Research & Beyond

It's being a long time I was not around to update my blog and was busy with my Ph.D. duties. Since 2013, I have conducted several research works on various health specialties and published more than 150 publications in high-impact journals, and reached high citations. I wish to share my research journey that may help to motivate early career PharmD students and clinical pharmacists. Personally, I believe that most PharmD students are demoralized due to a lack of competitive faculties and facilities. I was one among you, who understand your pain. I approached several faculties during my PharmD journey and expecting their help, but they never did. 

As most of the followers already know, Akshaya is an exceptional PharmD and has proven my competencies at international platforms. I started this blog to provide the scope and share my view with my PharmD's and other health professionals. I do post related to research-exclusive things. Something I post about health, novel therapies, advances, and outside clinical pharmacy field. 

PharmD's should never miss their opportunity to learn and the ivory tower of knowledge, theory, and research; they should be out there, in the world. PharmD's should be embodied with curiosity and learning, teaching others, and advancing the research. We – people of therapeutic experts – should be thinkers, writers, dreamers, and knowledge-collectors regardless of whether we are an 'expert' in that knowledge. It's our day job to be experts; it should be our passion to be constantly searching for something new to learn. 

So, my journey comprises academia, research, and beyond. Nothing more, nothing less. But my dream is still alive. 

Warm regards,

Akshaya Bhagavathula

Solving Antibiotic Resistance

There has been much recent talk about how to target the rising tide of antibiotic resistance across the world, one of the biggest threats to global health today. While there is no doubting the size of the problem facing scientists, healthcare professionals and the pharmaceutical industry, there are innovative ways we can target antibiotic resistance in the short term.

With only a few antibiotics in development and a long drug development process (often 10-15 years), there is concern that what is being done to combat antibiotic resistance may be 'too little, too late'.

While any antimicrobial resistance is concerning, the increasing incidence of antibiotic-resistant Gram-negative bacteria has become a particular problem as strains resistant to multiple antibiotics are becoming common and no new drugs to treat these infections (eg, carbapenem-resistant Enterobacteriaceae) will be available in the near future. These Gram-negative bacteria are considered the most critical priority in the list of the 12 families of bacteria that pose the greatest threat to human health that was just released by the World Health Organization.

An innovative strategy that is gaining momentum is the synergistic use of antibiotics with FDA-approved non-antibiotics. Using this novel approach, an FDA-approved non-antibiotic drug is combined with a specific antibiotic that enables it to breach the outer membrane barrier and so restore the activity of an antibiotic. Several researchers had described how combining antibiotics with other non-antibiotic drugs or compounds can boost their effectiveness against Gram-negative 'superbugs'.

For example, loperamide, an anti-diarrheal medication sold in most pharmacies, enhances the effectiveness of eight different antibiotics (all in the tetracycline class). In particular, when added to the tetracycline antibiotic minocycline, along with the Parkinson's disease drug benserazide, it significantly increased antibiotic activity against multi-drug resistant Pseudomonas aeruginosa, a causative agent in hospital-acquired infections such as ventilator-associated pneumonia.

Polymyxins are a type of antibiotics that target Gram-negative bacterial infections and have traditionally been used as a last resort to treat serious infections such as those caused by Gram-negative 'superbugs' Klebsiella pneumoniae, P. aeruginosa and Acinetobacter baumannii. Resistance to polymyxins is not common, but in late 2015 the first transferable resistance gene to colistin (polymyxin E) was discovered (plasmid-borne mcr-1 gene). This caused significant concerns, as once resistance to polymyxins is established, often no other treatments are available.

Some interesting findings have ensued, with a number of different combinations having a beneficial effect. Some notable examples that increased antibiotic activity when combined with polymyxin B include: ivacaftor and lumacaftor, two new drugs used to treat cystic fibrosis; and closantel, a drug used to treat parasitic worm infections.

Another interesting combination that has shown promise against methicillin-resistant Staphylococcus aureus (MRSA), according to Schneider and co-authors, is combining the antibiotics ampicillin or oxacillin with berberine. Berberine is extracted from the roots, stems and bark of plants such as barberry.

n 2005, the Drugs for Neglected Diseases initiative identified fexinadole as a potential treatment for sleeping sickness and it is now undergoing a Phase III trial. This drug had been developed as an antimicrobial in the 1970s, but only reached pre-clinical development.

In addition to the above, researchers are looking for new, untested sources of antimicrobial activity to try and develop new drugs. A recent success in this area was, teixobactin, a new antibiotic developed by NovoBiotic Pharmaceuticals, discovered by using an 'iChip' to culture and isolate soil bacteria in situ.

"Non-antibiotic strategies are just as important, such as developing vaccines or probiotic therapies to prevent infections, as they can help to reduce the overuse of antibiotics. They will never completely replace antibiotics, but can help to preserve our existing antibiotics so they still work when needed."

