Alcoholism
Content
Alcoholism and Related Problems The recommended maximum alcohol intake a week is 21 units for men and 14 units for women. In 2009 knowledge of daily benchmarks and measuring alcohol in units had increased among both men and women. The proportion of adults who had heard of daily benchmarks increased from 69% in 2006 to 90% in 2009.[1] Morbidity statistics In 2010/2011 there were 190,900 admissions where the primary diagnosis was attributable to the consumption of alcohol.[2] Moderate (12.5-<50 g/day) to heavy (>50 g/day) alcohol intake is associated with an increased risk of oesophageal cancer.[3] Younger people were more likely than older people to exceed the daily benchmarks:[2] Over 56% of young men aged 16 to 24 had drunk more than twice the recommended level on at least one day during the previous week. This compares with 6% of men aged 75 and over. 52% of women in the youngest age group had exceeded twice the recommended level on at least one day compared with only 3% of those aged 75 and over. Having initially risen, the proportion of young women who drink heavily has fallen, although the statistics should be treated with caution due to the small sample size. The proportion of 16 to 24 year-old women who had drunk more than six units on at least one day in the previous week fell from 24% in 2009 to 17% in 2010. Mortality statistics The WHO report says that alcohol use results in the death of 2.5 million people annually. Nearly 4% of all deaths are related to alcohol. Most alcohol-related deaths are caused by injuries, cancer, cardiovascular diseases and liver cirrhosis. Globally, 6.2% of all male deaths are related
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to alcohol, compared to 1.1% of female deaths. Worldwide, 3.2 lakh young people aged 15-29 years die annually from alcohol-related causes, resulting in 9% of all deaths in that age group. Alcohol raises the risk of as many as 60 different diseases, according to a recent study in the medical journal `Lancet'. Health problems related to alcohol[6] These result from continued use of excessive amounts of alcohol. Binge drinking and chronic drinking of alcohol are more likely to cause harm.[7] Medical problems
• •
Liver: alcoholic hepatitis, cirrhosis, liver cancer. Gastrointestinal tract: oral cavity cancer, oesophageal neoplasm, oesophageal varices, pancreatitis.
•
Cardiovascular system: atrial fibrillation, hypertension, strokes and cardiomyopathy with heart failure.
•
Neurological system: acute intoxication with loss of consciousness, withdrawal, seizures, subdural haemorrhage, peripheral neuropathy, Wernicke-Korsakoff syndrome and cerebellar degeneration.
Psychiatric problems
• • • •
Alcohol dependence syndrome Suicidal ideation Depression Anxiety
Miscellaneous
• •
Loss of libido Fetal alcohol syndrome
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Social problems related to alcohol[6]
• • • •
Impaired performance at work. Relationship problems. Violent crimes - eg, domestic violence and drink driving offences. Antisocial behaviour.
Medical problems related to alcohol Affects of alcohol on the liver[8] Alcoholic liver disease includes fatty liver, alcoholic hepatitis and cirrhosis. These three conditions probably represent a spectrum of liver damage resulting from continued abuse of alcohol.[9]
•
In fatty liver, there is an accumulation of fat within the hepatocytes. This is reversible with abstention from alcohol. Alcoholic hepatitis presents as acute right upper quadrant (RUQ) pain with jaundice, fever and marked derangement of LFTs. At a microscopic level there is inflammation of the liver.
•
•
In liver cirrhosis, the hepatocytes are damaged so much that they are replaced by scar tissue which is permanent. Alcoholic hepatitis and cirrhosis may co-exist. Alcoholic hepatitis and cirrhosis may lead to encephalopathy, portal vein hypertension and hepatorenal syndrome. This group of patients is also at increased risk of infections and they are usually also malnourished.
•
Treatment involves abstinence from alcohol, and good nutrition. There is no specific therapy for alcohol-related hepatitis and cirrhosis. It is important to look for, and promptly treat, the complications which include ascites, spontaneous bacterial peritonitis, hepatic encephalopathy and oesophageal varices.
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•
Patients with ascites may need to be maintained on high doses of diuretics. Again, abstinence from alcohol is crucial.
