AMNV introduction (frequent recurrences despite appropriate preventive antiviral treatment and/or clinical resistance to suppressive antiviral treatment of an ongoing clinical relapse), genotypical resistance to herpes simplex virus 1 documentation, immune status, clinical types and number of HSK episodes before and during AMNV treatment, adverse effects observed during AMNV treatment, and best corrected visual acuity., Results: Of 6 patients, 4 (66%) did not experience a single recurrence during AMNV therapy while 2 others had recurrences (1 over 24 months of treatment and 2 over 23 months, ie two-fold less frequently than with conventional preventive treatment). On the overall history of these 6 patients, AMNV appeared to be associated with a reduction in HSK recurrences, with a mean of only 0.02 ± 0.04 episodes/month during follow-up under AMNV as compared to 0.14 ± 0.04 episodes/month in the year preceding AMNV introduction ( P = 0.03). Improvement in vision acuity was also observed (mean best corrected visual acuity 0.17 ± 0.12 logarithm of the minimum angle of resolution at the end of follow-up vs. 0.30 ± 0.35 before AMNV onset), albeit nonsignificant probably due to the limited number of patients ( P = 0.38). Neither clinical nor biological adverse effects were observed while under AMNV during the follow-up (16.5 ± 5.8 months)., Conclusions: Although there was no control group, AMNV may be a valuable option to reduce ACVR HSK recurrences., Competing Interests: D. Boutolleau has been an occasional consultant on subjects outside the scope of this work for bioMérieux, Qiagen, DiaSorin Molecular and Roche Diagnostics. M. Labetoulle has been an occasional consultant on subjects outside the scope of this work for Alcon, Allergan, Bausch and Lomb, Dompe, Horus, GSK, MSD, Novartis, Santen, Shire, and Thea. A. Rousseau has been an occasional consultant on subjects outside the scope of this work for Thea, Horus Pharma, Allergan, Alnylam, Glaukos, Bauch and Lomb. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Strontium isotope ( 87 Sr/ 86 Sr) analysis with reference to strontium isotope landscapes (Sr isoscapes) allows reconstructing mobility and migration in archaeology, ecology, and forensics. However, despite the vast potential of research involving 87 Sr/ 86 Sr analysis particularly in Africa, Sr isoscapes remain unavailable for the largest parts of the continent. Here, we measure the 87 Sr/ 86 Sr ratios in 778 environmental samples from 24 African countries and combine this data with published data to model a bioavailable Sr isoscape for sub-Saharan Africa using random forest regression. We demonstrate the efficacy of this Sr isoscape, in combination with other lines of evidence, to trace the African roots of individuals from historic slavery contexts, particularly those with highly radiogenic 87 Sr/ 86 Sr ratios uncommon in the African Diaspora. Our study provides an extensive African 87 Sr/ 86 Sr dataset which includes scientifically marginalized regions of Africa, with significant implications for the archaeology of the transatlantic slave trade, wildlife ecology, conservation, and forensics., Competing Interests: Competing interests: The authors declare no competing interest., (© 2024. The Author(s).)

[Figure: see text].

Background: Hypertension afflicts most patients with chronic kidney disease (CKD) and contributes to kidney disease progression, cardiovascular disease, and death in this patient population. The evidence and clinical guidelines support lowering blood pressure (BP) goals in patients with CKD. We evaluated if BP control improved among US adults with CKD., Methods and Results: In the NHANES (National Health and Nutrition Examination Survey) for the periods 2011 to 2014, 2015 to 2016, and 2017 to 2020, we identified individuals with CKD defined as estimated glomerular filtration rate 20 to 59 mL/min per 1.73 m 2 or urinary albumin/creatinine ratio≥30 mg/g. The following systolic BP categories were evaluated: <120, 120 to 129, 130 to 139, and ≥140 mm Hg. All measures were tested for differences between year groups accounting for sample strata, clusters, and weights. During the periods of 2011 to 2014, 2015 to 2016, and 2017 to 2020, the prevalence of CKD was stable at 14%, 13%, and 13%, respectively ( P =0.4). Among those with CKD, the proportion of individuals with self-reported hypertension or taking BP medications increased from 66 in 2011 to 2014, to 69 and 86% in 2015 to 2016 and 2017 to 2020, respectively ( P <0.0001). Although the number of BP medications prescribed increased significantly over time, less than half of the individuals with CKD had well-controlled BP based on the current guidelines., Conclusions: Although BP recognition has improved among those with CKD, a significant number of individuals with CKD do not meet their BP goal.

