Mortality reduction in ICU-admitted COVID-19 patients in Suriname after treatment with convalescent plasma acquired via gravity filtration

Background Although convalescent plasma (CP) treatment is a potential therapeutic option for patients with COVID-19, there is a paucity of data from studies in low-resource settings. The efficacy and safety of CP therapy in intensive care unit (ICU) patients with COVID-19 in Suriname was evaluated. A novel gravity-based filtration method was used to obtain CP. The design was an open-label, multi-centre, non-randomized prospective clinical trial performed in two hospitals in Suriname, from June 2020, to December 2020. A pre-planned interim analysis is reported in 78 PCR-confirmed COVID-19 patients admitted to the ICU with severe or lifethreatening symptoms. CP in combination with standard treatment (n = 28) was compared to standard treatment alone (control) (n = 50), stratified by disease severity. The primary endpoint was 28-day ICU mortality. Secondary (exploratory) endpoints were changes two days after treatment initiation in pulmonary oxygen exchange capacity (PF ratio) and chest xray (CXR) score. Findings The median age of patients was 52 years with 43 [55.1%] being male. Twenty-eight day mortality occurred in 18% (5/28) of the CP group vs 36% (18/50) of the control group. Survival probability was significantly higher in the CP group compared to the control group with standard care (P=0.027). When stratifying into disease severity, the survival probability was the lowest for the control group with life-threatening disease (P=0.0051). CP treatment of severe COVID-19 resulted in a higher probability of survival, with a hazard ratio (HR) of 0.22 (95% CI, 0.074-0.067), correcting for age, the presence of diabetes and COVID-19 severity. Age significantly increased the mortality risk (HR, 1.08 [95%CI, 1.022-1.14]; P =0.006). In the severe group, CP resulted in an improved CXR score (P =0.0013) and increase in PF ratio (P = 0.011) as compared to standard therapy. The gravity-based plasmapheresis method used for CP production was well-tolerated and no adverse events were observed in the donors. Interpretation Among patients with severe or life-threatening COVID-19, CP therapy in combination with standard treatment resulted in 78% reduction of 28-day ICU mortality (HR = 0.22) compared to standard treatment alone. Both CXR-score and PF ratio changes represent indicators of treatment effect of CP after two days and can easily be implemented in low-resource settings. The novel CP production method was effective and represents a practical solution for low and middle income countries (LMICs) to produce CP locally. Although interpretation is limited by the non-randomised design of the trial, these results offer a potential route for broader implementation of CP treatment in LMICs.

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Mortality Reduction in ICU-Admitted COVID-19 Patients in Suriname after Treatment with Convalescent Plasma Acquired Via Gravity Filtration

Anesthesia and Clinical Research ◽

10.31487/j.acr.2021.02.03 ◽

2021 ◽

pp. 1-12

Author(s):

Rosita Bihariesingh ◽

R Bansie ◽

J Froberg ◽

N Ramdhani ◽

...

Keyword(s):

Standard Treatment ◽

Therapeutic Option ◽

Production Method ◽

Exchange Capacity ◽

Icu Mortality ◽

Open Label ◽

Middle Income ◽

Filtration Method ◽

Probability Of Survival ◽

Severe Group

Introduction: Although convalescent plasma (CP) treatment is a potential therapeutic option for patients with COVID-19, there is a paucity of data from intensive care unit (ICU) patients with COVID-19 in low-resource settings, such as Suriname. CP was produced by a novel gravity-based filtration method. Methods: In an open-label, multi-center, non-randomized prospective clinical trial, patients with severe or life- threatening COVID-19 symptoms (n=28) with CP treatment were compared with standard treatment alone (n=50). A pre-planned interim analysis is reported. The primary endpoint was a 28-day ICU mortality. Secondary endpoints were changes two days after treatment initiation in pulmonary oxygen exchange capacity (PF ratio) and chest x-ray (CXR) score. Results: Mortality occurred in 18% (CP: 5/28) vs. 36% (Control:18/50). CP treatment of severe COVID-19 resulted in a higher probability of survival, with a hazard ratio (HR) of 0.22 (95% CI, 0.074-0.067), correcting for age, the presence of diabetes and COVID-19 severity. In the severe group, CP resulted in an improved CXR score (P = 0.0013) and increase in PF ratio (P = 0.011) as compared to standard therapy. The gravity-based plasmapheresis method used for CP production was well-tolerated and no adverse events were observed in the donors. Discussion: CP therapy in combination with standard treatment resulted in 78% reduction of 28-day ICU mortality (HR = 0.22) compared to standard treatment alone. Both CXR-score and PF ratio changes represent effective indicators for the treatment effect of CP after two days. The novel CP production method was effective and represents a practical solution for Low- and middle-income countries to produce CP.

