HM groups should provide informational brochures to admitted patients

I am trying to find out two pieces of information. First, is there a national association of hospitalists that oversees and gives guidance to all of the regional and national hospitalists that are now in practice? If this defines your group, great. On to my second question: Is there an established policy or doctrine that is recommended for hospitals in regard to disclosure to patients that they are indeed a hospitalist type of hospital? If so, could you advise how I might obtain a written copy? Thank you.

C.G. Lemaire, Virginia

Dr. Hospitalist responds: According to the 2008 American Hospital Association survey, about half of the nation’s hospitals have hospitalists. In hospitals with 200 or more beds, 83% have hospitalists. The field has grown rapidly since its inception in the late 1990s. There are an estimated 28,000 hospitalists in the U.S.

Most hospitalists recognize the Society of Hospital Medicine (SHM) as the professional society that represents their interests. I am not aware of any established SHM policy that mandates or suggests that a hospital disclose to patients the fact that hospitalists work there, nor do I believe that one is necessary. Hospitalists are medical doctors whose interest is the care of hospitalized patients. This is analogous to critical-care physicians, whose interest is care of the patients in hospital intensive-care units, or ED physicians, who care for patients in hospital emergency departments. There is neither a requirement nor expectation for hospitals to notify patients of the availability of these types of physicians working at a hospital.

I understand patient expectations can be different. Most patients expect to see ED physicians when they visit a hospital ED. But this was not always the case. Several decades ago, the field of emergency medicine was in its infancy, and most hospitals did not have ED physicians. I am certain most patients were surprised to see an ED physician instead of their primary-care physician (PCP). But patients came to realize ED physicians were trained specifically to care for ED patients and were available to care for them when their PCP was not available. I think patients will become familiar with hospitalists and expect to see one when they are hospitalized—but until that time arrives, I do think it is reasonable for everyone involved to help set that expectation for patients.

Ideally, HM programs should develop brochures explaining a hospitalist’s role in the care of hospitalized patients, as well as the relationship between hospitalists and PCPs (see “Satisfaction Scorecard,” January 2009, p. 57). These brochures should be distributed not only to hospitalized patients, but to outpatients in PCP offices. The primary-care clinic waiting room is a great place for these brochures.

PCPs should discuss the role of hospitalists when they send a patient to the hospital for admission. It is important for hospitalists and PCPs to know that patients are more likely to be accepting if they understand: 1) the PCP supports this model of care; 2) the hospitalist and PCP are communicating about the patient’s care; and 3) the hospitalist is available to the patient while the PCP is in their clinic.

SHM’s Web site also has a sample brochure, which can be used to introduce and inform patients about the hospitalists’ role in their care. Download the form at www.hospitalmedicine.org/samplebrochure.

Know your contract before signing the dotted line

My contract says that as a hospitalist, I will work 18 shifts a month, each being a nine-hour duration, and on average 2,000 hours per year. It does not add up to 2,000 hours. Does night call count toward the number of hours? Do weekends and holidays count toward the number of hours?

Anshu Sood, MD

Dr. Hospitalist responds: If I understand you correctly, you are working 1,944 hours annually (18 shifts per month x 12 months x nine hours per shift). You did not tell me whether your compensation is based on the number of hours you work or whether you collect a salary regardless of the number of hours you work. If you collect a salary, sounds like you are scheduled to work fewer hours than expected.

That being said, I also don’t know the other details of your employment agreement. Does your employment agreement include paid vacation and sick time? Perhaps that might explain the difference. Another plausible explanation is that your compensation includes payment for sign-out and sign-in time at the beginning and end of each shift (18 shifts/month x 12 months x 9.25 hours/shift = 1,998 hours). Regardless of the explanation, your question made me wonder: Why are the details of your job description unclear to you, and why are you asking me rather than your employer for clarification? I urge all hospitalists to clearly understand their employment agreements before accepting any job offer. Any differences should be resolved before signing the contract. It is worth the time and money to seek the advice of an attorney familiar with physician employment contracts. The attorney’s job is to review your agreement and explain the terms of the contract, as well as point out what is missing. TH

HM groups should provide informational brochures to admitted patients

I am trying to find out two pieces of information. First, is there a national association of hospitalists that oversees and gives guidance to all of the regional and national hospitalists that are now in practice? If this defines your group, great. On to my second question: Is there an established policy or doctrine that is recommended for hospitals in regard to disclosure to patients that they are indeed a hospitalist type of hospital? If so, could you advise how I might obtain a written copy? Thank you.

C.G. Lemaire, Virginia

Dr. Hospitalist responds: According to the 2008 American Hospital Association survey, about half of the nation’s hospitals have hospitalists. In hospitals with 200 or more beds, 83% have hospitalists. The field has grown rapidly since its inception in the late 1990s. There are an estimated 28,000 hospitalists in the U.S.

Most hospitalists recognize the Society of Hospital Medicine (SHM) as the professional society that represents their interests. I am not aware of any established SHM policy that mandates or suggests that a hospital disclose to patients the fact that hospitalists work there, nor do I believe that one is necessary. Hospitalists are medical doctors whose interest is the care of hospitalized patients. This is analogous to critical-care physicians, whose interest is care of the patients in hospital intensive-care units, or ED physicians, who care for patients in hospital emergency departments. There is neither a requirement nor expectation for hospitals to notify patients of the availability of these types of physicians working at a hospital.

I understand patient expectations can be different. Most patients expect to see ED physicians when they visit a hospital ED. But this was not always the case. Several decades ago, the field of emergency medicine was in its infancy, and most hospitals did not have ED physicians. I am certain most patients were surprised to see an ED physician instead of their primary-care physician (PCP). But patients came to realize ED physicians were trained specifically to care for ED patients and were available to care for them when their PCP was not available. I think patients will become familiar with hospitalists and expect to see one when they are hospitalized—but until that time arrives, I do think it is reasonable for everyone involved to help set that expectation for patients.

Ideally, HM programs should develop brochures explaining a hospitalist’s role in the care of hospitalized patients, as well as the relationship between hospitalists and PCPs (see “Satisfaction Scorecard,” January 2009, p. 57). These brochures should be distributed not only to hospitalized patients, but to outpatients in PCP offices. The primary-care clinic waiting room is a great place for these brochures.

PCPs should discuss the role of hospitalists when they send a patient to the hospital for admission. It is important for hospitalists and PCPs to know that patients are more likely to be accepting if they understand: 1) the PCP supports this model of care; 2) the hospitalist and PCP are communicating about the patient’s care; and 3) the hospitalist is available to the patient while the PCP is in their clinic.

SHM’s Web site also has a sample brochure, which can be used to introduce and inform patients about the hospitalists’ role in their care. Download the form at www.hospitalmedicine.org/samplebrochure.

Know your contract before signing the dotted line

My contract says that as a hospitalist, I will work 18 shifts a month, each being a nine-hour duration, and on average 2,000 hours per year. It does not add up to 2,000 hours. Does night call count toward the number of hours? Do weekends and holidays count toward the number of hours?

Anshu Sood, MD

Dr. Hospitalist responds: If I understand you correctly, you are working 1,944 hours annually (18 shifts per month x 12 months x nine hours per shift). You did not tell me whether your compensation is based on the number of hours you work or whether you collect a salary regardless of the number of hours you work. If you collect a salary, sounds like you are scheduled to work fewer hours than expected.

That being said, I also don’t know the other details of your employment agreement. Does your employment agreement include paid vacation and sick time? Perhaps that might explain the difference. Another plausible explanation is that your compensation includes payment for sign-out and sign-in time at the beginning and end of each shift (18 shifts/month x 12 months x 9.25 hours/shift = 1,998 hours). Regardless of the explanation, your question made me wonder: Why are the details of your job description unclear to you, and why are you asking me rather than your employer for clarification? I urge all hospitalists to clearly understand their employment agreements before accepting any job offer. Any differences should be resolved before signing the contract. It is worth the time and money to seek the advice of an attorney familiar with physician employment contracts. The attorney’s job is to review your agreement and explain the terms of the contract, as well as point out what is missing. TH

HM groups should provide informational brochures to admitted patients

I am trying to find out two pieces of information. First, is there a national association of hospitalists that oversees and gives guidance to all of the regional and national hospitalists that are now in practice? If this defines your group, great. On to my second question: Is there an established policy or doctrine that is recommended for hospitals in regard to disclosure to patients that they are indeed a hospitalist type of hospital? If so, could you advise how I might obtain a written copy? Thank you.

C.G. Lemaire, Virginia

Dr. Hospitalist responds: According to the 2008 American Hospital Association survey, about half of the nation’s hospitals have hospitalists. In hospitals with 200 or more beds, 83% have hospitalists. The field has grown rapidly since its inception in the late 1990s. There are an estimated 28,000 hospitalists in the U.S.

Most hospitalists recognize the Society of Hospital Medicine (SHM) as the professional society that represents their interests. I am not aware of any established SHM policy that mandates or suggests that a hospital disclose to patients the fact that hospitalists work there, nor do I believe that one is necessary. Hospitalists are medical doctors whose interest is the care of hospitalized patients. This is analogous to critical-care physicians, whose interest is care of the patients in hospital intensive-care units, or ED physicians, who care for patients in hospital emergency departments. There is neither a requirement nor expectation for hospitals to notify patients of the availability of these types of physicians working at a hospital.

I understand patient expectations can be different. Most patients expect to see ED physicians when they visit a hospital ED. But this was not always the case. Several decades ago, the field of emergency medicine was in its infancy, and most hospitals did not have ED physicians. I am certain most patients were surprised to see an ED physician instead of their primary-care physician (PCP). But patients came to realize ED physicians were trained specifically to care for ED patients and were available to care for them when their PCP was not available. I think patients will become familiar with hospitalists and expect to see one when they are hospitalized—but until that time arrives, I do think it is reasonable for everyone involved to help set that expectation for patients.

Ideally, HM programs should develop brochures explaining a hospitalist’s role in the care of hospitalized patients, as well as the relationship between hospitalists and PCPs (see “Satisfaction Scorecard,” January 2009, p. 57). These brochures should be distributed not only to hospitalized patients, but to outpatients in PCP offices. The primary-care clinic waiting room is a great place for these brochures.

PCPs should discuss the role of hospitalists when they send a patient to the hospital for admission. It is important for hospitalists and PCPs to know that patients are more likely to be accepting if they understand: 1) the PCP supports this model of care; 2) the hospitalist and PCP are communicating about the patient’s care; and 3) the hospitalist is available to the patient while the PCP is in their clinic.

SHM’s Web site also has a sample brochure, which can be used to introduce and inform patients about the hospitalists’ role in their care. Download the form at www.hospitalmedicine.org/samplebrochure.

Know your contract before signing the dotted line

My contract says that as a hospitalist, I will work 18 shifts a month, each being a nine-hour duration, and on average 2,000 hours per year. It does not add up to 2,000 hours. Does night call count toward the number of hours? Do weekends and holidays count toward the number of hours?

Anshu Sood, MD

Dr. Hospitalist responds: If I understand you correctly, you are working 1,944 hours annually (18 shifts per month x 12 months x nine hours per shift). You did not tell me whether your compensation is based on the number of hours you work or whether you collect a salary regardless of the number of hours you work. If you collect a salary, sounds like you are scheduled to work fewer hours than expected.

That being said, I also don’t know the other details of your employment agreement. Does your employment agreement include paid vacation and sick time? Perhaps that might explain the difference. Another plausible explanation is that your compensation includes payment for sign-out and sign-in time at the beginning and end of each shift (18 shifts/month x 12 months x 9.25 hours/shift = 1,998 hours). Regardless of the explanation, your question made me wonder: Why are the details of your job description unclear to you, and why are you asking me rather than your employer for clarification? I urge all hospitalists to clearly understand their employment agreements before accepting any job offer. Any differences should be resolved before signing the contract. It is worth the time and money to seek the advice of an attorney familiar with physician employment contracts. The attorney’s job is to review your agreement and explain the terms of the contract, as well as point out what is missing. TH

Pregabalin (Lyrica) is a novel analogue of the neurotransmitter gamma aminobutyric acid (GABA) with analgesic, anticonvulsant, and anxiolytic activity. Its approval by the US Food and Drug Administration (FDA) in 2007 for the treatment of fibromyalgia made it the first drug approved for this indication. Until then, management of fibromyalgia entailed drugs to treat pain, sleep, fatigue, and psychological disorders, and a strong emphasis on exercise and physical therapy.

Those who still question the validity of fibromyalgia as a diagnosis object to drug companies “benefiting” from the sale of such drugs.¹ But many hail pregabalin as an important advance in our understanding of the pathogenesis of fibromyalgia and how to treat it. A key question remains: How will pregabalin fit into the treatment of this often-challenging disease?

FROM FIBROSITIS TO FIBROMYALGIA

Fibromyalgia is a syndrome characterized by widespread pain. Chronic muscular pain is a common problem, but fibromyalgia is distinguished from other pain disorders by additional findings, such as consistent areas of tenderness (tender points), nonrestorative sleep, severe fatigue, and frequent psychological comorbidities such as depression and anxiety.

Fibromyalgia was originally termed “fibrositis” in 1904 by Sir William Gowers, who described it as a painful condition of the fibrous tissue, which he believed was due to inflammation in the muscles.^2,3 For several decades, research was dedicated to looking for pathology in the muscle tissue, which was thought to be the major source of pain for most patients with fibromyalgia.

