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Breathing abnormalities induced by sleep— ie, sleep disordered breathing (SDB)— is now recognized as a common condition with serious adverse consequences. “Sleep Apnea” is a term that refers to diminished breathing during sleep and is characterized by extended pauses in breathing (apnea events). It is a condition associated with a variety of factors and can be very significant to patients with chronic pain. There are two types of sleep apnea: “Central Sleep Apnea” and “Obstructive Sleep Apnea” as well as a combination of the two, termed “Mixed Sleep Apnea.”
Symptoms of Sleep Apnea
Loud and chronic snoring
Choking, snorting, or gasping during sleep
Long pauses in breathing
Daytime sleepiness, no matter how much time you spend in bed
Waking up with a dry mouth or sore throat
Restless or fitful sleep
Insomnia or nighttime awakenings
Waking up feeling out of breath
Forgetfulness and difficulty concentrating
Moodiness, irritability, or depression
When to see a doctor:
Consult a medical professional if you experience, or if your partner observes, the following:
1. Snoring loud enough to disturb the sleep of others or yourself
2. Shortness of breath that awakens you from sleep
3. Intermittent pauses in your breathing during sleep
4. Excessive daytime drowsiness, causing you to fall asleep while you’re working, watching television or driving
Many people do not realize that snoring can be a sign of something potentially serious, and not everyone who has sleep apnea snores. Ask your doctor about any sleep problem that leaves you chronically fatigued, sleepy and irritable. Excessive daytime drowsiness (hypersomnia) may be due to other disorders, such as narcolepsy.
Central Sleep Apnea (CSA)
“Central sleep apnea” (CSA) is diminished breathing during sleep that occurs due to reduced respiratory drive as a consequence of a central nervous system disorder, stroke, spinal cord injury or when medications suppress the brain’s drive to make one breathe. There are many medications that suppress the brain’s drive to breathe during sleep including opiates (pain medications like Lorcet, oxycodone, morphine and methadone), benzodiazepines (like Xanax, Valium and Klonopin), sedatives (sleeping pills) and many psychiatric medications (such as antidepressants) , muscle relaxers (especially Soma) and, most importantly, alcohol. It is this suppression of breathing associated with use of these medications and/or alcohol that is why overdosing with these medications causes death.
Obstructive Sleep Apnea (OSA)
The most common form of SDB is obstructive sleep apnea (OSA), diminished breathing during sleep related to airway obstruction that may result from nasal obstruction (such as with deviated nasal septums) and/or throat obstruction (generally manifested as snoring). When a person has significant airway obstruction during sleep, it results in reduced air flow and reduced oxygen in their blood. The increased airway resistance associated with airway obstruction leads to partial (hypopnea) or complete (apnea) upper airway collapse and is characterized by frequent breathing pauses due to sleep-related changes in muscle tone usually related to snoring.
Snoring generally becomes worse during the deep stages of sleep when muscles become most relaxed. When the oxygen levels drop, the brain signals the sleeper to arouse from their deep sleep to light sleep so that breathing becomes more effective and the oxygen levels increase again. After awhile, the person cycles from their light sleep back again to deep sleep until their oxygen levels drop again and they are driven back to light sleep. Deep sleep is necessary for the maintenancy of healthy brain function. When a person repeatedly is disrupted from their deep sleep and cycled back to light sleep (fragment sleep), they become sleep deprived with the consequences noted below.
Prevalence of Sleep Apnea
The estimated prevalence of OSA has increased substantially over the last two decades, most likely due to the obesity epidemic. It is now estimated by some that 26 percent of adults between the ages of 30 and 70 years have sleep apnea whereas other estimates indicate 3-7% in men and 2-5% in women in the general population have sleep apnea. The percentages are much higher (> 50%) in those people with cardiac or metabolic disorders such as obesity or diabetes. Combined with current estimates that 1 out of 5 North Americans suffers from chronic pain and 1 out of 5 of chronic pain patients take chronic opioids for their pain, the number of of people with sleep apnea and pain patients with sleep apnea is staggering. While the incidence of untreated sleep apnea is unknown, it is estimated that more than half the population with sleep apnea are either unaware and/or untreated for their sleep apnea.
