Why do pandemic viral infections come in waves?

Hello readers and welcome to yet another very short post. I have been very busy over the past months, can barely make it to write anything, especially when considering the fact that I am still in the early stages of my book on Nosocomial Infections. A book that was planned to be written in one year (2019) and published for free as an online project on the following year (2020); but this pandemic we all know just forced me to postpone due to a range of life restrictions/lockdowns.

Even though I struggle like never before to even read the bear minimum for keeping myself afloat in this immense pool of information that is Life Sciences, I don't wish to abandon this project altogether. It is important for my personal and professional education, and as long as there are others reaching out to me and reading my posts, I believe the knowledge I acquire and share can be, and is indeed, relevant for other intrepid scientific minds.

Hence, I accepted that the ritual of posting in this blog might be affected in periodicity, but cannot be disregarded at all. I will eventually complete the last post (immediately before this one) where I am still trying to find the time to adequately read through my friend's article (don't want to be lenient with that); but I also want to start posting a bit more on The Toxicologist Today. I then came up with the conclusion that short answers to immediate questions that suddenly populate my brain, due to professional requests or just personal doubts I eventually come across with, are the best way to keep in constant contact with you guys. 

So, whenever a topic comes to my mind or emerges from a  natural doubt I might have, I will share it with all of you for awareness, simply because it might be an interesting subject also playing in your mind! But don't worry, I'll make it short (way shorter than this post :D), clear and concise, and I'll make the referencing also short, straightforward, but robust (with significant reliable studies/institutions behind them).

Hope you like it. Shall we start? This one has been assaulting me for quite some time...

Why do pandemic viral infections come in waves?

Apparently pandemic viral infections comprise 6 phases of alertness, as per the World Health Organisation (WHO). And throughout the post-peak period, the strength of the pandemic disease will have been reduced in developed countries with appropriate health surveillance. It will do so until its infectivity proneness has dropped below the former peak registered levels [1]. This means that after the peak period one witnesses a decrease of pandemic activity but only until the virus regains a new viral infectivity/potency due to natural mutations that will bring infection to yet another peak level, until herd immunity starts appearing and a certain dormancy of infectivity is observed. The different peaks/waves can be distanced by many months and relaxation of control measures can be irresponsible, depending obviously on the strength and adequacy of the available scientific responses.

In a nutshell, the first wave results in deaths and disability linked to the viral infection itself; the second wave impacts on subjects who are volatile in the medium-term as a result of failures in the approach during the first wave; and the third wave reveals the consequences of the "virus on the social determinants of health and its effects on the next generation", as per Fisayo and Tsukagoshi (2020),  [2].

[1] About Pandemic Phases, World Health Organisation, [https://www.euro.who.int/en/health-topics/communicable-diseases/influenza/data-and-statistics/pandemic-influenza/about-pandemic-phases], last access on the 02Jun2021, last update unknown 

[2] Fisayo, T, Tsukagoshi, S. (2020). "Three waves of the COVID19 Pandemic". Postgrad Med J, 97, pp. 332.

Photo kindly provided by Erik Mclean on Unsplash

On the management of Paediatric Vesicoureteral Reflux

For any parent/carer dealing with a child diagnosed with Vesicoureteral Reflux, the state of alarm is constant, and consequently a certain emotional burden can be identified. For having all possible variables that infer in the child's quality of life, under perfect control, can be time-consuming and quite tricky. Nevertheless, it is primordial to first have a complete understanding of the disease basics, so whoever is caring for the affected child can understand that there are clinical responses addressing the problem and that the issue itself is characterised by grey areas where agreements had to be made between experts in the area. Why? Due to lack of consensus. 

Vesicoureteral Reflux is not immediately an easily describable succession of rigid events, there are underlying little aspects that can confuse the diagnostic and bring personal opinions from clinicians to the debate table. 

What is Vesicoureteral Reflux?

This relates to a flow of urine that is contrary to normal motion. Going from the bladder into the ureter and, sometimes/eventually, depositing into the renal system (e.g., kidney). 

Can it happen to any child?

For most subjects this type of reflux derives from an existing physiological anomaly of the ureterovesical junction occurring from birth (congenital anomaly), but it can also emerge from other origins such as: 

a) from high-pressure passing urine from secondary to posterior urethral valves, 

b) due to a neuropathic bladder (where associated peripheral nerves are dysfunctional),

c) due to a voiding dysfunction (incapacity to urinate as normally expected). 

How many are affected?

About forty percent of children experiencing a urinary tract infection (UTI) show signs of reflux according to [1], thus, considering that two to five percent of girls and one to two percent of boys experience a urinary tract infection before reaching puberty [2] the numbers and their underlying inference speak for itself. 

