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Friday, January 22, 2016

Cancer Prevention

Dr. James Manos (MD)
January 22, 2016




                       Prevention of cancer



‘Prevention is better than cure’ (Hippocrates, ancient Greek doctor – the father of Western medicine, 460 – 370 B.C.)

Note: in this text, the writer expresses his point of view. Some advice is empirical, so you should consult your family doctor beforehand.

Prevention of cancer

·         A family history of malignancy and other diseases is essential.
·         Genetic counseling on high-risk patients with strong family history.
·         Screening/ preventing programs in high-risk groups.
·         For people aged twenty or older who get periodic health exams, a cancer-related check-up should include health counseling and, depending on a person’s age and gender, exams for cancers of the thyroid, oral cavity, skin, lymph nodes, testes, and ovaries, as well as for some other diseases besides cancer.

·         How someone can reduce cancer risk:

·         Staying away from all forms of tobacco.

·         There is no safe form of tobacco.
·         It’s also important to stay away from tobacco smoke (secondhand smoke). It also causes cancer, as well as other health problems.
·         Get to and stay at a healthy weight.
·         Get moving with regular physical activity.
·         Eat healthy with plenty of fruits and vegetables.
·         Limit how much alcohol he/she drinks (if he/she drinks).
·         Protects his/her skin.
·         Know his/herself, his/her family history, and his/her risks.
·         Gets regular check-ups and cancer screening tests.


·         Getting and staying at a healthy weight.

·         Being overweight or obese can increase the risk for many types of cancer. Someone can control his/her weight with choices about healthy eating and exercise.
·         Avoiding excessive weight gain throughout life
·         Everyone should balance the calories he/she takes in with the amount of physical activity he/she does.
·         If someone is overweight, he should try to get to a healthy weight and stay there. Losing even a small amount of weight has health benefits. Watching the portion sizes is essential to weight control – especially for foods high in fat and sugar. Low-fat and fat-free doesn’t always mean low-calorie, so we should read labels and try to eat vegetables, fruits, and whole grains instead of higher-calorie foods.


·         Get moving.

·         Adults should get at least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity activity each week (or a combination of these), preferably spread throughout the week.
·         Children and adolescents: should get at least 1 hour of moderate- or vigorous-intensity activity each day, with vigorous activity on at least 3 days each week.
·         Moderate activity is anything that makes someone breathe as hard as you do during a brisk walk. During moderate activities, someone will notice a slight increase in heart rate and breathing. Vigorous activities are performed at a higher intensity. They cause an increased heart rate, sweating, and a faster breathing rate.
·         People should limit the amount of time they spend sitting. 
·         Doing physical activities above usual, regardless of activity level, can have many health benefits.

·         Eating healthy.

·         People should eat at least 2 ½ cups of vegetables and fruits daily. They contain many vitamins and minerals, fiber, antioxidants, and substances. Because they are generally low in fat and calories, they may also help people stay at a healthy weight, which helps reduce the risk of cancer.
·         People should choose whole-grain bread, pasta, and cereal instead of processed (refined) grains. People should look for whole wheat, pumpernickel, rye, or oats as the first ingredient on the food label.
·         People should limit the amount of processed meats they eat (like cold cuts, bacon, and hot dogs) and the intake of red meats, such as beef, pork, and lamb. 
    If someone eats red meat, they should try lean meats and smaller portions. Also, he/she should try skinless poultry, fish, or legumes (peas and beans) as healthier protein sources.

·         Alcohol

·         People should limit how much alcohol they drink
·         Men should have no more than 2 drinks per day, and women should have no more than 1 drink per day. A drink is 12 ounces of regular beer, 5 ounces of wine, or 1 ½ ounces of 80-proof distilled spirits.

