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Infection Apr 2023The coronavirus disease 2019 (COVID-19) pandemic has been a global health emergency since December 2019, leading to millions of deaths worldwide and placing significant... (Review)
Review
BACKGROUND
The coronavirus disease 2019 (COVID-19) pandemic has been a global health emergency since December 2019, leading to millions of deaths worldwide and placing significant pressures, including economic burden, on individual patients and healthcare systems. As of February 2022, remdesivir is the only US Food and Drug Administration (FDA)-approved treatment for severe COVID-19. This systematic literature review (SLR) aimed to summarise economic evaluations, and cost and resource use (CRU) evidence related to remdesivir during the COVID-19 pandemic.
METHODS
Searches of MEDLINE, Embase the International Health Technology Assessment (HTA) database, reference lists, congresses and grey literature were performed in May 2021. Articles were reviewed for relevance against pre-specified criteria by two independent reviewers and study quality was assessed using published checklists.
RESULTS
Eight studies reported resource use and five reported costs related to remdesivir. Over time, the prescription rate of remdesivir increased and time from disease onset to remdesivir initiation decreased. Remdesivir was associated with a 6% to 21.3% decrease in bed occupancy. Cost estimates for remdesivir ranged widely, from $10 to $780 for a 10-day course. In three out of four included economic evaluations, remdesivir treatment scenarios were cost-effective, ranging from ~ 8 to ~ 23% of the willingness-to-pay threshold for the respective country.
CONCLUSIONS
Economic evidence relating to remdesivir should be interpreted with consideration of the broader clinical context, including patients' characteristics and the timing of its administration. Nonetheless, remdesivir remains an important option for physicians in aiming to provide optimal care and relieve pressure on healthcare systems through shifting phases of the pandemic.
Topics: United States; Humans; COVID-19; Cost-Benefit Analysis; Pandemics; COVID-19 Drug Treatment
PubMed: 36224452
DOI: 10.1007/s15010-022-01930-8 -
Nefrologia 2021Hepatitis C is an important agent of liver damage in patients with chronic kidney disease and the advent of DAAs has dramatically changed the management of HCV positive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hepatitis C is an important agent of liver damage in patients with chronic kidney disease and the advent of DAAs has dramatically changed the management of HCV positive patients, including those with advanced CKD. Sofosbuvir is the backbone of many anti-HCV regimens based on DAAs but it remains unclear whether it is appropriate for HCV-infected patients with stage 4-5 CKD.
STUDY AIMS AND DESIGN
We performed a systematic review of the literature with a meta-analysis of clinical studies in order to evaluate the efficacy and safety of SOF-based DAA regimens in patients with stage 4-5 CKD. The primary outcome was sustained viral response (as a measure of efficacy); the secondary outcomes were the frequency of SAEs and drop-outs due to AEs (as measures of tolerability). The random-effects model of DerSimonian and Laird was adopted, with heterogeneity and stratified analyses.
RESULTS
Thirty clinical studies (n=1537 unique patients) were retrieved. The pooled SVR12 and SAEs rate was 0.99 (95% confidence intervals, 0.97; 1.0, I=99.8%) and 0.09 (95% CI, 0.05; 0.13, I=84.3%), respectively. The pooled SVR12 rate in studies with high HCV RNA levels at baseline was lower, 0.87 (95% CI, 0.75; 1.0, I=73.3%) (P<0.001). The pooled drop-out rate due to AEs was 0.02 (95% CI, -0.01; 0.04, I=16.1%). Common serious adverse events were anemia (n=26, 38%) and reduced eGFR (n=14, 19%). SAEs were more common in studies adopting full-dose sofosbuvir (pooled rate of SAEs 0.15, 95% CI, 0.06; 0.25; I=80.1%) and in those based on ribavirin (0.15, 95% CI, 0.07; 0.23, I=95.8%). Six studies (n=69 patients) reported eGFR levels at baseline/post- antiviral therapy; no consistent changes were found.
CONCLUSIONS
SOF-based regimens appear safe and effective in patients with stage 4-5 CKD. Serum creatinine should be carefully monitored during therapy with SOF in patients with CKD. Randomized controlled studies in order to expand our knowledge on this point are under way.
