-
JAMA Network Open Mar 2024With the widespread use of anti-SARS-CoV-2 drugs, accumulating data have revealed potential viral load rebound after treatment. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
With the widespread use of anti-SARS-CoV-2 drugs, accumulating data have revealed potential viral load rebound after treatment.
OBJECTIVE
To compare COVID-19 rebound after a standard 5-day course of antiviral treatment with VV116 vs nirmatrelvir-ritonavir.
DESIGN, SETTING, AND PARTICIPANTS
This is a single-center, investigator-blinded, randomized clinical trial conducted in Shanghai, China. Adult patients with mild-to-moderate COVID-19 and within 5 days of SARS-CoV-2 infection were enrolled between December 20, 2022, and January 19, 2023, and randomly allocated to receive either VV116 or nirmatrelvir-ritonavir.
INTERVENTIONS
Participants in the VV116 treatment group received oral 600-mg VV116 tablets every 12 hours on day 1 and 300 mg every 12 hours on days 2 through 5. Participants in the nirmatrelvir-ritonavir treatment group received oral nirmatrelvir-ritonavir tablets with 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 hours for 5 days. Participants were followed up every other day until day 28 and every week until day 60.
MAIN OUTCOMES AND MEASURES
The primary outcome was viral load rebound (VLR), defined as a half-log increase in viral RNA copies per milliliter compared with treatment completion. Secondary outcomes included a reduction in the cycle threshold value of 1.5 or more, time until VLR, and symptom rebound, defined as an increase of more than 2 points in symptom score compared with treatment completion. The primary outcome and secondary outcomes were analyzed using the full analysis set. Sensitivity analyses were conducted using the per protocol set. Adverse events were analyzed using the safety analysis set.
RESULTS
The full analysis set included 345 participants (mean [SD] age, 53.2 [16.8] years; 175 [50.7%] were men) who received VV116 (n = 165) or nirmatrelvir-ritonavir (n = 180). Viral load rebound occurred in 33 patients (20.0%) in the VV116 group and 39 patients (21.7%) in the nirmatrelvir-ritonavir group (P = .70). Symptom rebound occurred in 41 of 160 patients (25.6%) in the VV116 group and 40 of 163 patients (24.5%) in the nirmatrelvir-ritonavir group (P = .82). Viral whole-genome sequencing of 24 rebound cases revealed the same lineage at baseline and at viral load rebound in each case.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial of patients with mild-to-moderate COVID-19, viral load rebound and symptom rebound were both common after a standard 5-day course of treatment with either VV116 or nirmatrelvir-ritonavir. Prolongation of treatment duration might be investigated to reduce COVID-19 rebound.
TRIAL REGISTRATION
Chinese Clinical Trial Registry Identifier: ChiCTR2200066811.
Topics: Adult; Male; Humans; Middle Aged; Female; COVID-19; COVID-19 Drug Treatment; China; Ritonavir; SARS-CoV-2; Adenosine; Recurrence
PubMed: 38477921
DOI: 10.1001/jamanetworkopen.2024.1765 -
International Journal of Molecular... Feb 2024The term 'gene doping' is used to describe the use of any unauthorized gene therapy techniques. We developed a test for five likely candidate genes for equine gene...
The term 'gene doping' is used to describe the use of any unauthorized gene therapy techniques. We developed a test for five likely candidate genes for equine gene doping: , , , and . The test is based on real-time polymerase chain reaction (PCR) and includes separate screening and confirmation assays that detect different unique targets in each transgene. For doping material, we used nonviral (plasmid) and viral (recombinant adeno-associated virus) vectors carrying complementary DNA for the targeted genes; the vectors were accurately quantified by digital PCR. To reduce non-specific amplification from genomic DNA observed in some assays, a restriction digest step was introduced in the PCR protocol prior to cycling to cut the amplifiable targets within the endogenous genes. We made the screening stage of the test simpler and faster by multiplexing PCR assays for four transgenes (EPO, FST, IGF1, and ILRN1), while the GH1 assay is performed in simplex. Both stages of the test reliably detect at least 20 copies of each transgene in a background of genomic DNA equivalent to what is extracted from two milliliters of equine blood. The test protocol was documented and tested with equine blood samples provided by an official doping control authority. The developed tests will form the basis for screening official horseracing samples in Australia.
