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Chronic fatigue syndrome (CFS) is not a new disorder. In the 19th century the term neurasthenia, or nervous exhaustion, was applied to symptoms resembling CFS. From the 1930s through the 1950s, outbreaks of disease marked by prolonged fatigue were reported in the United States and many other countries. Beginning in the early to mid-1980s, interest in chronic fatigue syndrome was revived by reports in America and other countries of various outbreaks of long-term debilitating fatigue.
A federal advisory committee organized by the Department of Health and Human Services is charged with making recommendations around the syndromes or conditions described by the terms Myalgic Encephalomyelitis or Encephalopathy, Chronic Fatigue Syndrome, Chronic Fatigue and Immune Dysfunction Syndrome, and Neuroendocrine Immune Disorder.
Unexplained chronic fatigue describes fatigue that lasts for more than 6 months, impairs normal activities, and has no identifiable medical or psychological problems to account for it. Fatigue is just one symptom of the condition. In addition to fatigue, people may complain of other problems, such as difficulty with memory or concentration, headaches, or sore muscles or joints.
The symptoms of CFS may be categorized as follows:
Although the exact causes of CFS are not known, researchers think infection, immune system problems, genetics, and the effects of stress on hormone production may play roles in different patients.
CFS occurs in both sexes, at all ages, and in all racial and ethnic groups. The Centers for Disease Control and Prevention (CDC) estimates that more than 1 million people in the U.S. have the disease, and millions more have similar symptoms but do not meet the full criteria for a CFS diagnosis. Fewer than 20% of CFS patients in this country have been diagnosed, according to the CDC.
People who are in their 40s and 50s most often experience chronic fatigue. Studies have found that four out of five people with CFS are women, although women do not appear to have more severe symptoms than men with the disorder.
Children and adolescents can also have CFS, although it is less common than in adults. Most studies indicate that girls are more likely than boys to develop CFS.
Depression is very common in the general population. It affects up to one-fifth of all Americans at some point in their lives, and most depressed people feel fatigued.
The link between psychological disorders and chronic fatigue syndrome is problematic because so many of the symptoms overlap. The rates of depression are very high in CFS patients, possibly higher than in patients with other conditions (notably fibromyalgia and multiple chemical sensitivity).
Depression can lead to suicide, which may explain the increased suicide rate in people with CFS. For this reason, depression should be diagnosed and treated promptly in patients with CFS.
Studies report that most children and adolescents with CFS have psychiatric disorders. Psychological factors in childhood may increase the risk of developing CFS later in life.
There is some evidence that stress may trigger CFS in people who are at risk for the disease because of genetic factors. People who experienced trauma during childhood -- including sexual and emotional abuse -- are significantly more likely to develop CFS than those who did not experience any trauma. Researchers say the stress of abuse may trigger the condition through its effects on the central nervous system, immune system, and neuroendocrine system (which is related to both nerves and hormones). However, most people who experience childhood trauma do not go on to develop CFS.
A number of conditions overlap or coexist with chronic fatigue syndrome and have similar symptoms. Patients with CFS may also have a diagnosis of fibromyalgia, multiple chemical sensitivity, or both. It is not clear whether these and other conditions are risk factors for CFS, are direct causes, have common causes, or have no relationship at all with CFS.
Fibromyalgia. Fibromyalgia causes prolonged fatigue and widespread muscle aches. It is the disease most often confused with CFS. The two conditions also commonly appear together. In fact, many experts believe fibromyalgia and CFS are different forms of the same condition. Up to 30% of children diagnosed with chronic fatigue syndrome may also have fibromyalgia.
CFS patients experience severe fatigue, whereas fibromyalgia patients experience more pain. The connection between the two conditions may have to do with an increased response to stimulation (called central sensitization), which is thought to cause fibromyalgia and may also contribute to CFS.
People with fibromyalgia have at least 11 tender points -- sites that are very sensitive and painful when touched firmly. The sites often include the:
Some patients with CFS have similar tender pressure points.
Other common fibromyalgia symptoms include repeated sore throat, headache, low fever, and depression. Like CFS, fibromyalgia is chronic and not curable.