Affects of alcohol on the gastrointestinal tract Alcohol increases the risk of oral cancers. This is especially associated with spirits and the risk is increased with concomitant use of tobacco. Adenocarcinoma of the stomach and oesophagus is thought to be related to alcohol use. Some of these cases may be genetically determined.[10] Portal hypertension is a complication of cirrhosis and leads to a raised venous pressure in veins in the oesophagus and stomach. These swollen veins are superficial and bleed easily. Bleeding from oesophageal varices is serious and is associated with a high level of morbidity and mortality.[11] Management of bleeding varices is a medical emergency and requires adequate resuscitation (patients may need to be intubated to protect their airway). Blood transfusions are necessary and correction of abnormal clotting with vitamin K and fresh frozen plasma (FFP) may also be required. Various options for treatment are available including vasoactive drugs, obturation with glue and balloon tube tamponade. Both acute and chronic pancreatitis are associated with excessive alcohol consumption. One study found that consumption of spirits was more likely than wine or beer to cause acute pancreatitis.[6] The pathophysiology of alcohol-related pancreatitis is not clearly understood. Patients usually present with epigastric pain with vomiting. The amylase is high in acute pancreatitis but may be normal in patients with chronic pancreatitis. Pancreatitis can be associated with a number of complications such as shock, sepsis and abscess formation. Longterm complications include diabetes mellitus and weight loss from steatorrhoea. See separate articles Acute Pancreatitis and Chronic Pancreatitis for more details. Affects of alcohol on the cardiovascular system
•
Excessive alcohol use is associated with hypertension and subsequent target organ damage such as strokes, myocardial events and renal failure.[12]
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•
It is also associated with a dilated cardiomyopathy with heart failure and atrial fibrillation which may revert to sinus rhythm.[13]
Again, abstinence from alcohol is paramount. PatientPlus
• • • •
Alcoholism and Alcohol Abuse - Recognition and Assessment Acute Alcohol Withdrawal and Delirium Tremens Alcoholism and Alcohol Abuse - Management Wernicke-Korsakoff Syndrome
Affects of alcohol on the nervous system[14]
•
Acute alcohol intoxication can present with blackouts, head injuries and subdural haemorrhages. Alcohol withdrawal is associated with fits which may be unresponsive to anti-epileptics.
•
The Wernicke-Korsakoff syndrome results from lack of thiamine (commonly seen in alcoholics due to malnutrition). Wernicke's syndrome occurs acutely and patients present with confusion, visual impairment (diplopia) and ataxia. Korsakoff's syndrome occurs more chronically and is characterised by memory deficits and confabulation .
See separate article Wernicke-Korsakoff Syndrome for more details. Alcohol withdrawal Alcohol withdrawal occurs within a few hours of not having a drink and can last beyond 48 hours. Patients experience hallucinations, anxiety and a coarse peripheral tremor. On examination, patients may be pyrexial, tachycardic and hypertensive. They may also develop seizure and auditory and visual hallucinations. Delirium tremens is the severe end of the spectrum of alcohol withdrawal and consists of a severe form of the above symptoms; it may be associated with circulatory collapse and ketoacidosis.
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Alcohol dependence This is characterised by the following:
• • • • •
A strong desire to drink. Difficulty controlling alcohol intake. Physiological withdrawal when intake is reduced. Tolerance, such that increasing amounts are required to produce the same effect. Harm resulting from continued alcohol use - eg, work or relationship problems.
Prevention When you think of addictions, you normally think about alcohol, In our culture, people who work hard or take good care of their bodies are admired. And society puts a stamp of approval on sexuality. As long as behavior — drinking, work, exercise — is balanced, it is OK. But a fine line exists between balanced behavior and addiction. Going over the line develops an addiction. Let’s take a look at the most widely recognized of addictions — alcoholism. Alcoholism is a disease that includes four symptoms: 1. Craving — a strong need or compulsion to drink; 2. Loss of control — the inability to limit one’s drinking on any given occasion; 3. Physical dependence — withdrawal symptoms, such as nausea, sweating, shakiness, and anxiety. These occur when alcohol use is stopped after a period of heavy drinking. 4. Tolerance — the need to drink greater amounts of alcohol in order to “get high.” When people have an alcohol problem, individuals who are close to them find it hard to discuss the problem. They hope it will go away. Sometimes they don’t even see the problem — often because the addicts indulge privately or because they themselves have a problem.
