What is flu?
Flu, or influenza, is a viral illness that occurs predominantly in the winter months in South Africa. It is easily confused with the common cold, which is also a winter viral illness, although caused by another virus.
Flu spreads easily from person to person through droplet distribution when an infected person coughs or sneezes or, quite commonly, through hand-to-hand contact.
Influenza viruses can infect the nose, throat, sinuses, upper airways and lungs. In healthy children, young adults and middle-aged people the disease is mostly mild. Flu can, however, be life-threatening in older people, babies, toddlers and in people of any age who have certain underlying conditions.
Those who are at highest risk of contracting flu should do all they can to prevent and avoid the illness and should be treated as soon as possible if complications develop.
The three types of flu viruses
There are three types of influenza viruses: types A, B and C. Influenza A and B generally cause indistinguishable diseases, although illness due to influenza B can be milder than that caused by influenza A. Influenza C causes a mild respiratory infection in young children. You may be infected with any combination of the viruses in the same season, even, although rarely, at the same time.
The notation of influenza viruses
Influenza A viruses have two kinds of protein spikes on the outermost layer (or envelope). These spikes (called haemagglutinin and neuraminidase) are distinguishing features of each virus, and represent the way in which influenza viruses are named. A typical influenza strain might be named A/Moscow/10/99(H3N2), where A represents the type of influenza, Moscow the place of origin, 10 the 10th virus isolated from the place of origin in the particular year, 99 the year it was isolated, and H3N2 the specific spikes present on the outside of the virus’ envelope.
There are 15 different haemagglutinin molecules of which only the first three regularly infect humans, and nine neuraminidase molecules, of which the first two infect humans. Only one of each type of spike can be present on any virus. Humans are occasionally infected by H5 influenza A (bird flu) viruses, but cannot pass these on to other humans.
How does the flu virus spread?
- Step 1 An infected person sheds the virus from their nose and throat. This starts at about the same time flu symptoms begin and continues for about a week. By coughing or sneezing the virus is then transmitted in one of three ways:
- Step 2a The virus can be spread in large droplets, regarded as the most common method of spreading.
- Step 2b It can also be spread by infectious aerosols, which are tiny particles in the air, small and light enough not to settle on surfaces. These aerosols can typically stay in suspension for up to 60 minutes.
- Step 2c The virus can contaminate hands, tissues, handkerchiefs or other objects after the affected person has sneezed or coughed. If someone else touches these objects, they may contract the virus.
- Step 3 When the virus reaches the cells of your airways – either because of breathing in droplets or aerosols or because you’ve touched an infected surface – it can establish an infection and has thus successfully spread.
In the general community, preschool and school children are most likely to get flu. This is because children have little pre-existing immunity and are highly susceptible to the viruses, which they then bring home to their families.
The highest infection rate is among school-aged children younger than 10 to 12 years, and among people in old-age homes. Closed communities, such as homes for the elderly, university campuses and military bases, are prone to outbreaks of influenza, which run their course over a few weeks.
Symptoms of flu
Some, or all, of these symptoms of uncomplicated influenza may be present:
- A high fever (often higher than 39°C) with chills. The fever is highest in children and least marked in the elderly.
- Dry cough
- Sore throat
- Blocked nose or nasal discharge
- Sweating and shivering
- Muscle aches and pains, especially in the legs (the “I've been run over by a bus” feeling)
- A general feeling of being unwell
- Fatigue and wanting to sleep all day
Symptoms can occur abruptly, and it is sometimes possible to pinpoint the exact hour of the day that symptoms began. Children often vomit and have diarrhoea, but these symptoms are infrequent in adults. In addition, flu complications may occur.
Both children and adults can develop serious complications when they have flu. These include:
Primary influenza virus pneumonia
This form of pneumonia occurs when the flu virus has caused severe lung damage. You’ll start with the usual symptoms of flu, but the fever will persist, your cough will worsen and you’ll become extremely short of breath. In severe cases, you may have a bluish tinge and become confused due to a lack of oxygen.
This form of pneumonia is very serious and will require intensive respiratory support in a hospital. Most people who develop primary viral pneumonia have underlying heart and lung disease and should therefore have a yearly flu vaccination.
