Long term stability of HBsAg,anti-HBc and anti-HCV in dried blood spot samples and eluates

BackgroundDried blood spots (DBS) are a useful specimen collection tool in situations where venous access is problematic, however, detection of biomarkers from this specimen type is subject to variation depending on storage conditions and storage time.ObjectivesThe objective of this study is to assess the detection of HBsAg, anti-HBc and anti-HCV from DBS after storage.Study designDBS specimens were stored at −70 °C, −20 °C, 4 °C, 22 to 28 °C and 37 °C either with or without desiccant. Eluates were also prepared from DBS specimens and stored at −20 °C and −70 °C. DBS cards and eluates were tested for HBsAg, anti-HBc and anti-HCV at baseline on day 0 and thereafter at intervals of 14, 70 and 200 days.ResultsLoss of detection of both HBsAg and anti-HBc was evident by the first time point (14 days) in all storage conditions except for the samples (DBS and eluates) stored at −20 °C or −70 °C. Both HBsAg and anti-HBc stored under these conditions showed minimal variation up to the final time point (200 days) of storage. The detection of anti-HCV did not differ between the 22 to 28 °C, 4 °C, −20 °C and −70 °C DBS nor the −20 °C or the −70 °C stored eluates over the 200 day time period.ConclusionWe suggest that extended storage of DBS intended for downstream testing is best carried out by freezing either the DBS, or eluate, at −20 °C or −70 °C as soon as possible following collection for optimal detection of HBsAg, anti-HBc and anti-HCV.     

Silk fibroin and Nettle extract promote wound healing in a rat model: A histological and morphometrical study

IntroductionConsidering the anti-inflammatory, antimicrobial ability, and antioxidant effects besides stimulating ability of silk fibroin (SF) in cell migration and proliferation of Nettle, the current study aimed to investigate the effect of Nettle leaf extract (NLE) and SF on histology, morphometrical parameters and apoptosis on the wound in the rat model.Materials and methodsWistar rats are divided into 5 groups, including 1-control (rats with healthy skin and no treatment); 2-wound (without any treatment); 3-SF (administration of silk fibroin solution for 14 consecutive days); 4- Nettle (administration of Nettle ointment for 14 consecutive days), and 5- Eucerin group (administration of Eucerin substance for 14 consecutive days) and then assessed wound area by photography, angiogenesis, inflammation, and thickness of epidermis using hematoxylin and eosin (H&E) staining, collagen deposition, and structure of dermis layers evaluated by Masson's trichrome staining and the apoptosis index determined by tunnel assay on days 7, 14 and 21.Resultsphotographic illustrations showed that the wound surface environment on the seventh day in group 4 was significantly different from group 2 (p < 0.002). The rate of wound healing on the fourteenth day was higher in groups 3 and 4 than in group 2 (p < 0.001). Also, at this time, group 4 was significantly different from group 3 and group 5 (p = 0.003 and p = 0.000, respectively). There was a significant difference in epidermal thickness between the wound group and other experimental groups (p < 0.05). The number of apoptotic cells at the wound edges on the seventh day in both group 3 and group 4 had a significant decrease compared to other groups of wounds (p = 0.000), but there was a significant increase on the fourteenth day. Also, on the 21st day, a significant decrease in apoptotic cells was observed in both group 3 and group 4 compared to other wound groups (p = 0.000).Discussion and ConclusionNettle and SF maintain cell homeostasis and accelerate wound closure by reducing cell apoptosis and enhancing cell proliferation on the seventh day, but by increasing the apoptosis of fibroblast cells on the fourteenth day, they lead to remodeling and keratinocytes migration to epidermis formation. Increased apoptosis also seems to be one of the pathophysiological mechanisms to prevent the formation of keloid and hypertrophic scar tissue. SF and Nettle extract, by increasing cell proliferation and migration of different cell types to the site of injury, control the remodeling process by inducing and regulating apoptosis in the first two weeks of wound healing and accelerating the process of collagen deposition and epithelialization.     

