Jan
08
2022

Sleep Training to Prevent Insomnia and Depression

By | depression, Insomnia, sleep

A new study describes that sleep training to prevent insomnia and depression is desirable. Notably, the study published in JAMA Psychiatry took 291 people age 60 years and older and followed them for three years. In this case half the participants received treatment with sleep training, the other half treatment with cognitive behavioral therapy. The other half was the control who received sleep education therapy from a public health educator. It is important to realize that both groups received 120 minutes weekly group sessions for two months. That is to say, following training of 2 months the subjects were followed for 36 months. It must be remembered that they completed monthly questionnaires to monitor for depression and insomnia. At the end of the study almost 1/3 of the cognitive behavioral group still were free of insomnia.

The control group who received sleep education therapy initially showed no longer any

improvement. In other words, the initial progress did not last with sleep education only. The study was also published in CNN.

Results about rates of depression

Those subjects of the cognitive behavioral therapy group who had a sustained remission of their insomnia disorder had a rate of 82.6% less depression. This was in comparison to the subjects who did not sustain their treatment against insomnia. Dr. Pim Cuijpers commented that the results of the study show “a completely new and innovative way” of tackling the growing problem of depression. Dr. Cuijpers is a professor of Clinical Psychology at the Free University of Amsterdam.

A brief background about depression in older patients

Depression is common in people above the age of 60. About 30-50% of this age group develop depression. Part of this could be that older people often do not get enough sleep as middle-age or younger adults do. Melatonin production declines with older age and this may play a role in insomnia of older people. On the other hand, one of the major symptoms of depression is a lack of sleep. It seems that a lack of REM sleep, the deep sleep that makes us dream, is responsible for both troubles, sleeping (insomnia) and depression.

Cognitive behavioral therapy administered by a therapist is effective for insomnia

It is important that a therapist administers the cognitive behavioral therapy. There are recordings available online that provide cognitive therapy, but they are not individualised. Dr. Irwin said: “That’s why CBT-I is so effective in person, because the therapist is helping that individual navigate and negotiate with themselves — and it can be really hard work,” Irwin added. “I believe that’s also why CBT-I apps or online tools often don’t work — people get frustrated, disappointed or angry at themselves, and they basically stop the work.”

The rationale for cognitive behavioral therapy (CBT)

CBT for insomnia has five components: Stimulus control, sleep restriction, sleep hygiene, relaxation and cognitive behavioral therapy. Researchers gave the program the name CBT-I. Sleep hygiene and relaxation involve these sleeping habits: going to bed at the same time every day, eliminating noise and blue light from electronic devices. Also, you want to keep your bedroom cool, take warm baths and do yoga for relaxation.

Stimulus control and sleep restriction

Stimulus control involves getting out of bed, if you can’t sleep. Dr. Irvin said: “Most people stay in bed, fretting about not falling asleep, which then turns the bed into a negative space. Instead, people are taught to get up after 10 minutes of tossing and turning, do quiet, non-stimulating activities, and not to come back to bed until they are sleepy.” Sleep restriction means that a person lies in bed only to sleep plus 30 minutes. It is a way to make people with insomnia get out of bed instead of lying there awake.

Cognitive behavioral therapy

Cognitive behavioral therapy disrupts irrational thoughts and beliefs about sleep. Patients with insomnia often think “I can never sleep” or “I might die if I don’t sleep tonight.” A therapist has training to help the patient find a way back to a more realistic mindset. Eventually the patient accepts the bed as a welcoming place.

Cognitive behavioral therapy is effective in preventing depression

Dr. Irwin pointed out that chronic insomnia often leads to depression. A dangerous consequence of depression can be preoccupation with suicide. A certain percentage of patients with depression in any age group want to kill themselves. This is where cognitive behavioral therapy can intervene and make a huge difference. As mentioned earlier almost 1/3 of patients who received cognitive behavioral therapy for two months retained their normal sleep pattern. It was among this group that 82.6% had no depression compared to a control group. These are very important statistics. Dr. Irwin said: “We have shown that we can actually target insomnia with cognitive behavior therapy and prevent depression from occurring”.

