Tuesday, December 22, 2009

The vitamin jab that shrinks tumours in a day

A vitamin jab that shrinks tumours in a day is being hailed as a powerful new treatment for cancer.

British researchers who are testing the therapy say injecting an extract of vitamin E into the bloodstream has a rapid effect.

Within 24 hours, tumours begin to shrivel and after ten days they have almost completely disappeared.

So far, research has focused on the vitamin's ability to find and destroy skin cancers.

But scientists from the University of Glasgow and the University of Strathclyde, who led the research, are confident it will work for other types of tumours, too.

Vitamin E is vital for helping the body to fight illness and is found in foods such as vegetable oils, cereals, nuts, green vegetables and eggs.

It is rich in antioxidants that protect against disease by blocking damage from free radicals - harmful molecules that attack cells in much the same way as rust rots a car

But for the past few years, one particular compound found in vitamin E has attracted attention as a potential medicine that can attack cancer once it has set in.

Tocotrienol is an extract of vitamin E found in abundance in palm oil, cocoa butter, barley and wheat germ.

In the mid-Nineties, scientists carrying out laboratory tests discovered the ability of tocotrienol to halt the growth of breast cancer cells.

Since then, there have been several studies to see if injecting the vitamin extract into the body can help women who have a tumour.

But most failed, for several reasons.

First, much of the extract ended up floating around the bloodstream, as there was no easy way of directing it towards the cancer.

Second, very high quantities of tocotrienol can be toxic to healthy tissue as well as cancerous ones. And there is the added concern that vitamin E supplements have in the past been linked to an increased risk of lung cancer.

The latest breakthrough gets round all of these by smuggling the vitamin extract past healthy cells and making sure it hits its only target - the tumour.

To do this, scientists encapsulated the vitamin extract inside thousands of microscopic bubbles made from fat.

This meant the tocotrienol could travel through the body without damaging healthy cells.

Then, to make sure the cargo-laden bubbles headed straight for the tumour, the researchers coated them with the protein transferrin.

'This new formulation proved to be efficient and has had extremely encouraging results'

This has the job of escorting iron through the bloodstream to where it is needed, so that it can be absorbed by cells.

Cancer cells need a rich supply of iron in order to keep reproducing. This means they have large numbers of receptors on their surface designed to attract transferrin and the iron it is carrying.

By disguising the tumour-busting vitamin inside a bubble, the scientists were able to sneak it inside the cancer cell, where it launched its attack.

'This new formulation proved to be efficient and has had extremely encouraging results,' says research leader Dr Christine Dufés.

A separate British trial, due to end in 2012, is looking at whether vitamin E can stop bladder cancer returning in patients who are in remission.

Cancer Research UK voiced concerns about vitamin E supplements' previous link with lung cancer and said the new treatment's safety would have to be thoroughly tested before it could be widely used.

'This research is at an early stage and more work is needed before we'll know if this could be a viable tool in the future,' says health information officer Dr Jodie Moffat.

'Previous studies have found high doses of vitamin supplements can actually increase the risk of certain types of cancer, which highlights just how important testing with people is.' 


The disappearing bandage that fights infections and saves lives

A bandage that gradually releases infection-fighting drugs and then dissolves once the wound has healed could help thousands of burns victims.

The high-tech dressing, pioneered at Tel Aviv University in Israel, is designed to combat the high rate of infections among burns patients.

It's estimated that as many as 70 per cent of patients with very severe burns die from infections that penetrate the body through damaged skin and wounds.

Standard care involves regular cleaning and changing of bandages, which can disrupt the healing process.

One of the major problems doctors face is that if these kinds of wounds are too dry, they won't heal fully; if they are too moist, there is a high risk of contamination by bacteria.

To get round this, Israeli scientists have developed special fibres that are woven in such a way that they can 'store' significant quantities of antibiotic drugs.

These fibres are used to make a dressing that sits on top of a burn and allows the medicine to seep slowly into the wound. 

The fibres are also biodegradable, which means that after a few days they dissolve harmlessly, removing the need to change the bandage constantly and expose the wound.

Tests show the experimental dressing can wipe out dangerous bacteria within days.

'We've developed the first wound dressing that releases antibiotics and biodegrades in a controlled manner,' says Professor Meital Zilberman, who is a member of the research team.


