Current Medical Diagnosis & Treatment 2015

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Disease Prevention & Health Promotion

Michael Pignone, MD, MPH René Salazar, MD

GENERAL APPROACH TO THE PATIENT

The medical interview serves several functions. It is used to collect information to assist in diagnosis (the “history” of the present illness), to understand patient values, to assess and communicate prognosis, to establish a therapeutic relationship, and to reach agreement with the patient about further diagnostic procedures and therapeutic options. It also serves as an opportunity to influence patient behavior, such as in motivational discussions about smoking cessation or medication adherence. Interviewing techniques that avoid domination by the clinician increase patient involvement in care and patient satisfaction. Effective clinician-patient communication and increased patient involvement can improve health outcomes.

 Patient Adherence

For many illnesses, treatment depends on difficult fundamental behavioral changes, including alterations in diet, taking up exercise, giving up smoking, cutting down drinking, and adhering to medication regimens that are often complex. Adherence is a problem in every practice; up to 50% of patients fail to achieve full adherence, and one-third never take their medicines. Many patients with medical problems, even those with access to care, do not seek appropriate care or may drop out of care prematurely. Adherence rates for short-term, self-administered therapies are higher than for long-term therapies and are inversely correlated with the number of interventions, their complexity and cost, and the patient’s perception of overmedication.

As an example, in HIV-infected patients, adherence to antiretroviral therapy is a crucial determinant of treatment success. Studies have unequivocally demonstrated a close relationship between patient adherence and plasma HIV RNA levels, CD4 cell counts, and mortality. Adherence levels of > 95% are needed to maintain virologic suppression. However, studies show that over 60% of patients are < 90% adherent and that adherence tends to decrease over time.

Patient reasons for nonadherence include simple forgetfulness, being away from home, being busy, and changes in daily routine. Other reasons include psychiatric disorders (depression or substance abuse), uncertainty about the effectiveness of treatment, lack of knowledge about the consequences of poor adherence, regimen complexity, and treatment side effects.

Patients seem better able to take prescribed medications than to adhere to recommendations to change their diet, exercise habits, or alcohol intake or to perform various self-care activities (such as monitoring blood glucose levels at home). For short-term regimens, adherence to medications can be improved by giving clear instructions. Writing out advice to patients, including changes in medication, may be helpful. Because low functional health literacy is common (almost half of English-speaking US patients are unable to read and understand standard health education materials), other forms of communication—such as illustrated simple text, videotapes, or oral instructions—may be more effective. For non–English-speaking patients, clinicians and health care delivery systems can work to provide culturally and linguistically appropriate health services.

To help improve adherence to long-term regimens, clinicians can work with patients to reach agreement on the goals for therapy, provide information about the regimen, ensure understanding by using the “teach-back” method, counsel about the importance of adherence and how to organize medication-taking, reinforce self-monitoring, provide more convenient care, prescribe a simple dosage regimen for all medications (preferably one or two doses daily), suggest ways to help in remembering to take doses (time of day, mealtime, alarms) and to keep appointments, and provide ways to simplify dosing (medication boxes). Single-unit doses supplied in foil wrappers can increase adherence but should be avoided for patients who have difficulty opening them. Medication boxes with compartments (eg, Medisets) that are filled weekly are useful. Microelectronic devices can provide feedback to show patients whether they have taken doses as scheduled or to notify patients within a day if doses are skipped. Reminders, including cell phone text messages, are another effective means of encouraging adherence. The clinician can also enlist social support from family and friends, recruit an adherence monitor, provide a more convenient care environment, and provide rewards and recognition for the patient’s efforts to follow the regimen. Collaborative programs that utilize pharmacists to help ensure adherence are also effective.

Adherence is also improved when a trusting doctor-patient relationship has been established and when patients actively participate in their care. Clinicians can improve patient adherence by inquiring specifically about the behaviors in question. When asked, many patients admit to incomplete adherence with medication regimens, with advice about giving up cigarettes, or with engaging only in “safer sex” practices. Although difficult, sufficient time must be made available for communication of health messages.

Medication adherence can be assessed generally with a single question: “In the past month, how often did you take your medications as the doctor prescribed?” Other ways of assessing medication adherence include pill counts and refill records; monitoring serum, urine, or saliva levels of drugs or metabolites; watching for appointment nonattendance and treatment nonresponse; and assessing predictable drug effects such as weight changes with diuretics or bradycardia from beta-blockers. In some conditions, even partial adherence, as with drug treatment of hypertension and diabetes mellitus, improves outcomes compared with nonadherence; in other cases, such as HIV antiretroviral therapy or treatment of tuberculosis, partial adherence may be worse than complete nonadherence.

 Guiding Principles of Care

Ethical decisions are often called for in medical practice, at both the “micro” level of the individual patient-clinician relationship and at the “macro” level of the allocation of resources. Ethical principles that guide the successful approach to diagnosis and treatment are honesty, beneficence, justice, avoidance of conflict of interest, and the pledge to do no harm. Increasingly, Western medicine involves patients in important decisions about medical care, eg, which colorectal screening test to obtain or modality of therapy for breast cancer or how far to proceed with treatment of patients who have terminal illnesses (see Chapter 5).

The clinician’s role does not end with diagnosis and treatment. The importance of the empathic clinician in helping patients and their families bear the burden of serious illness and death cannot be overemphasized. “To cure sometimes, to relieve often, and to comfort always” is a French saying as apt today as it was five centuries ago—as is Francis Peabody’s admonition: “The secret of the care of the patient is in caring for the patient.” Training to improve mindfulness and enhance patient-centered communication increases patient satisfaction and may also improve clinician satisfaction.

Coleman CI et al. Dosing frequency and medication adherence in chronic disease. J Manag Care Pharm. 2012 Sep;18(7):527–39. [PMID: 22971206]

Desroches S et al. Interventions to enhance adherence to dietary advice for preventing and managing chronic diseases in adults. Cochrane Database Syst Rev. 2013 Feb 28;2:CD008722. [PMID: 23450587]

Inadomi JM et al. Adherence to colorectal cancer screening: a randomized clinical trial of competing strategies. Arch Intern Med. 2012 Apr 9;172(7):575–82. [PMID: 22493463]

Viswanathan M et al. Interventions to improve adherence to self-administered medications for chronic diseases in the United States: a systematic review. Ann Intern Med. 2012 Dec 4;157(11):785–95. [PMID: 22964778]

HEALTH MAINTENANCE & DISEASE PREVENTION

Preventive medicine can be categorized as primary, secondary, or tertiary. Primary prevention aims to remove or reduce disease risk factors (eg, immunization, giving up or not starting smoking). Secondary prevention techniques promote early detection of disease or precursor states (eg, routine cervical Papanicolaou screening to detect carcinoma or dysplasia of the cervix). Tertiary prevention measures are aimed at limiting the impact of established disease (eg, partial mastectomy and radiation therapy to remove and control localized breast cancer). Tables 1–1 and 1–2 give leading causes of death in the United States and estimates of deaths from preventable causes.

Table 1–1. Leading causes of death in the United States, 2011.

Table 1–2. Deaths from all causes attributable to common preventable risk factors. (Numbers given in the thousands.)

Many effective preventive services are underutilized, and few adults receive all of the most strongly recommended services. The three highest-ranking services in terms of potential health benefits and cost-effectiveness include discussing aspirin use with high-risk adults, tobacco-use screening and brief interventions, and immunizing children. Other high-ranking services with data indicating substantial room for improvement in utilization are screening adults aged 50 and older for colorectal cancer, immunizing adults aged 65 and older against pneumococcal disease, and screening young women forChlamydia.

Several methods, including the use of provider or patient reminder systems (including interactive patient health records), reorganization of care environments, and possibly provision of financial incentives (though this remains controversial), can increase utilization of preventive services, but such methods have not been widely adopted.

Cruz M et al. Predicting 10-year mortality for older adults. JAMA. 2013 Mar 6;309(9):874–6. [PMID: 23462780]

Danaei G et al. The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med. 2009 Apr 28;6(4):e1000058. [PMID: 19399161]

Krogsbøll LT et al. General health checks in adults for reducing morbidity and mortality from disease: Cochrane systematic review and meta-analysis. BMJ. 2012 Nov 20;345:e7191. [PMID: 23169868]

Maciosek MV et al. Greater use of preventive services in U.S. health care could save lives at little or no cost. Health Aff (Millwood). 2010 Sep;29(9):1656–60. [PMID: 20820022]

Scott A et al. The effect of financial incentives on the quality of health care provided by primary care physicians. Cochrane Database Syst Rev. 2011 Sep 7;(9):CD008451. [PMID: 21901722]

US Burden of Disease Collaborators. The state of US health, 1990–2010: burden of diseases, injuries, and risk factors. JAMA. 2013 Aug 14;310(6):591–608. [PMID: 23842577]

PREVENTION OF INFECTIOUS DISEASES

Much of the decline in the incidence and fatality rates of infectious diseases is attributable to public health measures—especially immunization, improved sanitation, and better nutrition.