In the mid-1970s, Dr. H. Moldofsky, a noted sleep researcher, reported on abnormalities of the alpha-delta component of nonrapid-eye-movement sleep in these patients. He subsequently collaborated with Dr. Hugh A. Smythe, who helped define the fibromyalgia tender points. Fibrositis was subsequently renamed fibromyalgia syndrome, since it was agreed that there was no true inflammation in muscles or fibrous tissue.

In 1990, the American College of Rheumatology published “classification criteria” for the disease.⁴ The criteria include two main features:

• A history of widespread pain (“widespread” being defined as in the axial distribution, in both the left and right sides of the body, and above and below the waist), which must be present for 3 months or more, and
• Tenderness in at least 11 of 18 specified points that is elicited when a pressure of 4 kg (the amount of pressure required to blanch a thumbnail) is applied in steady increments starting at 1 kg.

Although pain is subjective and therefore difficult to assess, the classification criteria did make it easier to study the disease in a uniform way and led to an explosion of research in this field.

FUNCTIONAL ABNORMALITIES NI THE CENTRAL NERVOUS SYSTEM

Research to date points to the pain in fibromyalgia as being mediated by changes in the central nervous system rather than in the musculoskeletal system, as was initially thought.

In the dorsal horn of the spinal cord, nociceptive (pain-sensing) neurons from the periphery synapse with the second-order neurons that carry the pain signal to the brain. In fibromyalgia, several processes seem to amplify the signal.

Central sensitization is defined as enhanced excitability of neurons in the dorsal horn. Its features include augmented spontaneous neuronal activity, enlarged receptive field areas, and enhanced responses generated by large- and small-caliber primary afferent fibers. It can result from prolonged or strong activity in the dorsal horn neurons, and it leads to the spread of hyperactivity across multiple spinal segments.^5–7

While much of the evidence for central sensitization in fibromyalgia is from animal studies, the phenomenon has also been studied in humans. Desmeules et al⁸ found that, compared with people without fibromyalgia, those with fibromyalgia had significantly lower thresholds of pain as assessed subjectively and measured objectively using the nociceptive flexion R-III reflex, which the authors described as “a specific physiologic correlate for the objective evaluation of central nociceptive pathways.”

Wind-up. Prolonged stimulation of C fibers in the dorsal horn can result in the phenomenon of wind-up, which refers to the temporal summation of second pain.

A painful stimulus evokes two pain signals. The first signal is brief and travels rapidly to the spinal cord via myelinated fibers (A fibers). The second signal, which is related to chronic pain and is described as dull, aching, or burning, travels more slowly to the dorsal horn via unmyelinated fibers (C fibers), the synapses of which use the neurotransmitter glutamate. Temporal summation is a phenomenon observed in experiments in which a series of painful stimuli are applied at regular intervals of about 2 seconds; although each stimulus is identical in intensity, subjects perceive them as increasing in intensity. The reason: during this repetitive stimulation, N-methyl-d-aspartate (NMDA) receptors become activated, leading to the removal of a magnesium block within the receptor. This results in an influx of calcium into the neuron and activation of protein kinase C, nitric oxide synthase, and cyclooxygenase. Ultimately, the firing rates of the nociceptive neurons are increased and the peripheral pain signal is strongly amplified.⁶

Wind-up has been shown to lead to characteristics of central sensitization related to C-fiber activity in animals.⁷ Staud et al⁹ studied wind-up in patients with and without fibromyalgia using series of repetitive thermal stimulation to produce temporal summation. Though wind-up was evoked in both groups, differences were observed both in the magnitude of sensory response to the first stimulus within a series and in the amount of temporal summation within a series.

Elevated excitatory neurotransmitters. In 1994, Russell et al¹⁰ showed that the concentration of substance P, an excitatory neurotransmitter, was three times higher in the cerebrospinal fluid of people with fibromyalgia than in normal controls.

Harris and colleagues¹¹ reported that glutamate, another excitatory neurotransmitter, is elevated within the brain in people with fibromyalgia. They further showed that the levels of glutamate within the insula of the brain are directly associated with the levels of both experimental pressure-evoked pain thresholds and clinical pain ratings in fibromyalgia patients.

Evidence from imaging studies. Other objective evidence of central sensitization in fibromyalgia patients comes from studies using novel imaging.

Gracely et al¹² performed functional magnetic resonance imaging (MRI) in people with and without fibromyalgia while applying pressure to their thumbs with a thumbscrew-type device. At equal levels of pressure, the people with fibromyalgia said the pressure hurt more, and specific areas of their brains lit up more on functional MRI. When the experimenters increased the pressure in the people without fibromyalgia until this group subjectively rated the pain as high as the fibromyalgia patients rated the lower level of pressure, their brains lit up to a similar degree in the same areas. These findings provide objective evidence of significantly lower pain thresholds in patients with fibromyalgia than in healthy controls, and they support the theory of central augmentation of pain sensitivity in fibromyalgia.

Staud et al¹³ also used functional MRI and found greater brain activity associated with temporal summation in fibromyalgia patients compared with controls. (In this experiment, the painful stimulus consisted of heat pulses to the foot.)

Drugs other than pregabalin that modulate the dorsal horn activity of the pain pathway include opioids, tramadol (Ultram), gabapentin (Neurontin), GABA agonists such as baclofen (Lioresal), antidepressants, alpha-2 adrenergic agonists (phenylephrine), and 5-HT3 antagonists such as ondansetron (Zofran), but none has been consistently effective for fibromyalgia.^5,14

PREGABALIN

Pregabalin is an alpha-2-delta ligand similar to GABA, but it does not act on GABA receptors. Rather, it binds with high affinity to the alpha-2-delta subunit of voltage-gated presynaptic calcium channels, resulting in reduction of calcium flow through the channels, which subsequently inhibits the release of neurotransmitters including glutamate, norepinephrine, and substance P.^15–17 Animal studies suggest that the decrease in the levels of these excitatory neurotransmitters is the mechanism of action of pregabalin, resulting in its analgesic, anticonvulsant, and anxiolytic benefit.¹⁵ Another potential mechanism of pregabalin is enhancement of slow-wave sleep, demonstrated in one study in healthy human subjects.¹⁸

Besides fibromyalgia, pregabalin is also approved for the treatment of diabetic peripheral neuropathy, postherpetic neuralgia, generalized anxiety disorder, and social anxiety disorder, and as adjunctive therapy for partial-onset seizure in adults.

Pharmacokinetics

Pregabalin is quickly absorbed, primarily in the proximal colon (bioavailability > 90%), and has highly predictable and linear pharmacokinetics.¹⁵ Food consumption does not affect its absorption or elimination but can delay its peak plasma concentration, which occurs at 1.5 hours. Its elimination half-life is approximately 6 hours.¹⁵ Because it does not bind to plasma proteins, it freely crosses the blood-brain barrier. The drug reaches its steady-state concentration within 2 days of starting therapy.

Its clearance is not affected by the sex or race of the patient, but its total clearance may be lower in the elderly because of age-related loss of renal function. Patients on hemodialysis may require a supplemental dose after dialysis because hemodialysis removes the pregabalin.

The drug is not metabolized by the P450 system in the liver, so it interacts only minimally with drugs that do use the P450 system. However, its clearance may be decreased when it is used concomitantly with drugs that can reduce the glomerular filtration rate, such as nonsteroidal anti-inflammatory drugs, aminoglycosides, and cyclosporine.¹⁵

Efficacy

The efficacy of pregabalin in fibromyalgia was evaluated in several recent trials.¹⁹

Crofford et al¹⁶ assessed pregabalin’s effects on pain, sleep, fatigue, and health-related quality of life. Some 529 patients with fibromyalgia were randomized in a double-blind fashion to four treatment groups: placebo, and pregabalin 150 mg/day, 300 mg/day, and 450 mg/day. The baseline mean pain scores (a 0-to-10 scale derived from daily diary ratings) were 6.9 in the placebo group, 6.9 for the pregabalin 150 mg/day group, 7.3 for the pregabalin 300 mg/day group, and 7.0 for the pregabalin 450 mg/day group.

The pain scores declined in all groups, but at 8 weeks, the mean score had declined 0.93 points more in the group receiving pregabalin 450 mg/day than in the placebo group (P ≤ .001). The scores in the groups taking pregabalin 150 mg/day and 300 mg/day were not significantly different from those in the placebo group. Significantly more patients in the 450-mg/day group (29%, vs 13% in the placebo group) had at least 50% improvement in pain at the end of the study. Patients in both the 300-mg/day group and the 450-mg/day had statistically significant improvement in their quality of sleep, in fatigue, and on the Patient Global Impression of Change (PGIC) scale.

Arnold et al²⁰ conducted a trial with 750 patients in which three doses of pregabalin were compared with placebo: 300 mg/day, 450 mg/day, and 600 mg/day. The primary end point was also the change in pain score from baseline (using the 0-to-10 scale derived from a daily pain diary). The mean baseline pain score was 6.7.

At 14 weeks, the mean pain score was lower than at baseline in all the groups, but it had declined 0.71 more in the pregabalin 300-mg/day group than in the placebo group, 0.98 points more in the 450-mg/day group, and 1.0 points more in the 600-mg/day group. All three pregabalin groups also showed significant improvement on the PGIC scale, and patients in the 450-mg/day and 600-mg/day groups showed statistically significant improvement in the Fibromyalgia Impact Questionnaire (FIQ) score. All three pregabalin treatment groups also had significantly better patient-reported sleep outcomes than in the placebo group, both in measures of overall sleep and quality of sleep. With the exception of a significant improvement of anxiety on 600 mg/day, there was no significant difference between the treatment and placebo groups in the secondary outcomes of depression and anxiety symptoms and fatigue.

Duan et al²¹ presented a pooled analysis of this and a similarly designed double-blind, placebo-controlled trial (the results of which were not available individually) at the 71st annual meeting of the American College of Rheumatology in November 2007. The analysis included 1,493 patients with a mean baseline pain score of 6.9. Compared with the mean pain score in the placebo group, those in the pregabalin groups had declined more by the end of the study: 0.55 points more with 300 mg/day, 0.71 points more with 450 mg/day, and 0.82 points more with 600 mg/day. This pooled analysis also showed significant improvement in PGIC score with all pregabalin doses and in the FIQ score with 450 mg/day and 600 mg/day.

The FREEDOM trial²² (Fibromyalgia Relapse Evaluation and Efficacy for Durability of Meaningful Relief) evaluated the durability of effect of pregabalin in reducing pain and symptoms associated with fibromyalgia in 1,051 patients who initially responded to the drug.

The patients received 6 weeks of open-label treatment with pregabalin and then 26 weeks of double-blind treatment (dose adjustment was allowed based on efficacy and tolerability for the first 3 weeks). The time to loss of therapeutic response was significantly longer with pregabalin than with placebo. Loss of therapeutic response was defined as worsening of pain for two consecutive visits or worsening of fibromyalgia symptoms requiring alternative therapy.

By the end of the double-blind phase, 61% of those in the placebo group had loss of therapeutic response compared with only 32% in the pregabalin group. The time to worsening of the FIQ score was also significantly longer in the pregabalin group than in the placebo group.

Dizziness and sleepiness were the most common adverse events in these studies.

In the 8-week study by Crofford et al,¹⁶ dizziness was dose-related, occurring in 10.7% of those receiving placebo (one patient withdrew because of dizziness), 22.7% of those receiving 150 mg/day (two patients withdrew), 31.3% of those receiving 300 mg/day (four patients withdrew), and 49.2% of those receiving 450 mg/day (five patients withdrew). Somnolence was also dose-related, occurring in 4.6% in the placebo group, 15.9% in the 150-mg/day group (two patients withdrew due to somnolence), 27.6% in the 300-mg/day group (three withdrew), and 28.0% in the 450-mg/day group (five withdrew).

The 14-week study by Arnold et al²⁰ also showed higher frequencies of adverse events with higher doses. The rates of dizziness were 7.6% with placebo, 27.9% with pregabalin 300 mg/day, 37.4% with 450 mg/day, and 42.0% with 600 mg/day. The rates of somnolence were 3.8% with placebo, 12.6% with 300 mg/day of pregabalin, 19.5% with 450 mg/day, and 21.8% with 600 mg/day. Dizziness and somnolence were also the most common adverse effects that led to discontinuation of pregabalin, with rates of 4% and 3%, respectively.

The open-label phase of the FREEDOM trial showed rates of 36% for dizziness and 22% for somnolence among pregabalin-treated patients.

Weight gain and peripheral edema were also common adverse effects in these studies.²² Definitions of weight gain varied, and edema was not accompanied by evidence of cardiac or renal dysfunction.

Less common side effects seen more frequently in the treated groups included dry mouth, blurred vision, and difficulty with concentration and attention. The package insert also warns of angioedema, hypersensitivity reaction, mild asymptomatic creatine kinase elevation, decreased platelet count (without bleeding), and prolongation of the PR interval on electrocardiography.

Pregabalin is a schedule V controlled substance; in clinical studies, abrupt or rapid discontinuation of the drug led to insomnia, nausea, headache, or diarrhea in some patients, suggesting symptoms of dependence. In clinical studies involving a total of more than 5,500 patients, 4% of patients on pregabalin and 1% of patients on placebo reported euphoria as an adverse effect,¹⁹ suggesting possible potential for abuse.