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Experts I have consulted suggest talking about this with our patients, even if we are not alcoholism counselors, because if we care, we can at least offer encouragement and referral to experts within the community. Making the decision to help patients in this area depends on how much time you take with your patients, how comfortable you are talking about these issues, and how well prepared you are to talk about the disease. Before you bring up the subject with any patient, tap into your community’s resources. Find out what types of treatment centers are available, how to make referrals to them, and what other types of resources the patient may use, use as Alcoholics Anonymous. • • • • Cut down — Have you felt the need to cut down on your drinking? Annoyed — Have you ever been annoyed when someone criticizes your drinking? Guilty — Have you ever felt guilty about your drinking? Eye-opener — Have you ever felt the need for an eye-opener in the morning?
One question answered with a "yes" may indicate a possible problem with alcohol. If you answered "yes" to two or more questions, you probably have a problem that requires attention. If the CAGE test suggests that you have a problem with alcohol, do not attempt to solve the problem on your own. Few people can do this. Here are some general guidelines for your discussion with patients: 1. Assume a non-judgmental attitude. 2. Be aware of your own preconceptions about the abuse of alcohol. 3. Acknowledge that the problem is difficult to talk about. 4. Assure the patient you are interested in his or her health. 5. Assure confidentiality.
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6. Ask if the patient is in recovery. People undergo several stages of change and receptivity concerning addiction. It’s helpful to be aware of these stages and to try to recognize which state a person may be in: • Precontemplation. The individual does not even think about the need to stop what he is doing and may believe there is no problem. When you come across such an individual, planting “seeds” for future recovery can be helpful. • Contemplation. The person has already begun thinking she may have a problem. You can tip the balance between making changes and not making changes. •Preparation. The patient has been thinking about where to go for help. You can be helpful by reinforcing his decision and help him to determine the best course of action. • Action. The person has signed up for help. You can aid by being supportive. • Maintenance. The individual has been through treatment and is remaining sober and straight. Your role is to be encouraging and supportive. • Termination. If you see signs of relapse, offer support. Alcoholism — or any addiction — is not a weakness; it is a disease. Learn about it. And approach the subject with compassion. You can be a vehicle for healing the soul as well as the spine. References: 1. Nichols M, Scarborough P, Allender S, et al; What is the optimal level of population alcohol consumption for chronic disease prevention in England? Modelling the impact of changes in average consumption levels. BMJ Open. 2012 May 30;2(3). pii: e000957. doi: 10.1136/bmjopen-2012-000957. Print 2012. 2. Drinking: adult's behaviour and knowledge - 2009 Report, UK National Statistics 3. Statistics on Alcohol: England, NHS Information Centre, 2012
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4. Islami F, Fedirko V, Tramacere I, et al ; Alcohol drinking and esophageal squamous
cell carcinoma with focus on light-drinkers and never-smokers: a systematic review and meta-analysis. Int J Cancer. 2011 Nov 15;129(10):2473-84. doi: 10.1002/ijc.25885. Epub 2011 Apr 7. 5. More men dying in the UK as a result of alcohol, Office for National Statistics, 2012. 6. Prevention and reduction of alcohol misuse - Evidence briefing (2nd edition), NICE/Health Development Agency, March 2005 7. Sadr Azodi O, Orsini N, Andren-Sandberg A, et al; Effect of type of alcoholic beverage in causing acute pancreatitis. Br J Surg. 2011 Nov;98(11):1609-16. doi: 10.1002/bjs.7632. Epub 2011 Aug 3. 8. Nichols M, Scarborough P, Allender S, et al; What is the optimal level of population alcohol consumption for chronic disease prevention in England? Modelling the impact of changes in average consumption levels. BMJ Open. 2012 May 30;2(3). pii: e000957. doi: 10.1136/bmjopen-2012-000957. Print 2012. 9. Guidelines on the Management of Alcoholic Liver Disease, European Association for the Study of the Liver (2012) 10. Zhu H, Jia Z, Misra H, et al; Oxidative stress and redox signaling mechanisms of alcoholic liver disease: updated experimental and clinical evidence. J Dig Dis. 2012 Mar;13(3):133-42. doi: 10.1111/j.1751-2980.2011.00569.x. 11. Terry MB, Gammon MD, Zhang FF, et al; Alcohol dehydrogenase 3 and risk of esophageal and gastric adenocarcinomas. Cancer Causes Control. 2007 Nov;18(9):1039-46. Epub 2007 Jul 31. 12. Sarangapani A, Shanmugam C, Kalyanasundaram M, et al; Noninvasive prediction of large esophageal varices in chronic liver disease patients. Saudi J Gastroenterol. 2010 Jan-Mar;16(1):38-42.
