Hope on horizon for patients with Hepatitis C: Sofosbuvir for 99% less comes to india

Wonder Hepatitis C drug almost here.....at 99% reduced price

Hepatitis C is a viral disease that mainly affects the liver and is transmitted parenterally ( through contaminated blood products, syringes etc), vertically (from mother to child in womb) and sexually.

More than 40% of patients infected with the virus develop chronic infection because the body is unable to eliminate the virus from the system.

Progression of chronic hepatitis is usually slow and culminates within 10-20 years of acquiring infection into cirrhosis and chronic liver failure that may be fatal without transplantation. About 4 out of every 100 patients with cirrhosis due to hepatitis C develop cancerous growths (hepatocellular carcinoma) in the liver that significantly reduces their survival. Alcoholism, obesity, diabetes mellitus, immunosuppressive medication and HIV infection are risk factors for early progression of chronic hepatitis to cirrhosis and liver failure.

In the absence of a reliable vaccine, treatment of chronic hepatitis C has so far yielded less than optimal results (40-55% sustained viral response). Silent undetected progression of disease, multiple genotypes of virus and  poor tolerance of patients to medications ( particularly those with cirrhosis) contribute to the poor response.

Inability of cirrhotic patients to tolerate medications and reduced effectiveness results in most patients having detectable virus in blood at time of transplantation. Reinfection of new liver occurs within hours of transplantation and inflammation of graft starts weeks to months after transplantation depending on various factors like viral load, type of liver graft, immunosuppression, age and other factors. Post transplant recurrence of hepatitis C is more difficult to treat due to the presence of immunosuppression and sustained virological response is between 15-50% in various studies. A significant number of patients may need a second graft between 5-25 years after transplantation for recurrence of hepatitis C and cirrhosis.

Treatment of chronic hepatitis C has hinged on mainly two drugs: the antiviral drug Ribavarin (RBV) and the immunobodulator drug Interferon (IFN). Most regimens for treatment of hepatitis B include RBV and IFN (usually in pegylated form). Genotype 1 infection in particular has significantly poor response to PEG-IFN and RBV. Recently it has been identified that those patients that have infection with CC subtype of IL28 gene has double the response when compared to CT or TT genotypes.

Further research into HCV treatment resulted in a new class of molecules called Protease inhibitors that inhibit viral enzymes 
 Bocepravir and Telaprevir were the first generation of protease inhibitors introduced for management of chronic hepatitis in untreated as well as previously treated patients with chronic HCV and compensated cirrhosis. Addition of a protease inhibitor to combination of IFN & RBV significantly increased the sustained viral response rate ( by 15-30%) for difficult to treat genotype 1 patients over IFN&RBV alone except in treatment experienced patients who were null responders. Monotherapy is not recommended because rapid resistance results.

Simepravir (SPV) is a second generation protease inhibitor effective against HCV introduced about a year ago. It is never used a monotherapy. For genotype 1 a patients , SPV in combination with IFN & RBV for both treatment naive and experienced patients with genotype 1 infection. It can also be effective in combination with RBV and Sofosbuvir for patients who cannot tolerate toxic IFN therapy. SPV based triple therapy is a superior alternative to first generation protease inhibitors and is better tolerated. It can also be used as an alternative to Sofosbuvir in combination with a longer course of IFN & RBV. One of the main disadvantages in the high cost .....about 70000 USD ( approximately Rs 43 lakh) for a 12 week course.

Sofosbuvir (SBV) is also a polymerase inhibitor effective against HCV introduced about a year ago. It is effective for all genotypes of HCV but FDA approved only for 1,2,3 &4. It can be used with RBV with or without PEG-IFN and has shown promise in treatment naive, experienced as well as HIV coinfected patients of chronic hepatitis C and compensated cirrhosis. It has high acceptability due to fewer side-effects and interactions, once daily dosing and pan-genotypic activity. For genotypes 2 & 3 an all oral regimen of SBV and RBV is effective. For 1,3,4 & 5 genotypes addition of PEG-IFN is recommended but for those who cannot tolerate IFN, combination of SBV,SMV with or without RBV is showing promise.