Secondary bacterial pneumonia
This is more common than viral pneumonia and occurs when bacteria cause a secondary infection in the lungs. Typical symptoms include recurrence of fever, shortness of breath and productive cough (when secretions come up during coughing) four to 14 days after the symptoms have almost disappeared.
This complication is most often caused by bacteria called Streptococcus pneumonia, Staphylococcus aureus and Haemophilus influenzae type B.
Some doctors recommend that people in high-risk groups be vaccinated against pneumococcal pneumonia as well as influenza.
Exacerbations of chronic lung diseases
It is well known that infection with viruses called rhinoviruses and coronaviruses may worsen chronic lung diseases – such as chronic obstructive pulmonary disease (COPD) – but influenza virus infection may be responsible for up to 25% of these exacerbations.
Otitis media and croup (in children)
As every mother knows, young children are prone to middle ear infections (otitis media) whenever they have an upper respiratory tract infection. In the majority of cases the ear infection is caused by the virus itself and is not a secondary bacterial infection, so antibiotics are seldom necessary.
Children may also develop croup (a viral infection of the vocal cords and large main airways) as a result of flu and other respiratory-tract virus infections.
Myositis and myocarditis
In rare cases inflammation of the muscles of the body (myositis) can occur. It’s more common in children and painful tender leg muscles are a symptom.
Also very rarely, the heart muscle may become inflamed (myocarditis). Symptoms include tiredness, shortness of breath, heart palpitations, a rapid pulse and discomfort in the chest.
Because myositis and myocarditis are more likely if the muscles are put under stress, it’s not a good idea to exercise while you have the flu (or any other viral illness).
Complications of the nervous system and brain
Young children with flu may have fever fits (called febrile convulsions), as is possible in any illness involving a high temperature.
Children with fever should never be given aspirin or medication containing aspirin. It is associated with a potentially fatal disease called Reye’s syndrome. Although the causes of Reye’s syndrome are unknown, it is almost exclusively seen in children who have been given aspirin to treat fever associated with virus infections.
Reye’s syndrome is a very serious condition affecting the brain and liver. Symptoms may include vomiting, lethargy, altered consciousness, seizures and respiratory arrest. The majority of children will recover from Reye’s syndrome, but in some cases permanent brain damage and death might follow.
Other central nervous system complications that have been associated with influenza virus infection include Guillain-Barré syndrome, encephalitis and transverse myelitis, but these are very rare.
It is impossible to accurately determine the true number of influenza infections, as many infections are not reported to healthcare institutions. In the United States, an estimated 5 to 20% of the population are annually infected with influenza viruses,which translates to 50 million cases. Worldwide, between 3 and 5 million cases of severe illness occurs, with an estimated 250 000 to 500 000 influenza-related deaths. About 21 percent of people living in the same house as an infected child or adult will contract flu, according to American studies.
Course of illness
Symptoms start about 48 hours after exposure to the virus, although this period may vary from one to four days. You typically have continuous fever for about three days, although other symptoms such as cough, lethargy and a general feeling of being unwell may persist for longer.
You’re considered “infectious” when the virus is shed from your airways. This can occur from the day of infection and can continue for eight days – even longer in people with decreased immunity. Most people have an uneventful recovery after treatment for symptoms only.
The first step in the diagnosis of influenza is a clinical suspicion. You or your general practitioner may suspect flu based on your symptoms and the occurrence of the illness in the community. At the peak of the flu season, laboratory tests will show that up to 70% of everyone suspected of having flu do in fact have it. (Other respiratory viruses could however cause a similar clinical picture.)
Influenza infection can only be confirmed by a laboratory test: throat and/or nasal swabs are taken and the virus is grown in cell culture. After the virus has multiplied in culture, it can be detected in many ways, for instance by adding red blood cells or using a fluorescence microscope.
More recently developed techniques include the use of methods to detect the presence of the genetic information (RNA) of the virus, termed reverse-transcription polymerase chain reaction (RT-PCR).
How to keep flu at bay
By far the most effective way to prevent flu is to have the annual flu vaccine.
Many cold and flu viruses are acquired from people who don’t yet show any symptoms, and it’s always difficult to contain viruses that travel through the air. You can’t really help being exposed to these viruses. However, there are some general measures you can take to give yourself the best chance of avoiding infection.
At home or work
- Wash your hands frequently and don’t touch your nose, eyes or mouth unnecessarily.
