NIH pilot predictive medicine by studying healthy people’s DNA

A new study by National Institutes of Health researchers has turned traditional genomics research on its head. Instead of trying to find a mutation in the genomic sequence of a person with a genetic disease, they sequenced the genomes of healthy participants, then analyzed the data to find “putative,” or presumed, mutations that would almost certainly lead to a genetic condition.

Out of almost 1,000 volunteers whose genomes were examined, about 100 had genomic variants predicting that they would have a rare disease. Almost half of them indeed had the disease when researchers went back and carefully evaluated them, said Leslie G. Biesecker, M.D., chief of the Medical Genomics and Metabolic Genetics Branch (MGMGB) at the National Human Genome Research Institute (NHGRI) and corresponding author of the study published June 4, 2015, in the American Journal of Human Genetics.

“We were surprised that this many individuals had positive findings in a group of individuals that is basically healthy,” said Jennifer Johnston, Ph.D., lead author and staff scientist with the Clinical Genetics Section of the MGMGB.  The research is part of ClinSeq, a large-scale, NIH research study that explores the fundamental medical, molecular and bioinformatic challenges facing individualized genome sequencing in a clinical research setting.

Once they identified participants with genomic mutations, researchers called them back to the clinic to give them a customized work-up. They called this method of looking at the person after looking at the genomic data “iterative phenotype.” Researchers sifted through more than 100,000 variants per participant – nearly all harmless – and studied only potentially harmful mutations that were found in about 100 of the 951 participants. Of those hundred or so patients, 79 were followed up, and they confirmed that 34 had the specific condition linked to their genetic mutation. These findings indicate that 3 percent or more of the U.S. population may have a genetic condition compared to previous estimates of less than 0.02 percent.

“We achieved about a 50 percent accuracy of predicting disease in people not knowing anything about their health status beforehand,” Dr. Biesecker said. In other words, the researchers changed the odds of these patients having one of these diseases from something like 1 in 50,000 to 1 in 2.

Given this accuracy, Dr. Biesecker is upbeat about the future of genomic medicine. “These results show that you can dramatically improve your predictions based on genome sequence information.”

NHGRI Director Eric Green, M.D., Ph.D, agreed, adding: “Today, we tend to deliver medical care based on the expected response of the average patient, and yet we know that this is far from perfect. Eventually, we want to deliver medical care based on individual genomic differences that enable more precise ways to prevent and treat disease. These findings move us closer to that reality.”

The team also found that having a mutation did not always lead to a condition that looked like a textbook case. Indeed, 20 of 79 of the participants with harmful mutations and an associated physical change didn’t know they might have a genetic condition. Sometimes these physical changes were so mild that the participant had neither sought a diagnosis nor reported them to the research team during enrollment in the study. While it may seem unnecessary to find these mild cases, one key aspect of genomics is that the same mutation can affect family members with different levels of severity.

“A couple of the participants with LDLR (low density lipoprotein receptor) mutations thought they just had garden variety high cholesterol, when in fact they had familial hypercholesterolemia,” said Dr. Biesecker. This led to more aggressive cholesterol screening in other family members, including children as young as eight, because early treatment can delay heart attacks and prolong life.

Researchers found other evidence that genetic conditions are underestimated. That is because, until now, knowledge about genetic conditions has mostly been based on family health history or ill people who walk into a clinic. This has led researchers to study only those who are more severely affected and not those who are mildly affected or not affected at all, which eventually leads to an overestimation of the condition’s severity and an underestimation of its prevalence. The problem (ascertainment bias) has long been known and acknowledged by genetics researchers. They have only recently been able to address it as DNA sequencing costs have plummeted.

At this rate, just above 9 million people, about the population of New Jersey, may be living with some sort of genetic condition. The authors caution that not all healthy people need to have their genomes sequenced, emphasizing that this is a proof-of-concept study that may lead to a better understanding of how these mutations affect health. “We want to add DNA sequencing to the physician’s toolbox,” Dr. Biesecker said. “It is fine to take care of patients once they are sick and that’s appropriate, but wouldn’t it be better to find some patients before they are sick and take care of them?”

Treating Baby or Young Child With a Cold

What can parents do when their babies and young children have a cold? It depends on the child’s age.

Although most colds in children don’t have serious complications, they can cause great worry to caregivers, and are among the top reasons for visiting a doctor. FDA doesn’t recommend over-the-counter (OTC) cold and cough medicines for children younger than 2. For infants and children younger than 2, those medicines may have serious and potentially life-threatening side effects.

So what’s a worried parent to do? Here are some tips from FDA on how to safely treat your child’s cold.