Consequences of Untreated OSA
If a person has significant airway obstruction, this cycling back and forth between deep sleep to light sleep can occur literally hundreds of times during a night’s sleep. The end result is that the person never actually gets enough deep sleep. Deep sleep is the time during which we get the most benefits from sleep. Without enough deep sleep we do not feel well rested and we are considered sleep deprived. Those with sleep deprivation tend to suffer from fatigue, daytime drowniness, irritablility, depression, weight gain, increased risk for high blood pressure and diabetes and poor pain control. So it is important to identify those who have significant airway obstruction because it is treatable and those who get treatment will have more energy and less fatigue, better moods, and better pain control.
Those with untreated sleep apnea have double the risk of a work place accident and 15x the likelihood of being involved in a motor vehicle accident. A recent study found that people with severe, untreated sleep apnea had a significant reduction in white matter integrity in multiple brain areas, which was accompanied by impairments to cognition, mood and daytime alertness. One year of CPAP therapy (see below) led to an almost complete reversal of this brain damage.
Risk Factors for OSA
People who experience excessive daytime sleepiness who fall asleep easily while sitting inactively, talking with someone or reading or watching TV are at greater risk of having sleep apnea. Risk factors for OSA include: loud snoring, observed periods when breathing stops momentarily during sleep, obesity (especially with BMI >35), males>females, thick necks and age >50 y/o. Other contributing risks include menopause, alcohol and cigarette use, craniofacial structure abnormalities and family history.
Sleep Apnea and Opioids
Identifying and treating sleep apnea in patients with chronic pain is especially important. First, patients with poor quality sleep as a result of their untreated sleep apnea will have greater difficulty tolerating their pain due to their increased fatigue and irritability. But, importantly, patients with chronic pain who take opiates and other medications that suppress breathing may worsen their sleep apnea, especially central sleep apnea and may be less responsive to the drop in oxygen associated with their sleep apnea. This can result in prolonged drops of oxygen resulting in a heart attack or simply not waking up. This is the mechanism believed to be a contributing factor to the recent increased incidence of accidental deaths related to increased use of prescription pain medications.
Who is at Risk with Opioids and When?
Unintentional deaths related to sleep apnea with opioids is likely to affect patients on steady doses of usual medications. They have developed tolerance to their medications and do not appear to be at high risk. However, if one takes extra doses of their medications, adds new medications that may suppress breathing or if they drink alcohol, they may tip into a dangerous situation. Or if their obstructive sleep apnea goes untreated and worsens, thay may get into a dangerous situation. This risk is most worrisome if a patient has surgery and takes more pain medications in their post-operative period.
It is evident that the higher the dose of opioids, the more likely, and the more severe central sleep apnea will occur. Studies are mixed but it is estimated that up to more than 46% of chronic opioid patients may have severe sleep apnea and 71% have moderate sleep apnea. Interestingly, a large study showed that chronic pain patients not taking opioids had a greater incidence of sleep apnea than those taking opioids. Furthermore, the presence of other medications frequently prescribed to chronic pain patients are also thought to potentially contribute to risk for sleep apnea. Most obvious are the benzodiazepines (Xanax, Valium, Klonopin etc.) which are well known to contribute to respiratory depression. Less obvious are the antidepressants, antipsychotics, muscle relaxers and possibly antihistamines as possible contributors to sleep apnea. Studies are needed.
Another risk variable in the case of opioids and sleep apnea may occur when a person undergoes a pain procedure or otherwise experiences an abrupt and significant reduction in pain. It is believed that the presence of pain provides stimulation of respiratory drive and sudden pain reduction can reduce respiratory drive to the point of placing a patient on a steady opioid regimen at risk for respiratory depression. For this reason, it is recommended that a patient reduce their usual opioid dosing, especially routine long-acting opioids, when experiencing a marked reduction in their pain after an interventional pain procedure such as an epidural steroid injection or nerve ablation.
Diagnosis of Sleep Apnea
Ultimately, the guidelines remain unclear as to who should be tested for sleep apnea – should it be based on apparent risk factors, suggestive symptoms or a combination of both? Each clinician will consider obtaining a sleep study on a patient based on their own experience and education. Should you have concerns about sleep apnea, please consult your physician.