Dosing

As a result of the above studies, the recommended starting dose of pregabalin for fibromyalgia is 150 mg/day in two or three divided doses, gradually increased to 300 mg/day within 1 week based on tolerability and efficacy. The dose may be increased to a maximum of 450 mg/day. The 600-mg dose was found to have no significant additional benefit, but it did have more adverse effects and therefore is not recommended. It is important to note that in these studies multiple medications for pain and insomnia were prohibited, so data on drug interactions with pregabalin are limited.

Few achieve complete remission, but most patients feel better

Several studies of the natural history of fibromyalgia have shown that very few patients experience complete remission of the disease, even after many years. Therefore, one should try to set up realistic expectations for patients, with the goal of achieving functional improvement in activities of daily living and a return to one’s predisease state.

In the longest follow-up study, 39 patients in Boston, MA, were prospectively followed for over 10 years. No patient achieved complete remission: all of them reported some fibromyalgia-related symptoms at the end of the study.²³ However, 66% of them felt a little to a lot better than when first diagnosed, 55% felt well or very well, and only 7% felt poorly.

Other studies have also shown complete remission to be rare.^24,25 A 5-year follow-up study investigating fibromyalgia patients’ perceptions of their symptoms and its impact on everyday life activities demonstrated that the social consequences of fibromyalgia’s symptoms are severe and constant over time.²⁶

Evidence of favorable outcomes was reported in one study in which 47% of patients reported moderate to marked improvement in overall fibromyalgia status upon 3-year follow-up,²⁷ and in another study, in which remission was objectively identified in 24.2% of patients 2 years after diagnosis.²⁸

OTHER THERAPIES

Although there have been many studies of pharmacologic therapies for fibromyalgia to date, the trials had significant limitations, such as short duration, inadequate sample size, nonstandardized measures of efficacy, question of regression to the mean, and inadequate blinding, resulting in insufficient evidence to recommend one drug over another.

Tricyclic antidepressants. Two meta-analyses and a clinical review have supported the efficacy of tricyclic antidepressants in improving symptoms in fibromyalgia patients.^29–31

Selective serotonin reuptake inhibitors (SSRIs) have not been well studied, and the small size and methodologic shortcomings of these studies make it difficult to draw conclusions about the efficacy of SSRIs in reducing pain in fibromyalgia patients.^30,31

Duloxetine (Cymbalta) and milnacipran (Savella) are serotonin and norepinephrine reuptake inhibitors.^32–34 A randomized, double-blind placebo-controlled trial evaluated duloxetine in 520 fibromyalgia patients with and without major depressive disorder. Pain scores improved significantly over 6 months in duloxetine-treated patients at doses of 60 and 120 mg/day.³³ Duloxetine became the second drug approved for the treatment of fibromyalgia in 2007, and milnacipran became the third in 2009.

WHAT ROLE FOR PREGABALIN?

Pregabalin may reduce pain in some patients with fibromyalgia. However, the presenting symptoms can vary significantly, and symptoms can vary even in individual patients over time. Therefore, in most patients with fibromyalgia, a multidisciplinary approach is used to treat pain, sleep disturbance, and fatigue, along with comorbidities such as neurally mediated hypotension and psychiatric disorders. Because treatment of fibromyalgia often involves multiple drugs in addition to exercise and behavioral therapies, future studies should examine combinations of drugs and the use of drugs in conjunction with nondrug treatments.

Pregabalin advances our knowledge of fibromyalgia through improving the understanding of central sensitization and how brain neurotransmitters control central pain perceptions. Drug treatment must still be part of the comprehensive management of this disease. Physician and patient education about the current understanding of the disease is paramount in setting realistic goals for treatment.¹⁴ Future strategies to manage fibromyalgia will be based on the pathophysiology of this complex condition.

Pregabalin (Lyrica) is a novel analogue of the neurotransmitter gamma aminobutyric acid (GABA) with analgesic, anticonvulsant, and anxiolytic activity. Its approval by the US Food and Drug Administration (FDA) in 2007 for the treatment of fibromyalgia made it the first drug approved for this indication. Until then, management of fibromyalgia entailed drugs to treat pain, sleep, fatigue, and psychological disorders, and a strong emphasis on exercise and physical therapy.

Those who still question the validity of fibromyalgia as a diagnosis object to drug companies “benefiting” from the sale of such drugs.¹ But many hail pregabalin as an important advance in our understanding of the pathogenesis of fibromyalgia and how to treat it. A key question remains: How will pregabalin fit into the treatment of this often-challenging disease?

FROM FIBROSITIS TO FIBROMYALGIA

Fibromyalgia is a syndrome characterized by widespread pain. Chronic muscular pain is a common problem, but fibromyalgia is distinguished from other pain disorders by additional findings, such as consistent areas of tenderness (tender points), nonrestorative sleep, severe fatigue, and frequent psychological comorbidities such as depression and anxiety.

Fibromyalgia was originally termed “fibrositis” in 1904 by Sir William Gowers, who described it as a painful condition of the fibrous tissue, which he believed was due to inflammation in the muscles.^2,3 For several decades, research was dedicated to looking for pathology in the muscle tissue, which was thought to be the major source of pain for most patients with fibromyalgia.

In the mid-1970s, Dr. H. Moldofsky, a noted sleep researcher, reported on abnormalities of the alpha-delta component of nonrapid-eye-movement sleep in these patients. He subsequently collaborated with Dr. Hugh A. Smythe, who helped define the fibromyalgia tender points. Fibrositis was subsequently renamed fibromyalgia syndrome, since it was agreed that there was no true inflammation in muscles or fibrous tissue.

In 1990, the American College of Rheumatology published “classification criteria” for the disease.⁴ The criteria include two main features:

• A history of widespread pain (“widespread” being defined as in the axial distribution, in both the left and right sides of the body, and above and below the waist), which must be present for 3 months or more, and
• Tenderness in at least 11 of 18 specified points that is elicited when a pressure of 4 kg (the amount of pressure required to blanch a thumbnail) is applied in steady increments starting at 1 kg.

Although pain is subjective and therefore difficult to assess, the classification criteria did make it easier to study the disease in a uniform way and led to an explosion of research in this field.

FUNCTIONAL ABNORMALITIES NI THE CENTRAL NERVOUS SYSTEM

Research to date points to the pain in fibromyalgia as being mediated by changes in the central nervous system rather than in the musculoskeletal system, as was initially thought.

In the dorsal horn of the spinal cord, nociceptive (pain-sensing) neurons from the periphery synapse with the second-order neurons that carry the pain signal to the brain. In fibromyalgia, several processes seem to amplify the signal.

Central sensitization is defined as enhanced excitability of neurons in the dorsal horn. Its features include augmented spontaneous neuronal activity, enlarged receptive field areas, and enhanced responses generated by large- and small-caliber primary afferent fibers. It can result from prolonged or strong activity in the dorsal horn neurons, and it leads to the spread of hyperactivity across multiple spinal segments.^5–7

While much of the evidence for central sensitization in fibromyalgia is from animal studies, the phenomenon has also been studied in humans. Desmeules et al⁸ found that, compared with people without fibromyalgia, those with fibromyalgia had significantly lower thresholds of pain as assessed subjectively and measured objectively using the nociceptive flexion R-III reflex, which the authors described as “a specific physiologic correlate for the objective evaluation of central nociceptive pathways.”

Wind-up. Prolonged stimulation of C fibers in the dorsal horn can result in the phenomenon of wind-up, which refers to the temporal summation of second pain.

A painful stimulus evokes two pain signals. The first signal is brief and travels rapidly to the spinal cord via myelinated fibers (A fibers). The second signal, which is related to chronic pain and is described as dull, aching, or burning, travels more slowly to the dorsal horn via unmyelinated fibers (C fibers), the synapses of which use the neurotransmitter glutamate. Temporal summation is a phenomenon observed in experiments in which a series of painful stimuli are applied at regular intervals of about 2 seconds; although each stimulus is identical in intensity, subjects perceive them as increasing in intensity. The reason: during this repetitive stimulation, N-methyl-d-aspartate (NMDA) receptors become activated, leading to the removal of a magnesium block within the receptor. This results in an influx of calcium into the neuron and activation of protein kinase C, nitric oxide synthase, and cyclooxygenase. Ultimately, the firing rates of the nociceptive neurons are increased and the peripheral pain signal is strongly amplified.⁶

Wind-up has been shown to lead to characteristics of central sensitization related to C-fiber activity in animals.⁷ Staud et al⁹ studied wind-up in patients with and without fibromyalgia using series of repetitive thermal stimulation to produce temporal summation. Though wind-up was evoked in both groups, differences were observed both in the magnitude of sensory response to the first stimulus within a series and in the amount of temporal summation within a series.

Elevated excitatory neurotransmitters. In 1994, Russell et al¹⁰ showed that the concentration of substance P, an excitatory neurotransmitter, was three times higher in the cerebrospinal fluid of people with fibromyalgia than in normal controls.

Harris and colleagues¹¹ reported that glutamate, another excitatory neurotransmitter, is elevated within the brain in people with fibromyalgia. They further showed that the levels of glutamate within the insula of the brain are directly associated with the levels of both experimental pressure-evoked pain thresholds and clinical pain ratings in fibromyalgia patients.

Evidence from imaging studies. Other objective evidence of central sensitization in fibromyalgia patients comes from studies using novel imaging.

Gracely et al¹² performed functional magnetic resonance imaging (MRI) in people with and without fibromyalgia while applying pressure to their thumbs with a thumbscrew-type device. At equal levels of pressure, the people with fibromyalgia said the pressure hurt more, and specific areas of their brains lit up more on functional MRI. When the experimenters increased the pressure in the people without fibromyalgia until this group subjectively rated the pain as high as the fibromyalgia patients rated the lower level of pressure, their brains lit up to a similar degree in the same areas. These findings provide objective evidence of significantly lower pain thresholds in patients with fibromyalgia than in healthy controls, and they support the theory of central augmentation of pain sensitivity in fibromyalgia.

Staud et al¹³ also used functional MRI and found greater brain activity associated with temporal summation in fibromyalgia patients compared with controls. (In this experiment, the painful stimulus consisted of heat pulses to the foot.)

Drugs other than pregabalin that modulate the dorsal horn activity of the pain pathway include opioids, tramadol (Ultram), gabapentin (Neurontin), GABA agonists such as baclofen (Lioresal), antidepressants, alpha-2 adrenergic agonists (phenylephrine), and 5-HT3 antagonists such as ondansetron (Zofran), but none has been consistently effective for fibromyalgia.^5,14

PREGABALIN

Pregabalin is an alpha-2-delta ligand similar to GABA, but it does not act on GABA receptors. Rather, it binds with high affinity to the alpha-2-delta subunit of voltage-gated presynaptic calcium channels, resulting in reduction of calcium flow through the channels, which subsequently inhibits the release of neurotransmitters including glutamate, norepinephrine, and substance P.^15–17 Animal studies suggest that the decrease in the levels of these excitatory neurotransmitters is the mechanism of action of pregabalin, resulting in its analgesic, anticonvulsant, and anxiolytic benefit.¹⁵ Another potential mechanism of pregabalin is enhancement of slow-wave sleep, demonstrated in one study in healthy human subjects.¹⁸

Besides fibromyalgia, pregabalin is also approved for the treatment of diabetic peripheral neuropathy, postherpetic neuralgia, generalized anxiety disorder, and social anxiety disorder, and as adjunctive therapy for partial-onset seizure in adults.

Pharmacokinetics

Pregabalin is quickly absorbed, primarily in the proximal colon (bioavailability > 90%), and has highly predictable and linear pharmacokinetics.¹⁵ Food consumption does not affect its absorption or elimination but can delay its peak plasma concentration, which occurs at 1.5 hours. Its elimination half-life is approximately 6 hours.¹⁵ Because it does not bind to plasma proteins, it freely crosses the blood-brain barrier. The drug reaches its steady-state concentration within 2 days of starting therapy.

Its clearance is not affected by the sex or race of the patient, but its total clearance may be lower in the elderly because of age-related loss of renal function. Patients on hemodialysis may require a supplemental dose after dialysis because hemodialysis removes the pregabalin.

The drug is not metabolized by the P450 system in the liver, so it interacts only minimally with drugs that do use the P450 system. However, its clearance may be decreased when it is used concomitantly with drugs that can reduce the glomerular filtration rate, such as nonsteroidal anti-inflammatory drugs, aminoglycosides, and cyclosporine.¹⁵

Efficacy

The efficacy of pregabalin in fibromyalgia was evaluated in several recent trials.¹⁹

Crofford et al¹⁶ assessed pregabalin’s effects on pain, sleep, fatigue, and health-related quality of life. Some 529 patients with fibromyalgia were randomized in a double-blind fashion to four treatment groups: placebo, and pregabalin 150 mg/day, 300 mg/day, and 450 mg/day. The baseline mean pain scores (a 0-to-10 scale derived from daily diary ratings) were 6.9 in the placebo group, 6.9 for the pregabalin 150 mg/day group, 7.3 for the pregabalin 300 mg/day group, and 7.0 for the pregabalin 450 mg/day group.