Multiple Chemical Sensitivity. Multiple chemical sensitivity (MCS) is a condition in which certain chemicals appear to cause symptoms similar to those of CFS. MCS has also been observed in people with CFS. The following criteria can help identify MCS:
As with CFS and fibromyalgia, there is debate as to whether MCS is a specific medical condition or is psychologically based. Everyone is exposed to many chemicals on a daily basis, and it is very difficult to determine whether chemicals are responsible for specific symptoms.
Eating Disorders. Eating disorders, notably bulimia and anorexia, have been observed in patients with CFS. The conditions often have overlapping risk factors, although it is unclear whether one causes the other.
Other Conditions that Commonly Coexist With CFS. The following conditions also may occur along with CFS and are more common in CFS patients than in healthy people:
Theories abound about the causes of chronic fatigue syndrome. No primary cause has been found that explains all cases of CFS, and no blood tests or brain scans can definitively diagnose the condition.
Convergence of Factors. A number of experts believe that CFS develops from a combination of different factors, which may include the following:
Most patients report having a moderate-to-serious physical illness (such as a long-term viral infection) or emotional event (like an episode of depression) before developing CFS. Some experts believe that these factors, alone or in combination, may interact with nervous system and gene abnormalities to trigger CFS.
Still, it is not clear what sequence of events actually leads to the fatigue and other symptoms of this disorder. And experts cannot point to any specific brain or nervous system problem that triggers the condition.
Because most symptoms of CFS resemble those of a viral illness, many researchers have focused on the possibility that a virus or some other infection causes the syndrome in some cases.
Still, not all CFS patients show signs of infection. Although experts have long been divided on whether infections play any role in this disorder, both viral-related and non-viral CFS may exist.
Viruses. The theory that CFS has a viral cause is based on observations such as:
CFS has been linked with genes that:
However, no clear pattern has been found, and researchers have been unable to determine how these genes may contribute to CFS symptoms.
Abnormal levels of certain chemicals in the brain system known as the hypothalamus-pituitary-adrenal (HPA) axis have been proposed as a cause of CFS. This system controls important functions, including sleep, the stress response, and depression. Of particular interest to researchers are certain chemicals and other factors controlled by the HPA axis:
It is still not clear whether any of these changes are causes of chronic fatigue syndrome, or are only findings in some patients.
CFS has sometimes been referred to as the "chronic fatigue immune dysfunction syndrome." A number of studies have found irregularities of the immune system. Sometimes the immune system over-reacts, and sometimes it under-reacts, but no consistent picture has emerged to confirm that CFS is a disease of the immune system.
Allergies. Some studies have reported that a majority of CFS patients have allergies to foods, pollen, metals (such as nickel or mercury), or other substances. One theory is that allergens, like viral infections, may trigger a cascade of immune abnormalities that lead to CFS. However, most allergic people do not have CFS.
Autoimmune Abnormalities. The risks for chronic fatigue syndrome are similar to the risks for a number of autoimmune diseases. However, it is not clear whether people with CFS have the autoantibodies (antibodies that attack the body's own tissues) found in people with autoimmune disorders. It is not likely that CFS is caused by autoimmunity.
Some patients who fit the criteria for chronic fatigue syndrome also have symptoms of a condition known as neurally mediated hypotension (NMH). NMH causes a dramatic drop in blood pressure when a person stands up, even for as little as 10 minutes. Its immediate effects can be light-headedness, nausea, and fainting. However, studies have reported no higher incidence of NMH in chronic fatigue patients.
Psychological, personality, and social factors are strongly associated with chronic fatigue in most patients. The complex relationship between physical and emotional factors has yet to be fully understood, however. Studies have not found any consistent association between emotional or personality disorders and CFS. Psychological factors, then, are unlikely to be a primary cause of CFS. However, they may play a role in increasing susceptibility to the disorder. In many cases, CFS leads to psychological and social problems.
It is very difficult to diagnose chronic fatigue syndrome. Even experts do not have a clear definition of what chronic fatigue actually is, or what mechanisms in the brain or nervous system are responsible for it. The best diagnostic approach is to determine whether the patient matches the criteria for CFS and rule out other possible causes of symptoms.