UTIs are the commonest bacterial disease present in the first three 3 months of life in humans, according to [3]; tolling to about over 10% of reported serious febrile events of bacterial origin in infants 2 to 6 months of age [4]; reflux nephropathy is a liability factor when considering inflammation of the lining of renal pelvis and parenchyma, resulting in injury to the kidney and scarring (lesions that are irreversible and that in case of progressive kidney disease can cause kidney failure). In that sense, reflux nephropathy can result in extremely nefarious consequences such as renal insufficiency or end-stage renal disease (that when moderate to severe can then trigger renin-mediated hypertension) [5].

How is the management of disease approached?

The very first objective in the management of vesicoureteral reflux in children is to avoid pyelonephritis [a], renal injury and other complications derived from the impact of reflux in the urinary system.

Clinicians do know that vesicoureteral reflux is common, but presently there is very little consensus to the best way to manage the disease (even among clinical experts) [6]. It is exactly because of the lack of consensus in regard to how this medical issue should be treated that the American Urological Association (AUA) gathered a group of experts to produce a treatment guide directed to children diagnosed with vesicoureteral reflux, with scope on vesicoureteral reflux in children diagnosed following a urinary tract infection [7]. If you happen to visit the document online bear in mind that it is preconditioned to children aged 10 years and younger with unilateral or bilateral reflux with or without scarring. In addition, it also entails that treatment recommendations are to be made jointly with the parents of the sick child. I suspect that is because of individual behavioural patterns of the patient, day-to-day habits and the different spaces the child might be involved in. All this can impact tremendously in the practical outcome.

As stated in the document "Only a few recommendations can be derived purely from scientific evidence of a beneficial effect on health outcomes [...] Evidence of the efficacy of medical management on health outcomes is available only for Grades I–IV reflux".

What is recommended?

To maintain information as reliable as possible in regard to what is postulated in the original document, and because the document is quite long (I had to read it over the course of several weeks, see HERE). I decided to copy directly from the original. However, this is purely a summary of very important information that requires interpreting by involved clinicians. The present information is only for informative purposes to empower parents towards a more informed conversation with their children's doctors. It should not be interpreted as a priori direct medical advice towards a certain decision. Because consensus, as already discussed, is difficult in this area, even among experts, treatment options are the result of a selection by 8 out of 9 panel members and are, therefore, categorised as guidelines. As expected, treatment is advised by the panel based on a number of conditions, for example, nature of injury, grading of injury (I to IV, see end of post) and age. 

Having said all this, the available approaches are:

(1) No treatment (including intermittent antibiotic therapy); 

(2) Bladder training; 

(3) Continuous antibiotic prophylaxis; 

(4) Antibiotic prophylaxis and bladder training; 

(5) Antibiotic therapy, bladder training and anticholinergics (drugs that block the action of the neurotransmitter acetylcholine); 

(6) Open surgical repair: "although proven to cure reflux in 90–98 percent of patients, has not been demonstrated to improve health outcomes other than pyelonephritis; for this outcome, the evidence suggests that children with Grade III or IV reflux receiving continuous antibiotic prophylaxis are 2.5 times more likely to develop pyelonephritis than children who have undergone successful antireflux surgery" [...] Thus, evidence-based recommendations provide limited practical guidance for the clinician.

(7) Endoscopic repair.

"These modalities are described in Chapter 1. The recommendations assume that the patient has uncomplicated reflux (e.g., no breakthrough UTI, voiding dysfunction, duplex systems [where the ureter with the ureterocele can drain the top half of the kidney whereas the other ureter drains the lower half resulting in frequent UTIs, possibly reflux, and if not treated potential kidney damage], or other comorbid conditions); [...]

An important variable in the scope of treatment is the presence of concurrent voiding dysfunction, a common occurrence among children with reflux. Because resolution of voiding dysfunction may be accompanied by resolution or diminution of reflux such children may require more aggressive treatment with antibiotics, anticholinergics, and bladder training (e.g., timed voiding, biofeedback, parental monitoring of voided volumes). Surgical repair of reflux is less successful in children with voiding dysfunction, and thus a higher threshold is necessary before surgery is recommended in such patients. Children with reflux should therefore be assessed for voiding dysfunction as part of their initial evaluation.

[8]

[1] Bourchier, D., Abbott, G. D., Maling, T. M. (1984). "Radiological abnormalities in infants with urinary tract infections". Arch Dis Childv, 59(7); pp. 620–624.

[2] Jodal, U. and Winberg, J. (1987). "Management of children with unobstructed urinary tract infection". Practical Pediatric Nephrology, 1, pp. 647–656(1987). 

[3] Krober, M. S., Bass, J. W., Powell, J. M., Smith, F. R., Seto, D. S. (1985). "Bacterial and viral pathogens causing fever in infants less than 3 months old". Am J Dis Child, 139(9):, pp. 89-92.