Inspired by recent article: Antibiotics and non-antibiotics combination

by 

Dr. Akshaya Srikanth Bhagavathula

Pharm.D India

Injectable Antiretroviral Therapy: The Future

HIV therapy has dramatically improved over the past few decades due to advances in new drug discoveries and reformulations allowing for simple oral regimens. These advancements have helped to combat resistance and reduce pill burden for patients. Once-daily antiretroviral regimens are quickly becoming new standards for new patients; however, adherence is still a concern. But what if patients no longer had to take a pill every day? This could be possible with the new, long-acting injectable antiretrovirals cabotegravir and Edurant.

The components of the injectable regimen consist of a non-nucleoside reverse transcriptase inhibitor (NNRTI), Edurant (rilpivirine, Janssen Therapeutics), and a new integrase strand transfer inhibitor (INSTI), cabotegravir (ViiV Healthcare). Rilpivirine is a second-generation NNRTI approved in 2011 for the indication of treatment-naive patients with HIV-1 RNA less than 100,000 copies/mL. Its increased potency, longer half-life (oral: 50 hours; intramuscular: 20-40 days) and reduced adverse effect profile in comparison with a first-generation NNRTI such as Sustiva (efavirenz, Bristol-Myers Squibb) made it ideal to combine with the new INSTI.

The discovery of integrase inhibitors in the late 2000s was pivotal for drug regimens as these agents were associated with few adverse reactions and were very effective for treatment-naive patients. Despite being new agents, Isentress (raltegravir, Merck) and Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide, Gilead Sciences), already have documented resistance in treatment-naive and previously treated patients, thus prompting the development of the second-generation Tivicay (dolutegravir, ViiV Healthcare), an INSTI that is more sustained against resistance and has an improved administration profile. Cabotegravir, a potent analog of dolutegravir, possesses a long half-life (oral: 40 hours; intramuscular: 30-90 days), allowing for once-daily dosing with no need for a booster.

Impact of an injectable regimen

Current results appear promising for this new injectable therapy option. It is unique to have a two-drug regimen for maintenance therapy of HIV, but thus far development of resistance does not appear significant. The utility of an injection could pose several challenges for the patient. Adherence may continue to be an issue given that the initial induction phase is similar to many other current once-daily oral regimens. Patients still need to prove adherence to the oral regimen before starting an injectable maintenance therapy. Additionally, adherence to an injectable may pose its own setbacks. While satisfaction was reported to be high, it may be unfavorable to request that patients visit the clinic every 1 to 2 months when it could be reduced to once- or twice-yearly visits. If patients are able to administer the injections at home, this regimen could be a game-changer for those who are nonadherent. However, a gluteal injection may be too complicated for self-administration. The company expressed the possibility of investigating administration of the thigh, which sounds very reasonable as a new standard regimen. Lastly, the cost of these injectables will be another debate as current oral regimens are well-covered by insurance companies. The price of these new formulations is not currently available, but to incentivize use, they will likely need to be comparable to oral regimens.

More results from the phase 2b study and a future phase 3 study will determine if this is a feasible therapy regimen from an efficacy and safety standpoint. The once-daily, triple-therapy oral regimens show good tolerability and low resistance rates, making this regimen fit within the current standards. The major appeal to an injectable regimen would be the potential for improved adherence. This could dramatically change a patient’s quality of life as they are able to return to a pill-less (or at the least, a lower pill burden) life.

Source: LATTE Trial

by

Dr.Akshaya S Bhagavathula, Pharm.D

Egg Consumption doubles Cardiometabolic Risk

The gut flora or microbiota is undoubtedly crucial to the digestive process. However, there is growing interest in the role of the gut microbiota as an environmental factor influencing propensity for cardiometabolic disease. Studies have implicated the gut microbiota in susceptibility to obesity and insulin resistance; germ-free mice fed a high-fat, high-carbohydrate Western-style diet were protected against diet-induced obesity, glucose intolerance and insulin resistance.

More recently, research has linked dietary lipid intake, the gut microbiota and increased risk for atherosclerosis.(2,3) Cholesterol-rich foods, such as egg yolks, contain phosphatidylcholine which is hydrolysed by phospholipase enzymes to release choline. The gut microbiota then convert choline to trimethylamine (TMA), whichundergoes oxidation in the liver to trimethylamine N-oxide (TMAO), released into the plasma.

In mice susceptible to atherosclerosis fed a diet supplemented with phosphatidyl choline, there was an increase in plasma levels of TMAO concomitant with increased atherosclerotic plaque development. Mechanistically, increased dietary choline was associated with suppression of multiple macrophage scavenger receptors which protect against atherosclerosis.3 These data therefore implicate excess dietary choline as an emerging modifiable risk factor for cardiovascular disease, mediated by the gut microbiota.