In May 2006, the Centers for Disease Control and Prevention (CDC) released a revised definition for chronic fatigue syndrome. In the revised definition, chronic fatigue syndrome falls under the broader category of chronic fatigue, which is defined as unexplained fatigue that lasts for 6 months or longer. Chronic fatigue is part of an even broader category called prolonged fatigue, which is fatigue that lasts for 1 month or more.
Patients with CFS must meet the following criteria:
In 2007, the British National Institute for Health and Clinical Excellence (NICE) released new guidelines for diagnosing and treating CFS in adults and children. According to these guidelines, CFS may be diagnosed if the person has disabling fatigue that starts suddenly, lasts a long time, keeps coming back, and can't be explained by another condition.
People with CFS also can have the following symptoms:
After ruling out other possible causes, the doctor should consider a diagnosis of CFS if symptoms have lasted for 4 months in adults or 3 months in children. Children should be diagnosed by a pediatrician.
A doctor should first take a careful personal and family medical history (which may include a psychological profile), and perform a thorough physical examination. Patients should be prepared to answer questions such as:
The doctor may also ask about any changes in weight, or request that a patient monitor his or her morning and afternoon body temperatures. Patients should report any drugs they are taking, including vitamins and over-the-counter or herbal medications.
The following tests are typically recommended to rule out other conditions that can cause persistent fatigue:
No one blood, urine, or other laboratory test can diagnose CFS. If any test is abnormal, it is not useful for diagnosing CFS specifically, and the doctor should look for other possible causes.
Research has discovered certain components in urine that are unique in people with CFS, and that may someday be used as markers to diagnose the disease. Potential blood markers, including antibodies to Epstein-Barr virus, increased levels of isoprostanes, and decreased levels of alpha-tocopherol (vitamin E) -- have also been found in some people with CFS.
Many other common conditions can lead to temporary exhaustion, including:
In most of these cases, getting enough rest can relieve fatigue.
However, long-term fatigue and other CFS symptoms can be signs of more serious medical or psychological problems. It is important to rule out other conditions that can cause these symptoms by performing a careful evaluation and laboratory tests.
Infectious Mononucleosis and Epstein-Barr Virus. Infectious mononucleosis causes fatigue and swollen glands. It primarily affects adolescents and young adults. Research finds that fatigue may last for a year or more in a small percentage of adolescents who have had mononucleosis. Females and people with more severe fatigue are more likely to develop chronic fatigue syndrome after mononucleosis. Blood tests can detect the Epstein-Barr virus (EBV), which causes mononucleosis.
Autoimmune Diseases. Some diseases, including systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis are caused by autoimmunity, a condition in which the person's immune system attacks the body's own tissues. These diseases, like CFS, occur more often in women than in men. The early symptoms of these conditions, such as muscle and joint pain and fatigue, may mimic CFS symptoms. Most of these conditions can be confirmed with laboratory or x-ray/radiologic tests. However, some autoimmune diseases may develop slowly. Doctors should keep track of any changes in symptoms over time to rule out these serious illnesses.
Post-Lyme Disease Syndrome. Rarely, patients who have been treated with antibiotics for Lyme disease continue to have symptoms that resemble the symptoms of chronic fatigue syndrome. It is not clear whether these symptoms are caused by Lyme disease.
Depression and Severe Mental Disorders. The Centers for Disease Control (CDC), which established the definitions for chronic fatigue syndrome, recognizes depression as one of the symptoms of CFS. More than a third of CFS patients may be depressed. However, according to the CDC, people with major depression or other severe psychiatric disorders, including bipolar disorder and schizophrenia, does not meet the criteria for chronic fatigue syndrome.
Symptoms of major depression include the following:
A person who has several of these symptoms and no physical symptoms (such as a sore throat, aches and pains, or fever) is likely to have major depression. The longer fatigue has continued without physical symptoms, the more likely that the diagnosis is depression.
A persistent form of minor depression called dysthymia may be more difficult to differentiate from CFS and may actually account for some CFS cases. Dysthymia has many of the same symptoms as major depression, but these symptoms are less intense and last much longer -- at least 2 years. The symptoms of dysthymia have been described as a "veil of sadness" that covers most activities.
Patients with depression generally perceive their illnesses differently than people with CFS:
Many patients with CFS become depressed and anxious because they feel so exhausted all the time. CFS may also lead to stress due to social isolation and poverty. These problems can contribute to, and even cause emotional disorders, which can worsen CFS.
