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Scientific Reports Jun 2024Severe acute respiratory syndrome coronavirus 2 had devastating consequences for human health. Despite the introduction of several vaccines, COVID-19 continues to pose a...
Severe acute respiratory syndrome coronavirus 2 had devastating consequences for human health. Despite the introduction of several vaccines, COVID-19 continues to pose a serious health risk due to emerging variants of concern. DNA vaccines gained importance during the pandemic due to their advantages such as induction of both arms of immune response, rapid development, stability, and safety profiles. Here, we report the immunogenicity and protective efficacy of a DNA vaccine encoding spike protein with D614G mutation (named pcoSpikeD614G) and define a large-scale production process. According to the in vitro studies, pcoSpikeD614G expressed abundant spike protein in HEK293T cells. After the administration of pcoSpikeD614G to BALB/c mice through intramuscular (IM) route and intradermal route using an electroporation device (ID + EP), it induced high level of anti-S1 IgG and neutralizing antibodies (P < 0.0001), strong Th1-biased immune response as shown by IgG2a polarization (P < 0.01), increase in IFN-γ levels (P < 0.01), and increment in the ratio of IFN-γ secreting CD4 (3.78-10.19%) and CD8 (5.24-12.51%) T cells. Challenging K18-hACE2 transgenic mice showed that pcoSpikeD614G administered through IM and ID + EP routes conferred 90-100% protection and there was no sign of pneumonia. Subsequently, pcoSpikeD614G was evaluated as a promising DNA vaccine candidate and scale-up studies were performed. Accordingly, a large-scale production process was described, including a 36 h fermentation process of E. coli DH5α cells containing pcoSpikeD614G resulting in a wet cell weight of 242 g/L and a three-step chromatography for purification of the pcoSpikeD614G DNA vaccine.
Topics: Vaccines, DNA; Spike Glycoprotein, Coronavirus; Animals; Humans; SARS-CoV-2; Mice; COVID-19; HEK293 Cells; Mice, Inbred BALB C; COVID-19 Vaccines; Mutation; Antibodies, Viral; Antibodies, Neutralizing; Female; Immunogenicity, Vaccine; Immunoglobulin G
PubMed: 38879684
DOI: 10.1038/s41598-024-64690-5 -
BMC Palliative Care Jun 2024Clinical evidence for the rapidity and effectiveness of fentanyl buccal soluble film (FBSF) in reducing pain intensity of breakthrough cancer pain (BTcP) remains...
BACKGROUND
Clinical evidence for the rapidity and effectiveness of fentanyl buccal soluble film (FBSF) in reducing pain intensity of breakthrough cancer pain (BTcP) remains inadequate. This study aimed to evaluate the efficacy of FBSF proportional to the around-the-clock (ATC) opioid regimens in rapidly relieving the intensity of BTcP episodes by determining the percentage of patients requiring further dose titration.
METHODS
The study procedure included a dose-finding period followed by a 14-day observation period. Pain intensity was recorded with a Numeric Rating Scale (NRS) at onset and 5, 10, 15, and 30 min after FBSF self-administration. Meaningful pain relief was defined as the final NRS score ≤ 3. Satisfaction survey was conducted for each patient after treatment using the Global Satisfaction Scale.
RESULTS
A total of 63 BTcP episodes occurred in 30 cancer patients. Only one patient required rescue medication at first BTcP episode and then achieved meaningful pain relief after titrating FBSF by 200 µg. Most BTcP episodes relieved within 10 min. Of 63 BTcP episodes, 30 (47.6%), 46 (73.0%), and 53 (84.1%) relieved within 5, 10, and 15 min after FBSF administration. Only grade 1/2 adverse events were reported, including somnolence, malaise, and dizziness. Of the 63 BTcP episodes, 82.6% were rated as excellent/good satisfaction with FBSF.
CONCLUSION
FBSF can be administrated "on demand" by cancer patients at the onset of BTcP, providing rapid analgesia by achieving meaningful pain relief within 10 min.