Friday, December 11, 2009

The Influence of TheTourniquet on blood draw

[1] Various methods are used to obtain specimens for hematocrit determination in neonates. We evaluated arterial sampling and found this method to be acceptable. Arterial values correlated closely with simultaneously obtained venous samples. Venous blood obtained with a tourniquet had a significantly higher hematocrit than that obtained without a tourniquet.

[2] Influence of tourniquet application on venous blood sampling for serum chemistry, hematological parameters, leukocyte activation and erythrocyte mechanical properties

Background: Venous blood sampling is usually performed using a tourniquet to help locate and define peripheral veins to achieve successful and safe venipuncture. Despite widespread usage of tourniquets for venipuncture by medical and laboratory staff, very few are aware of the effects of tourniquet application on laboratory parameters. In addition, definitive guidelines regarding when and how to use a tourniquet for blood sampling are lacking. The aim of the present study was to define the optimal sampling time after tourniquet removal to avoid adverse impact on laboratory analytes.

Methods: Blood oxygen and carbon dioxide partial pressure, pH, oxyhemoglobin saturation (satO2), hematological parameters, serum electrolyte concentrations, erythrocyte, deformability and aggregation, leukocyte activation and nitrite/nitrate concentrations obtained 180 s after tourniquet release were compared with baseline values for 10 healthy subjects.

Results: Blood gases, hematological parameters and serum electrolyte levels were not affected by the application and removal of a tourniquet. However, there were significant decreases in erythrocyte deformability at 90, 120, 180 s, and increases in erythrocyte aggregation at 5 and 30 s following removal of the tourniquet. A significant increase in granulocyte respiratory burst at 60 s was observed, confirming leukocyte activation due to application of the tourniquet. There were no significant alterations of blood nitrite/nitrate levels.

Conclusions: Our blood sampling technique which mimicked the application and release of a tourniquet indicated unaltered values for routine blood gases, hematological testing and serum electrolyte levels. Conversely, hemorheological measurements can be affected. Therefore, it is strongly recommended that tourniquet application should be avoided during blood sampling or, if this is not possible, the procedure should be well standardized and details of the sampling method should be reported.

[3] Additives and order of draw

The tubes in which blood is transported back to the laboratory contain a variety of additives or none at all. It is important to know which the laboratory requires for which test. In general whole blood needs to be mixed with EDTA which chelates calcium to prevent it clotting, unless the clotting time is the test to be measured in which citrates is used. The majority of biochemistry tests are performed on serum and so either a plain tube or a clotting accelerator is used. This clotting accelerator can interfere with some assays and so a plain tube is recommended in these cases but will obviously delay the result. Some assays also want whole blood but the EDTA can interfere and in this case Lithium Heparin is an alternative.

With the vacuum tube system, the needle pierces the top of the sample tube and will potentially come into contact with the additives in the tube. As it is a hollow needle some of this can be carried into the next tube and contaminate it. The most likely additive to cause trouble is EDTA which will affect the coagulation time assays and by chelating some of the metal ions may interfere with some of the biochemistry results(especially potassium). Thus EDTA samples should be drawn last in most cases and plain tubes drawn first.


 Therefore : the serum calcium level will not get affected by using the tourniquet.

Tuesday, September 15, 2009

How drugs work

Prescription Drugs Special Report

Ever wonder how the medications you take act in your body? This brief guide explains how several classes of popular drugs work.

Thousands of medications are in use today. Here are some of the most common mechanisms by which these drugs achieve their effects:

Antibiotic Drugs -- The development of safe and effective drugs to cure infections was arguably the most significant advance in drug development of the 20th century. Perhaps the most famous example is penicillin, which is derived from a toxin produced by the fungus Penicillium notatum that contaminated a laboratory experiment. The Scottish scientist Alexander Fleming noticed that the Penicillium fungus had done something to kill the bacterium Staphylococcus, which is responsible for many human infections.

Antibiotics have several modes of action. Penicillin disrupts the cell walls of bacteria, causing them to die. Some other antibiotics interfere with the ability of microorganisms to manufacture essential proteins or to reproduce.

Replacement-Therapy Drugs -- Some drugs work by replacing a substance the body lacks. For example, an iron supplement can correct iron deficiency, and daily insulin injections can treat diabetes. Another common example of a replacement-therapy drugs is a synthetic form of natural thyroid hormone (levothyroxine) that remedies the effects of a thyroid gland that has stopped working or was removed because of disease.