Following the legalization of recreational Cannabis in Canada in 2018, the associated waste, including Cannabis roots, has significantly increased. Cannabis roots, comprising 30%-50% of the total plant, are often discarded despite their historical use in Ayurvedic medicine for treating inflammatory and infectious disorders. This study evaluates the phytochemical and therapeutic properties of Cannabis root extracts from a high tetrahydrocannabinolic acid, low cannabidiolic acid cultivar (variety Alien Gorilla Glue). We performed ultra high-performance liquid chromatography coupled with mass spectrometry (UPLC-QTOF-MS) to identify the chemical components of the Cannabis roots. Extracts using water, ethanol and acid-base solvents were tested for antioxidant activity through free radical scavenging, metal chelation, and lipoperoxidation inhibition assays. Mitochondrial membrane protection was assessed using flow cytometry with the MitoPerOx probe in THP-1 monocytic leukemia cells. Anti-inflammatory potential was evaluated by measuring interleukin-6 levels in lipopolysaccharide-stimulated THP-1 cells. Bactericidal/fungicidal efficacy against Escherichia coli , Staphylococcus aureus , and Candida albicans was determined using the p -iodonitrophenyltetrazolium assay. Additionally, we investigated the anticholinesterase activity of Cannabis root extracts, given the potential role of plant alkaloids in inhibiting cholinesterase, an enzyme targeted in Alzheimer's disease treatments. UPLC-QTOF-MS analysis suggested the presence of several phenolic compounds, cannabinoids, terpenoids, amino acids, and nitrogen-containing compounds. Our results indicated significant antioxidant, bactericidal, and anticholinesterase properties of Cannabis root extracts from both soil and hydroponic cultivation. Extracts showed strong antioxidant activity across multiple assays, protected mitochondrial membrane in THP-1 cells, and exhibited anti-inflammatory and bactericidal/fungicidal efficacy. Notably, soil-cultivated roots displayed superior anti-inflammatory effects. These findings demonstrate the remarkable antioxidant, anti-inflammatory, and anti-microbial activities of Cannabis roots, supporting their traditional uses and challenging their perception as mere waste. This study highlights the therapeutic potential of Cannabis roots extracts and suggests avenues for further research and application., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gagné, Merindol, Boucher, Boucher and Desgagné-Penix.)

Rationale: The airway microbiome has the potential to shape chronic obstructive pulmonary disease (COPD) pathogenesis, but its relationship to outcomes in milder disease is unestablished. Objectives: To identify sputum microbiome characteristics associated with markers of COPD in participants of the Subpopulations and Intermediate Outcome Measures of COPD Study (SPIROMICS). Methods: Sputum DNA from 877 participants was analyzed using 16S ribosomal RNA gene sequencing. Relationships between baseline airway microbiota composition and clinical, radiographic, and mucoinflammatory markers, including longitudinal lung function trajectory, were examined. Measurements and Main Results: Participant data represented predominantly milder disease (Global Initiative for Chronic Obstructive Lung Disease stage 0-2 obstruction in 732 of 877 participants). Phylogenetic diversity (i.e., range of different species within a sample) correlated positively with baseline lung function, decreased with higher Global Initiative for Chronic Obstructive Lung Disease stage, and correlated negatively with symptom burden, radiographic markers of airway disease, and total mucin concentrations ( P  < 0.001). In covariate-adjusted regression models, organisms robustly associated with better lung function included Alloprevotella , Oribacterium , and Veillonella species. Conversely, lower lung function, greater symptoms, and radiographic measures of small airway disease were associated with enrichment in members of Streptococcus , Actinobacillus , Actinomyces , and other genera. Baseline sputum microbiota features were also associated with lung function trajectory during SPIROMICS follow-up (stable/improved, decline, or rapid decline groups). The stable/improved group (slope of FEV 1 regression ⩾66th percentile) had greater bacterial diversity at baseline associated with enrichment in Prevotella , Leptotrichia , and Neisseria species. In contrast, the rapid decline group (FEV 1 slope ⩽33rd percentile) had significantly lower baseline diversity associated with enrichment in Streptococcus species. Conclusions: In SPIROMICS, baseline airway microbiota features demonstrate divergent associations with better or worse COPD-related outcomes.

