Insomnia Screening and Treatment
Mental Health Guidelines Committee, April 2013
Insomnia occurs frequently in HIV-infected patients and during all stages of HIV disease [Reid et al. 2005]. Although insomnia is not unique to the HIV-infected population, insomnia screening should be part of routine HIV care due to the potentially negative effects of insomnia on health, including HIV disease progression.
What is insomnia? Difficulty falling asleep; frequent awakenings during sleep; early morning awakening; or non-restorative sleep despite adequate sleep duration
Possible causes: 1) Major life events, such as the death of a loved one; 2) Changes in sleeping environment (e.g., when in the hospital); 3) Physical and mental health disorders; 4) Prescription or OTC medication use; 5) Use or relapse of use of alcohol or other substances [Feige et al. 2007; Brower 2003; Mahfoud et al. 2009]
Possible consequences of insomnia: Fatigue, irritability, elevated blood pressure, excessive daytime sleepiness; non-adherence to ART [Ammassari et al. 2001]; increase in pain symptoms and worsening of physical health conditions [Ancoli-Israel 2006]; relapse of psychiatric symptoms (e.g., anxiety, depression, mania).
Sleep assessment evaluation checklist for clinicians: Suggest the patient keep a sleep log, which could include the following:
- Events prior to bedtime, including emotional stressors and the consumption of alcohol or caffeine-containing beverages
- Time spent awake in bed before falling asleep
- Number, time, and length of awakenings
- Final time of morning awakening
- Time spent awake in bed before rising
- Frequency and duration of naps during the day
- Patient or bed partner observations of snoring, interrupted breathing, abnormal leg movements
Substance use etiologies: Caffeine, nicotine, alcohol, illicit drug use (particularly stimulants)
- Alcohol may help induce sleep, but its use is associated with sleep disruptions)
Mental health etiologies (the most common contributor to insomnia is the presence of a mental health disorder ):
- Depression and anxiety disorders
- Severe psychiatric disorders, including mania and psychosis
- Side effects of psychotropic medications, including selective seratonin-reuptake inhibitors (SSRIs)
- Respiratory: dyspnea and sleep apnea
- Gastrointestinal: gastroesophageal reflux
- Endocrinologic: hyperthyroidism, menopause
- Neurologic: cognitive impairment, neuropathy, periodic limb movements in sleep or restless limb syndrome
- Cardiopulmonary: lung disease, congestive heart failure
- Nephrologic/urologic: chronic kidney disease, frequent urination and incontinence
- ART medications (e.g., efavirenz, lamivudine)
- Calcium channel blockers
- Immunomodulators (e.g., interferons, interleukin-2)
- Diuretics taken at bedtime
Sleep Hygiene Strategies
Encourage the following “To Do’s”:
- Take warm baths before bed
- Exercise for at least 30 min/day most days of the week
- Maintain a bedtime routine (e.g., going to bed and waking up at a set time)
- Make bedroom cool, dark, and quiet
- Place the clock out of sight
- If unable to fall asleep after 20 minutes, leave bed and do something relaxing (e.g., reading); return to bed later
Discourage the following “Don’ts”:
- Consuming caffeine (coffee, tea, chocolate, soda), alcohol, or nicotine before bedtime
- Eating a large meal just before bedtime
- Napping during the day
- Exercising within 2 hours of bedtime
- Working, eating, reading, or watching television in bed.
Cognitive behavioral strategies: Referral to a sleep specialist to assist patients with cognitive-behavioral techniques may benefit some individuals with insomnia. Techniques include: cognitive therapy, relaxation training, sleep restriction, and phototherapy.
- Assess for patient use of OTC agents for insomnia and offer to prescribe an FDA-approved agent as a better option (e.g., offer ramelteon instead of OTC melatonin)
- Avoid prescribing medications for sleep disturbance that have narrow therapeutic ranges and potential for abuse (e.g., barbiturates, choral hydrate, and meprobamate)
- Limit to 1 week the use of antihistamines for promoting sleep in order to avoid worsening of symptoms due to long-term use
- Advise patients of the potential side effects of melatonin-agonist therapy, including OTC preparations, particularly severe hypersensitivity reactions
- Do not prescribe tricyclic antidepressants to patients with cardiac conduction problems; although some clinicians prescribe these agents for insomnia, most are not FDA-approved for this purpose
Checklist of questions when selecting a pharmacologic agent for insomnia:
- Will this agent improve symptoms that may be contributing to the patient’s insomnia (e.g., depression, anxiety, neuropathic pain, etc.)?