Therefore Sofosbuvir is considered a breakthrough wonder drug for HCV currently and is expected to figure in more and more regimens for HCV. The prohibitive cost of 84000 USD ( 55 lakh INR) has been the main deterrent in greater availability and application of the drug even among insured patients in the western world. The greatest benefit of SBV seems to be in genotype 1 patients which accounts for more than 60% patients in the USA. SBV monotherapy was effective in more than 70% patients in achieving SVR while in combination with IFN & RBV the SVAR rate was more than 90% even among null-responders.

In India the prevalence of HCV is between 3-5 % of the population with 20-25% of patients with chronic liver disease being due to HCV infection. Genotype 3 is the commonest in India (66%) while Genotype 1 is less common (13%). 

Reduction of SBV costs by nearly 99% to USD 900 ( 55000 Rs)  for 12 weeks by the company, is therefore a hugely welcome step to liver physicians caring for patients with HCV infection, particularly null-responders, relapsers or patients with genotype 1 and those who cannot tolerate IFN therapy. Though still out of reach of many patients in India, it will be an option for insured or reimbursed patients who could have more effective treatment to prevent the development of cirrhosis or liver cancer or requirement of liver transplantation in the future.

World Organ Donation Day....Be an organ donor, wipe tears from many a eye

We make a living by what we get, but we make a life by what we GIVE

One donor can save as many as 9 lives

If you had the ability to save 9 lives...wouldn't you?

 After brain-death, organs like heart, lungs, intestines, pancreas, liver and kidneys as well as tissues like cornea of the eye, blood vessels, bones, tendons can be donated to save or improve the lives of many others. Immediately after the heart has stopped beating in certain situations the kidneys and liver can be rapidly harvested and used for transplantation. However beyond a few minutes after the heart stops beating,only  tissues can  be used for donation.

In India, donation after heart stops beating (donation after cardiac death ) has not yet been introduced for multiple reasons. The law allows organ retrieval from brain dead (but heart beating) donors and living related donors.

There is a massive shortage of donor organs in India
Organ donation rate in India is among the lowest in the world standing at 0.08 donations per million deaths as compared to 10-30 per million deaths seen in most parts of the western world. A single organ donor can provide a liver, two kidneys, intestine, pancreas, heart, two lungs that can potentially save the lives of nine others who are suffering from failure of their own organs. In addition sight of two blind persons can be restored. Tissues such as bone, tendons and skin from a single donor can be used to restore function and improve life of several people. As a result of this, the nearly 70 lakh Indian patients with corneal blindness, 3 lakh with dialysis dependent renal failure and 1 lakh with advanced liver disease need nothing short of a miracle to happen in order to get a cornea, kidney or liver from a brain dead (deceased donor). 

Major hurdles in organ donation
Legal
Social
Procedural

Legal hurdles
The Human Organ Transplant Act passed by parliament in 1995 has been passed by most state assemblies. The law has performed commendably in streamlining the process of organ donation, brain death declaration and significantly reducing if not eliminating the ghastly organ trade. However certain well-meaning but probably ill conceived rules have inadvertently prevented organ donation from really taking off. The recently introduced amendments would probably help increase the facilitation when they are in effect.
Prominent among the hurdles are:
For organ harvesting to be performed the hospital where the donor is must only be a transplant center or a registered non-transplant retrieval centre

Brain death declaration required certification by four doctors one of whom must be a neurologist or neurosurgeon

The person in charge of the body (next of kin) has to consent for donation to proceed even if it overrules the brain-dead persons expressed living intention in the form or donor card or living will.

This excludes a large number of hospitals with ICUs and potentially brain dead donors from offering organs for donation. As a result less than 10% potential organ donors in India end up donating organs as opposed to more than 25% in the rest of the world.

Social
The social, cultural and religious issues are myriad. 

Despite most religions teachings
 having no major objections to organ donation, most families decline donation on religious grounds based on misconceptions that a person without organs will not be allowed in heaven or a person who is not buried or cremated with all organs will be reborn without those organs.