Topics: Animals; Horses; Erythropoietin; Australia; Plasmids; DNA; Real-Time Polymerase Chain Reaction
PubMed: 38473816
DOI: 10.3390/ijms25052570 -
Journal of Clinical Microbiology Apr 2024Scaling up of newer innovations that address the limitations of the dried blood spot and the logistics of plasma monitoring is needed. We employed a multi-site,...
UNLABELLED
Scaling up of newer innovations that address the limitations of the dried blood spot and the logistics of plasma monitoring is needed. We employed a multi-site, cross-sectional assessment of the plasma separation card (PSC) on blood specimens collected from all consenting adults, assenting young and pediatric patients living with HIV from 10 primary healthcare clinics in South Africa. Venous blood for EDTA-plasma samples was collected and analyzed according to the standard of care assay, while collected capillary blood for the PSC samples was analyzed using the Roche COBAS AmpliPrep/Cobas TaqMan (CAP/CTM) HIV-1 Test at the National Reference laboratories. McNemar tests assessed the differences in concordance between the centrifuged plasma and dried plasma spots. The usability of PSC by blood spotting, PSC preparation, and pre-analytical work was assessed by collecting seven-point Likert-scale data from healthcare and laboratory workers. We enrolled 538 patients, mostly adults [ = 515, 95.7% (95% CI: 93.7%-97.1%)] and females [ = 322, 64.2% (95% CI: 60.0%-68.1%)]. Overall, 536 paired samples were collected using both PSC- and EDTA-plasma diagnostics, and 502 paired PSC- and EDTA-plasma samples assessed. Concordance between the paired samples was obtained for 446 samples. Analysis of these 446 paired samples at 1,000 copies per milliliter threshold yielded an overall sensitivity of 87.5% [95% CI: 73.2%-95.8%] and specificity of 99.3% [95% CI: 97.9%-99.8%]. Laboratory staff reported technical difficulties in most tasks. The usability of the PSC by healthcare workers was favorable. For policymakers to consider PSC scale-up for viral load monitoring, technical challenges around using PSC at the clinic and laboratory level need to be addressed.
IMPORTANCE
Findings from this manuscript emphasize the reliability of the plasma separation card (PSC), a novel diagnostic method that can be implemented in healthcare facilities in resource-constrained settings. The agreement of the PSC with the standard of care EDTA plasma for viral load monitoring is high. Since the findings showed that these tests were highly specific, we recommend a scale-up of PSC in South Africa for diagnosis of treatment failure.
Topics: Adult; Female; Humans; Child; Sensitivity and Specificity; HIV-1; Viral Load; South Africa; Cross-Sectional Studies; Edetic Acid; Reproducibility of Results; HIV Infections; RNA, Viral
PubMed: 38470024
DOI: 10.1128/jcm.01649-23 -
Heliyon Mar 2024Ultrasound Needle, which is an improved ultrasonic horn device, has shown great potential for promoting the diffusion of thrombolytic drugs within clots and enhancing...
OBJECTIVES
Ultrasound Needle, which is an improved ultrasonic horn device, has shown great potential for promoting the diffusion of thrombolytic drugs within clots and enhancing clot lysis efficiency. However, the clot lysis efficiency of different thrombolytic drugs with the synergy of Ultrasound Needle remains unknown. In this study, we aimed to compare the lysis efficiency of the non-fibrin-specific drug urokinase and fibrin-specific drug reteplase with the synergy of Ultrasound Needle.
MATERIALS AND METHODS
Twenty-five milliliters of human blood was incubated for 1.5 h to form in vitro clots and then received the corresponding treatment protocols: control group (normal saline), US group (10 min of Ultrasound Needle treatment), UK group (30000IU of urokinase), r-PA group (2 mg of reteplase), US + UK group, and US + r-PA group. After treatment, the morphological changes of the clots were analyzed by B-mode ultrasound imaging and hematoxylin and eosin (H&E) staining. Lysis efficiency was evaluated based on the relative end weight (final weight/initial weight). The fibrin density of the different groups after treatment was assessed by immunofluorescence staining.
RESULTS
Morphological examination and relative end weight analysis showed that combination therapies induced a more thorough dissolution of clots compared with single therapies, and the US + r-PA group exhibited higher lysis efficiency than the US + UK group. In addition, immunofluorescence staining showed that the US + r-PA group had fewer remaining thrombus fibrins than the US + UK group after treatment.
CONCLUSIONS
The Ultrasound Needle can significantly improve the clot lysis efficiency of both fibrinolytic drugs, and fibrin-specific reteplase exhibited superior lysis efficiency over non-fibrin-specific urokinase with the synergy of the Ultrasound Needle.
