Author: Taylor Swift

Research: Telemental healthcare connected with elevated outpatient make contact with, hospitalization stick to-ups

Research: Telemental healthcare connected with elevated outpatient make contact with, hospitalization stick to-ups

[ad_1]

The use of telehealth to supply solutions for people with significant mental health issues (SMI) demonstrates assure, but does not automatically make improvements to rates of consumption for treatment. It stays unclear whether an expansion of these providers would increase high quality of care.

These have been amongst the success of a cohort research published in JAMA Network Open up on June 27 that included 118,670 sufferers with schizophrenia or related psychotic disorders, and/or bipolar I problem in non-metropolitan counties.

The analyze observed the use of telehealth expert services enhanced the premiums of affected person observe-up with healthcare gurus right after hospitalization, along with a “modest increase” in speak to with outpatient specialty psychological healthcare professionals.

“However, no substantive changes in treatment adherence were being mentioned and an increase in hospitalizations was observed,” the report mentioned.

The maximize in hospitalizations does not always necessarily mean that the use of the telehealth resulted in poorer treatment, and ending with a healthcare facility take a look at, the report cautioned, but somewhat the use of telehealth authorized health care experts to effectively recognize and stabilize patients owning an acute disaster.

WHY THIS Matters

As treatment delivery becomes a lot more dispersed, patients have a lot more choices to seek out care exterior of conventional health programs.

Even so, this access to numerous care channels has developed a new issue: the digital fragmentation of health care. Group well being facilities have turned to telehealth to strengthen their solutions.

While use of telehealth or telemedicine systems has been rapidly evolving, supplied a force ahead owing to the pandemic, research is minimal about the deployment of specialty psychological healthcare and medicine adherence by way of telehealth engineering.

In rural places, entry to specialty care remains a obstacle for individuals with severe mental disorders, the report mentioned. There is currently an lively discussion in numerous states relating to no matter if to lengthen pandemic-related non permanent expansions of telemedicine for psychological sickness care.

Other electronic services, which includes the use of tablets, have served carry mental wellness applications to patients in rural locations.

According to yet another review revealed in JAMA Network Open, furnishing a video clip-enabled tablet to veterans dwelling in rural spots lessened unexpected emergency office visits and suicidal behaviors.

THE Bigger Trend

Research compiled in 2018 experienced previously described the feasibility of making use of telemedicine in the procedure of schizophrenia and psychotic disorders.

In accordance to Trilliant Health’s developments analysis, which centered on U.S. telehealth use amongst March 2020 and November 2021, about a quarter of Us residents used telehealth in the course of COVID-19.

Even so, other researchers have uncovered therapists engaging with a greater proportion of purchasers from decreased socioeconomic position groups, people on Medicaid and households ended up significantly less most likely to retain applying telehealth following the pandemic.

Use of telehealth for behavioral health and fitness is also on the rise, in accordance to the report. However, new electronic wellbeing instruments presented by shops, which includes Amazon and Walmart, as very well as product choices from Apple, Google and a slew of startups could guide to much more advanced and efficacious telehealth offers across a wide spectrum of care.

HIMSSCast: Henry Ford director of virtual care talks telehealth

HIMSSCast: Henry Ford director of virtual care talks telehealth

[ad_1]

What are some of the most crucial subject areas in telehealth these days?

  • Standardizing and optimizing telehealth integration into care pathways
  • Conducting complete exams during online video visits
  • Electronic and telehealth literacy
  • Telehealth sustainability and federal government advocacy

That’s according to this podcast’s quite specific visitor, Courtney Stevens, director of virtual care at Henry Ford Health Technique, dependent in Detroit.

Established in 1915 by Henry Ford himself, Henry Ford Wellbeing Process is a non-gain, built-in wellness technique fully commited to improving people’s lives by means of excellence in the science and art of healthcare and healing. Henry Ford Health Process features Henry Ford Professional medical Team, with much more than 1,900 medical professionals and researchers working towards in much more than 50 specialties at locations all through Southeast and Central Michigan, and five acute care hospitals.

Like what you hear? Subscribe to the podcast on Apple Podcasts, Spotify or Google Engage in!

Speaking factors:

  • Standardizing and optimizing telehealth integration into treatment pathways
  • Improved adoption and results
  • Progressive purposes of virtual treatment
  • Resources and systems that can be utilized to execute a in depth assessment with telemedicine
  • Asynchronous modes of telehealth
  • Digital and telehealth literacy
  • Client training and support
  • Telehealth sustainability and government advocacy
  • Can the healthcare market maintain the momentum of telehealth developed by the pandemic

Additional about this episode:

How distant affected individual checking increases treatment, saves money for continual treatment

Strengthening rural care and health fairness with telemedicine

Telehealth with a technician in the home reduces invest by 22% for Scottsdale Medical doctor Team

How telehealth can enable inpatient care, and what a hybrid potential seems like

The troubles of telemental overall health, and how they can be get over

Twitter: @SiwickiHealthIT
Electronic mail the author: bsiwicki@himss.org
Health care IT News is a HIMSS Media publication.

Monkeypox conditions triple in Europe, WHO states, Africa concerned

Monkeypox conditions triple in Europe, WHO states, Africa concerned

[ad_1]

LONDON (AP) — The Planet Health Organization’s Europe chief warned Friday that monkeypox scenarios in the region have tripled in the last two weeks and urged countries to do extra to make sure the beforehand exceptional disease does not turn into entrenched on the continent.

And African health and fitness authorities claimed they are treating the increasing monkeypox outbreak as an crisis, calling on abundant nations around the world to share minimal supplies of vaccines to stay away from equity troubles found throughout the COVID-19 pandemic.

WHO Europe chief Dr. Hans Kluge reported in a assertion that amplified efforts were being essential despite the U.N. wellness agency’s conclusion final week that the escalating outbreak did not but warrant getting declared a international well being unexpected emergency.

“Urgent and coordinated motion is vital if we are to flip a corner in the race to reverse the ongoing unfold of this disease,” Kluge stated.

To date, much more than 5,000 monkeypox instances have been reported from 51 nations around the world that really don’t generally report the ailment, according to the U.S. Facilities for Sickness Manage and Prevention. Kluge explained the range of infections in Europe signifies about 90% of the world wide full, with 31 nations in the WHO’s European location possessing determined circumstances.

Kluge stated data noted to the WHO exhibit that 99% of circumstances have been in gentlemen — the majority in males that have intercourse with guys. But he claimed there had been now “small numbers” of cases amid residence contacts, such as youngsters. Most individuals reported indications like a rash, fever, tiredness, muscle mass ache, vomiting and chills.

Scientists alert anybody who is in near actual physical make contact with with anyone who has monkeypox or their clothing or bedsheets is at hazard of an infection. Vulnerable populations like youngsters and expecting girls are considered extra most likely to put up with significant condition.

About 10% of individuals have been hospitalized for procedure or to be isolated, and 1 human being was admitted to an intensive treatment unit. No deaths have been documented.

Kluge mentioned the challenge of stigmatization in some nations may well make some men and women cautious of seeking health care and reported the WHO was operating with associates which includes organizers of gay satisfaction events.

In the U.K., which has the greatest monkeypox outbreak past Africa, officers have mentioned the disorder is spreading in “defined sexual networks of homosexual, bisexual, or adult males who have intercourse with adult males.” British wellbeing authorities said there ended up no indicators suggesting sustained transmission over and above those populations.

A major WHO adviser reported in May well that the spike in cases in Europe was likely tied to sexual action by gentlemen at two rave functions in Spain and Belgium.

Ahead of gay satisfaction functions in the U.K. this weekend, London’s leading general public health medical professional requested men and women with symptoms of monkeypox, like swollen glands or blisters, to remain household.

Yet in Africa the WHO claims that in accordance to detailed facts from Ghana monkeypox cases were just about evenly split between males and women of all ages, and no distribute has been detected amongst males who have intercourse with gentlemen.

WHO Europe director Kluge also claimed the procurement of vaccines “must apply the rules of fairness.”

The principal vaccine remaining employed versus monkeypox was at first formulated for smallpox and the European Medicines Company reported this week it was commencing to examine whether it must be approved for monkeypox. The WHO has claimed provides of the vaccine, produced by Bavarian Nordic, are incredibly confined.

International locations such as the U.K. and Germany have currently started vaccinating men and women at large threat of monkeypox the U.K. not long ago widened its immunization method to largely homosexual and bisexual males who have numerous sexual partners and are believed to be most vulnerable.

Right until May possibly, monkeypox experienced under no circumstances been acknowledged to trigger substantial outbreaks past components of central and west Africa, exactly where it is been sickening men and women for decades, is endemic in numerous nations around the world and generally brings about limited outbreaks when it jumps to men and women from contaminated wild animals.

To date, there have been about 1,800 suspected monkeypox situations in Africa, which includes a lot more than 70 fatalities, but only 109 have been lab-confirmed. The lack of laboratory diagnosis and weak surveillance usually means lots of circumstances are going undetected.

“This unique outbreak for us means an crisis,” claimed Ahmed Ogwell, the acting director of the Africa Centers for Disorder Control.

The WHO claims monkeypox has unfold to African nations exactly where it hasn’t previously been noticed, which includes South Africa, Ghana and Morocco. But extra than 90% of the continent’s bacterial infections are in Congo and Nigeria, according to WHO Africa director, Dr. Moeti Matshidiso.

Vaccines have under no circumstances been applied to cease monkeypox outbreaks in Africa officers have relied largely on call tracing and isolation.

The WHO pointed out that equivalent to the scramble last calendar year for COVID-19 vaccines, countries with provides of vaccines for monkeypox are not yet sharing them with Africa.

“We do not have any donations that have been offered to (poorer) countries,” reported Fiona Braka, who heads the WHO emergency reaction workforce in Africa. “We know that people nations that have some shares, they are primarily reserving them for their have populations.”

Matshidiso stated the WHO was in talks with brands and countries with stockpiles to see if they could possibly be shared.

“We would like to see the worldwide spotlight on monkeypox act as a catalyst to beat this condition at the time and for all in Africa,” she reported Thursday.

___

Mutsaka noted from Harare, Zimbabwe.

Be a part of THE Conversation

Conversations are opinions of our audience and are matter to the Code of Carry out. The Star does not endorse these views.

The Effects of Vitamin C on the Multiple Pathophysiological Stages of COVID-19

The Effects of Vitamin C on the Multiple Pathophysiological Stages of COVID-19

[ad_1]


posted: Jul. 01, 2022.

The Effects of Vitamin C on the Multiple Pathophysiological Stages of COVID-19 

Citation: Miranda-Massari, J.R.; Toro, A.P.; Loh, D.; Rodriguez, J.R.; Borges, R.M.; Marcial-Vega, V.; Olalde, J.; Berdiel, M.J.; Riordan, N.H.; Martinez, J.M.; et al. The Effects of Vitamin C on the Multiple
Pathophysiological Stages of COVID-19. Life 2021, 11, x. https://doi.org/10.3390/xxxxx

Academic Editor(s): Jeanne A Drisko and Qi Chen

Received: 4 November 2021

Accepted: 28 November 2021

Published: date

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Copyright: © 2021 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

The Effects of Vitamin C on the Multiple Pathophysiological Stages of COVID-19

Jorge R. Miranda-Massari 1,2, Alondra P. Toro 3, Doris Loh 4, Jose R. Rodriguez 2,5, Raul Morales Borges 6,
Victor Marcial-Vega 7, Jose Olalde 8, Miguel J. Berdiel 9, Neil H. Riordan 10, Juan Manuel Martinez 11, Armando Gil 12, and Michael J. Gonzalez 2,3,13,*

1    Medical Sciences Campus, School of Pharmacy, University of Puerto Rico, San Juan 00936, PR, USA;
[email protected]

2    Program of Naturopathic Sciences, DP University, San Juan 00918, PR, USA; [email protected]

3    Medical Sciences Campus, School of Public Health, University of Puerto Rico, , San Juan 00936, PR, USA; [email protected]

4    Independent Researcher, TX, USA; [email protected]

5    PhD Clinical Psychology Program, San Juan Campus, Carlos Albizu University, San Juan 00901, PR, USA;
[email protected]

6    Ashford Institute of Hematology & Oncology, Integrative Optimal Health of Puerto Rico, San Juan 00907, PR, USA; [email protected]

7    School of Medicine, Universidad Central del Caribe, Bayamon 00960, PR, USA; [email protected]

8    Centro Médico Regenerativo, Caguas 00918, PR, USA; [email protected]

9    Berdiel Clinic, Ponce 00717, PR, USA; [email protected]

10   Medistem Panama, Technology Park (City of Knowledge), Panama 91767, CA, USA; [email protected]

11   Ortho-Regenerative Medicine, Chía 250001, Colombia; [email protected]

12   Gil Pharmaceutical, Ponce 00730, PR, USA; [email protected]

13   School of Chiropractic, Universidad Central del Caribe, Bayamon 00960, PR, USA

*    Correspondence: [email protected]

Abstract: Currently available anti-viral drugs may be useful in reducing the viral load but are not providing the necessary physiological effects to reduce the SARS-CoV-2 complications efficiently. Treatments that provide better clinical outcomes are urgently needed. 

Vitamin C (ascorbic acid, AA) is an essential nutrient with many biological roles that have been proven to play an important part in immune function; it serves as an antioxidant, an anti-viral, and exerts anti-thrombotic effects among many other physiological benefits.

Research has proven that AA at pharmacological doses can be beneficial to patients with acute respiratory distress syndrome (ARDS) and other respiratory illnesses, including sepsis. In addition, High-Dose Intravenous Vitamin C (HDIVC) has proven to be effective in patients with different viral diseases, such as influenza, chikungunya, Zika, and dengue. Moreover, HDIVC has been demonstrated to be very safe. Regarding COVID-19, vitamin C can suppress the cytokine storm, reduce thrombotic complications, and diminish alveolar and vascular damage, among other benefits. Due to these reasons, the use of HDIVC should be seriously considered in complicated COVID-19 patients. In this article, we will emphasize vitamin C’s multiple roles in the most prominent pathophysiological processes presented by the COVID-19 disease.

Keywords: COVID-19; ascorbic acid; intravenous vitamin C; pathophysiology of COVID-19;
Sars-Cov-2

1. Introduction

More than 100 million COVID-19 cases have been reported worldwide. This novel virus has caused a global health crisis. SARS-CoV-2 has three problematic characteristics. First, it seems to infect with a relative smaller viral load compared to other viruses, which makes it very contagious. Second, SARS-CoV-2 mutates fast, which can make available emergency vaccines less effective against new emerging strains, such as the Delta variant, which is characterized for manifesting more severe symptoms and being even more contagious than the original strain. Third, this virus causes a dangerous inflammation response that generates numerous free radicals and inflammatory molecules that can be highly cytotoxic and damaging. 

Meanwhile, hospitals have been treating infected patients with anti-viral drugs, such as remdesivir, hydroxychloroquine, and lopinavir. A recent study concluded that these drugs appeared to have little or no effect on hospitalized COVID-19 patients [1]. These and other reasons should ignite our interest to keep searching for treatments that can activate efficiently systemic defenses in order to generate better clinical outcomes for complicated COVID-19 patients.

One of the most important aspects to combat the SARS-CoV-2 is to have an optimized immune system that works properly and efficiently. In order for this system to function well, it needs a wide range of specific cofactors. One of these cofactors is vitamin C, also known as ascorbic acid. This powerful, water-soluble antioxidant is involved in many biological processes of the immune response [2]. Furthermore, this vitamin has shown potent anti-viral and anti-inflammatory activities in a variety of different viral infections [3,4]. Although oral vitamin C produces adequate concentrations to produce physiologic effects, pharmacologic concentrations require high intravenous doses that may be able to produce therapeutic benefits to COVID-19 patients.

Vitamin C is part of a comprehensive strategy to COVID-19. An ambulatory early management protocol of COVID-19 from an international consensus of experienced clinicians [5] proposed a multifaceted highly targeted sequential multidrug treatment that include vitamins, minerals, antimicrobials, steroids, colchicine, and possibly antithrombotic agents to assist the body deal with the viral load and the possible inflammatory and complications. A study in patients following this protocol demonstrated that early ambulatory treatment resulted in 87.6% reduction in hospitalization and 74.9% reduction in deaths [6].

Intravenous vitamin C has been successfully used in the hospitalized COVID-19 protocols [7]. It has been suggested that since vitamin C has both anti-inflammatory and antiviral effects, its use may help reduce drug dosing and toxicity [8]. Vitamin C, when given in high doses, is even extremely safe [9], and it can be easily excreted through the urine.

In this article, we will emphasize how vitamin C can attenuate many of the pathophysiological stages presented by the SARS-CoV-2 infection. Additionally, based on this information, we suggest that the administration of adequate dose of intravenous vitamin C combined with proven conventional supportive medications could provide COVID-19 patients with better clinical outcomes due to the multiple beneficial physiological properties it can exert. Moreover, AA is relatively non-toxic, and side effects are minimal.

Although oral intake of vitamin C does have a role in health maintenance, risk reduction and prevention, and prevention of infections, this article is focused on the more potent effects that can be achieved with pharmacologic concentrations.

2. High-Dose Intravenous Vitamin C (HDIVVC): Its Relevance

There are multiple ways vitamin C can be administered. It can be given either orally or intravenously. However, both methods have different physiological effects. In particular, there are studies that established differences between oral and IV vitamin C [10]. It was demonstrated that blood levels of vitamin C in patients were much higher by IV vitamin C than oral dosing. Because IV vitamin C is 100% bioavailable, it has the capacity to replenish tissues more efficiently and rapidly. Oral vitamin C at single doses of 200 mg is complete, and Cmax is about 60 min. However, it must be noted that under normal conditions in a healthy subject, bioavailability is reduced, which means that, for example, only about 33% a dose of 1250 mg or 412.5 mg will be absorbed when using a regular vitamin C formulation [11,12]. The decreased bioavailability of the larger oral doses is caused by saturation of the absorption mechanisms [13]. The oral dose must be absorbed by the small intestine, while IV vitamin C bypasses this route and is more readily available. Therefore, it is important to state that, to have better physiological effects that may lead to better clinical outcomes, IV vitamin C is the most potent method to attain higher blood concentrations. 