Religious teachings & organ donation

Steeped in  traditions and illiteracy, many sections of society find it difficult to accept that their loved one whose heart is still beating is actually not with them anymore. Added to this dangerous mix is a motley crew of community elders, village panchayats and ill informed practitioners of traditional medicine who parochially impose their views on the family of the brain-dead patient offering unrealistic hopes that their patient will miraculously recover from his irreversible coma. This often creates anger and a trust deficit between the brain-dead persons family and counselors who are perceived to be in pursuit of profit at the expense of the life of their loved one.

All the above however pales in front of the rank indifference and apathy shown by medical professionals towards the entire process of organ donation. In the absence of motivation from being a part of a transplant center, a majority of medical professions continue to manage patients with irreversible coma without broaching the subject of organ donation or a reluctant to discuss the issue with patient family citing fears of angry backlash from family members.An equal number of medical professionals themselves harbor numerous misconceptions and misgivings regarding organ donation. The medical education in India until recently had no inclusion of organ donation and brain death in its curriculum. 

Procedural 
 In a survey it was estimated that there has been a 51% increase in unnatural deaths in the decade 2002-2012. Nearly 32.6 accidental occur in India per 100,000 population. In 2012-2013 there were nearly 4,00,000 accidental deaths of which more than 94% were unnatural. nearly 42% of these occur following rail or road traffic accidents. Out of all accidental deaths, approximately 10-15% are due to irreversible injury to brain. Therefor at current estimates, there are between 30000-40000 potential candidates for donation after brain death amongst accidental deaths annually. However less than 500 donations happen across the country in any given year.

Ignoring the legal and social hurdles for a moment, this has not only a lot to do with poor trauma and transport services for maintaining these victims till they reach hospital but also to red-tapism, tedious and laborious paperwork and alarming apathy on part of investigating officers, forensic experts and other agencies in allowing organ donation to proceed in the brain dead individual is a victim in a crime or accident scene.

All is not lost...through tireless campaigning by several individuals, organisations and agencies of governments who have awakened albeit belatedly to the issue, the organ donation rate has nearly quadrupled over the last 10 years. There is a lot of distance to be covered. At a mere 1-2 donations per million deaths, this country can meet its transplant needs so that nobody with organ failure has to die waiting for an organ.

The medical fraternity should lead by example by pledging their organs and encouraging their friends and family to register to be donors. 

At my center, to commemorate World Organ Donation Day, we took a pledge to donate all our usable organs after our death and to work to encourage our friends and family towards registering themselves as organ donors.

"We, the doctors and staff of Continental Hospital, on the occasion of World Organ Donation Day, hereby unconditionally pledge to donate all our usable organs and tissues following our death to save the lives of others. We take this pledge in the presence of the almighty and our soul as our witnesses.

We also swear to work towards educating our families and friends about organ donation and also to encourage them to be organ donors and give the gift of life to others after they are gone"

Organ donation logo

Pledge board signing

 
I invite and urge all readers to join this movement with a poem I penned sometime ago

Your body is but a shrine
That envelops your soul
A gift from your maker
To help discharge your earthly role

When it's time and end is nigh
Your soul readies to depart
The body, it's shell
Free from your essence
Is but a wilted flower
Devoid of fragrance

Consigned to flames or ceremonially buried
To tune of hymns, chants and litanies varied
Into wasteful ashes or earth shall return
All precious body parts turn by turn
Many a heart, kidneys and liver
In needy others which could still deliver



Arise, its never too early to make the choice
Gift your organs after you've left
Save many lives that remain bereft
Wipe tears from many a eye
That's the only way to leave this world on a high!

 
 
 
  

Liver Metastasis (Secondary liver cancer): is it the end of the road?

Liver metastasis (Secondary liver cancer) is not the end of the road in the era of modern liver surgery & transplantation

Cancer deposits within the liver from a site outside the liver are called liver metastases or secondary liver cancers. In fact more than 50% cancers in the liver do not originate in the liver cells but are metastasis from other sites.

Liver is the third commonest site for development of secondary deposits from cancer anywhere in the body. For cancers originating in the stomach, intestine, pancreas, gallbladder/bile duct, colon and rectum; it is the second commonest site after local lymph nodes.

Why is the liver a common site for liver metastasis?