Relieving Cold Symptoms

There’s no cure for the common cold, a viral infection that cannot be treated with antibiotics, says FDA’s pediatrician Amy M. Taylor, M.D., M.H.S.

“A cold is self-limited, and patients will get better on their own in a week or two without any need for medications. For older children, some OTC medicines can help relieve the symptoms—but won’t change the natural course of the cold or make it go away faster,” says Taylor, a medical officer in FDA’s Division of Pediatric and Maternal Health.

Coughs are a normal symptom of a cold and aren’t all bad. “Coughs help the body clear the mucus out of the airway and protect the lungs; so you don’t want to suppress all coughs,” Taylor says.

Non-drug treatments for coughs include drinking plenty of fluids, especially warm drinks to soothe the throat.

When to Call a Doctor

Not every sniffle or cough merits a trip to the doctor’s office. When in doubt, parents should call their healthcare provider. “Call your pediatrician at the first sign of illness whenever a baby 3 months or younger is sick,” Taylor advises.

For all children, call a doctor if you see any of these symptoms:

• A fever in an infant 2 months or younger.
• A fever of 102 or higher at any age.
• Signs of labored breathing, including nostrils widening with each breath, wheezing, fast breathing, the ribs showing with each breath.
• Blue lips.
• Not eating or drinking, with signs of dehydration.
• Ear pain.
• Excessive crankiness or sleepiness.
• If the cough lasts for more than three weeks.
• If the child is getting worse.

Those symptoms can signal that your child has something more serious than a cold.

“You have to know your child,” Taylor says. “With small infants, fever is a major concern, and you need medical advice. If you are worried about your child’s symptoms, at any age, call your pediatrician for advice.”

What About Fevers?

Fever helps the body fight off an infection and does not always need to be treated. But if your child is uncomfortable because of fever or other symptoms of a cold, there are alternatives to cough and cold medicine to help them feel more comfortable. Taylor says they include the following actions:

• Using a clean cool-mist vaporizer or humidifier in a small area near the child’s bed may help moisten the air and decrease the drying of the nasal passages and throat.
• For infants with a stuffy nose, use saline or salt water drops/spray to moisten the nasal passages and loosen the mucus. Then clean the nose with a bulb syringe.
• Acetaminophen or ibuprofen can be used to reduce fever, aches and pains. Take care to use the correct dose. FDA recently published new manufacturing and labeling recommendations for acetaminophen-containing medications used to treat colds, fevers
• and headaches in children.

Giving the Right Dose

“We found that parents often can make errors with liquid medications. It’s often difficult for them to correctly measure liquid medications because they don’t understand what a milliliter is or may be confused about the difference between a teaspoon and a tablespoon,” Taylor says.

How can parents be sure to give the correct dose to their children? Follow the directions on the “Drug Facts”label. FDA encourages drug manufacturers to provide a dosing instrument, such as a syringe or a cup, marked with the correct measurements. Use them—and not household spoons—to measure medication.

”If you have questions or need advice, do ask the pharmacist,” Taylor adds. “She or he can tell you which dosing instrument to use, how much medication to give and how often.”

In the United States, adults have on average about three colds per year, and children have them even more often. Caregivers might be tempted to give children pain relievers, decongestants and other medications for a cold. But often it’s best to fight this common childhood illness with rest and care.

Related Consumer Updates

• Knowing Concentration Before Giving Acetaminophen to Infants
• Reducing Fever in Children: Safe Use of Acetaminophen
• Giving Medication to Children
• Giving Medicine to Children (Video)
• Don't Double Up on Acetaminophen
• OTC Cough and Cold Products: Not For Infants and Children Under 2 Years of Age

1/24/14 Health News: Green Tea Impedes Blood Pressure Medication - 5 Min. Test Identifies Exposure to Second Hand Cigarette Smoke - India Polio Free

’Green Tea 'Can Impede Nadolol Blood Pressure Medicine'

Green tea can weaken the effects of a commonly prescribed blood pressure pill, experts warn. Japanese researchers found the herbal drink blocks special cell transporters that normally help the body absorb the beta-blocker medicine. In tests, people who drank green tea alongside taking their tablets ended up with lower circulating blood levels of the drug nadolol. Experts say consumers need to be aware of this interaction.continue reading