Primary tumors of the lacrimal sac (PTLS) are a rare subtype of ocular adnexa tumors, with potentially life-threatening clinical course. There has been growing evidence of human papilloma virus (HPV) as an etiological agent in these tumors.In this retrospective observational case series, we report three cases of PTLS. All three underwent an initial dacryocystorhinostomy revealing a tissular mass in the lacrimal sac. Histological findings were respectively epithelial papilloma, epithelial Malpighian papilloma, and undifferentiated epidermoid carcinoma. PCR evaluation identified HPV serotype 6 in the first case and 16 in the third, and high p16 expression was found in the second case.These three cases of PTLS with HPV detection complement 36 other cases identified in the literature, further incriminating HPV in the pathogenesis of these neoplasms. Ophthalmologists must remain wary of chronic lacrimal occlusion symptoms, and resort to CT scan and orbital Doppler sonography whenever first-line treatment fails.

The pathophysiology behind sodium retention in heart failure with preserved ejection fraction (HFpEF) remains poorly understood. We hypothesized that patients with HFpEF have impaired natriuresis and diuresis in response to volume expansion and diuretic challenge, which is associated with renal hypo-responsiveness to endogenous natriuretic peptides. Nine HFpEF patients and five controls received saline infusion (0.25 mL/kg/min for 60 min) followed by intravenous furosemide (20 mg or home dose) 2 h after the infusion. Blood and urine samples were collected at baseline, 2 h after saline infusion, and 2 h after furosemide administration; urinary volumes were recorded. The urinary cyclic guanosine monophosphate (ucGMP)/plasma B-type NP (BNP) ratio was calculated as a measure of renal response to endogenous BNP. Wilcoxon rank-sum test was used to compare the groups. Compared to controls, HFpEF patients had reduced urine output (2480 vs.3541 mL; p = 0.028), lower urinary sodium excretion over 2 h after saline infusion (the percentage of infused sodium excreted 12% vs. 47%; p = 0.003), and a lower baseline ucGMP/plasma BNP ratio (0.7 vs. 7.3 (pmol/mL)/(mg/dL)/(pg/mL); p = 0.014). Patients with HFpEF had impaired natriuretic response to intravenous saline and furosemide administration and lower baseline ucGMP/plasma BNP ratios indicating renal hypo-responsiveness to NPs., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: In a post hoc analysis, we examined whether postrandomization diuretics use can explain and/or mediate the beneficial effects of intensive systolic BP lowering on cardiovascular disease and all-cause mortality in the Systolic Blood Pressure Intervention Trial (SPRINT)., Methods: SPRINT was a randomized, controlled trial of 9361 participants comparing the effects of intensive (systolic BP target <120 mm Hg) versus standard (systolic BP target <140 mm Hg) BP control on a primary composite cardiovascular end point in participants aged 50 years or older with systolic BP of 130-180 mm Hg. In time-varying multivariable Cox analyses, we assessed hazard ratios (HRs) of cardiovascular end points and all-cause mortality in participants on thiazide type, loop and/or potassium (K) sparing, or no diuretics. We also conducted mediation analysis to formally assess the role of diuretics in the effects of intensive systolic BP lowering., Results: At baseline, diuretics were prescribed in 46% and 48% of participants in standard and intensive systolic BP-lowering groups, respectively, and in 46% and 74% in the corresponding groups during the trial. The lower risk of cardiovascular end points in the intensive group (HR, 0.75; 95% confidence interval [CI], 0.64 to 0.89) persisted after adjustment for postrandomization time-varying diuretics use (HR, 0.74; 95% CI, 0.62 to 0.89). Across the entire study population, time-varying diuretics use was not associated with cardiovascular end points (compared with no diuretics, HR for thiazide type, 0.89; 95% CI, 0.73 to 1.10, and loop/K sparing, 1.29; 95% CI, 0.97 to 1.73). However, thiazide-type diuretics were associated with lower risk of cardiovascular end points in the intensive (HR, 0.62; 95% CI, 0.46 to 0.85) but not in the standard (HR, 1.07; 95% CI, 0.82 to 1.39) group. In mediation analysis, HRs for total effect, direct effect (not mediated through diuretics use), and indirect effect (mediated through diuretics) of the intervention on cardiovascular end points were 0.66 (95% CI, 0.54 to 0.79), 0.67 (95% CI, 0.54 to 0.81), and 0.98 (95% CI, 0.88 to 1.10), respectively. The results were largely similar for all-cause mortality., Conclusions: The favorable effects of intensive systolic BP lowering on cardiovascular end points and all-cause mortality in SPRINT were independent of and not mediated by time-varying diuretics use. However, thiazide-type diuretics use associated with benefit if intensive systolic BP lowering was targeted., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

