Posted: 09 Dec 2020 06:30 AM PST

The Covid-19 pandemic has infected more than 68 million individuals worldwide and killed 1.5 million people, including more than 285,000 Americans. And many hospitals are now running short on beds for the sickest patients.

Approximately one in 25 people with Covid-19 need hospitalization, and about 9 percent of hospitalized Covid-19 patients end up having acute respiratory distress syndrome (ARDS). Hospital care does not guarantee survival, with Covid-19 killing about 2.1 percent of people who get it in the US.

We don't always know why the SARS-CoV-2 virus that causes Covid-19 ravages some people so much more horribly than others. But one thing many of these severe patients have in common is an overly active immune response.

This intense immune reaction to the virus often has features of cytokine storm syndrome (CSS). And, fortunately, we have drugs to treat this sort of immune response generally, including one President Trump took while he was sick with Covid-19, dexamethasone.

But these drugs must be given at the right time to Covid-19 patients specifically experiencing CSS, not simply all patients with severe Covid-19, to get the best outcomes. In short, we must optimize the drugs we already have. And there is still a lot we need to learn about how these sorts of treatments work in the case of Covid-19.

What we know about cytokine storms in Covid-19

Cytokine storm syndrome is an umbrella term for a variety of hyper-inflammatory reactions to various insults and triggers. It can be brought on by other viruses, such as influenza and Epstein-Barr virus, as well as blood cell-related malignancies such as lymphoma and leukemia.

The diagnosis of CSS is complicated. There is no single agreed-upon set of criteria for deciding if someone has CSS without their already having another related underlying condition.

Pinpointing it in people with Covid-19 is even trickier, in part because levels of key blood markers are not as high as the levels seen in patients with CSS in other contexts. Additionally, severe lung inflammation is generally a late development in CSS, but it's early in Covid-19.

Nevertheless, like other CSS patients, those with severe Covid-19 often develop multi-organ dysfunction syndrome in which organ damage appears to be caused primarily by excessive immune system activation and/or blood clotting, rather than by the virus itself.

These patients also have other overlaps with general CSS cases, including fever, liver dysfunction, low blood counts (particularly low lymphocyte counts), and very elevated markers of inflammation.

We still don't know, however, exactly how Covid-19 triggers this hyper-inflammation. It only occurs in a subset of infected individuals, and there may be genetic risk factors. For other cytokine storm syndromes, 30 to 40 percent of patients do harbor mutations in genes that alter the immune response to infection. Time and further research will tell if something similar occurs with Covid-19.

Since the pandemic began, we have also learned more about the timeline of how these severe cases often go. And this can help determine how best to treat people.

For symptomatic individuals, infection with Covid-19 comes in phases, with the early days (the first week) dominated by viral replication leading into features of a flu-like illness (such as fever, cough, or diarrhea). In up to 20 percent of adults with symptomatic infection, shortness of breath with low blood oxygen levels may develop five to 10 days after the onset of symptoms.

And things can deteriorate rapidly from there. Hospitalized patients requiring oxygen support can quickly (often within hours) progress to requiring ICU management for ARDS, low blood pressure, and subsequent multi-organ dysfunction.

Confirmed predictors of patients at risk of developing more severe complications include being older than 60 and having obesity, underlying cardiovascular disease, and/or a history of asthma or other chronic respiratory disease. Recent studies have also identified several blood test abnormalities at the time of early symptom onset that are predictive of a patient developing more severe complications later.

But these sorts of tests are not routinely done. And it still doesn't tell doctors exactly how best to treat these individuals who end up getting life-threateningly ill.

Antiviral drugs don't help cytokine storms, but we are learning how some other drugs can

We do have some ways to attack the virus itself. Antiviral approaches are likely to be most beneficial early in the disease course when symptoms are first present and the virus is still infectious. But even then they haven't by any means been a cure-all.

At present, remdesivir, a nucleotide analog that has received emergency use authorization from the Food and Drug Administration, has been demonstrated to somewhat shorten hospital stays but has not been shown to improve survival. Other treatments hyped by the current administration, including hydroxychloroquine, have not proven to be effective.

Because none of the antiviral approaches have thus far been proven to increase survival rates or prevent the development of ARDS or multi-organ dysfunction syndrome, we need treatments for patients fighting CCS in order to save more lives.

The most accessible and comprehensive anti-inflammatory approach to treating Covid-19 associated CSS involves the use of glucocorticoids (anti-inflammatory steroids). These include prednisone, methylprednisolone, and dexamethasone, the steroid given to President Trump. Many hospitals have adopted dexamethasone as the standard of care for hospitalized patients with Covid-19 pneumonia.

These steroids not only inhibit cytokine production but also broadly tamp down many other aspects of the immune response, which makes them helpful in reducing harmful inflammation but also tricky to use — especially in the case of an infection.