Drugs That Act on Enzymes -- Many body processes involve enzymes, which are proteins that facilitate biochemical reactions. An enzyme might, for example, bind to a molecule and break it down into smaller pieces, as occurs during digestion. Or an enzyme might build a larger molecule by joining small molecular building blocks.

Modulating the undesirable action of enzymes can correct disease processes. In fact, the top-selling drugs in the world, the cholesterol-lowering "statin" drugs, inhibit the action of a liver enzyme called HMG-CoA reductase. HMG-CoA reductase performs a key step in the biochemical assembly line that manufactures cholesterol. By blocking this enzyme, statin drugs foil the process, reducing blood levels of cholesterol -- particularly LDL, the "bad" cholesterol that raises the risk of heart disease.

Drugs That Act on Cell Receptors -- Cell receptors are structures on the surfaces of body cells. They are often compared to locks. The "key" that fits into the lock (a protein or some other molecule) is called a ligand. When the ligand binds to the surface of the receptor, forming a chemical bond, it signals the machinery inside the cell to do something.

For example, insulin binds to cell receptors and allows sugar (glucose) in the blood to enter cells. Some new drugs, such as the osteoporosis drug raloxifene (Evista), actually alter the shape of a receptor in ways that modify its action. Evista binds to the estrogen receptor, helping to prevent the bone loss associated with reduced estrogen.

Receptor-Blocking Drugs --
Sometimes known as antagonists, these drugs prevent the natural ligand "keys" from entering the cell receptor "locks," much as two people can't occupy the same seat in musical chairs.

In beta-blockers, an important class of cardiac drugs, the active ingredient is a molecule that prevents the hormone noradrenaline from binding to receptors in the heart. Blocking these "beta1" receptors slows the contractions of the heart muscle and makes them less forceful, which leads to reduced demand on the heart muscle and also lowers blood pressure.

Drugs That Alter Cell Transport --
There are still other ways to interfere with the transfer of molecular messages.

For example, the antidepressant drug fluoxetine (Prozac) is a selective serotonin reuptake inhibitor (SSRI). This drug works by preventing (or inhibiting) brain cells from collecting (or "re-uptaking") and subsequently processing for recycling used molecules of the brain messenger chemical known as serotonin. Thus, Prozac has the effect of increasing the amount of this messenger molecule available to brain cells, which helps to alleviate the symptoms of depression for many people.

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Thursday, July 9, 2009

Clinical trials: A chance to try evolving therapies

Keep Taking the Tablets

Clinical trials offer you a chance to try new treatments. Should you participate in a clinical trial? Learn more about how clinical trials work. Courtesy: Mayo Clinic staff

You may have heard about clinical trials — studies of possible new treatments or medications — but wonder what exactly they are and if one might be right for you. Choosing to participate in a clinical trial can be a complex decision. You first need to understand what clinical trials are and how they're used to test new treatments.

What are clinical trials?

Clinical trials are research studies designed to find answers to specific health questions. Clinical trials often look at new drugs or new combinations of drugs (new or old), new surgical procedures or devices, or new ways to use existing treatments. Clinical trials can also look at other aspects of care, such as:

  • Preventing diseases
  • Screening for and diagnosing health problems
  • Quality of life for people with chronic illnesses

Before a new approach can be tested in a clinical trial, it must already have shown some benefit in laboratory testing, animal experiments or in testing with a small group of volunteers.

The goal of clinical trials is to determine if a new treatment both works and is safe. In fact, new medications cannot be sold in the United States until they have been through clinical trials. Therapies that prove effective during clinical trials may go on to become approved and widely available treatment options.

Who can participate in clinical studies?

Researchers are typically looking for people with the specific disease they're studying. Some trials are limited to people who haven't started treatment, while others focus on people for whom standard treatment has failed. Healthy people are needed for some trials. Researchers also consider age, sex and race, among other factors, when selecting people for clinical trials.

Why do people volunteer for clinical trials?

If treatment for your disease isn't available or the standard treatment hasn't worked for you, you might consider a clinical trial. Clinical trials can provide access to new or experimental treatments that otherwise aren't available. However, there is no guarantee that the treatment will be effective for you. In addition, clinical trials may use a placebo — a pill or liquid that looks like the new treatment but has no active ingredients — as a comparison for the drug being tested. You can't control whether you receive the placebo or the new treatment. Despite these caveats, clinical trials offer hope for many people and an opportunity to help researchers find better treatments for people in the future.