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Cash transfers may increase the no-show rate for surgical patients in low-resource settings: A randomized trial

10.1101/2021.03.20.21254039 ◽

2021 ◽

Author(s):

Mark G Shrime ◽

Elizabeth A Harter ◽

Becky Handforth ◽

Christine L Phillips ◽

Hendrika W C Bos ◽

...

Keyword(s):

Conditional Cash Transfer ◽

Cash Transfers ◽

Cash Transfer ◽

Surgical Patients ◽

Control Group ◽

Low Resource Settings ◽

Low Resource ◽

Resource Setting ◽

Transfer Group ◽

Unconditional Cash Transfer

Background: Over two-thirds of the world's population cannot access surgery when needed. Interventions to address this gap have primarily focused on surgical training and ministry-level surgical planning. However, patients more commonly cite cost--rather than governance or surgeon availability--as their primary access barrier. We undertook a randomized, controlled trial (RCT) to evaluate the effect on compliance with scheduled surgical appointments of addressing this barrier through a cash transfer. Methods: 453 patients who were deemed surgical candidates by a nursing screening team in Guinea, West Africa, were randomized into three study arms: control, conditional cash transfer, and labeled unconditional cash transfer. Arrival to a scheduled surgical appointment was the primary outcome. The study was performed in conjunction with Mercy Ships. Results: The overall no-show rate was five-fold lower in Guinea than previously published estimates, leading to an underpowered study. In a post-hoc analysis, which included non-randomized patients, patients in the control group and the conditional cash transfer group demonstrated no effect from the cash transfer. Patients in the unconditional cash transfer group were significantly less likely to arrive for their scheduled appointment. Subgroup analysis suggested that actual receipt of the unconditional cash transfer, instead of a lapse in the transfer mechanism, was associated with failure to show. Conclusion: We find that cash transfers are feasible for surgical patients in a low-resource setting, but that unconditional transfers may have negative effects on compliance. Although demand-side barriers are large for surgical patients in low-resource settings, interventions to address them must be designed with care.

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An Accurate and Rapid Color-Based Point-of-Care Assay for the Detection of Severe Anemia in Low Resource Settings

Blood ◽

10.1182/blood.v124.21.688.688 ◽

2014 ◽

Vol 124 (21) ◽

pp. 688-688

Author(s):

Patrick T. McGann ◽

Erika Tyburski ◽

Vysolela de Oliveira ◽

Brigida Santos ◽

Russell E. Ware ◽

...

Keyword(s):

