Staphylococcus aureus binding to Seraph® 100 Microbind® Affinity Filter: Effects of surface protein expression and treatment duration.

INTRODUCTION: Extracorporeal blood purification systems represent a promising alternative for treatment of blood stream infections with multiresistant bacteria. OBJECTIVES: The aim of this study was to analyse the binding activity of S. aureus to Seraph affinity filters based on heparin coated beads and to identify effectors influencing this binding activity. RESULTS: To test the binding activity, we used gfp-expressing S. aureus Newman strains inoculated either in 0.9% NaCl or in blood plasma and determined the number of unbound bacteria by FACS analyses after passing through Seraph affinity filters. The binding activity of S. aureus was clearly impaired in human plasma: while a percent removal of 42% was observed in 0.9% NaCl (p-value 0.0472) using Seraph mini columns, a percent removal of only 10% was achieved in human plasma (p-value 0.0934). The different composition of surface proteins in S. aureus caused by the loss of SarA, SigB, Lgt, and SaeS had no significant influence on its binding activity. In a clinically relevant approach using the Seraph® 100 Microbind® Affinity Filter and 1000 ml of human blood plasma from four different donors, the duration of treatment was shown to have a critical effect on the rate of bacterial reduction. Within the first four hours, the number of bacteria decreased continuously and the reduction in bacteria reached statistical significance after two hours of treatment (percentage reduction 64%, p-value 0.01165). The final reduction after four hours of treatment was close to 90% and is dependent on donor. The capacity of Seraph® 100 for S. aureus in human plasma was approximately 5 x 108 cells. CONCLUSIONS: The Seraph affinity filter, based on heparin-coated beads, is a highly efficient method for reducing S. aureus in human blood plasma, with efficiency dependent on blood plasma composition and treatment duration.

Non-adherence to anti-tubercular treatment during COVID-19 pandemic in Raipur district Central India.

BACKGROUND: Non-adherence is major factor in failure of any drug regimen. The significance of non-adherence is so much that WHO states that increasing the effectiveness of Adherence Interventions may have far greater impact on health of population than any improvement in specific medical treatments. Incidence of non-adherence to Anti Tubercular Treatment (ATT) usually ranges from 8.4% to 55.8%. This study aims to find out the reasons of Non-adherence to ATT in patients receiving anti-tubercular treatment at DIRECTLY OBSERVED TREATMENT SHORTCOURSE (DOTS) Centre at District Tuberculosis Centre (DTC), Kalibadi, Raipur during COVID-19 pandemic. METHODS: A cross sectional study was conducted at Department of Pharmacology, Pt. JNM Medical College and DTC Kalibadi Raipur. 55 Patients taking ATT fulfilling inclusion and exclusion criteria were interviewed using structured questionnaire. The data obtained was analysed to know causes of non-adherence. RESULTS: Study was carried out between March & April 2020. In our study, 80% subjects were male and 20% were female. The main reasons for Non-adherence were Side-effects of drug in 36% cases, missing medication intentionally in 34% cases, lack of encouragement by family members in 32% cases, patient's unawareness of consequences of skipping medication in 25% cases, unaware of treatment duration in 22%, not feeling any change, forgetting to take medication, and burden of concomitant medication besides ATT, each in 20% cases, 13% cases had difficulty in procuring medication due to lockdown, 5% cases did not go to collect their medicine due to fear of contracting COVID-19 infection. CONCLUSIONS: Our study shows reasons for Non-adherence are multi-factorial with drug side -effects & intentionally skipping medication being major factors.

Effects of intravesical BCG maintenance therapy duration on recurrence rate in high-risk non-muscle invasive bladder cancer (NMIBC): Systematic review and network meta-analysis according to EAU COVID-19 recommendations.