How do you enroll in a clinical trial?

Your doctor might recommend a clinical trial to you, or you might find out about a trial on your own. Often patient advocacy groups let their members know about clinical trials that are recruiting. If you live in a large city, your local newspaper may carry advertisements for clinical trials at nearby research centers. The National Institutes of Health posts listings of thousands of clinical trials online.

Once you find out about a trial you're interested in:

  • Talk to your doctor. Your doctor might be familiar with the drug or therapy involved in the trial. Your doctor can discuss with you the benefits and risks of the clinical trial and whether you might be eligible to participate.
  • Contact the clinical trial coordinator. This person is often listed with the clinical trial announcement. You or your doctor can take this step. You or your doctor will talk with the study coordinator about your health and whether you meet the criteria for the study.
  • Schedule a pretrial screening. You'll undergo various tests to help the researchers decide whether you qualify for the clinical trial. You'll also get a chance to talk to the investigators about what the trial involves, as well as its risks and benefits.

How much will you know about the treatment being investigated?

It's crucial that you have enough information about the study and the treatment being investigated to make a well-informed decision. To ensure that you do, the study facilitators provide what's called an informed consent document. You must read and sign an informed consent form before being allowed into the trial. This informed consent document contains information you need to know about the study before deciding whether to participate. Some of the information on an informed consent document includes:

  • What will happen during the clinical trial, including tests you may be given
  • Known risks and benefits of the experimental treatment
  • How long you'll be expected to participate in the clinical trial
  • Other treatments that might be helpful to you instead of the treatment being tested
  • Whom to contact with questions

The form must explain this information in words you can understand. Researchers aren't allowed to pressure you into signing up for a trial. Signing the informed consent form means you agree to participate in the trial. It isn't a contract. If you later decide to leave the study, you may do so without any penalty.

If your child will be enrolled in a clinical trial, you will go through the informed consent process together. As the parent or guardian, you will have to give permission for your child to participate. Depending on your child's age, researchers may also ask your child directly if he or she agrees to be in the study.

Questions to ask before participating in a clinical trial

If you have any questions about the trial, ask before you agree to participate. Questions you might want to ask include:

  • Who is in charge of this study?
  • Do the people running the study have a vested interest (conflict of interest) in the outcome?
  • What is this study trying to find out?
  • What will be expected of you?
  • Is it possible that you might receive a placebo?
  • What benefits or risks can you expect if you take part in this study?
  • How long will the study last?
  • What happens if your condition gets worse during the study?
  • Can you continue seeing your own doctor during the study?
  • Will you need to pay for any part of the study, including doctor visits and routine tests?
  • Who pays if you're unexpectedly injured in the trial?
  • How will your participation in the study affect your daily life?
  • What happens at the end of the study?
  • Will you be told the results of the study? When?
  • Who will know that you're participating in the study?

How are trials conducted?

Clinical trials follow a scientific action plan called a protocol. The protocol explains what will be done in the study and why. It outlines:

  • Who may participate
  • How many people will take part
  • What the treatment plan entails
  • The type and frequency of tests
  • How the results will be measured
  • The reasons that a study may be stopped
  • The situations in which researchers may stop giving the treatment to participants
  • The likely or known side effects of the treatment
  • The possible benefits of the treatment

To ensure the safety of people in the study, the organization that sponsors the study, such as the medical center or clinic where the work will be done, must approve the protocol. In addition, an institutional review board (IRB) at each study site reviews the protocol. The IRB includes people from the community as well as health care professionals. It reviews all protocols to be sure that participants are treated humanely and ethically. The IRB also looks at issues such as whether the likely benefit of the treatment is worth its risk. If the risks to participants are found to be too great, the IRB can require changes to the study protocol or even reject the study altogether. When reviewing a protocol, the IRB also checks to see if any of the researchers have substantial conflicts of interest.

A clinical trial may also have a data safety monitoring board overseeing it. This board is composed of people who aren't directly involved in conducting the study. The data safety monitoring board can stop the study at any time if they see that the treatment isn't working or it's causing too many side effects. A trial can also be halted by the data safety monitoring board if the treatment is proving to be better than the standard treatment. It may be working so well that it should be made available to people outside of the clinical trial.

