TB Serology: A boon or BAN?

Tuberculosis (TB) remains a major global healthcare issue with around 1.7 million deaths in 2009 due to TB and rising absolute number of cases each year due to the increasing global population, the emergence of drug resistance, and the detrimental effects of HIV coinfection.

The diagnosis of active TB is traditionally made using direct identification of the bacillus by smear microscopy or subsequent culture of Mycobacterium tuberculosis (M Tb). This requires appropriate specimens to examine, and time for the bacillus to grow. This can cause considerable difficulty if the infection is non-pulmonary, or if the patient does not expectorate sputum. Thus, invasive tests like surgical biopsy or bronchoscopy may have to be resorted to. Unlike in many other infections, culture of M Tb may be prolonged or difficult, hence numerous kits for the detection of antibodies to the pathogen have been marketed, as a means for rapid identification.


Serological testing can detect various classes of antibodies to the infective pathogen in the patients' serum (IgG, IgM, IgA). These antibodies are produced in response to antigenic substances or proteins on the surface of the bacterium.

Pulmonary Tuberculosis

Interferon-gamma release assays (IGRAs) are diagnostic tools for latent tuberculosis infection (LTBI). They are surrogate markers of Mycobacterium tuberculosis infection and indicate a cellular immune response to M. tuberculosis. IGRAs cannot distinguish between latent infection and active tuberculosis (TB) disease, and should not be used for diagnosis of active TB, which is a microbiological diagnosis. Clinical evaluation and additional tests (such as a chest radiograph, sputum smear, and culture) are needed to differentiate between a diagnosis of latent TB or active TB.
A positive IGRA result may not necessarily indicate active TB, and a negative IGRA result may not rule out active TB.

Because IGRAs are not affected by Bacille Calmette-Guérin (BCG) vaccination status, IGRAs are useful for evaluation of LTBI in BCG-vaccinated individuals, particularly in settings where BCG vaccination is administered after infancy or multiple (booster) BCG vaccinations are given.

QuantiFERON GOLD or TB-Gold also known as QFT-G is an interferon-γ release assay (IGRA) used in tuberculosis diagnosis. For QFT-G, the antigens include mixtures of synthetic peptides representing two M. tuberculosis proteins, ESAT-6 and CFP-10.


Findings from several systematic reviews and an independent evaluation of rapid tests suggest that serological tests for both pulmonary and extra- pulmonary TB are inaccurate. No test performs well enough to replace smear microscopy. Currently available commercial serological TB tests appear to do more harm than good because of the harm caused to patients through false-positive or false-negative tests results. Furthermore, these tests prove to be an economic burden to the country as well.

Echoing these concerns, in a recent editorial Singh and Katoch wrote, ‘Unfortunately, unethical medical practices provided major boost to these kits in recent years, without bothering much on quality of tests and implications of false-positive and false negative results...

In July 2011, WHO issued a policy stating that commercial serological tests provide inconsistent and imprecise estimates of sensitivity and specificity. There is no evidence that existing commercial serological assays improve patient outcomes, and high proportions of false-positive and false-negative results adversely impact patient safety. Overall data quality was graded as very low, with harms/risks far outweighing any potential benefits. It is, therefore, recommended that these tests should not be used in individuals suspected of active pulmonary or extra- pulmonary TB, irrespective of their HIV status.
Immediately following the WHO policy, the RNTCP published an advisory statement against the use of TB serological tests in India. More recently, an expert committee convened by the Drug Controller General of India has recommended a ban on import and sale of TB serological tests in India and this ban has been endorsed by the Indian health ministry.

Thus, the void in the diagnostics of tuberculosis which was to be filled up by these serology tests, has still remained a void. We hope that scientific research comes up soon with more reliable aids in the diagnosis of TB.

Diabetes: A new kid on the horizon?

Adding to the not so long list of anti diabetic drugs, is a new promising group -
The SGLT2 inhibitors. 