·         Reference (Retrieved: January 20, 2016):


For women:

·         Cervical cancer screening (American Cancer Society)

·         Pap test (cervical smear for cytology) for cervical cancer prevention starting from the beginning of sexual life.
  • Cervical cancer testing should start at age 21. Women under the age of 21 should not be tested.
  • Women between the ages of 21 and 29 should have a Pap test done every 3 years. HPV testing should not be used in this age group unless needed after an abnormal Pap test result.
  • Women between the ages of 30 and 65 should have a Pap test plus an HPV test (co-testing) done every 5 years. This is the preferred approach, but having a Pap test alone every 3 years is OK.
  • Women over 65 who have had regular cervical cancer testing with normal results in the past 10 years should not be tested for cervical cancer. Once testing is stopped, it should not be started again. Women with a history of serious cervical pre-cancer should continue to be tested for at least 20 years after that diagnosis, even if testing goes past age 65.
  • A woman who has had her uterus and cervix removed (a total hysterectomy) for reasons unrelated to cervical cancer and who has no history of cervical cancer or serious pre-cancer should not be tested.
  • All women vaccinated against HPV should still follow the screening recommendations for their age groups.
  • Some women – because of their health history (HIV infection, organ transplant, DES exposure, etc.) – may need a different screening schedule for cervical cancer. They should talk to their healthcare provider about their history.
·         Women over sixty-five who have had regular screening in the previous 10 years should stop cervical cancer screening if they haven’t had any severe pre-cancers (like CIN2 or CIN3) found in the last 20 years. Women with a history of CIN2 or CIN3 (cervical intraepithelial neoplasia) should continue testing for at least 20 years after the abnormality is found.
·         Women who have had a total hysterectomy (removal of the uterus and cervix) should stop screening (such as Pap tests and HPV tests) unless the hysterectomy was done as a treatment for cervical pre-cancer (or cancer). Women who have had a hysterectomy without removal of the cervix (called a supracervical hysterectomy) should continue cervical cancer screening according to the guidelines above.
·         Women of any age should NOT be screened yearly by any screening method.
·         Women who have been vaccinated against HPV should still follow these guidelines.
·         Reference (Retrieved: January 19, 2016):


                  Pelvic examination 


·         The American College of Obstetricians and Gynecologists (ACOG) has issued updated guidelines for annual ‘Well Woman’ assessments with specific recommendations on when to perform pelvic exams in asymptomatic women and when to begin clinical breast exams.
·         ACOG recommends that pelvic exams be performed only when indicated by medical history for patients younger than 21 years. No evidence supports the routine exam for an asymptomatic patient before age 21 years, ‘although it is recognized that pelvic pathology sometimes is identified by a pelvic examination on an asymptomatic patient.’ Speculum exams for cervical cancer screening should begin at the age of 21 years, irrespective of the sexual activity of the patient.
·         ACOG recommends yearly full pelvic examinations for patients aged 21 years and older but notes that the advice is based on ‘expert opinion, and limitations of the internal pelvic examination should be recognized.’ For example, the bimanual examination is useful for evaluating the uterus but has a low sensitivity for detecting ‘adnexal masses,’ which include ovarian cysts and ectopic pregnancies.
·         Although annual pelvic exams for women older than twenty-one seem ‘logical,’ the opinion notes that ‘[n]o evidence supports or refutes the annual pelvic examination or speculum and bimanual examination for the asymptomatic, low-risk patient.’ Also, no data exists on when and how often to perform the exam. Whether or not to perform a complete pelvic examination ‘should be a shared decision after a discussion between the patient and her health care provider.’
·         The exam is always appropriate for patients with symptoms ‘suggestive of female genital tract problems. These include menstrual disorders, vaginal discharge, infertility, or pelvic pain. Perimenopausal patients with abnormal uterine bleeding, changes in bowel or bladder function, or vaginal discomfort should have a pelvic examination. The exam is also called for in older, menopausal women with abnormal bleeding, vaginal bulge, urinary or fecal incontinence, or vaginal dryness.
·         Reference (Retrieved: January 19, 2016):