What are the stages of clinical trials?

When a treatment is tested in people, it always takes place in stages. Each stage has a different purpose. Treatments being tested must go through the testing in this order:

Phase I research
This is the first step in testing in humans. At this stage researchers study:

  • How much of the treatment to give
  • How it should be given and how often
  • What is the highest dose that can be given safely
  • How the body reacts to the treatment
  • Any harmful side effects

Earlier studies have often been done only in animals, so the new treatment may pose some risks when first tried in humans. Researchers try to minimize these risks by starting with a very small dose and then increasing it only if no or few side effects occur. Only a limited number of people — typically 20 to 80 — who would not be helped by existing treatments are included in a Phase I trial.

Phase II research
This stage focuses on determining whether a new approach works as intended. For example, does it shrink a tumor? Researchers also monitor participants for common short-term side effects that occur with the therapy. Some things aren't yet known about the treatment, so risks are still present. Several hundred people may participate in a Phase II study.

Phase III research
This phase usually begins only after a treatment has shown promise in Phases I and II. At this stage, participants are often randomly assigned — meaning neither you nor your doctor can choose which treatment you receive — the experimental treatment or the standard treatment. Randomization helps to avoid bias in the study's results.

Phase III trials provide more information about the safety of the experimental treatment and demonstrate whether the standard or the experimental treatment has better survival rates and fewer side effects. These trials usually include several hundred to several thousand people. Large trials make it easier to estimate what would happen if the experimental treatment were available to everyone with the condition.

What happens after a clinical trial is over?

After a Phase I or II trial, researchers decide whether to move on to the next phase or stop testing. When a Phase III trial is complete, researchers decide whether the results show enough medical importance that they should be sent to a peer-reviewed, scientific journal. Peer review means other medical experts review the trial to make sure the results are sound.

If the results are promising, the researchers or company they work for may submit an application to the FDA asking permission to make the experimental treatment available to the public. On average the approval process takes about a year, but it can take longer. Some drugs are approved in a matter of months. These drugs are considered priority drugs — drugs that provide a significant advance in treatment for a life-threatening condition. The FDA's goal is to rule on these drugs no more than six months after they've been submitted for approval.

Sometimes research continues even after the FDA approves a treatment. This research, called post-marketing or Phase IV research, tracks the side effects and results in people taking the newly approved drug or treatment. Phase IV trials aren't required for every treatment that's approved, but the FDA can ask a manufacturer to conduct a Phase IV trial to gather additional information about a drug's safety and optimal use. Sometimes companies choose to conduct Phase IV research to compare their product to a competitor's product.

Take time to think through your options

Learning about your disease and how to treat it can leave you feeling overwhelmed. It's important to give yourself time to process all the information about your options. Decide whether to participate in a clinical trial only after thinking about your preferences and talking with those close to you, with your doctor and with other health care professionals.

Monday, June 15, 2009

Breaking news: All human clinical trials to be registered

Now, all human clinical trials to be registered
15 Jun 2009, 0429 hrs IST

BANGALORE: In a significant move aimed at making clinical trials on human beings more ethical and transparent, the Drugs Controller of India has

ruled for the first time that all clinical trials taking place across the country in all areas of health - new drugs, treatments, therapies, surgical procedures and new medical devices - must be compulsorily registered. The rule will come into effect on Monday.

Simply put, clinical trials and research conducted on human beings can now be accessed by the general public too. Hitherto, research institutions and companies obtained permission from the regulatory authorities and registration of the trials was voluntary.

Now, the Drugs Controller General of India (DCGI) has asked the Indian Council of Medical Research to ensure that while granting permission for clinical trials, the applicants are advised to get the trial registered before initiation of the study. The new rule mandates that trials should be registered before the enrolment of the first patient. Not just fresh human trials but even ongoing trials must be registered, the DCGI has said.

"Over the last five years there has been accelerated growth in the number of clinical trials in India. There is a need to improve transparency and accountability in this field both for ethical and scientific reasons. In a way, it promotes greater trust and public confidence in clinical research. Primarily, it has been found that some research populations are particularly vulnerable and cannot give or refuse consent for themselves. The mandatory registration will avoid coercion or undue influence, sources told TOI.

