In our clinical practices, we have repeatedly cared for patients who came into our clinics because of a worrisome irregular breathing pattern characterized by a deep inspiration, and followed by a noisy expiration. We have referred to the set of clinical signs that these patients present with as “sigh syndrome.”

We have long suspected that sigh syndrome is an underdiagnosed and self-limited condition that is often mistaken for a serious respiratory disorder. In our experience, this syndrome runs a benign course. However, we believed that this syndrome had characteristic and consistent features, and should not be considered a diagnosis of exclusion.

Thus, we undertook a study to observe a group of subjects with these features to judge whether this subjectively alarming symptom complex is in fact harmless, and whether it is appropriate to respond to it as we had, by taking a stress-alleviating approach alone.

What is sigh syndrome?

Patients with sigh syndrome exhibit a compulsion to perform single but repeated deep inspirations, accompanied by a sensation of difficulty in inhaling a sufficient quantity of air. Each inspiration is followed by a prolonged, sometimes noisy expiration—namely, a sigh. Observing such abnormal breaths and confirming that the patient feels a concomitant inability to fill his lungs to capacity is sufficient to make the diagnosis.

This breathing compulsion is irregular in nature: It may occur once a minute or several times a minute, and this breathing pattern may continue—on and off throughout the day—for a few days to several weeks. In our experience, it provokes significant anxiety in patients, prompting them to seek medical advice. It does not occur when the patient is asleep, and it is not triggered by physical activity.

Both patient and doctor may, at first, be convinced that the problem reflects a serious illness. The 10 features of sigh syndrome (TABLE 1) constitute a proposed definition. All of our study subjects exhibited these 10 features.

TABLE 1
10 features of sigh syndrome

Sighing as an illness marker

Sighing has been described as one member of a group of signs exhibited by depressed or anxiety-ridden patients.¹ While Perin et al² were the first to point out the importance of distinguishing between sighing and respiratory disease, sighing per se has never been identified as a discrete illness marker.

A number of psychiatric disorders are already well known to incorporate breathing and chest symptoms along with widespread somatization. These include globus hystericus, neurocirculatory asthenia, and Tietze syndrome.^3-6 As such, the acute pain of precordial catch syndrome stands out as an example of a distinguishable, clear-cut clinical state devoid of any apparent organic basis.^7,8

Methods

How we recruited the patients

Data was collected from 3 family practice clinics in Israel from February 2002 to February 2005. We requested that these practices contribute data of consecutive clinical cases presenting with the 10 set symptoms of sigh syndrome (TABLE 1).

Data collected included basic demographics, the circumstances of the onset of symptoms, concurrent medical conditions, and any associated symptoms. We assessed the patients’ education level by asking questions pertaining to their years of schooling and college degrees. Patients rated their own economic status as being below, average, or above-average income.

The main outcome we examined was the clinical course of the sighing episodes during the ensuing months after their visit, in order to determine whether any patients developed a form of significant organic disease or a disorder that led to hospitalization.

Results

40 cases that cut across the socioeconomic spectrum

Forty patients were recruited for this study. Nineteen (47.5%) were male; their ages ranged from 7 to 53 (mean, 31.8; standard deviation, 13.7). Two patients (5%) were Ashkenazi Jews; 34 (85%) were of North African ethnicity (Sephardic Jews); the other 4 were of varied Asian and European ethnicity. The number of patients with North African ethnicity overrepresents that of the population in their communities. Additionally, 3 members of this group were from the same family.

There was no predilection toward any specific education level or socioeconomic status. The occupations of the subjects were diverse.

Their clinical characteristics

The clinical characteristics of the 40 patients are presented in TABLE 2. The subjects’ sighing began at various times of the day, without relationship to eating or any other activity, and disappeared during sleep. All patients reported the same feeling: that of an extra effort demanded to perform full inspiration. In many cases, adult patients were certain their complaints were a sign of cardiac or respiratory disease, and they were very concerned that there was some grave, underlying disorder.

History and examination failed to reveal evidence of any somatic findings related to breathing difficulty. Breathing rate was within normal limits in all cases.

The physicians’ initial encounters with these patients led to further examination in many cases: electrocardiography, blood oxygen saturation, and complete blood counts. However, no abnormalities were found on any of these tests. Medications, if prescribed at all during these consultations, were usually given to alleviate insomnia or anxiety. Further ancillary investigations or referrals were not ordered.

The sole notable finding on physical examination was a typical murmur (which had already been diagnosed) in a young girl with a congenital atrial septal defect. This 7-year-old developed repeated episodes of sigh syndrome just before her annual visit to the pediatric cardiologist; her mother believed that the child was frightened by the thought of possible future surgery.

TABLE 2
Clinical characteristics of the 40 patients studied—One third experienced a traumatic event

Traumatic events, anxiety disorders suggest stress as a cause

Thirteen patient histories disclosed a definite, recent, significant traumatic event that may have triggered the onset of sigh syndrome. Examples of 2 triggering events are the terrorist murder of several members of a neighbor’s family, and a near-miss with a mortar shell. One subject—a teenager—had recently been left alone in the dark with 2 younger siblings during a power blackout; another young woman said that the sighing episodes began when she decided to get married.

Ten patients had previously diagnosed neurotic disorders, mainly generalized anxiety; these included 2 cases of somatization disorder and 1 case of posttraumatic stress disorder. This information from the patients’ histories was documented in their medical files.

Episodes appear to be self-limited

In all patients, the episodes were self-limited. During the follow-up period, lasting an average of 18 months, none of the patients showed additional medical conditions—respiratory or otherwise—that could be linked to episodes of sigh syndrome. Recurrences of sighing episodes were reported by 24 subjects (60%) after the marker episode. One patient was diagnosed with carcinoma of the pancreas 2 years into follow-up, and later died.

Discussion

A benign, transient disorder

Aside from the solitary and unrelated death noted above, examination and follow-up in all 40 cases did not lead to an alternative diagnosis. Sigh syndrome thus seems to be an entirely benign and transient condition with no sequelae aside from possible recurrences.

Although the pathophysiology is unclear, our finding that 32.5% of patients had a recent traumatic incident strongly suggests a stress-related condition. Furthermore, 25% of the patients were already known to suffer from intermittent anxiety or somatoform disorders, although none were taking medications for these conditions. This adds support to the assumption that a mind-body interaction is underpinning the disorder. Large-scale migration, recent war or terrorist acts, or natural disaster are likely to increase the chances that the average physician will see a patient with sigh syndrome.

A tendency towards North African/Sephardic ethnicity, rather than European ethnicity—in addition to the cluster of 3 cases belonging to the same family—suggests the presentation may be a subconscious cultural, learned, or adopted expression of uneasiness.

Making your evaluation: History and physical are enough

The diagnostic evaluation of sigh syndrome—consisting of careful history-taking and a thorough physical examination—should be sufficient to differentiate it from an array of organic diseases. A physical examination is imperative to exclude other causes for this breathing abnormality.

Ancillary testing is rarely, if ever, indicated. It can perhaps be justified only if the condition is accompanied by an additional (if serendipitous) finding such as the cardiac murmur in the 7-year-old girl noted earlier. Physicians sometimes perform unnecessary investigations, being reluctant to base their diagnoses solely on their clinical expertise.⁹ A patient may interpret this testing as uncertainty or begin to doubt the diagnosis, thus augmenting—rather than reducing—any anxiety.¹⁰ The additional burden of the costs and possible side effects compound the futility of testing indiscriminately.¹¹

Identifying these symptoms with the name “sigh syndrome,” and basing this diagnosis on the history and physical examination, stresses certainty and familiarity with the diagnosis.⁹ Not only does this reassure the patient, but it eases communication between professionals and forms a basis for research.

Management: Reassure your patient

Management of sigh syndrome consists largely of providing reassurances to your patient. You should emphasize that the condition is real, albeit benign, and that you understand the concern it causes.

Further treatment is unnecessary, aside perhaps from addressing any associated anxiety. A self-limiting (if sometimes recurrent) course can be confidently predicted, and follow-up visits can safely be left to the patient’s own discretion. Since the major correlation with sigh syndrome seems to be stress and the experience of a recent traumatic event, you should always investigate these 2 possibilities when taking the history of a patient with suspected sigh syndrome.

Acknowledgments

This work was inspired and developed by arthur Furst, MD, who died following the submission of this manuscript. Dr Furst was a distinguished and dedicated family physician, a thorough researcher, and a renowned tutor. We dedicate this article to the fond memory of a true leader in the field of rural medicine, and an exceptionally funny and amicable colleague.

Correspondence
Abby Naimer Sody, MD, Gush Katif Health Center, Neve Dekalim, Goosh Katif, Israel 79779; sodyna@clalit.org.il

In our clinical practices, we have repeatedly cared for patients who came into our clinics because of a worrisome irregular breathing pattern characterized by a deep inspiration, and followed by a noisy expiration. We have referred to the set of clinical signs that these patients present with as “sigh syndrome.”

We have long suspected that sigh syndrome is an underdiagnosed and self-limited condition that is often mistaken for a serious respiratory disorder. In our experience, this syndrome runs a benign course. However, we believed that this syndrome had characteristic and consistent features, and should not be considered a diagnosis of exclusion.