Background: Whether there is any benefit in integrating culture-independent molecular analysis of the lower airway microbiota of people with cystic fibrosis into clinical care is unclear. This study determined the longitudinal trajectory of the microbiota and if there were microbiota characteristics that corresponded with response to treatment or predicted a future pulmonary exacerbation., Methods: At least one sputum sample was collected from 149 participants enrolled in this prospective longitudinal multi-centre study and total bacterial density and microbiota community measurements were determined and compared with clinical parameters., Results: In 114 participants with paired samples when clinically stable, ∼8 months apart, the microbiota remained conserved between timepoints, regardless of whether participants received acute intravenous antibiotic treatment or not. In 62 participants, who presented with an acute exacerbation, a decrease in community richness correlated best with patient response to antibiotic treatment. Analysis of baseline samples from 30 participants who exacerbated within 4 months of their stable sample being collected and 72 participants who remained stable throughout the study showed that community characteristics such as lower richness at baseline may be predictive of an exacerbation in addition to several clinical parameters. However, lasso regression analysis indicated that only lung function (p = 0.014) was associated with a future exacerbation., Conclusions: The airway microbiota remains stable over periods <1 year with modest shifts related to treatment apparent which might provide some additional insights to patient-level measurements., Competing Interests: Declaration of Competing Interest MMT and JSE report grants from Northern Ireland Health and Social Care Research and Development Office and MSM reports grants from National Institutes of Health HL084934, during the conduct of the study. NGMcE reports grants from US-Ireland partnership/Science Foundation Ireland/Health Research Board, during the conduct of the study. JSE and MMT also reports grants from the EU Innovative Medicines Initiative, outside the submitted work. MMT reports grants from Novartis, Basilea Pharmaceutica, Alaxia SAS, and Polyphor outside the submitted work. JSE reports grants, personal fees and clinical trial involvement with Vertex and clinical trial involvement with Celtaxsys and Corbus Pharmaceuticals, outside the submitted work. RCB reports personal fees from and has a patent pending with Parion Sciences, outside the submitted work. All other authors report no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cancer treatments have recently shifted from broad-spectrum cytotoxic therapies to more focused treatments, maximizing anticancerous activity while reducing toxicity to healthy cells. These modern anticancer therapies (MATs) encompass a wide range of innovative molecules that include immune checkpoint inhibitors and other targeted anticancer therapies, comprising antibody drug conjugates and inhibitors of signal transduction. Some MATs are associated with ocular surface adverse events that can cause severe discomfort and even lead to loss of vision. While these complications remain rare, they are probably underreported. It is likely that both oncologists and ophthalmologists will come across MATs-associated ocular surface-adverse events in their practices, owing to the increasing number of patients being treated with MATs. Rapid identification of ocular surface-adverse events is crucial, as early intervention can manage these conditions to avoid vision loss and reduce negative impacts on quality of life. We discuss characteristics of ocular surface pathologies attributed to MATs, describe the suspected underlying pathophysiological mechanisms, and outline the main lines of treatment., Competing Interests: Declaration of Competing Interest Rafael Boucher has nothing to disclose. Oscar Haigh has nothing to disclose. Emmanuel Barreau has nothing to disclose. Stephane Champiat: Honoraria: Amgen, Astellas, AstraZeneca, Bristol Myers Squibb, Eisai, Genmab, Janssen, Merck, Novartis