The aim according to the DCGI is to prevent bias generated by selective reporting of only "positive" findings as well as reduce unnecessary duplication of research through greater awareness of existing trials and results. On its part, the Indian Council of Medical Research through its Bio-ethics initiative has developed ethical guidelines for the conduct of trials and for ethics committees.

Sources also concurred that it is impossible to arrive at the number of clinical trials that are taking place in the absence of a single authority that maintains records. "Though permission may be obtained now, the general public who are the ultimate benefactors of the whole exercise of clinical research are not in the know of things,'' sources stated.

What needs to be registered?

* All interventional clinical trials conducted in India and involving Indian participants

* An interventional clinical trial is a research study that prospectively assigns people to one or more health-related interventions (preventive care, drugs, surgical procedures, behavioural treatments, etc.) to evaluate their effects on health-related outcome

* Thus, early and late trials, trials of marketed or non-marketed products, random or non-random trials - all should be registered

Tuesday, June 2, 2009

Give Blood Pressure Drugs to All

News Author: Fran Lowry 
CME Author: Désirée Lie, MD, MSEd

May 28, 2009 Blood-pressure-lowering drugs should be offered to everyone, regardless of their blood pressure level, as a safeguard against coronary heart disease and stroke, researchers who conducted a meta-analysis of 147 randomized trials (comprising 958,000 people) conclude in the May 19 issue of BMJ [1].

"Guidelines on the use of blood-pressure-lowering drugs can be simplified so that drugs are offered to people with all levels of blood pressure," write Drs Malcolm R Law and Nicholas Wald (Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine, Queen Mary University of London, UK). "Our results indicate the importance of lowering blood pressure in everyone over a certain age, rather than measuring it in everyone and treating it in some."

"Whatever your blood pressure, you benefit from lowering it further," Law told heartwire . "Everyone benefits from taking blood-pressure-lowering drugs. There is no one who does not benefit because their blood pressure is so-called normal."

Six years ago, Law and Wald advocated the use of a polypill--containing a statin, three blood-pressure-lowering drugs (each at half the standard dose), folic acid, and aspirin--which they maintained could prevent heart attacks and stroke if taken by everyone 55 years and older and by everyone with existing cardiovascular disease [2].

In the current meta-analysis, which included people aged 60 to 69, they singled out blood-pressure-lowering drugs to determine the quantitative efficacy of different classes of antihypertensive agents in preventing coronary heart disease (CHD) and stroke. They also sought to determine who should receive treatment.

All Antihypertensives Prevent CHD and Stroke

Overall, the results of the meta-analysis showed that in people aged 60 to 69 with a diastolic blood pressure before treatment of 90 mm Hg or a systolic blood pressure of 150 mm Hg, three drugs at half standard dose in combination (as in the polypill) reduced the risk of CHD by approximately 46% and of stroke by 62%. However, when used individually, a single antihypertensive agent at standard dose had about half this effect.

The five main classes of blood-pressure-lowering drugs--thiazides, beta blockers, angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, and calcium-channel blockers--were similarly effective in preventing CHD events and strokes, with the exception of calcium-channel blockers, which had a greater preventive effect on stroke than the other four agents (relative risk, 0.92; 95% confidence interval, 0.85 to 0.98).

People with and without cardiovascular disease derived equal benefit, with similar percentage reductions in CHD events and stroke, and regardless of what their blood pressure was before treatment. Even patients with blood pressures considered to be low--110 mm Hg systolic and 70 mm Hg diastolic--showed fewer CHD events and a reduced incidence of stroke when taking an antihypertensive.

Law and Wald also report that calcium-channel blockers reduced the incidence of heart failure by 19%, and that the other antihypertensive agents reduced heart failure by 24%.

In an accompanying editorial [3], Dr Richard McManus (University of Birmingham, UK) and Dr Jonathan Mant (University of Cambridge, UK) write that the findings of Law and Wald will contribute to debate on the management of hypertension in several areas. "Taken at face value, these findings provide tacit support for the use of a 'polypill' to lower the risk of cardiovascular disease in people likely to be at high risk (such as all people over the age of 55) without first checking their blood pressure."

In a comment to heartwire , McManus added that he believes that the findings reinforce the view that treatment to lower blood pressure should be offered on the basis of risk, regardless of blood pressure.

Friday, April 24, 2009

MMRV vaccine

CDC clarifies preference on childhood vaccines

WASHINGTON (Reuters) - Children who get a combined vaccine against measles, mumps, rubella and chicken pox are slightly more likely to have seizures compared to those getting two separate shots for the same diseases, U.S. officials said on Thursday.

