Effectiveness of ACB-IP 1.0 Universal Pathogen Free Concentrated Cocktail Convalescent Plasma in COVID-19 Infection

BACKGROUNDThe efficacy of SARS-CoV2 single donor convalescent plasma (CP) varied according to the application time and the amount of antibody that is administered. Single donor CP has some drawbacks; such as the insufficient levels of neutralizing antibody activities, the requirements of blood group compatibility, and the risk of infection transmission. In this study, the safety and efficacy of pathogen inactivated, isohemagglutinin-depleted (concentrated) and pooled CP product was investigated. MATERIALS AND METHODSA total of sixteen patients were treated with either single donor CP (N:9) or pathogen-free, concentrated, pooled CP (ACB-IP 1.0) (N:7).RESULTSFive out of six single donor plasma SARS-CoV2 antibody titers remained below 12 s/co, but the antibody titers of all ACB-IP 1.0 plasma were above 12 s/co. SARS-CoV2 total antibody titers of ACB-IP 1.0 plasma were statistically higher than the antibody titers of single donor CP. Mean total plasma neutralizing antibody activity of ACB-IP 1.0 plasma (1.5421) was found statistically higher than single donor CP (0.9642) in 1:256 dilution (ρ<0.01)The mortality rates of the patients treated with ACB-IP 1.0 plasma were statistically lower (p< 0.05) than the patients treated with single donor CP. The administration of either single donor CP or ACB-IP 1.0 plasma to the patients within eight days significantly shortened the length of hospitalization (ρ< 0.01).CONCLUSIONThe present study established ACB-IP 1.0 plasma product as a safe and potentially effective treatment for COVID-19, allowing rapid access to patients in need.TRIAL REGISTRATIONTrial Registration Number: NCT04769245Trial Registration Date: 17.03.2021

Endovascular treatment for acute ischemic stroke in patients with versus without atrial fibrillation: a matched-control study

Background and objective The effect of atrial fibrillation (AF) on outcomes of endovascular treatment (EVT) for acute ischemic stroke (AIS) is controversial. This study aimed to investigate the association of AF with outcomes after EVT in AIS patients. Methods Subjects were selected from ANGEL-ACT registry (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke) - a prospective consecutive cohort of AIS patients undergoing EVT at 111 hospitals in China between November 2017 and March 2019, and then grouped according to having a history of AF or not. After 1:1 propensity score matching, the outcome measures including the 90-day modified Rankin Scale (mRS) score, successful recanalization after final attempt, symptomatic intracranial hemorrhage (ICH) within 24 h, and death within 90 days were compared. Results A total of 1755 patients, 550 with AF and 1205 without AF, were included. Among 407 pairs of patients identified after matching, no significant differences were found in the mRS score (median: 3 vs. 3 points; P = 0.29), successful recanalization (87.2 vs. 85.3%; P = 0.42), symptomatic ICH (9. 4 vs. 9.1%; P = 0.86) and death (16.3 vs. 18.4%; P = 0.44) between patients with and without AF. Conclusion The findings of this matched-control study show comparable outcomes of EVT in Chinese AIS patients with and without AF, which do not support withholding EVT in patients with both AIS and AF. Trial registration NCT03370939 First registration date: 28/09/2017 First posted date: 13/12/2017

Rationale and Design of the Vasospastic Angina Treatment by Endothelin Receptor Antagonism (VERA) Trial

Background Pharmacological treatment of patients diagnosed with vasospastic angina (VSA) or microvascular angina (MVA) is challenging and often patients remain symptomatic. Endothelin (ET)-1 plays an important role in the regulation of the vascular tone and stimulation of ET-1 receptors can induce a potent and long-lasting vasoconstriction. Macitentan is a potent, inhibitor of the ETA receptor. Purpose This prospective, randomized, double-blind, placebo-controlled, sequential cross-over proof-of-concept trial is designed to investigate macitentan as a potential novel treatment for patients with VSA due to epicardial spasm or MVA due to microvascular spasm, together defined as coronary artery spasm (CAS).Methods and Results A total of 30 patients with CAS will receive treatment with either 10 mg of macitentan daily for 4 weeks followed by placebo for 4 weeks, or vice versa, in random order. The primary outcome is the reduction in angina, calculated as (1) the frequency of angina attacks * severity (on a VAS scale 1-10); and (2) the duration (in minutes) * severity (on a Visual Analogue Scale (VAS) pain scale 1-10) during medication use (macitentan or placebo) up to 2 weeks after discontinuation of the study medication. The primary analysis will assess the within-subject differences in the burden of anginal symptoms following treatment with macitentan versus placebo.Conclusions The VERA trial will be the first to evaluate the efficacy of the ETA receptor antagonist, macitentan, in the treatment of VSA due to epicardial spasm and MVA due to microvascular spasm.Trial Registration trialregister.nl, Identifier: NL7546. Registration date: 20 February 2019.