The liver receives blood from the arterial system like other organs and tissues. Additionally nutrient rich blood from the gastrointestinal tract also enters the liver through the portal vein. This dual blood supply exposes the liver to greater risk of receiving circulating tumor cells from cancers anywhere in the body.

The microscopic structure of the liver is unique. it has blood spaces called sinusoids that have lining like blood vessels; but with with gaps in between the adjacent cells. This allows cancer cells that arrive via blood to slip outside the wall into the liver substance more easily than in other organs.

The sinusoids described above are also lined by special immune cells called Kupffer cells that specialise in extraction of abnormal cells and proteins from the blood flowing in the sinusoids. Kupffer cells also extract cancer cells arriving via blood which helps them gain access to the liver.

Metastasis is fortunately an inefficient process!

Fortunately, metastasis is not an efficient process. Less than one in a million cells that reach the liver would develop into metastasis.

Once cells arrive in the liver they usually remain dormant in the absence of conducive environment for them to grow by stimulating factors or factors that enable them to received extra blood and nutrients that help them grow rapidly into metastasis. In certain cancers like breast cancer, the cancer releases factors in the blood that creates sites called pre-metastatic niches within the liver where , if the cancer cells reach, they have higher chances of developing into metastasis.

Cancer cells that come out of dormancy become cell clusters called micro-metastasis. Micrometastasis remain dormant within the liver unless they acquire potential to grown budding blood vessels (angiogenesis), which transforms them into metastatic deposits.

How many cancer patients develop liver metastasis?

As a result of improvement in survival for most cancers, cancer patients are surviving significantly longer for the last three decades than earlier.Advances in radiological techniques have increases the sensitivity of detection of liver metastasis than conventional techniques. In particular metabolic imaging like FDG-PET scanning has increased detecttion of metastasis by more than 25% in most cancers.

It is believed that more than 30% cancer patients will have liver metastasis detected during their lifetime and if autopsy is performed for all patients dying of cancer, 65% would have metastasis in the liver. Importantly in 15-30% of these patients, liver is the only site of metastatic deposits.

More than 30% of patients with cancer in colon and rectum have liver metastasis when the cancer is first detected (synchronous) and more than 70% develop liver metastasis after treatment of their colonic or rectal cancer (metachronous).

Liver metastasis is the end of the road....myth or fact?

Traditionally the detection of liver metastasis has been considered the end of the road for many years. Barring liver metastasis from slow growing and indolent neuroendocrine tumours, patients with liver metastasis are likely survive less than 2 years after diagnosis.

In the modern era of multidisciplinary cancer management, systemic chemotherapy has become more effective, safe and molecular targets within cancer cells have been identified in some cancers for specific non-cytotoxic targeted therapy. With these advances, survival even after detection for liver metastasis has progressively improved but yet long term survival (>5yrs) has been unachievable by this modality alone for most cancers. However chemotherapy alone cannot cure liver metastasis unless all cancer cells are conlusively shown to be killed within the metastasis. Sadly more than 50% liver metastasis that show reduction in size or completely disappear on scans (ghost lesions), have viable tumor cells under the microscope.

With improvements in technology, safe anaesthesia practices, better imaging and greater experience in liver surgery, the procedure has become safer and is regularly being performed with near 0% mortality.Liver surgery has been therefore increasingly applied to metastatic liver disease in the hope that removal of liver metastasis would help in prolonging survival. Despite good safety profile, long term survival with surgery alone has also been disappointing. Surgery is unable to treat micrometastasis, circulating tumor cells and dormant cells because they cannot be detected on current imaging modalities...therefore systemic therapy has to be married to surgery when treating liver metastasis for most patients if long term survival is to be achieved.

With greater experience, combination of systemic therapy and surgery has been introduced for management of liver metastasis with much better outcomes over the last 15 years with survival exceeding 50% at 5 years for liver metastasis from colon, rectum, breast, ovary/testis, neuroendocrine cancer using peri-operative systemic therapy and surgery in selected patients.

All over the world, surgeons haveperformed liver transplantation for patients with large metastasis from slow growing neuroendocrine tumors that are not amenable to excision, with good results (even better than for hepatocellular carcinoma) and this is accepted universally. One of the most famous recipients of a liver transplant for such metastasis was late Steve jobs of Apple.