These findings may be relevant in the light with recent research which showed an association between egg yolk consumption and carotid plaque burden. Individuals consuming 3 or more eggs per week had a significantly higher plaque burden that those with reduced consumption. This suggests that egg yolk consumption should be reduced or avoided in high-risk individuals with established cardiovascular disease. Consumption of a large egg (which equates to about 200 mg of dietary cholesterol) not only increases the susceptibility of low-density lipoproteins (LDL) to oxidation, but also increases postprandial lipaemia, and potentiates the adverse effects of dietary saturated fat. Additionally, egg consumption effectively halves postprandial clearance of atherogenic chylomicron remnants, which implies a need to re-consider egg yolk consumption in individuals with cardiometabolic disease, including those with diabetes. Indeed, in observational studies, regular egg consumption was associated with increased risk of new-onset diabetes, cardiovascular disease and all-cause mortality. These epidemiological data, together with the FOCUS paper, provide a strong rationale for a prospective randomized trial comparing the effects of consumption of eggs or egg white-based substitutes on hard clinical outcomes.  Currently, international guidelines are inconsistent in considering the dietary cholesterol. Currently, international guidelines are inconsistent in their consideration of dietary cholesterol. There are also misconceptions that because of the efficacy of statins in lowering plasma total cholesterol and LDL cholesterol, consideration of dietary cholesterol is less relevant in statin-treated patients. Yet even with intensive statin therapy, there remains about 70% residual cardiovascular risk.

by

Dr.Akshaya Srikanth, Pharm.D

Pharm.D in India: What is known and What is unknown ?

Doctor of Pharmacy (Pharm.D) in India has created a huge hike on young pharmacists, expecting the future is much better than the other branches of pharmacy. Pharm.D's syllabus is we framed with lot of debates and observations from the developed world to provide a competent clinical pharmacist for the better health care in India. See the syllabus the other health care professionals were excited to see the practicality of this course in their work place. But, theoretically Pharm.D has made a huge impact on the developed nations and developing nations to adopt the India Pharm.D syllabus a standard one to practice in their own countries. To the same, the Indian Pharm.D has many pitfalls in practicality, which is hard to answer the route cause. For instance, a competent clinical pharmacist needed more practical training which need much focus on patient care by training them in the wards and engaging them in all the activities that can make them to learn how to implement the clinical pharmacy and collaborative work with other health professionals. Due to lack of competitive faculties the scope of bed-side teaching was negligible. Its fact, when Pharm.D students enter into the wards, they see the nursing staff training their nurses, Doctors training their medicos but Pharm.D students were relaying on the medical doctors to provide some support as the faculties never likely to participate in the bed-side teaching and working with the health professionals in the wards.

Increasing number of colleges increased the demand of Pharm.D admission, but there is none to answer the practicality of their roles and jobs. Disparities in training and unsuccessful competencies with poor health care acceptance kept the Pharm.D's into dilemma. Furthermore, it also made a lot of confusion among the student minds and unable to fulfill their dreams. For instance, course such as  Pharmacoepidemiology and clinical research were elaborative in syllabus, but faculties unable to engage them in any activities such visiting clinical research sites, engaging them in some pharmacovigilance activities. Furthermore, the organizations well focusing on conferences for showoff and unnecessary hikes over the Pharm.D without know the practical barriers faced by the students. For instance, there are many pharmacy organizations inviting the international delegates to participate in the national and international conferences, but unable to engage the Indian Pharm.D's to get trained in overseas.

Now the number of Pharm.D's increasing and coming out with any vision. This is because of lack of planning and support from the Pharmacy board. This situation is especially burning in southern states where the number of colleges are more than that of other parts of India. All colleges promising to give admission but unable to secure them in jobs. The student associations such as "IPSF", and "IPA-SF" etc., are focusing on conferences and international fame rather to supporting the local Pharm.D students. The silence answers from the pharmacy leaders increasing the tensions in the student mind. There is much more needed to work at ground level, focusing on providing standard practical training rather basic theoretical knowledge, providing a scope and hope on the Pharm.D's for securing the jobs is crucial.

In conclusion, Pharm.D's are currently in great frustration and needed support from all phases for the future of clinical pharmacy in India. Further, clinical pharmacy is a practice of patient care through pharmaceutical care. If the theoretical knowledge can fulfill the dream then we are in world of delusion.
by
Dr.Akshaya Srikanth, Pharm.D
Pharm.D India

Feed your Brain with ECG Today

Many people think electrocardiograph (thusly called ECG or EKG) a tough talk to understand and interpret. This is not such a huge task or need to do specialization in cardiology. This is just cardiology, simple biological pipes and wires. ECGs are simpler still, being a moving real time map of the “wires” part and how they conduct electricity.  Reading EKGs only seems hard because most cardiologists use long (expensive) words.

Most healthy hearts pump blood through the body when stimulated by an electrical signal that travels along predetermined pathways.This causes the cardiac cells to contract in just the right order, resulting in a magical four chambered pumping action. 

An EKG is a graph tracing the strength and direction of this electrical signal. Leads equipped with conductive goo are placed on different parts of the body allowing a view of the heart from different angles. If the electrical activity of the heart at any given moment is traveling toward the lead being viewed, the line on the graph goes up (positive deflection).  If the electrical activity is traveling away from the lead, the line goes down (negative deflection). This graph is being traced by a stylus on a moving piece of graph paper. In a normal healthy heart, an ECG representing one complete heartbeat looks about like this :

That first petite little hump, affectionately called the P wave, represents the electrical signal that starts in a group of cells called the Sinoatrial Node. This signal then travels through the atria (the smaller and upper two chambers of the heart) causing them to contract and push blood in to the larger and more powerful ventricles below.