Protective effect of L-carnitine on platelet apoptosis during storage of platelet concentrate

BackgroundPlatelet apoptosis is considered as one of the important factors involved in platelet storage lesion (PSL) and affect the quality of platelets during storage. The beneficial effect of L-carnitine (LC) on platelet apoptosis during platelet concentrates (PCs) storage has not been fully investigated. The aim of this study was to evaluate the effects of LC on platelets of PC regarding their apoptosis markers during storage.MethodsTen PCs from healthy donors were investigated in this study. PCs were prepared by platelet rich plasma (PRP) method and stored at 22 ± 2° C with gentle agitation during storage. The effects of LC (15 mM) on the platelet apoptosis were assessed by analyzing different indicative presence or absence of LC. Sampling was performed to evaluate apoptosis markers during platelet storage.ResultsThe results indicated significantly higher mitochondrial membrane potential for LC-treated platelets than the untreated on the days 2 and 5 of storage (P_day2 = 0.001, P_day5 = 0.001). Phosphatidylserine (PS) exposure significantly increased on the untreated compared with LC-treated platelets on the second and third days of storage (P_day2 = 0.014, P_day3 = 0.012). Also, active caspase 3 was lower in the LC- treated platelets than the control group on the day 5 of storage (P_day5 = 0.004). Cytosolic cytochrome C was so significantly lower in LC-treated compared to the untreated platelets during storage time (P_day2 = 0.002, P_day3 = 0.001, Pday5 = 0.001).ConclusionThe results of this study indicate that the use of LC as an additive solution in platelets may be useful to reduce PSL by decreasing platelet apoptosis via mitochondrial pathway and increase platelet quality during storage.     

Effect of delay in processing and storage temperature on diagnosis of SARS-CoV-2 by RTPCR testing

PurposeA large number of new molecular or virology laboratories have been established to increase the testing capacity for SARS-CoV-2. Due to heavy workload, there is delay in testing of samples. In order to avoid the negative effect of delayed testing on RTPCR results guidelines are issued from WHO and CDC to transport samples in cold chain. However, in pandemic situations the recommended guidelines for transport and storage conditions are often compromised. This study was conducted to evaluate the effect of sample storage conditions at different temperatures on the results of RT PCR test.MethodsTotal 275 samples were included in this study, among these 126 samples tested positive and 149 samples tested negative. All samples were aliquoted into two and the aliquotes stored in duplicate at 4 ?°C and room temperature. All aliquots stored at both the temperatures were tested by RTPCR every 24 hours up to 5 days.ResultsDiagnostic accuracy decreased from day1 to day 5 at both the storage temperatures i,e 4 ?°C and room temperature in comparison to the initial day results. Positivity decreased on an average of 9.02% at 4 ?°C and at 9.27% at room temperature per day. Among total 126 positive samples on an average false negative and failure of internal control at 4 ?°C and room temperature was 8.86%, 8.22% and 3.64%, and 4.12%, respectively. All the samples with CT value ?< ?30 remained positive at both temperatures up to 5 days. Few samples with >30 CT value showed variable results i.e. positive, negative or internal control failure from day 1 (2nd day after sample collection) onwards.ConclusionsThere was no significant difference between RT PCR results of samples stored at 4 ?°C and room temperature up to 5 days of collection. However internal control failure was more in samples stored at room temperature. Therefore, samples received without cold chain also may be processed by RTPCR and should not be rejected.     

Preservation of erythrocytes of heterozygous SC sickle cell patients]

In order to evaluate the feasibility of the autologous transfusion in an alloimmunized sickle cell patient, changes in the hematologic and biochemical characteristics of erythrocytes stored for 42 days from two patients with sickle cell SC anemia were compared with control subjects' (Hb A) red blood cells. Erythrocytes were stored in Saline Adenosine Dextrose Mannitol at +4 degrees C. The cryopreservation storage was made and 51Cr red cell survival was measured in one patient. No significant difference in the hematologic and biochemical parameters of the SC red blood cells and the control subjects was observed during the storage at +4 degrees C. Red cell survivals determined in fresh cells, cells stored for 42 days at +4 degrees C and thawed cells from one patient demonstrate much shorter half-life values than those of normal red blood cells. Before application, our results need to be confirmed by the same protocol with another patient with sickle cell SC.     

