Four trials published in 2018 that may shape neurology practice

• A new treatment option for brain metastases: The usual survival period after brain metastases is 2-4 months. Brain metastasis generally means palliative care. In a study published online August 2018 in the New England Journal of Medicine (N Engl J Med. 2018;379:722-730), nivolumab combined with ipilimumab had clinically meaningful intracranial efficacy, concordant with extracranial activity, in patients with melanoma who had asymptomatic untreated brain metastases. Benefit in intracranial growth of metastases was seen in 57% of patients, 64% of patients did not show any progression of the disease, and the 6-month survival was 80%.

• Gut linked to pathophysiology of Parkinson’s disease: JAMA Neurology provided indirect evidence for role of systemic inflammation in the pathogenesis of Parkinson disease and inflammatory bowel disease in a retrospective cohort study of 144,018 patients with IBD (JAMA Neurol. 2018;75:939-46). Patients with IBD had a 28% higher incidence of Parkinson’s disease. A marked reduction in the incidence of Parkinson’s disease was observed when IBD patients were treated with anti–tumor necrosis factor therapy.

• No beneficial effect of aspirin for prevention of adverse CV events in moderate risk patients: The multicenter ARRIVE study compared the use of aspirin with placebo in more than 12,000 patients with moderate risk of heart disease (10-year risk of coronary heart disease 10-20%) (Lancet. 2018;392:1036-46). No beneficial effects with regard to the primary efficacy endpoint (composite outcome of time to first occurrence of cardiovascular death, myocardial infarction, unstable angina, stroke, or transient ischemic attack) were seen with aspirin after a follow-up period of 60 months.  Gastrointestinal bleeding events (mild) occurred more often with aspirin. Use of aspirin in moderate-risk patients needs to be individualized.

• Major bleeding risks offset primary prevention benefits of aspirin use in patients with diabetes: Aspirin use prevented serious vascular events in persons who had diabetes and no evident cardiovascular disease (19% risk reduction) in the ASCENT trial (N Engl J Med. 2018;379:1529-39). Major bleeding events occurred in 314 participants in the aspirin group vs 245 in the placebo group indicating a 30% increase in the risk of major bleeding. So, the absolute benefits were largely counterbalanced by the bleeding hazard. 

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA

Anger management: An anger episode may trigger an acute heart attack within 2 hours

Emotionally stressful events, and more specifically, anger, immediately precede and appear to trigger the onset of acute myocardial infarction (MI) and other cardiovascular events.

Outbursts of anger increase the risk of acute myocardial infarction, acute coronary syndrome, ischemic stroke, ruptured intracranial aneurysm and ventricular arrhythmia. This was corroborated by a systematic review and meta-analysis published in the European Heart Journal, which found a higher risk of cardiovascular events in the 2h after outbursts of anger (Eur Heart J. 2014 Jun 1;35(21):1404-10).

An earlier study from Deaconess Hospital, Harvard Medical School published in the journal Circulation in 1995 had shown that episodes of anger are capable of triggering the onset of acute myocardial infarction and that that this risk may be reduced by the use of aspirin (Circulation. 1995 Oct 1;92(7):1720-5). More than 1600 patients were studied, of which 39 were found to have episodes of anger in the 2 hours before the onset of MI. The relative risk of MI in the 2 hours after an episode of anger was 2.3. This risk was mitigated by aspirin. Compared to nonusers, patients who were taking aspirin regularly had a significantly lower relative risk; 1.4 vs 2.9, respectively.

These studies caution that heart patients on aspirin should continue to take aspirin to prevent anger-induced heart attack or stroke.

The description of anger comes in mythology as one of the five vices which need to be controlled to acquire spirituality. The description of anger in mythology is as under:

• Lord Shiva is also shown wearing a snake in his neck with hood directed inwards. Shiva is also said to have a blue neck or Neelkanth indicating that to control anger one should neutrilise then anger continuously (matted hairs) with cool mind (Moon) using positive flow of thoughts (ganga) with ego controlled (naag)
• Bhagavad Gita talks about anger in great details and tells that anger is as a result of unfulfilled of desires. As per Bhagavad Gita lust leads to anger and anger leads to ego.
• As per Lord Shiva, anger can be expressive and or suppressive. Expressive anger can lead to rupture of arterial blockage and suppressive anger can lead to arterial blockage. The best answer described by Lord Shiva is to manage and control the anger.
• Two forms of Goddess Durga and Kali also indicate when to get angry.
• As per mythology, one should learn to control anger but it also talks about allowable spiritual anger when it is done for the benefit of the mankind.