TRIAL REGISTRATION
This study was retrospectively registered 24 December, 2021 at Clinicaltrial.gov (NCT05209906): https://clinicaltrials.gov/study/NCT05209906 .
Topics: Humans; Fentanyl; Female; Male; Breakthrough Pain; Middle Aged; Analgesics, Opioid; Aged; Administration, Buccal; Adult; Pain Measurement; Cancer Pain; Pain Management; Neoplasms; Aged, 80 and over
PubMed: 38877477
DOI: 10.1186/s12904-024-01483-7 -
Scientific Reports Jun 2024Adjuvants enhance, prolong, and modulate immune responses by vaccine antigens to maximize protective immunity and enable more effective immunization in the young and...
Adjuvants enhance, prolong, and modulate immune responses by vaccine antigens to maximize protective immunity and enable more effective immunization in the young and elderly. Most adjuvants are formulated with injectable vaccines. However, an intranasal route of vaccination may induce mucosal and systemic immune responses for enhancing protective immunity in individuals and be easier to administer compared to injectable vaccines. In this study, a next generation of broadly-reactive influenza hemagglutinin (HA) vaccines were developed using the Computationally Optimized Broadly Reactive Antigen (COBRA) methodology. These HA vaccines were formulated with Mastoparan 7 (M7-NH) mast cell degranulating peptide adjuvant and administered intranasally to determine vaccine-induced seroconversion of antibodies against a panel of influenza viruses and protection following infection with H1N1 and H3N2 viruses in mice. Mice vaccinated intranasally with M7-NH-adjuvanted COBRA HA vaccines had high HAIs against a panel of H1N1 and H3N2 influenza viruses and were protected against both morbidity and mortality, with reduced viral lung titers, following challenge with an H1N1 influenza virus. Additionally, M7-NH adjuvanted COBRA HA vaccines induced Th2 skewed immune responses with robust IgG and isotype antibodies in the serum and mucosal lung lavages. Overall, this intranasally delivered M7-NH -adjuvanted COBRA HA vaccine provides effective protection against drifted H1N1 and H3N2 viruses.
Topics: Influenza Vaccines; Animals; Mice; Hemagglutinin Glycoproteins, Influenza Virus; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Adjuvants, Immunologic; Antibodies, Viral; Orthomyxoviridae Infections; Administration, Intranasal; Female; Mice, Inbred BALB C; Intercellular Signaling Peptides and Proteins; Adjuvants, Vaccine
PubMed: 38877101
DOI: 10.1038/s41598-024-64351-7 -
Scientific Reports Jun 2024We assessed the short-term effects of switching from intravitreal aflibercept (IVA) to intravitreal faricimab (IVF) on ocular blood flow in patients with...
We assessed the short-term effects of switching from intravitreal aflibercept (IVA) to intravitreal faricimab (IVF) on ocular blood flow in patients with treatment-resistant diabetic macular edema (DME). The medical records of 15 patients with DME who had received IVA injection ≥ 3 months before were retrospectively reviewed. The best-corrected visual acuity, central macular thickness (CMT) on optical coherence tomography, and mean blur rate (MBR) of all disc areas on laser speckle flowgraphy were measured before, 1 week after, and 4 weeks after IVA and IVF, respectively. The changes in visual acuity showed no significant difference after switching from IVA to IVF (P = 0.732). The mean CMT decreased significantly during the follow-up period (both P < 0.001). MBR showed no significant difference during the follow-up period (P = 0.26). However, it decreased significantly 4 weeks after IVF (P = 0.01) compared with the baseline value, but not 4 weeks after IVA (P = 0.074). A significant association was observed between decreased MBR and decreased CMT in patients who received IVF (correlation coefficient: 0.501, P = 0.005) but not in those who received IVA (P = 0.735). Thus, IVF maintained ocular blood flow reduction, although no significant differences in visual acuity and CMT changes were observed compared to IVA.