Diagnostic Tool ◽

Point Of Care ◽

Hemoglobin Concentration ◽

Capillary Blood ◽

Severe Anemia ◽

Low Resource Settings ◽

Low Resource ◽

Color Scale ◽

Hematology Analyzer ◽

Life Threatening

Abstract Background: Severe anemia is a leading cause of morbidity and mortality among children in low-resource countries, particulalrly in sub-Saharan Africa, where malaria is endemic and sickle cell disease is prevalent. In many low-resource regions, particularly more remote areas, laboratory diagnostics are not always readily available. The utility of available equipment can be limited by lack of technical expertise, maintenance, and trained personnel, as well as lack of affordable reagents and reliable power. In a setting where severe, life-threatening anemia is common, it is critical for providers to have access to a rapid and accurate diagnostic tool to determine which patients need acute evaluation and treatment. A simple, rapid, accurate, and disposable point-of-care assay (AnemoCheck¨) has recently been tested and published(Tyburski et al. JCI 2014, in press), Hemoglobin concentration is measured by assessing the color of a chemical solution containing hydrogen peroxide and 3,3',5,5'-tetramethylbenzidine, after mixing with 10μL blood. The AnemoCheck assay is self-contained and does not require electricity, complicated sensors, or additional equipment. The color scale of the original assay correlated well with mild anemia (Hb 9-13 g/dL) but was not designed to discriminate lower hemoglobin concentrations. Accordingly, the test was modified to allow the color scale to detect more severe anemia (Hb 2.5-9.1 g/dL), but needs to be tested in a real-world setting where severe anemia is prevalent. Methods: The primary objective of this study was to determine whether AnemoCheck tests could measure hemoglobin concentrations at least as accurately as currently used standard laboratory techniques in low resource settings where severe anemia is common. The study was performed in the sickle cell clinic at Hospital Peditrico David Bernardino, a large, public pediatric hospital in Luanda, Angola. After receiving informed consent from a parent or guardian, capillary blood was collected by fingerstick as per routine to measure hemoglobin using a BioSystems BTS-350 Hemoglobin Analyzer. A small sample of capillary blood was also collected for the AnemoCheck assay using a 10μL end-to-end capillary tube via capillary action (Sanguis Counting, Germany). Venous blood was also collected to measure hemoglobin using a calibrated hematology analyzer (Sysmex XT-2000i), which was considered the true hemoglobin concentration for comparison purposes. Hemoglobin was determined first by AnemoCheck by placing the 10μL capillary into a 2mL screw cap polypropylene tube containing the chemical reagents. The tube was then vigorously shaken and after 60 seconds, was compared to a standardized color scale and the hemoglobin concentration was determined. The AnemoCheck results were obtained and recorded before any additional machine-determined results were available, to avoid potential bias. Results: For this pilot study, samples were collected from 40 children for hemoglobin determination by all three methods. The range of hemoglobin concentrations, based on results from the Sysmex hematology analyzer, was 4.8 – 9.2 g/dL (median 7.0). As illustrated in the Figure, the hemoglobin values obtained from the AnemoCheck assay correlated well with the Sysmex hematology analyzer results, r=0.74, p<0.0001. The AnemoCheck results were more accurate than the hemoglobin values obtained by the BioSystems Hemoglobin Analyzer (r=0.47, p=0.020), which is the primary mode of hemoglobin determination in the clinic. On average, the hemoglobin obtained by AnemoCheck was within 0.5 g/dL of the Sysmex value (range 0-1.9 g/dL), compared to the Biosystems value (absolute mean difference=0.7 g/dL, range 0-2.2 g/dL). Figure 1 Figure 1. Conclusions: Laboratory diagnosis of anemia is expensive and difficult in low resource settings such as Angola, where severe anemia is common and life-threatening. Our pilot data demonstrate that a novel, point-of-care, color-based assay that does not require electricity or expensive reagents is able to accurately estimate low hemoglobin concentrations. Further refinements of the AnemoCheck assay will include photographic color assessment and automated hemoglobin estimation, which will be helpful in resource-poor settings. This test has the potential to become extremely useful diagnostic tool in low resource hospitals and health centers, where sophisticated equipment and reagents may not be available. Disclosures No relevant conflicts of interest to declare.

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SP16-2 Problems with standard treatment guidelines in low-resource settings

International Journal of Antimicrobial Agents ◽

10.1016/s0924-8579(13)70173-0 ◽

2013 ◽

Vol 42 ◽

pp. S18

Author(s):

E.R. Vlieghe

Keyword(s):

Standard Treatment ◽

Treatment Guidelines ◽

Low Resource Settings ◽

Low Resource ◽

Standard Treatment Guidelines

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Ethical issues in the design and conduct of stepped-wedge cluster randomized trials in low-resource settings

Trials ◽

10.1186/s13063-019-3842-1 ◽

2019 ◽

Vol 20 (S2) ◽

Cited By ~ 2

Author(s):

Kaustubh Joag ◽

Guillermo Ambrosio ◽

Edgar Kestler ◽

Charles Weijer ◽

Karla Hemming ◽

...