Five Minute Saliva Test to Identify Smokers Rolled Out to Health Schemes, UK

Smokers who need extra incentives to quit the cigarettes this new year should take note that even private health insurance premiums may be reduced if they can prove they have stopped for good - and with the aid of a pioneering test from the University of Birmingham, the proof can be easy to acquire. The Saliva SmokeScreen test is part of the PruHealth free Vitality Healthcheck programme to verify non-smoking in their policy holders, so they can qualify for its unique non-smoker cash back reward. The saliva test, which was developed by Dr Graham Cope continue reading

1.2 Billion Reasons to Celebrate: India Set To Be Polio-free

This is a landmark achievement for global public health and the worldwide effort to eradicate polio. India, which once had the highest number of polio cases in the world, is now polio-free, an achievement reports say the World Health Organisation will certify in February. But it's been a long road to get here. With poor sanitation, densely populated areas and large numbers of people living in extreme poverty, northern states like Uttar Pradesh and Bihar were the 'perfect storm' when it came to the spread of polio. And without the vital collaboration between the Indian government and the global polio eradication initiative – a partnership among Rotary International, Unicef, WHO and the US Centre for Disease Control and Prevention – this may not have been possible.continue reading

Licorice Used as Medicine. Is it Safe???

Licorice is a plant. You are probably most familiar with it as a flavoring in foods, beverages, and tobacco. The root is used to make medicine. Licorice is used for various digestive system complaints including stomach ulcers, heartburn, colic, and ongoing inflammation of the lining of the stomach (chronic gastritis).

Some people use licorice for sore throat, bronchitis, cough, and infections caused by bacteria or viruses. Licorice is also used for osteoarthritis, systemic lupus erythematosus (SLE), liver disorders, malaria, tuberculosis, food poisoning, and chronic fatigue syndrome (CFS).

Licorice is sometimes used along with the herbs Panax ginseng and Bupleurum falcatum to improve the function of the adrenal glands, especially in people who have taken steroid drugs long-term. Steroids tend to suppress the activity of the adrenal glands. The adrenal glands produce important hormones that regulate the body’s response to stress.

Licorice is also used in an herbal form called Shakuyaku-kanzo-to to increase fertility in women with a hormonal disorder called polycystic ovary syndrome. In combination with other herbs, licorice is also used to treat prostate cancer and the skin disorder known as eczema.

Some people use licorice as a shampoo to reduce oiliness in their hair.

Many “licorice” products manufactured in the U.S. actually don't contain any licorice. Instead, they contain anise oil, which has the characteristic smell and taste of “black licorice.”

Licorice interacts with many prescription medicines. Talk to your healthcare provider if you plan to start using licorice.

How effective is it?

Natural Medicines Comprehensive Database rates effectiveness based on scientific evidence according to the following scale: Effective, Likely Effective, Possibly Effective, Possibly Ineffective, Likely Ineffective, Ineffective, and Insufficient Evidence to Rate.

The effectiveness ratings for LICORICE are as follows:

Possibly effective for...

• Heartburn (dyspepsia), when a combination of licorice and several other herbs is used. These other herbs are peppermint leaf, German chamomile, caraway, lemon balm, clown’s mustard plant, celandine, angelica, and milk thistle. The combination is packaged as a product called Iberogast or STW5. It was developed in 1961 in Germany. Research suggests that taking 1 mL orally three times daily over a period of 4 weeks significantly reduces severity of acid reflux and associated pain, cramping, nausea, and vomiting.

Insufficient evidence to rate effectiveness for...

• Muscle cramps. Preliminary clinical research suggests taking a specific combination of licorice and peony (Shakuyaku-kanzo-to) might reduce muscle cramps in people with liver disease (hepatic cirrhosis) or in people undergoing treatment for kidney failure (hemodialysis).
• Hepatitis. There is some evidence that some of the chemicals in licorice might be effective in treating hepatitis B and hepatitis C when given intravenously (by IV). But the studies involved too few patients to draw firm conclusions.
• Stomach ulcers. There is some evidence that specially prepared licorice will speed the healing of stomach ulcers.
• Weight loss. There is conflicting information about the use of licorice for weight loss. Licorice seems to reduce body fat. However, it causes water retention that can offset any change in body weight.
• Atopic dermatitis (eczema). There is conflicting evidence about the effectiveness of licorice for treating eczema.
• Arthritis.
• Lupus.
• Infections.
• Infertility.
• Cough.
• Chronic fatigue syndrome (CFS).
• Prostate cancer.
• Other conditions.

More evidence is needed to rate the effectiveness of licorice for these uses.

The chemicals contained in licorice are thought to decrease swelling, thin mucus secretions, decrease cough, and increase the chemicals in our body that heal ulcers.

Are there safety concerns?