The pain scores declined in all groups, but at 8 weeks, the mean score had declined 0.93 points more in the group receiving pregabalin 450 mg/day than in the placebo group (P ≤ .001). The scores in the groups taking pregabalin 150 mg/day and 300 mg/day were not significantly different from those in the placebo group. Significantly more patients in the 450-mg/day group (29%, vs 13% in the placebo group) had at least 50% improvement in pain at the end of the study. Patients in both the 300-mg/day group and the 450-mg/day had statistically significant improvement in their quality of sleep, in fatigue, and on the Patient Global Impression of Change (PGIC) scale.

Arnold et al²⁰ conducted a trial with 750 patients in which three doses of pregabalin were compared with placebo: 300 mg/day, 450 mg/day, and 600 mg/day. The primary end point was also the change in pain score from baseline (using the 0-to-10 scale derived from a daily pain diary). The mean baseline pain score was 6.7.

At 14 weeks, the mean pain score was lower than at baseline in all the groups, but it had declined 0.71 more in the pregabalin 300-mg/day group than in the placebo group, 0.98 points more in the 450-mg/day group, and 1.0 points more in the 600-mg/day group. All three pregabalin groups also showed significant improvement on the PGIC scale, and patients in the 450-mg/day and 600-mg/day groups showed statistically significant improvement in the Fibromyalgia Impact Questionnaire (FIQ) score. All three pregabalin treatment groups also had significantly better patient-reported sleep outcomes than in the placebo group, both in measures of overall sleep and quality of sleep. With the exception of a significant improvement of anxiety on 600 mg/day, there was no significant difference between the treatment and placebo groups in the secondary outcomes of depression and anxiety symptoms and fatigue.

Duan et al²¹ presented a pooled analysis of this and a similarly designed double-blind, placebo-controlled trial (the results of which were not available individually) at the 71st annual meeting of the American College of Rheumatology in November 2007. The analysis included 1,493 patients with a mean baseline pain score of 6.9. Compared with the mean pain score in the placebo group, those in the pregabalin groups had declined more by the end of the study: 0.55 points more with 300 mg/day, 0.71 points more with 450 mg/day, and 0.82 points more with 600 mg/day. This pooled analysis also showed significant improvement in PGIC score with all pregabalin doses and in the FIQ score with 450 mg/day and 600 mg/day.

The FREEDOM trial²² (Fibromyalgia Relapse Evaluation and Efficacy for Durability of Meaningful Relief) evaluated the durability of effect of pregabalin in reducing pain and symptoms associated with fibromyalgia in 1,051 patients who initially responded to the drug.

The patients received 6 weeks of open-label treatment with pregabalin and then 26 weeks of double-blind treatment (dose adjustment was allowed based on efficacy and tolerability for the first 3 weeks). The time to loss of therapeutic response was significantly longer with pregabalin than with placebo. Loss of therapeutic response was defined as worsening of pain for two consecutive visits or worsening of fibromyalgia symptoms requiring alternative therapy.

By the end of the double-blind phase, 61% of those in the placebo group had loss of therapeutic response compared with only 32% in the pregabalin group. The time to worsening of the FIQ score was also significantly longer in the pregabalin group than in the placebo group.

Dizziness and sleepiness were the most common adverse events in these studies.

In the 8-week study by Crofford et al,¹⁶ dizziness was dose-related, occurring in 10.7% of those receiving placebo (one patient withdrew because of dizziness), 22.7% of those receiving 150 mg/day (two patients withdrew), 31.3% of those receiving 300 mg/day (four patients withdrew), and 49.2% of those receiving 450 mg/day (five patients withdrew). Somnolence was also dose-related, occurring in 4.6% in the placebo group, 15.9% in the 150-mg/day group (two patients withdrew due to somnolence), 27.6% in the 300-mg/day group (three withdrew), and 28.0% in the 450-mg/day group (five withdrew).

The 14-week study by Arnold et al²⁰ also showed higher frequencies of adverse events with higher doses. The rates of dizziness were 7.6% with placebo, 27.9% with pregabalin 300 mg/day, 37.4% with 450 mg/day, and 42.0% with 600 mg/day. The rates of somnolence were 3.8% with placebo, 12.6% with 300 mg/day of pregabalin, 19.5% with 450 mg/day, and 21.8% with 600 mg/day. Dizziness and somnolence were also the most common adverse effects that led to discontinuation of pregabalin, with rates of 4% and 3%, respectively.

The open-label phase of the FREEDOM trial showed rates of 36% for dizziness and 22% for somnolence among pregabalin-treated patients.

Weight gain and peripheral edema were also common adverse effects in these studies.²² Definitions of weight gain varied, and edema was not accompanied by evidence of cardiac or renal dysfunction.

Less common side effects seen more frequently in the treated groups included dry mouth, blurred vision, and difficulty with concentration and attention. The package insert also warns of angioedema, hypersensitivity reaction, mild asymptomatic creatine kinase elevation, decreased platelet count (without bleeding), and prolongation of the PR interval on electrocardiography.

Pregabalin is a schedule V controlled substance; in clinical studies, abrupt or rapid discontinuation of the drug led to insomnia, nausea, headache, or diarrhea in some patients, suggesting symptoms of dependence. In clinical studies involving a total of more than 5,500 patients, 4% of patients on pregabalin and 1% of patients on placebo reported euphoria as an adverse effect,¹⁹ suggesting possible potential for abuse.

Dosing

As a result of the above studies, the recommended starting dose of pregabalin for fibromyalgia is 150 mg/day in two or three divided doses, gradually increased to 300 mg/day within 1 week based on tolerability and efficacy. The dose may be increased to a maximum of 450 mg/day. The 600-mg dose was found to have no significant additional benefit, but it did have more adverse effects and therefore is not recommended. It is important to note that in these studies multiple medications for pain and insomnia were prohibited, so data on drug interactions with pregabalin are limited.

Few achieve complete remission, but most patients feel better

Several studies of the natural history of fibromyalgia have shown that very few patients experience complete remission of the disease, even after many years. Therefore, one should try to set up realistic expectations for patients, with the goal of achieving functional improvement in activities of daily living and a return to one’s predisease state.

In the longest follow-up study, 39 patients in Boston, MA, were prospectively followed for over 10 years. No patient achieved complete remission: all of them reported some fibromyalgia-related symptoms at the end of the study.²³ However, 66% of them felt a little to a lot better than when first diagnosed, 55% felt well or very well, and only 7% felt poorly.

Other studies have also shown complete remission to be rare.^24,25 A 5-year follow-up study investigating fibromyalgia patients’ perceptions of their symptoms and its impact on everyday life activities demonstrated that the social consequences of fibromyalgia’s symptoms are severe and constant over time.²⁶

Evidence of favorable outcomes was reported in one study in which 47% of patients reported moderate to marked improvement in overall fibromyalgia status upon 3-year follow-up,²⁷ and in another study, in which remission was objectively identified in 24.2% of patients 2 years after diagnosis.²⁸

OTHER THERAPIES

Although there have been many studies of pharmacologic therapies for fibromyalgia to date, the trials had significant limitations, such as short duration, inadequate sample size, nonstandardized measures of efficacy, question of regression to the mean, and inadequate blinding, resulting in insufficient evidence to recommend one drug over another.

Tricyclic antidepressants. Two meta-analyses and a clinical review have supported the efficacy of tricyclic antidepressants in improving symptoms in fibromyalgia patients.^29–31

Selective serotonin reuptake inhibitors (SSRIs) have not been well studied, and the small size and methodologic shortcomings of these studies make it difficult to draw conclusions about the efficacy of SSRIs in reducing pain in fibromyalgia patients.^30,31

Duloxetine (Cymbalta) and milnacipran (Savella) are serotonin and norepinephrine reuptake inhibitors.^32–34 A randomized, double-blind placebo-controlled trial evaluated duloxetine in 520 fibromyalgia patients with and without major depressive disorder. Pain scores improved significantly over 6 months in duloxetine-treated patients at doses of 60 and 120 mg/day.³³ Duloxetine became the second drug approved for the treatment of fibromyalgia in 2007, and milnacipran became the third in 2009.

WHAT ROLE FOR PREGABALIN?

Pregabalin may reduce pain in some patients with fibromyalgia. However, the presenting symptoms can vary significantly, and symptoms can vary even in individual patients over time. Therefore, in most patients with fibromyalgia, a multidisciplinary approach is used to treat pain, sleep disturbance, and fatigue, along with comorbidities such as neurally mediated hypotension and psychiatric disorders. Because treatment of fibromyalgia often involves multiple drugs in addition to exercise and behavioral therapies, future studies should examine combinations of drugs and the use of drugs in conjunction with nondrug treatments.

Pregabalin advances our knowledge of fibromyalgia through improving the understanding of central sensitization and how brain neurotransmitters control central pain perceptions. Drug treatment must still be part of the comprehensive management of this disease. Physician and patient education about the current understanding of the disease is paramount in setting realistic goals for treatment.¹⁴ Future strategies to manage fibromyalgia will be based on the pathophysiology of this complex condition.

Pregabalin (Lyrica) is a novel analogue of the neurotransmitter gamma aminobutyric acid (GABA) with analgesic, anticonvulsant, and anxiolytic activity. Its approval by the US Food and Drug Administration (FDA) in 2007 for the treatment of fibromyalgia made it the first drug approved for this indication. Until then, management of fibromyalgia entailed drugs to treat pain, sleep, fatigue, and psychological disorders, and a strong emphasis on exercise and physical therapy.

Those who still question the validity of fibromyalgia as a diagnosis object to drug companies “benefiting” from the sale of such drugs.¹ But many hail pregabalin as an important advance in our understanding of the pathogenesis of fibromyalgia and how to treat it. A key question remains: How will pregabalin fit into the treatment of this often-challenging disease?

FROM FIBROSITIS TO FIBROMYALGIA

Fibromyalgia is a syndrome characterized by widespread pain. Chronic muscular pain is a common problem, but fibromyalgia is distinguished from other pain disorders by additional findings, such as consistent areas of tenderness (tender points), nonrestorative sleep, severe fatigue, and frequent psychological comorbidities such as depression and anxiety.

Fibromyalgia was originally termed “fibrositis” in 1904 by Sir William Gowers, who described it as a painful condition of the fibrous tissue, which he believed was due to inflammation in the muscles.^2,3 For several decades, research was dedicated to looking for pathology in the muscle tissue, which was thought to be the major source of pain for most patients with fibromyalgia.

In the mid-1970s, Dr. H. Moldofsky, a noted sleep researcher, reported on abnormalities of the alpha-delta component of nonrapid-eye-movement sleep in these patients. He subsequently collaborated with Dr. Hugh A. Smythe, who helped define the fibromyalgia tender points. Fibrositis was subsequently renamed fibromyalgia syndrome, since it was agreed that there was no true inflammation in muscles or fibrous tissue.

In 1990, the American College of Rheumatology published “classification criteria” for the disease.⁴ The criteria include two main features:

• A history of widespread pain (“widespread” being defined as in the axial distribution, in both the left and right sides of the body, and above and below the waist), which must be present for 3 months or more, and
• Tenderness in at least 11 of 18 specified points that is elicited when a pressure of 4 kg (the amount of pressure required to blanch a thumbnail) is applied in steady increments starting at 1 kg.

Although pain is subjective and therefore difficult to assess, the classification criteria did make it easier to study the disease in a uniform way and led to an explosion of research in this field.

FUNCTIONAL ABNORMALITIES NI THE CENTRAL NERVOUS SYSTEM

Research to date points to the pain in fibromyalgia as being mediated by changes in the central nervous system rather than in the musculoskeletal system, as was initially thought.

In the dorsal horn of the spinal cord, nociceptive (pain-sensing) neurons from the periphery synapse with the second-order neurons that carry the pain signal to the brain. In fibromyalgia, several processes seem to amplify the signal.

Central sensitization is defined as enhanced excitability of neurons in the dorsal horn. Its features include augmented spontaneous neuronal activity, enlarged receptive field areas, and enhanced responses generated by large- and small-caliber primary afferent fibers. It can result from prolonged or strong activity in the dorsal horn neurons, and it leads to the spread of hyperactivity across multiple spinal segments.^5–7

While much of the evidence for central sensitization in fibromyalgia is from animal studies, the phenomenon has also been studied in humans. Desmeules et al⁸ found that, compared with people without fibromyalgia, those with fibromyalgia had significantly lower thresholds of pain as assessed subjectively and measured objectively using the nociceptive flexion R-III reflex, which the authors described as “a specific physiologic correlate for the objective evaluation of central nociceptive pathways.”

Wind-up. Prolonged stimulation of C fibers in the dorsal horn can result in the phenomenon of wind-up, which refers to the temporal summation of second pain.

A painful stimulus evokes two pain signals. The first signal is brief and travels rapidly to the spinal cord via myelinated fibers (A fibers). The second signal, which is related to chronic pain and is described as dull, aching, or burning, travels more slowly to the dorsal horn via unmyelinated fibers (C fibers), the synapses of which use the neurotransmitter glutamate. Temporal summation is a phenomenon observed in experiments in which a series of painful stimuli are applied at regular intervals of about 2 seconds; although each stimulus is identical in intensity, subjects perceive them as increasing in intensity. The reason: during this repetitive stimulation, N-methyl-d-aspartate (NMDA) receptors become activated, leading to the removal of a magnesium block within the receptor. This results in an influx of calcium into the neuron and activation of protein kinase C, nitric oxide synthase, and cyclooxygenase. Ultimately, the firing rates of the nociceptive neurons are increased and the peripheral pain signal is strongly amplified.⁶

Wind-up has been shown to lead to characteristics of central sensitization related to C-fiber activity in animals.⁷ Staud et al⁹ studied wind-up in patients with and without fibromyalgia using series of repetitive thermal stimulation to produce temporal summation. Though wind-up was evoked in both groups, differences were observed both in the magnitude of sensory response to the first stimulus within a series and in the amount of temporal summation within a series.