Your physician can screen for patients at high risk for sleep apnea and can refer you for a sleep study, or polysomnogram (PSG) to determine if there is a problem. A PSG consists of monitoring various functions while a patient is asleep, usually in a sleep lab with a dedicated technician to perform the monitoring of heart rate and rhythm, oxygen levels, breathing rate and patterns and sleep positioning.
The PSG allows identification and classification of sleep-related apneas and hypopneas. An apnea is defined as the complete cessation of airflow for at least 10 seconds. Apneas are further classified as obstructive, central, or mixed based on whether effort to breathe is present during the event. A hypopnea is defined as a reduction in airflow that is followed by an arousal from sleep or a decrease in oxygen saturation. Commonly used definitions of a hypopnea require a 25% or 50% reduction in airflow associated either with a reduction in oxygen saturation or an arousal from sleep. Sleep apnea severity is typically assessed with the apnea–hypopnea index (AHI), which is the number of apneas and hypopneas per hour of sleep. Mild sleep apnea is commonly defined as 5-15 AHI events/hr, moderate to severe sleep apnea as 15-30 AHI/hr and severe sleep apnea as > 30 AHI/hr. The same classification of central apnea index (CAI) and severity is based on the number of central sleep apnea events/hr.
There is a growing trend to perform PSGs in the comfort of the home by providing test equipment for home use. A diagnostic PSG is simply a PSG performed to establish the presence or absence of sleep apnea. A “split study” PSG means the first part of the PSG is diagnostic, the second part of the PSG is a “titration study” in which upon establishing the presence of sleep apnea in the initial diagnostic study, a treatment protocol is evaluated. A split study generally must be performed in a sleep lab with trained personnel.
Treatment of Sleep Apnea
OSA is most effectively treated with CPAP or BiPAP, which are pressurized breathing masks (nasal or full facial) are worn during sleep). OSA can also be treated with medications, sleep aids (including oral devices or surgery, depending on the cause of the obstruction. CSA can be treated by reducing medications that depress respiration but likely will also require a form of pressurized respiration. Treatment generally results in marked improvement in symptoms, including improved energy, better mood, reduced pain and reduced risk of accidental death.
Continuous Positive Airflow Pressure (CPAP), Bilevel Positive Airway Pressure (BiPAP) and Adaptive Seroventilation( ASV)
When the cause of sleep apnea is due to obstruction, the most effective treatment commonly employed is the use of breathing devices with masks that deliver air at a constant pressure (CPAP). The delivery of air at high pressure overcomes the limited airflow due to the obstruction and is very effective in most cases. However, the use of these masks/devices are often not tolerated well.
Adaptive Seroventilation (ASV), a relatively new form of pressurized breathing treatment, is another means of providing respiratory support for treating sleep apnea associated with congestive heart failure (CHF) or central sleep apnea associated with medications including opioids. ASV combines CPAP with variable pressures and can be a preferred treatment option with some studies indicating that ASV can be effective for opioid-related CSA when conventional CPAP is ineffective or not tolerated. A sleep specialist should be consulted when treating sleep apnea, especially with the use of pressurized breathing.
There are no FDA approved medications for the management of sleep apnea. The neurotransmitter serotonin is involved in respiratory control in the brain and there is limited evidence suggesting that medications that increase serotonin such as serotonin reputake inhibitors (SRIs) including some antidepressants, may reduce OSA severity.
In the management of central sleep apnea, there are some medications that provide benefit although they are insufficient as sole treatment.
Carbonic Anhydrase Inhibitors
Acetazolamide, a diuretic and carbonic anhydrase inhibitor diminishes the ventilator response of the peripheral chemoreceptors to hypoxia and reduces the ventilatory response to arousals. Acetazolamide can convert those with mixed obstructive and central sleep apnea to mostly obstructive and has been used to treat central apneas and Cheyne-Stokes breathing.. While the benefits of acetazolamide may be significant, the degree of residual sleep apnea is unacceptable, so acetazolamide should not be the sole approach to long-term management. Acetazolamide is a part of some specialists algorithm for the management of central sleep apnea.
