HRT DECREASE SUBSTANTIALLY CVD RISK IN WOMEN

Hormone-replacement therapy (HRT) in postmenopausal women with a mean age of 50 significantly reduced the risk of the combined end point of mortality, MI, or heart failure in a new randomized Danish study published online October 9, 2012 in BMJ [1]. The participants, who used HRT for more than 10 years, were not at significantly increased risk of breast cancer or stroke either, report Dr Louise Schierbeck (Hvidovre Hospital, Denmark) and colleagues.

"This is the longest randomized trial with hard end points, and we found a 50% reduction in cardiovascular end points for the women who took HRT, and there was no increased risk of cancer," Schierbeck told heartwire . The women were also followed for a further six years after discontinuation of randomized treatment, she noted.

Schierbeck says the findings, in 1000 women, confirm the "timing hypothesis." In 2002, primary results from the Women's Health Initiative (WHI) showed no cardiovascular benefit from HRT--something that had been suggested by numerous observational trials--and even an indication there may be harm; this led to the widespread abandonment of this therapy. But subsequent analyses of WHI, and data from other studies, have suggested that the time at which HRT is first prescribed is key. The women in this Danish study were 13 years younger, on average, than the women in WHI (mean age 63 years). "It doesn't make much sense to start treating women 13 years after menopause for menopausal symptoms. It's important to initiate the treatment at menopause and not many years later," she observes.

Asked to comment on the new findings, Dr Howard N Hodis (UCLA) told heartwire , "Until this came out there had been no trial to directly study the estrogen cardioprotective hypothesis. This is unique, because it is the only study to have looked at women, a priori, randomized basically at the time of or just a little beyond menopause. And that's a really important point that I think some of the detractors have glossed over. The women averaged 50 years old, just like the women that we treat who come in close to the menopause and say, 'I want hormones,' because they are having symptoms. So scientifically, this is a very important trial."

Ob/gyn Dr James Liu (Case Western Reserve University School of Medicine, Cleveland, OH) said: "This paper adds to the evolving data on HRT for newly menopausal women in the under-age-60 category. The study conclusions are worth noting and are statistically significant and congruent with older observational studies such as the Nurses' Health Study and the subgroup-stratified analyses of the WHI cohort from 50 to 60. Thus, there are two randomized trials that have congruent data." Among the "surprising points," says Liu, are no increase in breast cancer risk for the 16 years of follow-up and the fact that stroke risk was not increased.

Hodis also addressed criticisms that the new Danish trial is too small to yield any meaningful results. "Although the sample size is small, there are 16 years and 20 000 women-years of follow-up." Schierbeck concurs. "We had a very long study, so there are 10 000 person-years of randomized treatment, and we do have a significant outcome in 1000 women, so it's clinically relevant."

Greater-Than-50% Reduction in CV Events Without Increasing Cancer Risk

The 1006 healthy women aged 45 to 58 who were recently postmenopausal or had perimenopausal symptoms were participants in the Danish Osteoporosis Prevention Study and were randomized to receive HRT (n=502) or no treatment (control, n=504).

The primary end point was a composite of death, hospitalization for heart failure, and MI. Secondary end points were the individual components of the primary end point and admission to the hospital for stroke. Safety end points included death or a diagnosis of breast cancer or other cancer grouped together and admission to the hospital for pulmonary embolism or deep venous thrombosis (DVT).

The women in the treated group with an intact uterus received 2-mg synthetic 17-{:beta:}-estradiol for 12 days, 2 mg 17-{:beta:}-estradiol plus 1 mg  norethindrone acetate for 10 days, and 1 mg 17-{:beta:}-estradiol for six days (Trisekvens, Novo Nordisk, Denmark). In women who had undergone hysterectomy, first-line treatment was 2 mg 17-{:beta:}-estradiol a day (Estrofem, Novo Nordisk, Denmark). Other treatment modalities were offered to those who experienced side effects or insufficient relief of symptoms.

The planned duration of the study was 20 years. However, as the WHI data--which came out in 2002 around the time of the 10-year visit--indicated that use of HRT might result in more harm than benefit, the participants were advised to stop treatment. But they were followed for death, cardiovascular disease, and cancer for up to 16 years.

After 10 years of intervention, there was a 52% reduction in the primary composite end point of death, MI, or heart failure, and this was not associated with an increase in any cancer. Schierbeck said numbers were too small to draw any meaningful conclusions on venous thromboembolism (VTE), although she acknowledges that HRT is known to increase the risk of VTE but pointed out, "This is a less serious event than a CV event."