Sleep Training to Prevent Insomnia and Depression


Sleep Training to Prevent Insomnia and Depression

Conclusion

A new study in JAMA Psychiatry describes that sleep training to prevent insomnia and depression is feasible. Sleep researchers used cognitive behavioral therapy sessions for two months on subjects who suffered from insomnia. The treatment group had profound effects with respect to improving insomnia and depression. Almost 1/3 of subjects treated with cognitive behavioral therapy returned to a normal sleeping pattern. And this subgroup of patients had 82.6% less depression. The lead author, Dr. Irwin thinks that cognitive behavioral therapy could become the new way of how to treat and prevent depression.

Jul
25
2015

Light Can Interrupt Your Circadian Rhythm

By | Cardiovascular disease, Circadian rhythm, Sleeep

A light bulb company from Florida has decided to put warning labels on the light bulbs they manufacture to tell you that artificial light can have health consequences: light can interrupt your circadian rhythms.We do not easily see that it should matter whether you use artificial light at night or not.

Introduction

What we do know is that in the evening when we close our eyes and shut out the light the melatonin production gets elevated, we get sleepy, and we fall asleep. During our sleep the immune system receives a boost from the higher melatonin blood concentration, while cortisol takes a rest and levels are lower overnight. Melatonin is also a powerful anti-cancer agent and this would fit in with the study that found that a loss of the clock gene in shift workers was correlating to a worse prognosis regarding their breast cancer.

There are other diseases that can develop when the circadian rhythm is not maintained. Here are a few examples: neurodegenerative disease, cancer, depression, and sleep disorders.

This link shows how the internal central clock in the suprachiasmatic nucleus of the hypothalamus is responsible for keeping time inside of us. The suprachiasmatic nucleus is situated just above the optic chiasm, hence the name.

The clock gene influences the peripheral clock via the clock genes in each organ to be synchronized. If you disregard your internal clock, expose yourself to prolonged artificial lighting and delay going to sleep in time you will create a disorganized central/peripheral rhythm, which weakens the immune system, disrupts your normal hormone rhythms, and ultimately this can lead to disease.

Breast cancer from interrupted circadian rhythm

Women in California were followed with regard to developing breast cancer and nightly exposure to artificial light.

In this study the authors found a 1.34-fold higher breast cancer risk in premenstrual women exposed to high levels of ambient light at night compared to women who were not.

Similarly, a 2014 study showed a difference with regard to breast cancer rates in women who were working night shifts and women who worked normal hours.

The study showed a loss of clock genes in shift workers with breast cancer that was associated with a worse prognosis of their breast cancer compared to those who were not shift workers and had normal clock genes.

Is it a good idea to tell people that light bulbs can be harmful?

Fred Maxik, the Florida based Lighting Science Group chief officer thinks it is a good idea. Dr. Paolo Sassone-Corsi, the director of the Center of Epigenetics and Metabolism at the school of medicine at University of California Irvine who has authored many studies on the negative effect of artificial lighting on the circadian rhythm also thinks that labeling light bulbs is a good idea. He cautions that there are even more powerful light sources like TV’s and computers that can disrupt the circadian rhythm the later it gets in the evening. “And think about how many people look at Facebook at 2 a.m. That is way more disruptive, but this is certainly a good start; we need to keep increasing awareness in a larger population that light at the wrong time of day can harm you” Dr. Sassone-Corsi added.

It is somewhat nebulous what effects a disruption of the circadian rhythm has in our system. But we do know that sleep deprivation can cause overeating and obesity, memory loss, short attention span, diabetes, depression, car accidents, sudden cardiac arrest and sudden cardiac death due to deadly electrical heart rhythms (ventricular fibrillation).

This 2015 study suggests that melatonin should be used to treat people who are involved in shift work. This will help to reset the circadian rhythm to normal.

Origin of circadian rhythm disorders

Sleep disorders can start in childhood, usually when school starts with structured days and normal bedtime hours, followed by school holidays and weekends where late bedtime hours or irregular sleep habits are the rule. Circadian rhythm disorders are not disorders of sleep quality, but rather disorders in timing of sleep (Ref.1). Circadian rhythm disorders start usually when the child enters school, but can develop as late as in adolescence. 10 to 18% of children and adolescents have circadian rhythm disorders. It is not known why some children find it easy to switch between the irregular sleeping habits of summer to the regular sleeping habits during school days. But others are not able to switch and have problems in school with inattention, daytime sleepiness, irritability, hyperactivity and combativeness. Circadian rhythm disorder tends to persist and can turn into adult circadian rhythm disorder. There are also morning types and evening types (in medical lingo morning chronotypes and evening chronotypes).