and Roche. Principal Investigator of Clinical Trials for: Abbvie, Amgen, Boehringer Ingelheim, Cytovation, Eisai, Imcheck Therapeutics, Immunocore, Molecular Partners Ag, Merck, Ose Pharma, Pierre Fabre, Replimune, Sanofi Aventis, Seagen, Sotio A.S, Transgene. Advisory Board/Consulting: Alderaan Biotechnology, Amgen, AstraZeneca, Avacta, BioNTech, Celanese, Domain Therapeutics, Ellipses Pharma, Genmab, Immunicom, Inc., Nanobiotix, Nextcure, Oncovita, Pierre Fabre, Seagen, Tatum Bioscience, Tollys SAS, UltraHuman8. Travel and congress: Amgen, AstraZeneca, Bristol Myers Squibb, Merck, Ose Pharma, Roche, Sotio. As part of the Drug Development Department (DITEP): Principal/sub-Investigator of Clinical Trials for Abbvie, Adaptimmune, Adlai Nortye USA Inc, Aduro Biotech, Agios Pharmaceuticals, Amgen, Astex Pharmaceuticals, Astra Zeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, Beigene, BicycleTx Ltd, Blueprint Medicines, Boehringer Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Ca, Casi Pharmaceuticals, Inc, Celgene Corporation, Cellcentric, Chugai Pharmaceutical Co, Cullinan-Apollo, Curevarc, Daiichi Sankyo, Debiopharm, Eisai, Eisai Limited, Eli Lilly, Exelixis, Faron Pharmaceuticals Ltd, Forma Tharapeutics, Gamamabs, Genentech, Glaxosmithkline, H3 Biomedicine, Hoffmann La Roche Ag, Imcheck Therapeutics, Incyte Corporation, Innate Pharma, Institut De Recherche Pierre Fabre, Iris Servier, Iteos Belgium SA, Janssen Cilag, Janssen Research Foundation, Janssen R&D LLC, Kura Oncology, Kyowa Kirin Pharm. Dev, Lilly France, Loxo Oncology, Medimmune, Menarini Ricerche, Merck Sharp & Dohme Chibret, Merrimack Pharmaceuticals, Merus, Molecular Partners Ag, Nanobiotix, Nektar Therapeutics, Novartis Pharma, Octimet Oncology Nv, Oncoethix, Oncopeptides, Orion Pharma, Genomics, Ose Pharma, Pfizer, Pharma Mar, Pierre Fabre Medicament, Relay Therapeutics, Inc, Roche, Sanofi Aventis, Seattle Genetics, Sotio A.S, Syros Pharmaceuticals, Taiho Pharma, Tesaro, Transgene S.A, Turning Point Therapeutics, Xencor. Research Grants from Astrazeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Pfizer, Roche, Sanofi. Non-financial support (drug supplied) from Astrazeneca, BMS, Boehringer Ingelheim, GSK, Medimmune, Merck, NH TherAGuiX, Pfizer, Roche. Olivier Lambotte has been an occasional consultant for MSD, AbbVie, Boehringer, ViiV, and Gilead. Clovis Adam has nothing to disclose. Marc Labetoulle has been an occasional consultant on subjects outside the scope of this work for Alcon, Allergan, Bausch and Lomb, Dompe, Horus, MSD, Novartis, Santen, Shire, and Thea. Antoine Rousseau has been an occasional consultant on subjects outside the scope of this work for Thea, Horus Pharma, Allergan, Alnylam, Glaukos, Bauch and Lomb and Thea., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Diagnosis of herpes simplex keratitis (HSK) is mostly based on clinical findings, yet biological confirmation supports management of challenging cases. This study evaluated the place of real-time quantitative PCR (RT-qPCR) on tear samplings in the management of HSK. Clinical records of patients who underwent tear sampling tested by RT-qPCR for herpes simplex virus type 1 for an acute episode of corneal inflammation or defect between January 2013 and December 2021 were retrospectively reviewed, and results were compared to clinical diagnosis (i.e., HSK or not) based on biomicroscopic findings and medical history. Of 465 tested tear samples from 364 patients, a clinical diagnosis of active (ongoing) HSK was recorded in 240 cases, among which 76 were RT-qPCR positive (global sensitivity of 31.6%, specificity of 99.5%). Sensitivity of RT-qPCR was higher in epithelial (97.4%) and stromal keratitis with ulceration (48.7%), compared to other types of HSK (23.5% in keratouveitis, 13.6% in endotheliitis, 11.1% in postherpetic neurotrophic keratopathy, and 8.1% in stromal keratitis without ulceration). The highest viral loads were detected from epithelial and stromal keratitis with ulceration, while in HSK with no epithelial involvement, the viral load detected was 196-fold lower, on average. The proportion of clinically characterized HSK patients with negative tear samples was higher in patients receiving antiviral treatment ( P < 0.0001). RT-qPCR, performed on tear samples, can help in confirming diagnosis in case of presumed HSK, including clinical forms with no obvious epithelial involvement. The sensitivity of tear sampling is much higher whenever epithelial keratitis is present., Competing Interests: The authors declare no conflict of interest.