Lack of in-brace x-rays in compliant AIS patients wearing full-time TLSO braces associates with failure

Background In-brace correction and brace compliance with thoraco-lumbo-sacral orthotic (TLSO) braces are associated with successful treatment of adolescent idiopathic scoliosis (AIS). This paper compares patients who had consistent radiographic documentation of in-brace correction to those who did not. Methods All skeletally immature (Risser 0-2) patients were treated for AIS (25-45°) with full-time TLSO braces that had compliance temperature monitors. All patients wore their braces at least 12 h a day. Brace failure was defined as curve progression to a surgical magnitude (≥ 50°). All patients were followed until brace discontinuation. Results Ninety patients (F 82, M 8) with an average age of 12.1 (10.1-15.0) years, Risser grade 0 (0-2), BMI percentile 48.5 (0.0-98.8), and daily brace wear of 16.5 (12.1-21.6) h/day were treated for 24.3 (8.0-66.6) months. Patients went through 1.7 (1-4) braces on average. Forty-two out of 90 (46.7%) patients had some amount of brace time with an unknown in-brace correction, which, on average, was 66.1% of their total treatment course (11.5-100). On univariate analysis, patients that did not have a repeat in-brace x-ray with major brace adjustments or new brace fabrication tended to be more skeletally immature (Risser 0 and tri-radiate open, p = 0.028), wear more braces throughout their treatment (2.0 vs 1.4, p < 0.001), were treated for a longer period of time (27 vs 22 months, p = 0.022), and failed bracing more often (47.6% vs 22.9%, p = 0.014). Conclusions Patients who did not have new in-brace x-rays with major brace adjustments and/or new brace fabrication were 3.1 (95% CI 1.2-7.6) times more likely to fail bracing than patients who were re-checked with new in-brace x-rays. Trial registration ClinicalTrials.gov—NCT02412137, initial registration date April 2015 Level of evidence III

Financial indebtedness and suicide: A 1-year follow-up study of a population registered at the Swedish Enforcement Authority

Background: Economic hardship is an established suicidogenic factor. However, very little is known about whether financial difficulties in terms of debt problems, specifically, is related to suicide. This would seem to be an important research gap, not least at a time when the repercussions of the global financial crisis are still being felt by many people. Aims: This study sets out to examine whether experiencing financial indebtedness is related to suicide. Methods: For this purpose, people aged between 18 and 64 with a registration date for a debt in the Swedish Enforcement Authority register between 2015 and 2017 ( n = 180,842) are followed up for a 1-year period for death by suicide and compared with a sample from the general Swedish population ( n = 928,265). The analysis is based on penalized maximum likelihood logistic regressions. Results: Those who had experienced financial indebtedness were two and a half times more likely to commit suicide than those who had not lived through this experience (OR = 2.50), controlling for several demographic, socio-economic, and mental health conditions prior to the date of the registration at the Enforcement Authority. Conclusion: Debt repayment problems have a significant and detrimental impact on individuals’ risk of committing suicide, even when several other socioeconomic risk factors are controlled for. The results reinforce the importance of ongoing attempts to remove the issue of debt problem from its status as a rather hidden suicidogenic risk factor.

Self-reported health and life satisfaction in older emergency department patients: sociodemographic, disease-related and care-specific associated factors