Another important aspect to highlight is that the effect of vitamin C will depend on frequency of application and quantity given. Multiple reports providing higher doses of IV vitamin C in a range from 30 to 150 g showed beneficial effects in cancer patients [14]. Moreover, in addition to all the benefits that high-dose IV vitamin C exerts, it is important to point out that it is very safe and non-toxic. Recently, there was a study published using high-dose IV vitamin C on COVID-19 patients [15], and results showed multiple improvements but, most importantly, no adverse effects.

Although there is no consensus about how to classify the doses in terms of magnitude, for the purpose of this article, we will refer to intravenous vitamin C in the context of a pharmacological effect and therefore will consider a low intravenous total daily dose to be 6–12 g, moderate intravenous total daily dose to be 13–24 g, and high dose intravenous total daily dose to exceed 25 gm daily.

In conclusion, high-dose IV vitamin C will provide better physiological effects leading to improved clinical outcomes due to higher concentrations while being safe and non-toxic.

3. Anti-Viral Mechanisms of Vitamin C

As mentioned previously, vitamin C is an essential nutrient for the body with several beneficial properties that help support proper functioning of the immune system, of great interest being its anti-viral capacity. Vitamin C has direct and indirect mechanisms that can exert these anti-viral properties. It has been shown that vitamin C can inactivate in vitro a wide range of viruses [16]. Virus inactivation was shown to be dependent on oxygen and was concluded to be mediated through oxidation to viral nucleic acids [17]. There is a possibility that ascorbate may damage viral capsids and even inhibit viral replication when provided in large doses. An in-vitro study showed that pharmacological ascorbate killed influenza virus in cultured human bronchial epithelial cells [18].

On the other hand, an indirect mechanism was proven by multiple studies in which vitamin C exerts powerful antiviral activity [19]. In a clinical study of 178 patients with Epstein Barr viral (EBV) infection treated with high doses of intravenous vitamin C, an inverse correlation was found between EBV viral capsid antigen (VCA), IgM, and vitamin C in plasma in patients with mononucleosis and chronic fatigue syndrome. Patients with high levels of vitamin C had lower levels of antigens in the acute state of disease [20].

Vitamin C can promote the production of anti-viral proteins, such as interferon. In an in-vitro study, there was evidence that, in the presence of ascorbic acid plus glutathione, interferon was produced [21]. These proteins play a role in immune protection and interfere with viral replication by binding to the cell surface. Moreover, a study analyzed in a mice model the multiple effects model of high-dose oral vitamin C supplementation the initial stage of influenza A virus (H3N2) [22]. They concluded that ascorbic acid could exert anti-viral activity by increasing the production of interferon-α/β. In addition, an animal study supports additional antiviral mechanisms of vitamin C. The administration of high doses of vitamin C caused virus attenuation of H1N1 virus. This study also showed that the intervention produced decreased expression of susceptibility genes and increased production of NF-κΒ, leading to the production of type I interferon (IFNs) [23]. Additionally, ascorbic acid enhanced the interferon levels produced by human embryo skin and human embryo lung fibroblasts induced by Newcastle disease virus [24].

4. Clinical Reports

4.1. Non-COVID Viral Infections

There are several studies reporting good clinical outcomes employing IV vitamin C on patients infected with different types of viruses. In example, there was a case report of a 54-year-old patient with chikungunya (CHIKV) fever with severe joint pain and inflammation [25]. The infected patient was treated with high doses of IV vitamin C for two days. Symptoms resolved promptly without any side effects during or after the infusions. In another case report, a 25-year-old patient tested positive for influenza virus [26]. Supplementation of IV vitamin C was given, resulting in fast improvement and returning to normal on day four. Therefore, these cases highlighted the effectiveness of IV vitamin C against combating viral infections.

Vitamin C has demonstrated that it can inhibit manifestations of viral ARDS. A case report showed how high doses of IV vitamin C can help stabilize a patient and help with decreasing the recovery time [27].

Later, there was a trial with patients suffering from sepsis and ARDS [28], in which vitamin C infusions were administered. Interestingly, results showed that vitamin C decreased mortality and length of stay for infected patients. In addition, there was a case report of a woman suffering with ARDS and other complications, in which the patient was intubated, presented hypoxemia, and chest imaging revealed opacities. Despite various approaches, the patient remained critical. Once IV vitamin C was initiated, the patient’s chest imaging and oxygenation began to improve. Rapidly, the woman became stable [29].

Some recent studies suggest that the use of ascorbic acid as part of a protective protocol against SARS-CoV-2 can reduce mortality in patients hospitalized in intensive care units with sepsis. This ascorbic acid protocol can significantly reduce mortality from sepsis [30], reduce ICU stay length, and significantly reduce the time to resolution of shock [31]. The use of ascorbic acid injections also improved the ventricular function (EF) 72 h after surgery and reduced the length of ICU stay in patients undergoing coronary artery bypass surgery.

4.2. COVID Viral Infections

The proven ability of vitamin C against other types of viruses may very well be equally as effective in SARS-CoV-2. The following cases support this this premise:

A case report of a COVID-19 patient with early use of high-dose intravenous vitamin C (HDIVC) showed positive outcomes [32]. The patient presented with chest X-ray opacities and infiltrations, body pain, dry cough, and other symptomatology. As she tested positive for SARS-CoV-2, 25 g of vitamin C was administered once a day for three consecutive days. The following day of the first infusion, the patient noted a dramatic improvement. Her body pain and headache were gone. Additionally, the most important aspect to highlight is that the infusions did not cause any adverse effects to the infected patient.

In an unusual early recovery case of a critical COVID-19 patient given vitamin C [33], a 74-year-old woman presented with fever, cough, and shortness of breath, oxygen saturation of 87%, and bilateral rhonchi. Chest radiography was suspicious for pneumonia and test was positive for SARS-CoV2. The patient was initially started on oral hydroxychloroquine and azithromycin. On day six, she developed ARDS and septic shock, for which mechanical ventilation and pressor support were started, along with infusion of high-dose IV vitamin C (11 g/d). 

The patient improved clinically and was able to be taken off mechanical ventilation within five days. This report emphasizes the potential benefits of high-dose IV vitamin C in critically ill COVID-19 patients in terms of speedy recovery and reduced length of mechanical ventilation and ICU stay. In this case, ascorbate seems to attenuate lung injury produced by the viral infection. It has been seen that even though a COVID-19 patient had already presented complications and developed critical conditions, such as acute respiratory syndrome ARDS or DAD, high doses of vitamin C can help stabilize, improve patient condition, and even shorten the length of the disease caused by the SARS-CoV-2 virus.

A case series of 17 high-risk patients with advanced age and multiple comorbidities who tested positive for COVID-19 and had moderate to severe disease were treated with IV vitamin C (1 g every 8 h for 3 days) in addition to standard treatment for COVID-19 [34]. Results showed a significant decrease in inflammatory markers, including ferritin and D-dimer, and a trend to decreasing FiO2 requirements. This case series presents a 17.6% rate of need for mechanical ventilation, which is comparable to a recent study, and 12% mortality rate, which is smaller [35]. Despite a relatively low dose of IVC, it produced comparable outcomes with some possible improvements.

In the case of a 77-year-old female with a history cardiovascular disease that presented with a five-day history, worsening symptoms received a variety of antimicrobials, anti-inflammatory agents, monoclonal antibodies, and IV vitamin C (6 g bid). She did not respond and eventually succumbed. This case illustrates the importance of early treatment to avoid the complications, such as cytokine storm, especially in patients with significant comorbidities. Once the cytokine storm manifests, even with aggressive and comprehensive treatments, it seems the body is unlikely to recover [36].

In this case report, two patients were confirmed with SARS-Cov2 pulmonary infection with respiratory distress at ages 57 and 58 years old, with 6–7 days of symptoms. Patient prior medical history was not reported and presumably had no risk factors. They were treated with oxygen in one case and mechanical ventilation in the other. Medications included hydroxychloroquine (600 mg/day), azithromycin, steroids, vitamin C (3 g/day), zinc, diuretics, and enoxaparin, which were equally used for the two patients. Both patients responded to treatment and recovered. The treatments described started on day 6–7 of symptoms but is unclear if patients had previous treatment before admission. In conclusion, this report is not helpful to assess the utility of the vitamin C in COVID-19 because the vitamin dose used were low. In addition, the route of administration is not specified as well as the presence of risk factors or previous therapy before hospitalization [37].

In a retrospective case series, twelve patients were enrolled, including six severe and six critical patients. All patients received high-dose intravenous vitamin C (average 163 mg/kg in severe patients), but on average, about a 10% higher dose was given to critical patients. Patients had significant improvements in CRP, lymphocyte count, and CD4. Improvements in oxygenation and SOF score were also observed. Greater improvements were observed in severe than critical patients after HDIVC. It was concluded that high-dose IVC (11 g per day average or more for a 70-kg person) could be beneficial in aspects of inflammatory response and immune and organ function for treatment of COVID-19 patients [38].

A retrospective case-matched clinical study compared the outcome and clinical courses of patients with moderate COVID-19 patients treated with an HDIVC protocol (100 mg/kg/day) for seven days from admission with a control group treated without the HDIVC. The HDIVC and control groups each comprised 55 patients. For the primary outcomes, there was a significant difference in the number of patients that evolved from moderate to severe type between the two groups. There was a significant reduction in the number of patients in the HDIVC that evolved from moderate to severe disease (p = 0.03). Additionally, compared to the control group, there was a shorter duration of systemic inflammatory response syndrome (SIRS, p = 0.0004) and lower SIRS occurrence (p = 0.0086) during the first week. It was concluded that in this population, a dose of 7 g for a 70-kg person may be of value in preventing progression from moderate to severe disease [39].

In an open-label, randomized, and controlled trial on patients with severe COVID-19 infection, the case and control treatment groups each consisted of 30 patients. The control group received lopinavir/ritonavir and hydroxychloroquine, and the experimental group received IVC (6 g daily) added to the same regimen. The experimental group receiving IVC showed significant improvements in mean body temperature, which was significantly lower on the third day of hospitalization (p = 0.001) and peripheral capillary oxygen saturation (SpO2) (p = 0.014). However, the median length of hospitalization was significantly longer than the control group (8.5 days vs. 6.5 days) (p = 0.028). There was no significant difference in the length of intensive care unit (ICU) stay and mortality between the two groups. It is noticeable that there were significant clinical differences in the initial response, and it seems that 6 g was not enough to change the clinical outcomes [40].

Finally, a recent placebo-controlled pilot study of high dose intravenous ascorbate in 56 critically ill COVID-19 patients showed significantly reduced mortality. The trial was conducted in two hospitals located in Wuhan, China, and used a daily dose of 24 g of ascorbate divided in two doses. The ICU mortality rate was 22% (6 out of 27) in the ascorbate group and 38% (11 out of 29) in the placebo. This difference did not reach statistical significance because of the small number of patients. However, in the most critically ill (SOFA > 3), the difference in hospital mortality was even bigger: 18.5% in the ascorbate group vs. 38% in placebo, achieving statistical significance (p = 0.04) [41].

In summary, when examining the existing literature for the use of intravenous vitamin C in COVID-19 patients, there is consistence in the evidence of improvements in outcomes, such as fever, inflammation, cell blood count, oxygenation, and even clotting markers. The case studies and small studies discussed provide some indication that the time to begin treatment, the dose of vitamin C, the presence of comorbidities, and the severity all play a role in response and mortality. However, it seems that better outcomes are associated with higher doses.

5. Vitamin C Suppresses Oxidative Stress

Oxidative stress is an imbalance of antioxidant molecules and free radicals species in the body. This can cause damage of DNA, membranes, proteins, and others, which can result in complications and diseases [42]. These free radicals are also referred to as oxygen reactive species (ROS). Exhibiting low concentrations of ROS and having an adequate homeostasis of them is beneficial for the body since they are needed in the immune system to fight pathogens, such as viruses. However, in high concentrations, these reactive molecules are toxic and may exert very damaging effects. It has been observed that when there is a viral infection, viruses can induce via multiple pathways severe oxidative stress [43]. Viruses are often associated with oxidative stress that can result in RedOx imbalances that can cause damage to cells. Regarding coronaviruses and SARS-CoV-2, increased levels of oxidative stress in infected patients seems to have a detrimental effect in cells and organs [8].

Some studies have proposed that a precise disulfide-thiol balance is crucial for viral entry and fusion into the host cell and that oxidative stress generated from free radicals can affect this balance. It seems possible that oxidation of thiols to disulfides, under a mechanism of oxidative stress, would improve the affinity of SARS-CoV-2 S proteins for the ACE2 receptor and consequently increase the severity of COVID-19 infection [44]. Oxidative stress refers to the harmful effects from excessive free radicals or prooxidants in a biological system. Advanced age is a risk factor for COVID-19 morbidity and mortality. Age-related decline GSH systems and the impaired control of the thiol to disulfide balance alters RedOx balance of all tissues. Using a specialized computational system for molecular dynamics simulation and for binding energy calculations, it was determined that the binding affinity was significantly impaired when all the disulfide bonds of both ACE2 and SARS-CoV/CoV-2 spike proteins were reduced to thiol groups. If this was the case, providing the body with increased glutathione precursors and cofactors, as well as electron donors like vitamin C, which regenerates reduced glutathione, would result in decreased entrance of the virus, reduced viral load, and consequently reduced severity of the COVID-19 infection [45,46].

In addition, an association of oxidative stress in COVID-19 and the amplification and perpetuation of the cytokine storm, coagulopathy, cell hypoxia, and mitochondrial dysfunction has been shown, suggesting a possible therapeutic role of antioxidants and other agents to reduce oxidative stress [47].

There was a study on COVID-19 patients evaluating levels of antioxidants and oxidative stress markers that concluded that infected patients had significantly lower levels of antioxidants [48]. Moreover, they stated that severe COVID-19 patients are at higher risk of oxidative stress.

Although COVID infection is the likely cause of depleted antioxidant cofactors, that study was not designed to determine cause and effect.

The NHANEs has established that there is a significant proportion of the USA population deficient in nutrients, including vitamin C (46%), vitamin A (45%), vitamin E (84%), and Vitamin D (95%) [49]. In a study with five hospitalized patients with COVID-19, researchers observed a deficiency of vitamin D in 76% and of selenium in 42% of the patients [50]. Although vitamin D is not considered and antioxidant vitamin, vitamin D reduces renin-angiotensin-aldosterone system activation and consequently decreases ROS.

Activation of the renin-angiotensin-aldosterone system and consequent increase in angiotensin II and aldosterone, as seen in cardiometabolic syndrome, participates in altering insulin/IGF-1 signaling pathways and reactive oxygen species formation to induce endothelial dysfunction and cardiovascular disease [51].The mechanisms involved in these inhibitory effects of ANG II include the generation of ROS [52].

An animal study in a model of hyperoxia-induced acute lung injury (HALI) found that 50 mg/kg of parenteral vitamin C produces a significant decrease in the levels of airway HMGB1 in hyperoxia control (p p [53]. This study, while not related to a viral infection, demonstrated the role of high-dose vitamin C in reducing damage from oxidative stress, inflammation, and lung integrity, which are pathophysiologic processes relevant to COVID.

Since COVID-19 patients commonly have lower levels of vitamin C due to the physiological stress of the viral infection [54], replacement of this vitamin in the optimal amounts to control oxidative stress as well to other benefits for COVID-19 patients should be considered. While low vitamin C status is associated with severe COVID, we do not yet know if patients with low vitamin C levels (pre-infection) are at greater risk of developing severe COVID or if severe COVID infections cause people to lose vitamin C more quickly. While both are likely, knowing this could assist in promoting preventive and health promotion measures.

6. Vitamin C Inhibits the Cytokine Storm Due to Its Antioxidant Capacity

The severity of being infected by SARS-CoV-2 is related to the cytokine storm, which can occur in many tissues. In the lungs, and in particular the alveoli, it can cause a proinflammatory response that leads to pneumonia, ARDS, diffuse alveolar damage (DAD), multiorgan failure, and other complications. Studies in Wuhan, China, showed that patients with severe COVID-19 symptoms had higher levels of IL-6 and other inflammatory cytokines in their blood samples [55]. It is normal for the body to increment the secondary (humoral) immune response after a high viral load exposure, which subsequently causes the release of these inflammatory cytokines that attack foreign proteins, such as those presented by SARS-CoV-2. However, it is expected that the body itself will gradually lower the immune response. In COVID-19 patients, the immune response does not seem to lower, causing detrimental and fatal effects to many organs. Due to this, the role of the cytokine storm rampage seen in COVID-19 has generated interest from the medical-scientific community as a potential target for combating the SARS-CoV-2 complications that may lead to death.

Furthermore, the alveolus is a structure that is very much affected by the cytokine storm. A common finding of post-mortem autopsies from COVID-19 patients reveals a trend of patients with highly damaged alveolar structures. A study noted that all of the seven COVID-19 lung specimens observed had diffuse alveolar damage (DAD) [56]. Another study observing pathogenesis of two severely infected COVID-19 patients found that the DAD seen in acute respiratory distress syndrome (ARDS) was not unique to COVID-19 patients but occurs in both SARS and MERS infections as well [57], which indicates that ARDS may be responsible for the DAD observed in COVID-19 cases. Furthermore, a third study stated that the development and progression of ARDS seen in COVID-19 is closely related to the inflammatory cytokine storm [58]. Outlining this information, suppression of the cytokine storm is of particular interest because it can prevent further complications, such as DAD and ARDS. Moreover, if a treatment can decrease the possibilities of the generation and/or progression of the cytokine storm, it could greatly decrease the possibilities of mortality in COVID-19 patients since they are highly correlated [59].