Immunization remains the best means of preventing many infectious diseases. Recommended immunization schedules for children and adolescents can be found online athttp://www.cdc.gov/vaccines/schedules/hcp/child-adolescent.html and the schedule for adults is outlined in Table 30–7. Substantial vaccine-preventable morbidity and mortality continue to occur among adults from vaccine-preventable diseases, such as hepatitis A, hepatitis B, influenza, and pneumococcal infections. Strategies to improve vaccination rates include increasing community demand for vaccinations; enhancing access to vaccination services; provider- or system-based interventions, such as reminder systems; assigning vaccination responsibilities to non-physician personnel and interventions that activate patients through personal contact.

Evidence suggests annual influenza vaccination is safe and effective with potential benefit in all age groups, and the Advisory Committee on Immunization Practices (ACIP) recommends routine influenza vaccination for all persons aged 6 months and older, including all adults. When vaccine supply is limited, certain groups should be given priority, such as adults 50 years and older, individuals with chronic illness or immunosuppression, and pregnant women. An alternative high-dose inactivated vaccine is available for adults 65 years and older. Adults 65 years and older can receive either the standard dose or high-dose vaccine, whereas those younger than 65 years should receive a standard-dose preparation.

Increasing reports of pertussis among US adolescents, adults, and their infant contacts have stimulated vaccine development for older age groups. The ACIP recommends routine use of a single dose of tetanus, diphtheria, and 5-component acellular pertussis vaccine (Tdap) for adults aged 19–64 years to replace the next booster dose of tetanus and diphtheria toxoids vaccine (Td). Due to increasing reports of pertussis in the United States, clinicians may choose to give Tdap to persons aged 65 years and older (particularly to those who might risk transmission to at-risk infants who are most susceptible to complications, including death), despite limited published data on the safety and efficacy of the vaccine in this age group.

Both hepatitis A vaccine and immune globulin provide protection against hepatitis A; however, administration of immune globulin may provide a modest benefit over vaccination in some settings. A recombinant protein hepatitis E vaccine has been developed that has proven safe and efficacious in preventing hepatitis E among high-risk populations. Hepatitis B vaccine administered as a three-dose series is recommended for all children aged 0–18 years and high-risk individuals (ie, health care workers, injection drug users, people with end-stage renal disease). Adults with diabetes are also at increased risk for hepatitis B infection, and in October 2011, the ACIP recommended vaccination for hepatitis B in diabetic patients aged 19–59 years. In diabetic persons aged 60 and older, hepatitis B vaccination should be considered.

Human papillomavirus (HPV) virus-like particle (VLP) vaccines have demonstrated effectiveness in preventing persistent HPV infections, and thus may impact the rate of cervical intraepithelial neoplasia (CIN) II–III. The American Academy of Pediatrics (AAP) recommends routine HPV vaccination for girls aged 11–12 years. The AAP also recommends that all unvaccinated girls and women aged 13–26 years receive the HPV vaccine. In October 2011, the ACIP approved recommendations for routine vaccination of males 11 or 12 years of age with three doses of HPV4 (quadrivalent vaccine). Vaccination of males with HPV may lead to indirect protection of women by reducing transmission of HPV and may prevent anal intraepithelial neoplasia and squamous cell carcinoma in men who have sex with men. Despite the effectiveness of the vaccine, rates of immunization are low. Interventions addressing personal beliefs and system barriers to vaccinations may help address the slow adoption of this vaccine.

Persons traveling to countries where infections are endemic should take precautions described in Chapter 30 and at http://wwwnc.cdc.gov/travel/destinations/list.htm. Immunization registries—confidential, population-based, computerized information systems that collect vaccination data about all residents of a geographic area—can be used to increase and sustain high vaccination coverage.

The rate of tuberculosis in the United States has been declining since 1992. In 2011, the US tuberculosis rate was 3.4 cases per 100,000 population, a decrease of 6.4% from the 2010 rate. This represents the lowest recorded rate since national tuberculosis surveillance began in 1953. Skin testing for tuberculosis (see Table 9–13) and treating selected patients reduce the risk of reactivation tuberculosis. Two blood tests, which are not confounded by prior BCG (bacillus Calmette-Guérin) vaccination, have been developed to detect tuberculosis infection by measuring in vitro T-cell interferon-gamma release in response to two antigens (one, the enzyme-linked immunospot [ELISpot], [T-SPOT.TB] and the other, a quantitative ELISA [QuantiFERON-TBGold] test). These T-cell–based assays have an excellent specificity that is higher than tuberculin skin testing in BCG-vaccinated populations.

The Advisory Council for the Elimination of Tuberculosis has called for a renewed commitment to eliminating tuberculosis in the United States, and the Institute of Medicine has published a detailed plan for achieving that goal. Patients with HIV infection are at an especially high risk for tuberculosis. In 2010, there were an estimated 1.1 million incident cases of tuberculosis among the 34 million people living with HIV. Early initiation of antiretroviral therapy may help control the HIV-associated tuberculosis syndemic.

Treatment of tuberculosis poses a risk of hepatotoxicity and thus requires close monitoring of liver transaminases. Alanine aminotransferase (ALT) monitoring during the treatment of latent tuberculosis infection is recommended for certain individuals (preexisting liver disease, pregnancy, chronic alcohol consumption). ALT should be monitored in HIV-infected patients during treatment of tuberculosis disease and should be considered in patients over the age of 35. Symptomatic patients with an ALT elevation three times the upper limit of normal or asymptomatic patients with an elevation five times the ULN should be treated with a modified or alternative regimen.

In 2010, the Centers for Disease Control and Prevention (CDC) updated guidelines for the prevention and treatment of sexually transmitted diseases. Highlights of these guidelines include updated treatments for bacterial vaginosis and genital warts as well as antibiotic-resistant Neisseria gonorrhoeae, the prevalence of which has risen (see Chapter 30).

HIV infection is a major infectious disease problem in the world. Since sexual contact is a common mode of transmission, primary prevention relies on eliminating unsafe sexual behavior by promoting abstinence, later onset of first sexual activity, decreased number of partners, and use of latex condoms. Unfortunately, as many as one-third of HIV-positive persons continue unprotected sexual practices after learning that they are HIV-infected. Preexposure prophylaxis with antiretroviral drugs in men who have sex with men could have a major impact on preventing HIV infection, and studies evaluating the impact in other groups are underway. Postexposure prophylaxis is widely used after occupational and nonoccupational contact, and it has been estimated to reduce the risk of transmission by approximately 80%.

The CDC recommends universal HIV screening of all patients age 13–64, and the US Preventive Services Task Force (USPSTF) recommends that clinicians screen adolescents and adults age 15 to 65 years. In addition to reducing sexual transmission of HIV, initiation of antiretroviral therapy reduces the risk for AIDS-defining events and death among patients with less immunologically advanced disease.

In immunocompromised patients, live vaccines are contraindicated but many killed or component vaccines are safe and recommended. Asymptomatic HIV-infected patients have not shown adverse consequences when given live MMR and influenza vaccinations as well as tetanus, hepatitis B, H influenza type b and pneumococcal vaccinations—all should be given. However, if poliomyelitis immunization is required, the inactivated poliomyelitis vaccine is indicated. In symptomatic HIV-infected patients, live virus vaccines such as MMR should generally be avoided, but annual influenza vaccination is safe.

Herpes zoster, caused by reactivation from previous varicella zoster virus infection, affects many older adults and people with immune system dysfunction. Whites are at higher risk than other ethnic groups and the incidence in adults aged 65 and older may be higher than previously described. It can cause postherpetic neuralgia, a potentially debilitating chronic pain syndrome. A varicella vaccine is available for the prevention of herpes zoster. The ACIP recommends routine zoster vaccination, administered as a one-time subcutaneous dose (0.65 mL), of all persons aged 60 years or older. Persons who report a previous episode of zoster can be vaccinated; however, the vaccine is contraindicated in immunocompromised (primary or acquired) individuals. The durability of vaccine response and whether any booster vaccination is needed are still uncertain. The cost-effectiveness of the vaccine varies substantially, and the patient’s age should be considered in vaccine recommendations. One study reported a cost-effectiveness exceeding $100,000 per quality-adjusted life year saved. Despite its availability, uptake of the vaccine remains low at 2–7% nationally. Financial barriers (cost, limited knowledge of reimbursement) have had a significant impact on its underutilization.

Methicillin-resistant Staphylococcus aureus (MRSA), previously recognized as a nosocomial pathogen, has emerged as a common cause of staphylococcal infection in the outpatient setting; it accounts for more than 50% of outpatient staphylococcal infections. Strategies to prevent MRSA infection include screening asymptomatic carriers; however, universal screening of large populations is not cost-effective. Screening high-risk populations needs additional study. Diligent hand hygiene, rigorous infection control policies, and appropriate use of antibiotics remain key to preventing MRSA infections.

Cataldo MA et al. Methicillin-resistant Staphylococcus aureus: a community health threat. Postgrad Med. 2010 Nov;122(6):16–23. [PMID: 21084777]

Centers for Disease Control and Prevention (CDC). ACIP recommends all 11–12 year-old males get vaccinated against HPV. http://www.cdc.gov/media/releases/2011/a1025_ACIP_HPV_Vote.html

Centers for Disease Control and Prevention (CDC). Child, Adolescent & “Catch-up” Immunization Schedules, United States, 2014. http://www.cdc.gov/vaccines/schedules/hcp/child-adolescent.html

Centers for Disease Control and Prevention (CDC). HIV/AIDS, 2014. https://www.cdc.gov/hiv/basics/index.html.