Recently a group from Norway showed excellent results after liver transplantation for liver metastasis from colorectal cancer and the idea is evoking interest all over Europe. However this is yet to gain acceptability elsewhere.

A perusal of published literature on liver surgery for liver metastasis brings forth the following points

1. Liver resection, if safely performed, to remove all existing liver metastases is useful for all cancers
2. Patients should be selected based on medical fitness, extent of tumor in liver & experience of treating team
3. It must be part of multidisciplinary strategy that includes systemic therapy & interventional radiology
4. Best survival is obtained after complete excision of liver metastasis is obtained if the metastases are few in number, confined to the liver, if the metastasis are sensitive to chemotherapy and appear many years after the primary tumour has been treated.

Therefore in the modern era, in selected patients, liver metastasis is definitely not the end of the road. This statement is particularly true for patients with liver metastasis from cancer of the colon or rectum, neuroendocrine tumors, breast cancer, testicular & ovarian cancer and gastrointestinal stromal tumors (GIST).

All patients with liver metastasis benefit from liver directed therapy, choosing the appropriate therapy and at the right time is important for optimum outcome.

 

World Hepatitis Day 2014: Hepatitis is closer than you think....think again

Hepatitis....know it...confront it

Hepatitis is a term used for inflammation of the liver cells due to any cause

Causes of hepatitis

1. Viruses: hepatitis viruses A-H, non-hepatitis viruses: herpes, cytomegalovirus etc
2. Bacteria
3. Parasites
4. Drugs
5. Chemicals & toxins including alcohol

It can manifest in two forms

Acute hepatitis

Recurrent hepatitis

Chronic hepatitis

Common routes of transmission of hepatitis are through contaminated food and drink (feco-oral route), through blood & blood products (parenteral route) and sexual contact.

Transmission through placental circulation from pregnant infected mother to child in the womb is called vertical transmission.

Acute hepatitis is characterised by abdominal discomfort, low-moderate grade fever, nausea, lethargy and loss of appetite. Most viral infections are associated with feeling of uneasiness, weakness, body pain before development of jaundice (prodrome). Jaundice is the hallmark of acute hepatitis and is usually detected by yellow discolouration of eyes and passage of dark yellow urine. Liver function tests show raised bilirubin level (mainly conjugated) accompanied by elevated liver enzymes (AST, ALT and frequently ALP). Urine shows elevated bile salts. Massive elevation of enzymes >1500 IU is rare. High fever usually indicates concurrent inflammation within the biliary system (cholangitis).

Acute hepatitis is a self-limiting disease and in most cases with supportive care, complete uneventful recovery results over a period of a few weeks. Recovery may be prolonged in elderly patients, pregnant women, those receiving medication to reduce immunity or those who have pre-existing liver damage from alcohol, fatty liver or other causes.

Alcoholic hepatitis is a unique form of hepatitis that occurs after years of large consumption of alcohol. It usually follows a binge of alcohol but can occasionally seen in early phases of abstinence. 

It is a severe form of hepatitis that causes a systemic inflammatory state often associated with infection, kidney dysfunction and progression to liver failure. The underlying liver is usually pre-cirrhotic or frankly cirrhotic in patients with alcoholic hepatitis. Many patients with alcoholic hepatitis have muscle wasting and nutritional defects making them prone to infections and multi organ failure leading to significant mortality despite supportive care.

In less than 5% cases, the liver damage caused by inflammation overwhelms the body immunity and the capacity of the liver to repair and regenerate. In such situations patients may progressively and rapidly develop cardinal features of liver failure : Deep jaundice  Mental changes (Encephalopathy & Clotting dysfunction. This syndrome is called Acute liver failure if patient had normal liver to start with and Acute on chronic liver failure if patient has a recognised or unrecognised chronic liver disease to start with.

Both are very severe conditions and if condition does not respond to medical measures, can be fatal.

Chronic hepatitis is usually the result of persistent or recurrent damage or the failure of immunity to clear the acute infection or insult. Chronic hepatitis is seen in 20-30% most of which is due to hepatitis B or C virus infections. Common hepatitis virus A is never chronic while less common hepatitis can rarely cause chronic infection.