HPV (human papillomavirus)
·         There are more than 100 types of HPV. About thirty or so types can cause genital infections. Some can cause genital warts. Other types can cause cervical or other genital cancers. The additional 70 or so HPV types can cause infections and warts elsewhere on the body, such as on the hands. Certain HPV types are classified as ‘high-risk’ because they lead to abnormal cell changes and can cause genital cancers: cervical cancer and cancer of the vulva, anus, and penis. Researchers say that virtually all cervical cancers – more than 99% – are caused by these high-risk HPV viruses. The most common high-risk strains of HPV are types 16 and 18, which cause about 70% of all cervical cancers. If the body clears the infection, the cervical cells return to normal. But if the body does not fight the virus, the cells in the cervix can continue to change abnormally. This can lead to precancerous changes or cervical cancer. HPV can also invade the mouth during oral sex. Those infections usually cause no symptoms, but a lingering infection with a cancer-linked strain can lead to oropharyngeal cancer.
·         For sexually active women, HPV (human papillomavirus) immunization is recommended. The HPV virus is related to cervical cancer. HPV is suggested for females (3 doses) aged 9 – 26. Recently HPV vaccine has also been administered in men, especially for high-risk such as men who have sex with men (MSM).
·         Two vaccines are licensed for use in females, the bivalent HPV vaccine (HPV2) and quadrivalent HPV vaccine (HPV4), and one HPV vaccine for use in males (HPV4).
·         For females, HPV4 or HPV2 is recommended in a 3-dose series for routine vaccination at age 11 or 12 years and for those aged 13 through 26 years, if not previously vaccinated.
·         For males, HPV4 is recommended in a 3-dose series for routine vaccination at age 11 or 12 years and for those aged 13 through 21 years if not previously vaccinated. Males aged 22 through 26 years may be vaccinated.
·         HPV4 is recommended for men who have sex with men through age 26 years for those who did not get any or all doses when they were younger.
·         Vaccination is recommended for immunocompromised persons (including those with HIV infection) through age 26 years for those who did not get any or all doses when they were younger.
·         A complete series for either HPV4 or HPV2 consists of 3 doses. The second dose should be administered 4 to 8 weeks (minimum interval of 4 weeks) after the first dose; the third dose should be administered 24 weeks after the first dose and 16 weeks after the second dose (minimum interval of at least 12 weeks).
·         HPV vaccines are not recommended for use in pregnant women. However, pregnancy testing is not needed before vaccination. If a woman is found to be pregnant after initiating the vaccination series, no intervention is required; the remainder of the 3-dose series should be delayed until completion or termination of pregnancy.

·         Reference (Retrieved: January 20, 2016):


·         Breast self – examination & mammogram

·         Adult women of all ages are encouraged to perform a breast self-exam at least once a month.
·         For breast self-examinations, see:


·       The following guidelines are for women at average risk for breast cancer: 
·         Women with a personal history of breast cancer, a family history of breast cancer, a genetic mutation known to increase the risk of breast cancer (such as BRCA), and women who had radiation therapy to the chest before the age of thirty are at higher risk for breast cancer, not average risk.
·         Women ages 40 to 44 should have the choice to start annual breast cancer screening with mammograms if they wish to do so. The risks of screening, as well as the potential benefits, should be considered.
·         Women aged 45 to 54 should get mammograms every year.
·         Women aged fifty-five and older should switch to mammograms every 2 years or have the choice to continue yearly screening.
·         Screening should continue as long as a woman is in good health and is expected to live 10 more years or longer.
·         All women should know the benefits, limitations, and potential harms of breast cancer screening. They should also be familiar with how their breasts normally look and feel and report any changes to a healthcare provider immediately.
·         Regular mammograms can often help find breast cancer at an early stage when treatment is most likely to be successful. A mammogram can detect breast changes that could be cancer years before physical symptoms develop. Results from many decades of research show that women with regular mammograms are more likely to have breast cancer found early, less likely to need aggressive treatment [like surgery to remove the entire breast (mastectomy) and chemotherapy], and more likely to be cured.
·         Mammograms are not perfect. They miss some cancers. And sometimes, more tests will be needed to find out if something found on a mammogram is or is not cancer. There’s also a small possibility of being diagnosed with cancer that never would have caused any problems had it not been found during screening. Women must get mammograms to know what to expect and understand the benefits and limitations of screening.
·         Research does not show a clear advantage of physical breast exams done by either a health professional or by a woman herself for breast cancer screening. 
·         Women at elevated risk for breast cancer based on specific factors should get an MRI and a mammogram every year. This includes women who:
·         a) Have a lifetime risk of breast cancer of about 20 to 25 percent or higher, according to risk assessment tools based mainly on family history.
·         b) Have a known BRCA1 or BRCA2 gene mutation.
·         c) Have a first-degree relative (parent, brother, sister, or child) with a BRCA1 or BRCA2 gene mutation and have not had a genetic test for themselves.
·         d) Had radiation therapy to the chest when they were between the ages of 10 and 30 years.
·         e) Have Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome, or have first-degree relatives with one of these syndromes.
·         The American Cancer Society recommends against MRI screening for women whose lifetime risk of breast cancer is less than 15%.
·         There’s not enough evidence to make a recommendation for or against yearly MRI screening for women who have a moderately increased risk of breast cancer (a lifetime risk of 15% to 20% according to risk assessment tools that are based mainly on family history) or who may be at increased risk of breast cancer based on specific factors, such as:
·         a) Having a personal history of breast cancer, ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), atypical ductal hyperplasia (ADH), or atypical lobular hyperplasia (ALH).
·         b) Having dense breasts (‘extremely’ or ‘heterogeneously’ dense) as seen on a mammogram.
·         If MRI is used, it should be in addition to, not instead of, a screening mammogram. Although an MRI is a more sensitive test (it’s more likely to detect cancer than a mammogram), it may still miss some cancers that a mammogram would detect.
·         For most women at elevated risk, screening with MRI and mammograms should begin at age 30 years and continue for as long as a woman is in good health. However, the evidence is limited about the best age to start screening. This decision should be based on shared decision-making between patients and their healthcare providers, considering personal circumstances and preferences.