Thus, we undertook a study to observe a group of subjects with these features to judge whether this subjectively alarming symptom complex is in fact harmless, and whether it is appropriate to respond to it as we had, by taking a stress-alleviating approach alone.

What is sigh syndrome?

Patients with sigh syndrome exhibit a compulsion to perform single but repeated deep inspirations, accompanied by a sensation of difficulty in inhaling a sufficient quantity of air. Each inspiration is followed by a prolonged, sometimes noisy expiration—namely, a sigh. Observing such abnormal breaths and confirming that the patient feels a concomitant inability to fill his lungs to capacity is sufficient to make the diagnosis.

This breathing compulsion is irregular in nature: It may occur once a minute or several times a minute, and this breathing pattern may continue—on and off throughout the day—for a few days to several weeks. In our experience, it provokes significant anxiety in patients, prompting them to seek medical advice. It does not occur when the patient is asleep, and it is not triggered by physical activity.

Both patient and doctor may, at first, be convinced that the problem reflects a serious illness. The 10 features of sigh syndrome (TABLE 1) constitute a proposed definition. All of our study subjects exhibited these 10 features.

TABLE 1
10 features of sigh syndrome

Sighing as an illness marker

Sighing has been described as one member of a group of signs exhibited by depressed or anxiety-ridden patients.¹ While Perin et al² were the first to point out the importance of distinguishing between sighing and respiratory disease, sighing per se has never been identified as a discrete illness marker.

A number of psychiatric disorders are already well known to incorporate breathing and chest symptoms along with widespread somatization. These include globus hystericus, neurocirculatory asthenia, and Tietze syndrome.^3-6 As such, the acute pain of precordial catch syndrome stands out as an example of a distinguishable, clear-cut clinical state devoid of any apparent organic basis.^7,8

Methods

How we recruited the patients

Data was collected from 3 family practice clinics in Israel from February 2002 to February 2005. We requested that these practices contribute data of consecutive clinical cases presenting with the 10 set symptoms of sigh syndrome (TABLE 1).

Data collected included basic demographics, the circumstances of the onset of symptoms, concurrent medical conditions, and any associated symptoms. We assessed the patients’ education level by asking questions pertaining to their years of schooling and college degrees. Patients rated their own economic status as being below, average, or above-average income.

The main outcome we examined was the clinical course of the sighing episodes during the ensuing months after their visit, in order to determine whether any patients developed a form of significant organic disease or a disorder that led to hospitalization.

Results

40 cases that cut across the socioeconomic spectrum

Forty patients were recruited for this study. Nineteen (47.5%) were male; their ages ranged from 7 to 53 (mean, 31.8; standard deviation, 13.7). Two patients (5%) were Ashkenazi Jews; 34 (85%) were of North African ethnicity (Sephardic Jews); the other 4 were of varied Asian and European ethnicity. The number of patients with North African ethnicity overrepresents that of the population in their communities. Additionally, 3 members of this group were from the same family.

There was no predilection toward any specific education level or socioeconomic status. The occupations of the subjects were diverse.

Their clinical characteristics

The clinical characteristics of the 40 patients are presented in TABLE 2. The subjects’ sighing began at various times of the day, without relationship to eating or any other activity, and disappeared during sleep. All patients reported the same feeling: that of an extra effort demanded to perform full inspiration. In many cases, adult patients were certain their complaints were a sign of cardiac or respiratory disease, and they were very concerned that there was some grave, underlying disorder.

History and examination failed to reveal evidence of any somatic findings related to breathing difficulty. Breathing rate was within normal limits in all cases.

The physicians’ initial encounters with these patients led to further examination in many cases: electrocardiography, blood oxygen saturation, and complete blood counts. However, no abnormalities were found on any of these tests. Medications, if prescribed at all during these consultations, were usually given to alleviate insomnia or anxiety. Further ancillary investigations or referrals were not ordered.

The sole notable finding on physical examination was a typical murmur (which had already been diagnosed) in a young girl with a congenital atrial septal defect. This 7-year-old developed repeated episodes of sigh syndrome just before her annual visit to the pediatric cardiologist; her mother believed that the child was frightened by the thought of possible future surgery.

TABLE 2
Clinical characteristics of the 40 patients studied—One third experienced a traumatic event

Traumatic events, anxiety disorders suggest stress as a cause

Thirteen patient histories disclosed a definite, recent, significant traumatic event that may have triggered the onset of sigh syndrome. Examples of 2 triggering events are the terrorist murder of several members of a neighbor’s family, and a near-miss with a mortar shell. One subject—a teenager—had recently been left alone in the dark with 2 younger siblings during a power blackout; another young woman said that the sighing episodes began when she decided to get married.

Ten patients had previously diagnosed neurotic disorders, mainly generalized anxiety; these included 2 cases of somatization disorder and 1 case of posttraumatic stress disorder. This information from the patients’ histories was documented in their medical files.

Episodes appear to be self-limited

In all patients, the episodes were self-limited. During the follow-up period, lasting an average of 18 months, none of the patients showed additional medical conditions—respiratory or otherwise—that could be linked to episodes of sigh syndrome. Recurrences of sighing episodes were reported by 24 subjects (60%) after the marker episode. One patient was diagnosed with carcinoma of the pancreas 2 years into follow-up, and later died.

Discussion

A benign, transient disorder

Aside from the solitary and unrelated death noted above, examination and follow-up in all 40 cases did not lead to an alternative diagnosis. Sigh syndrome thus seems to be an entirely benign and transient condition with no sequelae aside from possible recurrences.

Although the pathophysiology is unclear, our finding that 32.5% of patients had a recent traumatic incident strongly suggests a stress-related condition. Furthermore, 25% of the patients were already known to suffer from intermittent anxiety or somatoform disorders, although none were taking medications for these conditions. This adds support to the assumption that a mind-body interaction is underpinning the disorder. Large-scale migration, recent war or terrorist acts, or natural disaster are likely to increase the chances that the average physician will see a patient with sigh syndrome.

A tendency towards North African/Sephardic ethnicity, rather than European ethnicity—in addition to the cluster of 3 cases belonging to the same family—suggests the presentation may be a subconscious cultural, learned, or adopted expression of uneasiness.

Making your evaluation: History and physical are enough

The diagnostic evaluation of sigh syndrome—consisting of careful history-taking and a thorough physical examination—should be sufficient to differentiate it from an array of organic diseases. A physical examination is imperative to exclude other causes for this breathing abnormality.

Ancillary testing is rarely, if ever, indicated. It can perhaps be justified only if the condition is accompanied by an additional (if serendipitous) finding such as the cardiac murmur in the 7-year-old girl noted earlier. Physicians sometimes perform unnecessary investigations, being reluctant to base their diagnoses solely on their clinical expertise.⁹ A patient may interpret this testing as uncertainty or begin to doubt the diagnosis, thus augmenting—rather than reducing—any anxiety.¹⁰ The additional burden of the costs and possible side effects compound the futility of testing indiscriminately.¹¹

Identifying these symptoms with the name “sigh syndrome,” and basing this diagnosis on the history and physical examination, stresses certainty and familiarity with the diagnosis.⁹ Not only does this reassure the patient, but it eases communication between professionals and forms a basis for research.

Management: Reassure your patient

Management of sigh syndrome consists largely of providing reassurances to your patient. You should emphasize that the condition is real, albeit benign, and that you understand the concern it causes.

Further treatment is unnecessary, aside perhaps from addressing any associated anxiety. A self-limiting (if sometimes recurrent) course can be confidently predicted, and follow-up visits can safely be left to the patient’s own discretion. Since the major correlation with sigh syndrome seems to be stress and the experience of a recent traumatic event, you should always investigate these 2 possibilities when taking the history of a patient with suspected sigh syndrome.

Acknowledgments

This work was inspired and developed by arthur Furst, MD, who died following the submission of this manuscript. Dr Furst was a distinguished and dedicated family physician, a thorough researcher, and a renowned tutor. We dedicate this article to the fond memory of a true leader in the field of rural medicine, and an exceptionally funny and amicable colleague.

Correspondence
Abby Naimer Sody, MD, Gush Katif Health Center, Neve Dekalim, Goosh Katif, Israel 79779; sodyna@clalit.org.il

In our clinical practices, we have repeatedly cared for patients who came into our clinics because of a worrisome irregular breathing pattern characterized by a deep inspiration, and followed by a noisy expiration. We have referred to the set of clinical signs that these patients present with as “sigh syndrome.”

We have long suspected that sigh syndrome is an underdiagnosed and self-limited condition that is often mistaken for a serious respiratory disorder. In our experience, this syndrome runs a benign course. However, we believed that this syndrome had characteristic and consistent features, and should not be considered a diagnosis of exclusion.

Thus, we undertook a study to observe a group of subjects with these features to judge whether this subjectively alarming symptom complex is in fact harmless, and whether it is appropriate to respond to it as we had, by taking a stress-alleviating approach alone.

What is sigh syndrome?

Patients with sigh syndrome exhibit a compulsion to perform single but repeated deep inspirations, accompanied by a sensation of difficulty in inhaling a sufficient quantity of air. Each inspiration is followed by a prolonged, sometimes noisy expiration—namely, a sigh. Observing such abnormal breaths and confirming that the patient feels a concomitant inability to fill his lungs to capacity is sufficient to make the diagnosis.

