Author Archives: cliff ng

A Rare, Deadly, Little-Known Disease? What are the Chances?

In February 2018, The World Health Organization (WHO) updated their list of priority diseases to research—diseases that most likely to lead to a global pandemic, including infamous diseases like Ebola (Figure 1), Middle East respiratory syndrome, and Zika. However, there’s one disease confusing many people, with the ominous name “Disease X”. Just what is this mysterious disease?

Figure 1: The Ebola virus magnified 108,000 times. Source: ARS Technica.

It turns out Disease X is the name given for an unknown disease, i.e. the WHO thinks it is likely a pathogen that we do not yet know about could cause the greatest devastation to humanity; this makes sense—if we don’t know how to respond to something, it would be probably have a dire impact.

But imagine this: we now know Disease X is a terrifying disease, with only mild symptoms the first few days, but is quickly followed by much more unpleasant symptoms and death, partially because we don’t know how to deal with it yet. We also know it’s a relatively rare disease.

Say you live in a village of 100 people, and the village’s water supply was infected so that anyone in the village has a 1% chance of contracting the disease. You don’t feel very well, so you take a test correctly identifying 95% of people with the disease. You then get the test, which identifies you as having the disease. At this point, you would probably be quite worried. How certain is it that you have the disease? You might think there’s a 95% chance—but fear not—it’s much lower than that! This is where Bayes’ Theorem (Figure 2) comes in handy.

Figure 2: Bayes’ Theorem (tailored for our example)

D represents you contracting the disease, and + represents being tested positive by the exam. P(D|+) would then be the probability of testing positive if you had the disease,  P(+) the probability of having the disease, and  the probability of a positive test (which consists of testing positive given that you have the disease, and testing positive when you don’t, i.e. a false positive). Plugging in these numbers, it turns out there is only a 16% chance of having the disease if you test positive!

This seems counterintuitive, but think about this: the test would likely identify someone with the disease, but also incorrectly identify 5% of the population as having the disease (Figures 3-4).

Figure 3: In a population of 100, 1 person will have the disease, while 5 people will be falsely identified. Graphic obtained from clker.com.

Figure 4: Your chances of having the disease are 1 in 6, or 16%. Graphic obtained from clker.com.

So if the test on average identifies 6 people as having the disease, how certain can we be that they actually all have the disease? That number would be 16% of 16% of 16%… six times: 0.002%, or basically zero.

In reality, most tests are less accurate than 95%. For example, a mammogram has a 18% chance of a false positive of breast cancer in healthy women.

Bayes’ Theorem has many applications in fields such as epidemiology (the study of the distribution of health and disease) and computer science. It’s so powerful, in fact, that this way of thinking has been given a name: Bayesian logic. So the next time you’re absolutely certain of something, you might want to think twice.

-Cliff Ng

 

Are Antidepressants as Effective at Treating Anxiety as Benzodiazepines?

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The most common psychiatric conditions are anxiety disorders and depressive disorders, with this being especially true for university students. The two medications designed to treat these two disorders are benzodiazepines (BDZ) and antidepressants (AD) for anxiety and depression respectively. However, in addition to depression, almost all antidepressants treat anxiety and many other psychiatric conditions effectively. In the recent years, there has been a shift from doctors prescribing BDZ to AD. If antidepressants do everything that benzodiazepines do, plus more, why are benzodiazepines still prescribed at all?

First, let’s see how these drugs work. Benzodiazepines work by increasing the action of GABA, a neurotransmitter (chemical in the nervous system) that helps the brain calm down. There are many types of antidepressants, including tricyclic antidepressants (TCA; now less commonly prescribed) and reuptake inhibitors (“modern antidepressants”), which generally work by increasing levels of serotonin in the brain, a neurotransmitter that helps regulate mood, leading to enhanced mood. Figure 1 shows some BDZ and AD used in the review this article discusses.

Figure 1: Left to right: alaprazomlam, a benzodiazepine; imipramine, a tricyclic antidepressant; venlafaxine, a selective serotonin-norepinephrine reuptake inhibitor.

For those interested, the following videos illustrate detailed mechanisms of how BDZ and AD work respectively.

To see if evidence truly supports the shift towards AD from BDZ, researchers reviewed 22 studies comparing BDZ to AD in treating anxiety disorders. To keep variables constant, they compared only results from studies comparing the use of BDZ and TCA to treat panic disorder (a specific type of anxiety disorder), while analyzing the other studies individually. There were 11 such results, and those for which data was provided are summarized in Figure 2.

Figure 2: Response rates to BDZ and AD found by various studies. Data complied by Offidani et al.

The researchers did not find consistent statistically significant results which suggested that AD treat panic disorder more effectively than BDZ. However, in addition, they also compared the adverse events (unpleasant effects caused by medication) of BDZ and AD. Although the number of studies supplying this information was small, they consistently found that adverse events were less frequently reported for BDZ than for AD (Figure 3), and statistical analysis revealed a significant difference.

Figure 3: Adverse events caused by BDZ and AD. Data complied by Offidani et al.

Furthermore, the researchers also compared the dropout rates for the studies (which all 11 studies reported). This is the percentage of participants who, for one reason or another, chose to discontinue participation in the study. While this does not necessarily indicate that the medication is not working properly or has adverse effects, the researchers did find that BDZ dropout rates were significantly lower than those of AD (Figure 4).