     Endometrial (uterine) cancer

   The American Cancer Society recommends that at the time of menopause, all women should be told about the risks and symptoms of endometrial cancer. Women should report any unexpected vaginal bleeding or spot to their doctors. Because of their history, some women may need to consider having a yearly endometrial biopsy. They should talk with a healthcare provider about their history.


General recommendations:

·         For sexually active women, HPV (human papillomavirus) immunization is recommended. The HPV virus is related to cervical cancer. HPV is suggested for females (3 doses) aged 9 – 26. Recently, the HPV vaccine has also been used in men, exceptionally high-risk groups such as men who have sex with men (MSM) (see above).
·         Skin, breast, and testicular (referred to as the testes) self-examination and physical examination. The breast and testicles should be self-examined after a warm bath for lumps.
·         Periodic complete skin examination recommended from ACS (especially skin cancer screening) by a dermatologist (skin doctor), especially on people with moles and other skin lesions, including skin lumps, and on white people with red or blond hair, blue or green eyes, or fair skin that freckles or burns easily, that are at increased risk.
·         Avoidance of UV sunlight and solarium and regular use of high SPF (sun protection factor) sunscreen (more than 15 SPF and with a high star rating for UVA protection) for the body & face (for the face, there are particular products) for the prevention of skin cancer and especially malignant melanoma.
·         Reassessment of smoking status; encouragement of cessation in every visit!
·         A smoker who refuses to quit smoking should, at least, regularly perform a CXR (chest X-ray) to screen for cancer and spirometry, as a lung function test, to check for COPD, especially if a chronic smoker.
·         Alcohol and cigarette smoking are also connected with mouth and larynx cancer.
·         Bladder Cancer screening for high-risk patients, e.g., workers in color industries.
·         Oral (mouth) cancer screening and screening for oral leukoplakia (a precancerous lesion), especially in smokers, alcohol abusers, and those using dental products containing Sanguinaria canadensis (bloodroot).


Prostate cancer

·       On men, prostate cancer screening with annual PSA (prostate-specific antigens) and digital rectal examination (and, if needed, a transrectal ultrasound TRUS).
In 2009, the American Cancer Society (ACS) Prostate Cancer Advisory Committee began the process of a complete update of recommendations for early prostate cancer detection. The ACS recommends that asymptomatic men with at least a 10-year life expectancy have an opportunity to make an informed decision with their healthcare provider about prostate cancer after receiving information about the uncertainties, risks, and potential benefits of prostate cancer screening. Prostate cancer screening should not occur without an informed decision-making process.
Men at average risk should receive this information beginning at the age of 50 years.
Men in higher-risk groups should receive this information before the age of 50 years. Men should receive this information directly from their healthcare providers or be referred to reliable and culturally appropriate sources. Patient decision aids help prepare men to decide on whether to be tested. 
The AUA (American Urological Association) commissioned an independent group to conduct a systematic review and meta-analysis of the published prostate cancer detection and screening literature. The protocol of the systematic review was developed a priori by the expert panel. 

1)    The Panel recommends against PSA screening in men under age 40 years (Recommendation – Evidence Strength Grade C).

There is a low prevalence of clinically detectable prostate cancer in this age group, no evidence demonstrating the benefit of screening, and likely the same harms of screening as in other age groups.

2)    The Panel does not recommend routine screening at average risk in men aged 40 to 54 years (Recommendation – Evidence Strength Grade C).
For men younger than age 55 years at higher risk (e.g., positive family history or African American race), decisions regarding prostate cancer screening should be individualized.