Elevated excitatory neurotransmitters. In 1994, Russell et al¹⁰ showed that the concentration of substance P, an excitatory neurotransmitter, was three times higher in the cerebrospinal fluid of people with fibromyalgia than in normal controls.

Harris and colleagues¹¹ reported that glutamate, another excitatory neurotransmitter, is elevated within the brain in people with fibromyalgia. They further showed that the levels of glutamate within the insula of the brain are directly associated with the levels of both experimental pressure-evoked pain thresholds and clinical pain ratings in fibromyalgia patients.

Evidence from imaging studies. Other objective evidence of central sensitization in fibromyalgia patients comes from studies using novel imaging.

Gracely et al¹² performed functional magnetic resonance imaging (MRI) in people with and without fibromyalgia while applying pressure to their thumbs with a thumbscrew-type device. At equal levels of pressure, the people with fibromyalgia said the pressure hurt more, and specific areas of their brains lit up more on functional MRI. When the experimenters increased the pressure in the people without fibromyalgia until this group subjectively rated the pain as high as the fibromyalgia patients rated the lower level of pressure, their brains lit up to a similar degree in the same areas. These findings provide objective evidence of significantly lower pain thresholds in patients with fibromyalgia than in healthy controls, and they support the theory of central augmentation of pain sensitivity in fibromyalgia.

Staud et al¹³ also used functional MRI and found greater brain activity associated with temporal summation in fibromyalgia patients compared with controls. (In this experiment, the painful stimulus consisted of heat pulses to the foot.)

Drugs other than pregabalin that modulate the dorsal horn activity of the pain pathway include opioids, tramadol (Ultram), gabapentin (Neurontin), GABA agonists such as baclofen (Lioresal), antidepressants, alpha-2 adrenergic agonists (phenylephrine), and 5-HT3 antagonists such as ondansetron (Zofran), but none has been consistently effective for fibromyalgia.^5,14

PREGABALIN

Pregabalin is an alpha-2-delta ligand similar to GABA, but it does not act on GABA receptors. Rather, it binds with high affinity to the alpha-2-delta subunit of voltage-gated presynaptic calcium channels, resulting in reduction of calcium flow through the channels, which subsequently inhibits the release of neurotransmitters including glutamate, norepinephrine, and substance P.^15–17 Animal studies suggest that the decrease in the levels of these excitatory neurotransmitters is the mechanism of action of pregabalin, resulting in its analgesic, anticonvulsant, and anxiolytic benefit.¹⁵ Another potential mechanism of pregabalin is enhancement of slow-wave sleep, demonstrated in one study in healthy human subjects.¹⁸

Besides fibromyalgia, pregabalin is also approved for the treatment of diabetic peripheral neuropathy, postherpetic neuralgia, generalized anxiety disorder, and social anxiety disorder, and as adjunctive therapy for partial-onset seizure in adults.

Pharmacokinetics

Pregabalin is quickly absorbed, primarily in the proximal colon (bioavailability > 90%), and has highly predictable and linear pharmacokinetics.¹⁵ Food consumption does not affect its absorption or elimination but can delay its peak plasma concentration, which occurs at 1.5 hours. Its elimination half-life is approximately 6 hours.¹⁵ Because it does not bind to plasma proteins, it freely crosses the blood-brain barrier. The drug reaches its steady-state concentration within 2 days of starting therapy.

Its clearance is not affected by the sex or race of the patient, but its total clearance may be lower in the elderly because of age-related loss of renal function. Patients on hemodialysis may require a supplemental dose after dialysis because hemodialysis removes the pregabalin.

The drug is not metabolized by the P450 system in the liver, so it interacts only minimally with drugs that do use the P450 system. However, its clearance may be decreased when it is used concomitantly with drugs that can reduce the glomerular filtration rate, such as nonsteroidal anti-inflammatory drugs, aminoglycosides, and cyclosporine.¹⁵

Efficacy

The efficacy of pregabalin in fibromyalgia was evaluated in several recent trials.¹⁹

Crofford et al¹⁶ assessed pregabalin’s effects on pain, sleep, fatigue, and health-related quality of life. Some 529 patients with fibromyalgia were randomized in a double-blind fashion to four treatment groups: placebo, and pregabalin 150 mg/day, 300 mg/day, and 450 mg/day. The baseline mean pain scores (a 0-to-10 scale derived from daily diary ratings) were 6.9 in the placebo group, 6.9 for the pregabalin 150 mg/day group, 7.3 for the pregabalin 300 mg/day group, and 7.0 for the pregabalin 450 mg/day group.

The pain scores declined in all groups, but at 8 weeks, the mean score had declined 0.93 points more in the group receiving pregabalin 450 mg/day than in the placebo group (P ≤ .001). The scores in the groups taking pregabalin 150 mg/day and 300 mg/day were not significantly different from those in the placebo group. Significantly more patients in the 450-mg/day group (29%, vs 13% in the placebo group) had at least 50% improvement in pain at the end of the study. Patients in both the 300-mg/day group and the 450-mg/day had statistically significant improvement in their quality of sleep, in fatigue, and on the Patient Global Impression of Change (PGIC) scale.

Arnold et al²⁰ conducted a trial with 750 patients in which three doses of pregabalin were compared with placebo: 300 mg/day, 450 mg/day, and 600 mg/day. The primary end point was also the change in pain score from baseline (using the 0-to-10 scale derived from a daily pain diary). The mean baseline pain score was 6.7.

At 14 weeks, the mean pain score was lower than at baseline in all the groups, but it had declined 0.71 more in the pregabalin 300-mg/day group than in the placebo group, 0.98 points more in the 450-mg/day group, and 1.0 points more in the 600-mg/day group. All three pregabalin groups also showed significant improvement on the PGIC scale, and patients in the 450-mg/day and 600-mg/day groups showed statistically significant improvement in the Fibromyalgia Impact Questionnaire (FIQ) score. All three pregabalin treatment groups also had significantly better patient-reported sleep outcomes than in the placebo group, both in measures of overall sleep and quality of sleep. With the exception of a significant improvement of anxiety on 600 mg/day, there was no significant difference between the treatment and placebo groups in the secondary outcomes of depression and anxiety symptoms and fatigue.

Duan et al²¹ presented a pooled analysis of this and a similarly designed double-blind, placebo-controlled trial (the results of which were not available individually) at the 71st annual meeting of the American College of Rheumatology in November 2007. The analysis included 1,493 patients with a mean baseline pain score of 6.9. Compared with the mean pain score in the placebo group, those in the pregabalin groups had declined more by the end of the study: 0.55 points more with 300 mg/day, 0.71 points more with 450 mg/day, and 0.82 points more with 600 mg/day. This pooled analysis also showed significant improvement in PGIC score with all pregabalin doses and in the FIQ score with 450 mg/day and 600 mg/day.

The FREEDOM trial²² (Fibromyalgia Relapse Evaluation and Efficacy for Durability of Meaningful Relief) evaluated the durability of effect of pregabalin in reducing pain and symptoms associated with fibromyalgia in 1,051 patients who initially responded to the drug.

The patients received 6 weeks of open-label treatment with pregabalin and then 26 weeks of double-blind treatment (dose adjustment was allowed based on efficacy and tolerability for the first 3 weeks). The time to loss of therapeutic response was significantly longer with pregabalin than with placebo. Loss of therapeutic response was defined as worsening of pain for two consecutive visits or worsening of fibromyalgia symptoms requiring alternative therapy.

By the end of the double-blind phase, 61% of those in the placebo group had loss of therapeutic response compared with only 32% in the pregabalin group. The time to worsening of the FIQ score was also significantly longer in the pregabalin group than in the placebo group.

Dizziness and sleepiness were the most common adverse events in these studies.

In the 8-week study by Crofford et al,¹⁶ dizziness was dose-related, occurring in 10.7% of those receiving placebo (one patient withdrew because of dizziness), 22.7% of those receiving 150 mg/day (two patients withdrew), 31.3% of those receiving 300 mg/day (four patients withdrew), and 49.2% of those receiving 450 mg/day (five patients withdrew). Somnolence was also dose-related, occurring in 4.6% in the placebo group, 15.9% in the 150-mg/day group (two patients withdrew due to somnolence), 27.6% in the 300-mg/day group (three withdrew), and 28.0% in the 450-mg/day group (five withdrew).

The 14-week study by Arnold et al²⁰ also showed higher frequencies of adverse events with higher doses. The rates of dizziness were 7.6% with placebo, 27.9% with pregabalin 300 mg/day, 37.4% with 450 mg/day, and 42.0% with 600 mg/day. The rates of somnolence were 3.8% with placebo, 12.6% with 300 mg/day of pregabalin, 19.5% with 450 mg/day, and 21.8% with 600 mg/day. Dizziness and somnolence were also the most common adverse effects that led to discontinuation of pregabalin, with rates of 4% and 3%, respectively.

The open-label phase of the FREEDOM trial showed rates of 36% for dizziness and 22% for somnolence among pregabalin-treated patients.

Weight gain and peripheral edema were also common adverse effects in these studies.²² Definitions of weight gain varied, and edema was not accompanied by evidence of cardiac or renal dysfunction.

Less common side effects seen more frequently in the treated groups included dry mouth, blurred vision, and difficulty with concentration and attention. The package insert also warns of angioedema, hypersensitivity reaction, mild asymptomatic creatine kinase elevation, decreased platelet count (without bleeding), and prolongation of the PR interval on electrocardiography.

Pregabalin is a schedule V controlled substance; in clinical studies, abrupt or rapid discontinuation of the drug led to insomnia, nausea, headache, or diarrhea in some patients, suggesting symptoms of dependence. In clinical studies involving a total of more than 5,500 patients, 4% of patients on pregabalin and 1% of patients on placebo reported euphoria as an adverse effect,¹⁹ suggesting possible potential for abuse.

Dosing

As a result of the above studies, the recommended starting dose of pregabalin for fibromyalgia is 150 mg/day in two or three divided doses, gradually increased to 300 mg/day within 1 week based on tolerability and efficacy. The dose may be increased to a maximum of 450 mg/day. The 600-mg dose was found to have no significant additional benefit, but it did have more adverse effects and therefore is not recommended. It is important to note that in these studies multiple medications for pain and insomnia were prohibited, so data on drug interactions with pregabalin are limited.

Few achieve complete remission, but most patients feel better

Several studies of the natural history of fibromyalgia have shown that very few patients experience complete remission of the disease, even after many years. Therefore, one should try to set up realistic expectations for patients, with the goal of achieving functional improvement in activities of daily living and a return to one’s predisease state.

In the longest follow-up study, 39 patients in Boston, MA, were prospectively followed for over 10 years. No patient achieved complete remission: all of them reported some fibromyalgia-related symptoms at the end of the study.²³ However, 66% of them felt a little to a lot better than when first diagnosed, 55% felt well or very well, and only 7% felt poorly.

Other studies have also shown complete remission to be rare.^24,25 A 5-year follow-up study investigating fibromyalgia patients’ perceptions of their symptoms and its impact on everyday life activities demonstrated that the social consequences of fibromyalgia’s symptoms are severe and constant over time.²⁶

Evidence of favorable outcomes was reported in one study in which 47% of patients reported moderate to marked improvement in overall fibromyalgia status upon 3-year follow-up,²⁷ and in another study, in which remission was objectively identified in 24.2% of patients 2 years after diagnosis.²⁸

OTHER THERAPIES

Although there have been many studies of pharmacologic therapies for fibromyalgia to date, the trials had significant limitations, such as short duration, inadequate sample size, nonstandardized measures of efficacy, question of regression to the mean, and inadequate blinding, resulting in insufficient evidence to recommend one drug over another.

Tricyclic antidepressants. Two meta-analyses and a clinical review have supported the efficacy of tricyclic antidepressants in improving symptoms in fibromyalgia patients.^29–31

Selective serotonin reuptake inhibitors (SSRIs) have not been well studied, and the small size and methodologic shortcomings of these studies make it difficult to draw conclusions about the efficacy of SSRIs in reducing pain in fibromyalgia patients.^30,31

Duloxetine (Cymbalta) and milnacipran (Savella) are serotonin and norepinephrine reuptake inhibitors.^32–34 A randomized, double-blind placebo-controlled trial evaluated duloxetine in 520 fibromyalgia patients with and without major depressive disorder. Pain scores improved significantly over 6 months in duloxetine-treated patients at doses of 60 and 120 mg/day.³³ Duloxetine became the second drug approved for the treatment of fibromyalgia in 2007, and milnacipran became the third in 2009.

WHAT ROLE FOR PREGABALIN?