Vitamin C can inhibit the cytokine storm in COVID-19 patients based on its antioxidant properties. The main concern of the cytokine storm is the inflammatory response it produces, and one of the principal functions of this vitamin in addition to its great antioxidant capacity is that it exerts anti-inflammatory properties. It has already been observed in human and animal models that high doses of vitamin C may decrease several inflammatory parameters, such as inflammatory cytokine release and activity. For example, it was discovered that when a high dose of IV vitamin C was given to critically ill COVID-19 patients, their levels of interleukin-6 (IL-6) were lower than the placebo group (Jing et al. 2020). In addition, there is evidence that vitamin C inhibits a variety of cytokines [60], A group of 12 cancer patients receiving 25–125 gm of intravenous vitamin C and achieving 5–18 mM of ascorbate plasma concentration experienced normalization of many of the cytokine levels measured. Cytokines that were most consistently elevated prior to treatments included M-CSF-R, leptin, EGF, FGF-6, TNF-α, β, TARC, MCP-1,4, MIP, IL-4, 10, IL-4, and TGF-β. Cytokine levels tended to decrease during the course of treatment.

The intense proinflammatory response to the SARS-CoV-2 infection can lead to the development of a life-threatening cytokine release syndrome (CRS), which can lead to acute respiratory syndrome (ARDS), leading to a high mortality rate in elderly subjects and other at-risk populations. Furthermore, vitamin C supplementation can generate stable, antigen-specific regulatory T cells in animal models of autoimmune or acute graft versus-host diseases. Vitamins may shift the proinflammatory T-helper lymphocytes (Th17)-mediated immune response arising in autoimmune diseases towards a T-cell regulatory phenotype [61,62].

On the other hand, some reviews postulate that vitamin C can help remove alveolar fluid caused by distress of the inflammatory response [63]. Parenteral vitamin C infusion protected mice from the harmful consequences of sepsis by several mechanisms, including attenuation of the proinflammatory response, enhancement of epithelial barrier function, increasing alveolar fluid clearance, and prevention of sepsis-associated coagulation abnormalities [64]. An in-vitro study found that vitamin C acts at multiple levels to exert its antiviral and protective functions in the lungs. significant upregulation of several metabolic pathways and interferon-stimulated genes (ISGs) along with a downregulation of pathways involved in lung injury and inflammation [65].

Therefore, AA is promising for preventing and treating the cytokine storm itself.

7. Vitamin C Lessens Alveolar Damage and Lung Complications

One area that SARS-CoV-2 is likely to invade is the lung tissue, and a correlation has been observed between the virus and alveolar damage. It is very common for infected patients to develop ARDS, which is associated with large amounts of inflammation and damage on the alveolar-capillary barrier. Additionally, infected COVID-19 patients suffer further complications, resulting in permanent alveolar damage. When an infected patient has developed complications, such as ARDS and DAD, there is higher chance of mortality, and prognosis may seem to worsen. For instance, it has been established that ARDS is one of the principal causes of high mortality in patients with COVID-19 [66]. In order to reduce mortality rates and provide the patient with better clinical outcomes, it is important to identify better treatment that can directly manage these complications.

A brief research letter reported that vitamin C levels were undetectable in more than 90% of COVID-19 patients suffering with ARDS [67]. In addition, an epidemiological study reported that up to 82% of critically ill COVID-19 adult patients with ARDS had low vitamin C values [68].

This is consistent with low plasma levels of vitamin C reported in critically ill patients and many other conditions. Septic shock patients have significantly depleted vitamin C levels compared with non-septic patients, likely resulting from increased metabolism due to the enhanced inflammatory response [69,70]. Low vitamin C levels are also observed in patients with infections [68], trauma patients [72], cancer patients [73], and diabetes patients [74]. Patients with these complications have low plasma levels and benefit from high quantities of vitamin C to efficiently compensate from its excessive utilization by their immune system due to an increased physiological stress. Therefore, the supplementation of IV vitamin C can be beneficial to help maintain optimal protective levels in these patients and consequently maintain cellular homeostasis.

Although more research needs to be done in order to fully validate the effect IV vitamin C has on ARDS, current information seems very promising and appears to exert many beneficial properties on patients with ARDS. Some of the cases were discussed previously in Section 4.

8. Vitamin C Suppresses Thrombosis and Prevents Vascular Tissue Damage

Current research has been stating that SARS-CoV-2 may predispose infected patients to thrombotic diseases causing alteration in the coagulation cascade and leading to a worse prognosis [75,76]. Thrombotic complications could also significantly contribute to mortality. Furthermore, the COVID-19 disease can have a prothrombic state, and it can be seen in multiple organs, such as lungs, spleen, and gut [77]. This dangerous complication is due to the excessive performance of the immune system trying to combat the virus, which generates significant amounts of clotting substances in the blood. It can be said that inflammation and coagulation are interrelated when we speak about SARS-CoV-2. Currently, one of the typical ways to treat these thrombotic complications on COVID-19 patients are blood thinners. However, these medications do not always prevent clotting in infected patients, and there are minimal studies proving reliability [78]. In addition, a study highlighted that despite administration of anticoagulation medication, COVID-19 patients continued to have thrombotic complications [79]. This coagulopathy described in COVID-19 is characterized by an increase in procoagulant factors, such as fibrinogen and D-dimers, which have been associated with higher mortality.

Moreover, another structure that seems damaged by this virus are the endothelial cells found in the blood vessels. Studies show that particles from SARS-CoV-2 and inflammatory cells were detected in endothelial cells of infected patients [80]. This could be directly correlated to the thrombotic complications since blood vessels require healthy endothelial cells in order to inhibit the formation of clots. Moreover, when a virus is present, it can provoke the phagocytosis of important proteins from cells such as endothelial cells, causing loss of vascular integrity, cessation of important anti-clotting reactions, and leading to severe complications.

One of the many properties of vitamin C is that it exerts an antithrombotic action. It could be beneficial for COVID-19 patients to receive IV vitamin C to prevent or decrease thrombotic complications. Moreover, a study concluded that providing vitamin C during early stages of the disease prevented coagulopathy and the formation of microthrombi, which are common complications of COVID-19 [81]. Another important research to highlight is IV vitamin C and evaluation of D-dimer levels. The D-dimer test is a blood test used to detect presence of blood clots. Clinicians constantly order this test since it has been proven to be the best laboratory diagnostic marker for COVID-19-associated hemostatic abnormalities and is directly related with mortality [82]. Recently, there was a study of 17 COVID-19 patients that were given IV vitamin C [34]. Results showed that not only did vitamin C decrease the mortality rate but some inflammatory markers, such as D-dimer levels, were also decreased.

Nearly 40% of the protein content in the body is composed of collagen [83]. Collagen is a molecule that plays an important role in the health of the vascular system. This protein strengthens and protects the integrity of blood vessels. Each blood vessel contains a layer of endothelial cells that contain and need collagen to work properly. Collagen polypeptide synthesis, posttranslational hydroxylations, and actions of the two hydroxylases are independently regulated by vitamin C [84]. Vitamin C also increases the synthesis and deposition of type IV collagen in the basement membrane, stimulating endothelial proliferation [85], promoting adhesion [86], inhibiting apoptosis [87], scavenging radical species, and sparing endothelial cell-derived nitric oxide to help modulate blood flow [88]. Since moderate and severe SARS-CoV2 infection produces high level of oxidative stress in many tissues, it therefore creates a higher demand for vitamin C Since vitamin C insufficiency among healthy people in USA is 45% [49], it must be presumed that the vast majority of COVID-19 patients are depleted; however, for optimal collagen synthesis, oral might be enough. Although it is unknown if collagen synthesis is a likely path to influence COVID response in the short term or in the long term, this mechanism is likely to have an impact in a matter of days.

In addition to those involved in collagen synthesis, there is increasing evidence that ascorbate is required for optimal function of many dioxygenase enzymes. Several of these enzymes modulate the transcription of proteins involved in endothelial function, proliferation, and survival, including hypoxia-inducible factor-1α and histone and DNA demethylases. Additionally, vitamin C has been found acutely able to tighten the endothelial permeability barrier [89] and thus may modulate access of ascorbate and other molecules into tissues and organs [90].

Moreover, functional endothelial cells have the capacity of exerting antithrombotic properties and also possess the ability to degrade clots, preventing thrombosis [91]. Therefore, having healthy functional blood vessels can contribute to prevent thrombotic complications in patients with COVID-19.

9. Vitamin C Protects Red Blood Cells and Averts Hemoglobinopathy and Iron Metabolism Dysregulation

The Fenton reaction results from hydrogen peroxide (H2O2) catalyzed by iron (II) (Fe2+) to form hydroxide (OH) and hydroxyl radical. Since the use of intravenous vitamin C at high doses promotes the formation of peroxide [92], the formation of hydroxyl radicals is increased. Human and mammal cells produce SOD, catalase, and peroxidases that can quickly reduce peroxide, therefore reducing damaging effects. Catalase is the most effective catalyst for the decomposition of H2O2 and is an abundant antioxidant enzyme commonly found in the liver, erythrocytes, and alveolar epithelial cells [93]. However, many cancer cells [94] and some bacteria and viruses lack this mechanism and are therefore vulnerable to the oxidative stress generated by this reaction. Obligate anaerobes usually lack all three enzymes. Oxidizing disinfectants, such as a 0.5% hydrogen peroxide solution, have been shown to be inactivate coronaviruses when used as a surface disinfectant [95]. An in-vitro study showed that catalase pathways are critically involved in intracellular ROS regulation, including the expression of the tumor suppressor gene p53 [96].

COVID-19 captures iron and generates reactive oxygen species to damage the human immune system. SARS-CoV-2 may also affect red blood cells and hemoglobin. Multiple proteins from SARS-CoV-2 can affect the hemoglobin pathway and cause dissociation of iron. In summary, the virus inhibited the immune system through by excessive ROS production [97]. SARS-CoV-2 proteins can interact with hemoglobin and cause denaturation of the molecule. These alterations could inhibit the ability of red blood cells to transport oxygen, leading to hypoxia. Moreover, the hemoglobin pathway can also be altered by the condition of ARDS, which is very common in COVID-19 patients. For example, it has been observed that patients with ARDS can have higher levels of cell-free hemoglobin (CFH) [98]. Having high levels of CFH can be detrimental since it can cause inflammation and alveolar injury [99]. In addition, cell-free hemoglobin has the unstable ferric form, and therefore, it can initiate a cascade of free radical chain reactions, causing more oxidative stress toxicity and tissue damage [100].

This hemoglobin pathway irruption caused by the virus or ARDS can worsen the respiratory condition in COVID-19 patients since the virus already compromises the respiratory system. In COVID-19 patients, if there is a decrease in functional hemoglobin, it can result in poor clinical outcomes [101]. Taking this into account, evaluations on how to decrease or inhibit the capacity of the virus to invade this pathway or affect the red blood cells in order to maintain better oxygenation levels and overall stability in patients should be considered.

Hemoglobin desaturation accompanied by iron metabolism dysregulation favors the following pathological pathways: hypoxemia and systemic hypoxia, reduction of nitric oxide, coagulation activation, ferroptosis with oxidative stress and lipid peroxidation, mitochondrial degeneration, and apoptosis [102]. This hemoglobin alteration can contribute to the oxygen-deprived multifaceted syndrome seen in many COVID-19 patients. Interestingly, the erythrocyte presents other SARS-CoV-2 receptors in addition to the ACE2, such as cyclophylins, furins, and TMPRSS2 [103].

Given the dynamics of hemoglobin during SARS-CoV-2 infection, it is important to mention that vitamin C is implicated in iron homeostasis. Vitamin C stimulates iron sequestration/removal from plasma and works with the haptoglobin system to limit the extent of damage after infection. Iron metabolism is modulated by ascorbate by stimulating ferritin synthesis, inhibiting degradation of lysosomal ferritin, and decreasing cellular iron efflux. Moreover, ascorbate cycling across the plasma membrane is the mechanism for ascorbate-stimulated iron uptake from low-molecular-weight iron-citrate complexes, which are important in the plasma of individuals with iron-overload disorders [104].

Silent hypoxia is described in COVID-19 patients, who show a progressive worsening hypoxia associated with normal CO2.This condition worsens in later stages, when CO2 increases. Finally, hyperferritinemia can increasingly affect alveolar/capillary cell membrane integrity/permeability, causing inflammation, edema, and lung necrosis and further complicating the pulmonary condition. Furthermore, hyperferritinemia may induce a series of injuries to many organs via autoimmunity, such as coagulopathies, macrophage activation syndrome, hemochromatosis like liver damage, and other ferroptosis-driven syndromes.

As for vitamin C, it is known that it can maintain hemoglobin iron complex in the ferrous state that allows binding of oxygen, and it can also improve heme iron/cell RedOx balance [102]. Vitamin C can indirectly decrease furin cleavage and reduce endothelial permeability to free heme [105]. Additionally, as mentioned earlier, vitamin C has antioxidant capacities that could help in managing the oxidative radicals produced by the cell-free hemoglobin. Lastly, the inflammation linked to high levels of CFH can be possibly managed by vitamin C due to its anti-inflammatory capacity. 

Vitamin C is required in high amounts in tissues to maintain vascular strength and integrity. The microvasculature, when depleted of vitamin C, loses its structural capacity, as shown in patients suffering scurvy. These derangements can further enhance coagulability issues and cause patients to be prone to both venous and arterial blood clots. Vitamin C improves the condition of critically ill complicated COVID-19 patients by its multiple beneficial physiological effects, which include attenuation of lipid peroxidation, reduction of vascular permeability, lessening microvascular dysfunction, preserving the endothelial function and microcirculatory flow, improving endogenous vasopressor synthesis, and increasing vasopressor sensitivity and hemodynamic stability, which ultimately leads to reduced organ injury and dysfunction that may save lives among the critically ill [106].

10. Vitamin C Protective Role on SARS-CoV-2 Multiple Organ Manifestations

It is known that lung tissue is the initial and primary target of invasion by the SARS-CoV-2 virus. However, is not uncommon for SARS-CoV-2 to invade other organs. It will all depend on the quantity and origin of receptors that each infected patient possesses. Increased research reveals that COVID-19 patients commonly exhibit multiorgan manifestations. For example, there have been reported cases of patients presenting kidney injury, gastrointestinal symptoms, cardiovascular issues, liver problems, and other complications [107]. In this sense, COVID-19 can be considered as a systemic disease. Additionally, research highlighted and observed via data analyses shows that multiple organs and tissues were vulnerable to SARS-CoV-2 virus and not only the lungs [108].

The renal system seems to be one of the most frequently targeted areas for SARS-CoV-2; in addition, autopsies have demonstrated that there is a percentage of COVID-19 patients that suffered from renal tropism [109]. This includes patients with or without kidney diseases. The study also highlighted that the presence of SARS-CoV-2 RNA in the kidney was associated with increased risk of premature death. Taking this into account, prevention and reduction of kidney injury or complications in order to decrease disease severity and provide better clinical outcomes in COVID-19 patients must be evaluated. Vitamin C has been observed to provide potential benefits against development of kidney disease. For example, vitamin C can help in controlling anemia in patients with chronic kidney disease, and it can have reno-protective effects since it improves the levels of urea, MDA, and catalase [110].

The brain consumes a large amount of glucose and oxygen, which indicates rapid metabolism with increased oxidative stress. Therefore, ascorbate is abundant in the brain tissue. Ascorbate accumulates in choroid plexus cells (CP) and then passes through the CSF into the brain [111]. More specifically, ascorbate enters CNS through SVCT2 present in CP on the basal side [112] of the CP and also probably through GLUT1[113]. The brain steady-state ascorbate concentrations are remarkably high, and in addition, it also has exceptional retention of vitamin C in its tissues during states of deficiency. To this time, it unknown what the brain concentrations are as plasma ascorbate rises to pharmacological levels.

Regarding the nervous system, SARS-CoV-2 can have the capacity to cross the blood-brain barrier and cause multiple symptomatology in infected patients. Recent studies discovered that brain autopsies from COVID-19 patients had cortical neurons with viral load of SARS-CoV-2 [114]. Moreover, possible infection and minimal immune cell infiltrates were noted, providing evidence for SARS-CoV-2 neuroinvasive capacities. Regarding how vitamin C could play a role in the different manifestations of the nervous system, it has been seen that ascorbate can help in neuronal repair, myelination, and function [11[M1] [JM2] 5]. Additionally, the review stated that vitamin C is an important antioxidant for the CNS since it scavenges ROS molecules, causing suppression of oxidative stress in the nervous system.

On the other hand, it has been deduced that one of the possibilities of neurological manifestations on COVID-19 patients is due to the excessive immune response and the cytokine storm [107]. Therefore, as established previously, it seems that the suppression or inhibition of the cytokine storm could help in preventing neuronal complications in addition to multiple organ manifestations in COVID-19 patients. As mentioned before, this could be done by providing HDIVVC since various studies have proven the different mechanisms of action this vitamin cofactor exerts regarding the cytokine storm.

 11. Conclusions

Despite its favorable physiologic effects of ascorbate, which are both potent and multiple, it should not be considered as a sole treatment for SARS-CoV-2, but it does provide the immune system the necessary boost to combat the virus more efficiently, shorten the length of the disease, and prevent fatal complications. This important vitamin cofactor plays many roles in suppressing the pathological processes exerted by SARS-CoV-2. Vitamin C has immuno-supportive, anti-viral, anti-inflammatory, antioxidant, anti-thrombotic, and many other beneficial properties. Because it has all these capacities, it can be concluded that vitamin C, especially HDIVVC, can be seen as an important component in the treatment for SARS-CoV-2. What is also important to highlight is that in practically all of the pathophysiological stages of SARS-CoV-2, vitamin C can have a potential role in diminishing its detrimental effects. This is due to the pleiotropic physiological effects that ascorbate exhibits, such as inhibiting the cytokine storm, reducing oxidative stress, decreasing inflammation, and preventing thrombotic complications, among others. Moreover, vitamin C has the capacity to reduce mortality in COVID-19 patients while providing better clinical outcomes that do not include harsh side effects to the body. Furthermore, by supplementing vitamin C to COVID-19 patients, research states that it can reduce the high doses of medications, like corticosteroids. Vitamin C is a safe and low-cost option that should be contemplated as part of the treatment of COVID-19 patients.