As immunosuppressants, these drugs are associated with a vast array of side effects, including secondary infections. The use of glucocorticoids to treat previous fatal coronavirus epidemics, SARS and MERS, reported mixed results. There was even concern that the use of glucocorticoids may increase mortality, so the World Health Organization strongly discouraged their use early on during the SARS-CoV-2 pandemic.

Nevertheless, out of desperation, clinicians overwhelmed by the pandemic resorted to these drugs to lower the massive numbers of Covid-19 deaths.

So far, several retrospective analyses have reported lower Covid-19 mortality in glucocorticoid-treated patients compared to control groups. A September meta-analysis done by the World Health Organization also concluded that glucocorticoids do save lives for some hospitalized Covid-19 patients, reducing all-cause mortality over four weeks from 40 percent to 32 percent.

A randomized placebo-controlled trial of 2,104 hospitalized Covid-19 patients, published in July, reported a statistically significant decrease in mortality with modest doses of dexamethasone for those on ventilators, from about 41 percent in the control group to about 29 percent in those receiving the steroid.

Those not requiring oxygen, and perhaps not experiencing CSS, trended toward worse outcomes (14 percent in the control group died versus almost 18 percent of those receiving the treatment). Similarly, a recent study reported that patients with notable markers of inflammation improved with glucocorticoids, but those with lower levels fared worse.

These studies underscore the importance of careful patient selection for these treatments, namely that they should be used specifically to treat CSS in Covid-19 patients, not simply all patients with severe Covid-19. Initiating glucocorticoids as early as possible in CSS patients who will benefit, but avoiding needlessly immunosuppressing other patients who will not benefit from (and may be harmed by) them is a challenging needle to thread. Looking for biomarkers for hyper-inflammation during hospitalization could help clinicians determine which patients are the best candidates for treatment with these potentially lifesaving drugs.

Ideally, more targeted anti-inflammatories would be best to deploy in an effort to further lower Covid-19 mortality rates. We have a few leads, documented in high-quality studies of specifically anti-cytokine treatments in Covid-19 CSS patients, but the research is ongoing.

More recent — but lower-quality — studies suggest that we might have luck using less risky, targeted immunomodulatory and immunosuppressive therapies, which have documented success treating non-Covid-19 CSS. Many of these treatments — including Tocilizumab (IL-6 blockade), IL-1 blockade, and emapalumab — have had mixed results and are still under investigation. Currently, for example, IL-6 blockade is not looking promising.

While we all eagerly await the availability of safe and effective vaccines to prevent infection with SARS-CoV-2 and subsequent Covid-19, we need to optimize antiviral treatments and therapies directed against the associated CSS when it develops. New iterations of antiviral approaches will hopefully decrease the development of hyper-inflammation.

But until these arrive, glucocorticoids and/or anti-cytokine approaches will likely be necessary to save lives. With glucocorticoids already being readily available globally and relatively inexpensive, they may be our best therapeutic option for treating Covid-19 CSS worldwide for now.

Randy Q. Cron, MD, PhD, is a professor of pediatrics and medicine and director of the Division of Pediatric Rheumatology at the University of Alabama at Birmingham. In November 2019, he published Cytokine Storm Syndrome, the first dedicated textbook on cytokine storms.

W. Winn Chatham, MD, is a professor of medicine, clinical immunology, and rheumatology; senior scientist at the Comprehensive Arthritis, Musculoskeletal, Bone and Autoimmunity Center (CAMBAC); and director of Rheumatology Clinical Services at the University of Alabama at Birmingham.

Scott W. Canna, MD, is an assistant professor of pediatrics and immunology at the University of Pittsburgh. He is a scholar of the Richard King Mellon Foundation Institute for Pediatric Research with expertise on auto-inflammation and cytokine storm disorders.

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Medical Cannabis for Pain Management: Is it Time to Modify the Practice Paradigm? - Clinical Advisor

Posted: 09 Dec 2020 08:30 AM PST

The widespread prescribing of opioids for the management of acute and chronic pain over the last decades made opioids readily available to the general public, creating a public health crisis.^1,2 As of 2017, it was estimated that more than 36 million people worldwide have opioid use disorder.^3,4 The majority of opioid users report acquiring these agents from relatives and/or friends, despite knowing the risk of addiction.^1.2

While the risk factors for and treatment of opioid addiction are well established, treating patients with acute and chronic pain remains a challenge. However, withdrawing opioids as a means of hazard reduction for addiction in a patient with chronic pain can have an adverse effects on the patient's well-being. This is not limited to medication withdrawal illness and recurrence of pain, but may also threaten the patient's perceived quality of life, compromising recovery.⁵

Because of the controversy surrounding opioid prescribing and use, there has been rising interest in alternative pain treatment regimens that could be clinically advantageous in reducing opioid use and complications associated with pain. One example is the use of medical cannabis. Though used since antiquity, only recently has public sentiment and state laws on medicinal cannabis use shifted to a more favorable frame. With 33 of the 50 states (and the District of Columbia) fully legalizing medical cannabis use, alternatives in treatment pathways that have classically been restrictive can now be entertained.^5-10

In 2017, it was estimated that 56% of patients who suffer from chronic pain use cannabis.^5,7 It is therefore incumbent on the medical community to consider the practicality and appropriateness of prescription use for cannabis, especially with rising public climate of approval and openness for dialogue.