[4] Allen, L. H., Lei, C., Douglas, B. (2006). "Incidence and Predictors of Serious Bacterial Infections Among 57- to 180-Day-Old Infants". Pediatrics, 117 (5), pp. 1695-1701.

[5] Martínez-Maldonado, M., (1998). "Hypertension in end-stage renal disease". Kidney International, 54(68), pp. S67-S72.

[6] Elder, Snyder, Peters, et al., 1992; International Reflux Study Committee, 1981.

[7] Management and Screening of Primary Vesicoureteral Reflux in Children (2010, amended 2017), American Urological Association, [https://www.auanet.org/guidelines/vesicoureteral-reflux-guideline], last visited on the 8th of January 2020, Last update in 2017. 

[8] Image kindly taken from Radiopaedia, [https://radiopaedia.org/cases/illustration-vesicoureteric-reflux-grading].

[a] Inflammation of both the lining of the renal pelvis and the parenchyma of the kidney especially due to bacterial infection, as per the Merriam-Webster dictionary.

Post Photo by Robina Weermeijer on Unsplash.

Inflammation, Good or Bad?

By working in medical communications you are presented several different questions on a daily
basis. Some are accessible and straightforward, and some others are very high profile and demand further research. Nevertheless, even after these are answered, based on the many sources of information available in-house and spread out there through official sources, now and then remaining question marks still surface. I suspect that one universal question that always pester people's minds, be them the general public or highly proficient medical professionals is the importance and relevance of inflammation.  

If you think about it we were always told that it is important to tackle inflammation to avoid it progressing and end up in febrile events and other tricky associated scenarios. However, inflammation in its pure sense and in a non-chronic autoimmune patient is a natural and necessary immune response our bodies trigger to refrain an external agent from affecting us. And this is a good thing, right? So why do we jump on to taking antiphlogistics at the very first sign of inflammation? 

My personal take on inflammation in generally healthy people has always been the same as for fever, i.e., let your body control it until you conscientiously recognise your body is either not controlling it adequately or has triggered hyper-reactive control measures. I rarely take any antipiretics if I'm not around 38 Celsius. I always let the body challenge itself. Then when I recognise it's not going to go there on its own, the pharmaceutical is at hands' reach. This is me, please do not use it as clinical guidance. I am not a healthcare professional, I am a professional in medical communications/information and this is solely my personal view as an avid science researcher. For the sake of what is your health and safety follow the advice given to you by your healthcare professionals.

Obligatory disclaimer shared, the remaining question here is actually of a double nature:

1) Is inflammation good or bad?

and

2) When do we know we must tackle the inflammatory process?

I did some literature search on this topic and was able to find some interesting information that is hereby compiled for you.

What is Inflammation?

On its own inflammation is a protocol developed by higher organisms to tackle any foreign agent of developing an invasive strategy that can undermine the stability of the system. In that sense, we humans have developed internal and external barriers that account participation of many agents, from anti-inflammatory foods, to structures like skin, nasal hair, or even mucus.

Being part of the human organism's natural defensive pathways and protective paraphernalia, inflammation is a gradual response process to infection and tissue damage as one of the primary steps of the healing process. When we consider that for producing muscle mass at the gym we need to break the muscle tissue, thus allowing it to grow and then refill it with the new generated cells, the process that encompasses it is inflammation!  But on the other hand, and so well simplified by the website Science-Based Medicine [1], when aging brings about chronic inflammation, the result, among other detrimental losses and consequences, is the cellular damage that can chronically lead to several ailments like the well known atherosclerosis (where plaque composed of fat, cholesterol, calcium ad other molecules build up in the arteries narrowing them overtime) [2] leading to very serious issues like stroke, heart attack, eventually death. There is also the almost universal example of the autoimmune condition rheumatoid arthritis, where the immune system mostly attacks synovial joints, heart and lungs and that results in swelling, stiffness and pain with devastating consequences for the quality of life of the affected patients [3]. 

In what consists the Inflammatory process?

Is Inflammation Good or Bad?

To answer this questions we must visualise an aid motion picture where one is continuously exercising and breaking muscle, not allowing the same any time to heal. Or for example, imagining the immune system sending patrol cells to destroy invaders but prolonging the destruction to such lengths that it wouldn't be even possible to discern anymore who is evil from who is good. Another figurative example can be the use of the water in a swimming pool to put down a lighting match. Unnecessary, is it not?). Water all over the place when you could have done the same with a bit of a glass of water!