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13. Higashiyama A, Okamura T, Watanabe M, et al; Alcohol consumption and cardiovascular disease incidence in men with and without hypertension: the Suita study. Hypertens Res. 2012 Aug 30. doi: 10.1038/hr.2012.133. 14. Conen D, Tedrow UB, Cook NR, et al; Alcohol consumption and risk of incident atrial fibrillation in women. JAMA. 2008 Dec 3;300(21):2489-96. 15. Alcohol and Health, Institute of Alcohol Studies, 2004 16. Alcohol dependence and harmful alcohol use; NICE Clinical Guideline (February 2011)
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to alcohol, compared to 1.1% of female deaths. Worldwide, 3.2 lakh young people aged 15-29 years die annually from alcohol-related causes, resulting in 9% of all deaths in that age group. Alcohol raises the risk of as many as 60 different diseases, according to a recent study in the medical journal `Lancet'. Health problems related to alcohol[6] These result from continued use of excessive amounts of alcohol. Binge drinking and chronic drinking of alcohol are more likely to cause harm.[7] Medical problems
• •
Liver: alcoholic hepatitis, cirrhosis, liver cancer. Gastrointestinal tract: oral cavity cancer, oesophageal neoplasm, oesophageal varices, pancreatitis.
•
Cardiovascular system: atrial fibrillation, hypertension, strokes and cardiomyopathy with heart failure.
•
Neurological system: acute intoxication with loss of consciousness, withdrawal, seizures, subdural haemorrhage, peripheral neuropathy, Wernicke-Korsakoff syndrome and cerebellar degeneration.
Psychiatric problems
• • • •
Alcohol dependence syndrome Suicidal ideation Depression Anxiety
Miscellaneous
• •
Loss of libido Fetal alcohol syndrome
2 |Page
Social problems related to alcohol[6]
• • • •
Impaired performance at work. Relationship problems. Violent crimes - eg, domestic violence and drink driving offences. Antisocial behaviour.
Medical problems related to alcohol Affects of alcohol on the liver[8] Alcoholic liver disease includes fatty liver, alcoholic hepatitis and cirrhosis. These three conditions probably represent a spectrum of liver damage resulting from continued abuse of alcohol.[9]
•
In fatty liver, there is an accumulation of fat within the hepatocytes. This is reversible with abstention from alcohol. Alcoholic hepatitis presents as acute right upper quadrant (RUQ) pain with jaundice, fever and marked derangement of LFTs. At a microscopic level there is inflammation of the liver.
•
•
In liver cirrhosis, the hepatocytes are damaged so much that they are replaced by scar tissue which is permanent. Alcoholic hepatitis and cirrhosis may co-exist. Alcoholic hepatitis and cirrhosis may lead to encephalopathy, portal vein hypertension and hepatorenal syndrome. This group of patients is also at increased risk of infections and they are usually also malnourished.
•
Treatment involves abstinence from alcohol, and good nutrition. There is no specific therapy for alcohol-related hepatitis and cirrhosis. It is important to look for, and promptly treat, the complications which include ascites, spontaneous bacterial peritonitis, hepatic encephalopathy and oesophageal varices.
3 |Page
•
Patients with ascites may need to be maintained on high doses of diuretics. Again, abstinence from alcohol is crucial.