PURPOSE: During the coronavirus disease 2019 (COVID-19) pandemic, the European Association of Urology (EAU) recommended that courses of intravesical bacillus Calmette-Guérin (BCG) therapy lasting more than 1 year could be safely terminated for patients with high-risk non-muscle-invasive bladder cancer (NMIBC). Thus, we conducted a systematic review and network meta-analysis according to EAU's COVID-19 recommendations. MATERIALS AND METHODS: A systematic review was performed following the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We conducted a network meta-analysis of recurrence rate in patients with NMIBC receiving induction therapy (M0) and those receiving maintenance therapy lasting 1 year (M1) and more than 1 year (M2). RESULTS: Nineteen studies of 3,957 patients were included for the network meta-analysis. In a node-split forest plot using Bayesian Markov Chain Monte Carlo (MCMC) modeling, there were no differences between the M1 and M2 groups in recurrence rate [odds ratio (OR) 0.95 (0.73-1.2)]. However, recurrence rate in the M0 group was higher than that in the M1 [OR 1.9 (1.5-2.5)] and M2 [OR 2.0 (1.7-2.4)] groups. P-score tests using frequentist inference to rank the treatments in the network demonstrated that the therapy used in the M2 group (P-score 0.8701) was superior to that used in the M1 (P-score 0.6299) and M0 groups (P-score 0). In rank-probability tests using MCMC modeling, the M2 group showed the highest rank, followed by the M1 and M0 groups. CONCLUSION: In the network meta-analysis, there were no differences between those receiving BCG maintenance therapies in terms of recurrence rate. In the rank tests, therapy lasting more than 1-year appears to be most effective. During the COVID-19 pandemic, 1-year maintenance therapy can be used, but after the COVID-19 pandemic, therapy lasting more than 1-year could be beneficial.

Extension of Tablo TrEatmeNt Duration (XTEND) study: successful 24 h prolonged therapy with Tablo in critical patients.

BACKGROUND: The Tablo® Hemodialysis System (Tablo) is an all in one, easy-to-learn device featuring integrated water purification, on demand dialysate production and two-way wireless data transmission and is approved for use in the acute, chronic, and home settings. Prior reports have demonstrated Tablo's ability to achieve clinical goals, seamlessly integrate into hospitals and reduce cost across a wide range of treatment times. Extension of the Tablo cartridge to 24 h allows prolonged therapy and even greater flexibility for prescribers in the acute setting. The objective is to report on the first ever experience with Tablo prolonged therapy between 12 and 24 h in critically ill patients treated at a single-center ICU. METHODS: Nursing staff were trained during a single training session on Tablo prolonged therapy. After a run-in period of five treatments, Tablo data were collected via real-time transmission to a cloud-based, HIPAA compliant platform and reviewed by site staff. Dialysis treatment delivery, clinically significant alarms, and clotting events were recorded. Sub-group analysis between COVID-19 positive and negative patients were reported. RESULTS: One hundred (100) consecutive Tablo prolonged treatments had a median prescribed treatment time of 24 h and a median achieved treatment time of 21.3 h. Median cartridge usage was 1.3 per treatment. The dialysis treatment time was delivered in 91% of treatments, with 6% ending early due to an alarm, and 3% ending due to clotting. Clinically significant alarms occurred at a median rate of 0.5 per treatment hour with a resolution time of 18 s. Median blood pump stoppage time related to these alarms was 2.3 min per treatment. Blood pump stoppage time was higher in the COVID-19 subgroup when compared to the non-COVID-19 subgroup. CONCLUSION: Tablo successfully achieves prescribed treatment time with minimal therapy interruptions from alarms or cartridge changes. This data demonstrates the effectiveness of Tablo in achieving personalization of treatments necessary for unstable patients and enabling successful delivery of extended therapy with minimal clotting. Tablo's prolonged therapy meets the needs of critically patients, including COVID-19 positive patients, requiring renal replacement therapy for greater than 12 h.

Effectiveness of prone position in acute respiratory distress syndrome and moderating factors of obesity class and treatment durations for COVID-19 patients: A meta-analysis.

OBJECTIVES: To examine the effectiveness of prone positioning on COVID-19 patients with acute respiratory distress syndrome with moderating factors in both traditional prone positioning (invasive mechanical ventilation) and awake self-prone positioning patients (non-invasive ventilation). RESEARCH METHODOLOGY: A comprehensive search was conducted in CINAHL, Cochrane library, Embase, Medline-OVID, NCBI SARS-CoV-2 Resources, ProQuest, Scopus, and Web of Science without language restrictions. All studies with prospective and experimental designs evaluating the effect of prone position patients with COVID-19 related to acute respiratory distress syndrome were included. Pooled standardised mean differences were calculated after prone position for primary (PaO2/FiO2) and secondary outcomes (SpO2 and PaO2) RESULTS: A total of 15 articles were eligible and included in the final analysis. Prone position had a statistically significant effect in improving PaO2/FiO2 with standardised mean difference of 1.10 (95%CI 0.60-1.59), SpO2 with standardised mean difference of 3.39 (95% CI 1.30-5.48), and PaO2 with standardised mean difference of 0.77 (95% CI 0.19-1.35). Patients with higher body mass index and longer duration/day are associated with larger standardised mean difference effect sizes for prone positioning. CONCLUSIONS: Our findings demonstrate that prone position significantly improved oxygen saturation in COVID-19 patients with acute respiratory distress syndrome in both traditional prone positioning and awake self-prone positioning patients. Prone position should be recommended for patients with higher body mass index and longer durations to obtain the maximum effect.