Topics: Antiviral Agents; Creatinine; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Kidney Failure, Chronic; RNA; Renal Insufficiency, Chronic; Ribavirin; Sofosbuvir; Sustained Virologic Response
PubMed: 36165141
DOI: 10.1016/j.nefroe.2021.11.011 -
Medicina (Kaunas, Lithuania) Aug 2022: Probiotic supplementation can prevent and alleviate gastrointestinal and respiratory tract infections in healthy individuals. Markers released from the site of... (Review)
Review
: Probiotic supplementation can prevent and alleviate gastrointestinal and respiratory tract infections in healthy individuals. Markers released from the site of inflammation are involved in the response to infection or tissue injury. Therefore, we measured the pre-exercise and postexercise levels of inflammation-related markers-tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, IL-10, interferon (IFN)-γ, salivary immunoglobulin A (IgA), IL-1β, IL-2, IL-4, and C-reactive protein (CRP)-in probiotic versus placebo groups to investigate the effects of probiotics on these markers in athletes. Probiotics contained multiple species (e.g., , etc.). : We performed a systematic search for studies published until May 2022 and included nine randomized clinical trials. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Fixed-effects meta-analyses and sensitivity analyses were performed. Subgroup analyses were conducted on the basis of the period of probiotic intervention and timing of postassessment blood sampling. : The levels of IFN-γ and salivary IgA exhibited a significant positive change, whereas those of TNF-α and IL-10 demonstrated a negative change in the probiotic group. The subgroup analysis revealed that the probiotic group exhibited significant negative changes in TNF-α and IL-10 levels in the shorter intervention period. For the subgroup based on the timing of postassessment blood sampling, the subgroup whose blood sample collection was delayed to at least the next day of exercise exhibited significant negative changes in their TNF-α and IL-10 levels. The subgroups whose blood samples were collected immediately after exercise demonstrated negative changes in their TNF-α, IL-8, and IL-10 levels. : Probiotic supplementation resulted in significant positive changes in the IFN-γ and salivary IgA levels and negative changes in the IL-10 and TNF-α levels. No significant changes in the IL-1β, IL-2, IL-4, IL-6, IL-8, or CRP levels were observed after probiotic use in athletes.
Topics: Athletes; Biomarkers; C-Reactive Protein; Humans; Immunoglobulin A; Inflammation; Interferon-gamma; Interleukin-10; Interleukin-2; Interleukin-4; Interleukin-6; Interleukin-8; Probiotics; Randomized Controlled Trials as Topic; Tumor Necrosis Factor-alpha
PubMed: 36143865
DOI: 10.3390/medicina58091188 -
Journal of Personalized Medicine Sep 2022DAA therapy is known to clear hepatitis C virus infection in patients with decompensated cirrhosis (DC). However, the safety and benefits of DAA in DC remain unclear,... (Review)
Review
DAA therapy is known to clear hepatitis C virus infection in patients with decompensated cirrhosis (DC). However, the safety and benefits of DAA in DC remain unclear, especially with the use of protease inhibitors (PI). Therefore, we evaluated the efficacy and clinical safety of DAA in DC patients and observed whether there was a discrepancy between PI-based and non-PI-based treatment. We searched Ovid-Medline, Ovid-EMBASE, Cochrane Library, and three local medical databases through October 2021 to identify relevant studies on the clinical safety and effectiveness of DAA in DC patients. The outcomes were sustained virologic response (SVR), overall mortality, the incidence rate of hepatocellular carcinoma (HCC), adverse events, improvement or deterioration of liver function, and delisting from liver transplantation (LT). Two independent reviewers extracted the data from each study using a standardized form. The pooled event rate in DC patients and relative effect (odds ratio (OR)) of PI-treated versus non-PI-based DAA in DC patients were calculated using a random-effects model. In patients with DC, the SVR rate was 86% (95% CI 83-88%), the development of HCC 7% (95% CI 5-9%), and mortality 6% (95% CI 4-8%). Improvement in liver function was observed in 51% (95% CI 44-58%) of patients, and 16% (95% CI 5-40%) were delisted from LT. PI-based treatment showed a similar rate of serious adverse events (23% vs. 18%), HCC occurrence (5% vs. 7%), and mortality (5% vs. 6%) to that of non-PI-based DAA treatment in DC patients. HCC occurrence and mortality rates were low in patients with DC following DAA treatment. PI-based treatment in DC patients was relatively safe when compared to non-PI-based treatment. Overall, DAA improved liver function, which may have allowed for delisting from LT.
PubMed: 36143302
DOI: 10.3390/jpm12091517 -
Frontiers in Immunology 2022This systematic review aimed to investigate immune-inflammatory and hypothalamic-pituitary-adrenal (HPA) axis biomarkers in individuals with non-specific low back pain...