This breathing compulsion is irregular in nature: It may occur once a minute or several times a minute, and this breathing pattern may continue—on and off throughout the day—for a few days to several weeks. In our experience, it provokes significant anxiety in patients, prompting them to seek medical advice. It does not occur when the patient is asleep, and it is not triggered by physical activity.

Both patient and doctor may, at first, be convinced that the problem reflects a serious illness. The 10 features of sigh syndrome (TABLE 1) constitute a proposed definition. All of our study subjects exhibited these 10 features.

TABLE 1
10 features of sigh syndrome

Sighing as an illness marker

Sighing has been described as one member of a group of signs exhibited by depressed or anxiety-ridden patients.¹ While Perin et al² were the first to point out the importance of distinguishing between sighing and respiratory disease, sighing per se has never been identified as a discrete illness marker.

A number of psychiatric disorders are already well known to incorporate breathing and chest symptoms along with widespread somatization. These include globus hystericus, neurocirculatory asthenia, and Tietze syndrome.^3-6 As such, the acute pain of precordial catch syndrome stands out as an example of a distinguishable, clear-cut clinical state devoid of any apparent organic basis.^7,8

Methods

How we recruited the patients

Data was collected from 3 family practice clinics in Israel from February 2002 to February 2005. We requested that these practices contribute data of consecutive clinical cases presenting with the 10 set symptoms of sigh syndrome (TABLE 1).

Data collected included basic demographics, the circumstances of the onset of symptoms, concurrent medical conditions, and any associated symptoms. We assessed the patients’ education level by asking questions pertaining to their years of schooling and college degrees. Patients rated their own economic status as being below, average, or above-average income.

The main outcome we examined was the clinical course of the sighing episodes during the ensuing months after their visit, in order to determine whether any patients developed a form of significant organic disease or a disorder that led to hospitalization.

Results

40 cases that cut across the socioeconomic spectrum

Forty patients were recruited for this study. Nineteen (47.5%) were male; their ages ranged from 7 to 53 (mean, 31.8; standard deviation, 13.7). Two patients (5%) were Ashkenazi Jews; 34 (85%) were of North African ethnicity (Sephardic Jews); the other 4 were of varied Asian and European ethnicity. The number of patients with North African ethnicity overrepresents that of the population in their communities. Additionally, 3 members of this group were from the same family.

There was no predilection toward any specific education level or socioeconomic status. The occupations of the subjects were diverse.

Their clinical characteristics

The clinical characteristics of the 40 patients are presented in TABLE 2. The subjects’ sighing began at various times of the day, without relationship to eating or any other activity, and disappeared during sleep. All patients reported the same feeling: that of an extra effort demanded to perform full inspiration. In many cases, adult patients were certain their complaints were a sign of cardiac or respiratory disease, and they were very concerned that there was some grave, underlying disorder.

History and examination failed to reveal evidence of any somatic findings related to breathing difficulty. Breathing rate was within normal limits in all cases.

The physicians’ initial encounters with these patients led to further examination in many cases: electrocardiography, blood oxygen saturation, and complete blood counts. However, no abnormalities were found on any of these tests. Medications, if prescribed at all during these consultations, were usually given to alleviate insomnia or anxiety. Further ancillary investigations or referrals were not ordered.

The sole notable finding on physical examination was a typical murmur (which had already been diagnosed) in a young girl with a congenital atrial septal defect. This 7-year-old developed repeated episodes of sigh syndrome just before her annual visit to the pediatric cardiologist; her mother believed that the child was frightened by the thought of possible future surgery.

TABLE 2
Clinical characteristics of the 40 patients studied—One third experienced a traumatic event

Traumatic events, anxiety disorders suggest stress as a cause

Thirteen patient histories disclosed a definite, recent, significant traumatic event that may have triggered the onset of sigh syndrome. Examples of 2 triggering events are the terrorist murder of several members of a neighbor’s family, and a near-miss with a mortar shell. One subject—a teenager—had recently been left alone in the dark with 2 younger siblings during a power blackout; another young woman said that the sighing episodes began when she decided to get married.

Ten patients had previously diagnosed neurotic disorders, mainly generalized anxiety; these included 2 cases of somatization disorder and 1 case of posttraumatic stress disorder. This information from the patients’ histories was documented in their medical files.

Episodes appear to be self-limited

In all patients, the episodes were self-limited. During the follow-up period, lasting an average of 18 months, none of the patients showed additional medical conditions—respiratory or otherwise—that could be linked to episodes of sigh syndrome. Recurrences of sighing episodes were reported by 24 subjects (60%) after the marker episode. One patient was diagnosed with carcinoma of the pancreas 2 years into follow-up, and later died.

Discussion

A benign, transient disorder

Aside from the solitary and unrelated death noted above, examination and follow-up in all 40 cases did not lead to an alternative diagnosis. Sigh syndrome thus seems to be an entirely benign and transient condition with no sequelae aside from possible recurrences.

Although the pathophysiology is unclear, our finding that 32.5% of patients had a recent traumatic incident strongly suggests a stress-related condition. Furthermore, 25% of the patients were already known to suffer from intermittent anxiety or somatoform disorders, although none were taking medications for these conditions. This adds support to the assumption that a mind-body interaction is underpinning the disorder. Large-scale migration, recent war or terrorist acts, or natural disaster are likely to increase the chances that the average physician will see a patient with sigh syndrome.

A tendency towards North African/Sephardic ethnicity, rather than European ethnicity—in addition to the cluster of 3 cases belonging to the same family—suggests the presentation may be a subconscious cultural, learned, or adopted expression of uneasiness.

Making your evaluation: History and physical are enough

The diagnostic evaluation of sigh syndrome—consisting of careful history-taking and a thorough physical examination—should be sufficient to differentiate it from an array of organic diseases. A physical examination is imperative to exclude other causes for this breathing abnormality.

Ancillary testing is rarely, if ever, indicated. It can perhaps be justified only if the condition is accompanied by an additional (if serendipitous) finding such as the cardiac murmur in the 7-year-old girl noted earlier. Physicians sometimes perform unnecessary investigations, being reluctant to base their diagnoses solely on their clinical expertise.⁹ A patient may interpret this testing as uncertainty or begin to doubt the diagnosis, thus augmenting—rather than reducing—any anxiety.¹⁰ The additional burden of the costs and possible side effects compound the futility of testing indiscriminately.¹¹

Identifying these symptoms with the name “sigh syndrome,” and basing this diagnosis on the history and physical examination, stresses certainty and familiarity with the diagnosis.⁹ Not only does this reassure the patient, but it eases communication between professionals and forms a basis for research.

Management: Reassure your patient

Management of sigh syndrome consists largely of providing reassurances to your patient. You should emphasize that the condition is real, albeit benign, and that you understand the concern it causes.

Further treatment is unnecessary, aside perhaps from addressing any associated anxiety. A self-limiting (if sometimes recurrent) course can be confidently predicted, and follow-up visits can safely be left to the patient’s own discretion. Since the major correlation with sigh syndrome seems to be stress and the experience of a recent traumatic event, you should always investigate these 2 possibilities when taking the history of a patient with suspected sigh syndrome.

Acknowledgments

This work was inspired and developed by arthur Furst, MD, who died following the submission of this manuscript. Dr Furst was a distinguished and dedicated family physician, a thorough researcher, and a renowned tutor. We dedicate this article to the fond memory of a true leader in the field of rural medicine, and an exceptionally funny and amicable colleague.

Correspondence
Abby Naimer Sody, MD, Gush Katif Health Center, Neve Dekalim, Goosh Katif, Israel 79779; sodyna@clalit.org.il

Old codes 99371–99373 that were used to report a call you made to a patient, or to consult or coordinate medical management with other health-care professionals, are deleted in 2008. In their place? A series of new codes that cover not only physician–patient contact but nonphysician–patient contact on the telephone.

Additional codes have also been added for non–face-to-face physician– provider contact regarding the care of a patient. Although these new codes may not be reimbursed by many payers, they do allow you to bill the patient for such services in many instances. They’ll also help the practice better track the care given by its providers.

Patient-initiated telephone contact

99441  Telephone evaluation and management service provided by a physician to an established patient, parent, or guardian not originating from a related E/M service provided within the previous 7 days nor leading to an E/M service or procedure within the next 24 hours or soonest available appointment; 5–10 minutes of medical discussion

99442  …11–20 minutes of medical discussion

99443  …21–30 minutes of medical discussion

98966   Telephone assessment and management service provided by a qualified nonphysician health care professional to an established patient, parent, or guardian not originating from a related assessment and management service provided within the previous seven days nor leading to an assessment and management service or procedure within the next 24 hours or soonest available appointment; 5–10 minutes of medical discussion

98967  …11–20 minutes of medical discussion

98968  …21–30 minutes of medical discussion

To use these codes, keep in mind a few rules:

• Contact must be initiated by the patient or the established patient’s guardian
  
• Don’t report the new codes if the patient is then seen for the problem within 24 hours after the call or at the next available urgent appointment. When that happens, the call is considered part of the pre-service work and may be counted as part of the billable E/M service
  
• Don’t report the new codes if the call relates to an E/M service that was reported by the provider within the prior 7 days—whether the provider did or did not request that the call be made
  
• Don’t report the new codes for any follow-up regarding a procedure that was performed while the patient is still in the postop period.
  