- Will this agent pose risks to the patient based on comorbid medical conditions?
- Will this agent pose risks based on interactions with other medications, (e.g., zolpidem, zaleplon, and eszopiclone should be used with caution in patients taking protease inhibitors)?
- Is this the optimal agent for a patient with a current or pasthistory of alcohol or sedative abuse/dependence?
- Can the patient afford the prescribed medication?
Agents with an FDA-approved indication for insomnia:
- Antihistamines: Diphenhydramine, doxylamine, hydroxyzine
- Non-benzodiazepine hypnotics: Zolpidem, zolpidem-CR, zaleplon, eszopiclone
- Melatonin agonist: Ramelteon
- Antidepressants: Trazodone, doxepin
- Benzodiazepine hypnotics: Flurazepam, quazepam, estazolam, triazolam, temazepam, lorazepam
Ammassari A, et al. J Acquir Immune Defic Syndr 2001;28:445-449.
Ancoli-Israel S. Am J Manag Care 2006;12(8 Suppl):S221-S229.
Brower KJ. Sleep Med Rev 2003;7:523–539.
Feige B, et al. Alcohol Clin Exp Res 2007;31:19-27.
Mahfoud Y, et al. Psychiatry 2009;6:38-42.
Reid S, et al. Psychosom Med 2005;67:260-269.
HIV Infection in Older Adults
Medical Care Criteria Committee, April 2015
Effective antiretroviral therapy (ART) has prolonged the lifespan of people living with HIV. Non-HIV/AIDS-related conditions now account for most morbidity and mortality among older people with HIV infection. Although ART reduces the effects of HIV disease and chronic inflammation, it does not restore normal immunologic function. The literature describes an aging HIV-infected population (between 50-65 years of age) with high rates of comorbid conditions compared with their non-HIV-infected counterparts. Medical care may be further complicated by neurocognitive decline and high rates of depression, alcohol and substance use, and social isolation. The goals of caring for older people with HIV infection are to minimize illness and frailty, optimize health and well-being, and prolong life.
This reference guide for care of older adults with HIV supplements, but does not replace, standard guidelines for all adults with HIV found on this website.
Initiation of ART in Patients Over 50
To prevent or delay disability, the following assessments are particularly important for older adults with HIV/AIDS:
- Total HIV and non-HIV disease burden and functional status
- Medication adherence, side effects, drug-drug interactions, need for dose adjustments
- Alcohol and substance use, including prescription drugs
- Mental and cognitive status
- Social support
Total Disease Burden and Functional Status
- Disease progression since last visit
- Consultations, specialty care visits, oral health care, ancillary tests, changes in medications
- New symptoms and diagnoses
- Changes in hearing and sight
- Basic and instrumental activities of daily living (ADLs)
- Pain, range of motion, gait
- Need for home care, assisted or congregate living, skilled nursing, or hospice services
- Hygiene: hair, nails, feet
Initiation of ART in Patients Over 50
- Older untreated HIV-infected persons have more rapid disease progression than younger persons [Phillips et al. 2004].
- Immunologic response is less robust in older patients [Gras et al. 2007; COHERE Study Group 2008]; however, patients >50 years of age who initiate therapy with higher CD4 counts are more likely to achieve better immunologic responses [Li et al. 2011].
- Patients who have longstanding HIV infection have increased susceptibility to inflammation-induced diseases and have diminished capacity to fight certain diseases [Fauci 2010].
Polypharmacy significantly increases the chances of serious drug-drug interactions, toxicity, and poor adherence.
- Current medications and adherence
- Potential drug interactions, adverse drug effects, allergies
- Dosing considerations: renal and hepatic function, pharmacokinetic changes with aging
Note: When patients report use of erectile dysfunction medications or products to relieve vaginal dryness, clinicians should use the opportunity to discuss safer-sex practices.
Screening tools: Urine screen; blood panel
Medication list and adherence verification:
- Create/update medication list, including over-the-counter drugs, supplements, and complementary and alternative medications.
- Verify current pharmacy and check prescription pattern and fill dates.