Constantly hitting one's cells with a protective army of patrol soldiers can become irritating for one's organism. That is exactly what happens with people when they eat particular foods they are sensitive too, be it lactose, honey, peanuts, you name it. If your body sends out those patrol cells in a normal approach you'd have a mild inflammation and allergic reaction (let's say). If your body is as nervous as Venezuela's Maduro or Turkey's Erdogan, your body would want to send five armies to seek for two little peanut buds and then end up beating up everything they found in the vicinity and further on. And that would progress to a senseless chronic beating up if you don't eventually tackle such unnecessary and unregulated defensive mechanisms with the common sense of an antiphlogistic tablet to refrain the body's immune system's rage.

Overall, inflammation plays a vital role when as a balanced natural response to a disruptive physical imbalance in one's injured organism. However, if one lets it overwork in its functions,  one'll suffer the consequences. And these can be devastating in chronic autoimmune or immunosuppressed patients.

For a list of anti-inflammatory natural products that you can use in your normal diet, please ACCESS HERE, HERE and HERE.

1. Inflammation: Both friend and foe, Science -Based Medicine, [https://sciencebasedmedicine.org/inflammation-both-friend-and-foe/], last visited on the 6th of June 2019, last update on the 27th of December 2011.

[2]. Atherosclerosis, National Heart, Blood and Lung Institute, [https://www.nhlbi.nih.gov/health-topics/atherosclerosis], last visited on the 6th of June 2019, last update unknown.

[3]. Diet and rheumatoid arthritis, The Association of UK Dietitians, [https://www.bda.uk.com/foodfacts/diet_rheumatoid_arthritis], last visited on the 6th of June 2019, last update on September 2018.

Post picture by Cristian Newman on Unsplash.

How to know if a pharmaceutical product is authentic (in the EU)?

It is typical for the Big Pharma to undergo certain regulatory updates aiming the betterment of the pharmacovigilance and quality processes. It's all for the sake of respecting and protecting the end-user. Serialisation is a big part of the whole grand scheme of things and is to know further developments this coming 9th of February 2019. This is the day the European Union will put into place two levels of requirements that will help verify the authenticity of a product, by 1) demanding all marketed pharmaceuticals to contain a unique identifier, thus enabling the verification of its authenticity and the authenticity of its associated parts; 2)  demanding an anti-tampering physical system to make sure the product has never been compromised.

But what is this Serialisation everyone is talking about these days? Serialisation is a sort of tracking system to assure pharmaceutical companies, healthcare professionals and patients that the products in their hands can be trusted. For that matter a series of unique identifiers (almost like a person's national citizen card) are produced, recorded and tracked so authenticity can always be checked and verified. Serialisation protects not only the end-customer, but also the profile of the pharmaceutical company as it shows that the company is in control of the different stages of the manufacturing and distribution processes, authenticity-wise.

How does serialisation work? In very simplistic terms, all pharmaceutical products contain a coding that work as their identification details. The product code is an assigned number that identifies a specific strength, dosage form, and formulation for a particular product/company. These codes are made of unique identifiers (code numbers) that can be found affixed on the saleable unit of any pharmaceutical product, and also at any underlying levels of packaging (cases, pallets, pouches, etc). The numbers and the way they are displayed can differ slightly from place to place (geographically speaking) due to different regulations. However, for some areas there is standardised referencing, e.g., the Global Trade Item Number (GTIN) standard. The GTIN standard, when properly assigned, is globally unique and assigned to a product at the stock keeping unit level, meaning NO OTHER PRODUCT ANYWHERE IN THE WORLD CAN EVER BE ASSIGNED THAT SAME GTIN. 

Is serialisation coding always the same? Some companies have chosen additional nomenclatures or reference numbers. For example, some use what is known as National Trade Item Number (NTIN). In addition, the National Healthcare Reimbursement Number (NHRN or NN for short) is used in a number  of countries to facilitate the reimbursement process. In the packaging and in the subsequent levels of product, any displayed Serial Number (SN) must relate to the particular unit (GTIN/NTIN) and also to a particular lot. In that sense, the serial number is a very specific identifier, related to all four components that make of serialisation a very useful scheme for one to be always sure that the product is reliable in its authenticity.

In summary, typically, units can have the human readable serialised code, the 2D bar code and an anti-tampering tape to ensure the product is fully controlled. The requirements now for the EU market is that hospitals, pharmacies and other medicines dispensers are responsible for scanning the data matrix on the pack and waiting for a confirmation of its authenticity before releasing the product to a patient. So pharmaceutical companies must check the components mentioned above and if they don't match up this will trigger what is known as a Level 5 alert, also known as Potential Falsification Alert. In case a compromised and/or non-authentic product is discovered, the information must be transferred to the National Competent Authorities for a serious investigation to be carried on, and the product must be immediately quarantined.

Let me know if this post was clear in helping you understand what serialisation is and how it does help protect you as a patient/end-user.