After 16 years, the reduction in the primary composite outcome was still present and still not associated with an increase in any cancer, something both Schierbeck and Hodis say is "reassuring," particularly in terms of breast cancer.

Results After 10 Years of Intervention in Danish Osteoporosis Prevention Study

End point	HRT group (n=502), n	Control group (n=504), n	Hazard ratio	95% CI	p
Primarya	16	33	0.48	0.26– 0.87	0.015
Mortality	15	26	0.57	0.30–1.08	0.084
Cancer	36	39	0.92	0.58–1.45	0.71
Breast cancer	10	17	0.58	0.27–1.27	0.17
DVT	2	1	2.01	0.18– 22.16	--b
Stroke	11	14	0.77	0.35–1.70	0.70

a. Composite end point of death, MI, or heart failure

b. Numbers too low to calculate p

Emotion Has Overtaken the Evidence in Discussions About HRT

Hodis says emotion has long overtaken reason in the HRT debate. "We have had observational studies for the past 50 years in this field, at least 40 of them, and they are all consistent--and you just don't see that in medicine--across two very important outcomes: they reduced cardiovascular disease and they reduced mortality" in women around the time of menopause, he asserts. "But when WHI was conducted, it was done in women who were 12 years or more past menopause. These are two completely different populations of women.

"In all of the emotions after WHI, that 'hormones are killing women'--which is absolutely ridiculous--nobody sat back and said, 'Where is the evidence to support that?' The guidance that unfortunately came out of the results of WHI was 'lowest dose for shortest period of time possible.' Now what we have is a well-conducted, 10-year randomized trial that clearly shows that short-term usage of these products is not going to derive maximum benefits for women."

And other "important" data have come out recently in support of HRT, he notes, including the KEEPSstudy, reported just last week. "This was the largest trial ever done to assess mood, and it showed positive effects in terms of anxiety, depression, and tension, and no adverse effects."

Schierbeck says: "It is a shame that so many women are anxious about HRT, because it's so important for life quality around the time of menopause." She agrees the current mantra seems to be that if a woman wants to use HRT to "go with the lowest dose for the shortest time," but she hopes that this study will have a major impact and influence international societies working on new guidelines.

Asked what she thinks the optimal duration of HRT should be, she said: "I don't think we can set a time limit on it. At least for 10 years, we didn't find any serious side effects."

Hodis says he does not believe there will be a seismic shift in recommendations, because doctors and women have lived in fear of HRT for so long, but "people will look at this and say we can feel comfortable going longer with therapy." Personally, he says, "I'm neither a proponent nor an opponent of HRT: I use these products in women, with or without symptoms, who want to be put on them, with caveats--for example, not if they have had blood clots. They do have risks, but they are so low, and certainly no higher than many other drugs we use."

Where Next? HRT and Chronic Disease Prevention

Hodis also believes there is a role for HRT in chronic disease prevention. "The data strongly indicate that hormones are an excellent prevention for chronic diseases, including bone fractures and heart disease." And although the reduction in deaths in the Danish study was not significant, Hodis says the totality of evidence points to HRT adding "almost two years" to the life of a woman, with the additional benefit that hormones "are cost-effective, coming in at around $2300 per quality-adjusted life-year [QALY]. There's nothing else in women that does that. Statins do not extend life and they cost $50 000 $100 000 per QALY."

But not everyone agrees. KEEPS and WHI trialist Dr JoAnn E Manson (Brigham and Women's Hospital, Boston, MA) maintained last week that HRT should be used only for the treatment of menopausal symptoms.

"We certainly would not say at this point in time to initiate hormone therapy for the express purpose of trying to prevent heart disease or cognitive decline; the evidence is not to that point," she said in an interview. "But for women who have menopausal symptoms and who are considering HRT to reduce their symptoms and improve their quality of life related to these symptoms, there were many favorable effects seen of taking HRT for four years."

Differences in Doses of Hormones, Medication Schedules

Liu says there are also some limitations to the Danish study that are pointed out by the authors, but others that are not. The latter include the fact that the medication used was lower dose than the 0.625-mg conjugated equine estrogen traditionally used [in the US] and in the WHI, although "there are some who may state that the 2-mg estradiol dose is similar," he observes. And the progestinused is different.