On the other hand, vitamin C has been used as a treatment for many diseases, such as cancer, colds, inflammatory disorders, and others. Additionally, ascorbic acid is an important water-soluble molecule that is excreted very easily through urine. However, it can exert multiple beneficial physiological effects. COVID-19 patients usually possess low levels of vitamin C due to the stress imposed by SARS-CoV-2 infection. As a result, higher quantities of this vitamin cofactor are needed in order for the immune system to function properly during a viral attack. There is no doubt that the use of HDIVVC will be beneficial to virally infected patients. More research needs to be done to provide better clinical outcomes to COVID-19 patients. It is necessary to search for other available treatments that are less invasive yet capable of optimizing immune responses in infected COVID-19 patients. Vitamin C seems to be this additional component needed for a better treatment of COVID-19 patients.

Author Contributions: Conceptualization, writing, review and editing, M.J.G. and J.R.M.-M.; Writing, review and editing, A.P.T., D.L., J.R.R., R.M.B., V.M.-V., J.O., M.J.B., N.H.R., J.M.M., A.G. All authors have read and agreed to the published version of the manuscript.

Funding: This research received no external funding

Institutional Review Board Statement: Not applicable.

Informed Consent Statement: Not applicable.

Data Availability Statement: Not applicable

Acknowledgments: No contribution or funding or donations to declare.

Conflicts of Interest: The authors declare no conflict of interest.

References

Pan, H.; Peto, R.; Karim, Q.A. Repurposed Antiviral Drugs for Covid-19—Interim WHO Solidarity Trial Results. N. Engl. J. Med. 2020, 384, 497–511, https://doi.org/10.1056/NEJMoa2023184.

Carr, A.C.; Maggini, S. Vitamin C and Immune Function. Nutrients 2017, 9, 1211, https://doi.org/10.3390/nu9111211.

Sorice, A.; Guerriero, E.; Capone, F.; Colonna, G.; Castello, G.; Costantini, S. Ascorbic acid: Its role in immune system and chronic inflammation diseases. Mini Rev. Med. Chem. 2014, 14, 444–452, https://doi.org/10.2174/1389557514666140428112602.

Colunga Biancatelli RML, Berrill M & Marik PM. The antiviral properties of vitamin C, Expert Re-view of Anti-infective Therapy. 2020, 18, 99–101, doi:10.1080/14787210.2020.1706483.

McCullough, P.A.; Alexander, P.E.; Armstrong, R.; Arvinte, C.; Bain, A.F.; Bartlett, R.P.; Berko-witz, R.L.; Berry, A.C.; Borody, T.J.; Brewer, J.H.; et al. Multifaceted highly targeted sequential multidrug treatment of early ambulatory high-risk SARS-CoV-2 infection (COVID-19). Rev. Cardi-ovasc. Med. 2020, 21, 517–530.

Procter, B.C.; Ross, C.; Pickard, V.; Smith, E.; Hanson, C.; McCullough, P.A. Early Ambulatory Multidrug Therapy Reduces Hospitalization and Death in High-Risk Patients with SARS-CoV-2 (COVID-19). Int. J. Innov. Res. Med Sci. 2021, 6, 219–221, https://doi.org/10.23958/ijirms/vol06-i03/1100.

Liu, F.; Zhu, Y.; Zhang, J.; Li, Y.; Peng, Z. Intravenous high-dose vitamin C for the treatment of severe COVID-19: Study protocol for a multicentre randomised controlled trial. BMJ Open. 2020, 10, e039519, https://doi.org/10.1136/bmjopen-2020-039519.

Hoang, B.X.; Shaw, G.; Fang, W.; Han, B. Possible application of high-dose vitamin C in the pre-vention and therapy of coronavirus infection. J. Glob. Antimicrob. Resist. 2020, 23, 256–262, https://doi.org/10.1016/j.jgar.2020.09.025.

Padayatty, S.J.; Sun, A.Y.; Chen, Q.; Espey, M.G.; Drisko, J.; Levine, M. Vitamin C: Intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS ONE, 2010, 5, e11414.

Padayatty, S.J.; Sun, H.; Wang, Y.; Riordan, H.D.; Hewitt, S.M.; Katz, A.; Wesley, R.A.; Levine, M. Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use. Ann. Intern. Med. 2004, 140, 533, https://doi.org/10.7326/0003-4819-140-7-200404060-00010.

 Levine, M.; Conry-Cantilena, C.; Wang, Y.; Welch, R.W.; Washko, P.W.; Dhariwal, K.R.; Park, J.B.; Lazarev, A.; Graumlich, J.F.; King, J.; et al. Vitamin C pharmacokinetics in healthy volunteers: Evidence for a recommended dietary allowance. Proc. Natl. Acad. Sci. USA 1996, 93, 3704–3709, https://doi.org/10.1073/pnas.93.8.3704.

Davis, J.L.; Paris, H.L.; Beals, J.W.; Binns, S.E.; Giordano, G.R.; Scalzo, R.L.; Schweder, M.M.; Blair, E.; Bell, C. Liposomal-encapsulated Ascorbic Acid: Influence on Vitamin C Bioavailability and Capacity to Protect Against Ischemia-Reperfusion Injury. Nutr. Metab. Insights 2016, 9, 25–30.

Lykkesfeldt, J.; Tveden-Nyborg, P. The Pharmacokinetics of Vitamin, C. Nutrients 2019, 11, 2412.

Riordan, H.D.; Casciari, J.J.; González, M.J.; Riordan, N.H.; Miranda-Massari, J.R.; Taylor, P.; Jack-son, J.A. A pilot clinical study of continuous intravenous ascorbate in terminal cancer patients. Puerto Rico Health Sci. J. 2005, 24, 269–276.

Gao, D.; Xu, M.; Wang, G.; Lv, J.; Ma, X.; Guo, Y.; Zhang, D.; Yang, H.; Jiang, W.; Deng, F.; et al. The efficiency and safety of high-dose vitamin C in patients with COVID-19: A retrospective co-hort study. Aging 2021, 13, 7020–7034, https://doi.org/10.18632/aging.202557.

Jariwalla, R.J.; Harakeh, S. Antiviral and Immunomodulatory Activities of Ascorbic Acid. In Sub-cellular Biochemistry. Subcellular Biochemistry (Ascorbic Acid: Biochemistry and Biochemical Cell Biology); Harris, J.R., Ed.; Springer: Boston, MA, USA, 1996; Volume 25, https://doi.org/10.1007/978-1-4613-0325-1_11.

Murata, A.; Uike, M. Mechanism of inactivation of bacteriophage MS2 containing single-stranded RNA by ascorbic acid. J. Nutr. Sci. Vitaminol. 1976, 22, 347–354.

Cheng, L.L.; Liu, Y.Y.; Li, B.; Li, S.Y.; Ran, P.X. An in vitro study on the pharmacological ascor-bate treatment of influenza virus. Chin. J. Tuberc. Respir. Dis. 2012, 35, 520–523.

Furuya, A.; Uozaki, M.; Yamasaki, H.; Arakawa, T.; Arita, M.; Koyama, A.H. Antiviral effects of ascorbic and dehydroascorbic acids in vitro. Int. J. Mol. Med. 2008, 22, 541–545.

Mikirova, NA & Hunninghake, R. Effect of high dose vitamin C on Epstein-Barr viral infection. Med Sci. Monit. 2014, 20, 725–732, https://doi.org/10.12659/msm.890423.

Schwerdt, P.R.; Schwerdt, C.E. Effect of ascorbic acid on rhinovirus replication in WI-38 cells. Proc. Soc. Exp. Biol. Med. 1975, 148, 1237–1243, https://doi.org/10.3181/00379727-148-38724.

Kim, Y.; Kim, H.; Bae, S.; Choi, J.; Lim, S.Y.; Lee, N.; Kong, J.M.; Hwang, Y.-I.; Kang, J.S.; Lee, W.J. Vitamin C Is an Essential Factor on the Anti-viral Immune Responses through the Production of Interferon-α/β at the Initial Stage of Influenza A Virus (H3N2) Infection. Immune Netw. 2013, 13, 70, https://doi.org/10.4110/in.2013.13.2.70.

Cai, Y.; Li, Y.F.; Tang, L.P.; Tsoi, B.; Chen, M.; Chen, H.; Chen, X.M.; Tan, R.R.; Kurihara, H.; He, R.R. A new mechanism of vitamin C effects on A/FM/1/47(H1N1) virus-induced pneumonia in re-straint-stressed mice. Biomed. Res. Int. 2015, 2015, 675149, https://doi.org/10.1155/2015/675149.

Dahl, H.; Degré, M. The effect of ascorbic acid on production of human interferon and the antivi-ral activity in vitro. Acta Pathol. Microbiol. Scand. 1976, 84B, 280–284, https://doi.org/10.1111/j.1699-0463.1976.tb01938.x.

Gonzalez MJ, Miranda-Massari, JR, Berdiel MJ, Duconge J, Rodríguez-López L, Hunninghake, R., Cobas-Rosario VJ. High dose intravenous Vitamin C and Chikungunya fever: A case report. J. Or-thomol. Med. 2014, 29, 154–156.

Gonzalez, MJ, Berdiel MJ, Olalde, J. Intravenous Vitamin C and Infectious Mononucleosis: A case report. J. Orthomol. Med. 2018, 33, 1–2.

Fowler Iii AA, Kim C, Lepler L, Malhotra R, Debesa O, Natarajan R, Fisher BJ, Syed A, DeWilde C, Priday A, Kasirajan, V. Intravenous vitamin C as adjunctive therapy for enterovirus/rhinovirus in-duced acute respiratory distress syndrome. World J Crit Care Med. 2017, 6, 85–90, doi:10.5492/wjccm.v6.i1.85.

Fowler AA 3rd, Truwit JD, Hite RD, Morris PE, DeWilde C, Priday A, Fisher B, Thacker LR 2nd, Natarajan R, Brophy DF, Sculthorpe R, Nanchal R, Syed A, Sturgill J, Martin GS, Sevransky J, Kashiouris M, Hamman S, Egan KF, Hastings A, Spencer W, Tench S, Mehkri O, Bindas J, Duggal A, Graf J, Zellner S, Yanny L, McPolin C, Hollrith T, Kramer D, Ojielo C, Damm T, Cassity E, Wieliczko, A., Halquist, M. Effect of Vitamin C Infusion on Organ Failure and Biomarkers of In-flammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial. JAMA. 2019, 322, 1261–1270, doi:10.1001/jama.2019.11825.

Bharara, A.; Grossman, C.; Grinnan, D.; Syed, A.; Fisher, B.; DeWilde, C.; Natarajan, R.; Fowler, A.A. Intravenous Vitamin C Administered as Adjunctive Therapy for Recurrent Acute Respiratory Distress Syndrome. Case Rep. Crit. Care 2016, 2016, 8560871, https://doi.org/10.1155/2016/8560871.

Marik, P.E.; Khangoora, V.; Rivera, R.; Hooper, M.H.; Catravas, J.; Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study. Chest 2017, 151, 1229–1238.

Iglesias, J.; Vassallo, A.V.; Patel, V.V.; Sullivan, J.B.; Cavanaugh, J.; Elbaga, Y. Outcomes of Meta-bolic Resuscitation Using Ascorbic Acid, Thiamine, and Glucocorticoids in the Early Treatment of Sepsis. Chest 2020, 158, 164–173.

Gonzalez, M.J., Berdiel, M.J., Olalde, J., Miranda-Massari, J.R., Marcial, V., & Aponte, A. Intra-venous vitamin C and an orthomolecular protocol as therapy for COVID19: A case report. J. Or-thomol. Med. 2020, 35, 1–3.

Waqas Khan, H.M.; Parikh, N.; Megala, S.M.; Predeteanu, G.S. Unusual Early Recovery of a Criti-cal COVID-19 Patient after Administration of Intravenous Vitamin, C. Am. J. Case Rep. 2020, 21, e925521, https://doi.org/10.12659/AJCR.925521.

Hiedra, R.; Lo, K.B.; Elbashabsheh, M.; Gul, F.; Wright, R.M.; Albano, J.; Azmaiparashvili, Z.; Aponte, G.P. The use of IV vitamin C for patients with COVID-19: A case series. Exp. Rev. Anti-Infect. Ther. 2020, 18, 1259–1261, https://doi.org/10.1080/14787210.2020.1794819.

Richardson, S.; Hirsch, J.S.; Narasimhan, M.; Crawford, J.M.; McGinn, T.; Davidson, K.W.; Barna-by, D.P.; Becker, L.B.; Chelico, J.D.; Cohen, S.L.; et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 2020, 323, 2052.

Douedi, S.; Miskoff, J. Novel coronavirus 2019 (COVID-19): A case report and review of treat-ments. Medicine. 2020, 99, e20207, https://doi.org/10.1097/MD.0000000000020207.

Bahloul, M.; Ketata, W.; Lahyeni, D.; Mayoufi, H.; Kotti, A.; Smaoui, F.; Kallel, N.; Daoud, E.; Bouaziz, M.; Kammoun, S. Pulmonary capillary leak syndrome following COVID-19 virus infec-tion. J. Med. Virol. 2021, 93, 94–96, https://doi.org/10.1002/jmv.26152.

Zhao, B.; Ling, Y.; Li, J.; Peng, Y.; Huang, J.; Wang, Y.; Qu, H.; Gao, Y.; Li, Y.; Hu, B.; et al. Bene-ficial aspects of high dose intravenous vitamin C on patients with COVID-19 pneumonia in severe condition: A retrospective case series study. Ann. Palliat. Med. 2021, 10, 1599–1609, https://doi.org/10.21037/apm-20-1387.

Zhao, B.; Liu, M.; Liu, P.; Peng, Y.; Huang, J.; Li, M.; Wang, Y.; Xu, L.; Sun, S.; Qi, X.; et al. High Dose Intravenous Vitamin C for Preventing the Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study. Front. Pharmacol. 2021, 12, 638556, https://doi.org/10.3389/fphar.2021.638556.

 Jamali Moghadam Siahkali S, Zarezade B, Koolaji S, SeyedAlinaghi S, Zendehdel A, Tabarestani M, Sekhavati Moghadam E, Abbasian L, Dehghan Manshadi SA, Salehi M, Hasannezhad M, Ghader-khani S, Meidani M, Salahshour F, Jafari F, Manafi N, Ghiasvand, F. Safety and effectiveness of high-dose vitamin C in patients with COVID-19: A randomized open-label clinical trial. Eur J Med Res. 2021, 26, 20, doi:10.1186/s40001-021-00490-1. PMID: 33573699; PMCID: PMC7877333.

Zhang J, Rao X, Li Y, Zhu Y, Liu F, Guo G, Luo G, Meng Z, De Backer D, Xiang, H., Peng, Z. Pilot trial of high-dose vitamin C in critically ill COVID-19 patients. Ann Intensive Care. 2021, 11, 5, doi:10.1186/s13613-020-00792-3. PMID: 33420963; PMCID: PMC7794643.

Pizzino, G.; Irrera, N.; Cucinotta, M.; Pallio, G.; Mannino, F.; Arcoraci, V.; Squadrito, F.; Altavilla, D.; Bitto, A. Oxidative Stress: Harms and Benefits for Human Health. Oxidative Med. Cell. Lon-gev. 2017, 2017, 8416763, https://doi.org/10.1155/2017/8416763.

Chernyak, B.V.; Popova, E.N.; Prikhodko, A.S.; Grebenchikov, O.A.; Zinovkina, L.A.; Zinovkin, R.A. COVID-19 and oxidative stress. Biochemistry 2020, 85, 1543–1553, https://doi.org/10.1134/s0006297920120068.

Suhail, S.; Zajac, J.; Fossum, C.; Lowater, H.; McCracken, C.; Severson, N.; Laatsch, B.; Narkie-wicz-Jodko, A.; Johnson, B.; Liebau, J.; et al. Role of Oxidative Stress on SARS-CoV (SARS) and SARS-CoV-2 (COVID-19) Infection: A. Review. Protein, J. 2020, 39, 644–656, https://doi.org/10.1007/s10930-020-09935-8.

Hati, S.; Bhattacharyya, S. Impact of thiol-disulfide balance on the binding of Covid-19 spike pro-tein with angiotensin-converting enzyme 2 receptor. ACS Omega 2020, 5, 16292–16298.

Busse, L.W.; Chow, J.H.; McCurdy, M.T.; Khanna, A.K. COVID-19 and the RAAS-a potential role for angiotensin II? Crit. Care 2020, 24, 136.

Cecchini, R.; Cecchini, A.L. SARS-CoV-2 infection pathogenesis is related to oxidative stress as a response to aggression. Med. Hypotheses 2020, 143, 110102, https://doi.org/10.1016/j.mehy.2020.110102.

Muhammad, Y.; Kani, Y.A.; Iliya, S.; Muhammad, J.B.; Binji, A.; Ahmad, A.E.-F.; Kabir, M.B.; Bindawa, K.U.; Ahmed, A. Deficiency of antioxidants and increased oxidative stress in COVID-19 patients: A cross-sectional comparative study in Jigawa, Northwestern Nigeria. SAGE Open Med. 2021, 9, 205031212199124, https://doi.org/10.1177/2050312121991246.

Reider, C.A.; Chung, R.Y.; Devarshi, P.P.; Grant, R.W.; Hazels Mitmesser, S. Inadequacy of Im-mune Health Nutrients: Intakes in US Adults, the 2005–2016 NHANES. Nutrients 2020, 12, 1735, https://doi.org/10.3390/nu12061735.

Im JH, Je YS, Baek J, Chung MH, Kwon HY, Lee JS. Nutritional status of patients with COVID-19. Int J Infect Dis. 2020 Nov;100:390-393, doi:10.1016/j.ijid.2020.08.018.

Cooper, S.A.; Whaley-Connell, A.; Habibi, J.; Wei, Y.; Lastra, G.; Manrique, C.; Stas, S.; Sowers, J.R. Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin re-sistance. Am. J. Physiol. Heart Circ. Physiol. 2007, 293, H2009–H2023.