Pregabalin may reduce pain in some patients with fibromyalgia. However, the presenting symptoms can vary significantly, and symptoms can vary even in individual patients over time. Therefore, in most patients with fibromyalgia, a multidisciplinary approach is used to treat pain, sleep disturbance, and fatigue, along with comorbidities such as neurally mediated hypotension and psychiatric disorders. Because treatment of fibromyalgia often involves multiple drugs in addition to exercise and behavioral therapies, future studies should examine combinations of drugs and the use of drugs in conjunction with nondrug treatments.

Pregabalin advances our knowledge of fibromyalgia through improving the understanding of central sensitization and how brain neurotransmitters control central pain perceptions. Drug treatment must still be part of the comprehensive management of this disease. Physician and patient education about the current understanding of the disease is paramount in setting realistic goals for treatment.¹⁴ Future strategies to manage fibromyalgia will be based on the pathophysiology of this complex condition.

Q: What is the most likely diagnosis?

• Contact dermatitis
• Herpes zoster
• Herpes simplex
• Pemphigus
• Bullous pemphigoid
• Graft-vs-host disease

A: The correct answer is herpes zoster (shingles), which represents reactivation of varicella-zoster virus.

The diagnosis of herpes zoster is usually based solely on the clinical presentation. It is typically characterized in immunocompetent patients by a unilateral vesicular eruption with a well-defined dermatomal distribution. But occasionally, as in this patient on immunosuppressant drugs, it presents with atypical skin lesions such as multiple huge bullae involving multiple dermatomes.^1,2

Patients treated with immunosuppressive agents after organ transplantation are at high risk of herpes zoster. A recent published retrospective study of adult kidney transplant recipients showed an average incidence of approximately 28 per 1,000 person-years.³

Treatment involves analgesics and sometimes antiviral drugs, and the decisions should take into account the patient’s age and immune status.¹

Q: What is the most likely diagnosis?

• Contact dermatitis
• Herpes zoster
• Herpes simplex
• Pemphigus
• Bullous pemphigoid
• Graft-vs-host disease

A: The correct answer is herpes zoster (shingles), which represents reactivation of varicella-zoster virus.

The diagnosis of herpes zoster is usually based solely on the clinical presentation. It is typically characterized in immunocompetent patients by a unilateral vesicular eruption with a well-defined dermatomal distribution. But occasionally, as in this patient on immunosuppressant drugs, it presents with atypical skin lesions such as multiple huge bullae involving multiple dermatomes.^1,2

Patients treated with immunosuppressive agents after organ transplantation are at high risk of herpes zoster. A recent published retrospective study of adult kidney transplant recipients showed an average incidence of approximately 28 per 1,000 person-years.³

Treatment involves analgesics and sometimes antiviral drugs, and the decisions should take into account the patient’s age and immune status.¹

Q: What is the most likely diagnosis?

• Contact dermatitis
• Herpes zoster
• Herpes simplex
• Pemphigus
• Bullous pemphigoid
• Graft-vs-host disease

A: The correct answer is herpes zoster (shingles), which represents reactivation of varicella-zoster virus.

The diagnosis of herpes zoster is usually based solely on the clinical presentation. It is typically characterized in immunocompetent patients by a unilateral vesicular eruption with a well-defined dermatomal distribution. But occasionally, as in this patient on immunosuppressant drugs, it presents with atypical skin lesions such as multiple huge bullae involving multiple dermatomes.^1,2

Patients treated with immunosuppressive agents after organ transplantation are at high risk of herpes zoster. A recent published retrospective study of adult kidney transplant recipients showed an average incidence of approximately 28 per 1,000 person-years.³

Treatment involves analgesics and sometimes antiviral drugs, and the decisions should take into account the patient’s age and immune status.¹

What are the reasons women ordinarily give for unintended pregnancy? The results of our study show that some of the more common ones are not included on standard risk-assessment surveys. If we hope to offer patients a meaningful course of intervention, it would help to understand the issues these women contend with.

Despite the availability of effective contraception, many women have unprotected intercourse that puts them at risk for unintended pregnancy. Among women in the United States who are age 18 or older, slightly more than 40% of live births result from unintended conception.¹ The reasons women have unprotected intercourse have not been clear. Of the few studies that have addressed this issue,² some have restricted their investigation to a few potential reasons^2-4 or have limited exploration to the reasons associated with a single episode of intercourse.⁵ The latter type of investigation is too narrow. A more comprehensive approach is needed because risk-taking is likely to be a complex phenomenon, with reasons changing as the context changes or as women try different forms of contraception.

We conducted focus groups with women who were risking unintended pregnancy.⁶ With results from the focus groups, we developed a survey to determine the relative prevalence of reasons given, and thereby direct future interventions at those that are most common.

Methods

We recruited participants from local primary care clinics serving financially disadvantaged populations. Flyers describing the study were posted, and interested women approached a research assistant stationed in the clinic. We explained the survey and reviewed eligibility criteria with those who inquired. Women who wished to participate gave verbal consent and were taken to a private area, where a research assistant administered the survey. The study was approved by the local institutional review board. We waived written consent because the survey was anonymous and we collected no identifiers.

Eligibility required that a woman be between the ages of 18 and 39 years, unmarried, and not be pregnant or trying to get pregnant. Women who reported having had a hysterectomy or tubal ligation or being menopausal were ineligible. We defined unprotected intercourse as vaginal intercourse with a fertile male without using a condom, hormonal method, diaphragm, intrauterine device (IUD), vaginal ring, Lea’s shield (a vaginal barrier contraceptive), emergency contraception, vaginal sponge, or cervical cap. These eligibility requirements were identical to those of the focus groups that had provided input for our survey questions.

Women who reported having unprotected sex in the past year were asked to choose from 42 possible reasons (foils) adapted from responses offered in the focus groups.⁶ When possible, we used the exact words uttered by focus group participants (eg, “I just went with the flow”). We asked women to select all the reasons that applied to them over the past year. The survey also included questions about previous pregnancies, use of home pregnancy test kits, and medical conditions that could affect an unintended pregnancy or fetus (preconceptual health status).

Analysis

We performed univariate analysis using the chi square test in the Statistical Analysis System package (SAS version 8.0, SAS Institute, Inc., Cary, NC). Age was evaluated as a dichotomous variable compared to the median.

Results

Demographics and health

The 151 respondents had a median age of 24 years, and a median household income of <$20,000 per year. Eighty-four women (56%) had unprotected intercourse in the past year. Of the 151 respondents, 56% were white and 41% were black. Twenty-two percent had not graduated from high school. Ten percent had recently been homeless, 9% had recently been jailed, 7% had a recent sexually transmitted disease, and 4% had traded sex for gain.

Median body mass index was 26. Fifty-one percent were smokers, 19% were binge drinkers, 11% had hypertension, and 5% had diabetes. Ninety-four (62%) of the respondents had at least 1 previous pregnancy (average of 2 live births), and 39% of them had used a home pregnancy test kit to diagnose their last pregnancy.

Reasons for unprotected intercourse

Of the 84 women who reported having unprotected intercourse in the past year, 1 woman selected all 42 of the reasons on the survey, with a single exception (“I don’t know where to get birth control/contraception”). On average, the women selected 9 reasons each. The most common reasons for having unprotected intercourse appear in the TABLE.

Lack of concern. Seventy-three women (87%) cited at least 1 of the following reasons: “just not thinking about birth control,” “not planning to have sex,” getting caught up in the “heat of the moment,” or “just went with the flow.” We categorized these reasons as lack of thought/preparation.⁶

Beliefs about relationship. Fifty-nine women (70%) cited relationship-related reasons: their partner would “be there” for them if they did get pregnant, or they were “in a long-term relationship and it was too much of a hassle to keep using birth control/condoms.”

Unacceptable side effects. Sixty-seven women (80%) cited method-related side effects, including weight gain, discomfort with condoms, and reduced pleasure. Of note, the most commonly cited reason was that condoms gave the woman discomfort.

Categories not mutually exclusive. These 3 categories—lack of thought/preparation, relationship-related reasons, and side effects—overlapped significantly, with 72 women (86%) choosing more than 1 of these categories, and 44 (52%) choosing all 3. Eighty-three of the 84 women (99%) chose at least 1 of these categories.

As stated, 55 women (65%) believed their partner would “be there” for them, and 43 of these had a previous pregnancy. Of the 43, 58% said their partner actually “was there” for them during the last pregnancy. The remainder had not had partner support during the last pregnancy, but believed their current partner would support them in the event of a future pregnancy.

Additional volunteered reasons. Beyond the reasons given in the TABLE, 23% said they forgot to take their pill, and 20% said they would not really mind that much if they got pregnant.

Between 10% and 18% of women cited each of the following reasons: judgment clouded by alcohol or drugs, thinking they could always get an abortion if they conceived, not wanting to ask their partner to use a condom, being scared of needles, being worried about vaginal bleeding, having a medical condition (smoking, obesity, etc.) that limited their choice of contraception, having a partner who objected to her using contraception, or feeling that contraception was unnatural.

Less than 10% of women cited the following reasons: problems with transportation to get to clinic, insurance that did not cover contraception or a preferred method of contraception, not liking the clinic or clinic personnel, inability to understand explanations by clinic personnel, cost, forced sex, a preference for rhythm method, feeling that a method was messy, family/friends being against her using contraception, religious objections, being embarrassed to buy contraception, or being unsure how to use contraception.

Few age or race differences. There was little difference in response between races, with the exception of being uncomfortable asking a partner to use condoms, which was noted by 23% of blacks and 2% of whites (P=.006). There were no significant differences by age.

Among the women who had unprotected intercourse, 79 (94%) had used some form of birth control at least once during the past year. Of these, 90% had used condoms, 34% had taken the Pill, 22% had used medroxyprogesterone acetate injectable suspension (Depo Provera), and 20% had used the norelgestromin/ethinyl estradiol transdermal system (Ortho Evra/“the patch”). Eighteen percent had used emergency contraception in the past year.

TABLE
Reasons women most commonly cited for unprotected intercourse

Discussion

The most common reasons for having unprotected intercourse reflected lack of thought/preparation, relationship issues, and concerns about side effects. Most women expressed reasons from more than 1 of these categories, suggesting they are interrelated.⁷

Preparation issues. Most women used contraception inconsistently rather than not at all. At times they were motivated to use contraception; at times they were not.

Relationship issues. Women in our study cited several relationship-related reasons that might explain inconsistent use of contraception. Many women felt that regular contraception became a “hassle” in long-term relationships. This is supported by studies showing that condoms may be reserved for partners who are considered at risk for disease, or that condom use may be thought to imply a lack of trust antithetical to a long-term relationship.⁸ Others believed their partner would “be there” for them if a pregnancy occurred and gave this as a reason for having unprotected intercourse. Regarding this belief, past experience to the contrary did not appear to dampen optimism about the future.

Side effect issues. Interestingly, the most commonly cited method-related side effect was that male condoms made the woman uncomfortable during intercourse. They cited discomfort for the man less frequently. Female discomfort has also been identified as a reason college women avoid condom use.⁹ Others have shown that women have difficulties with condom lubrication,¹⁰ although it is less of an issue for men.¹¹ This suggests that education about condoms should include informing women about lubrication options. However, education alone may not resolve this issue, and it is important to inform women about alternative contraceptive choices.

Our extensive list of reasons facilitated responses. On average, each woman identified 9 reasons why she had unprotected intercourse. This was likely a result of the large number of foils presented in the survey, which allowed women to give a fuller picture of their reasons than a more limited number of choices might allow.

For example, the Pregnancy Risk Assessment Monitoring System (PRAMS) survey offers just 6 foils, and they do not include the common thought/preparation and relationship issues. Broad surveys like PRAMS are necessarily concise about single issues. Free-text responses to the PRAMS survey show that respondents endorse reasons not reflected in the few foils.⁴

Moreover, we used the exact phrasing given by focus group participants whenever possible, which could increase selection of appropriate foils. This is why we included reasons such as wanting to “go with the flow.” We also included reasons that were cited by the focus groups, but which have rarely been included in surveys, such as condoms creating discomfort for women.

Implications of our findings. Slightly more than half of the women in the study were having unprotected intercourse and were at risk for unintended pregnancy. Although “unintendedness” is a concept that may not be widely recognized by individual women,⁷ it is a useful epidemiological construct that serves as a marker for adverse outcomes, such as low birth weight or premature labor.¹² In our study, women at risk for unintended pregnancy had a variety of medical conditions and health behaviors that could affect a pregnancy. Moreover, slightly more than one-third of participants thought they were unlikely to get pregnant despite having unprotected intercourse. This argues for improved preconceptional care in this population.¹³ Education may improve understanding of fertility, contraceptive options, risk reduction strategies, and communication techniques.

Limitations. The study is subject to several limitations. All responses were self-reported and subject to recall bias. The population was a convenience sample of financially disadvantaged women visiting outpatient clinics, and is not representative of other populations. Women attending a clinic might reasonably be expected to have access to health care and contraception, which might not be true of other populations. Thus, few women in our study cited cost or access to care as a reason for having unprotected intercourse.

Funding

This study was funded in part by the Michigan Department of Community Health.

Correspondence
Mary D. Nettleman, MD, MS, B 427 Clinical Center, East Lansing, MI 48824; [email protected]

What are the reasons women ordinarily give for unintended pregnancy? The results of our study show that some of the more common ones are not included on standard risk-assessment surveys. If we hope to offer patients a meaningful course of intervention, it would help to understand the issues these women contend with.