- “Contain” sneezes and coughs with disposable tissues (and make sure to dispose of them right away!) and wash your hands afterwards.
- Try not to touch objects around you when in public places, such as the rail of the escalator or your coughing colleague's pen or computer mouse.
- To minimise exposure, avoid close or prolonged contact with people with a cold or flu. With an incubation period of one to four days and a contagious period of seven days or longer, it’s best to avoid any person with flu for at least a week.
- There may be a role for vitamin A supplementation to prevent flu in children who are malnourished.
- Quit smoking. Those who smoke are more vulnerable to complications of respiratory infections.
- Clean surfaces – especially kitchen and bathroom counter tops – with disinfectant soap.
- Discourage your child from sharing food, utensils, handkerchiefs, napkins and towels with classmates.
- Toys may be contaminated with respiratory secretions. Look for childcare centres where plastic toys are washed daily and stuffed toys washed weekly.
- Teach your children to wash their hands before and after eating, after using the bathroom, after touching their faces, after spending time in public spaces, and after touching animals.
- Rather keep your toddler at home if a child at the crèche has the flu and yours is healthy. Similarly, keep a child at home who shows symptoms of flu to avoid infecting other children.
The flu shot
The best way to reduce your chances of contracting flu is by getting a flu vaccination. Although flu is generally not dangerous, it can cause serious complications and even death, especially in the elderly and the very young. That’s why you should rather avoid contracting this highly contagious disease, especially if you’re vulnerable.
New virus strains created each year
Because of slight changes (called mutations) in the genetic material of the influenza A and B viruses, new virus strains emerge each year. As a result vaccines have to be updated each season.
Three strains of influenza are generally included in the annual vaccine, based on the prediction of the strains likely to circulate in the community during a given season.
These small, almost yearly, genetic changes should not be confused with a major genetic “shift”. Such a shift could lead to the creation of a completely new influenza virus to which humans have not been exposed before and to which we have little or no resistance, such as the pandemic influenza A/H1N1 (swine flu).
How do influenza vaccines work?
Influenza vaccines are produced from inactivated (killed) viruses. They don’t contain the infective virus and can therefore not cause flu. They can be administered safely to people with weakened immune systems.
Within one to two weeks after receiving the vaccine, your body produces antibodies which will fight the virus if you’re exposed to it. Infection will be either prevented, or the severity of your symptoms will be reduced.
Although the antibodies will prevent infection with the three vaccine-included influenza strains (and several more closely related strains), there is no guarantee that you won’t get sick during winter.
The flu shot is usually given in one dose as an injection into the muscle (usually the upper arm). If children under nine have not been vaccinated before, they should receive a second vaccination one month later. Children under three should receive half the adult dose on two occasions, one month apart.
The latest vaccine – using live viruses made harmless, and administered in the form of a nasal spray – was introduced in the USA in 2008 and in Canada in 2009, but was not yet available in South Africa at the time of writing.
How effective is the influenza vaccine really?
No vaccine is 100% effective. Factors within any individual or relating to the vaccine may cause the vaccine not to take or not to provide full protection. This is even truer of flu vaccines, as scientists have to predict which strains are more likely to cause disease each year.
However, studies have shown that protection from the vaccine in healthy adults is 70%-90% when the strains are well matched, compared to 50%-80% when they are not well matched. In this group of people, the vaccine reduces hospital admissions by 90% and days off work by 43%.
These figures may change for certain groups:
- In older people in nursing homes, the vaccine confers a maximum of 40% protection against flu and reduces death from flu-related illness by 39%. These numbers marginally improve in the case of healthy senior citizens in the community.
- In children, the vaccine is reported to prevent 59%-82% of influenza cases, although the rates may be lower in children with asthma. If just a child is immunised, but not the other people in his household, the likelihood of others in the house contracting flu is reduced by 42%!
Who should be vaccinated?
Anyone who does not have a contraindication (see ‘Who should not be vaccinated?’) and who wants to reduce the likelihood of becoming ill with flu, should be vaccinated.
The immunisation recommendations of the National Advisory Group on Immunization (NAGI) of South Africa for 2010 are in order of priority:
1. Pregnant women, irrespective of stage of pregnancy
2. Those older than six months with underlying medical conditions, predisposing them to flu complications. These conditions include chronic lung disease, chronic heart disease, chronic neurological disease, chronic renal disease, mild to severe diabetes and related metabolic conditions and people on aspirin therapy.
