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Recent studies have reported that patients with von Willebrand disease treated perioperatively with a von Willebrand factor (VWF)/factor VIII (FVIII) concentrate with a ratio of 2.41 (Humate P/Haemate P) often present with VWF and/or FVIII levels outside of prespecified target levels necessary to prevent bleeding. Pharmacokinetic (PK)-guided dosing may resolve this problem. As clinical guidelines increasingly recommend aiming for certain target levels of both VWF and FVIII, application of an integrated population PK model describing both VWF activity (VWFAct) and FVIII levels may improve dosing and quality of care. In total, 695 VWFAct and 894 FVIII level measurements from 118 patients (174 surgeries) who were treated perioperatively with the VWF/FVIII concentrate were used to develop this population PK model using nonlinear mixed-effects modeling. VWFAct and FVIII levels were analyzed simultaneously using a turnover model. The protective effect of VWFAct on FVIII clearance was described with an inhibitory maximum effect function. An average perioperative VWFAct level of 1.23 IU/mL decreased FVIII clearance from 460 mL/h to 264 mL/h, and increased FVIII half-life from 6.6 to 11.4 hours. Clearly, in the presence of VWF, FVIII clearance decreased with a concomitant increase of FVIII half-life, clarifying the higher FVIII levels observed after repetitive dosing with this concentrate. VWFAct and FVIII levels during perioperative treatment were described adequately by this newly developed integrated population PK model. Clinical application of this model may facilitate more accurate targeting of VWFAct and FVIII levels during perioperative treatment with this specific VWF/FVIII concentrate (Humate P/Haemate P).Terminal complement inhibition is the standard of care for atypical hemolytic uremic syndrome (aHUS). The optimal duration of complement inhibition is unknown, although indefinite therapy is common. Here, we present the outcomes of a physician-directed eculizumab discontinuation and monitoring protocol in a prospective cohort of 31 patients that started eculizumab for acute aHUS (and without a history of renal transplant). Twenty-five (80.6%) discontinued eculizumab therapy after a median duration on therapy of 2.37 (interquartile range 1.06, 9.70) months. Eighteen patients discontinued per protocol and 7 because of nonadherence. Of these, 5 (20%) relapsed; however, relapse rate was higher in the case of nonadherence (42.8%) vs clinician-directed discontinuation and monitoring (11.1%). Four of 5 patients who relapsed were successfully retreated without a decline in renal function. One patient died because of recurrent aHUS and hypertensive emergency in the setting of nonadherence. [https://www.selleckchem.com/products/BIRB-796-(Doramapimod).html see more] Nonadherence to therapy (odds ratio, 8.25; 95% confidence interval, 1.02-66.19; P = .047) was associated with relapse, whereas the presence of complement gene variants (odds ratio, 1.39; 95% confidence interval, 0.39-4.87; P = .598) was not significantly associated with relapse. Relapse occurred in 40% (2 of 5) with a CFH or MCP variant, 33.3% (2 of 6) with other complement variants, and 0% (0 of 6) with no variants (P = .217). There was no decline in mean glomerular filtration rate from the date of stopping eculizumab until end of follow-up. In summary, eculizumab discontinuation with close monitoring is safe in most patients, with low rates of aHUS relapse and effective salvage with eculizumab retreatment in the event of recurrence.Doxorubicin plays an integral role in the treatment of patients with diffuse large B-cell lymphoma (DLBCL) but can be associated with significant toxicity. Treatment guidelines of British Columbia (BC) Cancer recommend the substitution of etoposide for doxorubicin in standard-dose R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) (R-CEOP) for patients who have a contraindication to anthracyclines; however, it is unknown if this compromises treatment outcome. We identified all patients with newly diagnosed DLBCL who were treated in BC with curative intent with R-CEOP (n = 70) within the study period. Outcome in this population was compared with a 21 case-matched control group (n = 140) treated with R-CHOP and matched for age, clinical stage, and International Prognostic Index score. The 10-year time to progression and disease-specific survival were not significantly different for patients treated with R-CEOP compared with patients in the R-CHOP control group (53% vs 62% [P = .089] and 58% vs 67% [P = .251], respectively). The 10-year overall survival was lower in the R-CEOP group (30% vs 49%, P = .002), reflecting the impact of underlying comorbidities and frailty of this population. R-CEOP represents a useful treatment alternative for patients with DLBCL and an absolute contraindication to the use of anthracyclines, with curative potential.Patients with plasma cell dyscrasias (PCDs) experience an increased burden of influenza, and current practice of single-dose annual influenza vaccination yields suboptimal protective immunity in these patients. Strategies to improve immunity to influenza in these patients are clearly needed. We performed a randomized, double-blind, placebo-controlled clinical trial comparing tandem Fluzone High-Dose influenza vaccination with standard-of-care influenza vaccination. Standard-of-care vaccination was single-dose age-based vaccination (standard dose, less then 65 years; high dose, ≥65 years), and patients in this arm received a saline placebo injection at 30 days. A total of 122 PCD patients were enrolled; 47 received single-dose standard-of-care vaccination, and 75 received 2 doses of Fluzone High-Dose vaccine. Rates of hemagglutinin inhibition (HAI) titer seroprotection against all 3 strains (H1N1, H3N2, and influenza B) were significantly higher for patients after tandem high-dose vaccination vs control (87.3% vs 63.2%; P = .003) and led to higher seroprotection at the end of flu season (60.0% vs 31.6%; P = .04). These data demonstrate that tandem high-dose influenza vaccination separated by 30 days leads to higher serologic HAI titer responses and more durable influenza-specific immunity in PCD patients. Similar vaccine strategies may also be essential to achieve protective immunity against other emerging pathogens such as novel coronavirus in these patients. This trial was registered at www.clinicaltrials.gov as #NCT02566265.