The “PR Interval” segment represents a delay in the signal at another grouping of cells called the AtrioVentricular Node.This delay allows time for the atria to completely deliver their bounty into the Ventricles. With perfect timing this signal continues through the Bundle of His.The signal splits and speeds along down the left and right bundle branches, making its way to the Purkinje fibers and turning north again.This stimulates those Ventricular beefcakes to contract and deliver their payload to the lungs and body (if hearts had biceps, the left ventricle would be the proverbial “gun show”….it’s such a glory hog!).

The journey causing this second contraction through the ventricles is represented by the QRS portion of the ECG. The larger T wave which then finishes off our heartbeat is the repolarization of the ventricles.I know what you’re thinking, either “what in the what now goes where?” or hopefully, “what wave represents the repolarization of the atria”? Well, the repolarization of the atria is buried in the larger signal of the QRS and therefore not visible on the graph.

This pattern is called normal sinus rhythm.  It is the basic ECG of any normal healthy heart. Naturally, there are variations of normal within the healthy population. For example, my boyfriend is very fit and has a *huge* R wave (hands off his big left ventricle ladies, it’s all mine! And don’t get me started on his early repolarization…and no…being early in this case is definitely not a bad thing). However, anything outside of the normal range is analyzed along with the patient’s symptoms to create a working diagnosis.There are several types of common abnormalities. A PR interval that is too long is called a first degree block. A QRS that takes longer than .12 seconds is likely to be caused by a delay in one or both bundle branches, called a bundle branch block. A complete lack of P waves, and in their place a squiggly line, combined with an irregular heartbeat is likely to be atrial fibrillation. What really gets a Paramedic or ER doctor excited is when they see an elevation of the ST segment in a few consecutive leads.This is referred to as an ST elevation myocardial infarction (heart attack) and generally results in a speedy trip to the catheterization. 

Feeding points:

1) Each small box on the modern ECG strip represents 0.04 seconds on the horizontal axis.

2) ECG paper is calibrated to move at 25mm per second past the stylus.

3) The ECG was invented by the Dutch Dr. Willhelm Einthoven in 1903, for which he received the Nobel Prize in 1924. More impressively, he also had a triangle named after him.

4) It is very rare, but possible for an ECG to show a flat line, called asystole, when in fact the heart is still beating and producing a pulse.  It is because of this that it’s common practice to confirm death in a patient by looking for asystole in more than one lead.

5) Conversely it is also possible, and more common, to have an ECG show heart activity, and even normal sinus rhythm, after a person has died and their heart is no longer pumping blood. This is called a PEA, pulseless electrical activity, and shows what is left of the heart’s intact electrical system after the muscle itself has failed.

I hope you understand well. 

Thanking you

Dr.Akshaya Srikanth B, PharmD

Cardiac Biomarkers

A blood screening technology has uncovered many biomarkers that improve the prediction of the risk for heart attack or stroke with in the next 15 years. The blood profiling technique may eventually help doctors to identify those people who would benefit the most from early treatment and high-throughput profiling of circulating metabolites may improve cardiovascular risk prediction over established rik prediction over established risk factors. 

Biomarkers can potentially be used to detect and monitor a wide range of cardiac conditions in the critical care setting. Currently the only biomarker acceptable for changing management in acute coronary syndrome is the troponin test. In the future, a tailored multi-marker approach may have use in guiding diagnosis and therapy – this is a long way off!

POTENTIAL USES OF CARDIAC BIOMARKERS

Myocardial Ischemia

·         Troponin

·         H-FABP

·         ischaemic modified albumin

Thrombosis

·         CRP

·         ESR

·         different binding proteins

·         Myocardial injury

·         Troponin (level peaks at 12h, proportional to infarct size, but altered by washout phenomenom after reperfusion therapy)

·         CK

·         CK-MB

·         myoglobin

·         AST

·         LDH

Novel: copeptin (C-terminal provasopressin), BNP/ NTproBNP, GP-BB, myleoperoxidase, pregnancy associated plasma protein A

Inflammation, endothelial activation and neutrophilic activation

·         CRP

·         ESR

·         PaPPA

·         endothelin/ CTproET-1

·         adrenomedullin/ MRproADM

·         myeloperoxidase

·         matrix metalloproteinases (MMP9, MMP2, TIMP1)

Heart failure

·         BNP/ NTproBNP

·         ANP/ N-ANP/ MRproANP

·         Troponin

·         IL18

·         CA125

·         Urocortin

Sepsis-induced myocardial dysfunction

·         Troponin

·         BNP/ NTproBNP

·         Right ventricular strain in pulmonary embolism

·         Troponin

·         BNP/ NTproBNP

ADVANTAGES AND DISADVANTAGES 

In addition these biomarkers mentioned above four new biomarkers were identified in 2015. The scientists identified over 200 biomarkers for body metabolism from a single blood sample using Nuclear Magnetic Resonance (NMR) spectroscopy. The perspectives of new biomarkers for future cardiovascular disease were Phenylalanine, a common amino acid, and the amount of monounsaturated fat in the blood; higher concentrations were linked with higher disease risk. These two biomarkers were as strong predictors of future heart disease as the measures bad cholesterol or blood pressure. In addition, higher blood levels of both omega-3 and omega-6 fatty acids were linked with lower risk for cardiovascular disease. All these molecules are normally present in everyone's blood, but it is the amount of these molecules that was shown to be reflecting the cardiovascular health. 