UNLABELLED
This systematic review aimed to investigate immune-inflammatory and hypothalamic-pituitary-adrenal (HPA) axis biomarkers in individuals with non-specific low back pain (NSLBP) compared to healthy control. The search was performed in five databases until 4 November 2021. Two reviewers independently conducted screenings, data extraction, risk of bias, and methodological quality assessment of 14 unique studies. All studies reported the source of the fluid analyzed: nine studies used serum, two used plasma, one used serum and plasma, and two studies used salivary cortisol. We found preliminary and limited evidence (only one study for each biomarker) of increased levels in growth differentiation factor 15 (GDF-15), interleukin-23 (IL-23), transforming growth factor-beta (TGF-β), and soluble tumor necrosis factor receptor 1 (sTNF-R1) in NSLBP. Inconsistent and limited evidence was identified for interleukin-10 (IL-10). Although C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels appear to increase in NSLBP, only one study per each biomarker reported statistically significant differences. Interleukin-1 beta (IL-1β), interleukin-17 (IL-17), interferon gamma (IFN-γ), and high-sensitivity CRP (hsCRP) showed no significant differences. Regarding cortisol, one study showed a significant increase and another a significant decrease. More robust evidence between GDF-15, IL-23, TGF-β, and sTNF-R1 with NSLBP is needed. Moreover, contrary to the findings reported in previous studies, when comparing results exclusively with healthy control, insufficient robust evidence for IL-6, TNF-α, and CRP was found in NSLBP. In addition, cortisol response (HPA-related biomarker) showed a dysregulated functioning in NSLBP, with incongruent evidence regarding its directionality. Therefore, our effort is to find adjusted evidence to conclude which immune-inflammatory and HPA axis biomarkers are altered in NSLBP and how much their levels are affected.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020176153, identifier CRD42020176153.
Topics: Biomarkers; C-Reactive Protein; Growth Differentiation Factor 15; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Interferon-gamma; Interleukin-10; Interleukin-17; Interleukin-1beta; Interleukin-23; Interleukin-6; Low Back Pain; Pituitary-Adrenal System; Receptors, Tumor Necrosis Factor; Transforming Growth Factor beta; Transforming Growth Factors; Tumor Necrosis Factor-alpha
PubMed: 36119028
DOI: 10.3389/fimmu.2022.945513 -
The Cochrane Database of Systematic... Sep 2022Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that has been approved for the treatment of depression, obsessive-compulsive disorder, and a variety of... (Review)
Review
BACKGROUND
Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that has been approved for the treatment of depression, obsessive-compulsive disorder, and a variety of anxiety disorders; it is available as an oral preparation. Fluvoxamine has not been approved for the treatment of infections, but has been used in the early treatment of people with mild to moderate COVID-19. As there are only a few effective therapies for people with COVID-19 in the community, a thorough understanding of the current evidence regarding the efficacy and safety of fluvoxamine as an anti-inflammatory and possible anti-viral treatment for COVID-19, based on randomised controlled trials (RCTs), is needed.
OBJECTIVES
To assess the efficacy and safety of fluvoxamine in addition to standard care, compared to standard care (alone or with placebo), or any other active pharmacological comparator with proven efficacy for the treatment of COVID-19 outpatients and inpatients.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register (including Cochrane Central Register of Controlled Trials, MEDLINE, Embase, ClinicalTrials.gov, WHO ICTRP, medRxiv), Web of Science and WHO COVID-19 Global literature on COVID-19 to identify completed and ongoing studies up to 1 February 2022.
SELECTION CRITERIA
We included RCTs that compared fluvoxamine in addition to standard care (also including no intervention), with standard care (alone or with placebo), or any other active pharmacological comparator with proven efficacy in clinical trials for the treatment of people with confirmed COVID-19, irrespective of disease severity, in both inpatients and outpatients. Co-interventions needed to be the same in both study arms. We excluded studies comparing fluvoxamine to other pharmacological interventions with unproven efficacy.
DATA COLLECTION AND ANALYSIS
We assessed risk of bias of primary outcomes using the Cochrane Risk of Bias 2 tool for RCTs. We used GRADE to rate the certainty of evidence to treat people with asymptomatic to severe COVID-19 for the primary outcomes including mortality, clinical deterioration, clinical improvement, quality of life, serious adverse events, adverse events of any grade, and suicide or suicide attempt.