Limited data exist on COVID-19 vaccination efficacy in patients with acute myeloid leukemia and myelodysplasia with excess blasts (AML/MDS-EB2). We report results from a prospective study, PACE (Patients with AML and COVID-19 Epidemiology). 93 patients provided samples post-vaccine 2 or 3 (PV2, PV3). Antibodies against SARS-COV-2 spike antigen were detectable in all samples. Neutralization of the omicron variant was poorer than ancestral variants but improved PV3. In contrast, adequate T-cell reactivity to SARS-COV-2 spike protein was seen in only 16/47 (34%) patients PV2 and 23/52 (44%) PV3. Using regression models, disease response (not in CR/Cri), and increasing age predicted poor T cell response., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Purpose: Polycythemia vera (PV) is characterized by JAK/STAT activation, thrombotic/hemorrhagic events, systemic symptoms, and disease transformation. In high-risk PV, ruxolitinib controls blood counts and improves symptoms., Patients and Methods: MAJIC-PV is a randomized phase II trial of ruxolitinib versus best available therapy (BAT) in patients resistant/intolerant to hydroxycarbamide (HC-INT/RES). Primary outcome was complete response (CR) within 1 year. Secondary outcomes included duration of response, event-free survival (EFS), symptom, and molecular response., Results: One hundred eighty patients were randomly assigned. CR was achieved in 40 (43%) patients on ruxolitinib versus 23 (26%) on BAT (odds ratio, 2.12; 90% CI, 1.25 to 3.60; P = .02). Duration of CR was superior for ruxolitinib (hazard ratio [HR], 0.38; 95% CI, 0.24 to 0.61; P < .001). Symptom responses were better with ruxolitinib and durable. EFS (major thrombosis, hemorrhage, transformation, and death) was superior for patients attaining CR within 1 year (HR, 0.41; 95% CI, 0.21 to 0.78; P = .01); and those on ruxolitinib (HR, 0.58; 95% CI, 0.35 to 0.94; P = .03). Serial analysis of JAK2 V617F variant allele fraction revealed molecular response was more frequent with ruxolitinib and was associated with improved outcomes (progression-free survival [PFS] P = .001, EFS P = .001, overall survival P = .01) and clearance of JAK2 V617F stem/progenitor cells. ASXL 1 mutations predicted for adverse EFS (HR, 3.02; 95% CI, 1.47 to 6.17; P = .003). The safety profile of ruxolitinib was as previously reported., Conclusion: The MAJIC-PV study demonstrates ruxolitinib treatment benefits HC-INT/RES PV patients with superior CR, and EFS as well as molecular response; importantly also demonstrating for the first time, to our knowledge, that molecular response is linked to EFS, PFS, and OS.

The human airways are complex structures with important interactions between cells, extracellular matrix (ECM) proteins and the biomechanical microenvironment. A robust, well-differentiated in vitro culture system that accurately models these interactions would provide a useful tool for studying normal and pathological airway biology. Here, we report the development and characterization of a physiologically relevant air-liquid interface (ALI) 3D airway 'organ tissue equivalent' (OTE) model with three novel features: native pulmonary fibroblasts, solubilized lung ECM, and hydrogel substrate with tunable stiffness and porosity. We demonstrate the versatility of the OTE model by evaluating the impact of these features on human bronchial epithelial (HBE) cell phenotype. Variations of this model were analyzed during 28 days of ALI culture by evaluating epithelial confluence, trans-epithelial electrical resistance, and epithelial phenotype via multispectral immuno-histochemistry and next-generation sequencing. Cultures that included both solubilized lung ECM and native pulmonary fibroblasts within the hydrogel substrate formed well-differentiated ALI cultures that maintained a barrier function and expressed mature epithelial markers relating to goblet, club, and ciliated cells. Modulation of hydrogel stiffness did not negatively impact HBE differentiation and could be a valuable variable to alter epithelial phenotype. This study highlights the feasibility and versatility of a 3D airway OTE model to model the multiple components of the human airway 3D microenvironment., (© 2023. The Author(s).)