Affects of alcohol on the gastrointestinal tract Alcohol increases the risk of oral cancers. This is especially associated with spirits and the risk is increased with concomitant use of tobacco. Adenocarcinoma of the stomach and oesophagus is thought to be related to alcohol use. Some of these cases may be genetically determined.[10] Portal hypertension is a complication of cirrhosis and leads to a raised venous pressure in veins in the oesophagus and stomach. These swollen veins are superficial and bleed easily. Bleeding from oesophageal varices is serious and is associated with a high level of morbidity and mortality.[11] Management of bleeding varices is a medical emergency and requires adequate resuscitation (patients may need to be intubated to protect their airway). Blood transfusions are necessary and correction of abnormal clotting with vitamin K and fresh frozen plasma (FFP) may also be required. Various options for treatment are available including vasoactive drugs, obturation with glue and balloon tube tamponade. Both acute and chronic pancreatitis are associated with excessive alcohol consumption. One study found that consumption of spirits was more likely than wine or beer to cause acute pancreatitis.[6] The pathophysiology of alcohol-related pancreatitis is not clearly understood. Patients usually present with epigastric pain with vomiting. The amylase is high in acute pancreatitis but may be normal in patients with chronic pancreatitis. Pancreatitis can be associated with a number of complications such as shock, sepsis and abscess formation. Longterm complications include diabetes mellitus and weight loss from steatorrhoea. See separate articles Acute Pancreatitis and Chronic Pancreatitis for more details. Affects of alcohol on the cardiovascular system
•
Excessive alcohol use is associated with hypertension and subsequent target organ damage such as strokes, myocardial events and renal failure.[12]
4 |Page
•
It is also associated with a dilated cardiomyopathy with heart failure and atrial fibrillation which may revert to sinus rhythm.[13]
Again, abstinence from alcohol is paramount. PatientPlus
• • • •
Alcoholism and Alcohol Abuse - Recognition and Assessment Acute Alcohol Withdrawal and Delirium Tremens Alcoholism and Alcohol Abuse - Management Wernicke-Korsakoff Syndrome
Affects of alcohol on the nervous system[14]
•
Acute alcohol intoxication can present with blackouts, head injuries and subdural haemorrhages. Alcohol withdrawal is associated with fits which may be unresponsive to anti-epileptics.
•
The Wernicke-Korsakoff syndrome results from lack of thiamine (commonly seen in alcoholics due to malnutrition). Wernicke's syndrome occurs acutely and patients present with confusion, visual impairment (diplopia) and ataxia. Korsakoff's syndrome occurs more chronically and is characterised by memory deficits and confabulation .
See separate article Wernicke-Korsakoff Syndrome for more details. Alcohol withdrawal Alcohol withdrawal occurs within a few hours of not having a drink and can last beyond 48 hours. Patients experience hallucinations, anxiety and a coarse peripheral tremor. On examination, patients may be pyrexial, tachycardic and hypertensive. They may also develop seizure and auditory and visual hallucinations. Delirium tremens is the severe end of the spectrum of alcohol withdrawal and consists of a severe form of the above symptoms; it may be associated with circulatory collapse and ketoacidosis.
5 |Page
Alcohol dependence This is characterised by the following:
• • • • •
A strong desire to drink. Difficulty controlling alcohol intake. Physiological withdrawal when intake is reduced. Tolerance, such that increasing amounts are required to produce the same effect. Harm resulting from continued alcohol use - eg, work or relationship problems.
Prevention When you think of addictions, you normally think about alcohol, In our culture, people who work hard or take good care of their bodies are admired. And society puts a stamp of approval on sexuality. As long as behavior — drinking, work, exercise — is balanced, it is OK. But a fine line exists between balanced behavior and addiction. Going over the line develops an addiction. Let’s take a look at the most widely recognized of addictions — alcoholism. Alcoholism is a disease that includes four symptoms: 1. Craving — a strong need or compulsion to drink; 2. Loss of control — the inability to limit one’s drinking on any given occasion; 3. Physical dependence — withdrawal symptoms, such as nausea, sweating, shakiness, and anxiety. These occur when alcohol use is stopped after a period of heavy drinking. 4. Tolerance — the need to drink greater amounts of alcohol in order to “get high.” When people have an alcohol problem, individuals who are close to them find it hard to discuss the problem. They hope it will go away. Sometimes they don’t even see the problem — often because the addicts indulge privately or because they themselves have a problem.
6 |Page
Experts I have consulted suggest talking about this with our patients, even if we are not alcoholism counselors, because if we care, we can at least offer encouragement and referral to experts within the community. Making the decision to help patients in this area depends on how much time you take with your patients, how comfortable you are talking about these issues, and how well prepared you are to talk about the disease. Before you bring up the subject with any patient, tap into your community’s resources. Find out what types of treatment centers are available, how to make referrals to them, and what other types of resources the patient may use, use as Alcoholics Anonymous. • • • • Cut down — Have you felt the need to cut down on your drinking? Annoyed — Have you ever been annoyed when someone criticizes your drinking? Guilty — Have you ever felt guilty about your drinking? Eye-opener — Have you ever felt the need for an eye-opener in the morning?