Amongst the orals, we have

• Biguanides like Metformin and Thiazolidinediones like Pioglitazone which reduce the insulin resistance.

• Sulfonylureas like Glimepiride, Gliclazide, and Glibenclamide and Glinides like Repaglinide which act on insulin secretion.

• Alpha Glucosidase inhibitors like Acarbose, Miglitol, and Voglibose which reduce the glucose absorption from the gastrointestinal tract.

• DPP-4 inhibitors like Sitagliptin and Saxagliptin and GLP1 agonist like Exenatide  which act by reducing Glucagon secretion.

Now we have a new group which could potentially act via the kidneys.

The kidney plays an important role in the maintenance of glucose homeostasis by reabsorbing almost all filtered glucose via sodium-glucose cotransporters (SGLTs). The SGLT2 cotransporter is the most important of these, as it mediates 90% of renal glucose reabsorption. Its expression and activity are increased in type 2 diabetes, causing increased amounts of glucose to be reabsorbed into the systemic circulation, thereby adding to the hyperglycemia derived from other pathogenic defects. The SGLT2 cotransporter has therefore been targeted as a site for intervention in the management of hyperglycemia in type 2 diabetes.

Several SGLT2 inhibitors, including dapagliflozin, canagliflozin, empagliflozin, and ipragliflozin have been developed and are currently under investigation for efficacy and safety as treatment for type 2 diabetes.

Dapagliflozin was approved by the European Commission on November 14, 2012, and on January 10, 2013, the USFDA advisory committee recommended approval for canagliflozin as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. These agents reduce plasma glucose concentration by inhibiting SGLT2-mediated reabsorption of filtered glucose at the proximal tubule, leading to glucosuria.

Investigational study data indicate that, in patients with early or long-standing type 2 diabetes, SGLT2 inhibitors are effective in reducing fasting plasma glucose, postprandial plasma glucose, and HbA1c, promote weight loss, and have a low risk of clinically significant hypoglycemia. Because their mechanism of action is independent of insulin, SGLT2 inhibitors complement the action of other antihyperglycemic agents, including insulin and metformin.

The only worry would be the costing of the drug. Like its predecessor, the DPP-4 inhibitor, if its priced equally high, the benefits to society at large would be equally low.

Calcium Controversy- Part 2

In my previous post I had discussed the evidence of vascular calcification and cardiovascular deaths in males taking calcium supplements unless specifically indicated. However, the importance of these supplements in post menopausal women has always been proved beyond doubt.

Now we have emerging evidence to the contrary.

A meta analysis revealed that calcium alone did not significantly reduce the risk of fractures while calcium with vitamin D did reduce the fracture risk by 12%. Vitamin D alone also does reduce incidence of fractures.

The National Institutes of Health-AARP Diet and Health Study has given new insights.

Among women, the current study suggests a neutral effect of both dietary calcium and calcium supplements on the risk for CVD. Physicians should keep in mind, however, that vitamin D and not calcium is principally responsible for preserving bone and preventing osteoporosis among women.

Take home message:

Vitamin D at a dose of at least 800 IU/day should be the primary treatment for women at average risk for osteoporosis. Until the questions regarding the long-term safety of calcium supplements in both sexes are better understood, it is reasonable to withhold calcium among women receiving preventive treatment for bone health.

The Calcium Controversy

It is well established that consumption of calcium-rich foods or calcium supplementation can help prevent osteopenia and osteoporosis,
especially in postmenopausal women. Consequently, calcium supplements are widely used to combat estrogen- and age-related declines in bone mineral density, especially in those with a diet deficient in calcium-rich foods.

Twist in the tale:

But recent data suggest that high calcium intake might increase the risk for myocardial infarction (MI)

or heart attack. It is uncertain exactly how calcium supplements work to increase MI risk, but calcium supplements can accelerate vascular calcification (calcium deposits on blood vessel walls).