In addition, the type of dosing is different: "The Danish study used cycle estrogen and progestin in a 28-day dose-pack form, and the pattern of estrogen-progestin administration is somewhat unique in that the last six days used a lower estradiol dose of 1 mg.  Thus, the estrogen exposure is not uniform across the 28 days. This dose is also different from women with hysterectomy who received 2-mg estradiol continuously. This contrasts with WHI, which used continuous combined estrogen/progestin daily for those women with a uterus."

And the data end points for the Danish study--due to its small size--are combined for women on estrogen alone (due to hysterectomy) and cyclic estrogen-progestin. "This analyses is different from the WHI approach, where there were two separate studies (those with a uterus were in a separate study from those with a hysterectomy) with larger cohort sizes."

Top 5 Health Tips for Gaining Lean Muscles Without Fat

Top 5 Health Tips for Gaining Lean Muscles Without Fat

Here in this Health Tips blog I am going to present an article which really helps every one especially the people who goes for a GYM.

Here are top 5 health pro tips that will help everyone to keep or maintain lean muscles without getting fat in your body.

1. Eat Clean and Hygienic Food Which has Lots and Lots of Calories

Eating clean and Hygienic food every day will help every individual to maintain their body with good shape. The food you in take much contains protein, low-glycemic carbs, health dietary fats and etc. Try to have some organic foods regularly in order to sustain much energy which will always help you to make you feel bit relaxed and happier through out the day.

2. Try to eat foods which contains much Carbohydrate

This is really a beautiful tips for having a lean muscles. Overdose of Carbs will leads to Hyper insulin which will ultimately leads to increase in Fat content in the human. But it is also not to avoid the Carbs in your meals totally. People are prone to sit in one place and do their work most of the time. It is better to center your carb consumption around your sitting place. Here are few carbs which are present in sweet potatoes, brown rice, whole grains, oatmeal..

3. Healthy fats don’t make you fat!

Dietary Fats don’t make you fat. Recent research has said that Fats have 9 calories per gram, but carbs and proteins have 5 calories per gram. Less calories per gram will help you in getting your muscles lean. Fats from rich source like avocado, whipped butter, eggs, nuts are a must if you want to put on size. Avoid eating saturated fats from junk foods, snacks, chips and eat.

4. Say no to SMOKE

This is the most important Health tips in order to Lean Muscles. Smoking is really bad for your health. But if you can quit the smoking, then your life will be better. Here in this post, i am going to tell you some important points and benefits of quitting the smoking and how it can be lead to a healthy lifestyle. 

Read this article Health Benefits of Quitting Smoking

5. High Intensity Cardio is a major key fact in fat loss

Don’t overdo Cardio, While High Intensity Cardio may be a solution for fat loss, going overboard with it'll solely kill your lean muscle. Bulking up is primarily regarding conserving calories and victimization them for the correct physical exercise. Limit your HIIT to 2-3 days per week and focus a lot of on strength coaching.

6. Lift only weights that are possible to you.

Lift only as heavy as you can. Many persons will try to lift heavy weights when compared to their weight, thinking that this would work out in making you lean. But it is not so. Lift only as heavy as you can and gradually scale up your weights.

FOOD WITH ORAL CANCER DRUGS?