Sowers, J.R. Hypertension, angiotensin II, and oxidative stress. N. Engl. J. Med. 2002, 346, 1999–2001.

Patel, V.; Dial, K.; Wu, J.; Gauthier, A.G.; Wu, W.; Lin, M.; Espey, M.G.; Thomas, D.D.; Ashby, J.C.R.; Mantell, L.L. Dietary Antioxidants Significantly Attenuate Hyperoxia-Induced Acute In-flammatory Lung Injury by Enhancing Macrophage Function via Reducing the Accumulation of Airway HMGB1. Int. J. Mol. Sci. 2020, 21, 977, https://doi.org/10.3390/ijms21030977.

Holford P, Carr AC, Jovic TH; et al. Vitamin C-An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19. Nutrients. 2020, 12, 3760. Published 2020 Dec 7, doi:10.3390/nu12123760.

Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; et al. Clini-cal features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020, 395, 497–506, https://doi.org/10.1016/S0140-6736(20)30183-5.

Ackermann, M.; Verleden, S.E.; Kuehnel, M.; Haverich, A.; Welte, T.; Laenger, F.; Vanstapel, A.; Werlein, C.; Stark, H.; Tzankov, A.; et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19. N. Eng. J. Med. 2020, 383, 120–128, https://doi.org/10.1056/nejmoa2015432.

Wang, C.; Xie, J.; Zhao, L.; Fei, X.; Zhang, H.; Tan, Y.; Nie, X.; Zhou, L.; Liu, Z.; Ren, Y.; et al. Al-veolar macrophage dysfunction and cytokine storm in the pathogenesis of two severe COVID-19 patients. EBioMedicine 2020, 57, 102833, https://doi.org/10.1016/j.ebiom.2020.102833.

Ye, Q.; Wang, B.; Mao, J. The pathogenesis and treatment of the `Cytokine Storm’ in COVID-19. J. Infect. 2020, 80, 607–613, https://doi.org/10.1016/j.jinf.2020.03.037.

Hojyo, S.; Uchida, M.; Tanaka, K.; Hasebe, R.; Tanaka, Y.; Murakami, M.; Hirano, T. How COVID-19 induces cytokine storm with high mortality. Inflamm. Regen. 2020, 40, 37, https://doi.org/10.1186/s41232-020-00146-3.

Mikirova, N.; Riordan, N.; Casciari, J. Modulation of Cytokines in Cancer Patients by Intravenous Ascorbate Therapy. Med. Sci. Monit. 2016, 22, 14–25, https://doi.org/10.12659/msm.895368.

Fiorino, S.; Gallo, C.; Zippi, M.; Sabbatani, S.; Manfredi, R.; Moretti, R.; Fogacci, E.; Maggioli, C.; Loffredo, F.T.; Giampieri, E.; et al. Cytokine storm in aged people with CoV-2: Possible role of vit-amins as therapy or preventive strategy. Aging Clin. Exp. Res. 2020, 32, 2115–2131, https://doi.org/10.1007/s40520-020-01669-y.

Kasahara, H.; Kondo, T.; Nakatsukasa, H.; Chikuma, S.; Ito, M.; Ando, M.; Kurebayashi, Y.; Seki-ya, T.; Yamada, T.; Okamoto, S.; et al. Generation of allo-antigen-specific induced Treg stabilized by vitamin C treatment and its application for prevention of acute graft versus host disease model. Int. Immunol. 2017, 29, 457–469, https://doi.org/10.1093/intim m/dxx06 0.

Hernández A, Papadakos PJ, Torres, A.; et al. Two known therapies could be useful as adjuvant therapy in critical patients infected by COVID-19 [Dos terapias conocidas podrían ser efectivas como adyuvantes en el paciente crítico infectado por COVID-19]. Revista Española de Anestesi-ología y Reanimación (English Edition). 2020, 67, 245–252, doi:10.1016/j.redare.2020.05.002.

Fisher BJ, Kraskauskas D, Martin EJ, Farkas D, Wegelin JA, Brophy D, Ward KR, Voelkel NF, Fowler AA 3rd, Natarajan, R. Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid. Am J Physiol Lung Cell Mol Physiol. 2012, 303, L20–L32, doi:10.1152/ajplung.00300.2011.

Teafatiller T, Agrawal S, De Robles G, Rahmatpanah F, Subramanian VS, Agrawal, A. Vitamin C Enhances Antiviral Functions of Lung Epithelial Cells. Biomolecules. 2021, 11, 1148. Published 2021 Aug 3, doi:10.3390/biom11081148.

Hasan, S.S.; Capstick, T.; Ahmed, R.; Kow, C.S.; Mazhar, F.; Merchant, H.; Zaidi, S.T.R. Mortality in COVID-19 patients with acute respiratory distress syndrome and corticosteroids use: A system-atic review and meta-analysis. Expert Rev. Respir Med. 2020, 14, 1149–1163, https://doi.org/10.1080/17476348.2020.1804365.

Chiscano-Camón, L.; Ruiz-Rodriguez, J.C.; Ruiz-Sanmartin, A.; Roca, O.; Ferrer, R. Vitamin C lev-els in patients with Sars-cov-2-associated acute respiratory distress syndrome. Crit. Care 2020, 24, 522, https://doi.org/10.1186/s13054-020-03249-y.

Tomasa-Irriguible, T.M.; Bielsa-Berrocal, L. COVID-19: Up to 82% critically ill patients had low Vitamin C values. Nutr. J. 2021, 20, 66, https://doi.org/10.1186/s12937-021-00727-z.

Carr, A.C.; Rosengrave, P.C.; Bayer, S.; Chambers, S.; Mehrtens, J.; Shaw, G.M. Hypovitaminosis C and vitamin C deficiency in critically ill patients despite recommended enteral and parenteral intakes. Crit. Care 2017, 21, 300, https://doi.org/10.1186/s13054-017-1891-y.

Carr, A.C.; Rowe, S. The Emerging Role of Vitamin C in the Prevention and Treatment of COVID-19. Nutrients 2020, 12, 3286, https://doi.org/10.3390/nu12113286.

Tanzer, F.; Ozalp, I. Leucocyte ascorbic acid concentration and plasma ascorbic acid levels in chil-dren with various infections. Mater. Med. Pol. 1993, 25, 5–8.

Long, C.L.; Maull, K.I.; Krishnan, R.S.; Laws, H.L.; Geiger, J.W.; Borghes, L.; Franks, W.; Lawson, T.C.; Sauberlich, H.E. Ascorbic acid dynamics in the seriously ill and injured. J. Surg. Res. 2003, 109, 144–148, https://doi.org/10.1016/s0022-4804(02)00083-5.

Mayland, C.R.; Bennett, M.I.; Keith Allan, K. Vitamin C deficiency in cancer patients. Palliat. Med. 2005, 19, 17–20.

Sinclair, A.J.; Taylor, P.B.; Lunec, J.; Girling, A.J.; Barnett, A.H. Low plasma ascorbate levels in pa-tients with type 2 diabetes mellitus consuming adequate dietary vitamin C. Diabetes Med. 1994, 11, 893–898.

Spiezia L, Boscolo A, Poletto F, Cerruti L, Tiberio I, Campello E, Navalesi P, Simioni, P. COVID-19-Related Severe Hypercoagulability in Patients Admitted to Intensive Care Unit for Acute Respira-tory Failure. Thromb Haemost. 2020, 120, 998–1000, doi:10.1055/s-0040-1710018.

López Castro, J. COVID-19 and thrombosis: Beyond a casual association. Medicina Clínica 2020, 155, 44, https://doi.org/10.1016/j.medcli.2020.04.014.

Hanff, T.C.; Mohareb, A.M.; Giri, J.; Cohen, J.B.; Chirinos, J.A. Thrombosis in COVID-19. Am. J. Hematol. 2020, 95, 1578–1589, https://doi.org/10.1002/ajh.25982.

Willyard, C. Coronavirus blood-clot mystery intensifies. Nature 2020, 581, 250–250, https://doi.org/10.1038/d41586-020-01403-8.

Helms, J.; Tacquard, C.; Severac, F.; Leonard-Lorant, I.; Ohana, M.; Delabranche, X.; Merdji, H.; Clere-Jehl, R.; Schenck, M.; Gandet, F.F.; et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: A multicenter prospective cohort study. Intensive Care Med. 2020, 46, 1089–1098, https://doi.org/10.1007/s00134-020-06062-x.

Huertas, A.; Montani, D.; Savale, L.; Pichon, J.; Tu, L.; Parent, F.; Guignabert, C.; Humbert, M. Endothelial cell dysfunction: A major player in SARS-CoV-2 infection (COVID-19)? Eur. Respir. J. 2020, 56, 2001634, https://doi.org/10.1183/13993003.01634-2020.

Tyml, K. Vitamin C and microvascular dysfunction in systemic inflammation. Antioxidants. 2017, 6, 49.

Soni, M.; Gopalakrishnan, R.; Vaishya, R.; Prabu, P. D-dimer level is a useful predictor for mortali-ty in patients with COVID-19: Analysis of 483 cases. Diabetes Metab. Syndr. Clin. Res. Rev. 2020, 14, 2245–2249, https://doi.org/10.1016/j.dsx.2020.11.007.

Farndale, R.W.; Sixma, J.J.; Barnes, M.J.; De Groot, P.G. The role of collagen in thrombosis and hemostasis. J. Thromb. Haemost. 2004, 2, 561–573, https://doi.org/10.1111/j.1538-7836. 2004.00665.x.

Murad, S.; Grove, D.; Lindberg, K.A.; Reynolds, G.; Sivarajah, A.; Pinnell, S.R. Regulation of colla-gen synthesis by ascorbic acid. Proc. Natl. Acad. Sci. USA. 1981, 78, 2879–2882, https://doi.org/10.1073/pnas.78.5.2879.

Shekhonin, B.V.; Domogatsky, S.P.; Idelson, G.L.; Koteliansky, V.E.; Rukosuev, V.S. Relative dis-tribution of fibronectin and type I, III, IV, V collagens in normal and atherosclerotic intima of hu-man arteries. Atherosclerosis. 1987, 67, 9–16.

Rixen, H.; Kirkpatrick, C.J.; Schmitz, U.; Ruchatz, D.; Mittermayer, C. Interaction between endo-thelial cells and basement membrane components. In vitro studies on endothelial cell adhesion to collagen types I, III, IV and high molecular weight fragments of IV. Exp. Cell Biol. 1989, 57, 315–323.

Tamareille, S.; Mignen, O.; Capiod, T.; Rucker-Martin, C.; Feuvray, D. High glucose-induced apoptosis through storeoperated calcium entry and calcineurin in human umbilical vein endothe-lial cells. Cell Calcium. 2006, 39, 47–55.

Taddei S, Virdis A, Ghiadoni L, Magagna A, Salvetti, A. Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. Circulation. 1998, 97, 2222–2229, doi:10.1161/01.cir.97.22.2222. PMID: 9631871.

May, J.M.; Qu, Z.C.; Qiao, H. Transfer of ascorbic acid across the vascular endothelium: Mecha-nism and selfregulation. Am. J. Physiol. Cell Physiol. 2009, 297, C169–C178.

May, J.M.; Harrison, F.E. Role of Vitamin C in the Function of the Vascular Endothelium. Antiox-id. Redox Signal. 2013, 19, 2068–2083, https://doi.org/10.1089/ars.2013.5205.

Yau, J.W.; Teoh, H.; Verma, S. Endothelial cell control of thrombosis. BMC Cardiovasc. Disord. 2015, 15, 130, https://doi.org/10.1186/s12872-015-0124-z.

Chen, Q.; Espey, M.G.; Krishna, M.C.; Mitchell, J.B.; Corpe, C.P.; Buettner, G.R.; Shacter, E.; Lev-ine, M. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen peroxide to tissues. Proc. Natl. Acad. Sci. USA. 2005, 102, 13604–13609.

Odajima, N.; Betsuyaku, T.; Nagai, K.; Moriyama, C.; Wang, D.H.; Takigawa, T.; Ogino, K.; Nishimura, M. The Role of Catalase in Pulmonary Fibrosis. Respir. Res. 2010, 11, 183.

Doskey, C.M.; Buranasudja, V.; Wagner, B.A.; Wilkes, J.G.; Du, J.; Cullen, J.J.; Buettner, G.R. Tu-mor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy. Redox Biol. 2016, 10, 274–284.

Kampf, G.; Todt, D.; Pfaender, S.; Steinmann, E. Persistence of coronaviruses on inanimate surfac-es and their inactivation with biocidal agents. J. Hosp. Infect. 2020, 104, 246–251.

Kang, M.Y.; Kim, H.-B.; Piao, C.; Lee, K.H.; Hyun, J.W.; Chang, I.-Y.; You, H.J. The critical role of catalase in prooxidant and antioxidant function of p53. Cell Death Differ. 2013, 20, 117–129.

Wenzhong L, Hualan, L. COVID-19: Captures iron and generates reactive oxygen species to dam-age the human immune system. Autoimmunity. 2021 Jun;54(4):213-224, doi:10.1080/08916934.2021.1913581.

Shaver, C.M.; Upchurch, C.P.; Janz, D.R.; Grove, B.S.; Putz, N.D.; Wickersham, N.E.; Dikalov, S.I.; Ware, L.B.; Bastarache, J.A. Cell-free hemoglobin: A novel mediator of acute lung injury. Am. J. Physiol.-Lung Cell. Mol. Physiol. 2016, 310, L532–L541, https://doi.org/10.1152/ajplung.00155.2015.

Habegger, L.; McNeil, J.B.; Kerchberger, V.E.; Ware, L.B.; Shaver, C.M.; Schmidt, E.P.; Bastarache, J.A. (2019). Cell-Free Hemoglobin Levels in the Distal Airspace of Patients with Acute Respiratory Distress Syndrome (ARDS) Are Associated with Markers of Lung Epithelial Injury, Airspace In-flammation, and Alveolar Permeability. Am. J. Respir. Crit. Care Med. 2019, 199, A2079–A2079, https://doi.org/10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a2079.

Loh, D. The potential of melatonin in the prevention and attenuation of oxidative hemolysis and myocardial injury from cd147 SARS-CoV-2 spike protein receptor binding Melatonin for hemolysis in COVID-19. 2020, 3, 380–416.

Chowdhury, S.F.; Anwar, S. Management of hemoglobin disorders during the covid-19 pandemic. Front. Med. 2020, 7, 306, doi.org/10.3389/fmed.2020.00306.

Cavezzi A, Troiani E, Corrao, S. COVID-19: Hemoglobin, iron, and hypoxia beyond inflammation. A narrative review. Clin Pract. 2020, 10, 1271, doi:10.4081/cp.2020.1271.

Radzikowska, U.; Ding, M.; Tan, G.; Zhakparov, D.; Peng, Y.; Wawrzyniak, P.; Wang, M.; Li, S.; Morita, H.; Altunbulakli, C.; et al. Distribution of ACE2, CD147, CD26, and other SARS-CoV-2 as-sociated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hyper-tension, and COVID-19 risk factors. Allergy 2020, 75, 2829–2845, https://doi.org/10.1111/all.14429.

Lane DJR and Richardson DR. The active role of vitamin C in mammalian iron metabolism: Much more than just enhanced iron absorption!. Free Radical Biology and Medicine. 2014, 75, 69–83. ISSN 0891-5849. https://doi.org/10.1016/j.freeradbiomed.2014.07.007.

Kuck, J.L.; Bastarache, J.A.; Shaver, C.M.; Fessel, J.P.; Dikalov, S.I.; May, J.M.; Ware, L.B. Ascorbic acid attenuates endothelial permeability triggered by cell-free hemoglobin. Biochem. Biophys. Res. Commun. 2018, 495, 433–437, https://doi.org/10.1016/j.bbrc.2017.11.058.

Wang, Y.; Lin, H.; Lin, B.W.; Lin, J.D. Effects of different ascorbic acid doses on the mortality of critically ill patients: A meta-analysis. Ann. Intensive Care 2019, 9, 58, https://doi.org/10.1186/s13613-019-0532-9.

Gavriatopoulou M, Korompoki E, Fotiou D, Ntanasis-Stathopoulos I, Psaltopoulou T, Kastritis E, Terpos E, Dimopoulos MA. Organ-specific manifestations of COVID-19 infection. Clin Exp Med. 2020, 20, 493–506, doi:10.1007/s10238-020-00648-x. Epub 2020 Jul 27. PMID: 32720223; PMCID: PMC7383117.

Zou, X.; Chen, K.; Zou, J.; Han, P.; Hao, J.; Han, Z. Single-cell RNA-seq data analysis on the re-ceptor ACE2 expression reveals the potential risk of different human organs vulnerable to 2019-nCoV infection. Front. Med. 2020, 14, 185–192, https://doi.org/10.1007/s11684-020-0754-0.

Braun, F.; Lütgehetmann, M.; Pfefferle, S.; Wong, M.N.; Carsten, A.; Lindenmeyer, M.T.; Nörz, D.; Heinrich, F.; Meißner, K.; Wichmann, D.; et al. SARS-CoV-2 renal tropism associates with acute kidney injury. Lancet 2020, 396, 597–598, https://doi.org/10.1016/s0140-6736(20)31759-1.

Kalantar-Zadeh, K.; Moore, L.W. Impact of Nutrition and Diet on COVID-19 Infection and Impli-cations for Kidney Health and Kidney Disease Management. J. Ren. Nutr. 2020, 30,179–181, https://doi.org/10.1053/j.jrn.2020.03.006.

Nualart, F.; Mack, L.; García, A.; Cisternas, P.; Bongarzone, E.R.; Heitzer, M.; Jara, N.; Martínez, F.; Ferrada, L.; Espinoza, F.; et al. Vitamin C transporters, recycling and the bystander effect in the nervous system: SVCT2 versus gluts. J. Stem Cell Res. Ther. 2014, 4, 209.

