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Thread: Covid 19: adjuvant approaches etc,

  1. #131
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    Study of interest:

    Crit Care. 2021; 25: 223.

    Evaluation of thiamine as adjunctive therapy in COVID-19 critically ill patients: a two-center propensity score matched study

    Abstract
    Background

    Thiamine is a precursor of the essential coenzyme thiamine pyrophosphate required for glucose metabolism; it improves the immune system function and has shown to reduce the risk of several diseases. The role of thiamine in critically ill septic patient has been addressed in multiple studies; however, it’s role in COVID-19 patients is still unclear. The aim of this study was to evaluate the use of thiamine as an adjunctive therapy on mortality in COVID-19 critically ill patients.
    Methods

    This is a two-center, non-interventional, retrospective cohort study for critically ill patients admitted to intensive care units (ICUs) with a confirmed diagnosis of COVID19. All patients aged 18 years or older admitted to ICUs between March 1, 2020, and December 31, 2020, with positive PCR COVID-19 were eligible for inclusion. We investigated thiamine use as an adjunctive therapy on the clinical outcomes in critically ill COVID-19 patients after propensity score matching.
    Results

    A total of 738 critically ill patients with COVID-19 who had been admitted to ICUs were included in the study. Among 166 patients matched using the propensity score method, 83 had received thiamine as adjunctive therapy. There was significant association between thiamine use with in-hospital mortality (OR = 0.39; 95% CI 0.19–0.78; P value = 0.008) as well as the 30-day mortality (OR = 0.37; 95% CI 0.18–0.78; P value = 0.009). Moreover, patients who received thiamine as an adjunctive therapy were less likely to have thrombosis during ICU stay [OR (95% CI) 0.19 (0.04–0.88), P value = 0.03].
    Conclusion

    Thiamine use as adjunctive therapy may have potential survival benefits in critically ill patients with COVID-19. Additionally, it was associated with a lower incidence of thrombosis. Further interventional studies are required to confirm these findings.

    https://www.ncbi.nlm.nih.gov/labs/pm...es/PMC8242279/
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  2. #132
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    Study of interest on Vite C:

    Vitamin C Intervention for Critical COVID-19: A Pragmatic Review of the Current Level of Evidence

    Life 2021 November 1, 11 (11)

    Severe respiratory infections are characterized by elevated inflammation and generation of reactive oxygen species (ROS) which may lead to a decrease in antioxidants such as vitamin C and a higher requirement for the vitamin. Administration of intravenous vitamin C to patients with pneumonia and sepsis appears to decrease the severity of the disease and potentially improve survival rate.

    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes pneumonia, sepsis and acute respiratory distress syndrome (ARDS) in severe cases, and is referred to as coronavirus disease 2019 (COVID-19). Patients with COVID-19 infection also appear to have depleted vitamin C status and require additional supplementation of vitamin C during the acute phase of the disease. To date there have been 12 vitamin C and COVID-19 trials published, including five randomised controlled trials (RCTs) and seven retrospective cohort studies.

    The current level of evidence from the RCTs suggests that intravenous vitamin C intervention may improve oxygenation parameters, reduce inflammatory markers, decrease days in hospital and reduce mortality, particularly in the more severely ill patients. High doses of oral vitamin C supplementation may also improve the rate of recovery in less severe cases. No adverse events have been reported in published vitamin C clinical trials in COVID-19 patients. Upcoming findings from larger RCTs will provide additional evidence on vitamin supplementation in COVID-19 patients.

    https://read.qxmd.com/read/34833042/...el-of-evidence
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  3. #133
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    A year + I have stressed this (see article linked in OP...), data piling up. Some times being right about a thing is more frustrating then satisfying when you know lives are at stake:

    Redox Biol. 2021 Sep; 45: 102041.

    SARS-CoV2 infection impairs the metabolism and redox function of cellular glutathione

    Abstract

    Viral infections sustain their replication cycle promoting a pro-oxidant environment in the host cell. In this context, specific alterations of the levels and homeostatic function of the tripeptide glutathione have been reported to play a causal role in the pro-oxidant and cytopathic effects (CPE) of the virus. In this study, these aspects were investigated for the first time in SARS-CoV2-infected Vero E6 cells, a reliable and well-characterized in vitro model of this infection. SARS-CoV2 markedly decreased the levels of cellular thiols, essentially lowering the reduced form of glutathione (GSH). Such an important defect occurred early in the CPE process (in the first 24 hpi). Thiol analysis in N-acetyl-Cys (NAC)-treated cells and membrane transporter expression data demonstrated that both a lowered uptake of the GSH biosynthesis precursor Cys and an increased efflux of cellular thiols, could play a role in this context. Increased levels of oxidized glutathione (GSSG) and protein glutathionylation were also observed along with upregulation of the ER stress marker PERK. The antiviral drugs Remdesivir (Rem) and Nelfinavir (Nel) influenced these changes at different levels, essentially confirming the importance or blocking viral replication to prevent GSH depletion in the host cell. Accordingly, Nel, the most potent antiviral in our in vitro study, produced a timely activation of Nrf2 transcription factor and a GSH enhancing response that synergized with NAC to restore GSH levels in the infected cells. Despite poor in vitro antiviral potency and GSH enhancing function, Rem treatment was found to prevent the SARS-CoV2-induced glutathionylation of cellular proteins. In conclusion, SARS-CoV2 infection impairs the metabolism of cellular glutathione. NAC and the antiviral Nel can prevent such defect in vitro.