COVID-19 and Its Implications for Thrombosis and Anticoagulation.

Venous thromboembolism, occlusion of dialysis catheters, circuit thrombosis in extracorporeal membrane oxygenation (ECMO) devices, acute limb ischemia, and isolated strokes, all in the face of prophylactic and even therapeutic anticoagulation, are features of novel coronavirus disease 2019 (COVID-19) coagulopathy. It seems well established at this time that a COVID-19 patient deemed sick enough to be hospitalized, should receive at least prophylactic dose anticoagulation. However, should some hospitalized patients have dosage escalation to intermediate dose? Should some be considered for full-dose anticoagulation without a measurable thromboembolic event and how should that anticoagulation be monitored? Should patients receive postdischarge anticoagulation and with what medication and for how long? What thrombotic issues are related to the various medications being used to treat this coagulopathy? Is antiphospholipid antibody part of this syndrome? What is the significance of isolated ischemic stroke and limb ischemia in this disorder and how does this interface with the rest of the clinical and laboratory features of this disorder? The aims of this article are to explore these questions and interpret the available data based on the current evidence.

PICO Questions and DELPHI Methodology for the Management of Venous Thromboembolism Associated with COVID-19.

Patients with coronavirus disease 2019 (COVID-19) have a higher risk of venous thromboembolic disease (VTE) than patients with other infectious or inflammatory diseases, both as macrothrombosis (pulmonar embolism and deep vein thrombosis) or microthrombosis. However, the use of anticoagulation in this scenario remains controversial. This is a project that used DELPHI methodology to answer PICO questions related to anticoagulation in patients with COVID-19. The objective was to reach a consensus among multidisciplinary VTE experts providing answers to those PICO questions. Seven PICO questions regarding patients with COVID-19 responded with a broad consensus: 1. It is recommended to avoid pharmacological thromboprophylaxis in most COVID-19 patients not requiring hospital admission; 2. In most hospitalized patients for COVID-19 who are receiving oral anticoagulants before admission, it is recommended to replace them by low molecular weight heparin (LMWH) at therapeutic doses; 3. Thromboprophylaxis with LMWH at standard doses is suggested for COVID-19 patients admitted to a conventional hospital ward; 4. Standard-doses thromboprophylaxis with LMWH is recommended for COVID-19 patients requiring admission to Intensive Care Unit; 5. It is recommended not to determine D-Dimer levels routinely in COVID-19 hospitalized patients to select those in whom VTE should be suspected, or as a part of the diagnostic algorithm to rule out or confirm a VTE event; 6. It is recommended to discontinue pharmacological thromboprophylaxis at discharge in most patients hospitalized for COVID-19; 7. It is recommended to withdraw anticoagulant treatment after 3 months in most patients with a VTE event associated with COVID-19. The combination of PICO questions and DELPHI methodology provides a consensus on different recommendations for anticoagulation management in patients with COVID-19.

Extracorporeal membrane oxygenation for COVID-19: evolving outcomes from the international Extracorporeal Life Support Organization Registry.

BACKGROUND: Over the course of the COVID-19 pandemic, the care of patients with COVID-19 has changed and the use of extracorporeal membrane oxygenation (ECMO) has increased. We aimed to examine patient selection, treatments, outcomes, and ECMO centre characteristics over the course of the pandemic to date. METHODS: We retrospectively analysed the Extracorporeal Life Support Organization Registry and COVID-19 Addendum to compare three groups of ECMO-supported patients with COVID-19 (aged ≥16 years). At early-adopting centres-ie, those using ECMO support for COVID-19 throughout 2020-we compared patients who started ECMO on or before May 1, 2020 (group A1), and between May 2 and Dec 31, 2020 (group A2). Late-adopting centres were those that provided ECMO for COVID-19 only after May 1, 2020 (group B). The primary outcome was in-hospital mortality in a time-to-event analysis assessed 90 days after ECMO initiation. A Cox proportional hazards model was fit to compare the patient and centre-level adjusted relative risk of mortality among the groups. FINDINGS: In 2020, 4812 patients with COVID-19 received ECMO across 349 centres within 41 countries. For early-adopting centres, the cumulative incidence of in-hospital mortality 90 days after ECMO initiation was 36·9% (95% CI 34·1-39·7) in patients who started ECMO on or before May 1 (group A1) versus 51·9% (50·0-53·8) after May 1 (group A2); at late-adopting centres (group B), it was 58·9% (55·4-62·3). Relative to patients in group A2, group A1 patients had a lower adjusted relative risk of in-hospital mortality 90 days after ECMO (hazard ratio 0·82 [0·70-0·96]), whereas group B patients had a higher adjusted relative risk (1·42 [1·17-1·73]). INTERPRETATION: Mortality after ECMO for patients with COVID-19 worsened during 2020. These findings inform the role of ECMO in COVID-19 for patients, clinicians, and policy makers. FUNDING: None.