3)    For men between the ages of 55 to 69 years, the Panel recognizes that the decision to undergo PSA screening involves weighing the benefits of preventing prostate cancer mortality in 1 man for every 1,000 men screened over a decade against the known potential harms associated with screening and treatment. For this reason, the Panel strongly recommends shared decision-making for men aged 55 to 69 considering PSA screening and proceeding based on a man's values and preferences (Standard – Evidence Strength Grade B).

The most significant benefit of screening appears to be in men ages 55 to 69 years.

4)    To reduce the harms of screening, a routine screening interval of two years or more may be preferred over annual screening in those men who have participated in shared decision-making and decided on screening. Compared to annual screening, screening intervals of two years are expected to preserve the majority of the benefits and reduce overdiagnosis and false positives (Option – Evidence Strength Grade C).
Additionally, intervals for rescreening can be individualized by a baseline PSA level.

5)    The Panel does not recommend routine PSA screening in men over 70 years or any man with less than a 10 to 15-year life expectancy (Recommendation – Evidence Strength Grade C).

Some men over seventy who are in excellent health may benefit from prostate cancer screening.

·         Reference (Retrieved: January 19, 2016): 


·         Colorectal cancer

·         The American Cancer Society believes that preventing colorectal cancer (and not just finding it early) should be a primary reason for getting tested. Having their polyps found and removed keeps some people from getting colorectal cancer. Tests with the best chance of finding both polyps and cancer are preferred.
·         Beginning at age 50, both men and women at average risk for developing colorectal cancer should use one of the screening tests below:
·         Tests that find polyps and cancer:
·         Flexible sigmoidoscopy every 5 years*
·         Colonoscopy every 10 years
·         Double-contrast barium enema every 5 years*
·         CT colonography (virtual colonoscopy) every 5 years*
·         Tests that mainly find cancer:
·         Guaiac-based fecal occult blood test (gFOBT) every year*,**
·         Fecal immunochemical test (FIT) every year*,**
·         Stool DNA test (sDNA) every 3 years*
·         (*)Colonoscopy should be done if test results are positive.
·         (**) Highly sensitive versions of these tests should be used with the take-home multiple sample method. An FOBT or FIT done during a digital rectal exam in the doctor's office is inadequate for screening.
·         In a digital rectal examination (DRE), a doctor examines the rectum with a lubricated, gloved finger. Although a DRE is often included as part of a routine physical exam, it is not recommended as a stand-alone test for colorectal cancer. This simple test, which is not usually painful, can detect masses in the anal canal or lower rectum. However, alone, it is not a good test for detecting colorectal cancer because of its limited reach.
·         Doctors often find a small stool in the rectum when doing a DRE. However, merely checking stool obtained this way for bleeding with an FOBT or FIT is not an acceptable screening method for colorectal cancer. Research has shown that this type of stool exam will miss more than 90% of colon abnormalities, including most cancers.
·         If someone is at an increased or elevated risk of colorectal cancer, he/she should begin colorectal cancer screening before age 50 and/or be screened more often. The following conditions make colorectal cancer risk higher than average:
·         A personal history of colorectal cancer or adenomatous polyps
·         A personal history of inflammatory bowel disease (ulcerative colitis or Crohn's disease)
·         A strong family history of colorectal cancer or polyps
·         A known family history of hereditary colorectal cancer syndromes such as familial adenomatous polyposis (FAP) or hereditary non-polyposis colon cancer (HNPCC).
·         Reference (Retrieved: January 20, 2016): 