Topics: Humans; Macular Edema; Male; Female; Intravitreal Injections; Recombinant Fusion Proteins; Receptors, Vascular Endothelial Growth Factor; Middle Aged; Diabetic Retinopathy; Aged; Retrospective Studies; Visual Acuity; Tomography, Optical Coherence; Angiogenesis Inhibitors; Regional Blood Flow; Eye
PubMed: 38877041
DOI: 10.1038/s41598-024-63435-8 -
Medicine Jun 2024Magnesium Sulfate (MgSO4) is a widely used adjuvant in anesthesia. Often administered with local anesthetics, it is known to reduce analgesic and opioid consumption... (Review)
Review
Magnesium Sulfate (MgSO4) is a widely used adjuvant in anesthesia. Often administered with local anesthetics, it is known to reduce analgesic and opioid consumption while extending the duration of analgesia. MgSO4 applications extend to orthopedic surgeries, cardiovascular and urogenital procedures, offering extended postoperative pain relief. While commonly administered through various routes, there is a research gap concerning the comparative efficacy of intrathecal (IT) and intravenous (IV) MgSO4 administration. This narrative review aims to provide a comparison between IT and IV administration of MgSO4 particularly following orthopedic procedures, where pain management is paramount. A comprehensive literature search was conducted across several electronic databases, trial registries, and gray literature from inception to 2023. Inclusion criteria encompassed studies investigating the effects of perioperative IT administration of magnesium compared to perioperative IV administration of MgSO4 in patients undergoing surgery, with no language restrictions. Our search identified 4326 articles, of which 9 randomized controlled trials met our inclusion criteria. We summarized these selected articles. Four studies discussed IT magnesium sulfate (MgSO4) administration, 2 focused on IT administration in orthopedic surgeries, and 3 explored both IV and IT administration of MgSO4 in orthopedic surgery. IT MgSO4 shows promise in postoperative pain management, delaying block onset and extending duration. Personalized administration choice, considering patient factors and surgery type, is crucial. Further research is needed to refine strategies for better patient outcomes, particularly following orthopedic surgeries.
Topics: Magnesium Sulfate; Humans; Pain, Postoperative; Orthopedic Procedures; Injections, Spinal; Administration, Intravenous; Pain Management; Analgesics
PubMed: 38875416
DOI: 10.1097/MD.0000000000038522 -
Medicine Jun 2024Infective endophthalmitis is an ophthalmic infection that in severe cases can cause complete loss of vision. In children, the defense against infection is low and eye... (Observational Study)
Observational Study
Infective endophthalmitis is an ophthalmic infection that in severe cases can cause complete loss of vision. In children, the defense against infection is low and eye tissue is not fully developed, leading to increased vulnerability to endophthalmitis. Children may be unable to understand the symptoms; thus, developing a method for prevention and treatment of this disease in children is important. Therefore, we analyzed the clinical and pathogenic characteristics of infectious endophthalmitis in children and provided evidence for clinical treatment. The clinical data of 78 children (78 eyes) with infectious endophthalmitis were retrospectively analyzed. The clinical characteristics, pathogen distribution, drug sensitivity, clinical medication, and treatments were summarized and analyzed. In total, 74 (94.87%) had ocular infections caused by trauma and 75 (96.15%) were from rural townships. A total of 108 sterile specimens were examined, with a positive detection rate of 37.04%. The sensitivity rates of Gram-positive cocci and bacilli to vancomycin were 100%. The sensitivity rates of Gram-negative bacilli to ceftazidime, piperacillin/tazobactam, amikacin, gentamicin, ciprofloxacin, and levofloxacin were 100%. Of the 78 patients, 53 (67.95%) received intravitreal injection and 54 (69.23%) underwent vitrectomy. Trauma is the main factor leading to infectious endophthalmitis in children, wherein Gram-positive bacteria are the most common pathogens. Thus, a timely understanding of the pathogen and drug sensitivity is needed. Intravitreal injection and vitrectomy are effective treatments.