Topiramate is an effective and safe treatment for headache, mood disorders, and seizures. It is also a partial carbonic anhydrase inhibitor which is how it may provide a beneficial effect on central sleep apnea. It has also been suggested that serotonin could also play a role in the mechanism of action of topiramate. Topiramate acts multifactorially through the blockade of sodium channels and kainate/AMPA receptors, enhancement of γ-aminobutyric acid (GABA)ergic transmission. It is speculated that other antiepileptic drugs with similar mechanisms of action, such as a zonisamide, may also be beneficial for the treatment of central apneas.
Clonidine is associated with diminished susceptibility to hypocapnic central apnea without significant effect on ventilation or upper airway mechanics. Use of clonidine does not decrease peripheral ventilatory responses which suggests a central rather than a peripheral effect of clonidine on the susceptibility to hypocapnic central apnoea. The hypotensive effect of clonidine nay impact clonidine’s clinical use, but the concept has merit.
Medical Marijuana – Cannabanoids
Recent research suggests that certain cannabanoids in marijuana may be effective in reducing the disordered breathing associated with sleep apnea. While studies are limited and consist of predominately animal research, initial findings are hopeful, especially given the fact that no other medication has been identified to be effective in treating sleep apnea.
A 2018 study that evaluated 73 adults with moderate or severe OSA and use of dronabinol (Marinol), a synthetic FDA-approved pharmaceutical THC, and use of night time doses ranging from 2.5 to 10mg. Dronabinol, however, is not FDA approved for treatment of sleep apnea. The study demonstrated significant effectiveness in reducing sleep-disordered breathing (AHI scores reduced 10.7 -12.9 points) and daytime sleepiness was significantly reduced (Epsworth Sleepiness Scale scores reduced by 2.3-3.8 points).
The safety and tolerability of dronabinol use is supported by the study. While nearly 90% of all participants reported at least one side effect while on treatment, this percentage did not differ between placebo and active treatment groups. Furthermore, neither the number nor severity of side effects differed between placebo and either the 2.5mg or 10mg dose dronabinol group.
The most frequently reported side effects (<10% occurrence) included sleepiness/drowsiness. headache, nausea/vomiting and dizziness/ lightheadedness. This low frequency of side effects did not differ between the two dosages. The severity of side effects was rated as mild for 73%, moderate for 25%, and severe for only 2% of those experiencing the side effects. It wzs zlso noted that although dronabinol is useful as an appetite stimulate in some groups of people, in this study weight gain was ot identified over the 6-week treatment period.
While this study argues that the impact of dronabinol on OSA lasts at least for 6 weeks, additional studies are needed to assess longer term effectiveness. Although the study size was too small to identify any definitive characterization of “good responders,” it was noted that participants with predominantly REM-related apnea appeared to exhibit the greatest treatment responses, as did younger and non-white individuals.
American Academy of Sleep Medicine (AASM) Recommendations – Medical Marijuana
Based on the available evidence, it is the position of the AASM that medical marijuana should not be used for the treatment of OSA. Their objections are primarily based on the limited research available and are directed largely at the fact that “medical marijuana” consists of a range of products with different amounts and ratios of pharmacologically active constituents and a wide range of delivery methods (eg, vaping, liquid formulation, oral capsules) that have not been studied. Different medical cannabis products and other synthetic extracts are likely to have different effects on the CB1 and CB2 receptors and therefore different degrees of effectiveness and different side effects.
With additional research and improved availability of pharmaceutical grade cannabanoid products with defined dosing and constituent ratios, it is likely that cannabanoids may prove to be an effective means of reducing the symptoms of sleep apnea, one treatment option that may be very desirable for those unable to tolerate positive pressure breathing symptoms or surgery.