Conferring with the medical team

99367   Medical team conference with interdisciplinary team of health care professionals, patient and/or family not present, 30 minutes or more; participation by physician

99368  …participation by nonphysician qualified health care professional

The interactions of an interdisciplinary team are more comprehensive and complex than the conversations that might take place during a regular E/M service. So, the rules for these codes are somewhat different:

• The patient must be an established patient who has a chronic health condition or multiple health conditions that require a team approach to manage
  
• The participants in the conference are familiar with the patient and have seen the patient within 60 days prior to the conference call
  
• Only one provider from the same specialty may report these codes for each conference
  
• The conference must be at least 30 minutes long; the clock starts at the beginning of the review of the patient’s case and ends at the conclusion of that review. Time spent writing reports on the conference can’t be counted.
  

Providing your services online

99444  Online evaluation and management service provided by a physician to an established patient, guardian, or health care provider not originating from a related E/M service provided within the previous 7 days, using the Internet or similar electronic communications network

98969  Online assessment and management service provided by a qualified nonphysician health care professional to an established patient, guardian, or health care provider not originating from a related assessment and management service provided within the previous 7 days, using the Internet or similar electronic communications network

Just as telephone calls are becoming a more common method of communicating with providers, online medical services are tracing a similar pattern of use. The Internet has allowed many patients to contact their physician (or nonphysician provider) directly; with assurances of privacy offered by current Internet communications systems, information can be readily shared between patient and physician.

Criteria for using these new codes are:

• The established patient or her guardian must have initiated the online evaluation request
  
• The provider’s response must be timely and must include permanent electronic or hard-copy documentation of the encounter
  
• The online service can only be reported once during a 7-day period for the same problem, but more than one provider can report his (her) separate online communication with the patient
  
• As with the rules for telephone contact with a patient, do not report the new codes if the provider has billed an E/M service related to the online query within the prior 7 days or within the postop period of a procedure.
  

Old codes 99371–99373 that were used to report a call you made to a patient, or to consult or coordinate medical management with other health-care professionals, are deleted in 2008. In their place? A series of new codes that cover not only physician–patient contact but nonphysician–patient contact on the telephone.

Additional codes have also been added for non–face-to-face physician– provider contact regarding the care of a patient. Although these new codes may not be reimbursed by many payers, they do allow you to bill the patient for such services in many instances. They’ll also help the practice better track the care given by its providers.

Patient-initiated telephone contact

99441  Telephone evaluation and management service provided by a physician to an established patient, parent, or guardian not originating from a related E/M service provided within the previous 7 days nor leading to an E/M service or procedure within the next 24 hours or soonest available appointment; 5–10 minutes of medical discussion

99442  …11–20 minutes of medical discussion

99443  …21–30 minutes of medical discussion

98966   Telephone assessment and management service provided by a qualified nonphysician health care professional to an established patient, parent, or guardian not originating from a related assessment and management service provided within the previous seven days nor leading to an assessment and management service or procedure within the next 24 hours or soonest available appointment; 5–10 minutes of medical discussion

98967  …11–20 minutes of medical discussion

98968  …21–30 minutes of medical discussion

To use these codes, keep in mind a few rules:

• Contact must be initiated by the patient or the established patient’s guardian
  
• Don’t report the new codes if the patient is then seen for the problem within 24 hours after the call or at the next available urgent appointment. When that happens, the call is considered part of the pre-service work and may be counted as part of the billable E/M service
  
• Don’t report the new codes if the call relates to an E/M service that was reported by the provider within the prior 7 days—whether the provider did or did not request that the call be made
  
• Don’t report the new codes for any follow-up regarding a procedure that was performed while the patient is still in the postop period.
  

Conferring with the medical team

99367   Medical team conference with interdisciplinary team of health care professionals, patient and/or family not present, 30 minutes or more; participation by physician

99368  …participation by nonphysician qualified health care professional

The interactions of an interdisciplinary team are more comprehensive and complex than the conversations that might take place during a regular E/M service. So, the rules for these codes are somewhat different:

• The patient must be an established patient who has a chronic health condition or multiple health conditions that require a team approach to manage
  
• The participants in the conference are familiar with the patient and have seen the patient within 60 days prior to the conference call
  
• Only one provider from the same specialty may report these codes for each conference
  
• The conference must be at least 30 minutes long; the clock starts at the beginning of the review of the patient’s case and ends at the conclusion of that review. Time spent writing reports on the conference can’t be counted.
  

Providing your services online

99444  Online evaluation and management service provided by a physician to an established patient, guardian, or health care provider not originating from a related E/M service provided within the previous 7 days, using the Internet or similar electronic communications network

98969  Online assessment and management service provided by a qualified nonphysician health care professional to an established patient, guardian, or health care provider not originating from a related assessment and management service provided within the previous 7 days, using the Internet or similar electronic communications network

Just as telephone calls are becoming a more common method of communicating with providers, online medical services are tracing a similar pattern of use. The Internet has allowed many patients to contact their physician (or nonphysician provider) directly; with assurances of privacy offered by current Internet communications systems, information can be readily shared between patient and physician.

Criteria for using these new codes are:

• The established patient or her guardian must have initiated the online evaluation request
  
• The provider’s response must be timely and must include permanent electronic or hard-copy documentation of the encounter
  
• The online service can only be reported once during a 7-day period for the same problem, but more than one provider can report his (her) separate online communication with the patient
  
• As with the rules for telephone contact with a patient, do not report the new codes if the provider has billed an E/M service related to the online query within the prior 7 days or within the postop period of a procedure.
  

Old codes 99371–99373 that were used to report a call you made to a patient, or to consult or coordinate medical management with other health-care professionals, are deleted in 2008. In their place? A series of new codes that cover not only physician–patient contact but nonphysician–patient contact on the telephone.

Additional codes have also been added for non–face-to-face physician– provider contact regarding the care of a patient. Although these new codes may not be reimbursed by many payers, they do allow you to bill the patient for such services in many instances. They’ll also help the practice better track the care given by its providers.

Patient-initiated telephone contact

99441  Telephone evaluation and management service provided by a physician to an established patient, parent, or guardian not originating from a related E/M service provided within the previous 7 days nor leading to an E/M service or procedure within the next 24 hours or soonest available appointment; 5–10 minutes of medical discussion

99442  …11–20 minutes of medical discussion

99443  …21–30 minutes of medical discussion

98966   Telephone assessment and management service provided by a qualified nonphysician health care professional to an established patient, parent, or guardian not originating from a related assessment and management service provided within the previous seven days nor leading to an assessment and management service or procedure within the next 24 hours or soonest available appointment; 5–10 minutes of medical discussion

98967  …11–20 minutes of medical discussion

98968  …21–30 minutes of medical discussion

To use these codes, keep in mind a few rules:

• Contact must be initiated by the patient or the established patient’s guardian
  
• Don’t report the new codes if the patient is then seen for the problem within 24 hours after the call or at the next available urgent appointment. When that happens, the call is considered part of the pre-service work and may be counted as part of the billable E/M service
  
• Don’t report the new codes if the call relates to an E/M service that was reported by the provider within the prior 7 days—whether the provider did or did not request that the call be made
  
• Don’t report the new codes for any follow-up regarding a procedure that was performed while the patient is still in the postop period.
  

Conferring with the medical team

99367   Medical team conference with interdisciplinary team of health care professionals, patient and/or family not present, 30 minutes or more; participation by physician

99368  …participation by nonphysician qualified health care professional

The interactions of an interdisciplinary team are more comprehensive and complex than the conversations that might take place during a regular E/M service. So, the rules for these codes are somewhat different:

• The patient must be an established patient who has a chronic health condition or multiple health conditions that require a team approach to manage
  
• The participants in the conference are familiar with the patient and have seen the patient within 60 days prior to the conference call
  
• Only one provider from the same specialty may report these codes for each conference
  
• The conference must be at least 30 minutes long; the clock starts at the beginning of the review of the patient’s case and ends at the conclusion of that review. Time spent writing reports on the conference can’t be counted.
  

Providing your services online

99444  Online evaluation and management service provided by a physician to an established patient, guardian, or health care provider not originating from a related E/M service provided within the previous 7 days, using the Internet or similar electronic communications network

98969  Online assessment and management service provided by a qualified nonphysician health care professional to an established patient, guardian, or health care provider not originating from a related assessment and management service provided within the previous 7 days, using the Internet or similar electronic communications network

Just as telephone calls are becoming a more common method of communicating with providers, online medical services are tracing a similar pattern of use. The Internet has allowed many patients to contact their physician (or nonphysician provider) directly; with assurances of privacy offered by current Internet communications systems, information can be readily shared between patient and physician.

Criteria for using these new codes are:

• The established patient or her guardian must have initiated the online evaluation request
  
• The provider’s response must be timely and must include permanent electronic or hard-copy documentation of the encounter
  
• The online service can only be reported once during a 7-day period for the same problem, but more than one provider can report his (her) separate online communication with the patient
  
• As with the rules for telephone contact with a patient, do not report the new codes if the provider has billed an E/M service related to the online query within the prior 7 days or within the postop period of a procedure.
  