- Ask patients to bring pill bottles to visits, compare with medication list, and perform pill counts.
- Cross-reference information with home health agency or other caregivers.
- Consider use of customized pill cards, pill boxes (for those who can fill them on their own), home delivery, prepackaging of medication, “easy-open” containers.
- Ensure that instructions on medication dosing are appropriately conveyed.
Conditions of aging that may affect adherence:
- Impaired hearing: Perform screening test to determine need for formal testing
- Impaired vision: Perform vision screening every 1-2 years in pts >65; every 1-3 years in pts 55-64; annually for pts with CD4
- Cognitive impairment: Assess cognitive function at baseline and at least annually*
- Polypharmacy (higher pill burden, greater cumulative side effects, medication fatigue): Perform medication review at every visit; discontinue medications that are no longer needed
- Social isolation and lack of support: Assess social support at least annually*
- Depression: Screen for depression at every visit*
- Substance use, including misuse of prescriptions: Screen for substance use at baseline and at least annually
*See next sections for sample screening tools and questions.
Alcohol and Substance Use
Patients >50 years of age are at risk for misuse of prescription drugs. As with all HIV-infected patients, clinicians should screen for alcohol and substance use at baseline and at least annually.
Signs of possible abuse of prescription medications (adapted from the Mayo Clinic):
- Frequent reports of “losing” prescriptions and requests for more to be written
- Seeking prescriptions from more than one doctor
- Taking higher doses than prescribed
- Mood swings
- Change in sleep patterns
- Poor decision-making
Mental Health and Cognitive Status
As with all HIV-infected patients, clinicians should perform a comprehensive mental health screening at baseline and at least annually.
- Depression, anxiety, PTSD
- Psychiatric history
- Cognitive function
- Suicidal/violent ideation
- Sleep habits and appetite
- Psychosocial status
Screening tools for cognitive function and depression are provided.
See Mental Health Screening (Quick Reference Guide) for sample screening tools for all components of the comprehensive mental health screening.
Cognitive Function Screening Tool: International HIV Dementia Scale (IHDS)
Memory-Registration: Give 4 words to recall (dog, hat, bean, red)-1 second to say each. Then ask the patient all 4 words after you have said them. Repeat the words if the patient does not recall them all immediately. Tell the patient you will ask for recall of the words again a bit later.
1. Motor Speed: Have the patient tap the first two fingers of the non-dominant hand as widely and as quickly as possible.
- 4 = 15 in 5 seconds
- 3 = 11-14 in 5 seconds
- 2 = 7-10 in 5 seconds
- 1 = 3-6 in 5 seconds
- 0 = 0-2 in 5 seconds
2. Psychomotor Speed: Have the patient perform the following movements with the non-dominant hand as quickly as possible:
- Clench hand in fist on flat surface.
- Put hand flat on surface with palm down.
- Put perpendicular to flat surface on the side of the 5th digit.
- Demonstrate and have the patient perform twice for practice.
3. Memory Recall: Ask the patient to recall the 4 words. For words not recalled, prompt with a semantic clue as follows: animal (dog); piece of clothing (hat); vegetable (bean); color (red).
Score: Give 1 point for each word spontaneously recalled. Give 0.5 point for each correct answer after prompting. (Maximum: 4 points)
Total Score: This is the sum of the scores on items 1–3. The maximum possible score is 12. Patients with a score of ≤10 should be evaluated further for possible dementia.
Note: Reprinted by permission of Wolters Kluwer Health [Sacktor et al. 2005].
Questions to Identify Depression (PHQ-2)
Over the past 2 weeks, how often have you been bothered by any of the following problems?
- Little interest or pleasure in doing things:
0 = Not at all
1 = Several days
2 = More than half the days
3 = Nearly every day
- Feeling down, depressed, or hopeless:
0 = Not at all
1 = Several days
2 = More than half the days
3 = Nearly every day
Score: A score of 3 or more indicates the need for further evaluation
Note: Reprinted from Kroenke et al. 2003.
Social Support and Daily Care
- Emergency contact information
- Name of case manager, care coordinator, agencies providing services
- Need for interpreter, family conference, advance directives, long-term care, or hospice discussion
- HIPAA consents for communicating with support network
Sample Screening Questions
- Do you do things socially with friends? What do you like to do?
- Is there anyone who could come with you to medical appointments?