L’âge des culots globulaires transfusés influence-t-il toujours le pronostic des patients en réanimation ?

ObjectiveFew studies have shown that aged packed red blood cells (RBC) transfusion negatively influenced the outcome of ICU patients, probably related to storage lesions which could be decreased by leukodepletion of RBC. The purpose of this study was to evaluate the impact of aged leukodepleted-RBC pack, on the outcome of ICU patients.DesignRetrospective, observational, cohort study in a Medical Intensive Care Unit.PatientsConsecutive patients admitted during the years 2005 and 2006, and requiring a transfusion. We recorded patient's demographic data, number of RBC unit and age of each RBC, length of ICU, mortality during ICU stay.ResultsFive hundred and thirty-four patients were included with global mortality was 26.6%, length of stay in ICU six days (3–14) and SAPS II 48 (35–62). RBC equaling to 5.9 were transfused per patients (22.7% < 14 days and 57.3% < 21 days). The number of RBC was significantly higher in the dead patients group, but the rate of RBC stored less than 21 days was not different (54% versus 60%; p = 0.21). In a multivariate logistic model, independent predictors of ICU death were SAPS II (OR = 1.02 per point, p < 0.001), number of RBC (OR = 1.08 per RBC, p < 0.001), length of stay in ICU (p < 0.001). Similar results were obtained while introducing the age of RBC as time dependent covariates in a multivariate Cox's model.ConclusionsRBC transfused in our ICU are old. The ICU outcome is independently associated with the number of leucodepleted RBC transfused, but not with their age.     

Platelet functionality in cold‐stored whole blood

Whole blood is currently being reintroduced as a blood product to be used in massive bleeding situations because it affords plasma, red cells and platelets in a balanced ratio and in a logistical advantageous way. Questions concerning the haemostatic potential of the platelets have arisen, especially in cold‐stored whole blood, as this is the major whole blood product in use. When reviewing current knowledge on this, there is an abundance of publications demonstrating that in vitro, platelets in cold‐stored whole blood have a haemostatic capacity up to 14 days, and even after 21 and 35 days of storage depending on type of additive solution. There is a paucity of data on clinical trials of cold‐stored platelets, whereas there is an abundance of previous clinical experience with whole blood, both cold‐stored and fresh, as an efficacious and safe product for use in pre‐ and in‐hospital patients with life‐threatening bleeding.     

Effects of irradiation on red cells stored in CPDA-1 and CPD-ADSOL (AS-1)

Red blood cells (pRBC) collected in citrate, phosphate, dextrose, adenine-formula 1 (CPDA-1) and citrate, phosphate, dextrose-adenine, manitol saline solution (CPD-ADSOL [AS-1]) anticoagulants are increasingly being stored for variable periods in transfusion service inventories following irradiation. While anecdotal reports of increased K+ following irradiation and storage have recently appeared in the literature, concomitant in vitro biochemical changes resulting from differences in anticoagulants have not been reported. Utilizing two venipunctures, two units each of 225 mL of blood from five volunteers were collected in anticoagulant-adjusted CPDA-1 and AS-1 bags. Within two hours of collection, each unit was equally divided. One of each pair was irradiated (2000 rads). Samples were analyzed on Days 0, 1, 3, 7, and every seven days to expiration. Irradiation resulted in a 2.3 fold increase in K+ during the first seven days of storage for both anticoagulants, although significantly greater K+ levels were observed in the CPDA-1 pairs compared to the AS-1 pairs. Comparison of glucose utilization, plasma free hemoglobin, 2,3-diphosphoglycerate (2,3-DPG) and lactate dehydrogenase between control and irradiated CPDA-1 and AS-1 pairs and between anticoagulants were documented.     