Illustrative case

A 70-year-old man with newly diagnosed hypertension comes to your office. You don’t want to prescribe a diuretic due to his history of gout. He has no history of coronary artery disease or heart failure.

What is the best antihypertensive agent for him?

Background: Guidelines do not reflect new evidence

Guidelines for the use of beta-blockers in the elderly do not reflect current evidence.

JNC recommendations

The 2003 JNC 7 Report recommended the same antihypertensive medications for adults of all ages.³ (JNC 7 is the most recent report from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.)

JNC 7 recommends thiazide diuretics for first-line treatment of hypertension, and recommends other drugs—including beta-blockers, calcium-channel blockers, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs)—for first-line therapy if a thiazide is contraindicated, or in combination with thiazides for higher initial blood pressure.

Compelling indications. Beta-blockers are recommended in the JNC 7 Report as first-line therapy in patients with “compelling indications” such as ischemic heart disease and heart failure.

Clinical context: Seniors taking beta-blockers to their detriment?

Many elderly patients are on beta-blockers, perhaps to their detriment. Treatment choices for hypertension can have an enormous impact on outcomes among older patients:

Two thirds of US adults 60 years of age and older have hypertension, mostly isolated systolic hypertension.^4,5

Multiple studies, including the Systolic Hypertension in the Elderly Program and the Systolic Hypertension in Europe, have shown that lowering blood pressure with pharmacologic interventions in older patients can reduce the risk of cardiovascular events and possibly dementia.⁶

Beta-blockers have been a mainstay of hypertension treatment for many decades and we suspect continue to be widely used as first-line therapy in patients for whom the evidence now indicates they are inferior.

Heart failure and angina are indications for beta-blockers

New evidence does not alter the 2003 JNC 7 recommendations to use beta-blockers as first-line therapy in patients with “compelling indications” such as ischemic heart disease and heart failure.

Study summaries

Two well-done reviews of beta-blocker trials show that they are inferior for first-line hypertension treatment in the elderly who do not have heart failure or angina.

2007 Cochrane review

The 2007 Cochrane review² analyzed randomized trials that compared beta-blockers for hypertension in adults 18 years of age and older to each of the other major classes of antihypertensives.

Conclusion. This meta-analysis showed a “relatively weak effect of beta-blockers to reduce stroke, and the absence of effect on coronary heart disease when compared with placebo or no treatment” and a “trend toward worse outcomes in comparison with calcium channel blockers, renin-angiotensin system inhibitors, and thiazide diuretics.”

This meta-analysis included all adults and did not make any conclusions based on age.

2006 CMAJ meta-analysis

The Kahn and McAlister meta-analysis¹ pooled data from 21 randomized hyper-tension trials (including 6 placebo-controlled trials) that evaluated the efficacy of beta-blockers as first-line therapy for hypertension in preventing major cardiovascular outcomes (death, nonfatal MI, or nonfatal stroke).

The results were analyzed by age group: trials enrolling patients with a mean age of 60 years or older at baseline vs trials enrolling patients with a mean age of under 60 years.

Conclusion. They concluded that in trials comparing other antihypertensive medications with beta-blockers, all agents showed similar efficacy in younger patients, while in older patients, beta-blockers were associated with a higher risk of both composite events and strokes ( TABLE ).

TABLE
Adverse outcomes more likely in seniors taking a beta-blocker vs other antihypertensives¹

What’s new?: The age distinction

These 2 meta-analyses^1,2 help overturn a long-held belief about the value of beta-blockers for the treatment of hypertension. Beta-blockers may not be a good first-line choice for any hypertensive patient—and the evidence clearly shows they are not a good first-line choice for patients over 60 years old.

Two earlier systematic reviews did raise the concern about using beta-blockers as first-line treatment for hypertension (even when thiazides are not contraindicated).

The first systematic review to raise this concern was a 1998 study of 10 hypertension trials in more than 16,000 patients, ages 60 and older. This review showed that diuretics were superior to beta-blockers in reducing cardiovascular and all-cause mortality—which supports the JNC 7 recommendation to choose a thiazide diuretic as the first-line drug of choice.⁷

The second study, a meta-analysis published in 2005, also concluded that beta-blockers should no longer be considered first-line therapy for hypertension, due to a 16% increase in the relative risk of stroke compared with other agents. This meta-analysis, however, did not report outcomes by patient age.⁸

Beta-blockers are not 1st-line, even if thiazides are contraindicated

What is new about the Kahn and McAlister evidence is that beta-blockers should not be the first-line drug of choice even when thiazide diuretics are contraindicated. Their study included a larger number of trials (21 trials vs 13 in the 2005 meta-analysis), which allowed the investigators to examine outcomes in patients younger than 60 and in those 60 years and older.

Caveats: Continue beta-blockers for the right reasons

Patients over 60 with ischemic heart disease or heart failure should still be prescribed beta-blockers for heart failure and angina. Also, in older patients with hypertension who need multiple agents to control their blood pressure, a beta-blocker could be added as a third or fourth agent in addition to a diuretic, ACE inhibitor, ARB, or calcium-channel blocker. Metoprolol is a good choice, as it is inexpensive and proven to reduce mortality in patients with a history of MI or heart failure.

Atenolol may underperform

In a meta-analysis of 31 trials, Freemantle⁹ found that after MI, acebutolol, metoprolol, propranolol, and timolol significantly reduced mortality, while there was no mortality reduction with atenolol. Similarly, in heart failure, only bisoprolol, metoprolol, and carvedilol have evidence to support a reduction in mortality.¹⁰

Although atenolol is one of the most commonly prescribed beta-blockers due to its low cost and once-daily dosing, it may be the least effective. In a systematic review of 9 hypertension studies, Carlberg¹¹ showed that atenolol was no more effective than placebo at reducing MI, cardiovascular mortality, or all-cause mortality, and that patients on atenolol had significantly higher mortality than those taking other antihypertensives. Khan and McAlister do not differentiate between atenolol and other beta-blockers in their meta-analysis.¹

Challenges to implementation: Letting go

The evidence supporting this change in practice has been accumulating over time. The change itself represents a significant reversal of long-standing belief in the value of beta-blockers as an antihypertensive agent. For each individual patient, the risk is not dramatic even though the cumulative “harm” from using a beta-blocker compared to other options is potentially staggering because so many people over 60 have hypertension.

We suspect that the main challenge will be changing the beliefs of both physicians and patients. Once doctors are convinced that beta-blockers are not indicated for uncomplicated hypertension in patients over 60, changing medications in the millions of older patients who have been taking a beta-blocker for some time and have become comfortable with it will take tact and excellent communication skills.

Providing patient information may help. Sources for patients are available free or at low cost at www.nhlbi.nih.gov/health/public/heart/index.htm#hbp. These materials explain that diuretics are inexpensive and are the preferred drugs for initial treatment of hypertension.

PURLs methodology
This study was selected and evaluated using FPIN’s Priority Updates from the Research Literature (PURL) Surveillance System methodology. The criteria and findings leading to the selection of this study as a PURL can be accessed at www.jfponline.com/purls.

Illustrative case

A 70-year-old man with newly diagnosed hypertension comes to your office. You don’t want to prescribe a diuretic due to his history of gout. He has no history of coronary artery disease or heart failure.

What is the best antihypertensive agent for him?

Background: Guidelines do not reflect new evidence

Guidelines for the use of beta-blockers in the elderly do not reflect current evidence.

JNC recommendations

The 2003 JNC 7 Report recommended the same antihypertensive medications for adults of all ages.³ (JNC 7 is the most recent report from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.)

JNC 7 recommends thiazide diuretics for first-line treatment of hypertension, and recommends other drugs—including beta-blockers, calcium-channel blockers, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs)—for first-line therapy if a thiazide is contraindicated, or in combination with thiazides for higher initial blood pressure.

Compelling indications. Beta-blockers are recommended in the JNC 7 Report as first-line therapy in patients with “compelling indications” such as ischemic heart disease and heart failure.

Clinical context: Seniors taking beta-blockers to their detriment?

Many elderly patients are on beta-blockers, perhaps to their detriment. Treatment choices for hypertension can have an enormous impact on outcomes among older patients:

Two thirds of US adults 60 years of age and older have hypertension, mostly isolated systolic hypertension.^4,5

Multiple studies, including the Systolic Hypertension in the Elderly Program and the Systolic Hypertension in Europe, have shown that lowering blood pressure with pharmacologic interventions in older patients can reduce the risk of cardiovascular events and possibly dementia.⁶

Beta-blockers have been a mainstay of hypertension treatment for many decades and we suspect continue to be widely used as first-line therapy in patients for whom the evidence now indicates they are inferior.

Heart failure and angina are indications for beta-blockers

New evidence does not alter the 2003 JNC 7 recommendations to use beta-blockers as first-line therapy in patients with “compelling indications” such as ischemic heart disease and heart failure.

Study summaries

Two well-done reviews of beta-blocker trials show that they are inferior for first-line hypertension treatment in the elderly who do not have heart failure or angina.