Clinical and virological course of patients with coronavirus disease 2019 in Jiangsu province, China: a retrospective, multi-center cohort study.

BACKGROUND: The clinical and virological course of patients with coronavirus disease 2019 (COVID-19) are lacking. We aimed to describe the clinical and virological characteristics of COVID-19 patients from 10 designated hospitals in 10 cities of Jiangsu province, China. The factors associated with the clearance of SARS-CoV-2 were investigated. METHODS: A total of 328 hospitalized patients with COVID-19 were retrospectively recruited. The epidemiological, clinical, laboratory, radiology and treatment data were collected. The associated factors of SARS-CoV-2 clearance were analyzed. RESULTS: The median duration of hospitalization was 16.0 days (interquartile range [IQR] 13.0-21.0 days). On multivariate Cox regression analysis, age > 60 years (hazard ratio [HR] 0.643, 95% confidence interval [CI] 0.454-0.911, P = 0.013) was associated with the delayed SARS-CoV-2 clearance, while the atomized inhalation of interferon α-2b could improve the clearance of SARS-CoV-2 (HR, 1.357, 95% CI 1.050-1.755, P = 0.020). Twenty-six (7.9%) patients developed respiratory failure and 4 (1.2%) patients developed ARDS. Twenty (6.1%) patients were admitted to the ICU, while no patient was deceased. CONCLUSIONS: Our study found that age > 60 years was associated with the delayed SARS-CoV-2 clearance, while treated with atomized inhalation of interferon α-2b could promote the clearance of SARS-CoV-2.

Impacts of the COVID-19 Pandemic on Cardiac Rehabilitation Delivery around the World.

Background: We investigated impacts of COVID-19 on cardiac rehabilitation (CR) delivery around the globe, including virtual delivery, as well as effects on providers and patients. Methods: In this cross-sectional study, a piloted survey was administered to CR programs globally via REDCap from April to June 2020. The 50 members of the International Council of Cardiovascular Prevention and Rehabilitation (ICCPR) and personal contacts facilitated program identification. Results: Overall, 1062 (18.3% program response rate) responses were received from 70/111 (63.1% country response rate) countries in the world with existent CR programs. Of these, 367 (49.1%) programs reported they had stopped CR delivery, and 203 (27.1%) stopped temporarily (mean = 8.3 ± 2.8 weeks). Alternative models were delivered in 322 (39.7%) programs, primarily through low-tech modes (n = 226,19.3%). Furthermore, 353 (30.2%) respondents were re-deployed, and 276 (37.3%) felt the need to work due to fear of losing their job, despite the perceived risk of contracting COVID-19 (mean = 30.0% ± 27.4/100). Also, 266 (22.5%) reported anxiety, 241(20.4%) were concerned about exposing their family, 113 (9.7%) reported increased workload to transition to remote delivery, and 105 (9.0%) were juggling caregiving responsibilities during business hours. Patients were often contacting staff regarding grocery shopping for heart-healthy foods (n = 333, 28.4%), how to use technology to interact with the program (n = 329, 27.9%), having to stop their exercise because they have no place to exercise (n = 303, 25.7%), and their risk of death from COVID-19 due to pre-existing cardiovascular disease (n = 249, 21.2%). Respondents perceived staff (n = 488, 41.3%) and patient (n = 453, 38.6%) personal protective equipment, as well as COVID-19 screening (n = 414, 35.2%), and testing (n = 411, 35.0%) as paramount to in-person service resumption. Conclusion: Given the estimated number of CR programs globally, these results suggest approximately 4400 CR programs globally have ceased or temporarily stopped service delivery. Those that remain open are implementing new technologies to ensure their patients receive CR safely, despite the challenges. Highlights: - COVID-19 has impacted cardiac rehabilitation (CR) delivery around the globe.- In this cross-sectional study, a survey was completed by 1062 (18.3%) CR programs from 70 (63.1%) countries.- The pandemic has resulted in at least temporary cessation of ~75% of CR programs, with others ceasing initiation of new patients, reducing components delivered, and/or changing of mode delivery with little opportunity for planning and training.- There is also significant psychosocial and economic impact on CR providers.- Alternative CR model (e.g., home-based, virtual) reimbursement advocacy is needed, to ensure safe, accessible secondary prevention delivery.