The seizures are not usually life-threatening and the U.S. Centers for Disease Control and Prevention said it was no longer expressing a preference that children get the so-called MMRV combined vaccine rather than two shots -- the MMR vaccine against measles, mumps and rubella (German measles) and a separate one against varicella (chicken pox).

The CDC said it made the change after seeing evidence that children who got the combined MMRV vaccine faced an elevated, but still very small, risk of suffering febrile seizures after vaccination compared to those who got the two shots.

A febrile seizure is a convulsion in young children associated with an increase in body temperature, often from an infection. While frightening, the seizures are not usually dangerous and only a small percentage of children who experience one go on to develop epilepsy.

Dr. John Iskander, the acting director of the CDC's Immunization Safety Office, said it remained very important that parents get their children vaccinated against these diseases.

"These are vaccines that have had enormous public health benefits," Iskander said.

The CDC said the availability of the MMRV vaccine, made by pharmaceutical company Merck, already was limited in the United States because of manufacturing constraints unrelated to vaccine safety, and was not expected to be widely available until 2009.

The CDC said a study examined the risk for febrile seizures seven to 10 days after vaccination among 43,353 children ages 12 months to 23 months who received the MMRV vaccine and 314,599 children of the same age who received the MMR vaccine and chicken pox vaccine administered separately.

It found a rate of febrile seizure of nine per 10,000 vaccinations among MMRV recipients, and four per 10,000 among children who got separate MMR and chicken pox shots. Of 166 children who had febrile seizures after either type of vaccination, 26 were hospitalized and none died, the CDC said.

(Reporting by Will Dunham; Editing by Maggie Fox and Eric Beech)


Tuesday, March 31, 2009

The polypill: Medicine's magic bullet

The capsule costs pennies, contains a simple cocktail of medicines, and halves the number of strokes and heart attacks. Doctors want to hand it out in the first mass medication for the middle-aged in Britain. So why are the big drug companies so uninterested?

The magic bullet, containing five medicines in a single capsule, sharply reduced cholesterol and blood pressure levels and has the potential to "halve cardiovascular events in average middle-aged individuals", the researchers say.

The finding is a major boost for a medication with huge potential against the worldwide epidemic of heart disease and stroke. Doctors say that, if further trials prove successful, all men aged over 50 and women aged over 60 should be offered the pill in what would be the first example of mass medication for the middle-aged in Britain.

Yet no Western pharmaceutical company has shown interest in developing the so-called polypill because it does not promise big profits. It would sell for pennies because its five constituent medicines are cheap, have been around for decades and their patents have expired.

In the UK, one in three men and one in four women die prematurely from heart disease and stroke. In 2005, cardiovascular disease caused more than 208,000 deaths, about four in 10 of all deaths. The idea of combating the heart disease epidemic by combining existing medicines into a drug cocktail called a "polypill" was first proposed six years ago. The pill contains aspirin to prevent blood clots, a statin to lower cholesterol and three blood pressure-lowering agents – a diuretic to remove water from the tissues, a beta-blocker to regulate the heart beat and an ACE inhibitor to relax the arterial muscles.

The current UK strategy of identifying and treating people at high risk of heart disease is failing because one-third of those who have a heart attack have no risk factors and one-third of those die. By giving the pill to everyone, the problem of identifying those at high risk is removed.

When the idea was published in the British Medical Journal in 2003, it was described as a "step of genius" and "possibly the most important paper the journal has published in 50 years". But progress in developing the idea has been slow, and the UK has been left behind.

Now, in the first trial to be published in a mainstream medical journal, researchers from McMaster University, Canada and St John's Medical College, Bangalore, have tested a version of the polypill in 2,000 people in 50 centres in India. The results, published in The Lancet, show that over 12 weeks the polypill reduced blood pressure and cholesterol in a similar way to its individual constituent drugs without increasing side effects. As patients are poor at taking multiple drugs, the single pill combination could "substantially improve adherence and therefore the benefits", they say.

Yesterday, Professor Malcolm Law of the Wolfson Institute of Preventive Medicine in London, one of the originators of the polypill concept, said he was encouraged by the results. "It shows you can make it, it works and it doesn't cause side effects," he said.