2007 Cochrane review

The 2007 Cochrane review² analyzed randomized trials that compared beta-blockers for hypertension in adults 18 years of age and older to each of the other major classes of antihypertensives.

Conclusion. This meta-analysis showed a “relatively weak effect of beta-blockers to reduce stroke, and the absence of effect on coronary heart disease when compared with placebo or no treatment” and a “trend toward worse outcomes in comparison with calcium channel blockers, renin-angiotensin system inhibitors, and thiazide diuretics.”

This meta-analysis included all adults and did not make any conclusions based on age.

2006 CMAJ meta-analysis

The Kahn and McAlister meta-analysis¹ pooled data from 21 randomized hyper-tension trials (including 6 placebo-controlled trials) that evaluated the efficacy of beta-blockers as first-line therapy for hypertension in preventing major cardiovascular outcomes (death, nonfatal MI, or nonfatal stroke).

The results were analyzed by age group: trials enrolling patients with a mean age of 60 years or older at baseline vs trials enrolling patients with a mean age of under 60 years.

Conclusion. They concluded that in trials comparing other antihypertensive medications with beta-blockers, all agents showed similar efficacy in younger patients, while in older patients, beta-blockers were associated with a higher risk of both composite events and strokes ( TABLE ).

TABLE
Adverse outcomes more likely in seniors taking a beta-blocker vs other antihypertensives¹

What’s new?: The age distinction

These 2 meta-analyses^1,2 help overturn a long-held belief about the value of beta-blockers for the treatment of hypertension. Beta-blockers may not be a good first-line choice for any hypertensive patient—and the evidence clearly shows they are not a good first-line choice for patients over 60 years old.

Two earlier systematic reviews did raise the concern about using beta-blockers as first-line treatment for hypertension (even when thiazides are not contraindicated).

The first systematic review to raise this concern was a 1998 study of 10 hypertension trials in more than 16,000 patients, ages 60 and older. This review showed that diuretics were superior to beta-blockers in reducing cardiovascular and all-cause mortality—which supports the JNC 7 recommendation to choose a thiazide diuretic as the first-line drug of choice.⁷

The second study, a meta-analysis published in 2005, also concluded that beta-blockers should no longer be considered first-line therapy for hypertension, due to a 16% increase in the relative risk of stroke compared with other agents. This meta-analysis, however, did not report outcomes by patient age.⁸

Beta-blockers are not 1st-line, even if thiazides are contraindicated

What is new about the Kahn and McAlister evidence is that beta-blockers should not be the first-line drug of choice even when thiazide diuretics are contraindicated. Their study included a larger number of trials (21 trials vs 13 in the 2005 meta-analysis), which allowed the investigators to examine outcomes in patients younger than 60 and in those 60 years and older.

Caveats: Continue beta-blockers for the right reasons

Patients over 60 with ischemic heart disease or heart failure should still be prescribed beta-blockers for heart failure and angina. Also, in older patients with hypertension who need multiple agents to control their blood pressure, a beta-blocker could be added as a third or fourth agent in addition to a diuretic, ACE inhibitor, ARB, or calcium-channel blocker. Metoprolol is a good choice, as it is inexpensive and proven to reduce mortality in patients with a history of MI or heart failure.

Atenolol may underperform

In a meta-analysis of 31 trials, Freemantle⁹ found that after MI, acebutolol, metoprolol, propranolol, and timolol significantly reduced mortality, while there was no mortality reduction with atenolol. Similarly, in heart failure, only bisoprolol, metoprolol, and carvedilol have evidence to support a reduction in mortality.¹⁰

Although atenolol is one of the most commonly prescribed beta-blockers due to its low cost and once-daily dosing, it may be the least effective. In a systematic review of 9 hypertension studies, Carlberg¹¹ showed that atenolol was no more effective than placebo at reducing MI, cardiovascular mortality, or all-cause mortality, and that patients on atenolol had significantly higher mortality than those taking other antihypertensives. Khan and McAlister do not differentiate between atenolol and other beta-blockers in their meta-analysis.¹

Challenges to implementation: Letting go

The evidence supporting this change in practice has been accumulating over time. The change itself represents a significant reversal of long-standing belief in the value of beta-blockers as an antihypertensive agent. For each individual patient, the risk is not dramatic even though the cumulative “harm” from using a beta-blocker compared to other options is potentially staggering because so many people over 60 have hypertension.

We suspect that the main challenge will be changing the beliefs of both physicians and patients. Once doctors are convinced that beta-blockers are not indicated for uncomplicated hypertension in patients over 60, changing medications in the millions of older patients who have been taking a beta-blocker for some time and have become comfortable with it will take tact and excellent communication skills.

Providing patient information may help. Sources for patients are available free or at low cost at www.nhlbi.nih.gov/health/public/heart/index.htm#hbp. These materials explain that diuretics are inexpensive and are the preferred drugs for initial treatment of hypertension.

PURLs methodology
This study was selected and evaluated using FPIN’s Priority Updates from the Research Literature (PURL) Surveillance System methodology. The criteria and findings leading to the selection of this study as a PURL can be accessed at www.jfponline.com/purls.

Illustrative case

A 70-year-old man with newly diagnosed hypertension comes to your office. You don’t want to prescribe a diuretic due to his history of gout. He has no history of coronary artery disease or heart failure.

What is the best antihypertensive agent for him?

Background: Guidelines do not reflect new evidence

Guidelines for the use of beta-blockers in the elderly do not reflect current evidence.

JNC recommendations

The 2003 JNC 7 Report recommended the same antihypertensive medications for adults of all ages.³ (JNC 7 is the most recent report from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.)

JNC 7 recommends thiazide diuretics for first-line treatment of hypertension, and recommends other drugs—including beta-blockers, calcium-channel blockers, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs)—for first-line therapy if a thiazide is contraindicated, or in combination with thiazides for higher initial blood pressure.

Compelling indications. Beta-blockers are recommended in the JNC 7 Report as first-line therapy in patients with “compelling indications” such as ischemic heart disease and heart failure.

Clinical context: Seniors taking beta-blockers to their detriment?

Many elderly patients are on beta-blockers, perhaps to their detriment. Treatment choices for hypertension can have an enormous impact on outcomes among older patients:

Two thirds of US adults 60 years of age and older have hypertension, mostly isolated systolic hypertension.^4,5

Multiple studies, including the Systolic Hypertension in the Elderly Program and the Systolic Hypertension in Europe, have shown that lowering blood pressure with pharmacologic interventions in older patients can reduce the risk of cardiovascular events and possibly dementia.⁶

Beta-blockers have been a mainstay of hypertension treatment for many decades and we suspect continue to be widely used as first-line therapy in patients for whom the evidence now indicates they are inferior.

Heart failure and angina are indications for beta-blockers

New evidence does not alter the 2003 JNC 7 recommendations to use beta-blockers as first-line therapy in patients with “compelling indications” such as ischemic heart disease and heart failure.

Study summaries

Two well-done reviews of beta-blocker trials show that they are inferior for first-line hypertension treatment in the elderly who do not have heart failure or angina.

2007 Cochrane review

The 2007 Cochrane review² analyzed randomized trials that compared beta-blockers for hypertension in adults 18 years of age and older to each of the other major classes of antihypertensives.

Conclusion. This meta-analysis showed a “relatively weak effect of beta-blockers to reduce stroke, and the absence of effect on coronary heart disease when compared with placebo or no treatment” and a “trend toward worse outcomes in comparison with calcium channel blockers, renin-angiotensin system inhibitors, and thiazide diuretics.”

This meta-analysis included all adults and did not make any conclusions based on age.

2006 CMAJ meta-analysis

The Kahn and McAlister meta-analysis¹ pooled data from 21 randomized hyper-tension trials (including 6 placebo-controlled trials) that evaluated the efficacy of beta-blockers as first-line therapy for hypertension in preventing major cardiovascular outcomes (death, nonfatal MI, or nonfatal stroke).

The results were analyzed by age group: trials enrolling patients with a mean age of 60 years or older at baseline vs trials enrolling patients with a mean age of under 60 years.

Conclusion. They concluded that in trials comparing other antihypertensive medications with beta-blockers, all agents showed similar efficacy in younger patients, while in older patients, beta-blockers were associated with a higher risk of both composite events and strokes ( TABLE ).

TABLE
Adverse outcomes more likely in seniors taking a beta-blocker vs other antihypertensives¹

What’s new?: The age distinction

These 2 meta-analyses^1,2 help overturn a long-held belief about the value of beta-blockers for the treatment of hypertension. Beta-blockers may not be a good first-line choice for any hypertensive patient—and the evidence clearly shows they are not a good first-line choice for patients over 60 years old.

Two earlier systematic reviews did raise the concern about using beta-blockers as first-line treatment for hypertension (even when thiazides are not contraindicated).