These new biomarkers can help to better assess the complex molecular processes behind the development of cardiovascular disease. The improved prediction of cardiovascular risk also suggests cost saving in healthcare by advanced biomarker profiling. The low-cost blood screening technology opens a treasure trove to understand the molecular mechanism of heart disease and other metabolic disease.

by 

Dr.Akshaya Srikanth Bhagavathula, Pharm.D 

for Pharm.D India

Trigeminal Neuralgia: The suicide disease

Trigeminal Neuralgia is a type of facial pain / headache causing sharp, shooting pain on one side of the face. It is one of the most painful diseases known to mankind. It is also called ‘suicide disease’, because of the severity of the pain.

Symptoms

People suffering from trigeminal neuralgia usually have a sharp, shooting, electric shock like pain on one side of the face / head. Trigeminal nerves are basically a set of 3 nerves that provide sensation to either side of the face. Trigeminal pain can affect different parts of the face. Initially the sharp pain is occasional and very short lasting. Gradually the pain becomes more permanent. It is more common in elderly people, over the age of 50 years. It is slightly more common in women.

Triggers Trigeminal Pain Attacks

Trigeminal neuralgia pain can be triggered by trivial things like cold air, touch, speaking, shaving, brushing teeth and chewing food. Pain is usually felt in the cheeks, lips, nose, ears, eyes, teeth, jaw, scalp or the entire side of the face. It almost always affects only one side of the face. Unlike migraine headache, the trigeminal pain does not change from one side of the face to the other. It is very common to find trigeminal neuralgia sufferers refusing to talk /open their mouth. They may cover that part of the face to avoid touch or air contact. Frequently they end up with dentists, thinking it is a dental problem.

How is trigeminal neuralgia diagnosed?

If trigeminal neuralgia is suspected, it is advisable to consult with a neuro physician or pain physician. After having the clinical history and performing a neurological examination, the physician may order a MRI or CT of the brain. Once diagnosis is confirmed, appropriate treatment is started.

How is trigeminal neuralgia treated?

Initial treatment for trigeminal neuralgia includes medications like carbamazepine (tegretol), oxcarbazepine, gabapentin, pregabalin, baclofen, etc. Typically, the medication is started at low doses and adjusted according the effect. With medications, mild cases of trigeminal neuralgia pain can be controlled. Taking long term medications can cause some side effects.

What are the advanced treatment options for trigeminal neuralgia?

If oral medications are not providing adequate satisfactory pain relief or if there are medication related side effects, other advanced options are available. Radiofrequency ablation of the trigeminal ganglion is newer modality of treatment available for trigeminal neuralgia sufferers. Radiofrequency thermal ablation of trigeminal ganglion, performed under x-ray guidance, provides safe, long term relief from trigeminal neuralgia pain.

It is a day care procedure performed under IV sedation. Once RF ablation is performed, patient can stop taking usual oral medications. Percutaneous pain interventional procedures like radiofrequency ablation of trigeminal ganglion are repeatable at a later date, if required. Trigeminal pain sufferers above 50 years of age are also good candidates for radiofrequency ablations. Older techniques like glycerol injections and balloon compression have been replaced by RF ablations now. Majority of insurance companies including the government schemes approve RF ablation for trigeminal neuralgia sufferers.

What is the role for surgery in trigeminal neuralgia?

Surgeries are reserved for patients, not responding to oral medications and conservative management. It may be suitable for trigeminal neuralgia due to secondary causes like tumours or trigeminal neuralgia in younger patients.Surgeries called microvascular decompression are offered by neurosurgeons for trigeminal neuralgia. Microvascular decompression surgeries have more risk involved and are costly. If performed successfully, these neuro surgeries can provide long term pain relief. Thanks to the advent of all the above mentioned treatments, trigeminal neuralgia sufferers don’t have to suffer in pain anymore.

by

Dr.Akshaya Srikanth B

LIPIDS AND STROKE: A RESEARCH UPDATE

Stroke, predominantly ischaemic stroke, is a leading cause of mortality, morbidity and  long-term disability. Moreover, the fact that one in four strokes occur in individuals who have previously had a stroke, highlights the need for urgent action to reduce the residual risk of recurrent events.

Guidelines recommend low-density lipoprotein cholesterol (LDL-C) as the primary lipid target for reducing the risk of recurrent stroke. However, mounting evidence suggests that other lipid parameters might be also predictive of cardiovascular risk and provide additional benefit. Little is so far known about the effects of non-traditional lipid factors or emerging biomarkers on recurrent stroke risk.