Are oral oncology drugs being mislabeled? Maybe.
Most oral cancer drugs stipulate that they should be taken in a fasting state, but some actually have better bioavailability when taken with food. This is particularly true for the new prostate cancer drug abiraterone acetate (Zytiga), which has a greater interaction with food than any other marketed drug, yet it is labeled to be taken when fasting.
These points are highlighted in a comment published in the October 20 issue of the Journal of Clinical Oncology by Mark J. Ratain, MD, professor of medicine and director of the Center for Personalized Therapeutics at the University of Chicago, Illinois.
"My major concern is safety," Dr. Ratain told Medscape Medical News. "Very few patients would anticipate that the consequences of taking their medications with food...would be an effective overdose."
In the case of abiraterone acetate, the dose of the drug could be increased 10-fold by eating breakfast half an hour after taking the drug, he writes.
Dr. Ratain notes that food interactions are described in the labeling of many drugs, but are notably absent in the labeling of new oral cancer agents.
Most drugs can be taken either with or without food, he explains, because the effects of food are not clinically significant to drug absorption. There are cases in which absorption is decreased by food; generally, the labeling on those drugs instructs that they be taken on an empty stomach. Similarly, labeling on drugs for which absorption is enhanced by food typically instructs that they be ingested with meals.
"However, a recent study of oral agents approved by the US Food and Drug Administration [FDA] in the last 10 years demonstrated that oral oncology drugs have generally been labeled fasting, despite food effects as large as a 4-fold increase in bioavailability," Dr. Ratain notes.
Bias in Labeling?
This apparent bias for fasting labeling in cancer drugs is exemplified with abiraterone, he notes. Abiraterone, which was approved earlier this year in the United States for the treatment of metastatic prostate cancer, has a greater food interaction than any drug currently on the market. Depending on the fat content, food can increase drug exposure 5- to 10-fold, yet it is labeled to be taken in a fasting state, Dr. Ratain points out.
The effect of a high-fat meal indicates "that absolute bioavailability in the fasting state is no more than 10%," says Dr. Ratain, and is likely due to the low absorption rate under fasting conditions; 77% of the drug is excreted as abiraterone (or its prodrug acetate) in the stool.
"In addition, there is marked interindividual pharmacokinetic variability, with a coefficient of variation in the plasma concentration area under the curve of 59% under labeled conditions," he notes.
It is unclear why this faulty labeling is occurring, or why the FDA has not been more stringent about proper labeling for oral oncology drugs, Dr. Ratain said. He told Medscape Medical Newsthat the FDA has not responded to his inquiries and "essentially stonewalled" him because of the confidentiality of their discussions with sponsors.
"The blame could be assigned to sponsors, the Office of Oncology Drug Products, and/or the Office of Clinical Pharmacology and Biopharmaceutics," he said. "Given that there are multiple sponsors, all of whom who have a different approach to oncology..., the evidence points to an FDA origin."
Oral Drugs Relatively New
Alex Adjei, MD, PhD, who was approached by Medscape Medical News for independent comment, explained that until recently, oncology drugs have generally been given intravenously; for other diseases, oral drugs have been in common use for many years.
Perhaps that is why there has not been that much attention on the food-effect data, Dr. Adjei hypothesized. He is chair of the Department of Medicine at Roswell Park Cancer Institute, in Buffalo, New York.
"In clinical trials, we tend to give the drugs on an empty stomach," he said. "So that was how the drug was tested and that was how it was approved. We don't go back and change the label."
Dr. Adjei pointed out that unlike intravenous drugs, there is considerable variation in the way oral drugs are absorbed. "We try to simplify it by giving them on an empty stomach," he said.
Food-Effect Data Ignored
In a study published last year (Clin Cancer Res. 2010;16:4446-4451), Dr. Ratain and his colleague, Soonmo Peter Kang, MD, also from the University of Chicago, evaluated the effect of food on 99 oral agents that received FDA approval from January 2000 to May 2009. They compared food-labeling patterns between oncology and nononcology drugs using Fisher's exact test.
Food had a significant effect on drug bioavailability in 34 of the 99 drugs evaluated. In cases where food markedly enhanced bioavailability, 8 of 9 nononcology drugs were labeled to be taken with food to take advantage of the food–drug interaction. However, all oncology agents were labeled to be taken in "fasted" states (P = .01).
"The food-labeling pattern of recently approved oral oncology drug products is inconsistent with fundamental principles of oral drug delivery," they write. "The labels of 3 agents (erlotinib, nilotinib, and lapatinib) minimized bioavailability through food restrictions, which is in contrast to the labeling principles used for all other classes of oral agents."
In an editorial that accompanied the study by Drs. Ratain and Kang (Clin Cancer Res. 2010;16:4305-4307), Rajul K. Jain, MD, from the University of Texas M.D. Anderson Cancer Center, Houston, and colleagues explained that the effects of food are complex, and that multiple factors determine final labeling recommendations. "When analyzing the label given to any product or product class, all of the potential influencing factors should be considered," they said.
They also noted that "sponsors are encouraged to conduct food-effect studies early in a product's development so the results can be implemented into larger clinical trials."
In his comment, Dr. Ratain refers back to that editorial, and points out that the agency has "expressed concern about the potential for high intraindividual variability in cancer patients resulting from variability in oral intake secondary to disease or concurrent medications." This appears to indicate a preference for labeling drugs to be used when fasting, even if their bioavailability would be substantially increased when taken with food.
He explains that there isn't any evidence that this concern applies to all oral oncology drugs, and that there is no evidence that intraindividual variability in diet is greater for cancer patients than for those with other life-threatening conditions who also take daily oral drugs.
"If the US Food and Drug Administration were truly concerned about intraindividual variability in diet, why has this never come up in the labeling of nononcology drugs?" he asks.
He notes that the FDA was aware of the food-effect data from early studies of abiraterone and could have required at least 1 randomized study to be conducted to review this, so that it could have been labeled to be taken with food. The FDA has the authority to require such studies as a postmarketing requirement, but chose not to.
With the risk for poor adherence to food-effect labeling, there is a risk for overdose or underdose of a given drug, with the more serious being overdose, Dr. Ratain says.
In addition to this safety issue, there are economic implications, Dr. Ratain notes.
The standard dose of abiraterone for men without liver problems is 1000 mg once daily. But because the bioavailability of the drug is greatly increased when taken with food, it would be interesting to have studies of abiraterone at a dose of 250 mg once daily, administered with a standard breakfast. If this approach is shown to be safe and effective, it could save patients and their payers approximately $3750 per month at current prices.
"It also would send a message to the pharmaceutical industry that flawed drug development has financial consequences," he notes, "along with potential risks of product liability because of defective labeling."
He concludes: "After all, given the high attrition rate for oncology drugs, do we really need to flush our few successful products down the toilet?"
Impracticalities of Dosing and Diet
Lawrence J. Lesko, PhD, FCP, former director of the Office of Clinical Pharmacology at the FDA's Center for Drug Evaluation and Research, and a coauthor of the editorial by Dr. Jain, pointed out that the principal of labeling is consistent safety.
"The most consistent way to take drugs is on an empty stomach," said Dr. Lesko, who is now at the Department of Pharmaceutics at the College of Pharmacy at the University of Florida in Gainesville. "It would be impractical to expect that patients are going to adhere to a specific diet when taking these drugs. And it is often unclear what 'food' may mean to the patient. Is it a glass of juice, breakfast cereal, a cheeseburger?"
The goal is to minimize the variability, he told Medscape Medical News. "Food studies are generally conducted in healthy volunteers and not cancer patients. Labeling can't be done on a theoretical basis; it has to reflect what was done in the study."
Dr. Lesko noted that another problem with tying an oral drug dose to food is that many cancer patients have problems with appetite, nausea and vomiting, and gastrointestinal motility. "Their appetite can change on any given day," he said. "Some days, they may not be able to tolerate a high-fat meal, for example, which raises the bioavailability of abiraterone. It would just be impractical to do this on a day-to-day basis."
The other issue that Dr. Ratain focuses on in his comment is the comparison of oncology and nononcology drugs, Dr. Lesko pointed out. "But you really can't compare them."
For most nononcologic agents, food doesn't matter, so it isn't that important how the product is labeled, he said.
But that is not the case with oral oncologic agents. "Every drug in oncology has a narrow therapeutic index, and taking the drug with food could affect the therapeutic range," he said. "The labels are intended to minimize variability and mimic approval data."