Influence of treatment with neutralizing monoclonal antibodies on the SARS-CoV-2 nasopharyngeal load and quasispecies

ObjectivesTo evaluate the impact of neutralizing monoclonal antibody (mAb) treatment and to determine whether the selective pressure of mAbs could facilitate the proliferation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with spike protein mutations that might attenuate mAb effectiveness.Patients and methodsWe evaluated the impact of mAbs on the nasopharyngeal (NP) viral load and virus quasispecies of mAb-treated patients using single-molecule real-time sequencing. The mAbs used were: Bamlanivimab alone (four patients), Bamlanivimab/Etesevimab (23 patients) and Casirivimab/Imdevimab (five patients).ResultsThe NP SARS-CoV-2 viral load of mAb-treated patients decreased from 8.2 log₁₀ copies/mL before administration to 4.3 log₁₀ copies/mL 7 days after administration. Five immunocompromised patients given Bamlanivimab/Etesevimab were found to have mAb activity-reducing spike mutations. Two patients harboured SARS-CoV-2 variants with a Q493R spike mutation 7 days after administration, as did a third patient 14 days after administration. The fourth patient harboured a variant with a Q493K spike mutation 7 days post-treatment, and the fifth patient had a variant with a E484K spike mutation on day 21. The emergence of the spike mutation was accompanied by stabilization or rebound of the NP viral load in three of five patients.ConclusionTwo-mAb therapy can drive the selection of resistant SARS-CoV-2 variants in immunocompromised patients. Patients given mAbs should be closely monitored and measures to limit virus spread should be reinforced.     

Determination of amino acid levels in the rat striatum,after administration of ethanol alone and associated with ketamine,a glutamatergic antagonist

The main goal of this study was to determine the amino acids (glutamate, aspartate, glutamine and tyrosine) levels in the rat striatum, after ethanol administration alone and/or associated with ketamine. In protocol 1 (Et + ketamine-1), ethanol was administered to male Wistar rats until the 7th day, and at the next day the group received only ketamine (25 mg/kg, i.p.) up to the 14th day. In protocol 2 (Et + ketamine-2), ethanol was also administered up to the 7th day, and was associated with ketamine from the 8th up to the 14th day. In other groups, animals were treated daily with ethanol (4 g/kg, p.o.), for 7 or 14 days or ketamine daily for 7 days. Controls were administered with distilled water for 7 days. Results showed that, in protocol 1, aspartate (ASP) levels increased after ketamine administration, as compared to the controls. This effect was inhibited in the group Et + ketamine-1. Ethanol (7 days) increased glutamate (GLU) levels, as compared to control, and this effect did not differ significantly from that observed in the ketamine group. When ketamine was administered after the ethanol withdrawal (protocol 1), no alterations in those amino acid concentrations were seen, as compared to the control and ketamine groups. A tendency for increasing GLU levels was observed, after administration of ethanol (14 days) or ketamine alone or associated (protocol 2), when compared to control values. In protocol 2, TYR levels decreased as related to controls and to the 14-day ethanol-treated group. We can assume that ketamine presents only an antagonist effect, in animals pretreated with ethanol, followed by ketamine administered from the 8th day on. This is due to the fact that NMDA receptors are already sensitized, leading to a decrease in these receptors functions and consequently to ASP and GLU releases.     

Dose-dependent effect of histamine on liver function markers in immunized rabbits

ObjectiveThe present study was designed to delineate the hepatotoxicological roles of histamine dose-dependently in immunized rabbits.MethodsThe cohort comprised of three groups (II, III and IV), containing 18 rabbits each, and received subcutaneous histamine 50 μg/kg, 100 μg/kg and 200 μg/kg, respectively for 10 days (b.i.d., starting from 3 days prior to immunization until 7 days after immunization). Group I (control, n = 18) received subcutaneous sterile distilled water for 10 days. They were subsequently immunized at day 3 with intravenous injection of SRBC (1 × 10⁹ cells/ml). Blood samples were collected on pre-immunization (pre-I) day 0, as well as on days 7-, 14-, 21-, 28- and 58-post-immunization (post-I). Biochemical parameters aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin [total bilirubin (TB), direct bilirubin (DB) and indirect bilirubin (IB)] were determined.ResultsGroups II and IV revealed a significant decrease (on day 0-pre-I) and a significant increase (on days 7-, 14-, 21-, 28- and 58-post-I) in ALT and AST levels, when compared with the corresponding values of groups I and III while group II showed a significant increase in ALT and AST levels as compared to group IV. ALP levels in groups II, III and IV showed a significant enhancement when compared with group I. Moreover, results of TB, DB and IB demonstrated increased levels in group III when compared with groups I, II and IV. The results were found statistically significant (p < 0.05).ConclusionShort-term treatment of histamine produces dose-dependent differential patterns of hepatic dysfunctions suggestive mild liver degeneration warranting further long-term studies.     