PubMed: 38463819
DOI: 10.1016/j.heliyon.2024.e26624 -
Plant Disease Mar 2024Panax notoginseng a perennial herb native to China, is widely grown in the Yunnan Province. (Yang et al. 2022). From July to August 2022, a new leaf spot disease was...
Panax notoginseng a perennial herb native to China, is widely grown in the Yunnan Province. (Yang et al. 2022). From July to August 2022, a new leaf spot disease was observed on fully expanded leaves of P. notoginseng from a planting base in the Xundian, Yunnan Province, China. Approximately 250 ha. of P. notoginseng is the cultivated area, and the incidence of leaf spot disease was around 10-15%. Round spots appeared on the infected leaves and as the disease progressed these leaves fell off the plant. A total 21 symptomatic leaves were randomly collected from the planting base to isolate the pathogens and further study in the laboratory. The surface of infected leaves were sanitized with 0.5% sodium hypochlorite for 2 min. and 75% alcohol for 1 min., and then rinsed thrice with sterile water. Once drying, the samples were placed on potato dextrose agar (PDA), plates and incubated at 25 °C for 5 days. The fungus was isolated from the symptomatic tissue, but only three isolates were preserved for further identification. Pure cultures of the representative strain Zhaochanglin 118 were obtained using the singlespore method, and the colonies obtained were dark-green to dark-black in appearance. The pycnidia were dark brown, solitary, or congregated with an inconspicuous neck. The conidia were colorless, ellipsoidal, and measured between 4.5 to 7 × 2 to 3 μm (n = 30). These morphological characteristics were similar to those described for Boeremia exigua (Valenzuela-Lopezi et al. 2018). The genomic DNA of the isolate was extracted using the DN14 cetyltrimethylammonium bromide rapid plant genome extraction kit. The internal transcribed spacer (ITS), RNA polymerase second largest subunit (RPB2) and translation elongation factor 1-alpha (TEF1) genes were amplified via polymerase chain reaction using the primers ITS1/ITS4 (White et al. 1990), Af/Cf (Matheny et al. 2002), and EF1-983F/EF1-2218R (Chen et al. 2015), respectively. All sequences were deposited in GenBank (OQ996531 for ITS; OR291158 for RPB2 and OR291159 for TEF1). A BLASTN homology search using the ITS nucleotide sequence indicated that this has 99.6% identity with the sequence MH859059, named B. exigua from CBS culture collection (517/519 bp); the RPB2 sequence has 97.5% identity with sequence GU371780, named B. exigua from CBS culture collection (704/722 bp); and the TEF1 sequence has 98.4% identity with sequence GU349080, named B. exigua from CBS culture collection (871/885 bp). To test Koch's postulates, a pathogenicity test was carried out on the leaves of six fully expanded P. notoginseng plants in the Xundian planting base. Conidial suspensions were prepared for one isolates at a concentration of 106 spores per milliliter. Three leaflets on different plants were applied with 20µl spore suspension and the other three leaflets were drop of 20 µl sterile distilled water. The whole experiment was repeated three times. The P. notoginseng plants were incubated under sterile conditions at 25°C for 7 days. Inoculated leaves showed the characteristic brown round spots, while control leaves were asymptomatic so, Koch's postulates were fulfilled by re-isolating the pathogen from symptomatic tissue, which was subsequently confirmed as B. exigua through morphological and molecular analyses. Koch's postulates were fulfilled. To our knowledge, this is the first report of B. exigua causing leaf spot disease in P. notoginseng in China, which lays a foundation for further study and developing disease control methods.
PubMed: 38457634
DOI: 10.1094/PDIS-12-23-2677-PDN -
Heliyon Mar 2024The measurement of carbamazepine levels in a biological sample is required to guide dosing, and prevent toxicity, and can be useful to assess medication adherence.
BACKGROUND
The measurement of carbamazepine levels in a biological sample is required to guide dosing, and prevent toxicity, and can be useful to assess medication adherence.
AIM
The primary aim of the presented study is to analyze carbamazepine levels in saliva and plasma samples of outpatients and to assess adherence to carbamazepine using saliva and plasma levels.