One question answered with a "yes" may indicate a possible problem with alcohol. If you answered "yes" to two or more questions, you probably have a problem that requires attention. If the CAGE test suggests that you have a problem with alcohol, do not attempt to solve the problem on your own. Few people can do this. Here are some general guidelines for your discussion with patients: 1. Assume a non-judgmental attitude. 2. Be aware of your own preconceptions about the abuse of alcohol. 3. Acknowledge that the problem is difficult to talk about. 4. Assure the patient you are interested in his or her health. 5. Assure confidentiality.
7 |Page
6. Ask if the patient is in recovery. People undergo several stages of change and receptivity concerning addiction. It’s helpful to be aware of these stages and to try to recognize which state a person may be in: • Precontemplation. The individual does not even think about the need to stop what he is doing and may believe there is no problem. When you come across such an individual, planting “seeds” for future recovery can be helpful. • Contemplation. The person has already begun thinking she may have a problem. You can tip the balance between making changes and not making changes. •Preparation. The patient has been thinking about where to go for help. You can be helpful by reinforcing his decision and help him to determine the best course of action. • Action. The person has signed up for help. You can aid by being supportive. • Maintenance. The individual has been through treatment and is remaining sober and straight. Your role is to be encouraging and supportive. • Termination. If you see signs of relapse, offer support. Alcoholism — or any addiction — is not a weakness; it is a disease. Learn about it. And approach the subject with compassion. You can be a vehicle for healing the soul as well as the spine. References: 1. Nichols M, Scarborough P, Allender S, et al; What is the optimal level of population alcohol consumption for chronic disease prevention in England? Modelling the impact of changes in average consumption levels. BMJ Open. 2012 May 30;2(3). pii: e000957. doi: 10.1136/bmjopen-2012-000957. Print 2012. 2. Drinking: adult's behaviour and knowledge - 2009 Report, UK National Statistics 3. Statistics on Alcohol: England, NHS Information Centre, 2012
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4. Islami F, Fedirko V, Tramacere I, et al ; Alcohol drinking and esophageal squamous
cell carcinoma with focus on light-drinkers and never-smokers: a systematic review and meta-analysis. Int J Cancer. 2011 Nov 15;129(10):2473-84. doi: 10.1002/ijc.25885. Epub 2011 Apr 7. 5. More men dying in the UK as a result of alcohol, Office for National Statistics, 2012. 6. Prevention and reduction of alcohol misuse - Evidence briefing (2nd edition), NICE/Health Development Agency, March 2005 7. Sadr Azodi O, Orsini N, Andren-Sandberg A, et al; Effect of type of alcoholic beverage in causing acute pancreatitis. Br J Surg. 2011 Nov;98(11):1609-16. doi: 10.1002/bjs.7632. Epub 2011 Aug 3. 8. Nichols M, Scarborough P, Allender S, et al; What is the optimal level of population alcohol consumption for chronic disease prevention in England? Modelling the impact of changes in average consumption levels. BMJ Open. 2012 May 30;2(3). pii: e000957. doi: 10.1136/bmjopen-2012-000957. Print 2012. 9. Guidelines on the Management of Alcoholic Liver Disease, European Association for the Study of the Liver (2012) 10. Zhu H, Jia Z, Misra H, et al; Oxidative stress and redox signaling mechanisms of alcoholic liver disease: updated experimental and clinical evidence. J Dig Dis. 2012 Mar;13(3):133-42. doi: 10.1111/j.1751-2980.2011.00569.x. 11. Terry MB, Gammon MD, Zhang FF, et al; Alcohol dehydrogenase 3 and risk of esophageal and gastric adenocarcinomas. Cancer Causes Control. 2007 Nov;18(9):1039-46. Epub 2007 Jul 31. 12. Sarangapani A, Shanmugam C, Kalyanasundaram M, et al; Noninvasive prediction of large esophageal varices in chronic liver disease patients. Saudi J Gastroenterol. 2010 Jan-Mar;16(1):38-42.
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13. Higashiyama A, Okamura T, Watanabe M, et al; Alcohol consumption and cardiovascular disease incidence in men with and without hypertension: the Suita study. Hypertens Res. 2012 Aug 30. doi: 10.1038/hr.2012.133. 14. Conen D, Tedrow UB, Cook NR, et al; Alcohol consumption and risk of incident atrial fibrillation in women. JAMA. 2008 Dec 3;300(21):2489-96. 15. Alcohol and Health, Institute of Alcohol Studies, 2004 16. Alcohol dependence and harmful alcohol use; NICE Clinical Guideline (February 2011)
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