- Is there anyone who you would call if you felt really sick?
- Does anyone help you shop, cook, do the laundry, or take care of the house?
Nutrition: How often do you eat? What do you eat for breakfast? Lunch? Dinner?
- What do you do for exercise? How often to do you leave the house?
- Do you ever use a cane, walker, or wheelchair?
- Do you drive? Do you use the subway, buses, or taxis? Can you manage stairs?
- Do you have friends or family members who could help with transportation?
- Have you ever fallen in your home or outside? Do you ever feel that you might?
- Is your telephone always working? Do you have a phone in your bedroom?
- Currently, does anyone hit you, bully you, or yell at you? Do you feel safe in your home and neighborhood?
- Do you manage your own money? Do you think that anyone is stealing from you or taking advantage of you financially?
Communicating with Older Patients
- Use respectful, preferred forms of address
- Engage the patient: maintain eye contact; use frequent, brief, affirmative responses; avoid rushing and interrupting; demonstrate empathy
Compensate for vision and hearing deficits:
- Ensure patients are wearing eyeglasses and/or working hearing aids, if needed
- Speak slowly and clearly; keep hands away from face
- Use large type, visual aids
Create opportunity for discussion of sex:
- Ask whether the patient is sexually active and has any problems to address
- Assess and enhance patient’s knowledge of safer-sex practices
Ensure understanding [NIA 2008]:
- Write down important information
- Avoid jargon, ask if clarification is needed
- Summarize plan and next steps
Discussing long-term care and hospice [Balaban 2000; Casarett et al. 2007]:
- Establish a supportive relationship, acknowledge patient feelings and concerns, and offer reassurance
- Identify and include other decision makers
- Help define expectations based on disease status and prognosis
- Discuss service needs, recommend level of care (home care, assisted living, skilled nursing, hospice), and establish consensus for treatment plan
Balaban RB. A physician’s guide to talking about end-of-life care. J Gen Intern Med 2000;15:195-200.
Casarett DJ, et al. “I’m not ready for hospice”: Strategies for timely and effective hospice discussions. Ann Intern Med 2007;146:443-449.
COHERE Study Group. Response to combination antiretroviral therapy: Variation by age. AIDS2008;22:1463-1473.
Fauci A. NIH statement on National HIV/AIDS and Aging Awareness Day Sept. 18, 2010. 2010 Sep 9. https://www.nih.gov/news-events/news-releases/nih-statement-national-hiv/aids-aging-awareness-day-sept-18-2010 [accessed 2018 Jun 1]
Fried LP, et al. Frailty in older adults: Evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146-M156.
Gras L, et al. CD4 cell counts of 800 cells/mm3 or greater after 7 years of highly active antiretroviral therapy are feasible in most patients starting with 350 cells/mm3 or greater. J Acquir Immune Defic Syndr 2007;45:183-192.
Justice AC, et al. Predictive accuracy of the Veterans Aging Cohort Study index for mortality with HIV infection: A North American cross cohort analysis. J Acquir Immune Defic Syndr 2013;62:149-163.
Katz S. Assessing self-maintenance: Activities of daily living, mobility, and instrumental activities of daily living. J Am Geriatr Soc 1983;31:721-727.
Kroenke K, et al. The Patient Health Questionnaire-2: Validity of a two-item depression screener. Med Care 2003;41:1284-1292.
Lawton MP, et al. Assessment of older people: Self-maintaining and instrumental activities of daily living. Gerontologist 1969;9:179-186.
Li X, et al. CD4+T-cell counts and plasma HIV-1 RNA levels beyond 5 years of highly active antiretroviral therapy. J Acquir Immune Defic Syndr2011;57:421-428.
National Institute on Aging (NIA). A Clinician’s Handbook: Talking With Your Older Patient. 2008. https://order.nia.nih.gov/publication/talking-with-your-older-patient-a-clinicians-handbook [accessed 2018 Jun 6]
Phillips A, et al. Short-term risk of AIDS according to current CD4 cell count and viral load in antiretroviral drug-naïve individuals and those treated in the monotherapy era. AIDS2004;18:51-58.
Sacktor NC, Wong M, Nakasujja N, et al. The International HIV Dementia Scale: A new rapid screening test for HIV dementia. AIDS2005;19:1367-1374.