He and Professor Nicholas Wald, joint authors of the 2003 BMJ paper, have had talks with the Government's Heart Czar, Roger Boyle, and the Medicines and Healthcare products Regulatory Agency (MHRA) about obtaining a licence. Progress has been held up by a lack of funding and charitable foundations are being approached for support. "We have a patent and work is underway to do the necessary studies to gain a product licence through the MHRA," said Professor Law.

Professor Boyle suggested in 2007 that all middle-aged men and women should take a daily statin, one of the constituents of the polypill. The National Institute for Health and Clinical Excellence (Nice) said last year that more than one million adults at high risk of heart disease were missing out on statins that could save their lives. Nice said GPs failed to identify those at risk because patients were not routinely assessed.

Peter Weissberg, medical director of the British Heart Foundation, said the trial was "good news" because it showed the polypill worked. But it was the first of a series of "very important steps" that had to be taken before it would be clear whether its benefits outweighed its drawbacks. "I am sure there will be a public health benefit in terms of heart attacks saved," he said. "But will there be some people who are inadequately treated? There is scepticism that at the end of the day, one size fits all is going to work. If we are going to medicate the population we have got to show it does reduce heart attacks and strokes. We have got to have a drug that is safe, effective and that people are prepared to take."

The Stroke Association said: "High blood pressure and cholesterol are major causes of stroke and it is important that people take medication to combat these risk factors. By combining these medications in one pill, it will make it easier for people to take their medication. However, it is important that more research and investigation is done into this pill to ensure its safety."
By Jeremy Laurance, Health Editor at The Independent

Tuesday, January 13, 2009

Good Clinical Practices

Answered by Dr Arun Bhatt in Pharmabiz.com

Q. What is the definition of a legally acceptable representative (LAR)?

As per Schedule Y, an LAR is a person who is able to give consent for or authorize an intervention in the patient as provided by the law(s) of India). This would usually include parents, adult children, adult siblings, and spouse.

Q. Can a daughter-in-law sign as LAR for her mother-in-law in informed consent process?

If mother-in-law is literate, you do not need an LAR. If mother-in-law illiterate, she can put her left hand thumb impression on the consent form. In this situation, you do not need an LAR but an impartial witness. In such a situation, the daughter-in-law will sign as an impartial witness.

Q. Do we need to take DCGI approval for conducting comparative efficacy trials on already marketed drugs in India? Which one will be the comparator product in such cases among different old drug brands?

You need to consider whether this study falls into one of the new drug categories as per Drugs & Cosmetics Rules and whether it is truly a Phase IV post-marketing trial. The relevant definitions are:

● Indian GCP definition
● Phase IV

Studies performed after marketing of the pharmaceutical product. Trials in phase IV are carried out on the basis of the product characteristics on which the marketing authorization was granted and are normally in the form of post-marketing surveillance, assessment of therapeutic value, treatment strategies used and safety profile. Phase IV studies should use the same scientific and ethical standards as applied in pre-marketing studies.

After a product has been placed on the market, clinical trials designed to explore new indications, new methods of administration or new combinations, etc. are normally considered as trials for new pharmaceutical products.

You do not need DCGI approval if the product is not a new drug as per the definition in Drugs & Cosmetic Act. However, you will need ethics committee approval.

The choice of comparator depends on the objectives of the study.

Q.What is Named Patient Programme in clinical trials? Do we require an additional approval from DCGI for conducting such studies in India?

Named patient programme or expanded access programme covers use of an unapproved drug outside clinical trial setting.

A patient with:

● advanced disease
● no approved treatment options
● no appropriate clinical trial options

May consider trying to get a new, unapproved drug outside of the clinical trial.

Access to a scientifically-tested drug outside of a clinical trial and prior to regulatory approval is usually referred to as compassionate use.

Expanded Access Programme (EAP)

A pharma company in the late stages of drug development including the Phase III clinical trial stage can offer EAP for patients who are unable to enroll in a clinical trial. The regulatory authority generally approves these programmes if the drug has demonstrated some effectiveness in the on-going clinical trials.

Q.What are Phase 0 studies?

FDA guidance document, Exploratory IND Studies, offers recommendations about safety testing, manufacturing, and clinical approaches that can be used in very early studies, sometimes called exploratory, or phase 0 trials.

Happy New Year!

Here's wishing everyone a healthy and happy New Year!