Licorice is LIKELY SAFE for most people when consumed in amounts found in foods. It is POSSIBLY SAFE when consumed in larger amounts use as medicine, short-term. However, it is POSSIBLY UNSAFE when used in large amounts for more than four weeks. Consuming 30 grams or more of licorice daily for several weeks can cause severe side effects including high blood pressure, low potassium in the blood, weakness, paralysis, and occasionally brain damage in otherwise healthy people. In people who eat a lot of salt or have heart disease, kidney disease, or high blood pressure, as little as 5 grams per day can cause these problems.

Other side effects of licorice use include tiredness, absence of a menstrual period in women, headache, water and sodium retention, and decreased sexual interest and function in men.

People who chew tobacco flavored with licorice might develop high blood pressure and other serious side effects.

Special precautions & warnings:

Pregnancy and breast-feeding: It is UNSAFE to take licorice by mouth if you are pregnant. It might cause a miscarriage or early delivery. Not enough is known about the safety of licorice during breast-feeding. Don’t use licorice if you are pregnant or breast-feeding.

High blood pressure: Licorice can raise blood pressure. Don’t consume large amounts of it if you have high blood pressure.

Heart disease: Licorice can cause the body to store water, and this can make congestive heart failure worse. Licorice can also increase the risk of irregular heartbeat. Don’t consume licorice if you have heart disease.

Hormone-sensitive conditions such as breast cancer, uterine cancer, ovarian cancer, endometriosis, or uterine fibroids: Licorice might act like estrogen in the body. If you have any condition that might be made worse by exposure to estrogen, don’t use licorice.

A muscle condition caused by nerve problems (hypertonia): Licorice can cause the level of potassium to drop in the blood. This can make hypertonia worse. Avoid licorice if you have hypertonia.

Low potassium levels in the blood (hypokalemia): Licorice can lower potassium in the blood. If your potassium is already low, licorice might make it too low. Don’t use licorice if you have this condition.

Sexual problems in men: Licorice can lower a man’s interest in sex and also worsen erectile dysfunction (ED) by lowering levels of a hormone called testosterone.

Kidney disease: Overuse of licorice could make kidney disease worse. Don’t use it.

Surgery: Licorice might interfere with blood pressure control during and after surgery. Stop taking licorice at least 2 weeks before a scheduled surgery.

Are there interactions with medications?

Major

Do not take this combination.

Warfarin (Coumadin)

Warfarin (Coumadin) is used to slow blood clotting. The body breaks down warfarin (Coumadin) to get rid of it. Licorice might increase the breakdown and decrease the effectiveness of warfarin (Coumadin). Decreasing the effectiveness of warfarin (Coumadin) might increase the risk of clotting. Be sure to have your blood checked regularly. The dose of your warfarin (Coumadin) might need to be changed.

Moderate

Be cautious with this combination.

Digoxin (Lanoxin)

Large amounts of licorice can decrease potassium levels in the body. Low potassium levels can increase the side effects of digoxin (Lanoxin).

Estrogens

Licorice seems to change hormone levels in the body. Taking licorice along with estrogen pills might decrease the effects of estrogen pills.

Some estrogen pills include conjugated equine estrogens (Premarin), ethinyl estradiol, estradiol, and others.

Ethacrynic acid (Edecrin)

Licorice can cause the body to get rid of potassium. Ethacrynic acid (Edecrin) can also cause the body to get rid of potassium. Taking licorice and ethacrynic acid (Edecrin) together might cause potassium to become too low.

Furosemide (Lasix)

Licorice can cause the body to get rid of potassium. Furosemide (Lasix) can also cause the body to get rid of potassium. Taking licorice and furosemide together might cause the potassium levels in your body to go too low.

Medications changed by the liver (Cytochrome P450 2B6 (CYP2B6) substrates)

Some medications are changed and broken down by the liver. Licorice might decrease how quickly the liver breaks down some medications. Taking licorice along with some medications that are broken down by the liver can increase the effects and side effects of some medications. Before taking licorice, talk to your healthcare provider if you take any medications that are changed by the liver.

Some of these medications changed by the liver include ketamine (Ketalar), phenobarbital, orphenadrine (Norflex), secobarbital (Seconal), dexamethasone (Decadron), and others.

Medications changed by the liver (Cytochrome P450 2C9 (CYP2C9) substrates)

Some medications are changed and broken down by the liver. Licorice might change how the liver breaks down some medications. Taking licorice along with medications that are broken down by the liver might increase or decrease the effects of these medications. Before taking licorice, talk to your healthcare provider if you are taking any medications that are changed by the liver.