Previous studies have indicated that atherogenic dyslipidaemia, the combination of elevated triglycerides and low plasma concentration of high-density lipoprotein cholesterol (HDL-C) may be implicated in recurrent stroke risk. For example, in the Vitamin Intervention for Stroke Prevention study database including 3680 patients with a recent 120 days noncardioembolic stroke, the triglycerides/high-density lipoprotein cholesterol (HDL-C) ration, often termed as the atherogenic index, was consistently and independently associated with stroke risk, with the highest triglycerides/HDL-C ratio quintile associated with a 56% increase in recurrent stroke risk versus reference (low quintile). Consistent findings were also reported for the Women's Health Initiative Observational Study in Postmenopausal women. 

Recent analyses from the PERFORM (Prevention of Cerebrovascular and Cardiovascular Events of Ischemic Origin With Terutroban in Patients With a History of Ischemic Stroke or Transient Ischemic Attack) and SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trials, discussed in this month’s Landmark trial, add to this body of evidence. Atherogenic dyslipidaemia, defined as low HDL-C (?40 mg/dL or 1.01 mmol/L) and elevated triglycerides (?150 mg/dL or 1.7 mmol/L), was an important contributor to residual cardiovascular risk in patients with a prior stroke or transient ischaemic attack (TIA) who were receiving best medical therapy, including statin. In both trials, patients with this dyslipidaemic profile had a 36-40% increased risk of recurrent stroke, despite other cardiovascular risk factors including LDL-C being well controlled by best evidence-based medicine.

The question remains: how best to address this high residual risk for recurrent stroke. Clinical trials of current therapies, including fibrates and niacin, have been less than definitive. Whether novel therapies offer future potential has yet to be addressed by prospective trials specifically targeting atherogenic dyslipidaemia. Indeed, the Residual Risk Reduction Initiative echoes the call to action made by the authors of this analysis for trials in this patient population. 

Finally, while much of the focus has been on lipid-related residual cardiovascular risk, a recent analysis from the Treating to New Targets Study also makes the case for consideration of non-lipid biomarkers. In patients with established coronary heart disease (CHD) at LDL-C goal, plasma levels of lipoprotein(a), neopterin, NT-proBNP, and sRAGE were all shown to be associated with the risk of recurrent major cardiovascular events. Lipoprotein(a) has already been linked with risk for ischaemic stroke, however, with the exception of niacin, current therapies are ineffective in targeting this lipoprotein. Whether novel agents in development may provide benefit has been the subject of much interest, given that monoclonal antibody therapy targeting PCSK9 has been shown to be effective in lowering liporprotein(a) levels by 25-30%, on top of statin therapy. Clinical trials in patients with a previous stroke are clearly needed to address the paucity of evidence relating to emerging biomarkers that may contribute to residual risk for recurrent stroke in patients receiving best evidence-based medicine. 

by

Dr.Akshaya Srikanth, PharmD.

2 of 3 Smokers Will Die Early If They Don’t Quit

Two-thirds of smokers will die early from their habit if they don’t quit, a new study suggests.

The findings indicate that it’s never too late to quit smoking, one expert said.

Researchers analyzed data from more than 200,000 people taking part in a study conducted by the Sax Institute in Australia. The study is a long-term investigation of healthy aging.

“We knew smoking was bad, but we now have direct independent evidence that confirms the disturbing findings that have been emerging internationally,” Emily Banks, scientific director of the Sax study and a researcher at the Australian National University, said in an institute news release.

“Even with the very low rates of smoking that we have in Australia, we found that smokers have around threefold the risk of premature death of those who have never smoked. We also found smokers will die an estimated 10 years earlier than nonsmokers,” she added.

Compared with not smoking, having just 10 cigarettes a day doubles the risk of dying early. And smoking a pack a day increases the risk four- to fivefold, according to the study published Feb. 24 in the journal BMC Medicine.

It was long thought that smoking-related diseases would kill about half of smokers early, but newer research has put the figure as high as 67 percent. 

My Suggestion: “It’s never too late to quit, no matter what your age or how much you smoke,”

by Dr.Akshaya Srikanth B, Pharm.D, BCPS.

Cola Raises Cancer Risk Due to Its Caramel Coloring

Research has found that 4-methylimidazole (4-Mel), the chemical that gives cola its

appealing caramel color is a potential carcinogen.

There aren't any federal regulations that restrict use of 4-Mel, but according to the report, more than half of Americans between age 6 to 64 drink enough soda on a regular basis to elevate their cancer risk.

Researchers from the Consumer Reports and the Center for a Livable Future at Johns Hopkins Bloomberg School of Public Health, tested 110 samples of cola and other soft drink beverages.

All of the samples, except for the clear beverages, contained 3.4 to 352.5 micrograms of 4-Mel per 12-ounce bottle or can. While there aren't federal regulations on how much of the chemical manufacturers can put in beverages, California does require companies to include a cancer warning label if the drink contains more than 29 micrograms in a 12-ounce bottle or can. The average person age 6 to 64 drank as much as two and a half cans of cola per day. Approximately one-third of children between ages 3 and 5 drank two-thirds of a can each day. People between age 16 and 44 were the most frequent cola drinkers, consuming as many as three cans per day.