Mental Health Screening
People with HIV are more likely to experience mental health symptoms than those in the general population [Bing et al. 2001]. Depression, anxiety, post-traumatic stress disorder (PTSD), and cognitive impairment are among the most common disorders. Risk for suicide or violence may be present. Any sudden change in cognitive function, consciousness, or behavior should prompt immediate assessment for delirium caused by an acute medical complication.
The complexity of mental health diagnosis and treatment in the setting of HIV often requires a collaborative approach between primary care and mental health providers. (Mental health providers include psychiatrists, psychologists, clinical social workers, and psychiatric nurse practitioners.)
Screening: For most patients, mental health screening requires approximately 10-20 minutes.
Referral: Refer to a mental health provider when a patient presents with:
- Risk for violence to self or others (see algorithm)
- Psychosis, including delusions, hallucinations, flight of ideas, disordered thinking
- Poor response or relapse of psychiatric symptoms while receiving medication/treatment
- Active substance abuse or relapse to substance use with mental health disorder (Refer to a program for dually diagnosed patients.)
Successful mental health referral involves communication between medical and mental health providers, as well as patient education.
Depression, Anxiety, and PTSD
Assessment: A brief screening tool, such as the PHQ-2, may be used for routine depression screening. For annual mental health screening, an answer of “yes” to any one of the following questions from the SAMISS questionnaire [Pence et al. 2005] should prompt further evaluation by a member of the healthcare team and, if necessary, referral to a mental health provider.
Questions to identify depression:
- In the past year, were you ever on medication or antidepressants for depression or nerve problems?
- In the past year, was there ever a time when you felt sad, blue, or depressed for more than 2 weeks in a row?
- In the past year, was there ever a time lasting more than 2 weeks when you lost interest in most things like hobbies, work, or activities that usually give you pleasure?
Questions to identify anxiety:
- In the past year, did you ever have a period lasting more than 1 month when most of the time you felt worried and anxious?
- In the past year, did you have a spell or an attack when all of a sudden you felt frightened, anxious, or very uneasy when most people would not be afraid or anxious?
- In the past year, did you ever have a spell or an attack when for no reason your heart suddenly started to race, you felt faint, or you couldn’t catch your breath?
Questions to identify post-traumatic stress disorder (PTSD):
- During your lifetime, as a child, or adult, have you experienced or witnessed traumatic event(s) that involved harm to yourself or to others?
- If “yes”: In the past year, have you been troubled by flashbacks, nightmares, or thoughts of the trauma?
- In the past 3 months, have you experienced any event(s) or received information that was so upsetting it affected how you cope with everyday life?
Question to identify mania:
- In the past year, when not high or intoxicated, did you ever feel extremely energetic or irritable and more talkative than usual?
Note: Questions have been reprinted by permission of Wolters Kluwer Health.
The International HIV Dementia Scale is a validated brief screening instrument that can be administered by non-neurologists and may detect early motor and cognitive slowing.
Cognitive Function Screening Tools: International HIV Dementia Scale (IHDS)
Memory-Registration: Give 4 words to recall (dog, hat, bean, red) — 1 second to say each. Then ask the patient all 4 words after you have said them. Repeat the words if the patient does not recall them all immediately. Tell the patient you will ask for recall of the words again a bit later.
- Motor Speed: Have the patient tap the first two fingers of the non-dominant hand as widely and as quickly as possible.
- 4 = 15 in 5 seconds
- 3 = 11-14 in 5 seconds
- 2 = 7-10 in 5 seconds
- 1 = 3-6 in 5 seconds
- 0 = 0-2 in 5 seconds
- Psychomotor Speed: Have the patient perform the following movements with the non-dominant hand as quickly as possible: 1) Clench hand in fist on flat surface. 2) Put hand flat on surface with palm down. 3) Put perpendicular to flat surface on the side of the 5th digit.
Demonstrate and have the patient perform twice for practice.
- 4 = 4 sequences in 10 seconds
- 3 = 3 sequences in 10 seconds
- 2 = 2 sequences in 10 seconds
- 1 = 1 sequence in 10 seconds
- 0 = unable to perform
- Memory-Recall: Ask the patient to recall the 4 words. For words not recalled, prompt with a semantic clue as follows: animal (dog); piece of clothing (hat); vegetable (bean); color (red).