<br /><br /> The Four Corners Youth Consortium was created to fill the gap in our understanding of youth concussion. This study is the first analysis of posttraumatic headache (PTH) phenotype and prognosis in this cohort of concussed youth.<br /><br /> To describe the characteristics of youth with PTH and determine whether the PTH phenotype is associated with outcome.<br /><br /> This cohort study examined outcomes from patients in a multi-institutional registry of traumatic brain injury (TBI) clinics from December 2017 to June 2019. Inclusion criteria included being between ages 5 and 18 years at enrollment and presentation within 8 weeks of a mild TBI. Data were analyzed between February 2019 and January 2021.<br /><br /> Mild TBI with standard care.<br /><br /> Time to recovery and headache 3 months after injury; measurement device is the Postconcussion Symptom Inventory (PCSI). PTH with migraine phenotype was defined as moderate-severe headache that is new or significantly worse compared with baseline and associated with nausea and/or photophobia and phonotype, there was no significant difference between sexes in recovery or PTH at 3 months.<br /><br /> PTH with a migraine phenotype is associated with persistent symptoms following concussion compared with nonmigraine PTH or no PTH. Given that female sex is associated with higher rates of migraine and migraine PTH, our finding may be one explanation for findings in prior studies that girls are at higher risk for persistent postconcussion symptoms than boys.<br /><br />PTH with a migraine phenotype is associated with persistent symptoms following concussion compared with nonmigraine PTH or no PTH. Given that female sex is associated with higher rates of migraine and migraine PTH, our finding may be one explanation for findings in prior studies that girls are at higher risk for persistent postconcussion symptoms than boys.<br /><br /> Caregivers of people with mental illness are at increased risk of developing depression, anxiety, and stress.<br /><br /> To investigate the effect of a compassion cultivation training (CCT) program on decreasing caregiver psychological distress.<br /><br /> This waitlist-controlled randomized clinical trial was conducted in 2 different community settings in Denmark. Caregivers were excluded if they had a diagnosed and untreated mental illness, addiction, meditation practice, or current psychotherapeutic treatment. Enrollment occurred between May 2018 and March 2019. A repeated measurement model was used to examine the impact of the intervention. The primary analysis was based on the intention-to-treat principle. Data analysis was conducted from June 4 to July 7, 2020.<br /><br /> Participants were randomized 1-to-1 to an 8-week CCT course or waitlist control. Block randomization was used with 40 participants in each block.<br /><br /> The main outcome was reduction in psychological distress, as measured by the Depression, Anxiety, Stress Scale (I, -4.27 to -0.73]; P = .006; stress, -3.76 [95% CI, -6.32 to -1.21]; P = .004), and the 6-month follow-up (adjusted mean difference depression -4.24 [95% CI, -6.97 to -1.52]; P = .002; anxiety, -2.12 [95% CI, -3.96 to -0.29]; P = .02; stress -3.79 [95% CI, -6.44 to -1.13]; P = .005).<br /><br /> These findings suggest that CCT was superior to the waitlist control in supporting caregivers' mental health. Statistically and clinically significant reductions in psychological distress were found and sustained at the 6-month follow-up. The improvements noted in this randomized clinical trial could serve to encourage implementation of future evidence-based programs for caregivers.<br /><br /> ClinicalTrials.gov Identifier NCT03730155.<br /><br />ClinicalTrials.gov Identifier NCT03730155.<br /><br /> Obstructive sleep apnea (OSA) is a highly prevalent global health concern and is associated with many adverse outcomes for patients.<br /><br /> To evaluate the utility of the STOP-Bang (snoring, tiredness, observed apnea, blood pressure, body mass index, age, neck size, gender) questionnaire in the sleep clinic setting to screen for and stratify the risk of OSA among populations from different geographical regions.<br /><br /> MEDLINE, MEDLINE In-process, Embase, EmCare Nursing, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, PsycINFO, Journals@Ovid, Web of Science, Scopus, and CINAHL electronic databases were systematically searched from January 2008 to March 2020. This was done to identify studies that used the STOP-Bang questionnaire and polysomnography testing in adults referred to sleep clinics.<br /><br /> Clinical and demographic data were extracted from each article independently by 2 reviewers. The combined test characteristics were calculated using 2 × 2 contingency tables. Random-effee predictive values of 77% (95% CI, 75%-78%) and 91% (95% CI, 90%-92%), respectively. The diagnostic accuracy of a STOP-Bang score of at least 3 to detect moderate to severe OSA was high (&gt;0.80) in all regions except East Asia (0.52; 95% CI, 0.48-0.56).<br /><br /> The results of this meta-analysis suggest that the STOP-Bang questionnaire can be used as a screening tool to assist in triaging patients with suspected OSA referred to sleep clinics in different global regions.<br /><br />The results of this meta-analysis suggest that the STOP-Bang questionnaire can be used as a screening tool to assist in triaging patients with suspected OSA referred to sleep clinics in different global regions.