Through this analysis, the researchers concluded that within the next 70 years, there could be at as many as 5,000 incidences of cancer directly related to cola consumption. But cracking down on the soft drink industry won't completely eliminate the chemical from the American diet. Unfortunately, dark-colored carbonated beverages are not the only source of 4-Mel. 

The chemical is also used in soy and barbecue sauce, pancake syrup and some soups. The study is published in PLOS One.

Read more: Cola Raises Cancer Risk Due to Its Caramel Coloring
by 
Dr.Akshaya Srikanth Bhagavathula, PharmD. BCPS.

Pharmacy students and Publications

Dear Sir/Madam,

I am doing a survey on "Pharmacy students perception towards engaging in scholarly journal publications", I wish your contribution in this survey is highly important. Kindly go through the link provided and do provide your valuable opinion. Please forward to your Pharmacy students and encourage them to participate.



Pharmacy students and Publications: Pharmacy, academics, journals, science

A New One-Pill-a-Day Treatment for HIV has been approved

As expected, there’s a new single pill regimen for HIV, this one containing abacavir (ABC)/lamivudine (3TC)/dolutegravir (DTG), and it’s called Triumeq. 

The most important study for this combination was the SINGLE study, which showed that ABC/3TC + DTG (given as two pills) was superior to TDF/FTC/EFV (given as one), the difference based primarily on tolerability advantage of the former. It was a novel double-blind study, as all three drugs were different in each treatment arm.

Another benefit DTG-based regimens — whether given with ABC/3TC or TDF/FTC as separate pills — is that to date, no treatment-naive patient with virologic failure has developed resistance to DTG. I suspect it will happen one of these days, but the data thus far suggest at the very least DTG resistance will be a rare event.

Needless to say, but will say it anyway for emphasis, all patients starting this regimen will need to be tested for HLA-B*5701 and found to be negative. Wonder if pharmacies will enforce this, or whether it will be left up to the prescribers. Here’s the landmark study that proved this testing essentially excludes severe hypersensitivity to ABC, quite an amazing story in pharmacogenomics.

An unresolved question is whether ABC is associated with an increased risk of cardiovascular disease. This FDA meta analysis of randomized clinical trials didn’t think so, but around half of the observational studies did, including the updated DAD study. NA-ACCORD data will be of great interest, whenever they appear.

As of Sunday, August 24, the price of ABC/3TC/DTG is not known (at least to me) — and it could be a real game changer, since both ABC and 3TC are already generic. Says Ben Young over on TheBody: “If ViiV Healthcare manages to set the price of Triumeq in accordance with the generic status of abacavir and lamivudine, the cost should be substantially lower than the price of the other single-tablet regimens that contain all on-patent components.” Yep.

I suspect people will call it “Trii” (rhymes with “Cy”, as in “Cy Young”) for a while, just like they called TDF/FTC/EVG/COBI “Quad”.

So what are some upcoming single-tablet regimens? Tenofovir alafenamide (TAF) with FTC/EVG/COBI. TAF/FTC/DRV/COBI. DTG/rilpivirine. And inevitably, generic TDF/3TC/EFV, which is widely available globally.

Regardless, sure beats the old days.

Know more how to improve adherence to HIV patients: MEDICATION ADHERENCE COUNSELING FOR HIV PATIENTS BY PHARMACIST

by
Dr.Akshaya Srikanth, PharmD.

Act Now, or Face Aatastrophic Post-Antibiotic Era

The Antibiotic Resistance Coalition, comprising civil society organisations and stakeholders from multiple sectors on six continents, has called on World Health Organization (WHO) Member States to pass a critical resolution (Combating antimicrobial resistance, including antibiotic resistance) at the 67th World Health Assembly that would spark concerted global action to control the escalating antimicrobial resistance crisis.

“Antimicrobial resistance—and particularly antibiotic resistance—is the most pressing public health issue facing the global community,” said Otto Cars, founder of ReAct (Action on Antibiotic Resistance). “If the resolution is not passed, and the WHO and its Member States do not act quickly, there will be disastrous global health consequences.” Public health researchers estimate that, each year, millions of people around the world are infected with antibiotic-resistant bacteria, and hundreds of thousands of them die. Without immediate action, that toll is expected to worsen.

“We are on the precipice of a post-antibiotic era,” said Tim Reed, executive director of Health Action International. “Without a radical shift in the way antibiotics are marketed and used—and unless we overcome the gap in antibiotics discovery—antibiotic resistance will continue to become one of

the greatest threats to humankind.”

The Antibiotic Resistance Coalition, in its declaration released today, asserts that consumer protection and public health must trump the pursuit of profit, and that effective antibiotics are global public goods. The

Coalition also calls for international leadership and action to, in part:

• Prohibit the promotion and advertising of antibiotics;

• Promote new, needs-driven and open research and development models based on the principle of de-linkage (divorcing price from research and development costs and sales volumes);

• Phase out the use of antimicrobials for routine disease prevention in livestock, and end their use, altogether, for growth promotion;

• Build robust systems, in all countries, to monitor and report antibiotic use and resistance trends in humans and animals; and

• Improve public awareness to support an ecological understanding of human-bacteria interaction and behaviour change around antibiotic use.