Chronic hepatitis can follow an indolent course being asymptomatic for years before detection. Until liver damage has exceeded the reserve of the liver, liver function tests may be normal apart from subtle alterations.

The chronic inflammation in the liver can lead to development of primary liver cancer ( hepatocellular carcinoma) in unto 4% patients with chronic hepatitis every year.

Chronic inflammation can also lead to progressive scarring and changes in the micro architecture  of the liver leading to fibrosis and eventually cirrhosis. Once cirrhosis develops, the average survival is less than 10 years in most cases. Progressive damage can lead to features of chronic liver failure like jaundice, accumulation of fluid in abdomen (ascites), clotting deficiency and mental changes (hepatic encephalopathy). Reduction in liver function reduces immunity leading to increased propensity for infections and strain on other organ systems. In such a state average survival is less than one year.

Once cirrhosis develops the risk for developing hepatocellular carcinoma doubles to 8% per year.

As in most diseases, prevention is better than cure

Prevention of hepatitis

1. Consumption of safe food and drink
2. Vaccination: hepatitis B, hepatitis A
3. Avoid alcohol & IV drug abuse
4. Avoid unprotected high-risk sexual activity
5. Avoid contaminated syringes, needles, blood and blood products
6. Manage body weight & keep diabetes in check

Early detection of hepatitis

1. Periodic health checks
2. Screening of high risk patients
• children of parents with liver cancer or hepatitis
• siblings & spouses of patients with liver cancer or hepatitis
• patients receiving blood products (haemophiliacs, thalassemics) or dialysis
• iv drug abuse history
• high risk unprotected sexual activity & commercial sex workers
• healthcare workers
• patients with suppressed immunity or those on immunity reducing drugs

Treatment of hepatitis

1. Most cases of acute hepatitis need only supportive care
2. No specific treatment available for most viral hepatitis except hepatitis B and C
3. Inciting cause should be detected, avoided and treated accordingly
4. If acute or acute on chronic liver failure results patients should receive ICU management including ventilator support: some patients who don't respond can be salvaged by urgent liver transplantation
5. Measures to prevent developing chronic hepatitis & cirrhosis should be taken
6. Patients with chronic hepatitis should be aggressively followed for detection of cirrhosis or development of cancer
7. Early cases of liver cancer can be cured by liver surgery if there is no cirrhosis. If thesre is cirrhosis, liver transplant is the best option
8. Patients with complications of liver cirrhosis can be salvaged with liver transplant
9. Measures to prevent recurrence of hepatitis should be instituted even after transplant

http://timesofindia.indiatimes.com/india/Open-secret-Doctors-take-cuts-for-referrals/articleshow/37350397.cms

Before all of you go tut-tutting in self-righteous condemnation of those this article seems aimed to demonise, it would be worthwhile to go into a few oft-forgotten facts

1. Healthcare is not a service or sacrifice...it is an industry and an economic activity and more so in the private sector. Blatant hypocrisy by couching it under the guise 'social service' has gone on for far too long in this country.
2. Healthcare needs of more than 75% of Indians are met by the private sector and private institutions are preferred by most patients even for primary and secondary care as opposed to poorly managed, inefficient public hospitals bursting at their seams with patients owing to a  merit-last recruitment policies, budgetary constraints, poor salaries and a cornucopia of oft repeated reasons.
3. More than 80% patients in this country pay out-of-pocket for their healthcare and therefore are healthcare clientele or consumers rather than merely patients.
4. Setting up of a healthcare facility in an urban area requires massive investments and capital expenditure owing to high land costs, high import duties on equipment that has low levels of indigenity and human resource costs to provide services to an increasingly demanding clientele.
5. Permissions and licensing of healthcare facility is extremely arbitrary and even if they exist on paper, rules are blatantly violated allowing almost anyone with access to land and funds to setup a healthcare facility.
6. There is hardly any regulation and credentialing of healthcare facilities with regard to outcomes and their ability to offer high-end services from the governments and with low penetration of health insurance, it is a free for all in terms of competitive bidding, promotional activities and advertising to entice patients often looking for a better deal rather than a better service when it comes to their healthcare needs.