Keyword(s):

Case Studies ◽

Randomized Trials ◽

Ethical Issues ◽

Control Group ◽

Cluster Randomized Trials ◽

Stepped Wedge ◽

Low Resource Settings ◽

Low Resource ◽

Cluster Randomized

Abstract Background Stepped-wedge cluster randomized trials (SW-CRTs) are increasingly popular in health-related research in both high- and low-resource settings. There may be specific ethical issues that researchers face when designing and conducting SW-CRTs in low-resource settings. Knowledge of these issues can help to improve the ethical conduct of SW-CRTs in a global health context. Methods We performed an ethical analysis of two studies using SW-CRT designs in low-resource settings: the Que Vivan Las Madres study conducted from 2014 to 2017 in Guatemala and the Atmiyata study conducted from 2017 to 2018 in rural parts of India. For both case studies, we identified and evaluated the classification of the study as research or nonresearch and the ethical issues regarding the justification of the design, including the delayed rollout of an intervention that had a promising effect. Results In our case studies, some minor ethical issues surfaced about the registration and stakeholder pressure on the order of randomization, but both included good justification for the design and delayed rollout. Our analysis did, however, demonstrate that careful consideration of the role of randomization and registration of the trials is important. Discussion SW-CRTs can provide an opportunity for rigorous evaluation of interventions destined to be rolled out on the basis of limited evidence. Furthermore, in SW-CRTs, the underlying objective is often to provide a robust evaluation of the effectiveness for generalized dissemination, and this makes the SW-CRT no less a research study than any other form of cluster randomized trial. Conclusion The design and conduct of stepped-wedge cluster randomized trials raises at least two ethical issues that need special consideration in both high- and low-resource settings: the justification for using the design, specifically the delayed rollout of the intervention to the control group, and the classification of the study as research or nonresearch. In our case studies, these issues did not seem to raise special ethical scrutiny in low-resource settings. Further ethical evaluation will hopefully result in specific ethical guidelines for the use of SW-CRTs in both high- and low-resource settings to contribute to responsible functioning of these trials and adequate protection of participants.

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Use of Convalescent Plasma in COVID-19 Patients: Guayaquil, Ecuador Experience.

Blood ◽

10.1182/blood-2020-142664 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 1-1

Author(s):

Carlos Plaza ◽

Brener Sabando ◽

Yaira Loor Morán ◽

Maria Alejandra Posligua ◽

Luis Layedra ◽

...

Keyword(s):