“Member States must deliver a strong mandate to the WHO to not only develop a pressing action plan on antimicrobial resistance, but also to ensure that public health is prioritised over commercial interests,” said Yoke Ling-Chee, program director with Third World Network. “Access to affordable and effective antibiotics is of particular importance for developing countries.”

The Antibiotic Resistance Coalition will deliver an intervention to the World Health Assembly prior to the vote. The Antibiotic Resistance Coalition is also inviting other civil society organisations around the world to sign its declaration, which is available at www.reactgroup.org/arcdeclaration 

Antimicrobial resistance is a general term that refers to resistance to a compound that kills or stops the growth of microorganisms, including bacteria, fungus, parasites and viruses. Antibiotic resistance refers specifically to resistance to anti-bacterial agents.

The Antibiotic Resistance Coalition consists of numerous civil society organisations and stakeholders from six continents working in the health, agriculture, consumer and development sectors. It advocates for policy change and action to prevent the post-antibiotic era from becoming a bleak reality. 

by 

Dr.Akshaya Srikanth, PharmD.

HYDROGEL: A New way to heal Knees ?

Bad or painful knees are one of the most common causes of pain in the elderly, and can start at quite an early age due to extra stress on the cartilage or due to injury. This damage is rarely healed by the body. 

Part of the reason this damage doesn't heal well is because the cartilage in the knee gets very little blood flow, which body parts need to fix problems on a cellular level. Part of the standard treatment for knee cartilage healing is to make tiny holes in the area and let the blood pour in to encourage a healing process.

There are two problems with this method. The first is that the new tissue rarely replaces all of the damaged tissue, meaning it is never a complete replacement. The second is that the space may fill with scar tissue instead of new cartilage, which isn't really a solution.

But a new method is seeing light recently, as published in the journal of Translational Medicine, scientists, including biomedical engineer Jennifer Elisseeff from Johns Hopkins University. This method proposes the use of a replacement material, a hydrogel with some special properties.

The gel, which looks a lot like jell-o and behaves a lot like it too, is injected into the knee as liquid. However, once it is exposed to UV light, it hardens, providing a sort of scaffold for stem cells to attach to and grow on. The way it is built involves many bindings and criss-crossing fibers, to provide a very strong and stable structure. 

To test this, Elisseeff and team tried the method on 15 patients. They poured the liquid hydrogel into the patients' torn cartilage. After that, the surgeons shined the UV light and hardened the polymers in the gel.

The results were very promising, the new cartilage filled 86% of the torn area. This was compared to 3 subjects who were treated in the standard way - for them, only 64% of the torn area was filled. 

In addition, the patients who got the hydrogel treatment reported considerably less pain than the control group patients. 

At the moment, larger studies are being held testing this method, but results seem promising, says Farshid Guilak, an orthopedic surgeon at Duke University, and adds that with the advance of stem cell treatments, the efficiency of this system will only grow, as we will be able to use the body's own cells to facilitate faster growing of cartilage, and get more people out of pain and on their feet.

by

Dr.Akshaya Srikanth, Pharm.D

Pharm.D India

Protect your BONES

Osteoporosis is a disease that damages the bones, weakens them and makes them brittle and breakable. There is a significant decrease in bone density, and this causes the bone to weaken and increases the risk of fractures.

Our bones are always building and breaking down bone tissue, when the balance between building and breaking is changed, then the bone density goes down. With age, this problem has a horrible way of increasing in occurrence.

Before you are 10 Golden Rules for the treatment and prevention of decreasing bone density:

1. Yes, you guessed it - Physical activity.
Physical activity, besides being the best thing you can do for yourselves, helps the bones become denser by putting pressure on them, which may prevent the disease to begin with. We recommend using weights.

2. Increase your calcium intake - Good sources: Green leaves, soy, sardines, broccoli and nuts. Regular bovine milk isn't that good a source of calcium because of its low absorption rate.

3. Increase your omega 3 intake - These fatty acids can be found in flax seeds of fish: Salmon, cod, and halibut - and are essential to keeping your bones strong.

4. Reduce caffeine and alcohol intake - Sorry, but coffee and alcohol 'release' calcium from the bones and damage the hormonal balance in the body important to keep them strong.

5. Reduce red meat - Seems like we're taking all the fun out of lunch, but eating red meat actually reduces the absorption of calcium in the body.

6. No smoking - Cigarette smoke damages bone density.

7. Eat nuts and almonds - These contain magnesium which is essential to the process of absorbing calcium.

8. Get at least 15 minutes of sun exposure a day - Exposing your skin to the sun a few minutes a day is the best way of getting your vitamin D, which function as a sort of glue and helps keep the bone density up.

9. Eat sunflower seeds - Contain zinc, a key mineral for maintaining strong bones.

10. Make sure you're not lacking in these elements, and take according to professional opinion: Boron, Silicone, vitamin C, vitamin D, calcium, magnesium, vitamin B12, vitamin B6 and folic acid.
by
Dr.Akshaya Srikanth, PharmD.