Bürzle, M.; Suzuki, Y.; Ackermann, D.; Miyazaki, H.; Maeda, N.; Clémençon, B.; Burrier, R.; Hedi-ger, M.A. The sodium-dependent ascorbic acid transporter family SLC23. Mol. Aspects Med. 2013, 34, 436–454.

Rice, M.E. Ascorbate regulation and its neuroprotective role in the brain. Trends Neurosci. 2000, 23, 209–216.

Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, Szigeti-Buck K, Yasumoto Y, Wang G, Castaldi C, Heltke J, Ng E, Wheeler J, Alfajaro MM, Levavasseur E, Fontes B, Ravindra NG, Van Dijk D, Mane S, Gunel M, Ring A, Kazmi SAJ, Zhang K, Wilen CB, Horvath TL, Plu I, Haik S, Thomas JL, Louvi A, Farhadian SF, Huttner A, Seilhean D, Renier N, Bilguvar K, Iwasaki, A. Neuroinvasion of SARS-CoV-2 in human and mouse brain. J Exp Med. 2021, 218, e20202135, doi:10.1084/jem.20202135.

May, J.M. Vitamin C Transport and Its Role in the Central Nervous System. Subcell. Biochem. 2011, 56, 85–103, https://doi.org/10.1007/978-94-007-2199-9_6.[M3]

 


 

 

 

[M1]Please cite ref 113, 114 and 115 in the main text. Please notice references need to be cited in numberial order.

 

 

[JM2]They were correctly displayed in the manuscripts I send. I used the same document called proof ref only numbers to correct this document.

 

 

[M3]Please cite ref 113-115 in the main text.

Master the Fundamental Principles of Poker and Some of Its Variants – Ideal Facts Globe

Master the Fundamental Principles of Poker and Some of Its Variants – Ideal Facts Globe

[ad_1]

Poker

A simple expertise of poker can aid you gain income in the poker activity. This post will assist you master the Fundamental Policies of Poker and some of its versions, which include the Betting intervals. This post also involves some tips on how to earn at poker. By the time you’re finished reading, you are going to be equipped to perform poker like the professional. But 1st, let’s take a closer seem at how poker video games work. How are the chips and money placed in the pot decided?

Procedures of poker

Poker procedures can differ significantly from sort to type, but the intention is often the exact – to have the ideal 5-card hand in a recreation of poker. This requires that all opponents fold just before the very last betting spherical. Each and every variant has its own established of principles – Straight Flush is a hand of five playing cards of the identical match, 4 of a Sort is 4 of a sort furthermore one random card, and Full Household is 3 of the very same rank and two playing cards of a reduced rank.

Fundamental procedures

Poker is a card game that has a whole lot of distinct guidelines and versions. For case in point, in a standard poker video game, the player who built the past intense motion need to exhibit their cards 1st. This implies that if you wager on the river, you have to display your playing cards before your opponent. This simple rule exists to prevent unneeded dialogue and moi battles. In addition, exhibiting your most effective hand is not regarded unethical.

Versions

There are numerous varieties of poker online games, but most of them follow the exact simple principles. The games are comparable in terms of the rankings of poker palms, and they all stick to the same typical play pattern. While lots of gamers stick to their favored on the net poker video game, many others like to experiment with different types of versions to obtain out which ones they enjoy the most. Texas Hold’Em poker is 1 of the most well-known variations, and there are a great number of variants available on the website.

Betting intervals

The length of the betting intervals may differ among the the different poker game titles. The initial participant to act should location a bet, and the gamers to his still left must elevate in proportion to the whole contribution of the participant just before them. If no other participant acts, the sport ends. The first spherical of betting entails placing a least wager, and afterwards rounds let the participant to elevate or look at. The ultimate spherical consists of a showdown, in which the winner is decided by the quantity of chips remaining in the pot after each round of betting.

Restrict games

Normally called a “sevens rule,” the sevens rule in restrict poker is the basis for determining the profitable opportunity of a hand. If a player’s initially card is increased than 7, it is known as a “burn card” and is discarded from the deck. Read through much more about this rule in Explanations. Also, in limit video games, a player can not check-increase. As with other poker variants, players have to identify their utmost time in a match prior to producing a closing final decision about betting.

Attribute of bluffing

Even though poker is a sport of probability, it can also be a game of ability and psychology. While you can understand standard procedures and techniques for profitable, there is no substitute for working experience. Irrespective of the skill degree, the important to profitable poker is to discover to mislead your opponents and acquire precise steps to get the laydown you want. Below are some suggestions to win poker palms:

We’re one of the world’s oldest democracies: Random facts to fill your heart with Canadian pride

We’re one of the world’s oldest democracies: Random facts to fill your heart with Canadian pride

[ad_1]

Twice, Canadians have invented a medical cure so revolutionary it caused people to rise from their death beds

Article content

Today is Canada’s 155th birthday, and the first Canada Day in three years that will feature the usual festivities of fireworks and public concerts. Before you head out to wave the maple leaf, bask in these random pieces of Canadiana and feel yourself filled with the spirit of our great dominion. 

Advertisement 2

Article content

We’re one of the world’s oldest continuously operating democracies. There are plenty of older countries, of course, but the vast majority of them have been hit by some form of revolution, coup or invasion in the last 155 years. By some counts, we’re the world’s fourth oldest democracy (although the Americans obviously beat us on this point).

The UK Parliament was aggressively bored by the 1867 Act of Parliament that created Canada. The British North America Act was such tedious reading to the House of Lords that the parliamentary record contains multiple instances of the Colonial Secretary of the time apologizing that it was taking so much time. “There are defects in it, no doubt,” reads one of his many slams of our founding document.  

Advertisement 3

Article content

In the 1960s, some maniac thought that a giant eye would be an excellent Canadian flag and mailed this design to Ottawa. Fortunately, we ignored him and went with a stylized red maple leaf instead. Click here to see more rejected flag designs.
In the 1960s, some maniac thought that a giant eye would be an excellent Canadian flag and mailed this design to Ottawa. Fortunately, we ignored him and went with a stylized red maple leaf instead. Click here to see more rejected flag designs. Photo by University of Saskatchewan Archives and Special Collections

Would you believe that a Canadian farm helped to smash communism? In 1983, Mikhail Gorbachev was just a young and unknown member of the Soviet politburo when – during a state visit to Canada – he went to a friendly dinner at the Ontario farm of federal cabinet minister Eugene Whelan. While there, he struck up a conversation with Aleksandr Yakovlev, the Soviet Ambassador to Canada. Both men soon realized that they shared the same doubts about deep flaws in the Soviet system. The three hours of intense dialogue that followed would become the root of glasnost and perestroika, the reforms that Gorbachev would implement upon becoming Soviet leader – unwittingly setting in motion a series of events that would dissolve the Soviet Union within just eight years of the Ontario meeting.

Advertisement 4

Article content

We’re one of the world’s most heterogenous countries. In 2013, a German researcher set out to rank countries by “cultural diversity” – basically, how many distinct types of ethnicities and languages could be counted within a population. Canada turned out to be the clear North American leader in the category, and one of the most culturally diverse countries overall. Representatives of literally every ethnic group around the world hold Canadian citizenship, and the same holds true for speakers of all but the most obscure world languages. And unlike many of the other countries that scored high on cultural diversity, we haven’t descended into any serious internecine warfare in recent decades.

George H.W. Bush had once planned to become a Canadian. The patriarch of one of the most successful political dynasties in the United States (and a U.S. president himself), Bush had been seriously considering crossing the border to join the Royal Canadian Air Force in 1941. At that time, the U.S. was still neutral in the Second World War, so any American looking to fight the Axis had to join a Canadian unit. But then Pearl Harbor happened, the United States was plunged into war with both Germany and Japan, and Bush was able to get his wish to see combat by enlisting with the U.S. military.  

Advertisement 5

Article content

Stan Rogers sings Northwest Passage, a song often called Canada’s “unofficial national anthem.” Rogers was killed in a 1983 fire aboard an Air Canada flight, and he remains one of the last people ever killed in an Air Canada accident; the airline has had no fatal mishaps in the 39 years since. Click here to see the song performed live in the memorial documentary One Warm Line.
Stan Rogers sings Northwest Passage, a song often called Canada’s “unofficial national anthem.” Rogers was killed in a 1983 fire aboard an Air Canada flight, and he remains one of the last people ever killed in an Air Canada accident; the airline has had no fatal mishaps in the 39 years since. Click here to see the song performed live in the memorial documentary One Warm Line. Photo by YouTube

Twice in history, Canadians have invented a medical innovation so revolutionary that it literally caused people to rise from their deathbeds. The first was the 1921 discovery of insulin by Frederick Banting. Until then, childhood diabetes was terminal; the only treatment was to slowly starve the patient to death. But with insulin, diabetic wards around the world were soon reporting “resurrections” of emaciated, comatose children. And then we did it again in the 1990s. It was a Canadian doctor, Julio Montaner, who discovered the “drug cocktail” that transformed AIDS from a guaranteed death sentence into a manageable chronic condition. Once again, wards around the world reported a “Lazarus effect” as patients on the edge of death suddenly faced the prospect of growing old.

Advertisement 6

Article content

Canada became a nation in part because the IRA kept invading us. The idea of merging a bunch of British colonies into a centralized country came about largely as a security measure. The United States had just finished pounding the hell out of the secessionist Confederacy in the American Civil War, and Canadians of the time feared that Washington could just as easily turns their cannons north. But it was an invasion by a completely unexpected power that sealed the deal: Starting in 1866 – just a year before Confederation – parts of colonial Canada started getting attacked by ragtag Irish armies angry at the British.  

An atomic bomb has never been set off on Canadian soil – which is somewhat unexpected given that we were a key contributor to the Manhattan Project and have plenty of empty space that we could a-bomb if we wanted to. But there was a period of time when Canadians had The Bomb. From 1964 to 1984, U.S.-made nuclear weapons were in the arsenal of the Canadian Armed Forces – and that’s in addition to all the nuclear weapons that the Americans secretly kept at their Canadian bases.

Advertisement

Comments

Postmedia is committed to maintaining a lively but civil forum for discussion and encourage all readers to share their views on our articles. Comments may take up to an hour for moderation before appearing on the site. We ask you to keep your comments relevant and respectful. We have enabled email notifications—you will now receive an email if you receive a reply to your comment, there is an update to a comment thread you follow or if a user you follow comments. Visit our Community Guidelines for more information and details on how to adjust your email settings.

COVID-19 cases up by more than 30% in Britain previous 7 days

COVID-19 cases up by more than 30% in Britain previous 7 days

[ad_1]

The hottest surge will come soon after an earlier boost of about 40% previous month, adhering to the big road functions, concerts and festivities held to mark 70 several years of Queen Elizabeth II’s reign.

The hottest surge comes soon after an previously boost of about 40% past month, subsequent the massive street events, concert events and festivities held to mark 70 a long time of Queen Elizabeth II’s reign.

The amount of new coronavirus cases across Britain has surged by much more than 30% in the final 7 days, new details showed on Friday, with conditions largely driven by the tremendous infectious omicron variants.

Information produced by Britain’s Office environment for Countrywide Data confirmed that far more than 3 million persons in the U.K. had COVID-19 very last 7 days, though there has not been an equal spike in hospitalizations. The quantity of COVID-19 fatalities also fell marginally in the last week.

“COVID-19 has not absent absent,” stated Dr. Mary Ramsay, of the Overall health Security Agency. “It is also sensible to use a experience covering in crowded, enclosed spaces,” she explained. Britain dropped just about all its coronavirus steps, including mask-donning and social distancing months ago and masks are not often noticed on community transportation.

The most recent bounce in Covid scenarios will come after an before maximize of about 40% final thirty day period, next the big road get-togethers, concerts and festivities held to mark the platinum jubilee celebrations marking 70 yrs of Queen Elizabeth II’s reign.

British officers claimed the hottest wave of COVID-19 bacterial infections were most likely brought about by omicron subvariants BA.4. and BA.5. Omicron has tended to cause a milder ailment than preceding variants like alpha or delta, but experts warn its capability to evade the immune technique usually means that men and women might be extra susceptible to staying reinfected, such as just after vaccination.

“The frequent bombardment of waves we are looking at does cause medical influence that is not to be underestimated,” claimed Dr. Stephen Griffin, an associate professor of medication at the University of Leeds, describing that any infection can direct to lengthy COVID.

Irrespective of widespread immunization throughout Britain, the defense from vaccines is possible fading and omicron and its subvariants have progressed to develop into much more infectious. Britain’s Health Safety Agency reported they had been viewing additional outbreaks in care homes for older persons and a increase in admissions to intense treatment models of people above 65.

Dr. Jonathan Van-Tam, a previous deputy main professional medical officer for the U.K., instructed the BBC that COVID-19 is now “much, a great deal, a great deal closer to seasonal flu” than when it 1st emerged. Still, he stated specialists should really be vigilant for any symptoms the virus was triggering a lot more severe sickness.

Germany’s Robert Koch Institute also claimed a identical rise in the coronavirus, with situations raising in particular amongst older folks, kids and adolescents. France has witnessed a leap in the COVID-19 hospitalization price and officers not long ago proposed that people get started donning masks once again on public transport.

Globally, the Globe Wellbeing Business stated this week that COVID-19 is expanding in much more than 100 nations around the world throughout the world. The U.N. wellbeing company warned that comfortable screening and surveillance steps signify it may perhaps be extra complicated to capture emerging variants before they unfold more commonly.

Mike Magee’s Guidance to the AMA on Reversal of Roe vs. Wade

Mike Magee’s Guidance to the AMA on Reversal of Roe vs. Wade

[ad_1]

BY MIKE MAGEE

Steady, civic societies are built on human believe in and self confidence. If you were forced to rebuild a modern society, leveled by warfare and devastation, in which would you start? This is the dilemma the U.S. Military faced at the shut of WW II, particularly when it came to rebuilding Germany and Japan, with any luck , into steady democracies. The Marshall Strategy answered the problem higher than, and its achievements in choosing health and fitness providers as a starting place was effectively documented by a lot of in the many years to appear, like the RAND Company. Their summary in 2007 reported in component, “Country-constructing attempts simply cannot be thriving unless of course satisfactory interest is paid out to the wellness of the populace.” 

They commenced with services for gals and children, the very place that a splinter of politicians and Supreme Court Justices has focused, replacing entrusted doctors with partisan bureaucrats in an method so clearly flawed that it forced a training course correction a 50 percent-century in the past in the form of Roe v. Wade.

The follow of Drugs is elaborate. Ideally it demands awareness, abilities, supportive infrastructure, proximity and presence. But most of all, it calls for trust, particularly in moments of urgency, with lives at stake, when an particular person, and family, and neighborhood are all on higher inform. When time is of the essence, and specially if one particular or far more folks are striving to make the right conclusion for two, instead than a single lifestyle, selections are impossibly personal and intricate.

This was extensively recognized by most medical professionals, such as those most devout and conservative nationwide in the troubling several years leading up to Roe v. Wade. As lately as 1968, the membership of the Christian Health-related Society refused to endorse a proclamation that labeled abortion as sinful. In 1971, America’s main conservative religious organization, the Southern Baptist Convention, went on history as encouraging its members “to work for legislation that would allow for the chance of abortion underneath these types of disorders as rape, incest, crystal clear evidence of severe fetal deformity, and thoroughly ascertained evidence of the chance of problems to the emotional, mental, and actual physical health of the mom.” In 1973, the two the Southern Baptist Convention and the Christian Professional medical Society chose not to actively oppose the Supreme Courtroom ruling versus a Texas legislation prohibiting abortion recognised as Roe v. Wade, and reaffirmed that posture in 1974 and 1976.

What they recognized was that the nation’s social capital, its political steadiness and safety, relied intensely on the compassion, being familiar with and partnership engendered in the patient-doctor connection. As most medical practitioners noticed it, what achievable good could appear from placing politicians in the center of these types of difficult, emotion-ridden, and remarkably private selections?

The American Health care Association’s ready reaction to the June 24, 2022, reversal to Roe v. Wade was immediate and speedy. They labeled the decision “an egregious allowance of federal government intrusion into the healthcare examination home, a immediate attack on the follow of drugs and the client-health practitioner relationship…” Their president, Jack Resneck Jr. M.D. went even further to say, “…the AMA condemns the high courtrooms interpretation in this circumstance. We will often have medical professionalsbacks and protect the observe of drugs, we will struggle to protect the affected person-medical professional romance..” But what specifically does that suggest?

Approaching 75, and a lifelong member of the American Clinical Affiliation, I expect I know the AMA, its history as well as its strengths and weaknesses, as properly as anyone. Aside from owning deep own associations with quite a few of the Board of Trustees above the years (some of whom quietly keep on to call me for information), I have analyzed the evolution of the patient-medical professional marriage in six countries over a span of forty many years.

People who know me properly, and who have pushed back against my critique of the group, know that my intentions are honorable and that the alarms that I audio reflect my belief that, for our profession to endure as noble, self-governing, and dedicated earlier mentioned all to the clients who let us to care for them, we need to have a nationwide organization with arrive at into each American town and city, and formal representation in just about every condition, and just about every specialty.

My problem today, irrespective of the sturdy messaging from Chicago, is that the AMA and its customers have not thoroughly absorbed that this is a “mission-critical” minute in the organization’s background. It is also an option to purposefully flex its muscle groups, expand its membership, and strengthen its priorities. The sturdy words, without actions to back them up, I believe that, will permanently seal the AMA’s fate, and obstacle Medicine’s standing as a “profession.”

Listed here are five actions that I think the AMA should consider instantly to make it apparent that physicians stand united with our people, in partnership with nurses and other well being experts, and that the actions of final week can not and will not stand.