Current guidelines suggest that most adults should receive between 1000 mg and 1200 mg of elemental calcium daily. Individuals who consume a healthy diet, rich in dairy products and calcium-fortified foods, should reach these thresholds without any supplements. Blood calcium levels increase much faster after taking calcium supplements than they increase after dietary calcium. High levels of calcium in the blood can thus cause vascular calcification.

The EPIC-Heidelberg study was undertaken to evaluate the associations of dietary calcium intake and calcium supplementation with MI, stroke(paralysis) risk, and overall cardiovascular mortality.
The results indicated that calcium supplement users experienced a statistically significant increase in MI risk when compared with those who did not use any supplements.


The National Institutes of Health trial was also based to study the same facts.
Supplemental calcium (1000 mg daily) was associated with a 19% increase in CV death, including heart disease death in men but not in women as compared to no calcium supplementation.


Now comes a another twist in the story:

Analysis of the EPIC-Heidelberg study revealed serious flaws. A 2009 study from the Mayo Clinic actually measured aortic valve and coronary calcification for up to three years after the patient started taking calcium supplements. They, however did not find any significant progression of calcification.
Thus, the validity of the results of the EPIC study was questioned.

Moral of the story:

Calcium rich foods

Calcium supplements should be reserved for patients who, through careful dietary history, do not consume adequate amounts of calcium, unless otherwise clinically indicated. The total calcium intake should not exceed 1200 mg per day. Perhaps the sage advice of getting one's vitamins and minerals primarily from dietary sources applies here too, at least for a majority of patients. Given the recent finding that calcium supplements may increase CV mortality in men, the consumption of calcium-rich foods, such as low-fat dairy products, beans, and green leafy vegetables, may be preferred over calcium supplements in men, unless otherwise clinically indicated.

Snoring: Benign or Malignant?

  A famous writer once said:
"Ain't there no way to find out why a snorer can't hear himself snore?"

Whether you call it by its slang name, "sawing logs," or its medical name, "stertor," snoring is common. You snore when something blocks the flow of air through your mouth and nose. The sound is caused by tissues at the top of your airway that strike each other and vibrate. Many adults snore, especially men. Snoring may increase with age.

However, snoring can also be a sign of a serious sleep disorder called sleep apnea. This means you stop breathing for periods of more than 10 seconds at a time while you sleep.

New research conducted by otolaryngologists at Henry Ford Hospital in Detroit finds that snoring is a bigger risk factor for stroke and heart attack than smoking, being overweight, or high cholesterol.

Tips for reducing snoring:

Lifestyle changes to stop snoring:

• Lose weight if you are overweight.

• Cut down or eliminate alcohol and other sedatives at bedtime.

• Avoid caffeine and heavy meals within two hours of going to bed, especially dairy products and soymilk.

• Avoid sleeping flat on your back. A tennis ball may be sewn to the back of the nighties to help the person turn back to sleeping on the side.

• Exercise can also help to stop snoring.

• Quit smoking.

• Establish regular sleep patterns. Create a bedtime ritual with your partner and stick to it. Hitting the sack in a routine way together can help you sleep better and often minimize snoring.

Bedtime remedies to help you stop snoring:

• Clear nasal passages. Having a stuffy nose makes inhalation difficult. You can do it naturally with a Neti pot or try nasal decongestants or nasal strips to help you breathe more easily while sleeping.   

• Keep bedroom air moist with a humidifier. Dry air can irritate membranes in the nose and throat.

• Reposition. Elevating your head four inches may ease breathing and encourage your tongue and jaw to move forward. There are specially designed pillows available to help prevent snoring by making sure your neck muscles are not crimped.

Throat exercises to stop snoring:

• Repeat each vowel (a-e-i-o-u) out loud for three minutes a few times a day.

• Place the tip of your tongue behind your top front teeth. Slide your tongue backwards for 3 minutes a day.

• Close your mouth and purse your lips. Hold for 30 seconds.