Some medications changed by the liver include celecoxib (Celebrex), diclofenac (Voltaren), fluvastatin (Lescol), glipizide (Glucotrol), ibuprofen (Advil, Motrin), irbesartan (Avapro), losartan (Cozaar), phenytoin (Dilantin), piroxicam (Feldene), tamoxifen (Nolvadex), tolbutamide (Tolinase), torsemide (Demadex), and warfarin (Coumadin).

Medications changed by the liver (Cytochrome P450 3A4 (CYP3A4) substrates)

Some medications are changed and broken down by the liver. Licorice might change how the liver breaks down some medications. Taking licorice along with medications that are broken down by the liver might increase or decrease the effects of some medications. Before taking licorice, talk to your healthcare provider if you are taking any medications that are changed by the liver.

Some medications changed by the liver include lovastatin (Mevacor), ketoconazole (Nizoral), itraconazole (Sporanox), fexofenadine (Allegra), triazolam (Halcion), and many others.

Medications for high blood pressure (Antihypertensive drugs)

Large amounts of licorice seem to increase blood pressure. By increasing blood pressure, licorice might decrease the effectiveness of medications for high blood pressure.

Some medications for high blood pressure include captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), amlodipine (Norvasc), Hydrochlorothiazide (HydroDIURIL), furosemide (Lasix), and many others.

Medications for inflammation (Corticosteroids)

Some medications for inflammation can decrease potassium in the body. Licorice might also decrease potassium in the body. Taking licorice along with some medications for inflammation might decrease potassium in the body too much.

Some medications for inflammation include dexamethasone (Decadron), hydrocortisone (Cortef), methylprednisolone (Medrol), prednisone (Deltasone), and others.

Water pills (Diuretic drugs)

Large amounts of licorice can decrease potassium levels in the body. "Water pills" can also decrease potassium in the body. Taking licorice along with "water pills" might decrease potassium in the body too much.

Some "water pills" that can deplete potassium include chlorothiazide (Diuril), chlorthalidone (Thalitone), furosemide (Lasix), hydrochlorothiazide (HCTZ, HydroDIURIL, Microzide), and others.

Are there interactions with herbs and supplements?

Herbs that affect the heart

Using too much licorice can decrease potassium in the body. This can damage the heart. Using licorice with herbs that can damage the heart might make this effect worse. Herbs that might damage the heart include digitalis, lily-of-the-valley, pheasant's eye, and squill.

Stimulant laxative herbs

Using too much licorice can decrease potassium in the body. Herbs that have a stimulant laxative effect can also lower potassium in the body. Using licorice along with these herbs can increase the risk of lowering potassium levels too much. Stimulant laxative herbs include aloe vera, alder buckthorn, European buckthorn, cascara sagrada, castor oil, rhubarb, and senna.

Are there interactions with foods?

Grapefruit juice

Drinking grapefruit juice when taking licorice might increase licorice's ability to cause potassium depletion.

Salt

Licorice use can increase sodium and water retention and increase blood pressure. Also, eating a lot of salt can make the side effects of licorice even worse.

What dose is used?

The following doses have been studied in scientific research:

BY MOUTH:

• For upset stomach: A specific combination product containing licorice (Iberogast, Medical Futures, Inc) and several other herbs has been used in a dose of 1 mL three times daily.

Other names

Acide Glycyrrhizique, Acide Glycyrrhizinique, Alcacuz, Alcazuz, Bois Doux, Bois Sucré, Can Cao, Chinese Licorice, Deglycyrrhized Licorice, Gan Cao, Gan Zao, Glabra, Glycyrrhiza, Glycyrrhiza glabra, Glycyrrhiza glabra typica, Glycyrrhiza glabra violacea, Glycyrrhiza glabra glandulifera, Glycyrrhiza Radix, Glycyrrhiza uralensis, Glycyrrhizae, Glycyrrhizic Acid, Glycyrrhizinic Acid, Isoflavone, Jethi-Madh, Kanzo, Lakritze, Licorice Root, Liquiritiae Radix, Liquirizia, Mulathi, Mulethi, Orozuz, Phytoestrogen, Phyto-œstrogène, Racine de Réglisse, Racine Douce, Radix Glycyrrhizae, Régalissse, Regaliz, Reglisse, Réglisse, Réglisse Déglycyrrhisée, Réglisse Espagnole, Réglisse Russe, Regliz, Russian Licorice, Spanish Licorice, Subholz, Sussholz, Sweet Root, Yashtimadhu, Yashti-Madhu, Yashti-Madhuka, Zhi Gan Cao.

Source National Institute of Health