Serotonergic Agents (Agents that increase serotonin levels)
There is limited evidence that medications that raise serotonin levels in certain parts of the brain may reduce symptoms of sleep apnea which is thought to have a serotonin-based mechanism underlying the disorder. Many commonly used antidepressants raise serotonin levels and may offer some benefit in sleep apnea. These antidepressants include some tricyclic antidepressants (amitriptyline/Elavil, desipramine, doxepin), SNRIs (duloxetine/Cymbalta and venlafaxine/Effexor) and the SSRIs (Prozac, Paxil, Celexa etc.). Research in the use of antidepressants in sleep apnea is very limited and they are not FDA-approved for use in sleep apnea. The role of serotonin in sleep apnea is not fully understood and there is research also that indicates serotonin may induce sleep disordered breathing in sleep apnea and certain agents (oleamide and THC) may block serotonin-induced exacerbation of sleep apnea.
While CPAP is the most consistently safe and effective treatment for OSA, it is not a cure and people are less likely to use it in the long term. Maxillomandibular advancement (MMA) is considered the most effective surgery for sleep apnea patients by increasing the posterior airway space so that the oxygen saturation in the arterial blood increases. In a study published in 2008, 93.3.% of surgery patients achieved an adequate quality of life. Surgery led to a significant increase in general productivity, social outcome, activity level, vigilance, intimacy and sex.
Overall risks of MMA surgery are low: a Stanford University Sleep Disorders Center study found only 4 failures in a series of 177 patients, or about one out of 44 patients. However, sit is not always clear as to who should be referred for surgery and when to do so: some factors in referral may include failed use of CPAP or device use; anatomy which favors rather than impeding surgery; or significant craniofacial abnormalities which hinder use of a CPAP device.
Dental devices serve to open the oral airway to enhance airflow but are only effective for mild to moderate sleep apnea.. Most dental devices are acrylic and fit inside your mouth, much like an athletic mouth guard. Others fit around your head and chin to adjust the position of your lower jaw. Two common oral devices are the mandibular repositioning device and the tongue retaining device. These devices open your airway by bringing your lower jaw or your tongue forward during sleep. There are a number of side effects from using this type of treatment, including soreness, saliva build-up, nausea, and damage or permanent change in position of the jaw, teeth, and mouth. It is very important to get fitted by a dentist specializing in sleep apnea, and to see the dentist on a regular basis for any dental problems that may occur. Ask your physician for a referral to a specialist in our area.
Other Treatment Options
In fact, there are many things one can do to treat sleep apnea, especially mild to moderate sleep apnea, that should be engaged.
Lose weight. The airway obstruction in OSA is most often related to obesity and the narrowing of the airway in the throat from fat in the neck. Even a small amount of weight loss can open up your throat and improve sleep apnea symptoms. If obesity can be reduced significantly or eliminated, OSA often resolves.
Quit smoking. Smoking is believed to contribute to sleep apnea by increasing inflammation and fluid retention in your throat and upper airway.
Avoid alcohol, sleeping pills, and sedatives, especially before bedtime, because they relax the muscles in the throat and interfere with breathing.
Avoid caffeine and heavy meals within two hours of going to bed and maintain regular sleep hours. Sticking to a steady sleep schedule improves sleep and apnea episodes decrease when one gets plenty of sleep.
Sleep on one side. Avoid sleeping on your back, as gravity makes it more likely for your tongue and soft tissues to drop and obstruct your airway.
The tennis ball trick. In order to keep yourself from rolling onto your back while you sleep, sew a tennis ball into a pocket on the back of your pajama top. Or wedge a pillow stuffed with tennis balls behind your back.
Elevate the head of your bed by 4 to 6 inches or elevate your body from the waist up by using a foam wedge. You can also use a special cervical pillow.
Open your nasal passages. Try to keep your nasal passages open at night using a nasal dilator, saline spray, breathing strips, or a neti pot. These efforts should improve airflow.
Studies show that throat exercises may reduce the severity of sleep apnea by strengthening the muscles in airway, making them less likely to collapse.
1. Press tongue flat against the floor of mouth and brush top and sides with toothbrush. Repeat brushing movement 5 times, 3 times a day.
2. Press length of tongue to roof of mouth and hold for 3 minutes a day.
3. Place finger into one side of mouth. Hold finger against cheek while pulling cheek muscle in at same time. Repeat 10 times then rest and alternate sides. Repeat sequence 3 times.
4. Purse lips as if to kiss. Hold lips tightly together and move them up and to the right the up and to the left 10 times. Repeat sequence 3 times.