Safety and Feasibility of a Protocolized Daily Assessment of Readiness for Liberation From Venovenous Extracorporeal Membrane Oxygenation.

BACKGROUND: Decannulation from venovenous extracorporeal membrane oxygenation (ECMO) at the earliest and safest possible time may improve outcomes and reduce cost. Yet, no prospective studies have compared weaning strategies for liberation from ECMO. RESEARCH QUESTION: Is a protocolized daily assessment of readiness to liberate from venovenous ECMO safe and feasible? STUDY DESIGN AND METHODS: We conducted a prospective, single-arm safety and feasibility study of a protocol for daily assessment of readiness to liberate from venovenous ECMO among consecutive adult patients receiving venovenous ECMO across four ICUs at a single center between June 20, 2020, and November 24, 2020. The ECMO-free protocol included three phases: (1) the safety screening, (2) non-ECMO Fio2 titration, and (3) the ECMO-free trial. Enrollment, interventions, and data collection were performed prospectively by trained study staff. RESULTS: Twenty-six patients received the ECMO-free protocol on 385 patient-days. The safety screening was passed during a total of 59 ECMO-free daily assessments (15.3%) among 20 patients. Every passed safety screening proceeded to an ECMO-free trial. Twenty-eight passed ECMO-free trials (47.5%) occurred among 16 patients (61.5%). No missed safety screenings, protocol deviations, or adverse events occurred. Of the 16 patients who passed an ECMO-free trial, 14 patients (87.5%) were decannulated. Among decannulated patients, 12 patients (85.7%) were decannulated on the same day as a passed ECMO-free trial, 6 patients (42.9%) were decannulated on the first day that they passed an ECMO-free trial, and 6 patients (42.9%) passed an ECMO-free trial at least twice consecutively before decannulation. The median time from first passed ECMO-free trial to decannulation was 2 days (interquartile range, 0-3 days). INTERPRETATION: The ECMO-free protocol is feasible and may identify patients for decannulation earlier than gradual approaches to weaning.

Role of the early short-course corticosteroids treatment in ARDS caused by COVID-19: A single-center, retrospective analysis.

PURPOSE: Severe coronavirus disease 2019 (COVID-19) is strongly related to interstitial pneumonia with frequent development of acute respiratory distress syndrome (ARDS). The role of corticosteroids (CS) treatment in these patients is still controversial. Some studies evidenced a possible role of an early short-term course of CS treatment in the treatment of severe pneumonia. PATIENTS AND METHODS: This is a single-center, retrospective study considering the patients with confirmed COVID-19 pneumonia admitted to our hospital between 9th March and 15th June 2020. Two groups were considered: early high-dose of methyl-prednisolone (eHDM; n â€‹= â€‹31) and the control group (n â€‹= â€‹52). Patients in the eHDM group received the dose of 5-8 â€‹mg/kg/day of methyl-prednisolone for 2 consecutive days. Primary outcome was the mortality evaluation; secondary outcomes were clinical improvement, side-effects and laboratory/radiographic changes. RESULTS: Significant differences between the two groups were: length of hospitalization (21.5 vs 28.4 days, p â€‹= â€‹0.026), length of non-invasive ventilation (NIV) or mechanical ventilation (11.5 vs 14.5 days, p â€‹= â€‹0.031), death (5 vs 12, p â€‹= â€‹0.006) and clinical improvement (16 vs 11, p=0.018). The following factors were related to in-hospital mortality in the multivariate analysis: comorbidities (OR â€‹= â€‹2.919; 95%CI â€‹= â€‹1.515-16.705; p<0.001), days from the onset of symptoms and the hospital admission (OR â€‹= â€‹1.404; 95%CI â€‹= â€‹1.069-12.492; p â€‹= â€‹0.011), PaO2/FiO2 (P/F) ratio (OR â€‹= â€‹3.111; 95%CI â€‹= â€‹2.334-16.991; p â€‹= â€‹0.009) and eHDM treatment (OR â€‹= â€‹0.741; 95%CI â€‹= â€‹0.129-0.917; p â€‹= â€‹0.007). CONCLUSION: The eHDM is an interesting and promising approach in the ARDS related to COVID-19 pneumonia, which reduces mortality, length of hospitalization and the need for mechanical ventilation.