• With mouth open, move jaw to the right and hold for 30 seconds. Repeat on left side.

• With mouth open, contract the muscle at the back of your throat repeatedly for 30 seconds. Tip: Look in the mirror to see the uvula (“the hanging ball”) move up and down.

Alternative remedies for snoring:

• Singing can increase muscle control in the throat and soft palate, reducing snoring caused by lax muscles.

Didgeridoo

• Playing the didgeridoo (native Australian wind instrument) can strengthen the soft palate and throat, reducing snoring.

• Continuous Positive Airway Pressure (CPAP). To keep your airway open during sleep, a machine at your bedside blows pressurized air into a mask that you wear over your nose or face.

• Dental appliances, oral devices, and lower jaw-positioners often resemble an athlete’s mouth guard. They help open your airway by bringing your lower jaw or your tongue forward during sleep.

• Traditional surgery such as Uvulopalatopharyngoplasty (UPPP), Thermal Ablation Palatoplasty (TAP), tonsillectomy, and adenoidectomy, increase the size of your airway by surgically removing tissues or correcting abnormalities.

• The Pillar procedure is also an effective surgery in which small plastic implants are inserted into the soft palate. Scar tissue grows around the implants, stiffening the soft palate, which stops vibrations that cause snoring.

THERE'S ONLY ONE CURE FOR SNORING: INSOMNIA

Dawoodi Bohra - Ye Dil Maange More !

A patient education program on Cardiac Awareness conducted under the guidance of Dr Aliasgar Bahrainwala at Hatemi Mohalla Hall on 9.2.13
The program was presided by Janab Amilsaheb Janab Ubai Bhaisaheb Nooruddin.

3 doctors from the renowned Saifee Hospital gave their valuable contributions as regards prevention and management of cardiac ailments which is rapidly rising in the community.
The Bohras are well known for their fondness of high caloric carb enriched sweets, delicacies and non veg savouries. They cannot resist the temptation to accept dinner invitations. The fast growing incidence of diabetes, hypertension, coronary artery disease and osteoarthritis amongst the community has led to many a program being conducted for patient awareness. Orthopedics, diabetologists, cardiologists and physicians get together and organize these fora with the permission of the spiritual head, Dr Syedna Mohammed Burhanuddin (TUS) and the cooperation of the local Mohalla Amilsaheb.
On the auspicious occasion of the 102nd Milad Mubarak of the Syedna, this cardiac program kicked off with the first speaker, Dr Shabbir Baldiwala, Physician (yours truly), explaining how to diagnose a heart attack and its emergency medical management. He also discussed the various treatment options available.

It was then, Dr Yunus Loya, Interventional Cardiologist, who took over and talked about Primary Angioplasty. And as Mr. Abuzar Zakir correctly said, the last but most important speaker of the day, Dr. Aliasgar Bahrainwala, Cardiac Surgeon, winded up the session with a small discussion about other treatment modalities available.

The Cola pandemic

Coca-Cola is a major international brand. 

It usually contains caramel color, caffeine and sweeteners such as sugar or high fructose corn syrup.

The primary modern flavoring ingredients in a cola drink are sugar, citrus oils (from oranges, limes, or lemon fruit peel), cinnamon, vanilla, and an acidic flavorant. Manufacturers of cola drinks add trace ingredients to create distinctively different tastes for each brand. Trace flavorings may include nutmeg and a wide variety of ingredients, but the base flavorings that most people identify with a cola taste remain vanilla and cinnamon. Acidity is often provided by phosphoric acid.

“Sugar-free" or "diet" colas typically contain artificial sweeteners only.