MAIN RESULTS
We identified two completed studies with a total of 1649 symptomatic participants. One study was conducted in the USA (study with 152 participants, 80 and 72 participants per study arm) and the other study in Brazil (study with 1497 high-risk participants for progression to severe disease, 741 and 756 participants per study arm) among outpatients with mild COVID-19. Both studies were double-blind, placebo-controlled trials in which participants were prescribed 100 mg fluvoxamine two or three times daily for a maximum of 15 days. We identified five ongoing studies and two studies awaiting classification (due to translation issues, and due to missing published data). We found no published studies comparing fluvoxamine to other pharmacological interventions of proven efficacy. We assessed both included studies to have an overall high risk of bias. Fluvoxamine for the treatment of COVID-19 in inpatients We did not identify any completed studies of inpatients. Fluvoxamine for the treatment of COVID-19 in outpatients Fluvoxamine in addition to standard care may slightly reduce all-cause mortality at day 28 (RR 0.69, 95% CI 0.38 to 1.27; risk difference (RD) 9 per 1000; 2 studies, 1649 participants; low-certainty evidence), and may reduce clinical deterioration defined as all-cause hospital admission or death before hospital admission (RR 0.55, 95% CI 0.16 to 1.89; RD 57 per 1000; 2 studies, 1649 participants; low-certainty evidence). We are very uncertain regarding the effect of fluvoxamine on serious adverse events (RR 0.56, 95% CI 0.15 to 2.03; RD 54 per 1000; 2 studies, 1649 participants; very low-certainty evidence) or adverse events of any grade (RR 1.06, 95% CI 0.82 to 1.37; RD 7 per 1000; 2 studies, 1649 participants; very low-certainty evidence). Neither of the studies reported on symptom resolution (clinical improvement), quality of life or suicide/suicide attempt.
AUTHORS' CONCLUSIONS
Based on a low-certainty evidence, fluvoxamine may slightly reduce all-cause mortality at day 28, and may reduce the risk of admission to hospital or death in outpatients with mild COVID-19. However, we are very uncertain regarding the effect of fluvoxamine on serious adverse events, or any adverse events. In accordance with the living approach of this review, we will continually update our search and include eligible trials as they arise, to complete any gaps in the evidence.
Topics: Clinical Deterioration; Fluvoxamine; Humans; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; COVID-19 Drug Treatment
PubMed: 36103313
DOI: 10.1002/14651858.CD015391 -
Frontiers in Immunology 2022Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved innate-like T cells capable of recognizing bacterial and fungal ligands derived from vitamin B...
Mining the multifunction of mucosal-associated invariant T cells in hematological malignancies and transplantation immunity: A promising hexagon soldier in immunomodulatory.
Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved innate-like T cells capable of recognizing bacterial and fungal ligands derived from vitamin B biosynthesis. Under different stimulation conditions, MAIT cells can display different immune effector phenotypes, exerting immune regulation and anti-/protumor responses. Based on basic biological characteristics, including the enrichment of mucosal tissue, the secretion of mucosal repair protective factors (interleukin-17, ), and the activation of riboflavin metabolites by intestinal flora, MAIT cells may play an important role in the immune regulation effect of mucosal lesions or inflammation. At the same time, activated MAIT cells secrete granzyme B, perforin, interferon γ, and other toxic cytokines, which can mediate anti-tumor effects. In addition, since a variety of hematological malignancies express the targets of MAIT cell-specific effector molecules, MAIT cells are also a potentially attractive target for cell therapy or immunotherapy for hematological malignancies. In this review, we will provide an overview of MAIT research related to blood system diseases and discuss the possible immunomodulatory or anti-tumor roles that unique biological characteristics or effector phenotypes may play in hematological diseases.
Topics: Cytokines; Hematologic Neoplasms; Humans; Interferon-gamma; Military Personnel; Mucosal-Associated Invariant T Cells
PubMed: 36052080
DOI: 10.3389/fimmu.2022.931764 -
International Journal of Molecular... Aug 2022Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral agent that causes Coronavirus disease 2019 (COVID-19), a disease that causes flu-like symptoms... (Review)
Review
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a viral agent that causes Coronavirus disease 2019 (COVID-19), a disease that causes flu-like symptoms that, when exacerbated, can have life-threatening consequences. COVID-19 has been linked to persistent symptoms, sequelae, and medical complications that can last months after the initial infection. This systematic review aims to elucidate the innate and adaptive immune mechanisms involved and identify potential characteristics of COVID-19 pathology that may increase symptom duration. We also describe he three different stages of COVID-19-viral replication, immune hyperactivation, and post-acute sequelae-as well as each phase's corresponding immune response. Finally, we use this multiphasic approach to describe different treatment approaches for each of the three stages-antivirals, immunosuppressants and monoclonal antibodies, and continued immunosuppressants-to fully curate the treatment to the stage of disease.
Topics: Antiviral Agents; Humans; Immunosuppressive Agents; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35955740
DOI: 10.3390/ijms23158606 -
Frontiers in Pharmacology 2022As a cause of respiratory tract infections in humans, influenza remains with high morbidity and mortality, with associated significant healthcare burden and increased...