  1. The AMA should really pull all economic assistance for all Republican candidates through the 2022 elections.
  2. The AMA need to actively motivate doctor “civil disobedience” wherever acceptable to safeguard the well being and nicely getting of all women of all ages, no matter of age, race, sexual identity, faith, or financial status.
  3. The AMA really should convene, less than the auspices of its’ Basic Counsel, Andra K. Heller, a formal tactic assembly with the lawful counsels of all condition and specialty healthcare societies to formulate an aggressive legal tactic to decrease the injury of the the latest Supreme Court docket motion.
  4. The AMA ought to actively market AMA volunteers to enable offer a whole assortment of women’s wellbeing treatment providers at federal institutions and on federal land, and stand up data web pages that coordinate vacation and costs must inter-point out journey be demanded for treatment access.
  5. The AMA must immediately make crystal clear that any restriction of prescribing authority of medicines in guidance of women’s health and fitness care, together with contraceptive medications and gadgets, and Plan B therapies will consequence in a coordinated nationwide disruption of wellness companies.

Mike Magee MD is a Professional medical Historian and the writer of “CODE BLUE: Within the Health care-Industrial Complicated.”

We struggle all the time since our twins have been born. Should we get divorced? | Request Annalisa Barbieri

We struggle all the time since our twins have been born. Should we get divorced? | Request Annalisa Barbieri

[ad_1]

I have been with my spouse for 10 years. Two several years in the past, immediately after fertility cure, I grew to become expecting with twins, now 18 months outdated. Whilst overjoyed, I feel our marriage has experienced.

We really like our young children dearly. But time and funds are very seriously impacting our relationship, to the extent that divorce has arrive up.

The childcare charges are so much, and we’ve both of those experienced to make massive sacrifices. I have had to lower a working day from my function 7 days – it doesn’t audio like substantially, but I’m an academic and have supplied up my one analysis day to consider treatment of the twins. I sense unfortunate and annoyed. I went into this job mainly to do investigate, not accurate unlimited essays and then devote the relaxation of the time with the little ones. I sense robbed, like I did a PhD for nothing.

All of my wages go to fork out for childcare, so I really feel trapped amongst scraping my pennies together, by no means getting enough function done, and feeling bitter that all my time/income is likely to the kids. Really do not get me improper – I know what is included in staying a parent, and I realize that sacrifice is component of it. I’m just still left with nothing at all in the engine.

My wife, in the meantime, gets to work her five-day-a-week task (her occupation is not as adaptable as mine), but she is fatigued as she has to do the job shifts. We struggle about cleansing, childcare time, what we do with our unique free of charge time, and revenue. She has reported she feels trapped in our relationship since we have the youngsters and the house.

I nevertheless adore her, she’s a wonderful mom and commonly a excellent man or woman, but I’m receiving to a stage exactly where I resent her. I never imagine she loves me any a lot more and question: should really we get divorced?

Not yet. It all seems incredibly tricky. You have the two experienced such a massive daily life transform. Fertility remedy can be gruelling, and when you do get expecting and have little ones the pressure to feel happy and grateful is immense.

You audio like you experienced a fulfilled (and ordered) existence in advance of you had small children, and the modify from autonomous grownup to parenthood can get time to get employed to. You say you “know what is involved” in currently being a dad or mum, but I’m not absolutely sure anyone really does until finally they get there. The continual alertness, getting readily available 24/7, staying interrupted all the time, the slumber deprivation, the aggressive tiredness with one’s associate. They can challenge a person’s sanity.

I ponder if your wife sees the small children as far more “your” duty – and that you sense this, as you gave beginning to them? I wished to know why the childcare appear out of your wages alone?

I consulted UKCP psychotherapist Fe Robinson: “When we’re below a ton of stress we shed that generosity of remaining equipped to see points from an additional person’s level of see.”

We equally imagine that’s occurring with you and your spouse. “Also,” claims Robinson, “when you are tired and overstretched, everything feels like a work – even the joyful stuff.”

Robinson puzzled what your assist network was. When we come to feel resentful, we frequently want our associates to recognise this and “save” us. This could possibly not materialize as you both of those sound exceptionally stretched.

It’s practical to bear in mind that this hyper-dependent phase – where childcare sucks all your finances – is not for ever. “Remember, from the expression following they turn a few you will get some cost-free childcare,” states Robinson. But ahead of you know it, they will be in college. Issues will change once more.

Robinson also sensed a “struggle with identity you’re an academic with a PhD – maybe you experience you’ve offered up who you are, still are not feeling rewarded in your practical experience of mothering”. Consider to try to remember: these things consider time.

Robinson proposed an training she does with couples: “I get them to picture different distinct futures, eg, ‘What would your everyday living be like if you continue to be as you are in 6 months/a 12 months/5 many years?’ and you then review that to other scenarios this sort of as ‘What would it be like if we break up?’”

You probably feel you just can’t afford couples treatment, but it can be transformative – and splitting up is pricey. Also, the childcare will not get a lot easier, just much more sophisticated. Divorcing will not make you richer either. Splitting up may well truly feel like the only response but, from what you have mentioned, your relationship is even now value preserving.

Indication up to our Inside of Saturday e-newsletter for an unique behind-the-scenes glance at the making of the magazine’s largest features, as perfectly as a curated listing of our weekly highlights.

Just about every 7 days Annalisa Barbieri addresses a relatives-similar difficulty sent in by a reader. If you would like information from Annalisa on a family members subject, make sure you send your problem to ask.annalisa@theguardian.com. Annalisa regrets she are not able to enter into private correspondence. Submissions are issue to our phrases and ailments.

Reviews on this piece are premoderated to assure the dialogue remains on the topics lifted by the report. Be sure to be mindful that there may perhaps be a short delay in reviews showing on the site.

Discussions With Annalisa Barbieri, series 2, is out there here.

Trainers have dropped their edge – slip on some loafers if you want to slice it this summertime | Jess Cartner-Morley

Trainers have dropped their edge – slip on some loafers if you want to slice it this summertime | Jess Cartner-Morley

[ad_1]

Life utilized to be so uncomplicated. Loafers were wise and trainers have been not. Loafers had been for work or for extravagant trainers were being for days off and anything that involved running just after a ball. But modern lifetime has a habit of getting much more and more sophisticated, and footwear is no exception. The old procedures no extended use.

This seems like superior news than it truly is, due to the fact it was practical when trainers had been shorthand for peaceful dressing. There was no debate about what to wear at the weekend, simply because trainers were the only shoe in city. And if you desired to put on a fit without sporting A Go well with, all you had to do was include trainers for an prompt subversive twist. Furthermore, if you were being donning a really gown on vacation but preferred to search a tiny little bit neat, not like you have been off on a sightseeing tour of historic monuments – not that there’s everything mistaken with historic monuments, but you know what I imply – you wore trainers. Converse, Stan Smiths, then Nike Air Power Types.

Inevitably, the wear-it-with-trainers trick received worn out by overuse. Bella Hadid wears Hugo Boss trainers, but so does Keir Starmer. Alexa Chung wears Superga, but see also the Duchess of Cambridge. Trainers have been comprehensively mainstreamed and while sporting trainers with anything, anywhere, has been handy – and cozy – it indicates trainers no extended have any sort of frisson.

Meanwhile, loafers, at the time the ultimate establishment shoe, have located their edge. This begun on the catwalk, where by loafers morphed into backless mules (challenging to dress in, so really trend) and then sprouted furry linings (impractical, which is also really trend). The regular-yet-subtle gold horsebit chain was supersized into a chunk of bling, the old-university slender define beefed up with chunky punk-style lug soles.

My all-time favorite loafers will generally be my common black Gucci kinds – the very low-critical, non-jazzy kind that are never ever in the store window any more, but nonetheless do good business enterprise – a true expense get which I have experienced for years and which are nevertheless as fantastic as new. But in the past several summers, I have uncovered the everyday living-shifting magic of a pair of white loafers.

You are not the white loafer form, I know – but nor was I. A contact way too P Diddy. A bit much too pristine for real lifetime. But then, reader, I bought a pair and, frankly, if I could marry my white loafers at this level, I would. Which is how considerably I enjoy them. They have a vaguely Panama-hat-adjacent air of summer time formality that brings a strike of the surprising with no being remotely difficult to have on.

Sign up to our Inside Saturday e-newsletter for an special at the rear of the scenes seem at the making of the magazine’s most important characteristics, as effectively as a curated checklist of our weekly highlights

A white shoe in summer season will make so many outfits do the job. Absolutely nothing kills the dreamy, solar-dazed vibe of light chinos or a floaty dress speedier than a black shoe. For most of the calendar year, my black loafers are excellent with a trench and excellent with a blazer and denims, but when the solar shines I want white shoes.

If you have nonetheless to be persuaded, start out with a two-tone design (brown and off-white is a vintage), mainly because at this level, trainers and loafers have practically swapped sites. Trainers have develop into the evident decision – which is why politicians and royals dress in them when they are trying to glance usual.

I still appreciate tremendous-very simple white trainers (currently partial to a pair of Keds) but loafers are a supremely handy substitute. They are just the proper sum of quirky, go with anything and are at ease enough to put on each and every day. Everyday living is nevertheless very very simple, when you have the suitable footwear.

Cristiano Ronaldo Seeks $626K From Woman’s Attorney In Vegas Rape Scenario

Cristiano Ronaldo Seeks $626K From Woman’s Attorney In Vegas Rape Scenario

[ad_1]

Cristiano Ronaldo’s legal staff has knocked the US district court docket, trying to get $626,000 from the lawyers of the Nevada girl, whose rape demand from the soccer star was dismissed previously this calendar year. 

Browse A lot more: Ronaldo’s £1.7m Bugatti Veyron Associated In A Crash In Spain 

District Judge Jennifer Dorsey dismissed the lawsuit citing the lack of evidence. Dorsey concluded that the plaintiff’s law firm relied on stolen paperwork and fabricated data. Ronaldo’s lawyer Peter Christiansen has asked the judge to make the woman’s lawyer Leslie Mark Stovall pay the amount of money. 

“Given Stovall’s abuses and flagrant misconduct, Stovall really should be created personally accountable for ensuring Ronaldo is reimbursed for having to defend versus his vexatious and lousy religion perform,” Christiansen explained, as quoted by the Involved Press.

Ronaldo was accused of breaching the agreement after owning allegedly paid out $375,000 to the woman in 2010 to preserve the incident to herself. Ronaldo’s authorized workforce by no means disputed that his consumer met the female, but generally taken care of the sexual intercourse was consensual. Meanwhile, Stovall argued that the lady was in no situation to refuse such a significant sum that Ronaldo compensated to drop the legal cost.

All through the last hearing last month, decide Dorsey slammed Stovall for flouting the court’s rules and rules, and also closed her solution to reopen the situation.

“I locate that the procurement and ongoing use of these documents was poor faith, and just disqualifying Stovall will not heal the prejudice to Ronaldo since the misappropriated documents and their private contents have been woven into the very cloth of plaintiff claims,” the ruling reported. 

Ronaldo at present plies his trade for Manchester United, in which he will enter the ultimate season of his agreement this season. He is a crucial cog of the aspect beneath transition, and the club has manufactured it very clear that he is not up for sale. 

Showcased Graphic Credit rating: @Cristiano/Instagram

COVID instances up by much more than 30% in Britain past 7 days

COVID instances up by much more than 30% in Britain past 7 days

[ad_1]

LONDON (AP) — The selection of new coronavirus instances throughout Britain has surged by extra than 30% in the previous 7 days, new information showed Friday, with scenarios mainly pushed by the tremendous infectious omicron variants.

Knowledge unveiled by Britain’s Workplace for Nationwide Studies showed that more than 3 million individuals in the U.K. had COVID-19 last week, though there has not been an equivalent spike in hospitalizations. The variety of COVID-19 deaths also fell marginally in the final week.

“COVID-19 has not long gone absent,” explained Dr. Mary Ramsay, of the Health and fitness Protection Agency. “It is also sensible to have on a facial area masking in crowded, enclosed areas,” she stated. Britain dropped just about all its coronavirus steps, like mask-sporting and social distancing months back and masks are not often noticed on community transportation.

The hottest jump in coronavirus scenarios arrives immediately after an before enhance of about 40% final thirty day period, pursuing the substantial road parties, concert events and festivities held to mark the platinum jubilee celebrations marking 70 many years of Queen Elizabeth II’s reign.

British officers stated the most up-to-date wave of COVID-19 bacterial infections had been most likely induced by omicron subvariants BA.4. and BA.5. Omicron has tended to lead to a milder illness than earlier variants like alpha or delta, but researchers alert its capacity to evade the immune program suggests that individuals may perhaps be much more vulnerable to currently being reinfected, like following vaccination.

“The regular bombardment of waves we are viewing does induce medical impact that is not to be underestimated,” claimed Dr. Stephen Griffin, an affiliate professor of drugs at the University of Leeds, outlining that any an infection can guide to extensive COVID.

In spite of widespread immunization throughout Britain, the defense from vaccines is probable fading and omicron and its subvariants have progressed to turn into much more infectious. Britain’s Well being Safety Agency reported they have been seeing additional outbreaks in treatment households for older people and a rise in admissions to intense treatment models of people today more than 65.

Dr. Jonathan Van-Tam, a previous deputy main medical officer for the U.K., informed the BBC that COVID-19 is now “much, a great deal, a lot nearer to seasonal flu” than when it initially emerged. Even now, he mentioned gurus ought to be vigilant for any indications the virus was creating much more intense sickness.

Germany’s Robert Koch Institute also documented a equivalent rise in the coronavirus, with conditions expanding specifically amongst older people, small children and youngsters. France has seen a leap in the COVID-19 hospitalization price and officials not long ago recommended that folks start off sporting masks again on public transport.

Globally, the Planet Health Group mentioned this 7 days that COVID-19 is raising in additional than 100 international locations globally. The U.N. health agency warned that relaxed screening and surveillance steps necessarily mean it may be additional complicated to capture rising variants just before they spread far more commonly.

___

Stick to AP’s coverage of the pandemic at https://apnews.com/hub/coronavirus-pandemic

Be a part of THE Discussion

Discussions are views of our readers and are matter to the Code of Perform. The Star does not endorse these views.

How Hospitals Can Progress In Selling price Transparency Compliance

How Hospitals Can Progress In Selling price Transparency Compliance

[ad_1]

How Hospitals Can Progress In Value Transparency Compliance

Paul Boal

By Paul Boal, vice president of innovation, Amitech Alternatives.

Consumerization has at last entered the health care realm. Individuals and insurance policy payers don’t just want a good care knowledge from healthcare facility methods they want clarity in the form of cost transparency. And they’re not the only types.

The two the federal government and the Facilities for Medicare & Medicaid Providers (CMS) have established transparency anticipations. Nonetheless, as The Wall Road Journal noted in December 2021, several hospitals have dragged their feet. And irrespective of about 335 warnings from CMS, no hospitals have been fined, according to Intense Healthcare reporting. Nevertheless, it’s only a make a difference of time prior to client-centric health care and upfront hospital pricing knowledge turn out to be the norm.

To be good, it can be tough to get all healthcare facility systems on the similar site. Nevertheless CMS expectations inquire for pricing info delivered by means of a complete, equipment-readable file, its directive has been interpreted in different ways by distinct healthcare facility units. There are virtually as quite a few file formats as there are clinic methods publishing details. After all, hospital pricing can be complicated based upon the patient’s demands, managing the gamut from day-to-day flat fees to fees dependent on the severity of the patient’s illnesses to bundled solutions that involve distinctive phrases for high quality of treatment.

Furthermore, the methodology for contracting and reporting will range from one particular insurance policy payer to one more. If a marketing consultant employs bad or incomplete facts to manual negotiations, the consequence can be much less than correct. For occasion, our organization has found a massive Arkansas supplier network work out unique costs for a variety of regional payers. How? It was publishing average price ranges, not contracted types. This led to confusion and annoyance for all stakeholders concerned and demanded hundreds of several hours of perform to unwind and clarify prior to real negotiations could choose spot.

Positive aspects to Prioritizing Regulatory Compliance in Health care

Regardless of the troubles of conference CMS price transparency requirements, several clinic devices have figured out how to raise compliance and attain the advantages of price transparency in healthcare.

Circumstance in position: Each month, we see two to a few hospitals achieve selling price transparency compliance by sharing newly updated details documents. And in Missouri, we noticed one particular of the strongest healthcare holdouts at last commence publishing its healthcare facility pricing details in December 2021. Why? Hospitals are observing that there is a business enterprise incentive to showcase information and facts that enhances, matches, or even refutes the pricing information and facts payers are giving to individuals.

Try to remember: People are probably to go to their insurance policies organizations for pricing just before inquiring a healthcare facility to give them a rate sheet. If the insurance policy companies’ pricing details does not match up with the monthly bill a affected individual will get from the clinic, problems happen. As these, good hospitals will be proactive and assure their pricing reconciles with insurance plan companies’ pricing so that sufferers have a seamless knowledge.

How Hospitals Can Boost Compliance at More quickly Charges

Eventually, it is one point to know that improving upon compliance is key to accomplishment and another to truly do it. For true modify to come about, hospitals have to start by carrying out the noticeable: begin in fact publishing at the very least some pricing details. We typically chat about the importance of “bare minimum” compliance, the place the clinic is publishing some payer-precise, negotiated costs. The charges could not be all-inclusive, but the facts offers a starting level for comparative, aggressive analyses. Look at the 50 hospitals in California that one particular of our shoppers has analyzed. Only 15 of them have facts that could be considered “fully” helpful, but the remaining 35 hospitals’ partial facts is barely ineffective.

According to figures gathered from The Washington Publish, only 5.6% of hospitals have been compliant with rate-transparency procedures as of mid-2021, but that range is likely considerably better if we’re allowing for partial or bare bare minimum contributions. Getting some pricing data is improved than owning none: It will make the shopper sense extra empowered and encourages noncompliant hospitals to post value transparency information, as well.

It is also vital for healthcare facility techniques, irrespective of the sum of pricing details they are sharing, to source and regulate info in a device-readable format. Some have not gotten a tackle on their information or contracts, and it’s vital that they start off. To operate an helpful business enterprise, they have to know what they count on to get paid as well as what they really get compensated — it is not just about regulatory compliance.