Centers for Disease Control and Prevention (CDC). Pertussis (whooping cough) outbreaks, 2013. http://www.cdc.gov/pertussis/outbreaks.html

Centers for Disease Control and Prevention (CDC). Adult Immunization Schedules, United States, 2014. http://www.cdc.gov/vaccines/schedules/hcp/adult.html.

Centers for Disease Control and Prevention (CDC). Trends in tuberculosis—United States, 2011. MMWR Morb Mortal Wkly Rep. 2012 Mar 23;61(11):181–5. [PMID: 22437911]

Centers for Disease Control and Prevention (CDC). Use of hepatitis B vaccination for adults with diabetes mellitus: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2011 Dec 23;60(5):1709–11. [PMID: 22189894]

Chou R et al. Screening for HIV: systematic review to update the 2005 U.S. Preventive Services Task Force recommendation. Ann Intern Med. 2012 Nov 20;157(10):706–18. [PMID: 23165662]

Gagliardi AM et al. Vaccines for preventing herpes zoster in older adults. Cochrane Database Syst Rev. 2012 Oct 17;10:CD008858. [PMID: 23076951]

Hurley LP et al. Barriers to the use of herpes zoster vaccine. Ann Intern Med. 2010 May 4;152(9):555–60. [PMID: 20439573]

Kelesidis T et al. Preexposure prophylaxis for HIV prevention. Curr HIV/AIDS Rep. 2011 Jun;8(2):94–103. [PMID: 21465112]

Lau D et al. Interventions to improve influenza and pneumococcal vaccination rates among community-dwelling adults: a systematic review and meta-analysis. Ann Fam Med. 2012 Nov–Dec;10(6):538–46. [PMID: 23149531]

Mazurek GH et al. Updated guidelines for using interferon gamma release assays to detect Mycobacterium tuberculosis infection—United States, 2010. MMWR Recomm Rep. 2010 Jun 25;59(RR-5):1–25. [PMID: 20577159]

Paisley RD et al. Whooping cough in adults: an update on a reemerging infection. Am J Med. 2012 Feb;125(2):141–3. [PMID: 22269615]

Parks NA et al. Routine screening for methicillin-resistant Staphylococcus aureus. Surg Infect (Larchmt). 2012 Aug;13(4):223–7. [PMID: 22913747]

Rey D. Post-exposure prophylaxis for HIV infection. Expert Rev Anti Infect Ther. 2011 Apr;9(4):431–42. [PMID: 21504400]

Ridda I et al. The importance of pertussis in older adults: a growing case for reviewing vaccination strategy in the elderly. Vaccine. 2012 Nov 6;30(48):6745–52. [PMID: 22981762]

Sanford M et al. Zoster vaccine (Zostavax): a review of its use in preventing herpes zoster and postherpetic neuralgia in older adults. Drugs Aging. 2010 Feb 1;27(2):159–76. [PMID: 20104941]

Suthar AB et al. Antiretroviral therapy for prevention of tuberculosis in adults with HIV: a systematic review and meta-analysis. PLoS Med. 2012;9(7):e1001270. [PMID: 22911011]

Williams WW et al; Centers for Disease Control and Prevention (CDC). Influenza vaccination coverage among adults—National Health Interview Survey, United States, 2008–09 influenza season. MMWR Morb Mortal Wkly Rep. 2012 Jun 15;61(Suppl):65–72. [PMID: 22695466]

Wolfe RM. Update on adult immunizations. J Am Board Fam Med. 2012 Jul–Aug;25(4):496–510. [PMID: 22773718]

Workowski KA et al; Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR Recomm Rep. 2010 Dec 17;59(RR-12):1–110. Erratum in MMWR Recomm Rep. 2011 Jan 14;60(1);18. [PMID: 21160459]

Zhu FC et al. Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomized, double-blind placebo-controlled, phase 3 trial. Lancet. 2010 Sep 11;376(9744):895–902. [PMID: 20728932]

PREVENTION OF CARDIOVASCULAR DISEASE

Cardiovascular diseases, including coronary heart disease (CHD) and stroke, represent two of the most important causes of morbidity and mortality in developed countries. Several risk factors increase the risk for coronary disease and stroke. These risk factors can be divided into those that are modifiable (eg, lipid disorders, hypertension, cigarette smoking) and those that are not (eg, age, sex, family history of early coronary disease). Impressive declines in age-specific mortality rates from heart disease and stroke have been achieved in all age groups in North America during the past two decades, in large part through improvement of modifiable risk factors: reductions in cigarette smoking, improvements in lipid levels, and more aggressive detection and treatment of hypertension. This section considers the role of screening for cardiovascular risk and the use of effective therapies to reduce such risk. Key recommendations for cardiovascular prevention are shown in Table 1–3. New guidelines issued in 2013 encourage regular assessment of global cardiovascular risk in adults 40–79 years of age without known cardiovascular disease.

Table 1–3. Expert recommendations for cardiovascular prevention methods: US Preventive Services Task Force (USPSTF).1

Goff DC Jr et al. 2013 ACC/AHA Guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013 Nov 12. [Epub ahead of print] [PMID: 24222018]

Sugerman DT et al. JAMA patient page. Statins. JAMA. 2013 Apr 3;309(13):1419. [PMID: 23549589]

Taylor F et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013 Jan 31;1:CD004816. [PMID: 23440795]

 Abdominal Aortic Aneurysm

One-time screening for abdominal aortic aneurysm (AAA) by ultrasonography in men aged 65–75 years is associated with a significant reduction in AAA-related mortality (odds ratio, 0.55 [95% CI, 0.36 to 0.86]) and possibly a reduction in all-cause mortality (OR = 0.98, 95% CI, 0.95, 1.00). Women do not appear to benefit from screening, and most of the benefit in men appears to accrue among current or former smokers. Recent analyses suggest that screening men aged 65 years and older is highly cost-effective.

Søgaard R et al. Cost effectiveness of abdominal aortic aneurysm screening and rescreening in men in a modern context: evaluation of a hypothetical cohort using a decision analytical model. BMJ. 2012 Jul 5;345:e4276. [PMID: 22767630]

 Cigarette Smoking

Cigarette smoking remains the most important cause of preventable morbidity and early mortality. In 2000, there were an estimated 4.8 million premature deaths in the world attributable to smoking, 2.4 million in developing countries and 2 million in industrialized countries. More than three-quarters (3.8 million) of these deaths were in men. The leading causes of death from smoking were cardiovascular diseases (1.7 million deaths), chronic obstructive pulmonary disease (COPD) (1 million deaths), and lung cancer (0.9 million deaths). Cigarettes are responsible for one in every four deaths in the United States: in 2005, over 250,000 deaths in men and over 225,000 deaths in women were attributable to smoking. Annual costs of smoking-related health care is approximately $96 billion per year in the United States, with another $97 billion in productivity losses. Fortunately, US smoking rates are declining; in 2012, 18% of US adults were smokers.

Nicotine is highly addictive, raises brain levels of dopamine, and produces withdrawal symptoms on discontinuation. Smokers die 5–8 years earlier than never-smokers. They have twice the risk of fatal heart disease, 10 times the risk of lung cancer, and several times the risk of cancers of the mouth, throat, esophagus, pancreas, kidney, bladder, and cervix; a twofold to threefold higher incidence of stroke and peptic ulcers (which heal less well than in nonsmokers); a twofold to fourfold greater risk of fractures of the hip, wrist, and vertebrae; four times the risk of invasive pneumococcal disease; and a twofold increase in cataracts.

In the United States, over 90% of cases of COPD occur among current or former smokers. Both active smoking and passive smoking are associated with deterioration of the elastic properties of the aorta (increasing the risk of aortic aneurysm) and with progression of carotid artery atherosclerosis. Smoking has also been associated with increased risks of leukemia, of colon and prostate cancers, of breast cancer among postmenopausal women who are slow acetylators of N-acetyltransferase-2 enzymes, of osteoporosis, and of Alzheimer disease. In cancers of the head and neck, lung, esophagus, and bladder, smoking is linked to mutations of the P53 gene, the most common genetic change in human cancer. Patients with head and neck cancer who continue to smoke during radiation therapy have lower rates of response than those who do not smoke. Olfaction and taste are impaired in smokers, and facial wrinkles are increased. Heavy smokers have a 2.5 greater risk of age-related macular degeneration.

The children of smokers have lower birth weights, are more likely to be mentally retarded, have more frequent respiratory infections and less efficient pulmonary function, have a higher incidence of chronic ear infections than children of nonsmokers, and are more likely to become smokers themselves.

In addition, exposure to environmental tobacco smoke has been shown to increase the risk of cervical cancer, lung cancer, invasive pneumococcal disease, and heart disease; to promote endothelial damage and platelet aggregation; and to increase urinary excretion of tobacco-specific lung carcinogens. The incidence of breast cancer may be increased as well. Of approximately 450,000 smoking-related deaths in the United States annually, as many as 53,000 are attributable to environmental tobacco smoke.

Smoking cessation reduces the risks of death and of myocardial infarction in people with coronary artery disease; reduces the rate of death and acute myocardial infarction in patients who have undergone percutaneous coronary revascularization; lessens the risk of stroke; slows the rate of progression of carotid atherosclerosis; and is associated with improvement of COPD symptoms. On average, women smokers who quit smoking by age 35 add about 3 years to their life expectancy, and men add more than 2 years to theirs. Smoking cessation can increase life expectancy even for those who stop after the age of 65.