The period of Uttarayana has started, which is the phase of a positive state of mind. But even then people with angry temperament, especially heart patients on aspirin should not miss their daily aspirin dose.

It is equally important to learn to manage one’s anger.

• As per Shiva Puran, anger management is described under Neelkanth role of Lord Shiva. The blue color means slow poison (one of them being anger) which is kept in the neck. It indicates that anger should not be expressed or suppressed but should be managed. Management involves continuously (Jatadhari) with cool mind (Moon), one should direct positive thoughts (Ganga) towards the reason for anger keeping the ego under control (Naag) with head directed in.
• As per Bhagwad Gita, anger is always resulting of non-fulfillment of desires. Therefore, one must act at the levels of desires.
• As per Marshal Rosenberg, indulging in non-violent communication helps in managing anger.

• Drugs like SSRI used in modern medicine, primarily focus on reducing irritability and chronic anger. They may take as long as 10 weeks to act. Aspirin is also recommended in people with un-managed anger to prevent occurrence of heart attack.

Anger recall is as bad as anger itself, which can be expressive or suppressive. Both are dangerous. Expressive anger causes plaque to rupture leading to heart attack or MI, while suppressive anger causes chronic sympathetic overactivity that helps plaque formation.  

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA

Feasibility of oral insulin shown in insulin-naive patients with type 2 diabetes

·         Oral insulin 338 (I338) can safely improve glycaemic control in insulin-naive patients with type 2 diabetes with no evidence of a difference compared with insulin glargine. The evidence for its feasibility has been published for the first time in The Lancet Diabetes & Endocrinology online Jan. 21, 2019. I338 is a long-acting, basal insulin analog formulated in a tablet with the absorption-enhancer sodium caprate. 

·         Updated AHA/ACC/HRS treatment guidelines for atrial fibrillation (AF) recommend a newer type of blood-thinning medications, non-vitamin K oral anticoagulants (NOACs) as the preferred alternative to warfarin for reducing the risk of stroke associated with AF.

·         Sudden cardiac death remains a daunting problem for at least three major reasons: (i) with a prevalence of 20% of total mortality in the industrial world it has a major impact on society; (ii) it has devastating psycho-social effects on the families of the victims who often are still in their prime; and (iii) it represents an unconquered scientific challenge for medicine and cardiology.

·         Smoking, diabetes, high cholesterol and high BP: one of the four risk factors is present in 80-90 % in cases of significant CHD and 95% cases of fatal accidents of CHD.

·         Children who spend more time on digital media and screens at ages 24 and 36 months are more likely to have worse scores on developmental screening tests at ages 36 and 60 months, as per a study published online Jan. 28, 2019 in JAMA Pediatrics.

·         New research suggests that positive personality traits may help to reduce the risk of developing type 2 diabetes among women. Emerging evidence shows that depression and cynicism also are associated with an increased risk of diabetes in addition to the traditional risk factors. In addition, high levels of hostility have been associated with high fasting glucose levels, insulin resistance, and prevalent diabetes.

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA

Government should introduce limit of 8 lakh for EWS for insurance cover

Not just medical care, social factors too play an important role in determining one’s health status. These factors are also responsible for the gaps in health among the various strata. Lack of availability and accessibility to resources that improve health among the socially disadvantaged groups are major factors contributing to this health inequity.

These social factors have been termed as social determinants of health and have been defined by the WHO’s Commission on SDH (CSDH) as “the conditions in which people are born, grow, live, work, and age including the health system.” According to the Commission, this means that health cannot be achieved by medical care alone; it is also a social phenomenon.

Among the 10 social determinants of health, social gradient has been deemed to be the strongest predictor of health and wellbeing. It is measured by variables such as income, education, occupation or housing. The lower the socioeconomic position, the higher the risk of poor health.

The extreme poor or the poorest of the poor are the worst off. The World Bank has defined “extreme poverty” as living on less than $1.90 per person per day. This amounts to Rs. 135 per person per day and around Rs 4000 per person per month. 

Much progress has been made to make health care accessible to the poor; but, inequities still persist.

The high out of pocket expenditure further add to the financial burden. Many people are pushed below poverty line on account of the high medical expenses in what has been termed as “the medical poverty trap”.

About 55 million Indians were pushed into poverty in a single year because of having to fund their own healthcare and 38 million of them fell below the poverty line due to spending on medicines alone, as per a study published in the British Medical Journal. Health expenditure is considered to be catastrophic if it constitutes more than 10% of overall household consumption or income (TOI, Jun 13, 2018).