Delayed sleep phase disorder

One of the most frequent subtypes of circadian rhythm disorder is the delayed sleep phase disorder. This is what is often found in adolescents who push for a later and later bedtime. The fact that they sleep in until 11 AM or 1 PM reinforces it. They like to shut their windows with a black curtain to keep the sunlight out. At night they like to spend time in front of a computer or the TV. They like to go to sleep only at 1, 2 or 3 AM. They may not be aware what is happening to them: the lack of morning sunlight exposure in the early morning hours of the day leads to a delayed setting of the dim light melatonin onset (DLMO) at the end of the day, which is regulated through the suprachiasmatic nucleus (a part of the hypothalamus). By taking frequent blood or saliva melatonin levels researchers have been able to measure corresponding melatonin levels at the time of the DLMO.

We know from research with astronauts in space travel that melanopsin is produced in the blue-light-sensitive photopigment in the ganglion cell layer of the eye. Melanopsin travels from there along the optic nerve into the suprachiasmatic nucleus, where it helps to set the circadian rhythm for the day.

The day is defined by first opening our eyes when we wake up, getting the first melanopsin dose in the circadian rhythm headquarters of the hypothalamus; two yours before we fall asleep we have the dim light melatonin onset where melatonin is just starting to rise, which makes us gradually tired. Maybe the cave men and women sat around the fireplace and told each other stories. We could listen to soft music in a less brightly lit area.

Treatment of delayed sleep phase disorder

It is important to note that people with a delayed sleep phase disorder (DSPD) do not have a sleep disorder: they have normal sleep at an abnormal time (Ref.1)

Here is how the sleep specialist treats delayed sleep phase disorder.

  1. Exposure to sunlight or to blue LED light at the time of awakening for 20 minutes to 1 hour is key to resetting the circadian rhythm to an earlier point than has been the case. This involves that the child, adolescent or adult has to get used to setting an alarm clock to a desired time in the morning. In order the preserve the resetting of the circadian rhythm towards the evening it is important that from 5 to 6 PM in the evening exposure to the bright lights is avoided. This includes light emission from TV’s, i-phones or computers. The eye would otherwise reset the circadian rhythm via the melanopsin mechanism to a later time.
  2. Melatonin treatment is used to advance or delay circadian rhythms. Melatonin also has a sedating effect, but only about 20% respond to that within 30 minutes by falling asleep. The doses in commercial products override the circadian rhythm effect. Sleep experts use much smaller doses of melatonin to reset the internal clock. Thinking of an adolescent who goes to sleep at 2 AM, the DLMO would be at midnight. To phase advance an individual like that a small amount of melatonin (0.5 to 1.0 mg) would be given at 6 to 8 PM (that is 4 to 6 hours before the DMLO point or 6 to 8 hours before the previous bedtime). The morning exposure to bright light works together with the early evening dose of a tiny dose of melatonin, which by itself is not enough to put the person to sleep at that time.
  3. Supportive sleep hygiene methods: It is important that the parents understand the underlying problem. If necessary, they may have to seek the advice of a sleep expert and discuss the details with him/her. 2 hours prior to bedtime the child needs to be exposed to dim light, which is light that does not have blue light in it. The level of dimness is such that reading is difficult. No TV, no cell phone or I pad is allowed. In this dim light atmosphere melatonin is expressed normally and will be produced and released by the pineal gland in higher amounts. Establish a regular bedtime with which all family members can agree. This is best kept on school days, holidays and weekends. If you would sleep in, you would switch your time machine in your head to another time zone further west and it would be an effort to switch it back! There are many children and adolescents who can switch back and forth easily, but the person with DSPD cannot switch easily and would get stuck again in the familiar late sleeping pattern.

Avoid cola and other caffeinated beverages, including green tea, as they stimulate. The bedroom should be dark, quiet and comfortable. Sound machines have not been shown to enhance sleep (Ref.1).