Although tobacco use constitutes the most serious common medical problem, it is undertreated. Almost 40% of smokers attempt to quit each year, but only 4% are successful. Persons whose clinicians advise them to quit are 1.6 times as likely to attempt quitting. Over 70% of smokers see a physician each year, but only 20% of them receive any medical quitting advice or assistance.

Factors associated with successful cessation include having a rule against smoking in the home, being older, and having greater education. Several effective interventions are available to promote smoking cessation, including counseling, pharmacotherapy, and combinations of the two. The five steps for helping smokers quit are summarized in Table 1–4.

Table 1–4. Actions and strategies for the primary care clinician to help patients quit smoking.

Common elements of supportive smoking cessation treatments are reviewed in Table 1–5. A system should be implemented to identify smokers, and advice to quit should be tailored to the patient’s level of readiness to change. Pharmacotherapy to reduce cigarette consumption is ineffective in smokers who are unwilling or not ready to quit. Conversely, all patients trying to quit should be offered pharmacotherapy except those with medical contraindications, women who are pregnant or breast-feeding, and adolescents. Weight gain occurs in most patients (80%) following smoking cessation. Average weight gain is 2 kg, but for some (10–15%), major weight gain—over 13 kg—may occur. Planning for the possibility of weight gain, and means of mitigating it, may help with maintenance of cessation.

Table 1–5. Common elements of supportive smoking treatments.

Several pharmacologic therapies have been shown to be effective in promoting cessation. Nicotine replacement therapy doubles the chance of successful quitting. The nicotine patch, gum, and lozenges are available over-the-counter, and nicotine nasal spray and inhalers by prescription. The sustained-release antidepressant drug bupropion (150–300 mg/d orally) is an effective smoking cessation agent and is associated with minimal weight gain, although seizures are a contraindication. It acts by boosting brain levels of dopamine and norepinephrine, mimicking the effect of nicotine. More recently, varenicline, a partial nicotinic acetylcholine-receptor agonist, has been shown to improve cessation rates; however, its adverse effects, particularly its effects on mood, are not completely understood and warrant careful consideration. No single pharmacotherapy is clearly more effective than others, so patient preferences and data on adverse effects should be taken into account in selecting a treatment. Recently, e-cigarettes have become popular; some serve as a nicotine-delivery device, but others deliver water vapor. Their efficacy in smoking cessation, however, has not been well evaluated, and some users may find them addictive.

Clinicians should not show disapproval of patients who failed to stop smoking or who are not ready to make a quit attempt. Thoughtful advice that emphasizes the benefits of cessation and recognizes common barriers to success can increase motivation to quit and quit rates. An intercurrent illness such as acute bronchitis or acute myocardial infarction may motivate even the most addicted smoker to quit.

Individualized or group counseling is very cost-effective, even more so than in treating hypertension. Smoking cessation counseling by telephone (“quitlines”) and text messaging-based intervention have both proved effective. An additional strategy is to recommend that any smoking take place out of doors to limit the effects of passive smoke on housemates and coworkers. This can lead to smoking reduction and quitting.

The clinician’s role in smoking cessation is summarized in Table 1–4. Public policies, including higher cigarette taxes and more restrictive public smoking laws, have also been shown to encourage cessation, as have financial incentives directed to patients.

Cahill K et al. Pharmacological interventions for smoking cessation: an overview and network meta-analysis. Cochrane Database Syst Rev. 2013 May 31;5:CD009329. [PMID: 23728690]

Carson KV et al. Training health professionals in smoking cessation. Cochrane Database Syst Rev. 2012 May 16;5:CD000214. [PMID: 22592671]

Centers for Disease Control and Prevention (CDC). Current cigarette smoking among adults—United States, 2011. MMWR Morb Mortal Wkly Rep. 2012 Nov 9;61(44):889–94. [PMID: 23134971]

Free C et al. Smoking cessation support delivered via mobile phone text messaging (txt2stop): a single-blind, randomised trial. Lancet. 2011 Jul 2;378(9785):49–55. [PMID: 21722952]

Lindson-Hawley N et al. Reduction versus abrupt cessation in smokers who want to quit. Cochrane Database Syst Rev. 2012 Nov 14;11:CD008033. [PMID: 23152252]

Moore D et al. Effectiveness and safety of nicotine replacement therapy assisted reduction to stop smoking: systematic review and meta-analysis. BMJ. 2009 Apr 2;338:b1024. [PMID: 19342408]

Mottillo S et al. Behavioural interventions for smoking cessation: a meta-analysis of randomized controlled trials. Eur Heart J. 2009 Mar;30(6):718–30. [PMID: 19109354]

Oza S et al. How many deaths are attributable to smoking in the United States? Comparison of methods for estimating smoking-attributable mortality when smoking prevalence changes. Prev Med. 2011 Jun;52(6):428–33. [PMID: 21530575]

Pierce JP et al. What public health strategies are needed to reduce smoking initiation? Tob Control. 2012 Mar;21(2):258–64. [PMID: 22345263]

Rigotti NA et al. Interventions for smoking cessation in hospitalised patients. Cochrane Database Syst Rev. 2012 May 16;5:CD001837. [PMID: 22592676]

Stead LF et al. Combined pharmacotherapy and behavioural interventions for smoking cessation. Cochrane Database Syst Rev. 2012 Oct 17;10:CD008286. [PMID: 23076944]

Tahiri M et al. Alternative smoking cessation aids: a meta-analysis of randomized controlled trials. Am J Med. 2012 Jun;125(6):576–84. [PMID: 22502956]

Whittaker R et al. Mobile phone-based interventions for smoking cessation. Cochrane Database Syst Rev. 2012 Nov 14;11:CD006611. [PMID: 23152238]

 Lipid Disorders (see Chapter 28)

Higher low-density lipoprotein (LDL) cholesterol concentrations and lower high-density lipoprotein (HDL) levels are associated with an increased risk of CHD. Cholesterol lowering therapy reduces the relative risk of CHD events, with the degree of reduction proportional to the reduction in LDL cholesterol achieved. The absolute benefits of screening for—and treating—abnormal lipid levels depend on the presence and number of other cardiovascular risk factors, including hypertension, diabetes mellitus, smoking, age, and gender. If other risk factors are present, cardiovascular risk is higher and the benefits of therapy are greater. Patients with known cardiovascular disease are at higher risk and have larger benefits from reduction in LDL cholesterol.

Evidence for the effectiveness of statin-type drugs is better than for the other classes of lipid-lowering agents or dietary changes specifically for improving lipid levels. Multiple large randomized, placebo-controlled trials have demonstrated important reductions in total mortality, major coronary events, and strokes with lowering levels of LDL cholesterol by statin therapy for patients with known cardiovascular disease. Statins also reduce cardiovascular events for patients with diabetes mellitus. For patients with no previous history of cardiovascular events or diabetes, meta-analyses have shown important reductions of cardiovascular events.

Guidelines for therapy are discussed in Chapter 28.

Cholesterol Treatment Trialists’ (CTT) Collaborators. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012 Aug 11;380(9841):581–90. [PMID: 22607822]

Mitchell AP et al. Statin cost effectiveness in primary prevention: a systematic review of the recent cost-effectiveness literature in the United States. BMC Res Notes. 2012 Jul 24;5:373. [PMID: 22828389]

Taylor F et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013 Jan 31;1:CD004816. [PMID: 23440795]

 Hypertension (see Chapter 11)

Over 66 million adults in the United States have hypertension. In over half of these adults (35.8 million), hypertension is not controlled. Among the 35.8 million whose hypertension is not well-controlled, nearly 40% are unaware of their elevated blood pressure; almost 16% are aware but not being treated, and 45% are being treated but the hypertension is not controlled. In every adult age group, higher values of systolic and diastolic blood pressure carry greater risks of stroke and heart failure. Systolic blood pressure is a better predictor of morbid events than diastolic blood pressure. Home monitoring is better correlated with target organ damage than clinic-based values. Clinicians can apply specific blood pressure criteria, such as those of the Joint National Committee, along with consideration of the patient’s cardiovascular risk and personal values, to decide at what levels treatment should be considered in individual cases.

Primary prevention of hypertension can be accomplished by strategies aimed at both the general population and special high-risk populations. The latter include persons with high-normal blood pressure or a family history of hypertension, blacks, and individuals with various behavioral risk factors such as physical inactivity; excessive consumption of salt, alcohol, or calories; and deficient intake of potassium. Effective interventions for primary prevention of hypertension include reduced sodium and alcohol consumption, weight loss, and regular exercise. Potassium supplementation lowers blood pressure modestly, and a diet high in fresh fruits and vegetables and low in fat, red meats, and sugar-containing beverages also reduces blood pressure. Interventions of unproven efficacy include pill supplementation of potassium, calcium, magnesium, fish oil, or fiber; macronutrient alteration; and stress management.

Improved identification and treatment of hypertension is a major cause of the recent decline in stroke deaths as well as the reduction in incidence of heart failure–related hospitalizations. Because hypertension is usually asymptomatic, screening is strongly recommended to identify patients for treatment. Despite strong recommendations in favor of screening and treatment, hypertension control remains suboptimal. An intervention that included patient education and provider education was more effective than provider education alone in achieving control of hypertension, suggesting the benefits of patient participation; another trial found that home monitoring combined with telephone-based nurse support was more effective than home monitoring alone for blood pressure control. Pharmacologic management of hypertension is discussed in Chapter 11.