Health Hazards:

               The Real Bears: http://youtu.be/myxwCEGcBYc

• Regular soft drink users have a lower intake of calcium, magnesium, ascorbic acid, riboflavin, and vitamin A.
• Colas, both those with natural sweetening and those with artificial sweetening, were associated with increased risk of chronic kidney disease most likely due to the phosphoric acid.
• The drink has also aroused criticism for its use of caffeine, which can cause physical dependence and addiction.
• A link has been shown between long-term regular cola intake and osteoporosis in older women (but not men).This was thought to be due to the presence of phosphoric acid.
• Frequent exposure of teeth to acidic drinks increases the risk of tooth damage through dental erosion.
• Colas are majorly responsible for the Obesity and Diabetes epidemic throughout the world because of the high sugar and caloric content. Approximately, 150 kcal in a 330ml can of coke.
• In addition, there are food dyes and other chemical additives in Coke products that are known carcinogens.
• Gastroesophageal reflux disease is very commonly associated with regular cola drinkers.

ASPARTAME AMIDST CONTROVERSY 

One of the commonest artificial sweeteners used in diet colas is "Aspartame". 

The artificial sweetener aspartame has been the subject of several controversies since its initial approval by the U.S. Food and Drug Administration (FDA) in 1974. The FDA approval of aspartame was highly contested, with critics alleging that the quality of the initial research supporting its safety was inadequate and flawed and that conflicts of interest marred the approval of aspartame. In 1987, the U.S. Government Accountability Office concluded that the food additive approval process had been followed properly for aspartame. The irregularities fueled a conspiracy theory, which circulated along with claims, unsupported by medical evidence, that numerous health conditions (such as multiple sclerosis, systemic lupus, methanol toxicity, blindness, spasms, shooting pains, seizures, headaches, depression, anxiety, memory loss, birth defects and death are caused by the consumption of aspartame in normal doses in the "Nancy Markle" email hoax.

The "Markle" email says that there is a conspiracy between the FDA and the producers of aspartame.

Pro:

The potential health risks have been examined and dismissed by numerous scientific research projects. With the exception of the risk to those with phenylketonuria, aspartame is considered to be a safe food additive by governments, worldwide, and major health and food safety organizations. FDA officials describe aspartame as "one of the most thoroughly tested and studied food additives the agency has ever approved" and its safety as "clear cut". The weight of existing scientific evidence indicates that aspartame is safe as a non-nutritive sweetener.

The acceptable daily intake (ADI) value for aspartame, as well as other food additives studied, is defined as the "amount of a food additive, expressed on a body weight basis, that can be ingested daily over a lifetime without appreciable health risk.The Joint FAO/WHO Expert Committee on Food Additives (JECFA) and the European Commission's Scientific Committee on Food has determined this value is 40 mg/kg of body weight for aspartame, while FDA has set its ADI for aspartame at 50 mg/kg.

The primary source for exposure to aspartame in the United States is diet soft drinks, though it can be consumed in other products, such as pharmaceutical preparations, fruit drinks, and chewing gum among others in smaller quantities. A 355 ml can of diet soda contains 180 milligrams of aspartame, and for a 75 kg (165 lb) adult, it takes approximately 21 cans of diet soda daily to consume the 3,750 milligrams of aspartame that would surpass the FDA's 50 milligrams per kilogram of body weight ADI of aspartame from diet soda alone.

Anti:

Aspartame accounts for over 75 percent of the adverse reactions to food additives reported to the FDA. Many of these reactions are very serious including seizures and death. A few of the 90 different documented symptoms listed in the report as being caused by aspartame include: Headaches/migraines, dizziness, seizures, nausea, numbness, muscle spasms, weight gain, rashes, depression, fatigue, irritability, tachycardia, insomnia, vision problems, hearing loss, heart palpitations, breathing difficulties, anxiety attacks, slurred speech, loss of taste, tinnitus, vertigo, memory loss, and joint pain."

Drinking diet soda daily is linked to a higher risk of stroke, heart attack and vascular-related deaths.

Evidence is increasing to suggest that excessive cola consumption can also lead to hypokalaemia, in which the blood potassium levels fall, causing an adverse effect on vital muscle functions.’

                

                    IS THIS THE RIGHT CHOICE, BABY???