Figure 4: Dropout rates of participants using BDZ and AD. Data complied by Offidani et al.

There were only 3 studies comparing modern antidepressants to BDZ. After analyzing the data, the researchers found no significant difference in response rate between the two groups, but they found similar results for adverse events and dropout rates.

While antidepressants are undoubtedly effective at treating both depression and anxiety, there is little evidence that they treat anxiety better than benzodiazepines. That being said, benzodiazepines seem to have fewer unpleasant side effects, and therefore should still have their place in modern day medicine if anxiety alone is the issue.

-Cliff Ng

References

Schacter, D. L.; Gilbert, D. T.; Nock, M.; Wegner, D. M. Psychology, 3rd ed.; Worth Publishers, Macmillan Learning: New York, NY, 2014.

Offidani, E.; Guidi, J.; Tomba, E.; Fava, G. A. Psychotherapy and Psychosomatics 201382(6), 355–362.

Offidani, E.; Guidi, J.; Tomba, E.; Fava, G. A. Supplementary Material for: Efficacy and Tolerability of Benzodiazepines versus Antidepressants in Anxiety Disorders: A Systematic Review and Meta-Analysis, 2013.

Diagnostic and Statistical Manual of Mental Disorders, 5th ed.; American Psychiatric Publishing: Washington, 2014.

Adverse Events, Near Misses, and Errors https://psnet.ahrq.gov/primers/primer/34/adverse-events-near-misses-and-errors (accessed Feb 24, 2018).

Gravitational Waves: Where Are We Now, and Why Do They Matter?

In the recent past, a groundbreaking discovery was made in physics, making headlines around the world. Regardless of whether you are a scientist or not, it is likely that you have heard about it: the discovery of evidence for gravitational waves. But what are gravitational waves, and why are they a big deal?

If I were to ask you to name some forces, you might think of, for example, gravity, friction, or magnetism, which come from us observing everyday interactions, like apples falling, rubbing an eraser, or paperclips sticking to magnets. In actuality, there are fundamentally only four types of forces in the universe (although scientists are now potentially suspecting a fifth one), with gravity being one of them.

To better understand gravity, we first need to look at one idea that Einstein is famous for: his idea of a space time continuum—that our universe is a 4-dimensional object formed by the 3 dimensions of space and 1 dimension of time (Figure 1). Gravitational waves are disturbances in this continuum resulting from the gravity between objects. Their existence was predicted by Einstein under his theory of relativity a century before their discovery.

Figure 1:An artist’s depiction of a probe measuring the curvature of spacetime around Earth. Source: NASA.

But despite us being held down by it, gravity is actually a very weak force (compared to the other forces), and this is what has made detecting gravitational waves so challenging. The strongest gravitational waves, for example, would result from something like the colliding of two massive black holes in the video below.

The discovery of gravitational waves was finally made by renowned physicists Rainer Weiss, Barry Barish, and Kip Thorne (for which they won the 2017 Nobel Prize in Physics) at LIGO: the Laser Interferometer Gravitational-Wave Observatory. Figure 2 illustrates how they made the discovery.

Figure 2: How LIGO and Virgo’s Detectors Work. Source: The Guardian (originally sourced from Scientific American).

For a more detailed explanation, along with challenges encountered, Derek Muller of Veritasium explains nicely in this video:

A year later, gravitational waves were detected for the fourth time. This time, it was done with three detectors: LIGO’s two detectors and the Advanced Virgo detector in Italy. This increased the accuracy of the location which astronomers can calculate the source of the waves roughly tenfold.

So why does any of this matter?

In the universe, there are phenomena which emit little to no light, such as black holes and neutron stars—the results of the core of a large star collapsing into itself after it explodes at the end of its life, i.e. a dead star. Because of this lack of light, they are very difficult to study, and we know little about them. But even though neutron stars are “dead”, they have fascinating properties, like magnetic fields a quadrillion times stronger than Earth’s. Scientists are hoping that we can use gravitational waves to study phenomena like them, and perhaps other similar objects we do not even know about. The universe is a vast place, with much to explore, and the discovery of gravitational waves has given us a powerful new tool to study this beautiful world.

-Cliff Ng

References

Drake, N.; Greshko, M. What Are Gravitational Waves, and Why Do They Matter? https://news.nationalgeographic.com/2017/10/what-are-gravitational-waves-ligo-astronomy-science/ (accessed Jan 13, 2018).

Macdonald, F. IT’S OFFICIAL: Gravitational Waves Were Just Detected With The Greatest Precision Ever https://www.sciencealert.com/new-ligo-virgo-gravitational-waves-neutron-stars-space-news-sept-2017 (accessed Jan 13, 2018).

Odenwald, S. What is a space time continuum? https://einstein.stanford.edu/content/relativity/q411.html (accessed Jan 13, 2018).

UCI physicists confirm possible discovery of fifth force of nature https://news.uci.edu/2016/08/15/uci-physicists-confirm-possible-discovery-of-fifth-force-of-nature/ (accessed Jan 13, 2018).

What are Gravitational Waves? https://www.ligo.caltech.edu/page/what-are-gw (accessed Jan 13, 2018).