Cheers

Image 1 kindly taken from CrestSolutions, [http://www.crestsolutions.ie/serialisation-pharma-turkey].

Image 2 kindly taken from The Pharmaceutical Journal, [https://www.pharmaceutical-journal.com/news-and-analysis/news/mhra-says-falsified-medicines-directive-could-cost-500m-over-ten-years/20205213.article?firstPass=false]. 

Head to Alzheimer's, the putative link between a football career and neurocognitive diseases

I'm a crazy football-head! I breath, read, feed on everything that relates to football. I beg you to call it Football, not Soccer. Whoever came up with this name should be trialled!!! But I don't take offence easy so you're all excused as long as you keep reading to the end of this post. 

Every Saturday night I sit and watch this football TV show 'Match of the Day' that has been going on forever in the UK.  And as always Gary Lineker, a former football player that needs no introductions, is there with his guest panel criticising/acclaiming the weekend football results, goals, saves, performances, Mourinho's grumpiness :P and the like. The program is just that, a gourmet menu of football for football fans. But there was one specific moment in a random episode where they sat down for a while debating the possible link between a long football career, full of headings (head against ball) and concussions, and the onset of neurocognitive degeneration. Seriously! It got so interesting that time I just wanted to learn more about it. Would it be possible a link between neurocognitive degeneration and a career in football due to constantly heading balls? I had to research about it and I found a number of articles that can shed light on this topic but nothing immediately on heading balls. Surprisingly, I also found out that there's a lot of research emerging on this topic and soon certain observations will mature into consistent conclusions ready for discussion.  

 [B]

As I said just now I wasn't able to find many articles immediately relating football head injuries resulting from the recurrent heading of a football ball. In addition, the science out there is still dominated by American institutions and therefore pretty much everything found verses American Football (rugby with medieval plastic armours!!!). These were in my opinion the most interesting pieces I was able to read:

Guskiewicz et al (2005) [1] - Cerebral concussion is a recurrent injury in football but the neurological effects that occur as a result are yet not so clear. Some authors researched the relationship between previous head injuries and the probability of cognitive impairment/Alzheimer's disease by analysing a group of retired professional footballers who had had a previous head injury. After statistical study of the results observed (Chi square statistical test with two degrees of freedom negating a chance relationship) it was concluded that the occurrence of dementia-related syndromes 'may' be triggered by recurrent cerebral injuries resulting from a career in football. Retired players that had experienced ≥3 concussions had five times more prevalence of mild cognitive impairment and 3 times more the number of memory loss episodes. The authors could not establish a clear bridge between the series of concussions and Alzheimer's disease, but were able to hypothesise that for retired professional players who had these injuries Alzheimer's disease was happening earlier when compared to the general American male population.

Omalu et al (2005) [2] -  Case-studies always have their huge limitations, especially if not cross-linked with other more embracing studies to draw the most complete scenario, however, these authors analysed the full autopsy (with comprehensive neuropathological examination) results of a former football player that had been complaining of cognitive impairment, mood disorder and parkinsonian symptoms. The positive link between the long-term neurodegenerative outcomes was established with many cerebral observations (particularly with the presence of diffuse amyloid (protein) plaques - one of the Hallmark's of Alzheimer's disease as due to chronic brain trauma they accumulate as insoluble plaques between neurons, contrarily to what happens in healthy brains where these protein 'pieces' are metabolised and eliminated from the organism [3]. In fact, amyloid-beta plaques can be found in patients just a few hours after traumatic brain injury occurs, and the link between these protein plaques and Alzheimer's disease has been thoroughly studied (check Johnson et al (2010) [4] for an idea on the mechanics of this link). Nevertheless, the most surprising fact considering this player is that there was no family history of Alzheimer's disease and no records of him having had any head trauma outside his football career!!!

Small et al (2013) [5] - Five retired National football League players with ages going from 45 to 73 years old were studied using positron emission tomography (PET) with FDDNP (a molecule that binds to plaques (see [6] for more information on how the process goes mechanically) against five control subjects of comparable age, education and BMI (body mass index). Researchers analysed their PET signals in cortical and subcortical regions and came to the conclusion that, even though the results are for a very limited population and do not come along autopsy validation, FDDNP signals were higher in players in comparison to the healthy control subjects, in all the studied subcortical regions and in the amygdala -  the areas responsible for post-trauma tau deposition. Tau proteins are molecules that stabilise the microtubules in the nerve cells.