    Full paper:

    https://www.ncbi.nlm.nih.gov/labs/pm...es/PMC8190457/
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  4. #134
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    Will, have you looked at any of the information on betadine nasal spray. I’ve seen a few “journalistic” articles downplaying it, but there seems to be actual scientific studies showing it to be a effective way to protect against infection.

  5. #135
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    Quote Originally Posted by Inkslinger View Post
    Will, have you looked at any of the information on betadine nasal spray. I’ve seen a few “journalistic” articles downplaying it, but there seems to be actual scientific studies showing it to be a effective way to protect against infection.
    Have not gotten too deep dive into the topic. Being topical, it would seem timing is everything and you'd wanna do it soon as you got home after being out and exposed. Some recommend 4-6 times per day, which is gonna be a real PITA. It's popular in places like India where they don't always have adequate PPE and such. Here's some papers I found:

    https://pubmed.ncbi.nlm.nih.gov/?lin...m_uid=33846691
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  6. #136
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    This actually connects to #133 above well if you can connect those dots, and the big picture stuff I have been stressing since the start. Now, we can even test for it (oxidative stress driven by ROS -> hyper immune response -> bad chit happens) and perhaps make predictions on how sick someone make get. Make no mistake, this game changing stuff, that will continue to get crickets from the mainstream, as well as some of the crew people view as alternatives to that.

    This is the first paper I have seen that found oxidative stress an aspect of mild cases of covid, and is a worth while read. The authors also suggest methods of mitigation also. This sentence caught my attention:

    “Severe COVID-19 is marked by extensive inflammatory pathology that can affect various organs within the body. Immune cell infiltration leads to the reduction of antioxidants and to the production of reactive oxygen species (ROS) that are thought to induce an inflammation-driven oxidative storm in COVID-19…


    For almost 2 years now (1), I posit that is in fact the primary driver of the damage and or death caused by that virus… The article has been updated just recently BTW. Onto this new paper:

    Mild Coronavirus Disease 2019 (COVID-19) Is Marked by Systemic Oxidative Stress: A Pilot Study
    Antioxidants 2021, 10(12), 2022;
    Abstract

    Oxidative stress has been implicated to play a critical role in the pathophysiology of coronavirus disease 2019 (COVID-19) and may therefore be considered as a relevant therapeutic target. Serum free thiols (R-SH, sulfhydryl groups) comprise a robust marker of systemic oxidative stress, since they are readily oxidized by reactive oxygen species (ROS).

    In this study, serum free thiol concentrations were measured in hospitalized and non-hospitalized patients with COVID-19 and healthy controls and their associations with relevant clinical parameters were examined. Serum free thiol concentrations were measured colorimetrically (Ellman’s method) in 29 non-hospitalized COVID-19 subjects and 30 age-, sex-, and body-mass index (BMI)-matched healthy controls and analyzed for associations with clinical and biochemical disease parameters. Additional free thiol measurements were performed on seven serum samples from COVID-19 subjects who required hospitalization to examine their correlation with disease severity. Non-hospitalized subjects with COVID-19 had significantly lower concentrations of serum free thiols compared to healthy controls (p = 0.014), indicating oxidative stress. Serum free thiols were positively associated with albumin (St. β = 0.710, p < 0.001) and inversely associated with CRP (St. β = −0.434, p = 0.027), and showed significant discriminative ability to differentiate subjects with COVID-19 from healthy controls (AUC = 0.69, p = 0.011), which was slightly higher than the discriminative performance of CRP concentrations regarding COVID-19 diagnosis (AUC = 0.66, p = 0.042).

    This study concludes that systemic oxidative stress is increased in patients with COVID-19 compared with healthy controls. This opens an avenue of treatment options since free thiols are amenable to therapeutic modulation.

    Full paper:

    https://www.mdpi.com/2076-3921/10/12/2022/htm

    And another:

    "A useful and sensitive marker in the prediction of COVID-19 and disease severity: Thiol"

    https://pubmed.ncbi.nlm.nih.gov/33588050/

    Data continues to grow, could save lives and see less hospitalizations, and it's crickets...

    (1) https://brinkzone.com/life-saving-st...complications/
    - Will

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    “Those who do not view armed self defense as a basic human right, ignore the mass graves of those who died on their knees at the hands of tyrants.”