Background Self-reported health (SRH) and life satisfaction (LS) are patient-reported outcomes (PROs) that independently predict mortality and morbidity in older adults. Emergency department (ED) visits due to serious health problems or accidents might pose critical life events for patients. This study aimed (a) to characterize older patients’ SRH and LS during the distinct event of an ED stay, and (b) to analyze concomitant associations of PROs with ED patients’ sociodemographic, disease-specific and care-related variables. Methods Study personnel recruited mostly older ED patients from three disease groups during a two-year period (2017–2019) in eight EDs in central Berlin, Germany, in the context of the health services research network EMANet. Cross-sectional data from the baseline patient survey and associated secondary data from hospital information systems were analyzed. Multilevel linear regression models with random intercept were applied to assess concomitant associations with SRH (scale: 0 (worst) to 100 (best)) and LS (scale: 0 (not at all satisfied) to 10 (completely satisfied)) as outcomes, including sensitivity analyses. Results The final sample comprised N = 1435 participants. Mean age was 65.18 (SD: 16.72) and 50.9% were male. Mean ratings of SRH were 50.10 (SD: 23.62) while mean LS scores amounted to 7.15 (SD: 2.50). Better SRH and higher LS were found in patients with cardiac symptoms (SRH: β = 4.35, p = .036; LS: β = 0.53, p = .006). Worse SRH and lower LS were associated with being in need of nursing care (SRH: β = − 7.52, p < .001; LS: β = − 0.59, p = .003) and being unemployed (SRH: β = − 8.54, p = .002; LS: β = − 1.27, p < .001). Sex, age, number of close social contacts, and hospital stays in the previous 6 months were additionally related to the outcomes. Sensitivity analyses largely supported results of the main sample. Conclusions SRH and LS were associated with different sociodemographic and disease-related variables in older ED patients. Nursing care dependency and unemployment emerged as significant factors relating to both outcomes. Being able to identify especially vulnerable patients in the ED setting might facilitate patient-centered care and prevent negative health outcomes. However, further longitudinal research needs to analyze trajectories in both outcomes and suitable intervention possibilities in the ED setting. Trial registration EMANet sub-studies were registered separately: German Clinical Trials Register (EMAAge: DRKS00014273, registration date: May 16, 2018; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00014273; EMACROSS: DRKS00011930, registration date: April 25, 2017; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011930); ClinicalTrials.gov (EMASPOT: NCT03188861, registration date: June 16, 2017; https://clinicaltrials.gov/ct2/show/NCT03188861?term=NCT03188861&draw=2&rank=1).

Modified FOLFIRINOX versus gemcitabine plus oxaliplatin as first-line chemotherapy for patients with locally advanced or metastatic cholangiocarcinoma: a retrospective comparative study

Background Gemcitabine plus platinum as the first-line chemotherapy for cholangiocarcinoma (CCA) has limited efficacy. The aim of this study was to evaluate the effectiveness of modified FOLFIRINOX (mFOLFIRINOX) compared to that of gemcitabine plus oxaliplatin (Gemox) for patients with locally advanced or metastatic CCA. Methods From January 2016 to December 2019, consecutive patients who were diagnosed with locally advanced or metastatic CCA were treated with either mFOLFIRINOX or Gemox as a first-line chemotherapy. The main endpoint was Progression free survival (PFS). The second endpoints were Overall survival (OS), Disease control rate (DCR) and incidence of severe toxicity (grade 3–4). Tumors were evaluated at baseline and thence every 4–6 weeks. The study was designed and carried out in accordance with the principles of the declaration of Helsinki, approved by the Ethics Committee of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine (XHEC-D-2020-154) and registered with ClinicalTrials.gov, number NCT04305288 (registration date: 12/03/2020). Results Of 49 patients in this study, 27 were in the FOLFIRINOX regimen group and 22 in the Gemox regimen group. There were no significant differences between groups in baseline characteristics. The DCR was 77.8% in the mFOLFIRINOX group and 63.5% in the Gemox group. The corresponding median PFS was 9.9 months (95% confidence interval [CI], 7.3–12.4) in the mFOLFIRINOX group versus 6.4 months (95% CI,3.6–9.2, p = 0.040) in the Gemox group. The corresponding median OS was 15.7 months (95% CI, 12.5–19.0) versus 12.0 months (95% CI, 9.3–14.8, p = 0.099). Significantly more grade 3–4 vomiting occurred in the mFOLFIRINOX than the Gemox groups (7 (25.9%) vs 1 (4.5%), p = 0.044). Conclusions First-line mFOLFIRINOX offered more promising results in patients with advanced or metastatic CCA.

Lack of In-Brace X-Rays in Compliant AIS Patients Wearing Full-Time TLSO Braces Associates with Failure

BackgroundIn-brace correction and brace compliance with Thoraco-Lumbo-Sacral Orthotic (TLSO) braces are associated with successful treatment of Adolescent Idiopathic Scoliosis (AIS). This paper compares patients who had consistent radiographic documentation of in-brace correction to those who did not.MethodsAll skeletally immature (Risser 0–2) patients were treated for AIS (25°-45°) with full-time TLSO braces that had compliance temperature monitors. All patients wore their braces at least 12 hours a day. Brace failure was defined as curve progression to a surgical magnitude (≥ 50°). All patients were followed until brace discontinuation.Results90 patients (F:82, M:8) with an average age of 12.1(10.1–15.0) years, Risser grade 0(0–2), BMI percentile 48.5(0.0-98.8), and daily brace wear of 16.5(12.1–21.6) hrs/day were treated for 24.3(8.0-66.6) months. Patients went through 1.7(1–4) braces on average. 42/90(46.7%) patients had some amount of brace time with an unknown in-brace correction, which, on average, was 66.1% of their total treatment course (11.5–100). On univariate analysis, patients that did not have a repeat in-brace x-ray with major brace adjustments or new brace fabrication tended to be more skeletally immature (Risser 0 and tri-radiate open, p = 0.028), wear more braces throughout their treatment (2.0 vs 1.4, p < 0.001), were treated for a longer period of time (27 vs 22 months, p = 0.022), and failed bracing more often (47.6% vs 22.9%, p = 0.014).ConclusionsPatients who did not have new in-brace x-rays with major brace adjustments and/or new brace fabrication were 3.1(95% CI 1.2–7.6) times more likely to fail bracing than patients who were re-checked with new in-brace x-rays.Trial Registration:ClinicalTrials.gov - NCT02412137, Initial Registration Date April 2015