Seven-versus 14-day course of antibiotics for the treatment of bloodstream infections by Enterobacterales: a randomized,controlled trial

ObjectiveTo prove that 7-day courses of antibiotics for bloodstream infections caused by members of the Enterobacterales (eBSIs) allow a reduction in patients' exposure to antibiotics while achieving clinical outcomes similar to those of 14-day schemes.MethodsA randomized trial was performed. Adult patients developing eBSI with appropriate source control were assigned to 7 or 14 days of treatment, and followed 28 days after treatment cessation; treatments could be resumed whenever necessary. The primary endpoint was days of treatment at the end of follow-up. Clinical outcomes included clinical cure, relapse of eBSI and relapse of fever. A superiority margin of 3 days was set for the primary endpoint, and a non-inferiority margin of 10% was set for clinical outcomes. Efficacy and safety were assessed together with a DOOR/RADAR (desirability of outcome ranking and response adjusted for duration of antibiotic risk) analysis.Results248 patients were assigned to 7 (n = 119) or 14 (n = 129) days of treatment. In the intention-to-treat analysis, median days of treatment at the end of follow-up were 7 and 14 days (difference 7, 95%CI 7–7). The non-inferiority margin was also met for clinical outcomes, except for relapse of fever (–0.2%, 95%CI –10.4 to 10.1). The DOOR/RADAR showed that 7-day schemes had a 77.7% probability of achieving better results than 14-day treatments.Conclusions7-day schemes allowed a reduction in antibiotic exposure of patients with eBSI while achieving outcomes similar to those of 14-day schemes. The possibility of relapsing fever in a limited number of patients, without relevance to final outcomes, may not be excluded, but was overcome by the benefits of shortening treatments.     

Lymphocyte count as a sign of immunoparalysis and its correlation with nutritional status in pediatric intensive care patients with sepsis: A pilot study

OBJECTIVES:Developing malnutrition during hospitalization is well recognized worldwide, and children are at a relatively higher risk for malnutrition than adults. Malnutrition can lead to immune dysfunction, which is associated with a higher mortality rate due to sepsis, the most frequent cause of death in pediatric intensive care units (PICUs). The aim of this study was to investigate whether malnourished patients are more likely to have relative or absolute lymphopenia and, consequently, worse prognoses.METHODS:We enrolled 14 consecutive patients with sepsis whose legal representatives provided written informed consent. Patients were classified as normal or malnourished based on anthropometric measurements. As an additional evaluation of nutritional status, serum albumin and zinc were measured on the 1^st and 7^th days of hospitalization. Lymphocyte count was also measured on the 1^st and 7^th days. Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT02698683","term_id":"NCT02698683"}}NCT02698683.RESULTS:Malnutrition prevalence rates were 33.3% and 42.8% based on weight and height, respectively. Laboratory analyses revealed a reduction of serum albumin in 100% of patients and reduction of zinc in 93.3% of patients. A total of 35% of patients had fewer than 500 lymphocytes/mm³ on their first day in the PICU. Lymphocyte counts and zinc concentrations significantly increased during hospitalization.CONCLUSIONS:Nutritional evaluations, including anthropometric measurements, were not correlated with lymphocyte counts. Lymphocyte counts concomitantly increased with zinc levels, suggesting that micronutrient supplementation benefits patients with sepsis.     