Ovarian cancer

·        Ovarian ultrasound, blood CA125 tumor marker, and genetic screening in high-risk women for ovary cancer.
·         Previous studies have looked at screening using a blood test for the CA 125 protein, a tumor marker often elevated in women with ovarian cancer, combined with an ultrasound exam of the ovaries. However, those studies did not demonstrate a clear benefit to screening. The UK study was much larger, and the follow-up period was longer. The researchers used a computer program called the Risk of Ovarian Cancer Algorithm (ROCA) to calculate the risks and benefits for women to be screened for ovarian cancer. The algorithm is based on age, risk status, and CA-125 levels over time. As a result of the study, the authors estimate that 641 women must be screened regularly for 14 years to save one life from ovarian cancer. However, several women had false-positive results, leading to unnecessary surgeries and serious medical complications.
·         There has been a lot of research to develop a screening test for ovarian cancer, but there hasn’t been much success. The 2 tests used most often to screen for ovarian cancer are the transvaginal ultrasound (TVUS) and the CA-125 blood test.
·         TVUS is a test that uses sound waves to look at the uterus, fallopian tubes, and ovaries by putting an ultrasound wand into the vagina. It can help find a mass (tumor) in the ovary but can't tell if it is cancer or benign. When it is used for screening, most of the masses found are not cancer.
·         CA-125 is a protein in the blood. In many women with ovarian cancer, levels of CA-125 are high. This test can be useful as a tumor marker to help guide treatment in women with ovarian cancer because an elevated level often goes down if treatment is working. However, checking CA-125 levels is not as useful as a screening test for ovarian cancer because common conditions other than cancer can also cause elevated levels of CA-125. In women who have not been diagnosed with cancer, an elevated CA-125 level is often caused by one of these other conditions, not ovarian cancer. Also, not everyone who has ovarian cancer has a high CA-125 level. When someone not known to have ovarian cancer has an abnormal CA-125 level, the doctor might repeat the test to ensure the result is correct. The doctor could also consider ordering a transvaginal ultrasound test. In studies of women at average risk of ovarian cancer, using TVUS and CA-125 for screening led to more testing and sometimes more surgeries. Still, it did not lower the number of deaths caused by ovarian cancer. Therefore, no significant medical or professional organization recommends routinely using TVUS or the CA-125 blood test to screen for ovarian cancer. Some organizations state that these tests may be offered to screen women with a high risk of ovarian cancer due to an inherited genetic syndrome. However, even in these women, it’s not clear that using these tests for screening lowers their chances of dying from ovarian cancer.

·         Reference (Retrieved: January 20, 2016): 


Lung cancer

·         The American Cancer Society does not recommend tests to check for lung cancer in people at average risk. However, screening guidelines exist for those at elevated risk of lung cancer due to cigarette smoking. Screening might be right for people who are all of the following:
·         55 to 74 years of age
·         In good health
·         Have at least a 30-pack-year smoking history AND are either still smoking or have quit within the last 15 years. (A pack-year is the number of cigarette packs smoked daily multiplied by the years a person has smoked tobacco. Someone who smoked a pack of cigarettes per day for 30 years has a 30-pack-year smoking history, as does someone who smoked 2 packs a day for 15 years).
·         Screening is done with an annual low-dose CT scan (LDCT) of the chest. If someone fits the list above, he/she should talk to a healthcare provider if he/she wants to start screening.


Thanks for reading!


Reference
         
      Bibliography & External Links

Bibliography
Longo D.L., Fauci A.S., Kasper D.L., Hauser S.L., Jameson J.L., Loscalzo J.L., Harrison’s Manual of Medicine, 18th edition, McGraw–Hill, 2013. 
Longmore M., Wilkinson I.B., Davidson E.H., Foulkes A., Mafi A.R., Oxford Handbook of Clinical Medicine, 8th edition, Oxford University Press, 2010.
Ahmed N., Clinical Biochemistry, Oxford University Press, 2010.
Simon C., Everitt H., Kendrick T., Oxford Handbook of General Practice, Oxford Medical Publications, 2nd edition, 2005.
Longmore M., Wilkinson I., Turmezei T., Kay Cheung C., Oxford Handbook of Clinical Medicine, Oxford Medical Publications, 7th edition, 2008.
Collier J., Longmore M., Brinsden M., Oxford Handbook of Clinical Specialties, Oxford Medical Publications, 7th edition, 2006.
Stone C.K., Humphries R.L., Current Diagnosis and Treatment in Emergency Medicine, McGraw–Hill LANGE, 6th edition, 2008.
Disease prevention & health maintenance, p. 1103 – 1130, Harrison’s Manual of Medicine, Fauci A.S., Braunwald E.B., Kasper D.L., Hauser S.L., Longo D.L., Jameson J.L., Loscalzo J., 17th edition, Mc Graw Hill Medical, 2009.  mcgraw-hillmedical.com 
Screening in the future, p. 160 – 161, Oxford Handbook of General Practice, C. Simon, H. Everitt, T. Kendrick, 2nd edition, Oxford University Press,2005. www.oup.com

Reference – Links (Disease prevention)  
(Retrieved January 16, 2016):

               






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