METHODS
Adults who used carbamazepine for at least one month were recruited from the outpatient clinic department of Princess Basma Hospital, a public hospital in Irbid. Saliva and blood samples (1 ml) were collected simultaneously from subjects, and using a microanalytical method with high-performance liquid chromatography coupled with an ultraviolet detector, the level of carbamazepine (in micrograms per milliliter) was ascertained. Analysis of adherence to carbamazepine was carried out using plasma and saliva levels.
RESULTS
A total of 69 consecutive patients attending the neurology clinic were recruited, of whom 85.5% had epilepsy. Approximately one-third (34.8%) used carbamazepine as monotherapy, whereas the remainder used a combination of antiepileptic drugs to control seizures. Overall, about two-thirds (71.9%) of the studied samples were non-adherent in either plasma or saliva samples. By referring to the plasma sample carbamazepine concentration, 75.4% of the respondents were adherents, 15.9% had under-adherence, and 8.7% had over-adherence. A total of 85.9% of the responders were adherent using the carbamazepine level in saliva samples. Plasma and saliva carbamazepine levels were linearly correlated to one another. Polypharmacy was commonly utilized with the patients, as 42% of the patients used two medications, with a range of 1-7 drugs used concomitantly. The predictor associated with higher plasma and saliva carbamazepine levels, as determined by multiple linear regression analysis, was the occurrence of seizures less than once a month, as compared to seizures with higher frequencies.
CONCLUSION
Saliva carbamazepine levels show the potential to be used as an alternative matrix to assess medication adherence, with a considerable correlation with the plasma carbamazepine level. Healthcare professionals can address routine care non-adherence through such measures.
PubMed: 38455560
DOI: 10.1016/j.heliyon.2024.e26736 -
The Journal of International Advanced... Jan 2024Cochlear implantation has become a standard of care for a child diagnosed with bilateral profound sensorineural hearing loss with a structured surgical standard...
Cochlear implantation has become a standard of care for a child diagnosed with bilateral profound sensorineural hearing loss with a structured surgical standard operating procedure. A 3-year-old boy with bilateral profound prelingual sensorineural deafness underwent a Med-EL Sonata Ti100 implant. We faced a peculiar situation intraoperatively after inserting the electrodes and closing the wound. The impedance recording indicated high ground path impedance with short-circuiting of few electrodes. As a bionic implant, its electronic components may at times malfunction both intraoperatively and/or postoperatively; therefore, neural response telemetry (NRT) was invented to check it. By using NRT and a few milliliters of normal saline, we were able to diagnose as well as rectify the malfunctioning of the implant.
Topics: Child, Preschool; Humans; Male; Cochlea; Cochlear Implantation; Cochlear Implants; Hearing Loss, Bilateral; Hearing Loss, Sensorineural; Saline Solution; Telemetry
PubMed: 38454296
DOI: 10.5152/iao.2024.231116 -
Frontiers in Medicine 2024Intravenous (IV) therapy is a crucial aspect of care for the critically ill patient. Barriers to IV infusion pumps in low-resource settings include high costs, lack of...
INTRODUCTION
Intravenous (IV) therapy is a crucial aspect of care for the critically ill patient. Barriers to IV infusion pumps in low-resource settings include high costs, lack of access to electricity, and insufficient technical support. Inaccuracy of traditional drop-counting practices places patients at risk. By conducting a comparative assessment of IV infusion methods, we analyzed the efficacy of different devices and identified one that most effectively bridges the gap between accuracy, cost, and electricity reliance in low-resource environments.
METHODS
In this prospective mixed methods study, nurses, residents, and medical students used drop counting, a manual flow regulator, an infusion pump, a DripAssist, and a DripAssist with manual flow regulator to collect normal saline at goal rates of 240, 120, and 60 mL/h. Participants' station setup time was recorded, and the amount of fluid collected in 10 min was recorded (in milliliters). Participants then filled out a post-trial survey to rate each method (on a scale of 1 to 5) in terms of understandability, time consumption, and operability. Cost-effectiveness for use in low-resource settings was also evaluated.
RESULTS
The manual flow regulator had the fastest setup time, was the most cost effective, and was rated as the least time consuming to use and the easiest to understand and operate. In contrast, the combination of the DripAssist and manual flow regulator was the most time consuming to use and the hardest to understand and operate.
CONCLUSION
The manual flow regulator alone was the least time consuming and easiest to operate. The DripAssist/Manual flow regulator combination increases accuracy, but this combination was the most difficult to operate. In addition, the manual flow regulator was the most cost-effective. Healthcare providers can adapt these devices to their practice environments and improve the safety of rate-sensitive IV medications without significant strain on electricity, time, or personnel resources.