Background: Sedentary behaviors are associated with adverse health outcomes in older adults. The feasibility of behavioral interventions in this population is unclear., Methods: In the Sit Less, Interact, Move More (SLIMM) trial of 106 participants who had obesity, those randomized to the SLIMM intervention ( N  = 54) were instructed to replace sedentary activities with stepping. An accelerometer was used to measure physical activity. In this secondary analysis, mixed effect models were used to examine the effects of the SLIMM intervention on sedentary and stepping durations and steps/day by age (<70 and ≥ 70 years)., Results: Mean ages in the <70 years ( N  = 47) and ≥70 years ( N  = 59) groups were 58 ± 11 and 78 ± 5. In the older subgroup, compared to standard-of-care ( N  = 29), the SLIMM intervention ( N  = 30) significantly increased stepping duration (13, 95%CI 1-24 min/d, p  = 0.038) and steps per day (1330, 95% CI 322-2338, p  = 0.01) and non-significantly decreased sedentary duration by (28,95% CI -61-5 min/d, p  = 0.09). In the age <70 subgroup, there was no separation between the standard of care ( N  = 23) and SLIMM ( N  = 24) groups., Discussion: In older adults who had obesity, SLIMM intervention significantly increased stepping duration and steps per day. Interventions targeting sedentary behaviors by promoting low intensity physical activity may be feasible in this population., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

Objective: To investigate if in-clinic measures of physical function and real-world measures of physical behavior and mobility effort are associated with one another and to determine if they predict future hospitalization in participants with chronic kidney disease (CKD)., Methods: In this secondary analysis, novel real-world measures of physical behavior and mobility effort, including the best 6-minute step count (B6SC), were derived from passively collected data from a thigh worn actigraphy sensor and compared to traditional in-clinic measures of physical function (e.g. 6-minute walk test (6MWT). Hospitalization status during 2 years of follow-up was determined from electronic health records. Correlation analyses were used to compare measures and Cox Regression analysis was used to compare measures with hospitalization., Results: One hundred and six participants were studied (69  ±  13 years, 43% women). Mean  ±  SD baseline measures for 6MWT was 386  ±  66 m and B6SC was 524  ±  125 steps. Forty-four hospitalization events over 224 years of total follow-up occurred. Good separation was achieved for tertiles of 6MWT, B6SC and steps/day for hospitalization events. This pattern persisted in models adjusted for demographics (6MWT: HR  =  0.63 95% CI 0.43-0.93, B6SC: HR  =  0.75, 95% CI 0.56-1.02 and steps/day: HR  =  0.75, 95% CI 0.50-1.13) and further adjusted for morbidities (6MWT: HR  =  0.54, 95% CI 0.35-0.84, B6SC: HR  =  0.70, 95% CI 0.49-1.00 and steps/day: HR  =  0.69, 95% CI 0.43-1.09)., Conclusion: Digital health technologies can be deployed remotely, passively, and continuously to collect real-world measures of physical behavior and mobility effort that differentiate risk of hospitalization in patients with CKD., Competing Interests: Kate Lyden is employed by VivoSense, Inc and previously consulted for wearable device manufacturers. The authors declared no other potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: The cause for differences in serum creatinine between Black and non-Black individuals incorporated into prior GFR-estimating equations is not understood. We explored whether social determinants of health can account for this difference., Methods: We conducted a secondary analysis of baseline data of the Modification of Diet in Renal Disease and Chronic Renal Insufficiency Cohort studies ( N =1628 and 1423, respectively). Data in both study cohorts were stratified by race (Black versus non-Black). We first evaluated the extent to which the coefficient of Black race in estimating GFR from creatinine is explained by correlations of race with social determinants of health and non-GFR determinants of creatinine. Second, we evaluated whether the difference between race groups in adjusted mean creatinine can be explained by social determinants of health and non-GFR determinants of creatinine., Results: In models regressing measured GFR on creatinine, age, sex, and race, the coefficient for Black race was 21% (95% confidence interval, 0.176 to 0.245) in Modification of Diet in Renal Disease and 13% (95% confidence interval, 0.097 to 0.155) in the Chronic Renal Insufficiency Cohort and was not attenuated by the addition of social determinants of health, alone or in combination. In both studies, the coefficient for Black race was larger at lower versus higher income levels. In models, regressing creatinine on measured GFR, age, and sex, mean creatinine was higher in Black versus non-Black participants in both studies, with no effect of social determinants of health., Conclusions: Adjustment for selected social determinants of health did not influence the relationship between Black race and creatinine-based estimated GFR., (Copyright © 2023 by the American Society of Nephrology.)