As a cause of respiratory tract infections in humans, influenza remains with high morbidity and mortality, with associated significant healthcare burden and increased financial burden. Traditional Chinese medicine injections (TCMIs) combined with oseltamivir (TCMIs + oseltamivir) are the representative therapeutic strategies for influenza, which is a compliant with clinical applications in China. The aim of this study was to describe the comparative efficacy and safety of TCMIs + oseltamivir in patients with influenza, based on the current evidence. PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, VIP information resource integration service platform databases, and the Chinese biomedical literature service system were searched to find randomized controlled trials where TCMIs + oseltamivir are the representative therapeutic strategies for influenza, from inception until October 2021, without language restriction. Two investigators independently screened eligibility criteria, extracted data, and appraised the risk of bias with the same criteria. We conducted a network meta-analysis using the Bayesian random method for each outcome and performed the sensitivity analysis, meta-regression, and Egger's and Begg's tests for the reliability and robustness of our results. Thirty-one trials including 2,893 participants proved eligible and reported on four TCMIs + oseltamivir oseltamivir. Network meta-analysis showed Yanhuning (YHN) +oseltamivir (MD = -1.7, 95% CrI: -2.5 to -0.88; SUCRA = 0.89; low certainty of evidence) in fever disappearance time, Tanreqing (TRQ) +oseltamivir (MD = -1.9, 95% CrI: -2.8 to -1; SUCRA = 0.97; low certainty of evidence) in cough disappearance time, and Xiyanping (XYP) +oseltamivir (OR = 5.9, 95% CrI: 3.1 to 11; SUCRA = 0.82; very low certainty of evidence) in the response rate to be more efficacious than oseltamivir alone with the best SUCRA. Based on the combined SUCRA value for primary outcomes, TRQ + oseltamivir is probably better in cough disappearance time, and XYP + oseltamivir and YHN + oseltamivir may be better in fever disappearance time than others. No significant difference in safety between the treatments. In patients with influenza, TCMIs + oseltamivir only partially improve flu symptoms. Overall therapeutic efficacy and safety are inconclusive, based on low to very low certainty of evidence. However, the safety remains uncertain, and TCMI treatments for influenza should be considered with caution. More high-quality studies examining the efficacy and safety of TCMIs are needed. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021286994.
PubMed: 35935865
DOI: 10.3389/fphar.2022.848770 -
Transboundary and Emerging Diseases Nov 2022Within-host model specified by viral dynamic parameters is a mainstream tool to understand SARS-CoV-2 replication cycle in infected patients. The parameter uncertainty... (Meta-Analysis)
Meta-Analysis
Within-host model specified by viral dynamic parameters is a mainstream tool to understand SARS-CoV-2 replication cycle in infected patients. The parameter uncertainty further affects the output of the model, such as the efficacy of potential antiviral drugs. However, gathering empirical data on these parameters is challenging. Here, we aim to conduct a systematic review of viral dynamic parameters used in within-host models by calibrating the model to the viral load data measured from upper respiratory specimens. We searched the PubMed, Embase and Web of Science databases (between 1 December 2019 and 10 February 2022) for within-host modelling studies. We identified seven independent within-host models from the above nine studies, including Type I interferon, innate response, humoral immune response or cell-mediated immune response. From these models, we extracted and analyse seven widely used viral dynamic parameters including the viral load at the point of infection or symptom onset, the rate of viral particles infecting susceptible cells, the rate of infected cells releasing virus, the rate of virus particles cleared, the rate of infected cells cleared and the rate of cells in the eclipse phase can become productively infected. We identified seven independent within-host models from nine eligible studies. The viral load at symptom onset is 4.78 (95% CI:2.93, 6.62) log(copies/ml), and the viral load at the point of infection is -1.00 (95% CI:-1.94, -0.05) log(copies/ml). The rate of viral particles infecting susceptible cells and the rate of infected cells cleared have the pooled estimates as -6.96 (95% CI:-7.66, -6.25) log([copies/ml] day ) and 0.92 (95% CI:-0.09, 1.93) day , respectively. We found that the rate of infected cells cleared was associated with the reported model in the meta-analysis by including the model type as a categorical variable (p < .01). Joint viral dynamic parameters estimates when parameterizing within-host models have been published for SARS-CoV-2. The reviewed viral dynamic parameters can be used in the same within-host model to understand SARS-CoV-2 replication cycle in infected patients and assess the impact of pharmaceutical interventions.
Topics: Animals; COVID-19; SARS-CoV-2; Antiviral Agents; Serologic Tests
PubMed: 35907777
DOI: 10.1111/tbed.14673