Topics: Humans; Endophthalmitis; Retrospective Studies; Child; Male; Female; Child, Preschool; Anti-Bacterial Agents; Infant; Eye Infections, Bacterial; Adolescent; Microbial Sensitivity Tests; Vitrectomy; Intravitreal Injections
PubMed: 38875407
DOI: 10.1097/MD.0000000000038456 -
Medicine Jun 2024Budesonide, capable of reducing vascular permeability, suppressing mucus secretion, and alleviating edema and spasms, is widely used in China for combined infectious... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Budesonide, capable of reducing vascular permeability, suppressing mucus secretion, and alleviating edema and spasms, is widely used in China for combined infectious disease treatment. This study assesses budesonide's efficacy and safety as an adjunct to azithromycin in pediatric Mycoplasma pneumonia management in China, aiming to establish a strong theoretical foundation for its clinical application.
METHODS
We conducted a comprehensive search for qualifying studies across 5 English databases and 4 Chinese databases, covering publications until October 31, 2023. Endpoint analyses were performed using standard software (Stata Corporation, College Station, TX). This study was conducted in compliance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
RESULTS
A total of 24 randomized controlled trials were involved in the current study, including 2034 patients. Our findings indicate that the combination of budesonide with azithromycin for the treatment of pediatric Mycoplasma pneumonia delivers superior therapeutic efficacy (Intravenous: odds ratio [OR], 0.156, P < .001; Sequential: OR, 0.163, P = .001; Oral: OR, 0.139, P < .001), improved pulmonary function (Forced expiratory volume in 1 second: weighted mean differences [WMD], -0.28, P = .001; Peak expiratory flow: WMD, -0.554, P = .002; Forced vital capacity: WMD, -0.321, P < .001), diminished lung inflammation (IL-6: WMD, 4.760, P = .002; c-reactive protein: WMD, 5.520, P < .001; TNF-α: WMD, 9.124, P < .001), reduced duration of fever, faster resolution of cough and rales, all without increasing the occurrence of adverse events.
CONCLUSION
The combination of budesonide and azithromycin demonstrates enhanced therapeutic effectiveness, promotes improved pulmonary function, shortens the duration of symptoms, and effectively mitigates the overexpression of inflammatory factors like c-reactive protein, TNF-α, and IL-6, all without an associated increase in adverse reactions in pediatric mycoplasma pneumonia.
Topics: Humans; Azithromycin; Pneumonia, Mycoplasma; Budesonide; Child; Drug Therapy, Combination; China; Anti-Bacterial Agents; Administration, Inhalation; Randomized Controlled Trials as Topic; Treatment Outcome; Child, Preschool; East Asian People
PubMed: 38875395
DOI: 10.1097/MD.0000000000038332 -
Medicine Jun 2024Diabetes nephropathy (DN), as one of the common complications of diabetes, is characterized by persistent albuminuria, decreased glomerular filtration rate, and elevated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diabetes nephropathy (DN), as one of the common complications of diabetes, is characterized by persistent albuminuria, decreased glomerular filtration rate, and elevated arterial blood pressure. At present, Xuebijing injection is widely used in the treatment of DN. However, few systematic reviews and meta-analysis related to Xuebijing injection intervention in DN were published. In order to more systematically and objectively evaluate the clinical efficacy of Xuebijing injection intervention in DN, we conducted systematic reviews and meta-analysis to verify it.
OBJECTIVE
The purpose of the research was to systematically evaluate the clinical efficacy of Xuebijing injection combined with alprostadil in the treatment of diabetic nephropathy.