Mechanical Ventilation ◽

Mortality Rate ◽

Standard Treatment ◽

Conflicts Of Interest ◽

Early Stage ◽

Therapeutic Option ◽

Specific Treatment ◽

Control Group ◽

Nasopharyngeal Swab ◽

Plasma Transfusion

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Hubei province, China in December 2019; pneumonia caused by the SARS-CoV-2 is named coronavirus disease 2019 (COVID-19).1 Several antiviral and anti-inflammatory therapies have been proposed such as hydroxychloroquine, remdesivir, interferon, IL-6 inhibitors, and convalescent plasma. Convalescent plasma has been used during outbreaks of Ebola, Middle East respiratory syndrome coronavirus, H5N1 avian influenza, and H1N1 influenza with mixed results. It has demonstrated reduce respiratory tract viral load, serum cytokine response, hospital stay, and mortality2. There is no specific treatment for COVID-19, however, evidence shows the use of convalescent plasma transfusion could be beneficial in patients infected with SARS-CoV-2, especially at the early stage of the disease3,4. Objectives The objective of this study was to describe the overall survival in patients treated with convalescent plasma transfusion versus the standard treatment at the time of the admission. Materials and Methods This study was performed in 3 hospitals from Guayaquil, Ecuador from April 1st until August 1st. We implemented a protocol using convalescent plasma in patients that had clinical features of severe COVID-19 infection. Convalescent plasma came from donors who had recovered from SARS-CoV-2 infection confirmed by a RT-PCR in the nasopharyngeal swab, being asymptomatic at least 15 days before the donation. We included in this cohort 78 patients who received 300mL of convalescent plasma, all patients were receiving standard treatment at the time of administration. We matched the experimental group with 65 controls selected randomly from the same day of admission. Results The median age was 58 and 62 years old in the case and control group, respectively. The median hospitalization stay was 15 days. The survival rate of patients who received convalescent plasma was higher than those who received standard treatment (64.1% vs 46.2%; p= 0.001). We analyzed mortality rate in patients who required mechanical ventilation at the time of plasma transfusion, the mortality rate was lower in CP transfused COVID-19 patients than the control group (53.8% vs 85.3%, p= 0.001). All patients who were not mechanical ventilation when administrated convalescent plasma transfusion have successfully recovered. None of the patients had no adverse reactions related to the transfusion. Conclusions The administration of convalescent plasma is an encouraging therapeutic option, in a developing country like ours, despite many adversities we are currently using this modality as an option in selected patients, specially in those that are in the early stages of the disease. In which many studies are demonstrating a higher benefit. Our results show the reduction of mortality rate in patients with SARS-CoV-2 infection treated with convalescent plasma, there are cofound factors that may underpower our study. But the adverse effect profile make these treatment a valid option in early stage severe life threading disease. we are encouraged by the initial reports to continue investigations of convalescent plasma and its benefits, while specific antiviral drugs or the vaccine against SARS-CoV-2 are being developed. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Convalescent Plasma Treatment in COVID 19

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Ischemic Stroke Risk Factors in Patients with Atrial Fibrillation Treated with New Oral Anticoagulants

Journal of Clinical Medicine ◽

10.3390/jcm10061223 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1223

Author(s):

Paweł Wańkowicz ◽

Jacek Staszewski ◽

Aleksander Dębiec ◽

Marta Nowakowska-Kotas ◽

Aleksandra Szylińska ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Therapeutic Option ◽

Oral Anticoagulants ◽

New Oral Anticoagulants ◽

Control Group ◽

Nonvalvular Atrial Fibrillation ◽

Life Threatening

The most commonly used therapeutic option for the prevention of ischemic stroke in patients with atrial fibrillation is new- or old-generation oral anticoagulants. New oral anticoagulants are at least as effective as old-generation oral anticoagulants in the prevention of ischemic stroke, with a reduced risk of life-threatening hemorrhage. Moreover, the constant monitoring of these drugs in the patient’s blood is not required during routine use. However, ischemic stroke can still occur in these patients. Therefore, the aim of this study was to investigate the pattern of risk factors for ischemic stroke in patients with atrial fibrillation treated with new oral anticoagulants. Our multicenter retrospective study involved 2032 patients with acute ischemic stroke. The experimental group consisted of 256 patients with acute ischemic stroke and nonvalvular atrial fibrillation, who were treated with new oral anticoagulants. The control group consisted of 1776 ischemic stroke patients without coexisting atrial fibrillation. The results of our study show that patients with atrial fibrillation treated with new oral anticoagulants are more likely to display thrombotic, proatherogenic, and proinflammatory factors in addition to the embolic factors associated with atrial fibrillation. Therefore, solely taking new oral anticoagulants is insufficient in protecting this group of patients from ischemic stroke.

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A Review on Diagnostic Methods for the Identification of Vibrio cholerae

Journal of Advances in Medicine and Medical Research ◽

10.9734/jammr/2020/v32i830474 ◽

2020 ◽

pp. 136-164

Author(s):

Tarh, Jacqueline Ebob

Keyword(s):