Mechanisms for Pain Management

Opioids have long been the mainstay of treatment in the management of moderate to severe pain associated with several disease states afflicting patients in both the acute and chronic care setting, despite limited evidence supporting their continued use.¹¹ The mechanism of action opioids has been binding to specific opioid receptor protein, that when occupied, limit the expression of pain perception on the part of the patient.¹¹ Yet, this protein is also involved with perception and expression of mood and stress, and can affect the immune system.¹¹ This is accomplished at the expense of receptor-derived dependence and side effects, most notably those of central nervous system (CNS) and respiratory depression.¹¹

This differs markedly from what is understood about the role of cannabis in pain modulation. Cannabis is believed to act on the endocannabinoid system; particularly receptors 1 (CB₁) and 2 (CB₂).¹² These receptors enhances the sensitivity of the CNS neurotransmitters to serotonin and dopamine, thereby providing stimulation of pain relief.^8,12 In so doing, this pathway also plays a role in euphoria and perception of decreased levels of stress, which is more pronounced from CB₁.¹²

Effectiveness of Cannabis for Chronic Pain

The pharmacokinetic properties of cannabis are dependent on the purity of the agent, route of administration, physiology of the user, as well as the condition being treated.^8,12 Cannabis has been most effective at treating chronic pain associated with non-specific neuropathy (including muscle spasticity), cancer pain, and rheumatoid arthritis.^5,10,12

Though synthetic derivatives are of interest as a product of abuse, the most commonly explored medical agents are non-synthetic.¹² One exception has been the US Food and Drug approval of dronabinol (tetrahydrocannabinal [THC]) for the treatment of nausea and vomiting associated with cancer chemotherapy and AIDS-associated anorexia. Dronabinol has also been shown to reduce chronic pain, but most commonly success was met only when the agent was combined with opioids.¹² At this time the evidence of adequate pain relief with synthetic cannabis as monotherapy is lacking and should therefore be discouraged.¹⁰

Medical cannabis can also be used as a way to reduce opioid use. A study in 2015, which included over 200 patients on a chronic opioid regimen, reported a reduction in opioid use by nearly 77% when cannabis was added to existing monontherapy.¹³ Similar findings were suggested in a Canadian study, where 300 patients provided a subjective assessment of pain reduction when cannabis was dispensed and added to their existing opioid regimen. A 71% reduction in prescription, illicit drug, and alcohol abuse was found for those who were receiving the medical cannabis.¹⁴ The patients also reported an additional untargeted reduction in nicotine dependency.¹⁴ The subjects also reported improved compliance with therapy and a preference to cannabis, believing that cannabis was "safer" than their existing treatment regimens, improved symptomatic relief, and was "more tolerated."¹⁴

Topics:

Pain Pain Management Smoking

Hot Tub Benefits: 7 Health Benefits of Soaking in a Hot Tub - Healthline

Posted: 08 Dec 2020 04:26 PM PST

It's been a long, hard day and soaking in a hot tub may be just the therapy you need to unwind and escape. Aside from helping you relax, it turns out that spending time in a hot tub may provide other benefits, too.

Whether you're a hot tub owner or make use of your gym's Jacuzzi, there are some important things you need to know to get the most out of your hot tub experience.

Let's explore some potential health benefits of soaking in a hot tub and when it may be safer to avoid it.

The potential benefits of using a hot tub vary from person to person. Much depends on your overall health and how you use it.

Below are 7 possible benefits of soaking in a hot tub.

1. Stress relief

One of the most obvious benefits of a hot tub is the potential to help ease the tensions of the day. The soothing effect of the warm water and massaging action may help relieve physical, emotional, and mental stress.

If you like, you can boost this stress-relieving effect even further with soft music, low lighting, or aromatherapy.

2. Muscle relaxation

The hot water and massaging action of the hot tub jets can be an effective way to help relax and soothe tight, tense muscles. This can help ease aches and pains.

A hot tub soak before exercising may also reduce the risk of injury.

3. Improved sleep

According to research, the simple relaxation gained from a soak in the hot tub may be enough to help you drift off into a more peaceful sleep.