The first systematic review to raise this concern was a 1998 study of 10 hypertension trials in more than 16,000 patients, ages 60 and older. This review showed that diuretics were superior to beta-blockers in reducing cardiovascular and all-cause mortality—which supports the JNC 7 recommendation to choose a thiazide diuretic as the first-line drug of choice.⁷

The second study, a meta-analysis published in 2005, also concluded that beta-blockers should no longer be considered first-line therapy for hypertension, due to a 16% increase in the relative risk of stroke compared with other agents. This meta-analysis, however, did not report outcomes by patient age.⁸

Beta-blockers are not 1st-line, even if thiazides are contraindicated

What is new about the Kahn and McAlister evidence is that beta-blockers should not be the first-line drug of choice even when thiazide diuretics are contraindicated. Their study included a larger number of trials (21 trials vs 13 in the 2005 meta-analysis), which allowed the investigators to examine outcomes in patients younger than 60 and in those 60 years and older.

Caveats: Continue beta-blockers for the right reasons

Patients over 60 with ischemic heart disease or heart failure should still be prescribed beta-blockers for heart failure and angina. Also, in older patients with hypertension who need multiple agents to control their blood pressure, a beta-blocker could be added as a third or fourth agent in addition to a diuretic, ACE inhibitor, ARB, or calcium-channel blocker. Metoprolol is a good choice, as it is inexpensive and proven to reduce mortality in patients with a history of MI or heart failure.

Atenolol may underperform

In a meta-analysis of 31 trials, Freemantle⁹ found that after MI, acebutolol, metoprolol, propranolol, and timolol significantly reduced mortality, while there was no mortality reduction with atenolol. Similarly, in heart failure, only bisoprolol, metoprolol, and carvedilol have evidence to support a reduction in mortality.¹⁰

Although atenolol is one of the most commonly prescribed beta-blockers due to its low cost and once-daily dosing, it may be the least effective. In a systematic review of 9 hypertension studies, Carlberg¹¹ showed that atenolol was no more effective than placebo at reducing MI, cardiovascular mortality, or all-cause mortality, and that patients on atenolol had significantly higher mortality than those taking other antihypertensives. Khan and McAlister do not differentiate between atenolol and other beta-blockers in their meta-analysis.¹

Challenges to implementation: Letting go

The evidence supporting this change in practice has been accumulating over time. The change itself represents a significant reversal of long-standing belief in the value of beta-blockers as an antihypertensive agent. For each individual patient, the risk is not dramatic even though the cumulative “harm” from using a beta-blocker compared to other options is potentially staggering because so many people over 60 have hypertension.

We suspect that the main challenge will be changing the beliefs of both physicians and patients. Once doctors are convinced that beta-blockers are not indicated for uncomplicated hypertension in patients over 60, changing medications in the millions of older patients who have been taking a beta-blocker for some time and have become comfortable with it will take tact and excellent communication skills.

Providing patient information may help. Sources for patients are available free or at low cost at www.nhlbi.nih.gov/health/public/heart/index.htm#hbp. These materials explain that diuretics are inexpensive and are the preferred drugs for initial treatment of hypertension.

PURLs methodology
This study was selected and evaluated using FPIN’s Priority Updates from the Research Literature (PURL) Surveillance System methodology. The criteria and findings leading to the selection of this study as a PURL can be accessed at www.jfponline.com/purls.

In studies of older patients, the prevalence of subjective memory complaints in community-based populations varies from 11% to 56%,^1,2 depending on sample selection and on how the complaints are assessed.¹ Subjective memory complaints may be associated with psychiatric symptoms—in particular, depression^3,4 and anxiety—as well as older age, lower education, and female gender.¹ In these studies, some association has been found between memory complaints and cognitive impairment on testing, even after adjustment for depressive symptoms.^4,5

Researchers have suggested that subjective memory complaints may be an early indicator for dementia,¹ and could therefore be considered as a marker for identification of dementia in general practice. However, these complaints may be the result of a wide range of conditions; longitudinal studies assessing the value of memory complaints in predicting dementia or cognitive decline have shown varying results.^6-8

The prevalence of subjective memory complaints among elderly patients consulting their GP is not known, and the clinical implication of these complaints is not well established. We conducted this study in order to investigate the prevalence and potential clinical implications of subjective memory complaints among elderly patients in general practice.

Methods

Recruiting the subjects

Seventeen general medical practices with 24 GPs located in the central district of Copenhagen, Denmark, participated in this study. These practices served a total of 40,865 patients, 2934 of whom were 65 years of age or older.

We asked all patients 65 years of age or older who consulted their GP in October and November 2002 to participate in the study, regardless of the reason for the encounter. We excluded patients who were not able to read Danish or not able to sign an informed consent form. We also excluded those with severe acute or terminal illness or a diagnosis of dementia.

Assessment of the patients

Participant questionnaire. Before the visit with their GP, we asked all qualifying patients to complete a questionnaire with items about self-reported health and memory status, as well as demographic questions. The item regarding memory status was phrased: “How would you evaluate your memory?” The categories were “excellent,” “good,” “less good,” “poor,” and “miserable.” Patients rating their memory as “less good,” “poor,” or “miserable” were classified as patients with subjective memory complaints, whereas patients rating their memory as “excellent” or “good” were defined as patients without subjective memory complaints.

Quality-of-life assessment. During their visit, the patients also completed the Danish Validated Version of EuroQoL-5D, which includes a visual analogue scale (VAS). EuroQoL-5D is a standardized instrument for use as a measure of health outcomes.⁹ Patients are asked to assess their health—in regards to mobility, self-care, everyday activities, pain, and anxiety—by checking 1 of 3 boxes. They are then asked to assess their general state of health on a VAS ranging from 0 to 100.

GP questionnaire. A questionnaire dealing with the GP’s clinical impression of dementia was developed together with 2 of the GPs and tested in a pilot survey. This questionnaire was completed by the GP for each patient before they administered the Mini Mental State Examination (MMSE), with no information from the completed participant questionnaire. The GPs could complete the questionnaire before or during the office visit.

MMSE. The MMSE, recommended in GP guidelines as a cognitive screening test, was given to the patients after the GPs completed their own questionnaires.¹⁰ The test is a 30-point questionnaire that assesses cognition; it includes simple questions and problems in a number of areas: time and place of the test, repeating lists of words, math problems, language use and comprehension, and copying a drawing. An MMSE score <24 has been widely used as an indication of the presence of cognitive impairment in population-based studies.

Registry data and ethics

The Danish National Health Register provided the information regarding the physicians and their practices.¹¹ The municipality of Copenhagen provided information regarding the nursing home status of patients.

The Scientific Ethical Committee for Copenhagen and Frederiksberg Municipalities evaluated the project. The Danish Data Protection Agency and the Danish College of General Practitioners Study Committee approved the project.

How we analyzed the data

All statistical analyses were performed using SAS, version 9.1 (SAS Institute Inc, Cary, NC). To avoid a possible cluster effect between the 17 practices, probabilities and corresponding 95% confidence intervals were estimated using a Generalized Estimating Equation (GEE) regression model. We used this method so that we could compare participants to nonparticipants, as well as to patients with subjective memory complaints and those without them. A backward elimination and a significance level of 5% to stay in model were used. Pearson’s chi-square was used to evaluate Goodness of Fit for the reduced model.

In the hypothesis-generating analysis, the following variables were included: age, gender, living with partner, receiving home care, school education, MMSE score, and EuroQoL-5D-VAS score. The EuroQoL-5D results were categorized into 3 groups: severe impairment (0 to 49 points), mild to moderate impairment (50 to 74), and normal (75 to 100). The MMSE was adjusted for age and education.

Results

Only quality-of-life scores predicted memory complaints

A total of 1180 patients 65 years of age and older consulted their GPs in the study period. From this group, we excluded 133 patients. Of the eligible 1047 patients, 775 (74.0%) patients agreed to participate in the study. These patents had a mean age of 74.8 years (standard deviation [SD], 7.1), and an average relationship with their GP of 11 years. Those who refused to participate in the study were more likely to be female and were less likely to complain about memory problems, according to the GP surveys.

The average MMSE score for these 775 patients was 28.2 (SD, 2.0), and the average EuroQoL-5D-VAS score was 70.9 (SD, 18.9). A total of 758 patients responded to the patient questionnaire regarding memory. Of these 758 patients, 177 (23.4%) reported memory complaints (that is, indicated their memory was “less good,” “poor,” or “miserable”). Only 33 (18.6%) of these 177 patients had previously consulted their GP regarding memory problems. The TABLE shows the characteristics of participants based on self-reported memory complaints.

In a hypothesis-generating analysis, we found that the only predictor for subjective memory complaints, as compared with those patients with good memory (stated as “excellent” or “good”), was an impairment of EuroQoL-5D-VAS: for a score of 0–49 points, the odds ratio (OR) for subjective memory complaints was 4.8; for a score of 50–74 points, the OR was 4.1. The patients’ gender, education, MMSE score, whether they lived alone or with a partner, and whether they were receiving home care did not seem to be independent predictors.

TABLE
Quality-of-life score was the only predictor of self-reported memory problems

Discussion

Other predictors of memory problems remain to be discovered

Depression,¹² other psychiatric conditions,^3,4 as well as certain medications may be associated with self-reported memory problems in elderly patients. These associations may explain why we found a correlation between reports of a lower quality of life and subjective memory complaints. Advanced age, female gender, and a low level of education have also been associated with a higher prevalence of memory complaints in other studies, but our study did not confirm any of these findings.