3. Frontline healthcare and emergency medical service personnel who come into direct contact with patients
4. HIV-infected adults with a CD4 count above 100 and all HIV-infected children, six months to five years of age
5. Caregivers of infants younger than six months in day-care centres
6. Everyone older than 65
7. Children between six months and five years old
8. People between five and 24 years old who live in hostels, boarding schools and similar institutional settings.
Breastfeeding moms may also receive the flu shot without affecting the safety of the infant.
Also remember that Haemophilus influenza type B is not the cause of flu, but a bacterium that causes meningitis, ear infection, pneumonia and other infections. A vaccine against this bacterium is routinely administered to babies as part of the government’s Extended Programme on Immunisation.
Who should not be vaccinated?
Some people shouldn't be vaccinated. Examples are:
- Babies younger than six months
- Be careful if you’re allergic to eggs (the protein albumin) because the vaccine virus is grown in eggs. But if necessary, even people allergic to eggs may be vaccinated under close medical supervision.
- Be wary if you’ve experienced side effects with previous vaccinations that contained components or constituents included in the current vaccine. Under certain conditions, you may receive the vaccine in two half doses.
- Rather delay your flu shot if you’re ill with a high fever or any acute illness.
- Although there are no known adverse effects on the fetus, vaccines are generally avoided in the first trimester of pregnancy. But as pandemic influenza H1N1 is known to cause complications in pregnant women, it’s best to take the vaccination irrespective of stage of pregnancy.
- If you have a bleeding disorder, you should not be vaccinated without first consulting a healthcare professional.
Consult your doctor/healthcare professional if you think you should not be vaccinated or if you’re uncertain.
Side effects might occur in some people
The vaccine cannot cause flu, as the virus in the vaccine is dead and not infectious. Possible side effects usually consist of a low-grade fever and mild flu-like symptoms, lasting eight to 24 hours after immunisation. These symptoms are caused by the response of your immune system to the vaccine.
- Mild soreness at the site of the injection is common and lasts one to three days.
- About 1 to 9% of people may experience fever, headache, sore muscles or other symptoms resembling flu that can start within twelve hours of receiving the flu shot. It will last only 24 hours. These symptoms are not uncommon in children and the elderly.
If you start experiencing these symptoms more than a day after you’ve been vaccinated, or if they last longer than two days, it is almost certainly due to an illness unrelated to the vaccine. Consult your doctor or healthcare professional in such a case.
When is the best time to be vaccinated?
It takes the immune system about two to three weeks to produce sufficient quantities of specific antibodies against the flu strains in the vaccine10. This means that the best time to be vaccinated against the flu is before the end of April, before the flu season typically starts. However, there is no cut-off date for flu vaccination; it can be given at any stage during the winter.
There are two classes of drugs currently available for the treatment and prevention of influenza infections, the adamantanes and the neuraminidase inhibitors.
The adamantanes – amantadine (Symmetrel®) and rimantadine (Flumadine®) – are for the treatment and prevention of influenza A virus infections only. However, they are no longer recommended as influenza A viruses have become resistant to them.
There are two neuraminidase inhibitors, oseltamivir (Tamiflu®)8 and zanamivir (Relenza®)9 currently available for the treatment and prevention of influenza A and B infections. Resistance to either of the neuraminidase inhibitors, but usually not both, have been detected in certain influenza strains.
Prevention of flu infection with antivirals should never be a substitute for vaccination, and should be reserved for people who cannot be vaccinated or are severely immunosuppressed.
Oseltamivir is an oral medication that has been approved by the American Food and Drug Administration (FDA) for the treatment of flu in people who are one year and older and who have not been sick for more than 48 hours. It has also been approved for the prevention of flu in people who are one year and older.
For adults and adolescents the dosage is one 75 mg capsule twice a day for five days for treatment, and one capsule a day for 10 days for prevention. Oseltamivir is also available in a suspension for children.
It’s important to take the full course of prescribed medication. The most common side effects are nausea and vomiting, so rather take the medication with food. Several studies have shown that if oseltamivir is taken within 48 hours of symptom onset, the duration of illness is shortened by one to one and a half days.
Zanamivir has been approved by the FDA for the treatment of flu in people who are seven years or older and who have not been sick for more than 48 hours, and for the prevention of influenza in people who are five years and older.