Light Can Interrupt Your Circadian Rhythm

Light Can Interrupt Your Circadian Rhythm

Conclusion

Circadian rhythm disturbances are more common than previously thought of. There is a certain percentage of children who enter the school system that develop delayed sleep phase disorder. This often stays with them into adolescence and can even carry on into adulthood. Two simple tools have been shown to treat this: early morning light exposure for 20 minutes to 1 hour and a small dose of evening melatonin to reset the circadian rhythm. There likely are thousands of untreated people with circadian rhythm disorders. As not all circadian rhythm disorders are the same it is advisable to seek the advice of sleep disorder expert, if sleep patterns are problematic.

 

References:

1. John H. Herman, Chapter 5, 35-43. “Circadian Rhythm Disorders”

Principles and Practice of Pediatric Sleep Medicine

Second Edition. Stephen H. Sheldon et al., 2014, Elsevier Inc.

Sep
28
2013

Sleepless Nights

By | Health, Hormones, Insomnia, Mental Health, Pain, Prevention, Sleep apnea, Substance abuse, Vitamins and supplements

Sleeping problems (insomnia) are very common. About 10% of the population suffers from chronic insomnia; 30% of the population suffers from occasional sleep problems. In a large outpatient population of a clinic consisting of 3500 patients who had at least one major clinical condition, 50% complained of insomnia, 16% had severe symptoms, 34% had mild symptoms (Ref.1). Insomnia is more common among women, and older people as well as in people with medical or psychiatric illnesses. Long-term studies have shown that the same insomnia problems persist throughout many years. It is not possible to offer a simple remedy for insomnia, because insomnia is a complex problem. Here I will discuss some of the causes of insomnia and also discuss some of the treatment options.

Symptoms of insomnia

The person who suffers from insomnia will usually state that they have problems falling asleep. Worries of the day suddenly circulate through their thoughts and they toss and turn nervously looking at the clock from time to time and getting more and more anxious that they cannot sleep. Others fall asleep OK, but in the middle of the night they wake up perhaps to visit the restroom, but then they cannot go back to sleep. Others wake up 2 hours before their normal alarm clock time and they feel their stomach rumbling making it impossible to fall back to sleep. Older people with chronic diseases and general poor health suffer more from insomnia. In this setting insomnia may be more related to the underlying disease rather than old age. Psychiatric disorders also are associated with more insomnia. Treat the underlying psychiatric illness, and the insomnia disappears.

Although insomnia is a sleep disturbance during the nighttime, people who are affected with this complain of daytime fatigue, of overstimulation, yet they catch themselves making frequent mistakes, and their inability to pay attention gets them involved in accidents and falls. Longitudinal studies have shown (Ref. 1) that people with chronic insomnia are more likely to develop psychiatric disease, such as major depression,  anxiety disorder and alcohol and substance abuse. Unfortunately these disorders can by themselves again cause insomnia, which reinforces chronic insomnia. Insomnia leads to poorer social and physical functioning, affects emotions, leads to a lack of vitality and physical endurance, contributes to worsening of pain and can affect general and mental health.

Research about insomnia

Much has been learnt from sleep studies using polysomnography monitoring during a full night’s sleep. These studies have been used mainly as a research tool. In such studies eye movements, brain wave activity, muscle activity, chest movements, airflow, heart beats, oxygen saturation and snoring (with a microphone) are all simultaneously recorded. This way restless leg syndrome, sleep apnea, snoring, seizure disorders, deep depression etc. that can all lead to insomnia can be diagnosed and separated from insomnia. The stages of sleep (wakefulness, stage 1 to 3 sleep and the REM sleep stage) can also be readily measured using polysomnography (Ref.2). According to this reference the majority of insomnia cases do not need this complex procedure done.

Sleepless Nights

Sleepless Nights

Causes of insomnia

Traditionally insomnia cases are classified into primary insomnia and secondary insomnia. Secondary insomnia is caused by all of the factors discussed below. When they are dealt with, we are left with cases of primary insomnia.

The following medical conditions can cause insomnia: heart disease, pulmonary diseases like asthma and chronic obstructive pulmonary disease (COPD); gastrointestinal disease like liver cirrhosis, pancreatitis, irritable bowel syndrome, ulcers, colitis, Crohn’s disease; chronic kidney disease; musculoskeletal disease like arthritis, fractures, osteoporosis; neurodegenerative disease like MS, Parkinson’s disease, Alzheimer’s disease; endocrine disease like diabetes, hyper- or hypothyroidism, adrenal gland fatigue and insufficiency; and chronic pain conditions. Also, psychiatric conditions like major depression, schizophrenia and anxiety disorders can cause insomnia.