Centers for Disease Control and Prevention (CDC). Vital signs: awareness and treatment of uncontrolled hypertension among adults—United States, 2003–2010. MMWR Morb Mortal Wkly Rep. 2012 Sep 7;61:703–9. [PMID: 22951452]

Glynn LG et al. Interventions used to improve control of blood pressure in patients with hypertension. Cochrane Database Syst Rev. 2010 Mar 17;(3):CD005182. [PMID: 20238338]

 Chemoprevention

Regular use of low-dose aspirin (81–325 mg) can reduce the incidence of myocardial infarction in men (see Chapter 10). Low-dose aspirin reduces stroke but not myocardial infarction in middle-aged women (see Chapter 24). Based on its ability to prevent cardiovascular events, aspirin use appears cost-effective for men and women who are at increased cardiovascular risk, which can be defined as 10-year risk over 10%. Results from a meta-analysis suggest that aspirin may also reduce the risk of death from several common types of cancer (colorectal, esophageal, gastric, breast, prostate, and possibly lung).

Nonsteroidal anti-inflammatory drugs may reduce the incidence of colorectal adenomas and polyps but may also increase heart disease and gastrointestinal bleeding, and thus are not recommended for colon cancer prevention in average risk patients.

Antioxidant vitamin (vitamin E, vitamin C, and beta-carotene) supplementation produced no significant reductions in the 5-year incidence of—or mortality from—vascular disease, cancer, or other major outcomes in high-risk individuals with coronary artery disease, other occlusive arterial disease, or diabetes mellitus.

Antithrombotic Trialists’ (ATT) Collaboration; Baigent C et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009 May 30;373(9678):1849–60. [PMID: 19482214]

Gaziano JM et al. Multivitamins in the prevention of cancer in men: the Physicians’ Health Study II randomized controlled trial. JAMA. 2012 Nov 14;308(18):1871–80. [PMID: 23162860]

Macpherson H et al. Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2013 Feb;97(2):437–44. [PMID: 23255568]

Rothwell P et al. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2011 Jan 1;377(9759):31–41. [PMID: 21144578]

Sesso HD et al. Multivitamins in the prevention of cardiovascular disease in men: the Physicians’ Health Study II randomized controlled trial. JAMA. 2012 Nov 7;308(17):1751–60. [PMID: 23117775]

PREVENTION OF OSTEOPOROSIS

See Chapters 26 and 42.

Osteoporosis, characterized by low bone mineral density, is common and associated with an increased risk of fracture. The lifetime risk of an osteoporotic fracture is approximately 50% for women and 30% for men. Osteoporotic fractures can cause significant pain and disability. As such, research has focused on means of preventing osteoporosis and related fractures. Primary prevention strategies include calcium supplementation, vitamin D supplementation, and exercise programs. Calcium supplementation can decrease fracture risk but may also increase risk of cardiovascular events. Vitamin D supplements alone do not appear to reduce fracture risk, although higher dosages (800 international units/d orally) may be effective.

Screening for osteoporosis on the basis of low bone mineral density is also recommended for women over age 60, based on indirect evidence that screening can identify women with low bone mineral density and that treatment of women with low bone density with bisphosphonates is effective in reducing fractures. However, real-world adherence to pharmacologic therapy for osteoporosis is low: one-third to one-half of patients do not take their medication as directed. The effectiveness of screening for osteoporosis in younger women and in men has not been established. Concern has been raised that bisphosphonates may increase the risk of certain types of fractures and osteonecrosis of the jaw, making consideration of the benefits and risks of therapy important when considering screening.

Bischoff-Ferrari HA et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med. 2012 Jul 5;367(1):40–9. [PMID: 22762317]

Bolland MJ et al. Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis. BMJ. 2011 Apr 19;342:d2040. [PMID: 21505219]

Chung M et al. Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med. 2011 Dec 20;155(12):827–38. [PMID: 22184690]

Giusti A et al. Atypical fractures of the femur and bisphosphonate therapy: a systematic review of case/case series studies. Bone. 2010 Aug;47(2):169–80. [PMID: 20493982]

Hiligsmann M et al. Cost-effectiveness of osteoporosis screening followed by treatment: the impact of medication adherence. Value Health. 2010 Jun–Jul;13(4):394–401. [PMID: 20102558]

Marjoribanks J et al. Long term hormone therapy for perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2012 Jul 11;7:CD004143. [PMID: 22786488]

Nelson HD et al. Screening for osteoporosis: an update for the U.S. Preventive Services Task Force. Ann Intern Med. 2010 Jul 20;153(2):99–111. [PMID: 20621892]

PREVENTION OF PHYSICAL INACTIVITY

Lack of sufficient physical activity is the second most important contributor to preventable deaths, trailing only tobacco use. A sedentary lifestyle has been linked to 28% of deaths from leading chronic diseases. Worldwide, approximately 30% of adults are physically inactive. Inactivity rates are higher in women, those from high-income countries (such as the Americas), and increase with age. Among teens age 13–15, 80% report doing fewer than 60 minutes of moderate to vigorous intensity per day and boys are more active than girls.

The US Department of Health and Human Services and the CDC recommends that adults and older adults engage in 150 minutes of moderate-intensity (such as brisk walking) or 75 minutes of vigorous-intensity aerobic activity (such as jogging or running) or an equivalent mix of moderate- and vigorous-intensity aerobic activity each week. In addition to the activity recommendations, the CDC recommends activities to strengthen all major muscle groups (abdomen, arms, back, chest, hips, legs, and shoulders) at least twice a week.

Patients who engage in regular moderate to vigorous exercise have a lower risk of myocardial infarction, stroke, hypertension, hyperlipidemia, type 2 diabetes mellitus, diverticular disease, and osteoporosis. Evidence supports the recommended guidelines of 30 minutes of moderate physical activity on most days of the week in both the primary and secondary prevention of CHD.

In longitudinal cohort studies, individuals who report higher levels of leisure time physical activity are less likely to gain weight. Conversely, individuals who are overweight are less likely to stay active. However, at least 60 minutes of daily moderate-intensity physical activity may be necessary to maximize weight loss and prevent significant weight regain. Moreover, adequate levels of physical activity appear to be important for the prevention of weight gain and the development of obesity. Physical activity also appears to have an independent effect on health-related outcomes such as development of type 2 diabetes mellitus in patients with impaired glucose tolerance when compared with body weight, suggesting that adequate levels of activity may counteract the negative influence of body weight on health outcomes.

Physical activity can be incorporated into any person’s daily routine. For example, the clinician can advise a patient to take the stairs instead of the elevator, to walk or bike instead of driving, to do housework or yard work, to get off the bus one or two stops earlier and walk the rest of the way, to park at the far end of the parking lot, or to walk during the lunch hour. The basic message should be the more the better and anything is better than nothing.

To be more effective in counseling about exercise, clinicians can also incorporate motivational interviewing techniques, adopt a whole practice approach (eg, use practice nurses to assist), and establish linkages with community agencies. Clinicians can incorporate the “5 As” approach:

  1. Ask (identify those who can benefit).
  2. Assess (current activity level).
  3. Advise (individualize plan).
  4. Assist (provide a written exercise prescription and support material).
  5. Arrange (appropriate referral and follow-up).

Such interventions have a moderate effect on self-reported physical activity and cardiorespiratory fitness, even if they do not always help patients achieve a predetermined level of physical activity. In their counseling, clinicians should advise patients about both the benefits and risks of exercise, prescribe an exercise program appropriate for each patient, and provide advice to help prevent injuries or cardiovascular complications.

Behavioral change interventions have been proven effective in increasing physical activity in sedentary older women, although evidence is lacking to support the use of pedometers to increase physical activity in this population. Although primary care providers regularly ask patients about physical activity and advise them with verbal counseling, few providers provide written prescriptions or perform fitness assessments. Tailored interventions may potentially help increase physical activity in individuals. Exercise counseling with a prescription, eg, for walking at either a hard intensity or a moderate intensity-high frequency, can produce significant long-term improvements in cardiorespiratory fitness. To be effective, exercise prescriptions must include recommendations on type, frequency, intensity, time, and progression of exercise and must follow disease-specific guidelines.

Several factors influence physical activity behavior, including personal, social (eg, family and work factors), and environmental (eg, access to exercise facilities and well-lit parks). Broad-based interventions targeting various factors are often the most successful, and interventions to promote physical activity are more effective when health agencies work with community partners. such as schools, businesses, and health-care organizations. Enhanced community awareness through mass media campaigns, school-based strategies, and policy approaches are proven strategies to increase physical activity.