Handwashing Adherence and the Trajectory of COVID-19 Pandemic: Findings from 14 Countries

Background: The COVID-19 pandemic has affected people’s engagement in health behaviors, especially those that protect individuals from SARS-CoV-2 transmission, such as handwashing/sanitizing. Associations between the pandemic’s trajectory and engagement in the protective behavior of handwashing are unclear. This study investigated whether adherence to the World Health Organization’s (WHO) handwashing guidelines is associated with (i) total cases of COVID-19 morbidity/mortality accumulated since the onset of the pandemic, (ii) recent cases (country-level COVID-19 morbidity/mortality in the 14 days prior to data collection), (iii) increases/acceleration in recent cases (country-level COVID-19 morbidity/mortality in the previous 14 days minus cases recorded 14-28 days earlier), and (iv) stringency of the national containment-and-health policies (in the 7 days prior to data collection).Methods: The observational study (#NCT04367337) enrolled 6,064 adults residing in Australia, Canada, China, France, Gambia, Germany, Israel, Italy, Malaysia, Poland, Portugal, Romania, Singapore, and Switzerland. Data on cross-situational handwashing adherence were collected via an online survey (March–July 2020). Individual data were matched with the WHO daily reports of COVID-19 and indices of containment-and-health policies. Country-level human development index and sociodemographic variables were controlled.Results: Multilevel regression models indicated that as the total cases of COVID-19 morbidity and mortality grew higher, handwashing adherence decreased. As increases in recent cases of COVID-19 morbidity and mortality occurred, handwashing adherence increased. Higher levels of containment-and-health policy index were associated with lower handwashing.Conclusions: Research investigating protective behaviors should account for indicators of fluctuations of COVID-19 morbidity/mortality, besides accounting for time since the beginning of the pandemic.Trial Registration: Clinical Trials.Gov, #NCT04367337, first registration date: 29/04/2020

Heterogeneity in design and analysis of ICU delirium randomized trials: a systematic review

Background There is a growing number of randomized controlled trials (RCTs) evaluating interventions to prevent or treat delirium in the intensive care unit (ICU). Efforts to improve the conduct of delirium RCTs are underway, but none address issues related to statistical analysis. The purpose of this review is to evaluate heterogeneity in the design and analysis of delirium outcomes and advance methodological recommendations for delirium RCTs in the ICU. Methods Relevant databases, including PubMed and Embase, were searched with no restrictions on language or publication date; the search was conducted on July 8, 2019. RCTs conducted on adult ICU patients with delirium as the primary outcome were included where trial results were available. Data on frequency and duration of delirium assessments, delirium outcome definitions, and statistical methods were independently extracted in duplicate. The review was registered with PROSPERO (CRD42020141204). Results Among 65 eligible RCTs, 44 (68%) targeted the prevention of delirium. The duration of follow-up varied, with 31 (48%) RCTs having ≤7 days of follow-up, and only 24 (37%) conducting delirium assessments after ICU discharge. The incidence of delirium was the most common outcome (50 RCTs, 77%) for which 8 unique statistical methods were applied. The most common method, applied to 51 of 56 (91%) delirium incidence outcomes, was the two-sample test comparing the proportion of patients who ever experienced delirium. In the presence of censoring of patients at ICU discharge or death, this test may be misleading. The impact of censoring was also not considered in most analyses of the duration of delirium, as evaluated in 24 RCTs, with 21 (88%) delirium duration outcomes analyzed using a non-parametric test or two-sample t test. Composite outcomes (e.g., rank-based delirium- and coma-free days), used in 11 (17%) RCTs, seldom explicitly defined how ICU discharge, and death were incorporated into the definition and were analyzed using non-parametric tests (11 of 13 (85%) composite outcomes). Conclusions To improve delirium RCTs, outcomes should be explicitly defined. To account for censoring due to ICU discharge or death, survival analysis methods should be considered for delirium incidence and duration outcomes; non-parametric tests are recommended for rank-based delirium composite outcomes. Trial registration PROSPERO CRD42020141204. Registration date: 7/3/2019.