Evidently, there is a need to reduce the health inequity.

This has been addressed in the National Health Policy 2017 as a key policy principle, which states “Reducing inequity would mean affirmative action to reach the poorest. It would mean minimizing disparity on account of gender, poverty, caste, disability, other forms of social exclusion and geographical barriers. It would imply greater investments and financial protection for the poor who suffer the largest burden of disease”.

Right to health and access to healthcare is a fundamental right under Article 21 of the Constitution. Article 41 also provides for ensuring assistance during old age, sickness, and disablement.

The Ayushman Bharat scheme, which provides up to Rs 5 lakh cover, is one step towards this end. This year, constitutional amendment bill providing for 10% reservation to the economically weaker sections of the General Category was notified. These are in a bracket of less than 8 lakh annual income.

Only by reducing the health inequity, can the goal of universal health coverage be realized.

In the coming budget, the government needs to bring this 8 lakh limit to the definition of EWS for the purpose of ESI, health subsidy and Ayushman Bharat subsidy. Those above this bracket should be able to buy their insurance on their own. 

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA

Ongoing saga of contaminated sartans

·         In the ongoing saga of contaminated sartans, Torrent Pharmaceuticals Limited has expanded its voluntary recall of losartan potassium and hydrochlorothiazide combination tablets to include six more lots, for a total of 16 lots of losartan-containing medicines recalled since December. The recall, to the consumer level, stems from the detection of the probable carcinogen N-nitrosodiethylamine (NDEA) in the active pharmaceutical ingredient (losartan) manufactured by Hetero Labs Limited. The recalled lots have NDEA levels above acceptable daily intake levels released by the US Food and Drug Administration (FDA).

·         Card diversions have beneficial effects on emotional wellness. In 2014, the University of Wisconsin-Madison completed an examination that discovered playing card diversions can enable individuals to remain rationally sharp in maturity, as detailed here and by Alzheimer’s Research UK. 90+ recommends that individuals who invest more energy taking part in mental exercises like card amusements might be at less danger of experiencing dementia. Other research like this New England Journal of Medicine ponder likewise proposes that relaxation exercises are related with a diminished danger of dementia. These reports unmistakably demonstrate that playing cards gives certifiable emotional wellness benefits, and particularly among the old.

·         Association between cholesterol levels and sepsis: Although low levels of low-density-lipoprotein cholesterol (LDL-C) seem to be associated with an increased risk for sepsis and admission to the intensive care unit (ICU) in patients hospitalized for infection, the relation appears to be connected to comorbidities rather than LDL-C levels per se, suggests a new study published online Jan. 18, 2019 in JAMA Network Open.

·         Patients with NAFLD are at an increased risk for CVD compared to matched controls, but histological parameters do not seem to independently predict this risk (Liver International. 2018;39(1):197-204).

·         Need for vitamin and nutritional supplements: Most people do not need to take vitamins or nutritional supplements because they can get all the nutrients they need by eating a healthy diet, as per a new patient resource published Jan. 7, 2019 in JAMA Internal Medicine. But there are more than 90,000 supplements on the US market that include a wide range of vitamins, minerals and chemicals.

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA

Will leprosy be eliminated from the country this year?

Leprosy was eliminated from India in 2005, yet leprosy continues to be prevalent in the country as is evident from the NLEP Annual data for the year 2017-18 on the status of leprosy in India. Elimination means a prevalence rate of less than 1 case per 10,000 population at national level.

As on March 2018, at least seven states had more than 5000 cases. With 14,338 cases, Bihar had the highest no. of cases followed by UP with 12, 583 cases; Maharashtra (9836 cases), West Bengal (9175 cases), Chattisgarh (6499 cases), Odisha (6325 cases) came next (Source: National Leprosy Eradication Programme website).

Three states still have a prevalence rate exceeding the required less than 1 case per 10,000 population: Chattisgarh (2.25), Bihar (1.18) and Odisha (1.38).

Leprosy is now being detected from parts of the country not known to be prevalent for leprosy. Also, cases of multibacillary leprosy(>5 lesions with involvement of≥2 nerves) as well as cases with deformities are being detected indicating advanced stage of the disease. This means late diagnosis or failure of early leprosy detection. Early detection is crucial to its elimination.

The special Leprosy Case Detection 15-day Campaign for early detection of leprosy cases in high endemic districts conducted in 2016 had identified more than 32,000 confirmed cases.