Many studies that are now arising on the mechanical damage of the brain have inherent methodological limitations. Hence, they must be taken merely as exploratory research. What does it mean? It means that these studies are merely tentative research studies to build up and interlink initial ideas that down the line will feed the very first dogmas/theories. Add to that a natural 'skepticism' from those who control the riches of the football market/organisation and you'll understand that even within NFL there is still some resistance in accepting the causal relation between consecutive head concussions and early cognitive decline later in life [7]. But the matter of fact is that there is definitely enough substance to at least indicate where the future research should go as results point towards a definitive incidence of cases where this link is scientifically verified and confirmed, as I have just explored above. Moreover, because not all players will immediately reveal signs of chronic traumatic encefalopathy [8] research out there needs to not only expand the range of observed population but also the depth of their scrutinising. For example, an interesting approach is the one taken by Marchi et al (2013) [9] where players were assessed after their matches took place and that allowed concluding that blood-brain barrier disruption occurred even in the absence of concussion, thus supporting the possibility that a long career of heading football balls could be linked to the early onset of Alzheimer's and other neurocognitive diseases.

I hope you've enjoyed today's post. Leave me a few comments or just drop a well-done message!

Any corrections or tips are also welcome.

[1] Guskiewicz, K. M., Marshall, S. W., Bailes, J. et al (2005). "Association between recurrent  concussion and late-life  cognitive impaiment in retired professional football players". Neurosurgery, 57(4), pp. 719-726.

[2] Omalu, B. I., DeKosky, S. T., Mynster, R. L. (2005). "Chronic traumatic encefalopathy in a National Football League player". Neurosurgery, 57(1). pp. 128-134.

[3] Amyloid plaques and neurofibrillary tangles, BrightFocus Foundation, [https://www.brightfocus.org/alzheimers/infographic/amyloid-plaques-and-neurofibrillary-tangles], last updated on the 21st of December 2017, last visited on the 1st of November 2018.

[4] Johnson, V. E., Stewart, W., Smith, D. H. (2010). "Traumatic brain injury and amyloid-beta pathology: a link to Alzheimer's disease?". Nature Reviews Neuroscience,11, pp. 361-370.

[5] Small,  G. W., Kepe, V., Siddhart, P. et al (2013). "PET scanning of brain Tau in retired National Football league players: Preliminary findings". The American Journal of Geriatric Psychiatry, 21(2), pp. 138-144.

[6] Ercoli, L. M.,  Siddarth, P., Kepe, V. et al (2009). "Differential FDDNP PET in non-demented middle aged and older adults". The American Journal of Geriatric Psychiatry, 17(5), pp. 397-406.

[7] Kain, D. J. (2009). "It's just a concussion: The National Football League's denial of a causal link between multiple concussions and later-life cognitive decline". HeinOnline [https://heinonline.org/HOL/LandingPage?handle=hein.journals/rutlj40&div=22&id=&page=], last visited on the 06-Nov-2018, last update unknown. 

[8] Hazrati, L-N., Tartaglia, M. C., Diamandis, P. et al (2013). "Absence of chronic traumatic encefalopathyin retired football players with multiple concussions and neurological symptomatology". Human Neuroscience, 7(222), pp. 1 -12.

[9] Marchi, N., Bazarian, J. J., Puvena, V. et al (2013). "Consequences of repeated blood-brain barrier disruption in football players". PLOS One, 8(3), pp. 1-11.

Post Photo by Kenny Webster on Unsplash

[B] Photo by John Torcasio on Unsplash

Nature's alternative to EpiPen?!

This article is the second part of the original post you can find HERE.

The risk of self-medicating is a serious hazard and can endanger lives, so the acceptable attitude is not to do it and always consult with your GP. But if you're in the middle of the Amazonian jungle being hunt down by wild pumas that haven't eaten for two weeks, and at the same time you are undergoing a really serious anaphylatic shock because of an Africanised honey bee sting (hold your breath!), with no medical staff around, no EpiPen on sight and struggling to breath (hold your breath again!!) ... and the bee division just got some backup reinforcements... what can you do? What can the natural elements of this beautiful organic pharmacy called Mother Earth can do for you?

With neither phones available nor rapid access from and to a hospital, you have to trust the handy plants you are surrounded by. However, it is likely the action of any plant with positive effects on allergies to be quite slow and mild compared to the urgency of an anaphylatic shock. And considering everyone is intelligent enough to try their best to avoid exposure to a known allergen, the only medical response to an anaphylatic shock is indeed an epinephrine injection commercially known as EpiPen. Even though there are other more affordable epinephrine auto-injectors, i.e., the class of drugs EpiPen is part of. Remember, I am not publicising any of these products but just informing you of their existence, I wish I was cashing something for advertising these products, the reality is that I'm not. But due to high-profile complaints regarding the ever increasing price of the most famous epinephrine auto-injector [1] I honestly believe that knowing of alternative products is a public responsibility. In fact, there are other alternatives available, like the Adrenaclick [2] or the Auvi-Q [3], and an article from 2006 predicted yet another one, tailored for those afraid of needles - the Epi-Pill [4]. For more information on commercial alternatives you can access the sub-page of the Division of the Asthma and Allergy Foundation of America entitled "Kids with Food Allergies". There you can find a very professional comparison between several other commercially available epinephrine auto-injectors with different aspects put into perspective, not solely price!!! [A]