Center for Disease Control and Prevention (CDC). How much physical activity do adults need? http://www.cdc.gov/physicalactivity/everyone/guidelines/adults.html

Hallal PC et al; Lancet Physical Activity Series Working Group. Global physical activity levels: surveillance progress, pitfalls, and prospects. Lancet. 2012 Jul 21;380(9838):247–57. [PMID: 22818937]

Hunter GR et al. Combined aerobic and strength training and energy expenditure in older women. Med Sci Sports Exerc. 2013 Jul;45(7):1386–93. [PMID: 23774582]

McMurdo ME et al. Do pedometers increase physical activity in sedentary older women? A randomized controlled trial. J Am Geriatr Soc. 2010 Nov;58(11):2099–106. [PMID: 21054290]

Orrow G et al. Effectiveness of physical activity promotion based in primary care: systematic review and meta-analysis of randomised controlled trials. BMJ. 2012 Mar 26;344:e1389. [PMID: 22451477]

Thomas GN et al. A systematic review of lifestyle modification and glucose intolerance in the prevention of type 2 diabetes. Curr Diabetes Rev. 2010 Nov;6(6):378–87. [PMID: 20879973]

PREVENTION OF OVERWEIGHT & OBESITY

Obesity is now a true epidemic and public health crisis that both clinicians and patients must face. Normal body weight is defined as a body mass index (BMI), calculated as the weight in kilograms divided by the height in meters squared, of < 25 kg/m2; overweight is defined as a BMI = 25.0–29.9 kg/m2, and obesity as a BMI > 30 kg/m2. Over the last several years, the prevalence of obesity in the USpopulation has increased dramatically. The most recent national data reveal that one-third of adults in the United States are obese, and prevalence rates are higher in blacks and Hispanics compared to non-Hispanic whites.

Risk assessment of the overweight and obese patient begins with determination of BMI, waist circumference for those with a BMI of 35 or less, presence of comorbid conditions, and a fasting blood glucose and lipid panel. Obesity is clearly associated with type 2 diabetes mellitus, hypertension, hyperlipidemia, cancer, osteoarthritis, cardiovascular disease, obstructive sleep apnea, and asthma.

Obesity is associated with a higher all-cause mortality rate. Data suggest an increase among those with grades 2 and 3 obesity (BMI > 35); however, the impact on all-cause mortality among overweight (BMI 25–30) and grade 1 obesity (BMI 30–35) is questionable. Nonetheless, there is a strong relationship between overweight and obesity and many chronic diseases. One of the most important sequelae of the rapid surge in prevalence of obesity has been a dramatic increase in the prevalence of diabetes. In addition, almost one-quarter of the US population currently has the metabolic syndrome. Both of these factors put affected obese individuals at high risk for the development of CHD.

Metabolic syndrome is defined as the presence of any three of the following: waist measurement of 40 inches or more for men and 35 inches or more for women, triglyceride levels of 150 mg/dL (1.70 mmol/L) or above, HDL cholesterol level < 40 mg/dL (< 1.44 mmol/L) for men and < 50 mg/dL (< 1.80 mmol/L) for women, blood pressure of 130/85 mm Hg or above, and fasting blood glucose levels of 100 mg/dL (5.55 mmol/L) or above. The relationship between overweight and obesity and diabetes, hypertension, and coronary artery disease is thought to be due to insulin resistance and compensatory hyperinsulinemia. Persons with a BMI ≥ 40 have death rates from cancers that are 52% higher for men and 62% higher for women than the rates in men and women of normal weight. Significant trends of increasing risk of death with higher BMIs are observed for cancers of the stomach and prostate in men and for cancers of the breast, uterus, cervix, and ovary in women, and for cancers of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney, non-Hodgkin lymphoma, and multiple myeloma in both men and women.

Clinicians must work to identify and provide the best prevention and treatment strategies for patients who are overweight and obese.

Prevention of overweight and obesity involves both increasing physical activity and dietary modification to reduce caloric intake. Adequate levels of physical activity appear to be important for the prevention of weight gain and the development of obesity. Despite this, only 49% of Americans are physically active at a moderate level and 20% at a more vigorous level. In addition, only 3% of Americans meet four of the five USDA recommendations for the intake of grains, fruits, vegetables, dairy products, and meat. Only one of four Americans eats the recommended five or more fruits and vegetables per day.

Clinicians can help guide patients to develop personalized eating plans to reduce energy intake, particularly by recognizing the contributions of fat, concentrated carbohydrates, and large portion sizes (see Chapter 29). Patients typically underestimate caloric content, especially when consuming food away from home. Providing patients with caloric and nutritional information may help address the current obesity epidemic. To prevent the long-term chronic disease sequelae of overweight or obesity, clinicians must work with patients to modify other risk factors, eg, by smoking cessation—see above) and strict blood pressure and glycemic control (see Chapters 11 and 27).

Lifestyle modification, including diet, physical activity, and behavior therapy has been shown to induce clinically significant weight loss. Other treatment options for obesity include pharmacotherapy and surgery (see Chapter 29). In overweight and obese persons, at least 60 minutes of moderate-high intensity physical activity may be necessary to maximize weight loss and prevent significant weight regain. Counseling interventions or pharmacotherapy can produce modest (3–5 kg) sustained weight loss over 6–12 months. Counseling appears to be most effective when intensive and combined with behavioral therapy. Pharmacotherapy appears safe in the short term; long-term safety is still not established. Lorcaserin, a selective 5-hydroxytryptamine (5-HT) (2C) agonist, has been shown to reduce body weight through a reduction of energy intake without influencing energy expenditure. It was approved by the US Food and Drug Administration (FDA) in June 2012 for adults with a BMI ≥ 30 or adults with a BMI ≥ 27 who have at least one obesity-related condition, such as hypertension, type 2 diabetes mellitus, or hypercholesterolemia.

Finally, clinicians seem to share a general perception that almost no one succeeds in long-term maintenance of weight loss. However, research demonstrates that approximately 20% of overweight individuals are successful at long-term weight loss (defined as losing ≥ 10% of initial body weight and maintaining the loss for ≥ 1 year). National Weight Control Registry members who lost an average of 33 kg and maintained the loss for more than 5 years have provided useful information about how to maintain weight loss. Members report engaging in high levels of physical activity (approximately 60 min/d), eating a low-calorie, low-fat diet, eating breakfast regularly, self-monitoring weight, and maintaining a consistent eating pattern from weekdays to weekends.

Flegal KM et al. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA. 2013 Jan 2;309(1):71–82. [PMID: 23280227]

Ogden CL et al. Prevalence of obesity in the United States, 2009–2010. NCHS Data Brief. 2012 Jan;(82):1–8. [PMID: 22617494]

Rock CL et al. Effect of a free prepared meal and incentivized weight loss program on weight loss maintenance in obese and overweight women: a randomized controlled trial. JAMA. 2010 Oct 27;304(16):1803–10. [PMID: 20935388]

CANCER PREVENTION

 Primary Prevention

Cancer mortality rates continue to decrease in the United States; part of this decrease results from reductions in tobacco use, since cigarette smoking is the most important preventable cause of cancer. Primary prevention of skin cancer consists of restricting exposure to ultraviolet light by wearing appropriate clothing and use of sunscreens. In the past two decades, there has been a threefold increase in the incidence of squamous cell carcinoma and a fourfold increase in melanoma in the United States. Persons who engage in regular physical exercise and avoid obesity have lower rates of breast and colon cancer. Prevention of occupationally induced cancers involves minimizing exposure to carcinogenic substances such as asbestos, ionizing radiation, and benzene compounds. Chemoprevention has been widely studied for primary cancer prevention (see above Chemoprevention section and Chapter 39). Use of tamoxifen, raloxifene, and aromatase inhibitors for breast cancer prevention is discussed inChapters 17 and 39. Hepatitis B vaccination can prevent hepatocellular carcinoma (HCC), and screening and vaccination programs may be cost-effective and useful in preventing HCC in high-risk groups such as Asians and Pacific Islanders. The use of HPV vaccine to prevent cervical and possibly anal cancer is discussed above. In addition to preventing anogenital cancers, HPV vaccines may have a role in the prevention of HPV-related head and neck cancers. Studies evaluating the long-term efficacy of the vaccine against non-anogenital cancers are ongoing.

Centers for Disease Control and Prevention (CDC). Cancer screening—United States, 2010. MMWR Morb Mortal Wkly Rep. 2012 Jan 27;61(3):41–5. [PMID: 22278157]

D’Souza G et al. The role of HPV in head and neck cancer and review of the HPV vaccine. Prev Med. 2011 Oct;53(Suppl 1):S5–S11. [PMID: 21962471]

Smith RA et al. Cancer screening in the United States, 2012: a review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin. 2012;62:129–42. [PMID: 22261986]

 Screening & Early Detection

Screening prevents death from cancers of the breast, colon, and cervix. Current cancer screening recommendations from the USPSTF are shown in Table 1–6. Despite an increase in rates of screening for breast, cervical, and colon cancer over the last decade, overall screening for these cancers is suboptimal. Interventions including group education, one-on-one education, patient reminders, reduction of structural barriers, reduction of out-of-pocket costs, and provider assessment and feedback are effective in promoting recommended cancer screening.

Table 1–6. Cancer screening recommendations for average-risk adults: US Preventive Services Task Force (USPSTF).1

Evidence from randomized trials suggests that screening mammography has both benefits and downsides. A 2011 Cochrane review estimated that screening with mammography led to a reduction in breast cancer mortality of 15% but resulted in 30% overdiagnosis and overtreatment. Currently, the appropriate form and frequency of screening for breast cancer remains controversial and screening guidelines vary. Clinicians should discuss the risks and benefits with each patient and consider individual patient preferences when deciding when to begin screening (see Chapters 17 and 42).