Leprosy: At a glance ·         Leprosy, also known Hansen's disease is an infectious disease caused by mycobacteria of the Mycobacterium leprae complex that involve the skin and peripheral nerves.  ·         Early diagnosis and a full course of treatment are critical for preventing lifelong neuropathy and disability.  ·         Leprosy is probably spread by the respiratory route. In the US, it is also a zoonosis; contact with armadillos has been documented in some cases.  ·         Leprosy is classified using the following categories: tuberculoid (TT), borderline tuberculoid (BT), mid-borderline (BB), borderline lepromatous (BL), lepromatous (LL), and indeterminate (I).  ·         Early physical exam findings include hypopigmented/reddish skin patches, diminished/loss of sensation in involved areas, paresthesias, painless wounds or burns and tender, enlarged peripheral nerves.  ·         The diagnosis is established when at least one of these physical findings is present and a skin biopsy obtained from the leading edge of the skin lesion confirms the presence of acid-fast bacilli in a cutaneous nerve.

Achieving and maintaining elimination status of Leprosy by 2018 was one of the targets under the National Health Policy 2017 (Source: Press Information Bureau, March 23, 2018).

A nationwide post-exposure prophylaxis was also launched last year with single-dose rifampicin for all contacts of leprosy cases detected as per the 2018 WHO guidelines on the diagnosis, treatment & prevention of leprosy.

The WHO guidelines recommend the “use of single-dose rifampicin (SDR) as preventive treatment for adult and child (2 years of age and above) contacts of leprosy patients, after excluding leprosy and tuberculosis (TB) disease and in the absence of other contraindications”.

Now the Govt. has planned elimination of leprosy under Sparsh leprosy Awareness Campaign (SLEC) by 2nd Oct, 2019 to commemorate the 150th Birth Anniversary of Mahatma Gandhi vide a letter from Dr Anil Kumar, Deputy Director General (Leprosy) DO No. X-11016/07/2015-Lep, dated 14th Sept. 2018 (Source: National Leprosy Eradication Programme website).

Will leprosy be eliminated from the country this year?

We hope for the best, but this target appears elusive for now.

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA

Non-traumatic hemorrhage, a cause of mortality in pancreatitis

·         A Salmonella outbreak impacting eight states in US has been linked to contact with pet hedgehogs. The outbreak has affected 11 people. Three cases have been reported in Missouri and two cases have been reported in Minnesota. Colorado, Maine, Mississippi, Nebraska, Texas and Wyoming each have one case as of Jan. 23. The CDC has previously warned that hedgehogs can carry Salmonella.

·         Fans of comedian Kevin Barnett were shocked earlier this week when news broke that the 32-year-old died suddenly while on vacation in Mexico. Now, the results of his autopsy are in, and it appears he died of “non-traumatic hemorrhage, caused by pancreatitis. Mortality in patients with acute pancreatitis is associated with the number of failing organs and the severity and reversibility of organ dysfunction. Persistent early systemic inflammatory response syndrome is associated with multiorgan dysfunction syndrome and death in patients with acute pancreatitis and is an early indicator of severity of acute pancreatitis. Alcohol as a cause of pancreatitis has been associated with an increased risk of pancreatic necrosis and need for intubation. A time interval between the onset of symptoms and hospital admission of less than 24 hours, as well as rebound tenderness and/or guarding were associated with increasing severity of pancreatitis.

·         President Trump’s health: His CT coronary calcium level is 133, and anything over 100 indicates heart disease, his LDL cholesterol level is 143, which is far above the ideal level (80) and his BMI is 29.9. That’s considered overweight and verging on obese. What does this mean?

Coronary artery calcium (CAC) scoring — In both men and women, CAC detected by CT is highly sensitive for the presence of ≥50 percent angiographic stenosis but only moderately specific, especially in individuals over 60 years of age. However, the absence of CAC is highly predictive of the absence of significant (greater than 50 percent) coronary artery stenosis. In three series, patients with no CAC had a probability of significant coronary stenosis of less than 1% (0 – No identifiable disease; 1 to 99 – Mild disease; 100 to 399 – Moderate disease;  ≥400 – Severe disease). For his coronary calcium score, he should have been losing weight and kept his LDL < 80. Celebrities should be role models for the society.

·         Feb. 1 is National Wear Red Day, when people are encouraged to wear red to raise awareness that heart disease is the number one killer of women.