BACKGROUND: Administrative health data provide a rich and powerful tool for health services research. Partnership between researchers and the Ontario First Nations HIV/AIDS Education Circle (OFNHAEC) allowed for comprehensive analyses of the health and economic impacts of hepatitis C virus (HCV) infection in First Nations populations across Ontario, using administrative data. Examples of meaningful involvement of First Nations partners in research using secondary data sources demonstrate how community-based participatory research principles can be adapted to empower First Nations stakeholders and decision-makers. The aim of this review is to summarize and reflect on lessons learned in producing meaningful and actionable First Nations HCV research using health administrative data, from the perspective of health services researchers who collaborated for the first time with First Nations partners. METHODS: We discuss how our relationship with OFNHAEC formed and how engagement contextualized findings and provided opportunities for fostering trust and mutual capacity building. Methods included adherence to data governance principles, agreements outlining ethical conduct, and establishing commitment between partners. RESULTS: Engagement with OFNHAEC enhanced cultural understandings in study conception, design, and analysis, and enabled meaningful lessons for both parties through contextualizing findings together. Partnership ensured attention to factors, such as strength-based approaches and limitations of administrative data in their representation of First Nations peoples, that are not considered in standard HCV health services research using administrative health data. CONCLUSIONS: Collaboration throughout the HCV research provided first-hand experience of the relevance, representation, and importance of incorporating First Nations perspectives in health services research using administrative data., (© Canadian Association for the Study of the Liver, 2023.)

Background: Lowering of systolic blood pressure (SBP) in patients with low diastolic blood pressure (DBP), can further lower DBP. This can potentially decrease cerebral perfusion and cognition. We examined the influence of baseline DBP on the effect of lowering SBP on cognition., Methods: This is a post hoc analysis of the Memory in Diabetes (MIND) substudy (N = 1,430) of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (NCT00000620). Standard neuropsychological tests (Digit Symbol Substitution Test [DSST], Mini-Mental State Examination [MMSE], Rey Auditory Verbal Learning Test [RAVLT], and Stroop test) were performed at baseline and months 20 and 40. We compared the effects of intensive (goal SBP <120 mm Hg) vs. standard (goal SBP <140 mm Hg) SBP control on the changes in the 4 test scores from baseline to the averages of months 20 and 40 across the range of baseline DBP using cubic spline terms., Results: Mean age was 63 ± 6 years, 55% were women and 66% White. Participates with lower baseline DBP were older, had more cardiovascular events and a longer duration of diabetes. There was no difference in the change in DSST (-0.22; 95% CI -0.97, 0.52), MMSE (-0.14; 95% CI -0.34, 0.06), RAVLT (-0.12; 95% CI -0.29, 0.06), and Stroop interference (-0.47; 95% CI -1.76, 0.82) in the intensive vs. standard SBP intervention. There was no interaction between baseline DBP and change in scores with the SBP intervention., Conclusions: Intensive SBP reduction does not adversely affect cognition, even in those with low baseline DBP., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Treating adverse risk myelodysplastic syndromes with azacitidine exacerbates thrombocytopenia. We report a study of eltrombopag in combination with azacitidine using a 3 + 3 cohort design. Patients with baseline platelets of <150 × 10 9 /l received eltrombopag ranging from 25 to 300 mg. An 8-day pre-phase of eltrombopag was followed by two cycles of combined therapy. Amongst 31 patients, there were no dose-limiting toxicities. The maximum tolerated dose (MTD) was 300 mg. Transient increases in bone marrow blasts at day 8 were common but no patient had protocol-defined progression following eltrombopag monotherapy. Marrow response rates after three and six treatment cycles were 32% and 29% respectively. In all, 70% of patients treated below and 36% treated at the MTD achieved a modified International Working Group 2006 platelet response at the end of cycle two. Of the platelet transfusion independent patients at baseline, 67% treated at the MTD became transfusion dependent during the first two cycles of treatment. Apart from lack of disease progression, our findings concur with a previously reported Phase III study (A StUdy of eltromboPag in myelodysPlastic SyndrOmes Receiving azaciTidine [SUPPORT]). We conclude that eltrombopag/azacitidine is safe in terms of conventional measures defined by adverse-event reporting. However, in light of SUPPORT and our own descriptive findings regarding efficacy, further combination studies in high-risk disease should be considered with caution., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)