Despite the availability of effective contraception, many women have unprotected intercourse that puts them at risk for unintended pregnancy. Among women in the United States who are age 18 or older, slightly more than 40% of live births result from unintended conception.¹ The reasons women have unprotected intercourse have not been clear. Of the few studies that have addressed this issue,² some have restricted their investigation to a few potential reasons^2-4 or have limited exploration to the reasons associated with a single episode of intercourse.⁵ The latter type of investigation is too narrow. A more comprehensive approach is needed because risk-taking is likely to be a complex phenomenon, with reasons changing as the context changes or as women try different forms of contraception.

We conducted focus groups with women who were risking unintended pregnancy.⁶ With results from the focus groups, we developed a survey to determine the relative prevalence of reasons given, and thereby direct future interventions at those that are most common.

Methods

We recruited participants from local primary care clinics serving financially disadvantaged populations. Flyers describing the study were posted, and interested women approached a research assistant stationed in the clinic. We explained the survey and reviewed eligibility criteria with those who inquired. Women who wished to participate gave verbal consent and were taken to a private area, where a research assistant administered the survey. The study was approved by the local institutional review board. We waived written consent because the survey was anonymous and we collected no identifiers.

Eligibility required that a woman be between the ages of 18 and 39 years, unmarried, and not be pregnant or trying to get pregnant. Women who reported having had a hysterectomy or tubal ligation or being menopausal were ineligible. We defined unprotected intercourse as vaginal intercourse with a fertile male without using a condom, hormonal method, diaphragm, intrauterine device (IUD), vaginal ring, Lea’s shield (a vaginal barrier contraceptive), emergency contraception, vaginal sponge, or cervical cap. These eligibility requirements were identical to those of the focus groups that had provided input for our survey questions.

Women who reported having unprotected sex in the past year were asked to choose from 42 possible reasons (foils) adapted from responses offered in the focus groups.⁶ When possible, we used the exact words uttered by focus group participants (eg, “I just went with the flow”). We asked women to select all the reasons that applied to them over the past year. The survey also included questions about previous pregnancies, use of home pregnancy test kits, and medical conditions that could affect an unintended pregnancy or fetus (preconceptual health status).

Analysis

We performed univariate analysis using the chi square test in the Statistical Analysis System package (SAS version 8.0, SAS Institute, Inc., Cary, NC). Age was evaluated as a dichotomous variable compared to the median.

Results

Demographics and health

The 151 respondents had a median age of 24 years, and a median household income of <$20,000 per year. Eighty-four women (56%) had unprotected intercourse in the past year. Of the 151 respondents, 56% were white and 41% were black. Twenty-two percent had not graduated from high school. Ten percent had recently been homeless, 9% had recently been jailed, 7% had a recent sexually transmitted disease, and 4% had traded sex for gain.

Median body mass index was 26. Fifty-one percent were smokers, 19% were binge drinkers, 11% had hypertension, and 5% had diabetes. Ninety-four (62%) of the respondents had at least 1 previous pregnancy (average of 2 live births), and 39% of them had used a home pregnancy test kit to diagnose their last pregnancy.

Reasons for unprotected intercourse

Of the 84 women who reported having unprotected intercourse in the past year, 1 woman selected all 42 of the reasons on the survey, with a single exception (“I don’t know where to get birth control/contraception”). On average, the women selected 9 reasons each. The most common reasons for having unprotected intercourse appear in the TABLE.

Lack of concern. Seventy-three women (87%) cited at least 1 of the following reasons: “just not thinking about birth control,” “not planning to have sex,” getting caught up in the “heat of the moment,” or “just went with the flow.” We categorized these reasons as lack of thought/preparation.⁶

Beliefs about relationship. Fifty-nine women (70%) cited relationship-related reasons: their partner would “be there” for them if they did get pregnant, or they were “in a long-term relationship and it was too much of a hassle to keep using birth control/condoms.”

Unacceptable side effects. Sixty-seven women (80%) cited method-related side effects, including weight gain, discomfort with condoms, and reduced pleasure. Of note, the most commonly cited reason was that condoms gave the woman discomfort.

Categories not mutually exclusive. These 3 categories—lack of thought/preparation, relationship-related reasons, and side effects—overlapped significantly, with 72 women (86%) choosing more than 1 of these categories, and 44 (52%) choosing all 3. Eighty-three of the 84 women (99%) chose at least 1 of these categories.

As stated, 55 women (65%) believed their partner would “be there” for them, and 43 of these had a previous pregnancy. Of the 43, 58% said their partner actually “was there” for them during the last pregnancy. The remainder had not had partner support during the last pregnancy, but believed their current partner would support them in the event of a future pregnancy.

Additional volunteered reasons. Beyond the reasons given in the TABLE, 23% said they forgot to take their pill, and 20% said they would not really mind that much if they got pregnant.

Between 10% and 18% of women cited each of the following reasons: judgment clouded by alcohol or drugs, thinking they could always get an abortion if they conceived, not wanting to ask their partner to use a condom, being scared of needles, being worried about vaginal bleeding, having a medical condition (smoking, obesity, etc.) that limited their choice of contraception, having a partner who objected to her using contraception, or feeling that contraception was unnatural.

Less than 10% of women cited the following reasons: problems with transportation to get to clinic, insurance that did not cover contraception or a preferred method of contraception, not liking the clinic or clinic personnel, inability to understand explanations by clinic personnel, cost, forced sex, a preference for rhythm method, feeling that a method was messy, family/friends being against her using contraception, religious objections, being embarrassed to buy contraception, or being unsure how to use contraception.

Few age or race differences. There was little difference in response between races, with the exception of being uncomfortable asking a partner to use condoms, which was noted by 23% of blacks and 2% of whites (P=.006). There were no significant differences by age.

Among the women who had unprotected intercourse, 79 (94%) had used some form of birth control at least once during the past year. Of these, 90% had used condoms, 34% had taken the Pill, 22% had used medroxyprogesterone acetate injectable suspension (Depo Provera), and 20% had used the norelgestromin/ethinyl estradiol transdermal system (Ortho Evra/“the patch”). Eighteen percent had used emergency contraception in the past year.

TABLE
Reasons women most commonly cited for unprotected intercourse

Discussion

The most common reasons for having unprotected intercourse reflected lack of thought/preparation, relationship issues, and concerns about side effects. Most women expressed reasons from more than 1 of these categories, suggesting they are interrelated.⁷

Preparation issues. Most women used contraception inconsistently rather than not at all. At times they were motivated to use contraception; at times they were not.

Relationship issues. Women in our study cited several relationship-related reasons that might explain inconsistent use of contraception. Many women felt that regular contraception became a “hassle” in long-term relationships. This is supported by studies showing that condoms may be reserved for partners who are considered at risk for disease, or that condom use may be thought to imply a lack of trust antithetical to a long-term relationship.⁸ Others believed their partner would “be there” for them if a pregnancy occurred and gave this as a reason for having unprotected intercourse. Regarding this belief, past experience to the contrary did not appear to dampen optimism about the future.

Side effect issues. Interestingly, the most commonly cited method-related side effect was that male condoms made the woman uncomfortable during intercourse. They cited discomfort for the man less frequently. Female discomfort has also been identified as a reason college women avoid condom use.⁹ Others have shown that women have difficulties with condom lubrication,¹⁰ although it is less of an issue for men.¹¹ This suggests that education about condoms should include informing women about lubrication options. However, education alone may not resolve this issue, and it is important to inform women about alternative contraceptive choices.

Our extensive list of reasons facilitated responses. On average, each woman identified 9 reasons why she had unprotected intercourse. This was likely a result of the large number of foils presented in the survey, which allowed women to give a fuller picture of their reasons than a more limited number of choices might allow.

For example, the Pregnancy Risk Assessment Monitoring System (PRAMS) survey offers just 6 foils, and they do not include the common thought/preparation and relationship issues. Broad surveys like PRAMS are necessarily concise about single issues. Free-text responses to the PRAMS survey show that respondents endorse reasons not reflected in the few foils.⁴

Moreover, we used the exact phrasing given by focus group participants whenever possible, which could increase selection of appropriate foils. This is why we included reasons such as wanting to “go with the flow.” We also included reasons that were cited by the focus groups, but which have rarely been included in surveys, such as condoms creating discomfort for women.

Implications of our findings. Slightly more than half of the women in the study were having unprotected intercourse and were at risk for unintended pregnancy. Although “unintendedness” is a concept that may not be widely recognized by individual women,⁷ it is a useful epidemiological construct that serves as a marker for adverse outcomes, such as low birth weight or premature labor.¹² In our study, women at risk for unintended pregnancy had a variety of medical conditions and health behaviors that could affect a pregnancy. Moreover, slightly more than one-third of participants thought they were unlikely to get pregnant despite having unprotected intercourse. This argues for improved preconceptional care in this population.¹³ Education may improve understanding of fertility, contraceptive options, risk reduction strategies, and communication techniques.

Limitations. The study is subject to several limitations. All responses were self-reported and subject to recall bias. The population was a convenience sample of financially disadvantaged women visiting outpatient clinics, and is not representative of other populations. Women attending a clinic might reasonably be expected to have access to health care and contraception, which might not be true of other populations. Thus, few women in our study cited cost or access to care as a reason for having unprotected intercourse.

Funding

This study was funded in part by the Michigan Department of Community Health.

Correspondence
Mary D. Nettleman, MD, MS, B 427 Clinical Center, East Lansing, MI 48824; [email protected]

What are the reasons women ordinarily give for unintended pregnancy? The results of our study show that some of the more common ones are not included on standard risk-assessment surveys. If we hope to offer patients a meaningful course of intervention, it would help to understand the issues these women contend with.

Despite the availability of effective contraception, many women have unprotected intercourse that puts them at risk for unintended pregnancy. Among women in the United States who are age 18 or older, slightly more than 40% of live births result from unintended conception.¹ The reasons women have unprotected intercourse have not been clear. Of the few studies that have addressed this issue,² some have restricted their investigation to a few potential reasons^2-4 or have limited exploration to the reasons associated with a single episode of intercourse.⁵ The latter type of investigation is too narrow. A more comprehensive approach is needed because risk-taking is likely to be a complex phenomenon, with reasons changing as the context changes or as women try different forms of contraception.

We conducted focus groups with women who were risking unintended pregnancy.⁶ With results from the focus groups, we developed a survey to determine the relative prevalence of reasons given, and thereby direct future interventions at those that are most common.

Methods

We recruited participants from local primary care clinics serving financially disadvantaged populations. Flyers describing the study were posted, and interested women approached a research assistant stationed in the clinic. We explained the survey and reviewed eligibility criteria with those who inquired. Women who wished to participate gave verbal consent and were taken to a private area, where a research assistant administered the survey. The study was approved by the local institutional review board. We waived written consent because the survey was anonymous and we collected no identifiers.

Eligibility required that a woman be between the ages of 18 and 39 years, unmarried, and not be pregnant or trying to get pregnant. Women who reported having had a hysterectomy or tubal ligation or being menopausal were ineligible. We defined unprotected intercourse as vaginal intercourse with a fertile male without using a condom, hormonal method, diaphragm, intrauterine device (IUD), vaginal ring, Lea’s shield (a vaginal barrier contraceptive), emergency contraception, vaginal sponge, or cervical cap. These eligibility requirements were identical to those of the focus groups that had provided input for our survey questions.

Women who reported having unprotected sex in the past year were asked to choose from 42 possible reasons (foils) adapted from responses offered in the focus groups.⁶ When possible, we used the exact words uttered by focus group participants (eg, “I just went with the flow”). We asked women to select all the reasons that applied to them over the past year. The survey also included questions about previous pregnancies, use of home pregnancy test kits, and medical conditions that could affect an unintended pregnancy or fetus (preconceptual health status).

Analysis

We performed univariate analysis using the chi square test in the Statistical Analysis System package (SAS version 8.0, SAS Institute, Inc., Cary, NC). Age was evaluated as a dichotomous variable compared to the median.

Results

Demographics and health

The 151 respondents had a median age of 24 years, and a median household income of <$20,000 per year. Eighty-four women (56%) had unprotected intercourse in the past year. Of the 151 respondents, 56% were white and 41% were black. Twenty-two percent had not graduated from high school. Ten percent had recently been homeless, 9% had recently been jailed, 7% had a recent sexually transmitted disease, and 4% had traded sex for gain.

Median body mass index was 26. Fifty-one percent were smokers, 19% were binge drinkers, 11% had hypertension, and 5% had diabetes. Ninety-four (62%) of the respondents had at least 1 previous pregnancy (average of 2 live births), and 39% of them had used a home pregnancy test kit to diagnose their last pregnancy.

Reasons for unprotected intercourse

Of the 84 women who reported having unprotected intercourse in the past year, 1 woman selected all 42 of the reasons on the survey, with a single exception (“I don’t know where to get birth control/contraception”). On average, the women selected 9 reasons each. The most common reasons for having unprotected intercourse appear in the TABLE.

Lack of concern. Seventy-three women (87%) cited at least 1 of the following reasons: “just not thinking about birth control,” “not planning to have sex,” getting caught up in the “heat of the moment,” or “just went with the flow.” We categorized these reasons as lack of thought/preparation.⁶

Beliefs about relationship. Fifty-nine women (70%) cited relationship-related reasons: their partner would “be there” for them if they did get pregnant, or they were “in a long-term relationship and it was too much of a hassle to keep using birth control/condoms.”