5. Place lips on a balloon. Take a deep breath through your nose then blow out through your mouth to inflate balloon as much as possible. Repeat 5 times without removing balloon from mouth.
Please discuss any concerns related to sleep apnea with your physician and seek further asssessment when advised.
Sleep Apnea – Overviews
- Sleep Apnea Summary – handout
- SLEEP-DISORDERED BREATHING: National Sleep Disorders Research Plan, 2003, NCSDR, NHLBI, NIH
- Burden of Sleep Apnea – Rationale, Design, and Major Findings of the Wisconsin Sleep Cohort Study – 2009
- The Epidemiology of Adult Obstructive Sleep Apnea – 2008
- Obstructive sleep apnea in adults: epidemiology, clinical presentation, and treatment options. – PubMed – NCBI
- Rising prevalence of sleep apnea in U.S. threatens public health – American Academy of Sleep Medicine (AASM)
- Central Sleep Apnea – 2007
Sleep Apnea – Opioids and Central Sleep Apnea
- Central sleep apnea – misunderstood and mistreated! – 2019
- Sleep-Disordered Breathing and Chronic Opioid Therapy
- Medium Increased Risk for Central Sleep Apnea but Not Obstructive Sleep Apnea in Long-Term Opioid Users – A Systematic Review and Meta-Analysis – 2016 ML F.
- Sleep Apnea Methadone and Benzodiazepine Therapy
- Assessing Sleep in Opioid Dependence – A Comparison of Subjective Ratings, Sleep Diaries, and Home Polysomnography in Methadone Maintenance Patients
- Obstructive Sleep Apnea is More Common than Central Sleep Apnea in Methadone Maintenance Patients with Subjective Sleep Complaints
- Drugs and Sleep Apneas A review of FPVD
- opioid-induced sleep apnea – is it a Real problem? – 2012
- Hypoxemia in patients on chronic opiate therapy with and without sleep apnea – 2008
- Sleep abnormalities associated with alcohol, cannabis, cocaine, and opiate use – a comprehensive review – 2008
- Adaptive Servoventilation for Treatment of Opioid-Associated Central Sleep Apnea – 2014
Sleep Apnea – Atypical Antipsychotics (Seroquel, Risperdal, Zyprexa, Clozaril)
- The impact of atypical antipsychotic use on obstructive sleep apnea – A pilot study and literature review
Sleep Apnea – Panic Disorder
Sleep Apnea – Treatment
- Treatment of obstructive sleep apnea
- Enhancing Adherence to Positive Airway Pressure Therapy for Sleep Disordered Breathing
- Treating Apnea May Help High Blood Pressure
- Adaptive Pressure Support Servoventilation – a Novel Treatment for Sleep Apnea Associated with Use of Opioids
Sleep Apnea – Treatment, Antidepressants
- Serotonin Reuptake Inhibitors in Obstructive Sleep Apnea with Depression: Associations in People With and Without Epilepsy – 2018
Sleep Apnea – Treatment, Cannabanoids (Marijuana)
- Medical Cannabis and the Treatment of Obstructive Sleep Apnea – An American Academy of Sleep Medicine Position Statement – 2018
- Cannabis, Cannabinoids, and Sleep: a Review of the Literature. – PubMed – NCBI
- Misc Abstracts @ Obstructive Sleep Apnea – 2017
- Cannabinoid May Be First Drug for Sleep Apnea – 2018
- Pharmacotherapy of Apnea by Cannabimimetic Enhancement, the PACE Clinical Trial – Effects of Dronabinol in Obstructive Sleep Apnea – 2018
Sleep Apnea – Treatment, Carbonic Anhydrase Inhibitors (Azeaxolamide & Topiramate)
- Alternative approaches to treatment of Central Sleep Apnea – 2014
- Pearls & Oy-sters- treatment of central sleep apnea with topiramate. – 2012
- Topiramate and breathing- serotonin mediated? – 2012
- Effects of Clonidine on Breathing during Sleep and Susceptibility to Central Apnoea – 2013
Emphasis on Education
Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.
For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.
Should you wish more information regarding any of the subjects listed – or not listed – here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.
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