Digital mammography is more sensitive in women with dense breasts and younger women; however, studies exploring outcomes are lacking. MRI is not currently recommended for general screening, and its impact on breast cancer mortality is uncertain; however, the American Cancer Society recommends it for women at high risk (≥ 20–25%), including those with a strong family history of breast or ovarian cancer. Screening with both MRI and mammography might be superior to mammography alone in ruling out cancerous lesions in women with an inherited predisposition to breast cancer.

All current recommendations call for cervical and colorectal cancer screening. Screening for testicular cancers among asymptomatic adolescent or adult males is not recommended by the USPSTF. Prostate cancer screening remains controversial, since no completed studies have answered the question whether early detection and treatment after screen detection produce sufficient benefits to outweigh harms of treatment. A 2013 Cochrane systematic review revealed that prostate cancer screening with PSA testing did not decrease all-cause mortality and may not decrease prostate cancer-specific mortality. Any benefits in terms of reduction in prostate cancer-related mortality would take more than 10 years to become evident. Men with less than 10–15 years life expectancy should be informed that screening for prostate cancer is unlikely to be beneficial. In May 2012, the USPSTF recommended against PSA-based screening for prostate cancer (Grade: D Recommendation).

Annual or biennial fecal occult blood testing reduces mortality from colorectal cancer by 16–33%. Fecal immunochemical tests (FIT) are superior to guaiac-based fecal occult blood tests (gFOBT) in detecting advanced adenomatous polyps and colorectal cancer, and patients are more likely to favor FIT over gFOBTs. The risk of death from colon cancer among patients undergoing at least one sigmoidoscopic examination is reduced by 60–80% compared with that among those not having sigmoidoscopy. Colonoscopy has also been advocated as a screening examination. It is more accurate than flexible sigmoidoscopy for detecting cancer and polyps, but its value in reducing colon cancer mortality has not been studied directly. CT colonography (virtual colonoscopy) is a noninvasive option in screening for colorectal cancer. It has been shown to have a high safety profile and performance similar to colonoscopy.

The USPSTF recommends screening for cervical cancer in women aged 21–65 years with a Papanicolaou smear (cytology) every 3 years or, for women aged 30–65 years who desire longer intervals, screening with cytology and HPV testing every 5 years. The USPSTF recommends against screening in women younger than 21 years of age and average-risk women over 65 with adequate prior screening. Receipt of HPV vaccination has no impact on screening intervals.

In 2012, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology published updated guidelines for management of abnormal results. Women whose cervical specimen HPV tests are positive but cytology results are otherwise negative should repeat co-testing in 12 months (option 1) or undergo HPV- genotype-specific testing for types 16 or 16/18 (option 2). Colposcopy is recommended in women who test positive for types 16 or 16/18. Women with ASCUS (atypical squamous cells of undetermined significance) on cytology and a negative HPV test result should continue routine screening as per age-specific guidelines.

Evidence suggests that chest CT is significantly more sensitive that chest radiography in identifying small asymptomatic lung cancers; however, controversy exists regarding the efficacy and cost-effectiveness of low-dose CT screening in high-risk individuals. The National Lung Screening Trial (NLST), a randomized clinical trial of over 53,000 individuals at high risk for lung cancer, revealed a 20% relative reduction and 6.7% absolute reduction in lung cancer mortality in those who were screened with annual low-dose CTs for 3 years compared with those who had chest radiographs. There were a greater number of false-positive results in the low-dose CT group compared with those in the radiography group (23.3% vs 6.5%) (see Chapter 39). The Multicentric Italian Lung Detection (MILD) study, a randomized trial of over 4000 participants comparing annual or biennial low-dose CT with observation revealed no evidence of a protective effect with annual or biennial low-dose CT screening.

The American Cancer Society recommends that clinicians with access to high quality lung cancer screening and treatment centers utilize an informed and shared decision making process to discuss low-dose CT screening in high-risk patients in relatively good health who meet NLST criteria (age 55–74 with a ≥ 30 pack-year smoking history, current smokers, or ≤ 15 years since quitting). Screening should not be viewed as an alternative to smoking cessation.

Buys SS et al; PLCO Project Team. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011 Jun 8;305(22):2295–303. [PMID: 21642681]

Deutekom M et al. Comparison of guaiac and immunological fecal occult blood tests in colorectal cancer screening: the patient perspective. Scand J Gastroenterol. 2010 Nov;45(11):1345–9. [PMID: 20560814]

Goodman DM et al. JAMA patient page: Screening tests. JAMA. 2013 Mar 20;309(11):1185. [PMID: 23512066]

Gotzsche PC et al. Screening for breast cancer with mammography. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD001877. [PMID: 21249649]

Ilic D et al. Screening for prostate cancer. Cochrane Database Syst Rev. 2013 Jan 31;1:CD004720. [PMID: 23440794]

Levi Z et al. A higher detection rate for colorectal cancer and advanced adenomatous polyp for screening with immunochemical fecal occult blood test than guaiac fecal occult blood test, despite lower compliance rate. A prospective, controlled, feasibility study. Int J Cancer. 2011 May 15;128(10):2415–24. [PMID: 20658527]

Moyer VA; U.S. Preventive Services Task Force. Screening for cervical cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012 Jun 19;156(12):880–91. [PMID: 22711081]

Moyer VA; U.S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012 Jul 17;157(2):120–34. [PMID: 22801674]

National Lung Screening Trial Research Team; Aberle DR et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011. Aug 4;365(5):395–409. [PMID: 21714641]

Oken MM et al; PLCO Project Team. Screening by chest radiograph and lung cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial. JAMA. 2011 Nov 2;306(17):1865–73. [PMID: 22031728]

Pastorino U et al. Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial. Eur J Cancer Prev. 2012 May;21(3):308–15. [PMID: 22465911]

Saslow D et al. American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. J Low Genit Tract Dis. 2012 Jul;16(3):175–204. [PMID: 22418039]

Tria Tirona M. Breast cancer screening update. Am Fam Physician. 2013 Feb 15;87(4):274–8. [PMID: 23418799]

U.S. Preventive Services Task Force. Screening for testicular cancer: U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern Med. 2011 Apr 5;154(7):483–6. [PMID: 21464350]

Wender R et al. American Cancer Society lung cancer screening guidelines. CA Cancer J Clin. 2013 Mar–Apr;63(2):107–17. [PMID: 23315954]

PREVENTION OF INJURIES & VIOLENCE

Injuries remain the most important cause of loss of potential years of life before age 65. Homicide and motor vehicle accidents are a major cause of injury-related deaths among young adults, and accidental falls are the most common cause of injury-related death in the elderly. Approximately one-third of all injury deaths include a diagnosis of traumatic brain injury. Other causes of injury-related deaths include suicide and accidental exposure to smoke, fire, and flames.

Motor vehicle accident deaths per miles driven continue to decline in the United States. Each year in the United States, more than 500,000 people are nonfatally injured while riding bicycles. The rate of helmet use by bicyclists and motorcyclists is significantly increased in states with helmet laws. Young men appear most likely to resist wearing helmets. Clinicians should try to educate their patients about seat belts, safety helmets, the risks of using cellular telephones while driving, drinking and driving—or using other intoxicants or long-acting benzodiazepines and then driving—and the risks of having guns in the home.

Long-term alcohol abuse adversely affects outcome from trauma and increases the risk of readmission for new trauma. Alcohol and illicit drug use are associated with an increased risk of violent death.

Males aged 16–35 are at especially high risk for serious injury and death from accidents and violence, with blacks and Latinos at greatest risk. For 16- and 17-year-old drivers, the risk of fatal crashes increases with the number of passengers. Deaths from firearms have reached epidemic levels in the United States and will soon surpass the number of deaths from motor vehicle accidents. Having a gun in the home increases the likelihood of homicide nearly threefold and of suicide fivefold. Educating clinicians to recognize and treat depression as well as restricting access to lethal methods have been found to reduce suicide rates.

Clinicians have a critical role in detection, prevention, and management of intimate partner violence (see Chapter 42). Inclusion of a single question in the medical history—”At any time, has a partner ever hit you, kicked you, or otherwise physically hurt you?”—can increase identification of this common problem. Another screen consists of three questions: (1) “Have you ever been hit, kicked, punched, or otherwise hurt by someone within the past year? If so, by whom?” (2) “Do you feel safe in your current relationship?” (3) “Is there a partner from a previous relationship who is making you feel unsafe now?” Assessment for abuse and offering of referrals to community resources creates potential to interrupt and prevent recurrence of domestic violence and associated trauma. Screening patients in emergency departments for intimate partner violence appears to have no adverse effects related to screening and may lead to increased patient contact with community resources. Clinicians should take an active role in following up with patients whenever possible, since intimate partner violence screening with passive referrals to services may not be adequate. A randomized control trial to assess the impact of intimate partner violence screening on violence reduction and health outcomes in women revealed no difference in violence occurrence between screened and nonscreened women. Evaluation of services for patients after identification of intimate partner violence should be a priority.

Physical and psychological abuse, exploitation, and neglect of older adults are serious underrecognized problems. Risk factors for elder abuse include a culture of violence in the family; a demented, debilitated, or depressed and socially isolated victim; and a perpetrator profile of mental illness, alcohol or drug abuse, or emotional and/or financial dependence on the victim. Clues to elder mistreatment include the patient’s appearance, recurrent urgent-care visits, missed appointments, suspicious physical findings, and implausible explanations for injuries.