PubMed: 38444409
DOI: 10.3389/fmed.2024.1326144 -
ACS Omega Feb 2024is introduced as a novel preconcentration method in this study. The approach has many benefits including low consumption of organic solvent and deionized water and...
Streamlined Water-Leaching Preconcentration Method As a Novel Analytical Approach and Its Coupling to Dispersive Micro-Solid-Phase Extraction Based on Synthetically Modified (Fe/Co) Bimetallic MOFs.
is introduced as a novel preconcentration method in this study. The approach has many benefits including low consumption of organic solvent and deionized water and operation time, energy-saving, no need for dispersion or evaporation, and implementation of more efficient preconcentration. Also, a methodological study was done on the synthesis of (Fe/Co) bimetallic-organic framework that eased the synthesis procedure, decreased its time, and enhanced its analytical performance by increasing its surface area, total pore volume, and average pore diameter parameters. To perform the extraction, bi-MOF particles were added into the solution of interest enriched with sodium sulfate. After vortexing to adsorb the analytes, centrifugation isolated the sorbent particles. A microliter-volume of acetonitrile and 1,2-dibromoethane mixture was used for desorption aim via vortexing. After the separation of the organic phase and transferring it into a conical bottom glass test tube, a milliliter volume of sodium chloride solution was applied to leach the organic phase. A gas chromatograph equipped with a flame ionization detector was applied for the injection of the extracted phase. The method was applied for the extraction and preconcentration of some pesticides from juice samples. Wide linear ranges (5.44-1600 μg L), low relative standard deviations (3.1-4.5% for intra- ( = 6) and 3.5-5.2% for interday ( = 4) precisions), high extraction recoveries (61-95%), enrichment factors (305-475), and low limits of detection (0.67-1.65 μg L) and quantification (2.21-5.44 μg L) were obtained for the developed method.
PubMed: 38434905
DOI: 10.1021/acsomega.3c08218 -
Journal of Infection and Chemotherapy :... Mar 2024Development of multi-, extensively-, and pandrug-resistant (MDR, XDR, and PDR) strains of Pseudomonas aeruginosa remains a major problem in medical care. The present...
Antimicrobial photodynamic effect of the photosensitizer riboflavin, alone and in combination with colistin, against pandrug-resistant Pseudomonas aeruginosa clinical isolates.
INTRODUCTION
Development of multi-, extensively-, and pandrug-resistant (MDR, XDR, and PDR) strains of Pseudomonas aeruginosa remains a major problem in medical care. The present study evaluated the effect of antimicrobial photodynamic therapy (aPDT) as a monotherapy and in combination with colistin against P. aeruginosa isolates.
METHODS
Two P. aeruginosa isolates recovered from patients with respiratory tract infections were examined in this study. Minimum inhibitory concentration (MIC) of colistin was determined by the colistin broth disk elution (CBDE) and the reference broth microdilution (rBMD) methods. aPDT was performed using the photosensitizer (Ps) riboflavin at several concentrations and a light-emitting diode (LED) emitting blue light for different irradiation times with or without colistin at 1/2 × MIC concentration.
RESULTS
Both PA1 and PA2 isolates were identified as colistin-resistant P. aeruginosa with a MIC ≥4 μg/mL by the CBDE and MICs of 512 μg/mL and 256 μg/mL, respectively, by the rBMD. In aPDT, neither riboflavin nor LED light alone had antibacterial effects. The values of colony forming units per milliliter (CFU/mL) in both isolates were significantly reduced by LED + Ps treatments in a time-dependent manner (LED irradiation time) and dose-dependent manner (Ps concentration). In comparison with control, treatment with Ps (50 μM) + LED (120 s) and Ps (100 μM) + LED (120 s) resulted in 0.27 log CFU/mL and 0.43 log CFU/mL reductions in PA1, and 0.28 log CFU/mL and 0.34 log CFU/mL reductions in PA2, respectively, (P < 0.01). The best results were obtained after the combination of aPDT followed by colistin, which increased bacterial reduction, resulting in a 0.41-0.7 log CFU/mL reduction for PA1 and 0.35-0.83 log CFU/mL reduction for PA2 (P = 0.001).
CONCLUSIONS
This study suggests the potential implications of aPDT in combination with antibiotics, such as colistin for treatment of difficult-to-treat P. aeruginosa infections.
PubMed: 38432556
DOI: 10.1016/j.jiac.2024.03.001