When CT Scan Fails to be a Cool Tool

Radiation on Spotlight

Hot, hot, and hot!  Wait, I am not referring to weather.  For those who may not know, in science community “hot” refers to “high” when it comes to radiation dose.  Recent full-body X-ray scan in the airport-screening procedure, increasing usages of the cone-beam CT scanners in dentists and orthodontists’ clinics, and damages caused by the CT head scan are all become news headlines.   With the advancement of radiation technologies in security and medical devices, more and more people start to worry about the trade-off between speed and scale of radiation scanners and dose and time of radiation exposure one receives.

Good News to Cheer

Lung cancer, one of the leading deadly cancers, causes ~157,300 deaths in the US alone.  Early discovery of small cancer tissue formation and surgical removal can prolong the lives of patients.  Recent good news revealed by the National Cancer Institute-sponsored clinical trial with over 53,000 participants (mainly smokers and ex-smokers) has shown that a 20 % reduction of mortality in participants screened by low dose helical CT scan instead of conventional chest X-ray.  Computed tomography (CT) scan utilizes radioactive atoms that emit X-rays to image detailed structures of a body.  The CT scan apparently has higher sensitivity, so it can lead to early detection and treatment.  However, CT scan is potentially a double-edged sword, warrant further study.

Bad News to Pay Attention

Although the CT scan has higher sensitivity than conventional X-ray, it also has high false positive (for lung abnormality) alarms, leading to unnecessary medical procedures and medication.  The CT scan is expensive with a price tag of at least $300 per screening.  The huge CT scan machine produces ~400 times higher dose of radiation compared with conventional X-ray.  In fact, experts have long been warning the FDA to regulate the CT scan on colon cancer screening due to its high radiation dose.  Now, there are several incidences whereby patients were severely hurt after high dose of radiation exposure, causing a variety of ailments, including hair loss, confusion and memory problems.

Proper Use of CT Scan is Crucial

What is the safest way to use CT scan and how?  There are many controversies among different interest groups, e.g. medical device makers, radiologists, patient advocate groups, insurance companies, and governmental regulators.  Each has its own stance on the risks and benefits of CT scan in prevention and diagnosis of various cancers.  Is there any ways to improve the safety of CT scan?  According to the FDA’s new release on preventing radiation overdose during CT scans, “education” becomes a key.  The CT scan manufactures need to better train the operators, because most overdose is a result of improper use of the scanner (i.e. operator error) not the machine malfunction.  When CT scan is properly used, it did not result radiation overdose.  I wonder why CT scan, such a sophisticated and expensive machine, was used with no clear and strict rules in the first place.  Now the FDA has stepped up to the investigation and followed up the cases of overdose, hopefully medical community is able to learn from past mistakes and seriously improve education, so the benefits of CT scan could outweigh risks of radiation exposure.

Until next post, keep on reading and writing!!

Type 2 Diabetes Drug Faces Uncertain Future

Avandia is on The Hot Seat

Among a dozen diabetes medications, GlaxoSmithKline’s Avandia (rosiglitazone) has recently drawn scrutiny by the FDA due to adverse side effects on the cardiovascular system. To make matter worse, the company is being subpoenaed by the US Department of Justice over its development and marketing practices for Avandia over a decade.  In 28 October’s Nature reported that:

In its third-quarter earnings report released on 21 October, drug giant GlaxoSmithKline (GSK) revealed that it is being subpoenaed by the US Department of Justice over the company’s development and marketing practices for the diabetes drug Avandia (rosiglitazone). The company, headquartered in London, came under fire in July when a US Senate committee concluded that GSK had known about the drug’s heart risks for more than a decade without reporting them to regulators. GSK denied the charge. Sales of Avandia are currently restricted in the United States and banned in Europe.

Three Bad Luck Drugs in The Treatment of Type 2 Diabetes

Three similar diabetes drugs belonging to “thiazolidinedione” class, Troglitazone (Rezulin by Daiichi Sanyko Co.), Rosiglitazone (Avandia by GlaxoSmithKline) and Pioglitazone (Actos by Takeda Pharmaceuticals), help increase insulin sensitivity and are widely used in the treatment of type 2 diabetes.  Unfortunately, Rezulin was withdrawn from the U.S. market in 2000 due to hepatotoxicity.  Recently, Avandia was restricted for use in type 2 diabetes treatment due to increased heart attack and stroke risks.  Similarly, Actos was faced postmarket safety review of potential increased risk of bladder cancer.

Drug Effects Are Not That Easy to Study

From a biomedical scientist’s point of view, seeing those drugs crashed and burned is very frustrating.  On average, it costs ~$1.8 billion and 10- to 15-year timeframe to develop and bring a drug to market, let alone a possible withdrawal by FDA even after a drug goes on the market.  Why is it so hard to come out a safe and efficient drug?  In this case, I think the answers may lie in the undiscovered biological properties of cell membranes.  It’s been shown that small molecule’s perturbation to lipid bilayers (an essential component of cell membranes) can influence membrane proteins’ (e.g. ion channels, ion transporters, and receptors) functions.  The effects of above three famous bilayer-modifying molecules belong to “thiazolidinedione” class of drug acting as peroxisome proliferators-activated receptors gamma (PPARg) ligands that have multiple and profound effects on gene regulation, development, and metabolism.  In other words, these drugs somehow influence the cell membrane properties through complicated mechanisms, thereby causing functional changes of many unknown and unidentified targets.  In drug development world, the cost of “unknown” is very difficult to put a price tag on it.

Drug Development Business Seeks a Balancing Act Between Risks and Benefits

Again, no drug is perfect without any safety issue.  It’s a balancing act of the risks and benefits measurement and management.  When one drug flops, more will come; it is the failure we learn to make things better (hopefully)!

Until next post, keep on reading and writing!!