So that you know and allow me to reinforce it once again, no herbs can do the magic trick so quickly and effectively whilst saving crucial time until further medical assistance is made available. Many websites talk about miraculous responses and dwell on the most fantasist first-aid cures for an anaphylatic shock. They irresponsibly promote the use of plant and homeopathic preparations based on Eucaliptus, Lavender, Lemon, Quercetins (a plant flavonoid with antioxidant and anti-inflammatory effects, however still to be fully studied for its safety and efficacy as an anaphylaxis antagonist) [5], Aconitum napellus, Apis mellifica, Cantharis, Carbolicum acidum, Hypericum, Ledum palustre, Urtica urens, etc etc etc... but we are not talking about tackling a mild allergy, we are talking about the need for an immediate life-saving approach that can promptly rescue a person until professional medical assistance is made available. Not some alleviation of mild symptoms!!!!!! All those plants and powders and miraculous herbs widespread mentioned through million websites with no scientific referencing whatsoever, will not do the job at all!!! The suggested immediate treatment to anaphylaxis is still epinephrine followed by a professional medical follow-up, as suggested by the World Allergy Organisation on their 2015 update on the evidence base [6]. And if you don't have the courage to read through 16 pages just jump straight to the "Initial Treatment To Anaphylaxis" on page 7 that reads:

"Anaphylaxis is a life-threatening medical emergency in which prompt intervention is critical. Principles of treatment remain unchanged; however, recommendations for treatment are based on evidence of increasingly high quality".

And maybe then also read the very important statement on page 8's Section "Long-term management of anaphylaxis in community settings: self treatment". This is the least one should do to be aware of the best present prophylactic and/or management methodologies. 

Have a shocking safe Easter!

[A] Epinehrine auto-injector available with a prescritpion in the United States,  Kids with Food Allergies, [http://www.kidswithfoodallergies.org/page/epinephrine-and-anaphylaxis-food-allergy.aspx#eai], last access on the 29th of March 2018, last update on February 2014.

[1] US Senator Charles Grassley's complaint letter, from the 22nd of August 2016  [https://www.grassley.senate.gov/sites/default/files/constituents/upload/2016-08-22%20CEG%20to%20Mylan%20(EpiPen).pdf], last accessed on the 29th of March 2018.

[2] Adrenaclick for anaphylatic emergencies, [http://adrenaclick.com/], last accessed on the 29th of March 2018, last update unknown.

[3] Auvi-Q epinephrine injection, [https://www.auvi-q.com/], last accessed on the 29th of March 2018, last update unknown. 

[4] An under-the-tongue alternative to EpiPen (2006), Harvard Health Letter, [https://www.health.harvard.edu/newsletter_article/an_under-the-tongue_alternative_to_epipen], last accessed on the 29th of March 2018.

[5]  Chirumbolo, S. (2011). "Quercetin as a potential anti-allergic drug: which perspectives", Iranian Journal of Allergy, Asthma and Immunology; 10(2), pp. 139-140.

[6] Simmons, F. E. R., Ebisawa, M. Sanchez-Borges, M. et al (2015), "2015 update on the evidence base: World Allergy Organisation Anaphylaxis Guidelines". World Allergy Organisation Journal, 8(32), pp. 1-16.

Why is adrenaline prescribed in an anaphylactic shock crisis?

As a Medical Information Officer I am constantly bombarded with situations where, among several other possibilities, allergic reactions are eventually reported as adverse events. However, I never got to be confronted with a patient undergoing anaphylactic shock. What I realised though is that most people out there do not have a precise or at least mildly accurate idea of what an anaphylactic shock is. They just know the term but lack the understanding. In addition, if you ask most of your friends and relatives why medical doctors prescribe adrenaline (epinephrine) to counteract an anaphylactic shock crisis, well above 90% will roll their shoulders in ignorance.

It's understandable that we cannot know it all about everything, but I have always been a curious bee. And the moment this question popped up in my head a few years ago, I had to research to address it immediately. By surprise, it happened to me today to find someone (outside work) who didn't know about the reason behind the use of epinephrine (adrenaline) as an antagonist of such systemic allergic chain of events.

As usual, I don't dwell on questions that have been vastly and adequately addressed in different websites through the Internet. When that is the case I refrain to comment on the matter. But this time I decided to just simplify the very good explanations you can find online, so that even those not naturally versed in the slightest medical science and terms, can make sense of all the jargon and conceptualizations involved. Thus, quite simply put, let us imagine:

• A bee stings your child in the neck... let's go for neck rather than hand to add a bit of a physical oddness and proximity with the heart that will enhance the emotional atmosphere of scare.