While the points above are by no means a complete list, it is important to analyse the origin of this condemn able practice of trading patients for a consideration to hospitals as if they are cattle or commodities.

Economic theory has often more to do with reality than morality in a consumerist society....which however much we may choose to deny, we have already become. Having made huge investments to offer facilities and infrastructure inadequately available or absent at public sector hospitals, private healthcare entrepreneurs are hard-pressed to recover the massive investments made because of the unregulated mushrooming of facilities clamouring for a slice of the pie of  paying patients. Government subsidised health schemes to decongest public hospitals and use under-utilised capacity in private hospitals are mired in red-tapism and impractical costings and therefore not much use in bridging the gap. In such a scenario, to recover their costs, private sector healthcare facilities are compelled to look for out-of-the-box solutions to increase their footfalls sometimes employing processes that could be frowned upon. When supply exceeds demand, it is a buyer's market and since reduction of prices would further harm their balance sheets, private institutions resort react by passing on part of the profits as an incentive or inducement to referring physicians. Once such a practice finds root, everyone is dragged into it to stay on the bandwagon.

Finally patients themselves need to be more discerning and not blindly follow a referral path suggested by their primary physician which I must hasten to add that this is happening already. By no means am I encouraging cynicism towards physicians, but  patients should stop being mindless and ask pertinent questions of their physicians regarding the plan of their management and referral and satisfy themselves to the greatest extent possible. 

The solution remains complex but it is high time we took steps in the right direction. I humbly suggest the following

1. Strict criteria should be followed while licensing healthcare facilities for performance of high end procedures and unregulated mushrooming of centres should be checked.
2. Rather that investing public money and duplicating high end capacity building in public hospitals, extra capacity in private hospitals should be utilised at a sensible price through well monitored schemes. This will help patients as well as reduce massive capex costs to governments while controlling this malpractice of incentives for referrals.

The above is by no means a complete list of solutions but is something that can be implemented without ruffling too many feathers. This will ensure in the intermediate term that referrals are guided by clinical needs rather than other considerations. 

Let me reiterate here that by no means am I condoning or encouraging the cut-practice system that has got stuck in a morass....this posting is merely an attempt to analyse the reasons for this rot. Acknowledgement of the problem is only part of the solution and not a solution in itself . It may allow one to be unabashedly self-righteous and score debating points on ethical forums but it, by no means, brings us remotely closer to a much-needed solution.

Brain death....what is it?

Anatomy of the brain

Traditionally, a person who does not have a beating heart and is not breathing is considered to have died. However with the advent of mechanical ventilation, a person who is not spontaneously breathing can be oxygenated for a significant period of time using a mechanical ventilator.

The human brain is the command & co-ordination center of all body activities. It consists of four parts: the cerebral cortex, the cerebellum, the mid-brain and the brain-stem (pons & medulla oblongata).
The cerebral cortex has multiple functions importantly cognition, sensation, purposeful movement, wakefulness, thinking, speech and memory. The mid-brain among others is responsible for pupillary function and eye movement as it houses the centres controlling nerves responsible for these reflexes. The cerebellum controls co-ordinated movements, gait and balance. The brain stem houses centres for all the other cranial nerves including those for conjugated eye movement, corneal reflex, tracheal and conjugated eye movements. The medulla oblongata houses the critical breathing and vasomotor centres that are responsible for spontaneous breathing and maintenance of coordinated heartbeat and circulation.

It follows therefore that irreversible and major damage to the brain function is incompatible with life. Due to autonomic reflex and local mechanisms, some organs including the heart may continue to function for a period ranging from hours to weeks, but long term survival is precluded in the absence of coordination provided by the brain.
The hallmarks of lack of brain and in particular brain-stem activity are
Deep coma ( absence of spontaneous movement, absence of response to deep pain)
Absence of spontaneous breathing
Loss of reflexes coordinated by nerves in the mid-brain & brain stem ie corneal reflex, pupillary reaction, cough & gag reflex, dolls eye reflex, cold caloric reflex

Such severe damage to the brain can result from various causes
Brain hemorrhage
Brain hypoxia (Due to cut-off of oxygen supply)
Brain injury
Rise in pressure in and around the brain (intra-cranial pressure) due to infection or tumours

Once the damage to the brain becomes irreversible, despite having a heart beat, the individual is unable to perceive any stimulus, unable to awaken, unable to move and has no spontaneous breathing. Such a person is considered to be Dead by neurological criteria or Brain dead.