Sleep Disturbances. Certain sleep disorders may cause persistent fatigue and can be confused with CFS:
Researchers have found that people with CFS have altered amounts of slow wave sleep, which could indicate a problem with sleep regulation. It is common for people with CFS to be restless sleepers, and to wake up feeling unrefreshed.
Conditions that Cause Joint Pain, Muscle Aches, or Both. A number of illnesses cause CFS symptoms, such as muscle aches and joint pain, fever, and fatigue.
Severe Obesity. People who are severely obese often have symptoms of chronic fatigue because of the stress imposed by their weight. People who are obese are also at higher risk for sleep apnea, which can confuse the diagnosis.
Other Medical Conditions that Usually Rule Out CFS. Many diseases, both minor and serious, can cause long-term fatigue, including:
Drugs and Alcohol. Fatigue is a side effect of many prescription and over-the-counter medications, such as antihistamines. In addition, dependence on or abuse of alcohol or illicit drugs may lead to chronic fatigue. Medications should be considered as a possible cause of fatigue in people who have recently started, stopped, or changed medicines. Caffeine withdrawal can also cause fatigue.
The severity of chronic fatigue syndrome varies. Often, patients with CFS report that they have trouble fulfilling both home and work responsibilities. Many people with CFS cannot work more than part-time, and they are unable to do even the simplest tasks, such as light housework.
Patients with CFS are more likely to lose their jobs, possessions, and support from friends and family than are people who have other conditions that cause fatigue.
Most patients say that while fatigue is the most debilitating symptom of CFS, mental impairment (such as an inability to concentrate or remember) is the most distressing symptom. The effects of CFS on mental function are complex. Some experts believe that the impaired mental functioning is due to depression, which is common in CFS patients.
Although general intelligence is not impaired, CFS patients may test lower in certain mental functions, particularly their speed and efficiency in processing complex information. Many also have memory impairments. This impaired mental function may occur, even if the person does not have depression or other psychiatric disorders.
Because the illness is hard to define, and there are few objective measures for recovery, experts have found it difficult to determine the long-term course of the disease. Although some studies have reported that more than half of patients who complain of chronic fatigue are still fatigued at 2 years, with long-term treatment many patients can improve and even make a real recovery.
Although CFS itself is not fatal, suicide can be a real risk. Continuing treatment for both CFS and depression can help reduce this risk.
Although children with symptoms of chronic fatigue have not been as well studied as adults, limited evidence suggests that CFS can be disabling in young people. Studies report that adolescents who meet the criteria for CFS experience anxiety, depression, and are often absent from school. Children with CFS may have more difficulty paying attention and remembering, which may explain why these kids have more trouble in school than their peers.
Still, some studies indicate that children have a better prognosis than adults and most will recover after 1 - 4 years. Several studies have found that cognitive-behavioral therapy is an effective treatment for adolescents with CFS.
There is no proven or reliable cure for CFS, and no drug has been developed specifically for this disorder. Because CFS remains poorly understood, many patients have problems finding good care. Overall, the recommended strategy for treatment includes a combination of the following:
Patients who stay as active as possible and try to have some control over their disorder have the best chance for improvement. It is important for patients to choose physicians who think of CFS as a medical condition with psychiatric components. They should be wary of any doctor who recommends excessive and expensive treatments that may have serious side effects and no proven benefits.
Patients with severe CFS that cannot be managed with lifestyle changes and medications should ask their doctor about enrolling in a clinical trial.
The power of the mind to improve health problems is significant, and treatments that promote a positive outlook are beneficial for any disease, including CFS. Seeing a therapist who is trained in cognitive-behavioral therapy (CBT) can help CFS patients regain a sense of control over their lives.
The Goals of Cognitive-Behavioral Therapy. The primary goals of CBT (or cognitive therapy) are to change any distorted perceptions patients have of the world and of themselves, so they can change their behavior accordingly. This means learning to think differently about fatigue, improving their ability to deal with stressful situations, and better managing their disorder. CBT can also help manage sleep problems and regulate activity levels. Cognitive therapy is particularly helpful for defining and setting limits, behaviors that are extremely important for CFS patients.