Due to the risk of severe bronchospasm, it should not be used for either treatment or prevention of influenza in people with an underlying airways disease, such as asthma and chronic obstructive pulmonary disease.
Zanamivir is available as a powder for inhalation and the recommended treatment dosage is two inhalations (10 mg) twice a day for five days. The recommended dosage for prevention is two inhalations once a day for 10 days.
If you have a history of allergic reactions to milk proteins such as lactose, you should not use zanamivir, as lactose powder is used as a carrier powder.
Studies have shown that if zanamivir is taken within 48 hours of symptom onset, the duration of illness is shortened by about a day.
General supportive treatment
When you have flu, it is important to stay in bed, rest and drink enough fluids to give your body time to fight the infection.
Over-the-counter medication may help relieve the symptoms, but will not fight the virus itself. Paracetamol, aspirin or ibuprofen may help to relieve fever, muscle aches and headache, while decongestants may help to treat nasal congestion.
Please bear in mind that the use of nasal decongestants for more than five consecutive days will worsen symptoms after discontinuation due to a rebound effect.
Suppressive cough mixtures may help clear up the dry cough, typical of flu. Pregnant women should be cautious about taking drugs and children under 16 should not receive aspirin. Influenza should never be treated with antibiotics, as it is caused by a virus and not a bacterium. Antibiotics should only be prescribed by a doctor when secondary bacterial infection is suspected.
Several vitamin supplements and natural/botanical remedies have been advocated to help with the treatment of colds and influenza, but there is scanty (if any) and conflicting scientific evidence regarding the use of these preparations. A meta-analysis of seven double-blind, randomised controlled trials evaluating the efficacy of vitamin C for the treatment of the common cold, found no statistically significant benefit in duration or severity of symptoms. There are conflicting results regarding the benefit of zinc lozenges in the treatment of common cold symptoms, with most studies showing from zero to a slight reduction in the duration of symptoms.
It is important to remember that high doses of vitamin C and zinc, which is commonly used in trials, may cause gastrointestinal side effects such as stomach pain, nausea and vomiting.
The majority of clinical trials that showed that high doses of vitamin A is beneficial in the treatment of viral respiratory tract infections have been conducted in underweight, malnourished, vitamin A-deficient children. No consistent benefit has been observed in healthy children or adults with viral respiratory-tract infections.
There is conflicting evidence regarding the use of Echinacea in the treatment of colds and flu. The results of the different trials cannot be compared as the products used contain different species of Echinacea, different parts of the plant and different preparations.
It is also important to remember that Echinacea should not be given to pregnant women, children, and people taking immunosuppressant or liver-toxic drugs. The long-term safety of Echinacea also remains unknown. The benefit of other natural remedies, including elderberry, andrographis, garlic and peppermint remain unknown.
Influenza and breastfeeding
The flu virus cannot be transmitted from mom to baby through breast milk. Continue breastfeeding if you have flu, as the antibodies you transmit to your baby via the breast milk helps to protect him or her from infection.
Influenza and pregnancy
Pregnant women, especially those in the second and third trimester, are at increased risk for developing severe seasonal influenza. In the case of pandemic H1N1, women at any stage of pregnancy appear to be at increased risk of developing severe and fatal influenza. That’s why current influenza vaccination recommendations include all pregnant women.
Influenza and sport
Refrain from strenuous exercise while you’re ill. If you are a professional athlete, remember that several ingredients of over-the-counter medications for cold and flu are banned by the respective governing bodies.
Flu and smokers
In smokers, the cilia (the tiny “brooms” of the airways which clear the lungs) are already damaged, which means that an important defence mechanism of the airways is compromised. They are further compromised by the flu, which can make one more vulnerable to complications such as secondary bacterial infection.
When should you see a doctor?
Under certain circumstances, you may need to consult your doctor when you have flu.
- If you have a high fever for more than a few hours that does not respond to over-the-counter medicine, and you are not certain whether it is due to flu, it’s a good idea to see a healthcare professional for an opinion.
- If your fever lasts longer than two days.
- If you feel sick and just don't seem to get better.
- If you have a cough that begins to produce phlegm.
- Any sign of complications of flu should prompt a visit to a healthcare professional.
- If you have difficulty breathing or feel a sharp pain when breathing.