It is important to differentiate this situation form other neurological syndromes like Persistent Vegetative State  or Minimally responsive state. The fundamental difference is that in these other conditions, brain stem function is partially or totally preserved despite the lack of response to stimuli and hence brain death is often also referred to as Brain stem death to emphasize the irreversible loss of brain stem functions.

To diagnose a comatose person on mechanical ventilator to have suffered brain death, the proximate cause of brain injury should be known or identifiable and irreversibility should be established. Generally to diagnose this condition clinically, one should reliably rule out presence of shock (severe reduction in blood pressure), hypothermia (body temperature <35 administration="" also="" anaesthesia="" be="" br="" intake="" narcotics="" of="" or="" out.="" ruled="" should="" soporifics=""> To establish that an individual has undergone Brain death the following is deemed necessary and sufficient

Deep coma (no spontaneous movement or response to call )
Absence of cranial nerve reflexes (corneal reflex, pupillary reaction to light, corneal & tracheal/pharyngeal reflex, dolls eye reflex)
Absence of spontaneous respiration despite rise in CO2 (Apnea test)

The Apnea test is mandatory for the declaration of brain-stem death. After ruling out hypothermia and hypoxia, the individual is pre-oxygenated and is disconnected from the ventilator and oxygen is delivered at 6L/min through a catheter into the trachea after baseline arterial blood gas analysis. Close watch is maintained for spontaneous chest wall movements due to respiratory excursions or actual breaths. After 8 minutes, the individual is reconnected  to the ventilator and arterial blood gases are analysed. If there is no spontaneous respiration despite adequate rise in PCO2 levels (usually 60 mm mercury or 20mm rise above baseline) during disconnection, the test is positive and irreversible brain stem damage is confirmed.

Most experts agree that in a case ( excluding infants) where cause of brain injury is not drug overdose or poisoning, a six hour period is sufficient to gauge for signs of recovery before brain death can be confirmed.

Other tests like EEG, Cranial doppler, Cerebral angiography, Evoked potential study or SPECT are not required to diagnose brain death but may be performed when the testing is equivocal.

With the advent of severe brain stem dysfunction, normal body function is severely deranged. Significant and progressive alterations occur in cardiovascular, metabolic, immune and endocrine systems that if untreated can lead to rapid progression to cardiac arrest.

 Rapid rise in the intracranial pressure can lead to herniation of the brain stem and pressure on the vasomotor centre causing instant cessation of circulation and cardiac death. Slower rises compromise blood flow to the brain and evoke initially a  fall in heart rate followed by sympathetic storm characterised by rapid heart rate and rise in blood pressure. Eventually heart damage and lack of blood supply to the vasomotor centre lead to collapse and cardiac arrest.
Process of brain stem death also leads to deranged function of the pituitary gland leading to reduction in thyroid hormone, anti-diuretic hormone (ADH) and cortisol release.  This derangement (in particular ADH) causes significant changes in ability of body to maintain temperature, blood glucose level and fluid electrolyte balance without significant extraneous support. Diabetes insipidus-like state induced by lack of ADH causes massive urinary water losses leading to cellular dehydration and rise in sodium levels. Brain death also leads to hyper-activation of the immune system, white cell activation and release of inflammatory substances like cytokines in the blood, similar to those seen in a systemic inflammatory response (SIRS) to infection. This further leads to loss of vascular tone, reduced blood supply to cells and shunting further depriving organs of blood and oxygen eventually leading to cell death. All these mechanisms are activated immediately after brain stem injury but the speed of impact may vary and with adequate monitoring and support, hours to days may elapse before circulatory collapse and cardiac arrest. However once brain death is established, recovery is impossible and cardiac arrest is only a matter of time.