The Procedure. CBT is usually performed over 6 - 20 sessions, each lasting about an hour. Patients are also given homework, which usually includes keeping a diary and attempting tasks they avoided in the past because of their negative attitude.
A typical CBT program may involve the following measures:
Using these techniques, you gradually shift from the idea that you are helpless against the fatigue that dominates your life to the perception that fatigue is only one negative experience among many positive ones.
Success Rates. One review of CFS trials reported that, of all therapies available to CFS patients, only cognitive behavioral therapy (CBT) and graded exercise showed conclusive benefits. CBT is effective at reducing the symptoms of fatigue, and it appears to be more effective than other psychological therapies. Although CBT doesn't bring patients completely back to normal, research has found that people who use the therapy have higher mental health scores, and are able to walk faster and with less fatigue than those who do not use CBT. Cognitive therapy may also be an effective treatment for adolescents with CFS. Young patients who receive CBT report improvements in fatigue, function, and school attendance. However, not all studies support the benefits of cognitive therapy for CFS.
It is important to note that different therapists have different assumptions about CBT and may use different techniques. For instance, some therapists believe that CFS is a purely psychological problem. They encourage patients to stop focusing on the physical causes of their condition and stop using assistive devices, and instead take part in challenging exercise programs. Other therapists do not attempt to change patients' beliefs, but instead focus on helping them conserve energy and better cope with the limitations of their illness. When considering CBT, patients and their families must be aware of these important differences in therapists.
Internet-Based CBT. CBT can also be delivered via the internet in programs such as FITNET (Fatigue in Teenagers on the interNET). In this program, a secure web portal is accessible to patients (and parents of adolescents). Therapy is delivered by trained psychotherapists through email communication. Adolescents are also asked to keep online personal diaries, answer questionnaires, and complete other online assignments recommended by the therapist. Care typically consists of 20 online sessions over a six month period. In adolescents, FITNET was shown to provide more rapid recovery of CFS in the short term compared to usual care (i.e., face-to-face therapy, graded exercise support). Long-term effectiveness was similar for both internet-based CBT and usual care.
A number of studies have reported the benefits of a graded exercise program, in which patients gradually perform more intense exercises as their abilities improve. Research has found that most CFS patients who are able to engage in exercise, particularly aerobic exercise, report less fatigue and better daily functioning and fitness. Exercise works best for CFS when combined with CBT and education.
Graded exercise may not work for all patients with CFS, however. Some CFS patients are so severely affected by their condition that they are unable to exercise. In all CFS patients, over-exercising can intensify symptoms. Some patients experience profound fatigue after even moderate exercise.
The following tips may help CFS patients who are starting on an exercise program:
Work with your health care provider to find a level of activity you can handle. Then gradually increase your activity level. Activity management should involve:
Although there is no evidence that any specific foods influence CFS, it's always a good idea to eat a healthy diet that includes:
Stress Reduction Techniques. Relaxation and stress-reduction techniques may help you manage chronic pain. These techniques also can help relieve the stress associated with CFS. They are not useful, however, as the main treatment for CFS.
A number of relaxation techniques are available, including:
Supportive Family and Groups. Having strong, supportive relationships with family and friends can help CFS patients get better. However, try not to impose unreasonable expectations on loved ones. Attending support groups in which you share experiences with fellow patients may be very helpful for improving your coping abilities.
No medications are specifically approved to treat CFS. However, some medications may be useful for pain or other symptoms, or in cases in which CFS has a specific medical cause. Doctors generally use combinations of drugs to accomplish specific goals, such as medication at night to improve sleep and medication in the morning to improve thinking and energy. Treatment is very individualized.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs). Patients with CFS may benefit from using NSAIDs -- common pain relievers that reduce pain and inflammation. Types of NSAIDs include aspirin, ibuprofen (Motrin, Advil, Nuprin), naproxen (Aleve, Naprosyn, Naprelan, Anaprox), and COX-2 inhibitors.