Health Benefits of Quitting Smoking - Health Tips

Health Benefits of Quitting Smoking

Smoking is really bad for your health. But if you can quit the smoking, then your life will be better.
Here in this post, i am going to tell you some important points and benefits of quitting the smoking and how it can be lead to a healthy lifestyle. The post deals with

Health Tips and the health benefits of stopping smoking.

1. Smoking Smell:

If you smoke, then your clothes, home, will smells very bad. This will make you away from your family and friends. Just try to follow these health tips and avoid the smoking and makes your lifestyle a better in future along with your families and friends.

2. No more chronic cough:

We all know that every people who smoke will cough more. Due to this the throat will get problem and drying between tongue and stomach.

3. Improve fertility:

If you are going to quit the smoking, then it helps in improving the lining of the worm and will help in increasing the men's sperm count and more potent.

4.Looks like young:

Stopping or quitting smoking will helps in making you young and your wrinkles will be good.The skin of the people who quits smoking will get more nutrients and oxygen.

5. Whiter teeth:

Your teeth will become whiter when you stop smoking.

6. Better Breathing:

People who quits smoking will breathe more easily and comfortably.

7. Less Stress:

The scientific shows that peoples who quits smoking are prone to lower stress.

8. More Energy:

Your blood circulation will be increased if you stop smoking. Quitting also helps in increasing your immune system.