  7. #137
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    Topic of interest, those following the lit are aware that the SSRI fluvoxamine has shown great promise as an effective treatment for covid per a recent study in the Lancet etc. (1, 2)
    What is the mechanism of action?

    Studies find it to have anti-inflammatory effects, but miss the actual reason why that is. Fluvoxamine appears to regulate Sig-1R receptors and It seems that Sig-1R also regulates generation of reactive oxygen species (ROS) in the mitochondria (3), which supports the model I proposed going on two years now as to what the driver is of the hyper immune response to covid begins and the primary targets of treatment:

    https://brinkzone.com/life-saving-st...complications/


    (1) https://www.thelancet.com/journals/l...448-4/fulltext
    (2) https://link.springer.com/article/10...65-021-01636-5

    (3) https://www.frontiersin.org/articles...019.00733/full
    - Will

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    “Those who do not view armed self defense as a basic human right, ignore the mass graves of those who died on their knees at the hands of tyrants.”

  8. #138
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    Covid Study Of Interest:

    Cohort study to evaluate the effect of vitamin D, magnesium, and vitamin B12 in combination on progression to severe outcomes in older patients with coronavirus (COVID-19)

    Nutrition
    Volumes 79–80, November–December 2020, 111017

    Abstract

    Objectives
    The aim of this study was to determine clinical outcomes of older patients with coronavirus (COVID-19) who received a combination of vitamin D, magnesium, and vitamin B12 (DMB) compared with those who did not. We hypothesized that fewer patients administered this combination would require oxygen therapy, intensive care support, or a combination of both than those who did not.

    Methods
    This was a cohort observational study of all consecutive hospitalized patients ≥50 y of age with COVID-19 in a tertiary academic hospital. Before April 6, 2020, no patients received the (DMB) combination. After this date, patients were administered 1000 IU/d oral vitamin D3, 150 mg/d oral magnesium, and 500 mcg/d oral vitamin B12 upon admission if they did not require oxygen therapy. Primary outcome was deterioration leading to any form of oxygen therapy, intensive care support, or both.

    Results
    Between January 15 and April 15, 2020, we identified 43 consecutive patients ≥50 y of age with COVID-19. Seventeen patients received DMB before onset of primary outcome and 26 patients did not. Baseline demographic characteristics between the two groups were significantly different by age. In univariate analysis, age and hypertension had a significant influence on outcome. After adjusting for age or hypertension separately in a multivariate analysis, the intervention group retained protective significance. Fewer treated patients than controls required initiation of oxygen therapy during hospitalization (17.6 vs 61.5%, P = 0.006). DMB exposure was associated with odds ratios of 0.13 (95% confidence interval [CI], 0.03–0.59) and 0.20 (95% CI, 0.04–0.93) for oxygen therapy, intensive care support, or both on univariate and multivariate analyses, respectively.

    Conclusions
    A vitamin D / magnesium / vitamin B12 combination in older COVID-19 patients was associated with a significant reduction in the proportion of patients with clinical deterioration requiring oxygen support, intensive care support, or both. This study supports further larger randomized controlled trials to ascertain the full benefit of this combination in ameliorating the severity of COVID-19.

    Paper: https://www.sciencedirect.com/scienc...002?via%3Dihub
    - Will

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    “Those who do not view armed self defense as a basic human right, ignore the mass graves of those who died on their knees at the hands of tyrants.”

  9. #139
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    All, a very promising study finding the simple combination of lactoferrin and the antihistamine Benadryl, may be a potent covid inhibitor. It’s in vitro, but concentrations are therapeutically relevant:

    https://news.yahoo.com/early-stage-r...002425317.html

    Study:

    https://www.mdpi.com/2076-0817/10/11/1514/htm
    - Will

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    “Those who do not view armed self defense as a basic human right, ignore the mass graves of those who died on their knees at the hands of tyrants.”

  10. #140
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    Interesting and promising study, quality and robustness of methodology needs to be examined:

    "Our study suggests that the treatment protocol of HCQ, AZM, and zinc with or without vitamin C is safe and effective in the treatment of COVID-19, with high dose IV vitamin C leading to a significantly quicker recovery.Importantly, our study confirms vitamin D deficiency to be a high-risk factor of severe COVID-19 disease and hospitalization, with 97% of our study’s patient cohort being vitamin D deficient, 55% of these being severely vitamin D deficient, and none had optimal levels.
    Future trials are warranted to evaluate the treatment with a combination of high-dose vitamin D3 in addition to HCQ, AZM, and zinc and high-dose intravenous vitamin C."

    Therapies to Prevent Progression of COVID-19, Including Hydroxychloroquine, Azithromycin, Zinc, and Vitamin D3 With or Without Intravenous Vitamin C: An International, Multicenter, Randomized Trial

    https://www.cureus.com/articles/7649...ndomized-trial
    - Will

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    www.BrinkZone.com


    “Those who do not view armed self defense as a basic human right, ignore the mass graves of those who died on their knees at the hands of tyrants.”

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