Patients should use only the lowest effective dose, because NSAIDs can cause heart problems (such as increased blood pressure and risk of heart attack), kidney problems, and stomach bleeding. Patients who are at increased risk for stomach bleeding and ulcers should either switch to another type of pain reliever, or take the NSAID along with a proton-pump inhibitor drug, such as omeprazole (Prilosec) or esomeprazole (Nexium), or with misoprostol (Cytotec). (Misoprostol can cause miscarriage and should not be used by women who may be pregnant.) While COX-2 inhibitors may cause less gastrointestinal distress, some of these medications have been taken off the market for other side effects. Patients should discuss with their doctors whether this drug is appropriate and safe for them.
People with high blood pressure, severe circulation disorders, or kidney or liver problems, as well as people who take diuretics or oral hypoglycemics must be closely monitored if they need to use NSAIDs on a long-term basis. Because NSAIDs reduce blood clotting, NSAID users should stop taking these drugs a week before surgery.
Other side effects of NSAIDs include:
Because of the association between depression and CFS, patients often try taking antidepressants, with varying degrees of success. Common side effects of many antidepressants include:
Almost all antidepressants interact with other drugs, and some of these interactions are very serious.
Tricyclic Antidepressants. Antidepressants known as tricyclics affect brain chemicals that are involved in managing pain. These medications may be particularly helpful for CFS patients. For example, the tricyclic amitriptyline (Elavil) is known to relieve many CFS symptoms, including sleeplessness and low energy levels. Other tricyclics include doxepin (Sinequan), desipramine (Norpramin), nortriptyline (Pamelor), clomipramine (Anafranil), and imipramine (Tofranil, Janimine). Tricyclics improve sleep and relieve pain. However, it can take 3 to 4 weeks for symptoms to improve.
Patients with CFS normally respond to much lower doses of tricyclics than those used to treat people with depression. In fact, many CFS patients cannot tolerate the higher doses commonly used to treat depression. As with all medications, tricyclics must be taken as directed. An overdose can be life-threatening.
Other Antidepressants. Other antidepressants, including bupropion (Wellbutrin), nefazodone (Serzone), or mirtazapine (Remeron) affect combinations of different neurotransmitters, and some may have moderate benefits for CFS patients. For example, nefazodone may improve mood, fatigue, and sleep disturbances.
SSRIs. The popular antidepressants known as selective serotonin-reuptake inhibitors (SSRIs) may be helpful for CFS patients who experience significant depression. These drugs include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil). Cymbalta (duloxetine) is a new antidepressant that is classified as a selective serotonin and norepinephrine reuptake inhibitor (SSNRI) because it affects both neurotransmitters. SSRIs should not be taken with tricyclics, because the combination may cause dangerous side effects.
Stimulants. Stimulant drugs, which are often used to treat attention deficit hyperactivity disorder (ADHD), may be helpful for patients with CFS who also have cognitive problems, such as difficulty concentrating and memory problems. Stimulants include Dexamphetamine, Adderall, methylphenidate (Ritalin) and Ritalin-like drugs such as Focalin, Concerta, Ritalin LA, and Metadate.
Strattera and Provigil are two other drugs that have been evaluated for the treatment of fatigue, but they have not been well studied.
Because of the difficulties in treating chronic fatigue syndrome, many patients seek alternative therapies. Some of these therapies, such as acupuncture, yoga, and relaxation techniques, may be helpful and are not dangerous.
Some people find that vitamin and mineral supplements relieve their CFS, but there is no scientific evidence that these supplements work. Herbal and dietary supplements that are sometimes used for CFS include coenzyme Q10, vitamin B12, vitamin C, magnesium, multivitamins, DHEA, ginseng, and acetylcarnitine. More research is needed to determine whether any herbs can actually benefit patients with CFS.
The FDA does not regulate herbal remedies or dietary supplements, which means manufacturers and distributors do not need FDA approval to sell their products. The amounts of the active ingredients in these remedies may not always match what is claimed on the label. Any substance that can affect the body's chemistry can, like any drug, produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Some herbs, such as St. John's wort, ginkgo, and comfrey may cause serious side effects and drug interactions.
Many problems occur with herbal remedies imported from Asia. One study reported that a significant percentage of these remedies contain toxic metals. Studies have suggested that up to 30% of herbal remedies imported from China have been laced with potent prescription drugs, such as phenacetin and steroids.
CFS patients should be wary of the following remedies:
Other alternative remedies with no proven benefit and possible dangerous side effects include:
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