Unacceptable side effects. Sixty-seven women (80%) cited method-related side effects, including weight gain, discomfort with condoms, and reduced pleasure. Of note, the most commonly cited reason was that condoms gave the woman discomfort.

Categories not mutually exclusive. These 3 categories—lack of thought/preparation, relationship-related reasons, and side effects—overlapped significantly, with 72 women (86%) choosing more than 1 of these categories, and 44 (52%) choosing all 3. Eighty-three of the 84 women (99%) chose at least 1 of these categories.

As stated, 55 women (65%) believed their partner would “be there” for them, and 43 of these had a previous pregnancy. Of the 43, 58% said their partner actually “was there” for them during the last pregnancy. The remainder had not had partner support during the last pregnancy, but believed their current partner would support them in the event of a future pregnancy.

Additional volunteered reasons. Beyond the reasons given in the TABLE, 23% said they forgot to take their pill, and 20% said they would not really mind that much if they got pregnant.

Between 10% and 18% of women cited each of the following reasons: judgment clouded by alcohol or drugs, thinking they could always get an abortion if they conceived, not wanting to ask their partner to use a condom, being scared of needles, being worried about vaginal bleeding, having a medical condition (smoking, obesity, etc.) that limited their choice of contraception, having a partner who objected to her using contraception, or feeling that contraception was unnatural.

Less than 10% of women cited the following reasons: problems with transportation to get to clinic, insurance that did not cover contraception or a preferred method of contraception, not liking the clinic or clinic personnel, inability to understand explanations by clinic personnel, cost, forced sex, a preference for rhythm method, feeling that a method was messy, family/friends being against her using contraception, religious objections, being embarrassed to buy contraception, or being unsure how to use contraception.

Few age or race differences. There was little difference in response between races, with the exception of being uncomfortable asking a partner to use condoms, which was noted by 23% of blacks and 2% of whites (P=.006). There were no significant differences by age.

Among the women who had unprotected intercourse, 79 (94%) had used some form of birth control at least once during the past year. Of these, 90% had used condoms, 34% had taken the Pill, 22% had used medroxyprogesterone acetate injectable suspension (Depo Provera), and 20% had used the norelgestromin/ethinyl estradiol transdermal system (Ortho Evra/“the patch”). Eighteen percent had used emergency contraception in the past year.

TABLE
Reasons women most commonly cited for unprotected intercourse

Discussion

The most common reasons for having unprotected intercourse reflected lack of thought/preparation, relationship issues, and concerns about side effects. Most women expressed reasons from more than 1 of these categories, suggesting they are interrelated.⁷

Preparation issues. Most women used contraception inconsistently rather than not at all. At times they were motivated to use contraception; at times they were not.

Relationship issues. Women in our study cited several relationship-related reasons that might explain inconsistent use of contraception. Many women felt that regular contraception became a “hassle” in long-term relationships. This is supported by studies showing that condoms may be reserved for partners who are considered at risk for disease, or that condom use may be thought to imply a lack of trust antithetical to a long-term relationship.⁸ Others believed their partner would “be there” for them if a pregnancy occurred and gave this as a reason for having unprotected intercourse. Regarding this belief, past experience to the contrary did not appear to dampen optimism about the future.

Side effect issues. Interestingly, the most commonly cited method-related side effect was that male condoms made the woman uncomfortable during intercourse. They cited discomfort for the man less frequently. Female discomfort has also been identified as a reason college women avoid condom use.⁹ Others have shown that women have difficulties with condom lubrication,¹⁰ although it is less of an issue for men.¹¹ This suggests that education about condoms should include informing women about lubrication options. However, education alone may not resolve this issue, and it is important to inform women about alternative contraceptive choices.

Our extensive list of reasons facilitated responses. On average, each woman identified 9 reasons why she had unprotected intercourse. This was likely a result of the large number of foils presented in the survey, which allowed women to give a fuller picture of their reasons than a more limited number of choices might allow.

For example, the Pregnancy Risk Assessment Monitoring System (PRAMS) survey offers just 6 foils, and they do not include the common thought/preparation and relationship issues. Broad surveys like PRAMS are necessarily concise about single issues. Free-text responses to the PRAMS survey show that respondents endorse reasons not reflected in the few foils.⁴

Moreover, we used the exact phrasing given by focus group participants whenever possible, which could increase selection of appropriate foils. This is why we included reasons such as wanting to “go with the flow.” We also included reasons that were cited by the focus groups, but which have rarely been included in surveys, such as condoms creating discomfort for women.

Implications of our findings. Slightly more than half of the women in the study were having unprotected intercourse and were at risk for unintended pregnancy. Although “unintendedness” is a concept that may not be widely recognized by individual women,⁷ it is a useful epidemiological construct that serves as a marker for adverse outcomes, such as low birth weight or premature labor.¹² In our study, women at risk for unintended pregnancy had a variety of medical conditions and health behaviors that could affect a pregnancy. Moreover, slightly more than one-third of participants thought they were unlikely to get pregnant despite having unprotected intercourse. This argues for improved preconceptional care in this population.¹³ Education may improve understanding of fertility, contraceptive options, risk reduction strategies, and communication techniques.

Limitations. The study is subject to several limitations. All responses were self-reported and subject to recall bias. The population was a convenience sample of financially disadvantaged women visiting outpatient clinics, and is not representative of other populations. Women attending a clinic might reasonably be expected to have access to health care and contraception, which might not be true of other populations. Thus, few women in our study cited cost or access to care as a reason for having unprotected intercourse.

Funding

This study was funded in part by the Michigan Department of Community Health.

Correspondence
Mary D. Nettleman, MD, MS, B 427 Clinical Center, East Lansing, MI 48824; [email protected]

The first metrics from SHM's Project BOOST mentorship program won't be ready until later this year, but the recent addition of more intervention sites comes as pilot institutions are reporting success in changing the discharge culture.

SHM recently announced 24 new sites for Project BOOST (Better Outcomes for Older Adults through Safe Transitions), bringing the number of participating institutions to 30. Each site features SHM mentors working with hospitalists to improve transitional care via a discharge planning toolkit.

Emmanuel King, MD, director of the Nurse Practitioner Hospitalist Service at the Hospital of the University of Pennsylvania in Philadelphia, says a major shift is implementing the "7P Risk Scale," a transitional-care checklist. Dr. King says some of his staff initially balked at depression screening and questions about health literacy, but when the tools were introduced and the checklist items were embraced, hospitalists felt "included in and comfortable with the process."

"Tweaking it to meet the needs of the team was a great idea," says Dr. King, assistant professor of clinical at UPenn's School of Medicine. "We've been able to get the team to buy in."

Tina Budnitz, MPH, SHM senior advisor for quality initiatives, says some early responses to Project BOOST have been better than expected, especially in the area of follow-up tasks.

"I was expecting people to say they were incredibly time-intensive," Budnitz says. "Some of the hospitalists got back to us and said, 'We think it's a good idea to call every patient, regardless of their risk status.' "

The first metrics from SHM's Project BOOST mentorship program won't be ready until later this year, but the recent addition of more intervention sites comes as pilot institutions are reporting success in changing the discharge culture.

SHM recently announced 24 new sites for Project BOOST (Better Outcomes for Older Adults through Safe Transitions), bringing the number of participating institutions to 30. Each site features SHM mentors working with hospitalists to improve transitional care via a discharge planning toolkit.

Emmanuel King, MD, director of the Nurse Practitioner Hospitalist Service at the Hospital of the University of Pennsylvania in Philadelphia, says a major shift is implementing the "7P Risk Scale," a transitional-care checklist. Dr. King says some of his staff initially balked at depression screening and questions about health literacy, but when the tools were introduced and the checklist items were embraced, hospitalists felt "included in and comfortable with the process."

"Tweaking it to meet the needs of the team was a great idea," says Dr. King, assistant professor of clinical at UPenn's School of Medicine. "We've been able to get the team to buy in."

Tina Budnitz, MPH, SHM senior advisor for quality initiatives, says some early responses to Project BOOST have been better than expected, especially in the area of follow-up tasks.

"I was expecting people to say they were incredibly time-intensive," Budnitz says. "Some of the hospitalists got back to us and said, 'We think it's a good idea to call every patient, regardless of their risk status.' "

The first metrics from SHM's Project BOOST mentorship program won't be ready until later this year, but the recent addition of more intervention sites comes as pilot institutions are reporting success in changing the discharge culture.

SHM recently announced 24 new sites for Project BOOST (Better Outcomes for Older Adults through Safe Transitions), bringing the number of participating institutions to 30. Each site features SHM mentors working with hospitalists to improve transitional care via a discharge planning toolkit.

Emmanuel King, MD, director of the Nurse Practitioner Hospitalist Service at the Hospital of the University of Pennsylvania in Philadelphia, says a major shift is implementing the "7P Risk Scale," a transitional-care checklist. Dr. King says some of his staff initially balked at depression screening and questions about health literacy, but when the tools were introduced and the checklist items were embraced, hospitalists felt "included in and comfortable with the process."

"Tweaking it to meet the needs of the team was a great idea," says Dr. King, assistant professor of clinical at UPenn's School of Medicine. "We've been able to get the team to buy in."

Tina Budnitz, MPH, SHM senior advisor for quality initiatives, says some early responses to Project BOOST have been better than expected, especially in the area of follow-up tasks.

"I was expecting people to say they were incredibly time-intensive," Budnitz says. "Some of the hospitalists got back to us and said, 'We think it's a good idea to call every patient, regardless of their risk status.' "

Hospitalists are not just general internists anymore, having successfully branched out into such subspecialties as cardiology, pulmonology, and gastroenterology, according to a March 12 study in the New England Journal of Medicine (2009;360:1102-12).

In the first quantitative national review to study hospitalists based on Medicare payment data, a team of researchers at the University of Texas Medical Branch at Galveston calculated that the percentage of internal medicine physicians practicing as hospitalists jumped to 19% in 2006 from 5.9% in 1995.

Perhaps more interesting is the number of cardiologists, pulmonologists, gastroenterologists, family physicians, and general practitioners who work as hospitalists totaled roughly 20% in 2006. The study defined hospitalists as those who generated more than 90% of their E/M claims from hospitalized patients.

HM appears to have even more room to grow, as more physicians move toward the HM model and away from primary care, according to an editorial accompanying the NEJM study. The editorial debated the value-adds and the complications caused by the presence of hospitalists in all phases of the care continuum. The authors also acknowledged the model is widely accepted as beneficial.

"The economic and practical forces that promoted the growth in the care of patients by hospitalists are intensifying, not lessening, and hospitalists are here to stay," according to the editorial, written by a trio of NEJM editors, including editor-in-chief Jeffrey M. Drazen, MD. "It is time to focus on how to enhance the value."

Hospitalists are not just general internists anymore, having successfully branched out into such subspecialties as cardiology, pulmonology, and gastroenterology, according to a March 12 study in the New England Journal of Medicine (2009;360:1102-12).

In the first quantitative national review to study hospitalists based on Medicare payment data, a team of researchers at the University of Texas Medical Branch at Galveston calculated that the percentage of internal medicine physicians practicing as hospitalists jumped to 19% in 2006 from 5.9% in 1995.

Perhaps more interesting is the number of cardiologists, pulmonologists, gastroenterologists, family physicians, and general practitioners who work as hospitalists totaled roughly 20% in 2006. The study defined hospitalists as those who generated more than 90% of their E/M claims from hospitalized patients.

HM appears to have even more room to grow, as more physicians move toward the HM model and away from primary care, according to an editorial accompanying the NEJM study. The editorial debated the value-adds and the complications caused by the presence of hospitalists in all phases of the care continuum. The authors also acknowledged the model is widely accepted as beneficial.

"The economic and practical forces that promoted the growth in the care of patients by hospitalists are intensifying, not lessening, and hospitalists are here to stay," according to the editorial, written by a trio of NEJM editors, including editor-in-chief Jeffrey M. Drazen, MD. "It is time to focus on how to enhance the value."

Hospitalists are not just general internists anymore, having successfully branched out into such subspecialties as cardiology, pulmonology, and gastroenterology, according to a March 12 study in the New England Journal of Medicine (2009;360:1102-12).

In the first quantitative national review to study hospitalists based on Medicare payment data, a team of researchers at the University of Texas Medical Branch at Galveston calculated that the percentage of internal medicine physicians practicing as hospitalists jumped to 19% in 2006 from 5.9% in 1995.

Perhaps more interesting is the number of cardiologists, pulmonologists, gastroenterologists, family physicians, and general practitioners who work as hospitalists totaled roughly 20% in 2006. The study defined hospitalists as those who generated more than 90% of their E/M claims from hospitalized patients.

HM appears to have even more room to grow, as more physicians move toward the HM model and away from primary care, according to an editorial accompanying the NEJM study. The editorial debated the value-adds and the complications caused by the presence of hospitalists in all phases of the care continuum. The authors also acknowledged the model is widely accepted as beneficial.

"The economic and practical forces that promoted the growth in the care of patients by hospitalists are intensifying, not lessening, and hospitalists are here to stay," according to the editorial, written by a trio of NEJM editors, including editor-in-chief Jeffrey M. Drazen, MD. "It is time to focus on how to enhance the value."