- Give 1 point for each word spontaneously recalled
- Give 0.5 point for each correct answer after prompting
- Maximum — 4 points
Total International HIV Dementia Scale Score: This is the sum of the scores on items 1-3. The maximum possible score is 12. Patients with a score of ≤10 should be evaluated further for possible dementia.
Reprinted with permission of Wolters Kluwer Health. Sacktor NC, Wong M, Nakasujja N, et al. The International HIV Dementia Scale: A new rapid screening test for HIV dementia. AIDS 2005;19:1367-1374
Sleep and Appetite
Insomnia occurs frequently in HIV-infected patients and during all stages of HIV disease [Reid and Dwyer 2005], and weight loss is a strong predictor of HIV disease progression [Colecraft 2008].
Additional resource: Insomnia Screening and Treatment (Quick Reference Guide)
Substance Use Screening
A positive screen with any one of the following tools indicates the need for additional evaluation. Many more tools are available. For additional information, see NYSDOH AI: Screening and Ongoing Assessment Guideline.
Single Alcohol Screening Question
“How many times in the past year have you had x or more drinks in 1 day?”
Where x = 4 for women and x = 5 for men, and one or more heavy drinking days in the past year is considered a positive screen.
Reprinted from the National Institute on Alcohol Abuse and Alcoholism. Helping Patients Who Drink Too Much: A Clinician’s Guide, 2005.
The Two-Item Conjoint Screen (TICS)
“In the last year, have you ever drunk or used drugs more than you meant to?”
“Have you felt you wanted or needed to cut down on your drinking or drug use in the last year?”
Where ≥1 positive may be suggestive of a problem.
Reproduced by permission of the American Board of Family Medicine. Brown RL, Leonard T, Saunders LA, et al. A two-item conjoint screen for alcohol and other drug problems. J Am Board Fam Pract 2001;14:95-106. Copyright © 2001, JABFM Online by American Board of Family Medicine.
CAGE-AID (CAGE-Adapted to Include Drugs)
“Have you ever felt the need to cut down on your use of alcohol or drugs?”
“Has anyone annoyed you by criticizing your use of alcohol or drugs?”
“Have you ever felt guilty because of something you’ve done while drinking or using drugs?”
“Have you ever taken a drink or used drugs to steady your nerves or get over a hangover (eye-opener)?”
Where a total of ≥2 may be suggestive of a problem.
Reproduced by permission of the Wisconsin Medical Society; cited from Brown RL, Rounds LA. Conjoint screening questionnaires for alcohol and other drug abuse: Criterion validity in primary care practice. Wisconsin Medical Journal 1995;94:135-140.
Acute Suicidal or Violent Ideation or Behavior
HIV-Related Triggers of Mental Distress
Clinicians should be aware of triggers that can cause mental distress, such as:
- Learning of HIV status and disclosure to sex partners, family, and friends
- Physical illness, diagnosis of an STI, introduction of ART medications, AIDS diagnosis
- Hospitalization (particularly first hospitalization)
- Life changes (death of a significant other, end of relationship, job loss)
- Necessity of making end-of-life permanency-planning decisions
Elements of Pyschosocial Assessment
The following assessment may help determine the need for additional support:
- Stability of housing,* employment, government assistance, and level of education
- Support network and safety:
- Does the patient have contact with family and friends? …Are they aware of the patient’s HIV status?
- Does the patient have a partner?…Is the patient afraid of his/her partner or someone else close?
- Legal issues, including end-of-life arrangements
*Contact information, housing, and support network should be closely monitored for patients with unstable living situations.
Use of full prescribing information, knowledge of drug-drug interactions, and patient education are important components of effective psychopharmacologic treatment. Consultation with a psychiatrist experienced in HIV treatment may be warranted. Consultation for providers in New York State can be obtained at Columbia University HIV Mental Health Training Project: HIV Mental Health Warmline (1-212-543-5413).
Bing EG, Burnam MA, Longshore D, et al. Arch Gen Psychiatry 2001;58:721-728.
Colecraft E. Proc Nutr Soc 2008;67:109-113.
Pence BW, et al. Validation of a brief screening instrument for substance abuse and mental illness in HIV-positive patients. J Acquir Immune Defic Syndr 2005;40:434-444.
Reid S, Dwyer J. Psychosom Med 2005;67:260-269.