Vibrio Cholerae ◽

Diarrheal Disease ◽

Variable Number Tandem Repeat ◽

Simultaneous Detection ◽

Diagnostic Methods ◽

Cholerae Strain ◽

Low Resource Settings ◽

Remote Areas ◽

Low Resource ◽

Life Threatening

The severe diarrheal disease Cholera, has gained public health importance because of its life-threatening effect. The detection of the causative agent of this disease (Vibrio cholerae (V. Cholerae) O1 or O139) from a specimen (stool, vomitus of food sample) remains a major concern in the world today. Phenotypic finger printing (the conventional methods) of the toxigenic V. cholerae strain, remains the gold standard for the laboratory diagnosis of cholera; especially during cholera epidemic outbreaks. Detection around the remote areas which are usually rampaged by these outbreaks is usually difficult due to lack of required diagnostic facilities in small laboratories. However, the use of phenotypic approaches have some major setbacks as they are usually labor-intensive and time consuming. This delays treatment commencement especially in life threatening cases.To alleviate these setbacks, rapid molecular typing techniques involving the Polymerase chain reaction (PCR) amplification, hybridization methods, Pulsed Field Gel Electrophoresis (PFGE), Multilocus Sequence Typing (MLST), Multiple-Locus Variable Number Tandem Repeat Analysis (MVLA), Fluorescent Amplified Fragment Length Polymorphism (FAFLP), Whole Genome Sequencing (WGS) etc. represent promising tools for early detection of the pathogen V. cholerae O1/O139 even in remote areas where laboratory resources are poor. Immunoassay-based techniques like enzyme-linked immune-sorbent assay (ELISA), coagglutination, immunofluorescence, and quartz crystal microbalance (QCM), are capital/labour intensive and expensive for low resource settings. Rapid diagnostic tests based on immune-chromatography principle have also been developed for simultaneous detection of V. choleraesero groups O1 and O139. These test kits are easy to use, transport, and fast. All these methods enable the subtyping of unrelated bacterial strains and they all operate with different accuracies, discriminatory ability, and reproducibility. This review sought to address some of the methods used in diagnosing the disease cholera, with the objective of identifying the best and easiest of the methods that can help to curb the cholera problem (deaths) often encountered, especially in low resource settings in the developing countries (Nigeria inclusive).

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Auricular vagal nerve stimulation in peripheral arterial disease patients

VASA ◽

10.1024/0301-1526/a000660 ◽

2017 ◽

Vol 46 (6) ◽

pp. 462-470 ◽

Cited By ~ 3

Author(s):

Gerald Hackl ◽

Andreas Prenner ◽

Philipp Jud ◽

Franz Hafner ◽

Peter Rief ◽

...

Keyword(s):

Primary Endpoint ◽

Nerve Stimulation ◽

Short Form ◽

Therapeutic Option ◽

Arterial Disease ◽

Walking Distance ◽

Control Group ◽

Sf 36 ◽

Peripheral Arterial ◽

Double Blinded

Abstract. Background: Auricular nerve stimulation has been proven effective in different diseases. We investigated if a conservative therapeutic alternative for claudication in peripheral arterial occlusive disease (PAD) via electroacupuncture of the outer ear can be established. Patients and methods: In this prospective, double-blinded trial an ear acupuncture using an electroacupuncture device was carried out in 40 PAD patients in Fontaine stage IIb. Twenty patients were randomized to the verum group using a fully functional electroacupuncture device, the other 20 patients received a sham device (control group). Per patient, eight cycles (1 cycle = 1 week) of electroacupuncture were performed. The primary endpoint was defined as a significantly more frequent doubling of the absolute walking distance after eight cycles in the verum group compared to controls in a standardized treadmill testing. Secondary endpoints were a significant improvement of the total score of the Walking Impairment Questionnaire (WIQ) as well as improvements in health related quality of life using the Short Form 36 Health Survey (SF-36). Results: There were no differences in baseline characteristics between the two groups. The initial walking distance significantly increased in both groups (verum group [means]: 182 [95 % CI 128–236] meters to 345 [95 % CI 227–463] meters [+ 90 %], p < 0.01; control group [means]: 159 [95 % CI 109–210] meters to 268 [95 % CI 182–366] meters [+ 69 %], p = 0.01). Twelve patients (60 %) in the verum group and five patients (25 %) in controls reached the primary endpoint of doubling walking distance (p = 0.05). The total score of WIQ significantly improved in the verum group (+ 22 %, p = 0.01) but not in controls (+ 8 %, p = 0.56). SF-36 showed significantly improvements in six out of eight categories in the verum group and only in one of eight in controls. Conclusions: Electroacupuncture of the outer ear seems to be an easy-to-use therapeutic option in an age of increasingly invasive and mechanically complex treatments for PAD patients.

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