Separate may not be equal: A preliminary investigation of clinical correlates of electronic psychiatric record accessibility in academic medical centers

ObjectivesElectronic Medical Records (EMR) have the potential to improve the coordination of healthcare in this country, yet the field of psychiatry has lagged behind other medical disciplines in its adoption of EMR.MethodsPsychiatrists at 18 of the top US hospitals completed an electronic survey detailing whether their psychiatric records were stored electronically and accessible to non-psychiatric physicians. Electronic hospital records and accessibility statuses were correlated with patient care outcomes obtained from the University Health System Consortium Clinical Database available for 13 of the 18 top US hospitals.Results44% of hospitals surveyed maintained most or all of their psychiatric records electronically and 28% made psychiatric records accessible to non-psychiatric physicians; only 22% did both. Compared with hospitals where psychiatric records were not stored electronically, the average 7-day readmission rate of psychiatric patients was significantly lower at hospitals with psychiatric EMR (5.1% vs. 7.0%, p = .040). Similarly, the 14 and 30-day readmission rates at hospitals where psychiatric records were accessible to non-psychiatric physicians were lower than those of their counterparts with non-accessible records (5.8% vs. 9.5%, p = .019, 8.6% vs. 13.6%, p = .013, respectively). The 7, 14, and 30-day readmission rates were significantly lower in hospitals where psychiatric records were both stored electronically and made accessible than at hospitals where records were either not electronic or not accessible (4% vs 6.6%, 5.8% vs 9.1%, 8.9 vs 13%, respectively, all with p = 0.045).ConclusionsHaving psychiatric EMR that were accessible to non-psychiatric physicians correlated with improved clinical care as measured by lower readmission rates specific for psychiatric patients.     

Adenosine triphosphate restoration and discocytic transformation of stored human erythrocytes

Erythrocytes in human blood stored for 120 days were collected by centrifugation after dispersion in buffered physiological saline. The aged erythrocytes thus collected were incubated with inosine, adenine, glucose or other media, and their shapes and ATP levels were studied by scanning electron microscopy and a luciferine-luciferase method. The aged erythrocytes incubated in a mixture of adenine and inosine markedly regained their ATP levels, and also showed a marked transformation from spiked spherocytes to normal discocytes. Incubation with inosine alone restored ATP levels of the aged erythrocytes to some extent, but did not result in morphological rejuvenation. Incubation in a mixture of citrate and glucose caused morphological rejuvenation, though it restored ATP levels less effectively than incubation in inosine alone. Incubation with adenine alone neither restored ATP levels nor resulted in morphological rejuvenation of the stored erythrocytes.     

Connective Tissue Growth Factor and Its Correlation to Other Growth Factors in Experimental Granulation Tissue

Connective tissue growth factor (CTGF) is upregulated in a variety of fibrotic disorders, probably secondary to the activation and production of transforming growth factor-beta (TGF- &#103 ). We have studied the expression of CTGF in a rat wound-healing model using Northern blot, in situ hybridization, and immunohistochemistry. The expression of CTGF mRNA in Northern blot and immunohistochemistry were correlated to the expression of TGF- &#103 1 and platelet-derived growth factor (PDGF). Northern hybridization showed the maximum expression of CTGF mRNA on day 14, whereas TGF- &#103 1 expression was maximal on days 7 and 14 and the time-related changes were smaller than for CTGF. PDGF A and PDGF B mRNA expressions were at maximum on day 14 and on day 21, respectively. In situ hybridization showed that fibroblast-like cells expressed CTGF most intensively, expression declining rapidly after day 14. CTGF mRNA and protein were found in blood vessel cells during the first week. In immunohistochemistry, all growth factors were expressed by fibroblast-like cells, macrophage-like cells, and blood vessels but CTGF-positive cells were fewer and were more restricted on days 5 and 7. These results demonstrate that CTGF expression together with TGF- &#103 and PDGF are upregulated in wound healing, and CTGF expression in blood vessels suggests that CTGF is involved in angiogenesis.     

Release of microvesicles from erythrocytes during storage in saline-adenine-glucose media

Storage of human erythrocytes in SAG media results in the release of membrane microvesicles with a diameter of about 190 nm. They can be separated from intact erythrocytes by centrifugation on a dextran barrier solution (density 1.078 g/l). Vesicles prepared from cold stored erythrocyte concentrates are like those released upon ATP depletion by erythrocytes incubated without glucose at 37 degrees C [15]. The course of vesiculation was followed by measuring acetylcholinesterase during storage of the erythrocyte concentrate for 35 days. Its activity remained constant within the storage units during the preservation period. This enzyme and phospholipids were released continuously in a proportional manner. The release of sialic acid amounted to about half of that of phospholipids. Owing to depletion of 2,3-bisphosphoglycerate the binding of ATP to haemoglobin increased and the concentration of free ATP declined. Addition of an ion-exchange resin to stored erythrocytes kept the pH constant, retarded the breakdown of 2,3-P2G and stabilized the concentration of free ATP. That inhibited the rate of irreversible vesiculation. Therefore, maintenance of 2,3-bisphosphoglycerate plus ATP during long-term storage of erythrocytes is a condition of keeping intact their membrane, metabolism and oxygen transport function.     