Amstadter AB et al. Prevalence and correlates of poor self-rated health in the United States: the national elder mistreatment study. Am J Geriatr Psychiatry. 2010 Jul;18(7):615–23. [PMID: 20220579]

Centers for Disease Control and Prevention (CDC). CDC Grand Rounds: reducing severe traumatic brain injury in the United States. MMWR Morb Mortal Wkly Rep. 2013 Jul 12;62(27):549–52. [PMID: 23842444]

Centers for Disease Control and Prevention (CDC). Vital signs: nonfatal, motor vehicle-occupant injuries (2009) and seat belt use (2008) among adults—United States. MMWR Morb Mortal Wkly Rep. 2011 Jan 7;59(51):1681–6. [PMID: 21209609]

Murphy K et al. A literature review of findings in physical elder abuse. Can Assoc Radiol J. 2013 Feb;64(1):10–4. [PMID: 23351969]

National Highway Traffic Safety Administration (NHTSA). Fatality Analysis Reporting System: national statistics summary, 2010. http://www-fars.nhtsa.dot.gov/Main/index.aspx

Turner S et al. Modification of the home environment for the reduction of injuries. Cochrane Database Syst Rev. 2011 Feb 16;(2):CD003600. [PMID: 21328262]

PREVENTION OF SUBSTANCE ABUSE: ALCOHOL & ILLICIT DRUGS

Substance abuse is a major public health problem in the United States. In the United States, approximately 51% of adults 18 years and older are current regular drinkers (at least 12 drinks in the past year). Maximum recommended consumption for adult women and those older than 65 years is three or fewer drinks per day (seven per week), and for adult men, four or fewer drinks per day (14 per week). The spectrum of alcohol misuse includes risky drinking (alcohol consumption above the recommended daily, weekly, or per occasion amounts), harmful use (a pattern causing damage to health), alcohol abuse (a pattern leading to clinically significant impairment or distress), and alcohol dependence (includes three or more of the following: tolerance, withdrawal, increased consumption, desire to cut down use, giving up social activities, increased time using alcohol or recovering from use, continued use despite known adverse effects). Estimating the prevalence of alcohol misuse is challenging; however, it has been suggested that 30% of the US population is affected. Underdiagnosis and treatment of alcohol misuse is substantial, both because of patient denial and lack of detection of clinical clues. Treatment rates for alcohol dependence have slightly declined over the last several years. Only a quarter of alcohol-dependent patients have ever been treated.

As with cigarette use, clinician identification and counseling about alcohol misuse is essential. An estimated 15–30% of hospitalized patients have problems with alcohol abuse or dependence, but the connection between patients’ presenting complaints and their alcohol use is often missed.

The Alcohol Use Disorder Identification Test (AUDIT) consists of questions on the quantity and frequency of alcohol consumption, on alcohol dependence symptoms, and on alcohol-related problems (Table 1–7). The AUDIT questionnaire is a cost-effective and efficient diagnostic tool for routine screening of alcohol use disorders in primary care settings. Choice of therapy remains controversial. However, use of screening procedures and brief intervention methods (see Chapter 25) can produce a 10–30% reduction in long-term alcohol use and alcohol-related problems. Brief advice and counseling without regular follow-up and reinforcement cannot sustain significant long-term reductions in unhealthy drinking behaviors.

Table 1–7. Screening for alcohol abuse using the Alcohol Use Disorder Identification Test (AUDIT).1

Time restraints may prevent clinicians from screening patients and single-question screening tests for unhealthy alcohol use may help increase the frequency of screening in primary care settings. Clinical trials support the use of screening and brief intervention for unhealthy alcohol use in adults. The National Institute on Alcohol Abuse and Alcoholism recommends the following single-question screening test: “How many times in the past year have you had X or more drinks in a day?” (X is 5 for men and 4 for women, and a response of > 1 is considered positive.) The single-item screening test has been validated in primary care settings.

Several pharmacologic agents are effective in reducing alcohol consumption. In acute alcohol detoxification, standard treatment regimens use long-acting benzodiazepines, the preferred medications for alcohol detoxification, because they can be given on a fixed schedule or through “front-loading” or “symptom-triggered” regimens. Adjuvant sympatholytic medications can be used to treat hyper-adrenergic symptoms that persist despite adequate sedation. Three drugs are FDA approved for treatment of alcohol dependence—disulfiram, naltrexone, and acamprosate. Disulfiram, an aversive agent, has significant adverse effects and consequently, compliance difficulties have resulted in no clear evidence that it increases abstinence rates, decreases relapse rates, or reduces cravings. Persons who receive short-term treatment with naltrexone have a lower chance of alcoholism relapse. Compared with placebo, naltrexone can lower the risk of treatment withdrawal in alcohol-dependent patients, and long-acting intramuscular formulation of naltrexone has been found to be well-tolerated and to reduce drinking significantly among treatment-seeking alcoholics over a 6-month period. In a randomized, controlled trial, patients receiving medical management with naltrexone, a combined behavioral intervention, or both, fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy with or without combined behavioral intervention. A depot formulation of naltrexone is available with good evidence for clinical efficacy. Topiramate is a promising treatment for alcohol dependence. A 6-month randomized trial of topiramate versus naltrexone revealed a greater reduction of alcohol intake and cravings in participants receiving topiramate. Topiramate’s side effect profile is favorable, and the benefits appear to increase over time. Clinicians should be aware that although topiramate appears to be an effective treatment for alcohol dependence, the manufacturer has not pursued FDA approval for this indication.

Over the last decade, the rate of prescription drug abuse has increased dramatically, particularly at both ends of the age spectrum. The most commonly abused classes of medications are pain relievers, tranquilizers, stimulants, and sedatives. Opioid-based prescription drug abuse, misuse, and overdose has reached epidemic proportions in the United States. Strategies to address this epidemic include establishing and strengthening prescription drug monitoring programs, regulating pain management facilities and establishing dosage thresholds requiring consultation with pain specialists; however, further evaluation is necessary to determine the impact of these strategies on opioid abuse and misuse. (See Chapter 5.)

Use of illegal drugs—including cocaine, methamphetamine, and so-called “designer drugs”—either sporadically or episodically remains an important problem. Lifetime prevalence of drug abuse is approximately 8% and is generally greater among men, young and unmarried individuals, Native Americans, and those of lower socioeconomic status. As with alcohol, drug abuse disorders often coexist with personality, anxiety, and other substance abuse disorders. Abuse of anabolic-androgenic steroids has been associated with use of other illicit drugs, alcohol, and cigarettes and with violence and criminal behavior.

As with alcohol abuse, the lifetime treatment rate for drug abuse is low (8%). The recognition of drug abuse presents special problems and requires that the clinician actively consider the diagnosis. Clinical aspects of substance abuse are discussed in Chapter 25.

Buprenorphine has potential as a medication to ameliorate the symptoms and signs of withdrawal from opioids and has been shown to be effective in reducing concomitant cocaine and opioid abuse. The risk of overdose is lower with buprenorphine than methadone and is preferred for patients at high risk for methadone toxicity. Evidence does not support the use of naltrexone in maintenance treatment of opioid addiction. Rapid opioid detoxification with opioid antagonist induction using general anesthesia has emerged as an approach to treat opioid dependence. However, a randomized comparison of buprenorphine-assisted rapid opioid detoxification with naltrexone induction and clonidine-assisted opioid detoxification with delayed naltrexone induction found no significant differences in rates of completion of inpatient detoxification, treatment retention, or proportions of opioid-positive urine specimens, and the anesthesia procedure was associated with more potentially life-threatening adverse events. Finally, cognitive behavior therapy, contingency management, couples and family therapy, and other types of behavioral treatment have been shown to be effective interventions for drug addiction.

Flórez G et al. Topiramate for the treatment of alcohol dependence: comparison with naltrexone. Eur Addict Res. 2011;17(1):29–36. [PMID: 20975274]

Garcia AM. State laws regulating prescribing of controlled substances: balancing the public health problems of chronic pain and prescription painkiller abuse and overdose. J Law Med Ethics. 2013 Mar;41(Suppl 1):42–5. [PMID: 23590739]

Jonas DE et al. Behavioral counseling after screening for alcohol misuse in primary care: a systematic review and meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med. 2012 Nov 6;157(9):645–54 [PMID: 23007881]

Kahan M et al. Buprenorphine: new treatment of opioid addiction in primary care. Can Fam Physician. 2011 Mar;57(3):281–9. [PMID: 21402963]

Manubay JM et al. Prescription drug abuse: epidemiology, regulatory issues, chronic pain management with narcotic analgesics. Prim Care. 2011 Mar;38(1):71–90. [PMID: 21356422]

National Institute on Drug Abuse. Topics in brief: prescription drug abuse—December 2011. http://www.drugabuse.gov/publications/topics-in-brief/prescription-drug-abuse

Schiller JS et al. Summary health statistics for U.S. adults: National Health Interview Survey, 2010, Table 27. Vital Health Stat 10. 2012 Jan;(252):94–96. [PMID: 22834228]

Soyka M et al. Emerging drugs to treat alcoholism. Expert Opin Emerg Drugs. 2010 Dec;15(4):695–711. [PMID: 20560783]