This list in not complete, but it gives you an idea of how complex the topic of insomnia is.
The physician who is seeing a patient with insomnia needs to rule out any of these other causes of insomnia to be certain that the only condition that is left to treat in the patient is insomnia itself. The other diagnoses have to be dealt with separately or else treatment of insomnia will fail.

Ref. 1 points to a useful model of how to think about causation of insomnia: there are three points to consider, namely predisposing, precipitating, and perpetuating factors. Let’s briefly discuss some of these.

Predisposing factors

We are all different in our personal make-up. If you are well grounded, chances are you are not susceptible to insomnia. Anxious persons or persons who have been through a lot of negative experiences in life will have personality traits that make them more prone to insomnia. Lifestyle choices such as late nights out, drinking with the buddies in a bar (extreme circadian phase tendencies) will have an impact on whether or not you develop insomnia.

Precipitating factors

A situational crisis like a job change or the death of a loved one can initiate insomnia.  However, there could be a medical illness such as a heart attack, a stroke or the new diagnosis of a psychiatric illness that has become a precipitating factor. Sleep apnea and restless leg syndrome belong into this group as well as would the stimulating effect of coffee and caffeine containing drinks. Jet lag and nighttime shift work can also be precipitating factors.

Perpetuating factors

Daytime napping to make up for lost sleep the night before can undermine sleep initiation the following night, which can lead to a vicious cycle. Similarly, the use of bedtime alcoholic drinks leads to sleep disruption later that night and can become a perpetuating factor, if this habit is maintained. Even the psychological conditioning of being anxious about whether or not you will fall asleep easily or not the next night can become a perpetuating factor.

I will return to this classification and the factor model of causation of insomnia when we address treatment options.

Drugs that can cause insomnia

One major possible cause for insomnia  can be side effects from medications that patients are on (would belong to the ‘perpetuating factors’ among causes). Physicians call this “iatrogenic insomnia”. The antidepressants, called selective serotonin reuptake inhibitors (SSRI’s) like Prozac are particularly troublesome with regard to causing insomnia as a side effect. Other antidepressants like trazodone (Desyrel) are used in small doses to help patients with insomnia to fall asleep. Some asthmatics and people with autoimmune diseases may be on prednisone, a corticosteroid drug. This can cause insomnia, particularly in higher doses; so can decongestants you may use for allergies; beta-blockers used for heart disease and hypertension treatment; theophylline, an asthma medication and diuretics. Central nervous stimulants like caffeine or illicit drugs can also cause insomnia. Hormone disbalance in general and hyperthyroidism specifically as well as Cushing’s disease, where cortisol levels are high will cause insomnia.

Treatment of insomnia

So, how should the physician approach a patient with insomnia? First it has to be established whether there is secondary insomnia present due to one of the predisposing, precipitating or perpetuating factors. In other words, is there secondary insomnia due to other underlying illnesses? If so, these are being addressed first. Lifestyle choices (staying up late every night) would have to be changed; alcohol and drug abuse and overindulging in coffee or caffeine containing drinks needs to be dealt with. Cognitive therapy may be beneficial when mild depression or anxiety is a contributing factor to insomnia.

The remaining insomnia (also medically termed “primary insomnia”) is now being treated.

The following general points are useful to get into the sleeping mode (modified from Ref. 3):

  1. Ensure your bedroom is dark, soundproof, and comfortable with the room temperature being not too warm, and you develop a “sleep hygiene”. This means you get to sleep around the same time each night, have some down time 1 hour or so before going to bed and get up after your average fill of sleep (for most people between 7 to 9 hours). Do not sleep in, but use an alarm clock to help you get into your sleep routine.
  2. Avoid caffeine drinks, alcohol, nicotine and recreational drugs. If you must smoke, don’t smoke later than 7PM.
  3. Get into a regular exercise program, either at home or at a gym.
  4. Avoid a heavy meal late at night. A light snack including some warm milk would be OK.
  5. Do not use your bedroom as an office, reading place or media center. This would condition you to be awake.  Reserve your bedroom use only for intimacy and sleeping.
  6. If you wake up at night and you are wide awake, leave the bedroom and sit in the living room doing something until you feel tired and then return to bed.
  7. A self-hypnosis recording is a useful adjunct to a sleep routine. Listen to it when you go to bed to give you something to focus on (low volume) and you will find it easier to stop thinking.