• Your child is allergic to the substances present in the bee sting injection and the body starts producing an allergic reaction. Don't forget that an allergy is just the immune system considering a substance to be foreign to the system and therefore an attack on that substance (known as allergen) is initiated. But sometimes the response is inappropriate and imbalanced leading to a systemic chain of events that put the whole cardio-respiratory system in alert.

• What happens next in the hypersensitive body is an anaphylactic response that, by means of biochemical and physiological procedures in your child's body, will try and block the access of that substance (allergen) to the vital organs. 

• Naturally, your child's body produces adrenaline that will ease the physiological extreme responses of her/his body to the allergen, meaning his/her body will try and block the effects of the allergen by reducing the blood flow and consequently constricting the airways. However, in a person with hypersensitive immune system the body needs a lot more adrenaline because it is in severe shock already, hence an immediate action is deemed necessary.

• The only available option is the epinephrine injection that is usually administered to the patient as an urgent first aid approach. 

• Why an injection? Simply because adrenaline is a natural hormone produced in humans and is easily degraded by the stomach acids. In the event of an anaphylactic shock your child will need higher doses of adrenaline than normal, and quickly accessed. The intramuscular injection of adrenaline with what is known as an EpiPen operates miracles.

• What does it do? Adrenaline will reduce the throat swelling and open your child's airways allowing him/her to breath naturally, it will normalise your child's blood pressure and overtime bring your child's impaired cardio-respiratory system to a normal point where medical intervention (if necessary) will be monitoring his/hr health.

I hope this quick-fix worked as an EpiPen for your questions in case you had any! Thanks for visiting The Toxicologist Today. Now, do you know what you can use if you're in the wild and have no access to a much needed EpiPen? Stick around and you'll find out in the coming post.

1st image kindly taken from EpiPen prescribing information, [https://www.epipen.com/hcp/about-epipen-and-generic.aspx].

2nd image kindly taken from The Telegraph, [https://www.telegraph.co.uk/news/health/news/8796536/Bee-sting-vaccine-on-the-NHS.html].

How does Napalm work?

Watching Forrest Gump for the fifth time or so, a few weeks ago,  my wife (yet again my wife), asked me if Bubba would survive whilst Forrest Gump was trying to find him. The air strike was imminent and Napalm was about to descend from them airplane' belies. That's when my wife asks me wearing this intrepid stare...

How does Napalm work?

Well the when and the why should always outrun the how in this specific case, it is indeed a sad story that deserves to be told to everyone, not only those who found themselves involved in the Vietnam war, or the preceding Cambodian armed conflicts. But this is not the right place to do it.

A QuickFix on Napalm urges one to visit Medscape's webpage on Napalm exposure.

Napalm is an incendiary substance produced by the combination of a gelling powder (like the one in baby's nappies only the Napalm one contains Naphtalene and Palmitic acid) and gasoline in different concentrations. This will form a white, cloudy, gelatinous inflammable matter, that is very stable (not temperamental like nitroglycerin) tolerating temperatures in between 4 to 66 degrees Celsius. Thermal stability on such a range of temperatures make of Napalm the "right" ingredient to roast tropical forests or debunk bunkers hidden deep in icy landscapes.

Sated curiosity?... just don't Napalm your coming Summer barbecues. Keep watching movies and reading The Toxicologist Today, it's safer and peaceful.

I WANT TO OVERDOSE

Medscape, Napalm exposure, [http://emedicine.medscape.com/article/833665-overview], last visited on the 29th of April 2014, last update unknown.

I want to overdose redirects you to the web page based on articles by Lisandro Irizarry, Assistant Professor at the Weill Cornell School of Medicine. 

How much caffeine is there in decaf coffee?

Welcome to QuickFix, the new label from The Toxicologist Today, where you get the answers to the most quotidian questions that you're ashamed to plead ignorance on or even ask your mates about. In the future I'll be covering issues that apparently everyone is an expert on, but only the actual experts can address them properly. 

My wife asked me the other day How much caffeine is there in decaf coffee?

The answer was found in 3 seconds and is posted here from the Nescafe.co.uk website. No hussle! No scientific jargon!, just an immediate QuickFix to save you time.

I want to overdose

Caffeine in decaf coffee, [http://www.nescafe.co.uk/caffeine_in_decaf_coffee_en_com.axcms], last visited on the 5th of April 2014, last update 

I want to overdose redirects you to the article by Ramalakshmi, K. Raghavan, B (1999). "Caffeine in coffee: Its removal. Why and how". Critical reviews in food science and nutrition, 39(5), pp.441-456.