Efficacy of favipiravir in adults with mild COVID-19: a randomized,double-blind,multicentre, placebo-controlled clinical trial

ObjectiveTo evaluate whether favipiravir reduces the time to viral clearance as documented by negative RT-PCR results for severe acute respiratory syndrome coronavirus 2 in mild cases of coronavirus disease 2019 (COVID-19) compared to placebo.MethodsIn this randomized, double-blinded, multicentre, and placebo-controlled trial, adults with PCR-confirmed mild COVID-19 were recruited in an outpatient setting at seven medical facilities across Saudi Arabia. Participants were randomized in a 1:1 ratio to receive either favipiravir 1800 mg by mouth twice daily on day 1 followed by 800 mg twice daily (n = 112) or a matching placebo (n = 119) for a total of 5 to 7 days. The primary outcome was the effect of favipiravir on reducing the time to viral clearance (by PCR test) within 15 days of starting the treatment compared to the placebo group. The trial included the following secondary outcomes: symptom resolution, hospitalization, intensive care unit admissions, adverse events, and 28-day mortality.ResultsTwo hundred thirty-one patients were randomized and began the study (median age, 37 years; interquartile range (IQR): 32–44 years; 155 [67%] male), and 112 (48.5%) were assigned to the treatment group and 119 (51.5%) into the placebo group. The data and safety monitoring board recommended stopping enrolment because of futility at the interim analysis. The median time to viral clearance was 10 days (IQR: 6–12 days) in the favipiravir group and 8 days (IQR: 6–12 days) in the placebo group, with a hazard ratio of 0.87 for the favipiravir group (95% CI 0.571–1.326; p = 0.51). The median time to clinical recovery was 7 days (IQR: 4–11 days) in the favipiravir group and 7 days (IQR: 5–10 days) in the placebo group. There was no difference between the two groups in the secondary outcome of hospital admission. There were no drug-related severe adverse events.ConclusionIn this clinical trial, favipiravir therapy in mild COVID-19 patients did not reduce the time to viral clearance within 15 days of starting the treatment.     

Mucociliary clearance,airway inflammation and nasal symptoms in urban motorcyclists

OBJECTIVES:There is evidence that outdoor workers exposed to high levels of air pollution exhibit airway inflammation and increased airway symptoms. We hypothesized that these workers would experience increased airway symptoms and decreased nasal mucociliary clearance associated with their exposure to air pollution.METHODS:In total, 25 non-smoking commercial motorcyclists, aged 18-44 years, were included in this study. These drivers work 8-12 hours per day, 5 days per week, driving on urban streets. Nasal mucociliary clearance was measured by the saccharine transit test; airway acidification was measured by assessing the pH of exhaled breath condensate; and airway symptoms were measured by the Sino-nasal Outcome Test-20 questionnaire. To assess personal air pollution exposure, the subjects used a passive-diffusion nitrogen dioxide (NO₂) concentration-monitoring system during the 14 days before each assessment. The associations between NO₂ and the airway outcomes were analyzed using the Mann-Whitney test and the Chi-Square test. Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01976039","term_id":"NCT01976039"}}NCT01976039.RESULTS:Compared with clearance in healthy adult males, mucociliary clearance was decreased in 32% of the motorcyclists. Additionally, 64% of the motorcyclists had airway acidification and 92% experienced airway symptoms. The median personal NO₂ exposure level was 75 mg/m³ for these subjects and a significant association was observed between NO₂ and impaired mucociliary clearance (p = 0.036).CONCLUSION:Non-smoking commercial motorcyclists exhibit increased airway symptoms and airway acidification as well as decreased nasal mucociliary clearance, all of which are significantly associated with the amount of exposure to air pollution.