METHODS
We searched the China National Knowledge Infrastructure (CNKI), China Biomedical Database (SinoMed), Weipu Database (VIP), Wanfang Database, PubMed, The Cochrane Library, Embase, Web of Science and other databases by computer, and searched the randomized controlled trials of Xuebijing injection combined with alprostadil in the treatment of DN at home and abroad from the establishment of the database to 2022. The main outcome indicators included blood glucose, and the secondary outcome indicators included blood lipid, renal function, urinary protein, and safety. Two evaluators independently screened the literature, extracted the data and evaluated the risk of bias in the included studies. RevMan 5.3 software was used to analyze the data.
RESULTS
A total of 14 randomized controlled trials were included, including 1233 cases, 618 cases in the treatment group and 615 cases in the control group. The results of meta-analysis demonstrated that compared with the control group, the treatment group could effectively reduce fasting plasma glucose [mean difference [MD] = -1.90, 95% CI (-2.40, -1.40), P < .00001], glycosylated hemoglobin A1c [MD = -2.38, 95% CI (-2.51, -2.25), P < .00001], 2h postprandial blood glucose [MD = -2.92, 95% CI (-3.95, -1.89), P < .00001], triacylglycerol [MD = -1.08, 95% CI (-1.66, -0.50), P = .0003], total cholesterol [MD = -1.17, 95% CI (-1.39, -0.95), P < .00001], low-density lipoprotein cholesterol [MD = -1.19, 95% CI (-1.60, -0.78), P < .00001], high-density lipoprotein cholesterol [MD = 0.32, 95% CI (0.23, 0.42), P < .00001], serum creatinine [MD = -42.95, 95% CI (-57.46, -28.43), P < .00001], blood urea nitrogen [MD = -2.24, 95%CI (-2.62,-1.86), P < .00001], blood β2 microglobulin [SMD = -1.49, 95% CI (-1.70, -1.28), P < .00001], urine β2 microglobulin [SMD = -0.81, 95% CI (-1.04, -0.58), P < .00001], 24-hour urinary protein quantification [MD = -0.20, 95% CI (-0.26, -0.14), P < .00001], urinary albumin excretion rate [SMD = -1.15, 95% CI (-1.38, -0.93), P < .00001].
CONCLUSION
Xuebijing injection combined with alprostadil has more advantages in treating DN compared to routine Western medicine.
Topics: Humans; Drugs, Chinese Herbal; Diabetic Nephropathies; Alprostadil; Drug Therapy, Combination; Injections; Randomized Controlled Trials as Topic; Blood Glucose; Treatment Outcome; Lipids
PubMed: 38875385
DOI: 10.1097/MD.0000000000032095 -
PloS One 2024Peripheral Intravenous Cannulas (PIVCs) are frequently utilised in the Emergency Department (ED) for delivery of medication and phlebotomy. They are associated with... (Observational Study)
Observational Study
Prospective observational study of peripheral intravenous cannula utilisation and frequency of intravenous fluid delivery in the emergency department-Convenience or necessity?
BACKGROUND
Peripheral Intravenous Cannulas (PIVCs) are frequently utilised in the Emergency Department (ED) for delivery of medication and phlebotomy. They are associated with complications and have an associated cost to departmental resources. A growing body of international research suggests many of the PIVCs inserted in the ED are unnecessary.
METHODS
The objective of this study was to determine the rates of PIVC insertion and use. This was a prospective observational study conducted in one UK ED and one Italian ED. Adult ED patients with non-immediate triage categories were included over a period of three weeks in the UK ED in August 2016 and two weeks in the Italian ED in March and August 2017. Episodes of PIVC insertion and data on PIVC utilisation in adults were recorded. PIVC use was classified as necessary, unnecessary or unused. The proportion of unnecessary and unused PIVCs was calculated. PIVCs were defined as unnecessary if they were either used for phlebotomy only, or solely for IV fluids in patients that could have potentially been hydrated orally (determined against a priori defined criteria). PIVC classified as unused were not used for any purpose.
RESULTS
A total of 1,618 patients were included amongst which 977 PIVCs were inserted. Of the 977 PIVCs, 413 (42%) were necessary, 536 (55%) were unnecessary, and 28 (3%) were unused. Of the unnecessary PIVCs, 473 (48%) were used solely for phlebotomy and 63 (6%) were used for IV fluids in patients that could drink.