Ultimately, hospitals ought to get inspiration from other entities that have efficiently adopted cost transparency styles. The most profitable healthcare corporations ideal now are individuals that realize and talk plainly with their prospects — not to point out have a great take care of on their fiscal pics. And there’s nothing at all completely wrong with clinic techniques finding out from their counterparts. A person Utah clinic procedure was initially-to-sector to comply with polices, reinforcing the system’s status for money competence. Mimicking the actions this method took could assistance other hospitals get closer to the exact standing.

It’s value on the lookout at the way educational healthcare establishments are managing laws, as well. Typically, these sorts of institutions have had to straddle quite a few fences and share resources in between common treatment supply and educational investigation. These that have been thriving with value transparency have uncovered that they can reward from publicizing their (generally) higher cost points, specifically if they handle really serious or sophisticated strategies. Patients really don’t always want inexpensive companies quite a few would instead decide for the greatest healthcare they can pay for. Therefore, selling price is not the deterrent a lot of units and institutions feared.

Next the pandemic, persons assume a far more experienced partnership with their healthcare providers. They are taking a really serious seem at where their healthcare expenditures are likely, and they’re keen to browse dependent on each reputation and value. Hospital techniques that satisfy CMS cost transparency prerequisites will not just stay clear of fines — they’ll experience the added benefits of a more powerful track record with the men and women and communities they serve.

Positions in healthcare

by Scott Rupp Amitech Answers, health care compliance, healthcare cost transparency, Paul Boal

Newborn System Security 101: Do This, Not That – Women’s Health and fitness Associates | Kansas City Women’s Health Vendors

Newborn System Security 101: Do This, Not That – Women’s Health and fitness Associates | Kansas City Women’s Health Vendors

[ad_1]

Baby Formulation Safety 101: Do This, Not That

July 1, 2022

baby formula mom and babyThe latest toddler system recollects, and formulation shortages have directed the spotlight on the great importance of system protection. 

Women’s Health and fitness Associates (WHA) is committed to ensuring our people, people, and the broader local community have obtain to risk-free and nourishing formulas. Do not hesitate to get in touch with our business with any components or toddler feeding concerns you may well have or for latest accepted formulation makes/batches.

Baby System Protection 101: Do This, Not That

Right here are our Best 10 guidelines for using system safety and minimizing the danger of foodborne sicknesses or avoidable tummy upset.

1. Pay back focus to CDC & Fda formula remember info

The CDC and FDA websites manage up to date details about formula recollects. Verify these websites often to make sure none of your powdered formula models/ton codes are referenced. Examine your formulation whole lot codes and end working with recalled batches right away. You can return recalled formula for a comprehensive refund from the retailer the place you acquired it.

2. Know the signals of foodborne ailment in infants

The most recent recalls have been linked to issues of bacterial infections in infants who consumed powdered toddler formulation produced in Abbott Nutrition’s facility in Sturgis, Michigan. Having said that, foodborne disease and bacterial an infection are pitfalls in any condition where by unsafe bacteria make their way into the infant food stream by way of unwashed hands, unsterilized bottles/feeding components, or other contamination sources.

Toddlers, specially infants three months aged or more youthful, are notably susceptible to the side effects of a tummy an infection, like dehydration from vomiting and diarrhea. Call your pediatrician or their 24-hour nurse hotline if you discover any of the following symptoms of foodborne sickness or tummy infection:

● Not wanting to eat or refusing feedings
● Abnormal vomiting or diarrhea
● Fever
● Unusually sharp or incessant crying
● Low-vitality
● Seizures (in incredibly uncommon but really serious circumstances)

3. Only purchase formulation made in the United states

Sure, the most latest recalls happened in a Usa facility. Nonetheless, the regulations and fast reporting instruments created into Food and drug administration regulations imply term unfold rapidly, and a remember was instantaneously positioned in impact. That is not the situation really should a identical predicament occur in a method produced in yet another region, in which foods production services are considerably less regulated, or warnings or reviews of suspected issues may possibly not spread quick sufficient to reach U.S. consumers.

4. DO: Wash arms and bottle equipment extensively

Anyone getting ready system ought to wash their fingers extensively with warm drinking water and soap right before mixing a new bottle. Similarly, the bottles, lids, nipples, formulation scoops, or any utensils employed to mix method should be sterilized involving makes use of. Browse the CDC’s webpage, How to Thoroughly clean, Sanitize, and Retail store Infant Feeding Things, for specific recommendations.

5. Don’t: obtain or use expired system

All method deals involve expiration dates. Confirm the stamped dates consistently. By no means use any formula just after the expiration date. Instead, throw expired method into the garbage to protect against it from currently being utilized unintentionally.

6. Really do not: microwave bottles to warm them

There is no have to have to warm method just before feeding it to your infant or toddler. However, do not use the microwave if you favor to warm it. Microwaving system can create warm pockets that burn up the baby’s mouth and throat. Instead, use heat running drinking water – thorough not to enable additional drinking water enter the nipple. Then, test the formula’s temperature by expressing a several drops on the back of your hand. If it is way too heat for your hand, it’s also heat for the baby.

7. DO: Use secure drinking drinking water, combined as instructed

The formulation is developed to be blended utilizing refreshing, risk-free drinking water. Get hold of your nearby well being section if you are doubtful of your tap water’s quality. Preserve sealed filtered h2o on hand for emergencies. Also, only use the method scoop delivered by the company. Various manufacturers have different-sized scoops and mixing instructions, so the scoops are not interchangeable.

8. DO: Use formula in just two hours right after it is combined

When you’ve combined the system, it ought to be employed within just two hrs. Any unfinished method should really be discarded following two hrs. It ought to in no way be saved in the fridge or frozen “for afterwards.” This puts system at danger for unsafe bacteria advancement. Once the baby commences ingesting from the bottle, the components should really be consumed within just a single hour. Nearly anything remaining right after that need to be discarded.

9. DO: Preserve method stored in a amazing, dry locale

Unopened formulation ought to be held in a cool, dry area, ideally with reasonably regular temperatures. When the container is open up, hold it sealed tightly with a lid in the very same spot, hardly ever in a fridge in which humidity concentrations and circulating contaminants could compromise its protection.

10. Don’t use formula that is been open up for extended than one thirty day period

Write the day you open a new can of system on the lid. At the time a can is opened, the contents must be used within just one thirty day period. Just after that, any remaining formulation ought to be thrown out.

WHA Is An Ally When Navigating Secure Toddler Feeding & Diet

Do you have questions about system or feeding your toddler? Would you like enter or steerage about some of your feeding issues? Is your infant displaying any indications of an infection, these types of as fever, absence of electrical power, or reluctance to feed?

Women’s Wellbeing Associates is your most effective ally, and we’re below to deliver the information, schooling, and support you will need. Connect with us at (913) 677-3113 or make contact with us on-line to agenda an appointment for non-emergency conditions. We’ll be there just about every phase to determine what is resulting in your baby’s upset and present the cure and help you both need.

Starting A Overall health Tech Startup? Right here Are 6 Instruments To Make investments In

Starting A Overall health Tech Startup? Right here Are 6 Instruments To Make investments In

[ad_1]

Setting up A Health and fitness Tech Startup? Listed here Are 6 Resources To Make investments In

Today, technological innovation has become a portion of day-to-day life. It has infiltrated pretty much each and every market, and this features health care. The adoption of fashionable tools has significantly boosted the sector’s productivity, supplied a competitive edge, and streamlined the execution of functions and individual care. Since of this, most hospitals and facilities are now seeking to have very similar technologies deployed in their areas of operation. 

If you’re looking to launch a overall health tech startup, make confident it’s cutting edge so that the market appreciates your manufacturer. Observe that technologies evolves rapidly, and your startup really should be ready to accommodate the most new developments. Under are the important equipment you should have in your startup.

  • Electronic Overall health Data (EHRs)

EHRs are digital info information utilized by health amenities to record client facts and prevent the laborous use and management of paperwork. These records include facts like: 

  • Patient’s residence 
  • Medications and checklist of allergies 
  • Medical histories, like immunization dates 
  • Laboratory exams and results 
  • Billing data 
  • Affected person wellness progress notes 

A healthcare facility can proficiently and correctly deal with a affected person when they have accessible and correct knowledge. A dependable healthcare system enterprise should really also be capable to embed the EHR in the functioning method of these types of gadgets to make certain seamless access and retrieval of electronic client documents. 

And apart from availing information to authorized customers immediately, EHRs aid in making decisions on the treatment method training course. Also, they assistance in coordinating affected individual treatment method by way of simplified interaction between distinct departments.

Most health care suppliers are now empowering their people to just take component in their healthcare actively. People can now use trackers, wearables, and sensors to deal with signs and symptoms and complete every day checkups on their personal. Your tech startup ought to include things like these technologies to be suitable in the market. IT option providers, this kind of as the ones more than at this web-site https://www.buchanan.com/ca/toronto-it-consulting/ could help you combine practical computer software into monitoring gadgets.  

Your startup really should incorporate wearable systems that monitor and add essential health and fitness info, this kind of as:

  • Caloric consumption
  • Heart rate 
  • System composition
  • Amount and good quality of slumber

This information and facts helps medical professionals evaluate patients’ conditions in genuine-time. It also enhances the current info taken through healthcare facility visits.

  • Artificial Intelligence (AI) Prognosis Equipment

The use of AI in the professional medical subject is developing at a main tempo. As a result, you ought to make certain your startup works by using these AI tools so that your clientele can advantage from it. 

Machine finding out can swiftly analyze indications offered in a offered scenario by evaluating them with the expertise foundation. The technological know-how offers strategies that physicians can use for the right analysis. The technological know-how requires into account all the details and increases the precision of prognosis. 

Also, AI systems can system big data volumes from diverse sources and effortlessly recognize styles that assist predict issues across unique populations. And other than that, AI optimizes surgical procedures treatments and enhances backlog visibility and predictability of instances.

  • Interactive Personalized Health Report (PHR)

Fashionable wellbeing applications are getting to be majorly client-centered. Consequently, your startup should really have an interactive PHR that boosts patient’s participation in their remedy ideas. 

PHR is an extension of the EHR software which is interactive and patient-targeted. This technology software helps make cure data of people with accrued health-related paperwork obtainable and workable. It quickly receives facts from the EHR through a world wide web browser. 

Therefore, people can very easily perspective their lab success and scheduled appointments and enter facts into their documents, which can help expert affected individual communication.

Telehealth can also be referred to as distant health, e-health and fitness, or m-health. As a tech startup, you should integrate this tool simply because of the pursuing two crucial causes: 

  • Digital healthcare facility visits: A superior health and fitness startup should really enable clients to chat or movie contact wellness vendors from their homes without touring to the healthcare facility. Virtual visits preserve the patient time and dollars. 
  • Distant overall health checking: Telehealth enables health care vendors to test a patient’s wellness remotely. It ensures negligible visits to the healthcare facility. 

Thus, as a tech startup, you ought to concentration on telehealth applications this kind of as

  • Web or cell purposes that add facts to the clinic database 
  • Devices that precisely evaluate blood force and oxygen stages and ship the data wirelessly 
  • Wearable equipment that can report tremors, overall body posture, and coronary heart rate 
  • Dwelling checking equipment for the elderly 
  • Products that notify people of impending appointments, dosage periods, and when to physical exercise

This sort of remarkable products will make your tech startup fascinating to the well being suppliers, and you can conveniently get them to obtain.

Your startup will have to include things like an E prescription. It’s applied instead of the paper types. Primarily, a physician inputs your dosage into a program and securely transmits it to pharmacies. The moment they get the ask for, they process your purchase appropriate away.  

The instrument is valuable due to the fact:

  • It increases the excellent of health by removing faults in composing
  • It would make treatment convenient by enabling the choosing of prescriptions from any pharmacy
  • Decreases concerns with interpretation
  • It gives correct instructions on dosage

All round, the instrument can be simply built-in with EHR devices to notify doctors of any allergies and give recommendations on option prescription drugs.

Conclusion

Information is the centre of all health care selections. Consequently, when constructing your overall health startup, you can produce greatest engagement if you have the most current technologies instrument that helps make the facts processing effective. The record earlier mentioned would be a excellent start make investments in them.  

Work in healthcare

by Scott Rupp AI analysis equipment, digital health information, electronic wellness reporters, well being IT

Grin and bare it: the unexpected increase of crotchless trousers

Grin and bare it: the unexpected increase of crotchless trousers

[ad_1]

Not articles with exposing our midriffs and chests this time, style has discovered a entire new space to leave undressed: the undercarriage.

Enter this summer’s funniest development: chaps, those people crotchless above-trousers that have been after the preserve of precise performing cowboys – and, of study course, actors enjoying at being cowboys.

Steve McQueen and Yul Brynner established the cultural benchmark for chaps in the 1960 western The Superb Seven – nothing really like a pair of durable suede chaps for introducing that potent swagger.

Right after all, if you want to symbolise a cowboy’s hard exterior, it is chaps that costume designers switch to – see also Benedict Cumberbatch, playing the aggressive alpha male rancher Phil Burbank in Jane Campion’s Oscar-winning film The Power of the Pet.

Whip off the undertrousers, while, as large fashion has accomplished in latest weeks, and the vibe is entirely additional Village People today.

This 7 days, the American designer Thom Browne drew gasps and giggles at Paris vogue week when he shut his menswear exhibit with a raunchy cowboy character dressed in wonderfully customized but fabulously risque tweed chaps with a matching jockstrap, cowboy hat and boots.

A model walks the runway during the Thom Browne Ready to Wear spring/summer 2023 show in Paris.
A model walks the runway throughout the Thom Browne All set to Use spring/summertime 2023 exhibit in Paris. Photograph: Victor VIRGILE/Gamma-Rapho/Getty Images

In the meantime, the Parisian menswear label Casablanca despatched out types carrying rancher-style chaps that exposed their bikini strains and derrieres. And a couple of weeks ago, the American rapper Megan Thee Stallion broke the world-wide-web by baring her bottom in chaps-style denims while modelling the most up-to-date Mugler assortment.

What could potentially describe the sudden arrival of “assless” chaps, as they’re known as stateside? In aspect, suggests Lorna Hall of the trendspotting company WGSN, “it’s about fashion’s western revival and 00s styling”. Chaps are a helpful advancement if you experience as if you are not really communicating your rodeo vibes with just the double denim, suede fringing and cowboy boots.

But of training course, it is extra than that. It’s about sexuality and our newfound possession of it, says Patricia Maeda of the trends forecasting company Manner Snoops. “That aligns with the psychological change publish-pandemic the place ladies want to rejoice existence and their bodies.” Guys too, with any luck ,.

Twerking, and its glorification of the humble bottom, has performed its portion in normalising the publicity of the nether region. Chaps have proved a vogue favourite for twerkers – amongst them, Doja Cat and Lizzo – offered that they offer an uninterrupted, bootylicious see.

Doja Cat performing in Indianapolis in January.
Doja Cat carrying out in Indianapolis in January. Photograph: Michael Hickey/Getty Photos

So does vogue in fact count on the rest of us to have on chaps – or basically to be amused when stars do? (Consider your decide on, from Christina Aguilera reprising her love of chaps at LA Pleasure before this thirty day period to Beyoncé’s own Ivy Park denim cutout edition.)

Surely, Thom Browne is eager for “whoever wants to have on them to use them, and to have exciting carrying out it”. And whilst they are not accurately traveling out of the outlets, interest is up: Depop reports a 10% improve in lookups for chaps between May possibly and June. Typically, civilians are donning them at festivals, in which the standard rules of sartorial decorum don’t implement – if you can pull off nudity, you can pull off a bare booty (Etsy even has a “festival chaps” segment).

“It’s about submit-pandemic hedonism and the strong urge to party,” suggests Hall. Nonetheless if you’re questioning why anybody would want to use bum-baring chaps to a celebration, the relationship, adds Hall, is the social gathering ingredient of Delight and the LGBTQ neighborhood. “There’s a subversive, attractive aspect to chaps, but it is mild and exciting.” Really should evidence be needed, see Ru-Paul’s Drag Race and its “chaps on the catwalk” category.

Feel once again, however, if you think this development is just one that you will be quietly sitting out. The trendspotters forecast that it is going to creep up on us: “All these matters impact how we force at the edges of what seems realistic to have on,” claims Hall. “Look at Rihanna and what occurred with maternity don.”

When the bum-baring variation may perhaps be greatest still left to competition attire, provides Maeda, “We’ve witnessed new interpretations of the item getting condition – particularly in denim – which are a whole lot much more wearable and de-fetishised.”

‘Waiting For Time 5 Now,’ Stranger Matters Period 2: Quantity 2 Very first Reactions Are In (Spoiler-Free)

‘Waiting For Time 5 Now,’ Stranger Matters Period 2: Quantity 2 Very first Reactions Are In (Spoiler-Free)

[ad_1]

The wait around arrives to an conclude, with Netflix dropping the 2nd volume of the fourth period of Stranger Matters currently. The anticipation for the past two episodes was so higher, that it inadvertently crashed Netflix’s servers right now. The very good news although is that all through the time of composing this piece, the servers show up to be back again on line. 

Ahead of we transfer on, let me assure you that this write-up will come without the need of spoilers. Suitable, so the previous time we saw Eleven and her posse, they were being break up into numerous groups either trying to find solutions to what is going on in Hawkins or decoding Eleven’s mysterious kidnapping. 

We also observed Hopper (David Harbour) escaping the Russian jail camp and reuniting with Joyce (Winona Ryder). And of training course, how can we fail to remember, everyone’s favorite (future) father Steve venturing into the upside-down, killing vicious, supernatural bats and making his way again household with Robin and Eddie, minus Nancy. 

The final two episodes of the year have a mixed runtime of approximately 4 several hours. The eighth episode titled, Papa, will run for 1 hour 20 minutes, whilst the time finale, The Piggyback, will be 2 hours and 20 minutes long. That’s much more than most element-duration films!

Even though the remaining two episodes will see the conclusion of the Vecna saga, it will also give us a clue as to where the exhibit is headed for its final year following calendar year. Coming back again to the subject at hand, here’s what the World wide web is expressing about it. 

(Image credits: Netflix)