Alibaba HR

Bismillah, alhamdulillah: does your HR do this?

Smoking starts young – so intervene young.

Vaping – a road to smoking and more

Bismillah, alhamdulillah: interesting nites from UpToDate today:

90 percent of adult smokers smoked their first cigarette before the age of 18.

Youth are particularly vulnerable to becoming dependent on nicotine, compared with adults.

(Only) a minority (12%) of adolescent smokers quit without intervention. 

The increasing use of “vaping” products by youth has been associated with an increased risk of subsequent use of traditional cigarettes, marijuana, opioids, and other illicit drugs.

Users of products with higher nicotine concentrations are more likely to have higher rates of vaping and smoking.

The majority of adolescents who smoke or vape report that they would like to quit, suggesting readiness for intervention.

We (UpToDate) recommend that clinicians initiate behavioral support for smoking cessation for all adolescents who smoke (Grade 1B). This may include a brief intervention by the clinician to discuss the potential advantages of quitting and to problem-solve about how to overcome barriers to quitting

For adolescents with symptoms of nicotine dependence, we suggest nicotine replacement therapy (NRT; typically with a nicotine patch or gum), in conjunction with a counseling intervention (Grade 2C). We suggest against the use of electronic cigarettes (vaping nicotine) for this purpose (Grade 2C). Although vaping nicotine can eliminate nicotine withdrawal symptoms, it may promote nicotine use and dependence and is also associated with other potential harms.

Reference

https://www.uptodate.com/contents/management-of-smoking-and-vaping-cessation-in-adolescents?sectionName=Assess%20readiness%20to%20quit&search=Vaping%20and%20readiness%20to%20quit%20among%20adolescents&topicRef=2841&anchor=H2510157086&source=see_link&mkt_tok=NTkxLVdKVy0xMTUAAAF7l-xPxCuvT7LngTgsoed1l8WQ1108QpG9EaAPdIYL88R9zer5EJPGlV-tvcLJGXMemQkcKi9-88igj0fQ5FoQePoJwLaRBXE5atxMQR3wHkS1#H33

All IgG is not equal – the story of afucosylation

Bismillah, alhamdulillah: Antibodies are Y shaped molecules. The head of the Y binds the antigen, such as the spike protein of the SARS-Co-V-2 virus. The head is known as Fab. The stem of the Y triggers the response of the immune system by binding to the right cell or immune fighting proteins called complement. This is known as the Fc portion.

The Fc portion’s strength of binding determines the level of immune response. The strength of this binding is INVERESELY correlated to a specific sugar called fucose. Fucose (not fructose) is a sugar found in seaweed and is added by to the Fc portion of human IgG by an enzyme in human cells. The less fucose there is the lower the fucosylation there is. If there is no fucose added, then this is known as afucosylation. About 6% of human IgG is like that. Fucosylation is a type of glycosylation which doctors use to measure the level of glucose in the blood over a period of three months.

The less fucosylation there is the STRONGER the immune response. So afucosylation is good if you want a strong immune response but potentially bad when the immune response is causing the disease as in COVID19.

The authors of this interesting research show that patients with critical illness due to COVID19 had a higher level of afucosylated IgG. This may also explain the negative effects of human plasma treatments for COVID which may be due to the increased percentage of IgG with afucosylation (is more IgG with no fucose). As this is linked to an increased cytokine response.

The type of IgG produced by antibodies and the number of afucosylated antibodies is an area of research but it maybe that subunit vaccines produce less afucosylated IgG compared to methods that produce potentially more such as mRNA vaccines. Further research is ongoing.

https://science.sciencemag.org/content/early/2020/12/22/science.abc8378?rss=1

Biochemistry of IgG and afucosylation

South African COVID19 Puzzle

Bismillah, alhamdulillah: A South African new lineage of SARS-CoV-2 has changes in the region of the genome that may cause both mono and polyclonal escape ie antibodies from serum are not capable of neutralizing this lineage.

The unknown question is what could happen if the UK and South African versions exchange genes. It seems the place where new lineages are being “brewed” could be immunocompromised patients who have prolonged viral excretion.

The TWiV team is puzzled, because historically viruses do not become more virulent and if the above holds true this would be unprecedented.

https://www.medrxiv.org/content/10.1101/2020.12.21.20248640v1.full-text

COVID vaccine – yes or no?