- If you fall into any of the high-risk categories recommended for vaccination, even a mild bout of flu should be treated by a health professional. This includes people with cancer, people on medication after organ transplantation and HIV-positive people.
How does a doctor diagnose flu?
Healthcare professionals can usually recognise flu by looking at the symptoms and signs alone.
Symptoms such as a high fever, a dry cough, nasal congestion and aching limbs make the diagnosis of flu very apparent. If it is known that flu is active in the community, then the diagnosis of flu becomes even more probable. The doctor’s suspicion can also be confirmed by a laboratory test.
The when and how of laboratory tests
Laboratory diagnosis of a viral respiratory illness might be attempted for one of the following reasons:
- When the illness is severe, requiring admission to hospital
- In children, where other viruses mimicking influenza may be the cause of disease
- When infection with more than one virus is suspected
- To help decide whether an antibiotic is necessary, because viral infections don’t respond to antibiotics
- For academic interest
How is a laboratory test performed?
How can a doctor treat flu?
- In low-risk cases and without signs of secondary bacterial infections, the doctor will treat the flu symptoms in very much the same way you would treat yourself: mainly with over-the-counter medications. When the diagnosis is clear and illness is uncomplicated, there is not much else to be done. Studies have shown that in the majority of cases the symptoms of flu will subside within three to four days with or without symptom-relieving medication.
- Over-the-counter cold and flu preparations cannot cure flu, but will relieve symptoms.
- In high-risk cases, antiviral drugs may be prescribed, or in people with a secondary bacterial infection appropriate antibiotics may be prescribed. Remember to complete all courses of prescribed antiviral drugs or antibiotics – this will prevent the development of resistant infections.
- In more severe cases, the doctor might consider hospitalisation of the patient.
Flu myths and facts
Many misconceptions about the flu virus and vaccine persist, despite the widespread impact of the disease and the benefit of vaccine.
Myth: Flu is no more than a nuisance, much like common cold that cannot be prevented.
Fact: Flu is a severe and sometimes life-threatening disease that causes 250 000-500 000 deaths worldwide annually. You can avoid getting it by going for a flu shot every year.
Myth: You can get flu from the injectable vaccination.
Fact: The injectable vaccine does not contain any live virus, so it is impossible to get flu from the vaccine. Minor side effects may occur in some people such as mild soreness, redness, swelling at the injection site, headache or a low-grade fever. Most of the side effects are due to the body’s immune response to the vaccine. In fact, these side effects are an indication that the vaccine is working. Vaccination is the best way to prevent flu and its complications.
Myth: It is not necessary to be immunised against flu every year because protection is carried over from previous vaccinations.
Fact: The flu virus strains circulating in the community change from year to year. Because of this, a new vaccine is made each year to protect against current strains. Vaccination is especially important if you have not had pandemic H1N1 (swine flu) yet.
Myth: Only the elderly are at risk for developing serious complications from the flu virus.
Fact: Influenza impacts people of all ages. Young children are at higher risk of severe infections than older children and adults, and pandemic H1N1 typically causes more severe disease in pregnant patients during any stage of pregnancy.
Myth: If I missed the chance to get an influenza vaccination before the winter season, I have to wait for next year.
Fact: It’s never too late to be vaccinated. The best time is before the flu season, but vaccination during the flu season is still beneficial as the virus circulates well into winter and early spring.
Myth: Too many vaccinations may overload a young child’s immune system.
Fact: Everyone’s immune system can respond to a vast number of proteins, such as those included in vaccines. It was estimated that an infant’s immune system can respond to 10 000 of these proteins at one time.
Myth: I can get pandemic H1N1 from eating pork.
Fact: To date there have been no reported cases of pandemic H1N1 infection in humans, due to the consumption of pork. As ingestion is not the normal route of infection, and the virus is readily destroyed by cooking at 70oC, the chance of this occurring is negligible15.
Reviewed by Dr Jane Yeats, Department of Virology, University of Cape Town 2006
Updated and reviewed by Dr Jean Maritz and Dr Leana Maree, medical virologists, Tygerberg Hospital and University of Stellenbosch 2010.
The information provided in this article was correct at the time of publishing. At Mediclinic we endeavour to provide our patients and readers with accurate and reliable information, which is why we continually review and update our content. However, due to the dynamic nature of clinical information and medicine, some information may from time to time become outdated prior to revision.