An older study evaluated passive body heating as a treatment for insomnia in older adults. The study was small and subjective but found that hot baths promoted significantly deeper and more restful sleep.

A 2012 study looked at the effects of hydrotherapy on physical function and sleep quality for people with fibromyalgia. It was a small study involving females between the ages of 30 and 65. The researchers concluded that hydrotherapy helped improve sleep quality along with other symptoms of fibromyalgia.

4. Pain relief

Soaking in a hot tub may relieve some types of pain by relaxing tense muscles, joints, and tendons.

If you have arthritis, the heat and massaging action may help ease the stiffness and inflammation that cause pain.

Water supports your body and takes weight off joints, which helps improve flexibility and range of motion. You might gain some of these benefits in a warm bath as well.

5. Better cardiovascular health

Relaxing in a hot tub can raise your heart rate and lower your blood pressure.

According to a 2016 study, hot water immersion may have "robust" effects on vascular function and blood pressure. The authors of the study suggested that passive heat therapy may help reduce cardiovascular risk and mortality, especially among those with limited ability to exercise.

Earlier research found that immersion in a hot tub for 10 minutes may lower blood pressure and is likely safe for most people with treated high blood pressure.

6. Improved insulin sensitivity

Some researchers hypothesize that regular thermal therapy using saunas or hot baths may improve impaired insulin sensitivity and be beneficial for managing diabetes.

Additionally, a 2015 review found that sauna and hot tub therapy may benefit people with obesity and diabetes.

7. Calorie burn

In a small 2016 study, participants soaked in a waist-high hot bath for an hour and burned about the same number of calories as a 30-minute walk. That's not to say that it should take the place of exercise, but it might help metabolism, particularly for those who find it hard to exercise.

If you have any concerns about using a hot tub, it's worth having a conversation with your doctor. This is especially important in the following situations:

Heart disease. Soaking in a hot tub can affect heart rate and blood pressure. This may be beneficial to some people with cardiovascular concerns but could be unsafe for others.
Pregnancy. It's easy to get overheated when you're pregnant, which can be harmful to you and your baby.

You may also want to avoid a hot tub if you have:

Skin injuries. Wait until cuts, open sores, or rashes have healed to reduce the risk of irritation and infection.
Low blood pressure. If you're prone to lightheadedness or fainting, you should probably avoid the hot tub as the hot water could lower your blood pressure further.
Urinary tract infection (UTI). Exposure to hot water when you have a UTI may worsen your symptoms.

Whether you use your own hot tub or one that belongs to a gym or community, check to make sure the tub is clean and properly maintained. The water should be cleaned and tested regularly. A poorly maintained hot tub can lead to a skin infection called hot tub folliculitis.

Movies, television, and even social media often depict people lounging in a hot tub for hours on end with a cocktail in their hand. This isn't ideal or safe. Here's how to go about your hot tub soak to maximize the benefits and minimize the risks:

Avoid very hot water. Make sure the water isn't too hot, with an absolute maximum of 104°F (40°C).
Stay hydrated. Hot tubs make you sweat and leave you dehydrated. Drink water plenty of water, but avoid alcohol before or during your soak.
Limit your time in the tub. Don't stay in too long, especially if you're not used to it. At the maximum temperature, set your limit at 10 to 15 minutes. You can stay in for longer at a lower temperature if you're used to it. Signs that you need to get out right away include:
- lightheadedness, dizziness
- skin redness
- shortness of breath
Wash afterward. When finished, remove your bathing suit and wash with soap and lukewarm water. Don't go immediately from the hot tub to icy cold water, as this could spike your blood pressure.

Regular soaking in a hot tub may provide several health benefits, such as muscle relaxation, pain relief, and improved sleep. Some studies suggest a wider variety of health benefits, but more research is needed to determine the specifics of hot tub therapy with particular conditions.

Hot tubs should be properly maintained to ensure health and safety. Consult with your doctor if you have health issues such as heart disease. You should also avoid the hot tub while pregnant or if you have an injury to your skin. When used carefully, hot tubs are safe for most people.

Severe Acute Respiratory Syndrome

“Covid-19 treatments: Why we need to learn to use steroids better - Vox.com” plus 2 more

“Covid-19 treatments: Why we need to learn to use steroids better - Vox.com” plus 2 more

What we know about cytokine storms in Covid-19

Antiviral drugs don't help cytokine storms, but we are learning how some other drugs can

Mechanisms for Pain Management

Effectiveness of Cannabis for Chronic Pain

Topics:

1. Stress relief

2. Muscle relaxation

3. Improved sleep

4. Pain relief

5. Better cardiovascular health

6. Improved insulin sensitivity

7. Calorie burn

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