Drugs and supplements for insomnia

1. In the past benzodiazepines, such as diazepam (Valium), lorazepam (Ativan), fluorazepam (Dalmane), temazepam (Restoril), triazolam (Halcion) and others were and still are used as sleeping pills. However, it was noted that there are significant side effects with this group of drugs. Notably, there is amnesia (memory loss), which can be quite distressing to people such as not remembering that someone phoned while under the influence of the drug, you promised certain things, but you cannot remember the following morning what it was. Another problem is the development of addiction to the drugs with worse insomnia when the drugs are discontinued. Many physicians have stopped prescribing benzodiazepines.

2. There are non-benzodiazepines drugs that are used as sleeping pills (hypnotics), such as Zaleplon (Sonata), Zolpidem (Ambien) and Eszopiclone (Lunesta).  They seem to be better tolerated.

3. Ramelteon, a melatonin agonist, is available by prescription in the US. It probably is the best-tolerated mild sleeping pill and works similar to melatonin, but is more expensive. Chances are that your physician likely would prescribe one of the non-benzodiazepines drugs or Ramelteon for you as they do not seem to be addicting.

4. However, there is an alternative: Many patients with insomnia tolerate a low dose of trazodone (Desyrel), which is an antidepressant with sleep restoring properties. A low dose of 25 to 50 mg at bedtime is usually enough for insomnia. This allows the patient to fall asleep within about 30 minutes of taking it, and sleep lasts through most of the night without a hangover in the morning. Many specialists who run sleep laboratories recommend trazodone when primary insomnia is diagnosed. However, this is still a drug with potential side effects as mentioned in the trazodone link, but 50 mg is only ¼ of the full dose, so the side effects will also be less or negligible.

5. I prefer the use of melatonin, which is the natural brain hormone designed to put us to sleep. Between 1 mg and 6 mg are sufficient for most people. We know from other literature that up to 20 mg of melatonin has been used in humans as an immune stimulant in patients with metastatic melanoma with no untoward side effects other than nightmares and some tiredness in the morning. A review from the Vanderbilt University, Holland found melatonin to be very safe as a sleeping aid. There are several melatonin receptors in the body of vertebrates (including humans), which are stimulated by melatonin.

6. Other natural methods are the use of L-Tryptophan at a dose of 500 mg at bedtime, which can be combined with melatonin. It is the amino acid contained in turkey meat, which makes you tired after a Thanksgiving meal. GABA is another supplement, which is the relaxing hormone of your brain, but with this supplement tolerance develops after about 4 to 5 days, so it is only suitable for very short term use. Herbal sleep aids are hops, valerian extract and passionflower extract. They are available in health food stores.

Conclusion

A lack of sleep (insomnia) is almost a given in our fast paced lives.

When it comes to treatment, all of the other causes of secondary insomnia need to be treated or else treatment attempts would fail. What is left is primary insomnia. This is treated as follows:

We need to review our sleeping habits, lifestyles and substance abuse. Remove what is detrimental to your sleep. Start with the least invasive treatment modalities such as self-hypnosis tapes, melatonin, L-Tryptophan or herbal extracts. Should this not quite do the trick, asks your doctor for advice. The non-benzodiazepines drugs or Ramelteon would be the next level up. It may be that an alternative such as low dose trazodone would be of help. Only, if all this fails would I recommend to go to the more potent sleeping pills (keep in mind the potential for addiction to them).

References

1. David N. Neubauer, MD (John Hopkins University, Baltimore, MD): Insomnia. Primary Care: Clinics in Office Practice – Volume 32, Issue 2 (June 2005)  © 2005, W. B. Saunders Company

2: Behrouz Jafari, MD and Vahid Mohsenin, MD (Yale Center for Sleep Medicine, Yale University School of Medicine, New Haven, CT, USA): Polysomnography. Clinics in Chest Medicine – Volume 31, Issue 2 (June 2010), © 2010 W. B. Saunders Company

3. Jean Gray, editor: “Therapeutic choices”, 5th edition, Chapter 8 by Jonathan A.E. Fleming, MB, FRCPC: Insomnia, © 2008, Canadian Pharmacists Association.

Last edited Sept. 28, 2014