CONCLUSIONS
More than half of PIVCs placed in the ED were unnecessary in this study. This suggests that clinical decision making about the benefits and risks of PIVC insertion is not being performed on an individual basis.
Topics: Humans; Emergency Service, Hospital; Prospective Studies; Female; Male; Middle Aged; Aged; Catheterization, Peripheral; Adult; Fluid Therapy; Cannula; Phlebotomy; Aged, 80 and over; Administration, Intravenous; United Kingdom
PubMed: 38875242
DOI: 10.1371/journal.pone.0305276 -
JAMA Network Open Jun 2024Guidelines recommend an analgesia-first strategy for sedation during mechanical ventilation, but associations between opioids provided during mechanical ventilation and...
IMPORTANCE
Guidelines recommend an analgesia-first strategy for sedation during mechanical ventilation, but associations between opioids provided during mechanical ventilation and posthospitalization opioid-related outcomes are unclear.
OBJECTIVE
To evaluate associations between an intravenous opioid dose received during mechanical ventilation and postdischarge opioid-related outcomes in medical (nonsurgical) patients.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study evaluated adults receiving mechanical ventilation lasting 24 hours or more for acute respiratory failure and surviving hospitalization. Participants from 21 Kaiser Permanente Northern California hospitals from January 1, 2012, to December 31, 2019, were included. Data were analyzed from October 1, 2020, to October 31, 2023.
EXPOSURES
Terciles of median daily intravenous fentanyl equivalents during mechanical ventilation.
MAIN OUTCOMES AND MEASURES
The primary outcome was the first filled opioid prescription in 1 year after discharge. Secondary outcomes included persistent opioid use and opioid-associated complications. Secondary analyses tested for interaction between opioid doses during mechanical ventilation, prior opioid use, and posthospitalization opioid use. Estimates were based on multivariable-adjusted time-to-event analyses, with death as a competing risk, and censored for hospice or palliative care referral, rehospitalization with receipt of opioid, or loss of Kaiser Permanente plan membership.
RESULTS
The study included 6746 patients across 21 hospitals (median age, 67 years [IQR, 57-76 years]; 53.0% male). Of the participants, 3114 (46.2%) filled an opioid prescription in the year prior to admission. The median daily fentanyl equivalent during mechanical ventilation was 200 μg (IQR, 40-1000 μg), with terciles of 0 to 67 μg, more than 67 to 700 μg, and more than 700 μg. Compared with patients who did not receive opioids during mechanical ventilation (n = 1013), a higher daily opioid dose was associated with opioid prescriptions in the year after discharge (n = 2942 outcomes; tercile 1: adjusted hazard ratio [AHR], 1.00 [95% CI, 0.85-1.17], tercile 2: AHR, 1.20 [95% CI, 1.03-1.40], and tercile 3: AHR, 1.25 [95% CI, 1.07-1.47]). Higher doses of opioids during mechanical ventilation were also associated with persistent opioid use after hospitalization (n = 1410 outcomes; tercile 3 vs no opioids: odds ratio, 1.44 [95% CI, 1.14-1.83]). No interaction was observed between opioid dose during mechanical ventilation, prior opioid use, and posthospitalization opioid use.
CONCLUSIONS AND RELEVANCE
In this retrospective cohort study of patients receiving mechanical ventilation, opioids administered during mechanical ventilation were associated with opioid prescriptions following hospital discharge. Additional studies to evaluate risks and benefits of strategies using lower opioid doses are warranted.
Topics: Humans; Male; Female; Analgesics, Opioid; Respiration, Artificial; Retrospective Studies; Middle Aged; Patient Discharge; Aged; California; Respiratory Insufficiency; Administration, Intravenous
PubMed: 38874921
DOI: 10.1001/jamanetworkopen.2024.17292