Bismillah, alhamdulillah: this is a common question that many people are facing right now. As with any new technology you will have early adopters and late adopters. This is normal.

Until the degree of confidence is very high among the public, it may be helpful to structure the way we approach the issue from a risk benefit perspective.

A simplified rule of thumb approach is given below for people who can take the vaccine and have no condition that excludes them from being medically eligible for a vaccine ie pregnancy, breast feeding etc.

70y or over
Take the vaccine as age is the strongest risk factor in adverse outcomes for COVID.

40-70y and worried
These people are also at risk of severe disease and death from COVID19. But may also me be physiologically young enough to feel their risk of severe disease is low. We know that the presence of chronic disease and occupational risk increases your chance of getting COVID19 and of significant disease. So an approach would be to add 5 years to your age for every comorbidity or occupational risk. If you have uncontrolled disease or high occupational risk add 10 years to age. If you get to 70y then taking the vaccine will make a lot of sense.

Example
50y man with well controlled blood pressure = 55y risk age.

50y man with high risk job +10, controlled diabetes +5, asthma +5 and high blood pressure +5 = 75y risk age.

16-40y and worried
Wait till at least 6 months of safety data out. Preferably 18-24 months safety profile before making your final decision.

If you are not worried then there is no reason to not take the vaccine and if you are fortunate enough to get access then you can do so.

Are the cut off’s above absolute? No, but they are just a guide to help someone worried about the long term risk of vaccination and the inevitable risk of the disease itself.

Hope that helps you think through any concerns and worries that you may have or are facing.

COVID19 vaccine – yes or no?

Doxycycline and COVID19

Bismillah, alhamdulillah, it gives me great pleasure to announce the publication of our trial protocol called DOXYCYCLINE ULTRA EARLY TREATMENT TRIAL (DUETT): A RANDOMIZED CONTROLLED TRIAL PROTOCOL FOR THE TREATMENT OF COVID-19 .

This has been a great achievement for my fellow colleagues at Rawdat Al Khayl Health Center, Dr Maysaa Ashkanani (First Physician In Charge), Dr Miaaz Zidan, Afshan Hasan and Mohamed Nourelsabah Metwally and could not have been achieved without the excellent pharmacological collaboration with Lahoucine Naim from SIDRA Medicine.

Doxycycline – a potential treatment for COVID

Though we are not currently in the position to implement the trial, the slowly accumulating evidence for the treatment potential for doxycycline is clearly calling for a trial which is targetted to primary care, suitably powered and well run. This paper is a call to the world’s trialists to put this into practice. Doxycycline, though an antibiotic, offers proven antiparasitic activity in the prevention of malaria. It also offers and antiviral activity. The abstract of the paper is quoted below:

ABSTRACT
The study aim is to compare doxycycline (a tetracycline) versus placebo for the treatment of patients with suspected COVID19 caused by SARS-CoV-2 (a positive single strand RNA virus) in an ultra early timeframe starting at the time of presentation of a patient at primary health care centers prior to a confirmed PCR result and ending at day seven or two serial negative PCR results are found whichever is earlier. The aim is to abort viral replication, reduce morbidity and mortality, and reduce the R0 of infection transmission. The following arguments support a biologically plausible use of tetracycline for the treatment of COVID19: (1) Metalloproteases (MMPs) are upregulated in human lung tissue in inflammatory lung disease (Greenlee et al. 2007), murine studies show increased expression of MMPs due to coronavirus infection (Zhou et al. 2005). Tetracyclines are known to chelate zinc from MMPs and inhibit MMP function (NYAS Publications). (2) Tetracyclines inhibit the replication of positive single strand RNA viruses such as West Nile virus replication (Michaelis et al. 2007) and Dengue virus replication in tissue culture (Yang et al. 2007). (3) Doxycycline decreases the inflammatory cytokines such as IL-6, IL-1β, and TNF within 3 days reaching a peak effect at 7 days(Castro et al. 2011). Doxycycline is therefore a treatment option that may be able to inhibit SARS-CoV-2 replication, morbidity and mortality and transmission.

KEYWORDS
COVID19,Doxycycline, Primary care, Treatment

LINK
https://www.ejmanager.com/mnstemps/172/172-1601443363.pdf?t=1608995241