·         Dengue patients should defer blood donation for up to 6-12 months post-infection: (Correction) Dr NK Bhatia, Medical Director, Mission Jan Jagriti Blood Bank is a renowned name in blood banking with more than three decades of experience the field. According to Dr NK Bhatia, “Dengue patients are not allowed to donate blood for one year after treatment. If there is a history of blood/blood products transfusion, the same deferral period applies. This is also true for Chikungunya patients. Any person who has a ‘normal’ viral fever is not allowed to donate blood for 7 days after the active phase is over. Some extend this duration to one month.”     

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA

Prior dengue infection protects children against Zika

Children who have previously been exposed to dengue virus appear to be protected from getting sick when infected with Zika virus, according to a study published Jan. 22, 2019 in PLoS Medicine by Aubree Gordon of the University of Michigan and Eva Harris of the University of California, Berkeley.

Prior and recent dengue virus infection was found to be associated with protection from symptomatic Zika virus infection. Children with prior dengue infection had 38% less risk of showing symptoms when infected with Zika than those who were dengue-free. Zika symptoms include fever, rash, conjunctivitis, muscle, joint pain and headache.

These findings support the hypothesis that prior dengue virus immunity might cross-protect against symptomatic Zika. The two already share many similarities: They belong to the same Flavivirusgenus. Both viruses are transmitted by the Aedes aegypti mosquito, which preys on the same populations.

In a patient with previous dengue infection, the second dengue infection may be more severe via antibody-dependent enhancement. But if the second attack occurs within six months of each other it may get nullified. 

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA

A round-up of happenings in medicine this week

Alcohol and the AF link: India is going through a new epidemic of atrial fibrillation (AF), which is linked to acute attacks of paralysis. Now a study published in the journal Heart Rhythm has shown that regular alcohol intake at moderate levels (8-21 drinks per week) is associated with electrical and structural changes in atrial myocardium.

Moderate alcohol consumption is an independent predictor of the atrial remodeling, characterized by significantly reduced atrial voltage and conduction velocities and increased atrial dimensions. The same was not found for mild alcohol intake levels, defined as two to seven drinks per week.

Screen all new cancer patients for hepatitis: A new study published online on January 17 in JAMA Oncology has found a large reservoir of patients with cancer and undiagnosed hepatitis virus infections and has suggested that all newly diagnosed cancer patients should be screened for hepatitis. They found that 6.5% had previously been infected with hepatitis B virus (HBV), 0.6% had chronic HBV infection, 2.4% had hepatitis C (HCV) infection, and 1.1% were infected with HIV.

Universal screening for HBV, HCV, and HIV infection is not routinely performed in patients diagnosed with cancer. Universal screening could prevent complications from hepatitis, such as liver failure and kidney disease. Immunosuppressive cancer drugs such as rituximab can cause some viruses to reactivate and multiply.

Valsartan and cancer: The US FDA said that some versions of the blood pressure-lowering drug valsartan contained trace amounts of a carcinogen for four years before regulators detected the impurity last summer, triggering a widespread recall of the tainted drugs.

FDA officials said the cancer risk for any person who took valsartan that had the carcinogen nitrosodimethylamine, or NDMA, is small. FDA scientists concluded there would be one more cancer case above average rates for every 8,000 people on the highest dose of valsartan for four years.

And now irbesartan has been recalled: In US, Prinston Pharmaceutical Inc has recalled one consumer-level lot of irbesartan and seven lots of irbesartan hydrochlorothiazide (HCTZ) tablets because of the presence of the probable carcinogen N-nitrosodiethylamine (NDEA), marking the latest recall of tainted sartan products produced in the United States.

This announcement on January 18, stems from the finding of NDEA in the active pharmaceutical ingredient (API) manufactured by China's Zhejiang Huahai Pharmaceuticals (ZHP), the company at the center of the tainted sartan crisis.

The recalled product was distributed nationwide to wholesale, distributor, repackager, and retail customers. It comes in 30- and 90-count bottles, with an expiration date of February 2021 for the one irbesartan lot and March 2021 for the seven irbesartan HCTZ lots.

A new sarcoma drug: Eli Lilly and Co.’s cancer drug Lartruvo should not be started in new patients, and those patients already taking it should ask their doctors if they should continue as a key study that failed to show the medicine prolonged lives. The drug was given accelerated approval by the US FDA in 2016 based on promising data from an early-stage study.

Dr KK Aggarwal

Padma Shri Awardee

President Elect Confederation of Medical Associations in Asia and Oceania   (CMAAO)

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Past National President IMA