Limitations of this study

This study had several limitations. It had some selection bias, which may decrease its generalizability. In addition, this study was not designed to clarify whether memory complaints could be an early indicator for onset of dementia, or whether these complaints are associated with mild cognitive impairment or existing dementia.

The collection of data was monitored on a weekly basis by site visits from a study nurse. However, we did not monitor the actual exams.

An MMSE score of <24 has been widely used as an indication of the presence of cognitive impairment in population-based studies.¹² However, research has shown that MMSE scores are affected by age, education, and cultural background; this may explain why the MMSE by itself is not sufficient to diagnose dementia.¹²

Future studies should focus on clinically relevant outcomes

Further prospective studies in GP settings are needed to examine the potential implications of subjective memory complaints. We suggest that in future studies, clinically relevant outcomes—such as death, nursing home placement, medication usage, or health care usage—be used as possible correlating factors.

Correspondence
Frans Boch Waldorff, MD, PhD, Research Unit of General Practice, Kommunehospitalet, Øster Farimagsgade 5, DK-1014 Copenhagen, Denmark; fbw@gpract.ku.dk

In studies of older patients, the prevalence of subjective memory complaints in community-based populations varies from 11% to 56%,^1,2 depending on sample selection and on how the complaints are assessed.¹ Subjective memory complaints may be associated with psychiatric symptoms—in particular, depression^3,4 and anxiety—as well as older age, lower education, and female gender.¹ In these studies, some association has been found between memory complaints and cognitive impairment on testing, even after adjustment for depressive symptoms.^4,5

Researchers have suggested that subjective memory complaints may be an early indicator for dementia,¹ and could therefore be considered as a marker for identification of dementia in general practice. However, these complaints may be the result of a wide range of conditions; longitudinal studies assessing the value of memory complaints in predicting dementia or cognitive decline have shown varying results.^6-8

The prevalence of subjective memory complaints among elderly patients consulting their GP is not known, and the clinical implication of these complaints is not well established. We conducted this study in order to investigate the prevalence and potential clinical implications of subjective memory complaints among elderly patients in general practice.

Methods

Recruiting the subjects

Seventeen general medical practices with 24 GPs located in the central district of Copenhagen, Denmark, participated in this study. These practices served a total of 40,865 patients, 2934 of whom were 65 years of age or older.

We asked all patients 65 years of age or older who consulted their GP in October and November 2002 to participate in the study, regardless of the reason for the encounter. We excluded patients who were not able to read Danish or not able to sign an informed consent form. We also excluded those with severe acute or terminal illness or a diagnosis of dementia.

Assessment of the patients

Participant questionnaire. Before the visit with their GP, we asked all qualifying patients to complete a questionnaire with items about self-reported health and memory status, as well as demographic questions. The item regarding memory status was phrased: “How would you evaluate your memory?” The categories were “excellent,” “good,” “less good,” “poor,” and “miserable.” Patients rating their memory as “less good,” “poor,” or “miserable” were classified as patients with subjective memory complaints, whereas patients rating their memory as “excellent” or “good” were defined as patients without subjective memory complaints.

Quality-of-life assessment. During their visit, the patients also completed the Danish Validated Version of EuroQoL-5D, which includes a visual analogue scale (VAS). EuroQoL-5D is a standardized instrument for use as a measure of health outcomes.⁹ Patients are asked to assess their health—in regards to mobility, self-care, everyday activities, pain, and anxiety—by checking 1 of 3 boxes. They are then asked to assess their general state of health on a VAS ranging from 0 to 100.

GP questionnaire. A questionnaire dealing with the GP’s clinical impression of dementia was developed together with 2 of the GPs and tested in a pilot survey. This questionnaire was completed by the GP for each patient before they administered the Mini Mental State Examination (MMSE), with no information from the completed participant questionnaire. The GPs could complete the questionnaire before or during the office visit.

MMSE. The MMSE, recommended in GP guidelines as a cognitive screening test, was given to the patients after the GPs completed their own questionnaires.¹⁰ The test is a 30-point questionnaire that assesses cognition; it includes simple questions and problems in a number of areas: time and place of the test, repeating lists of words, math problems, language use and comprehension, and copying a drawing. An MMSE score <24 has been widely used as an indication of the presence of cognitive impairment in population-based studies.

Registry data and ethics

The Danish National Health Register provided the information regarding the physicians and their practices.¹¹ The municipality of Copenhagen provided information regarding the nursing home status of patients.

The Scientific Ethical Committee for Copenhagen and Frederiksberg Municipalities evaluated the project. The Danish Data Protection Agency and the Danish College of General Practitioners Study Committee approved the project.

How we analyzed the data

All statistical analyses were performed using SAS, version 9.1 (SAS Institute Inc, Cary, NC). To avoid a possible cluster effect between the 17 practices, probabilities and corresponding 95% confidence intervals were estimated using a Generalized Estimating Equation (GEE) regression model. We used this method so that we could compare participants to nonparticipants, as well as to patients with subjective memory complaints and those without them. A backward elimination and a significance level of 5% to stay in model were used. Pearson’s chi-square was used to evaluate Goodness of Fit for the reduced model.

In the hypothesis-generating analysis, the following variables were included: age, gender, living with partner, receiving home care, school education, MMSE score, and EuroQoL-5D-VAS score. The EuroQoL-5D results were categorized into 3 groups: severe impairment (0 to 49 points), mild to moderate impairment (50 to 74), and normal (75 to 100). The MMSE was adjusted for age and education.

Results

Only quality-of-life scores predicted memory complaints

A total of 1180 patients 65 years of age and older consulted their GPs in the study period. From this group, we excluded 133 patients. Of the eligible 1047 patients, 775 (74.0%) patients agreed to participate in the study. These patents had a mean age of 74.8 years (standard deviation [SD], 7.1), and an average relationship with their GP of 11 years. Those who refused to participate in the study were more likely to be female and were less likely to complain about memory problems, according to the GP surveys.

The average MMSE score for these 775 patients was 28.2 (SD, 2.0), and the average EuroQoL-5D-VAS score was 70.9 (SD, 18.9). A total of 758 patients responded to the patient questionnaire regarding memory. Of these 758 patients, 177 (23.4%) reported memory complaints (that is, indicated their memory was “less good,” “poor,” or “miserable”). Only 33 (18.6%) of these 177 patients had previously consulted their GP regarding memory problems. The TABLE shows the characteristics of participants based on self-reported memory complaints.

In a hypothesis-generating analysis, we found that the only predictor for subjective memory complaints, as compared with those patients with good memory (stated as “excellent” or “good”), was an impairment of EuroQoL-5D-VAS: for a score of 0–49 points, the odds ratio (OR) for subjective memory complaints was 4.8; for a score of 50–74 points, the OR was 4.1. The patients’ gender, education, MMSE score, whether they lived alone or with a partner, and whether they were receiving home care did not seem to be independent predictors.

TABLE
Quality-of-life score was the only predictor of self-reported memory problems

Discussion

Other predictors of memory problems remain to be discovered

Depression,¹² other psychiatric conditions,^3,4 as well as certain medications may be associated with self-reported memory problems in elderly patients. These associations may explain why we found a correlation between reports of a lower quality of life and subjective memory complaints. Advanced age, female gender, and a low level of education have also been associated with a higher prevalence of memory complaints in other studies, but our study did not confirm any of these findings.

Limitations of this study

This study had several limitations. It had some selection bias, which may decrease its generalizability. In addition, this study was not designed to clarify whether memory complaints could be an early indicator for onset of dementia, or whether these complaints are associated with mild cognitive impairment or existing dementia.

The collection of data was monitored on a weekly basis by site visits from a study nurse. However, we did not monitor the actual exams.

An MMSE score of <24 has been widely used as an indication of the presence of cognitive impairment in population-based studies.¹² However, research has shown that MMSE scores are affected by age, education, and cultural background; this may explain why the MMSE by itself is not sufficient to diagnose dementia.¹²

Future studies should focus on clinically relevant outcomes

Further prospective studies in GP settings are needed to examine the potential implications of subjective memory complaints. We suggest that in future studies, clinically relevant outcomes—such as death, nursing home placement, medication usage, or health care usage—be used as possible correlating factors.

Correspondence
Frans Boch Waldorff, MD, PhD, Research Unit of General Practice, Kommunehospitalet, Øster Farimagsgade 5, DK-1014 Copenhagen, Denmark; fbw@gpract.ku.dk

In studies of older patients, the prevalence of subjective memory complaints in community-based populations varies from 11% to 56%,^1,2 depending on sample selection and on how the complaints are assessed.¹ Subjective memory complaints may be associated with psychiatric symptoms—in particular, depression^3,4 and anxiety—as well as older age, lower education, and female gender.¹ In these studies, some association has been found between memory complaints and cognitive impairment on testing, even after adjustment for depressive symptoms.^4,5

Researchers have suggested that subjective memory complaints may be an early indicator for dementia,¹ and could therefore be considered as a marker for identification of dementia in general practice. However, these complaints may be the result of a wide range of conditions; longitudinal studies assessing the value of memory complaints in predicting dementia or cognitive decline have shown varying results.^6-8

The prevalence of subjective memory complaints among elderly patients consulting their GP is not known, and the clinical implication of these complaints is not well established. We conducted this study in order to investigate the prevalence and potential clinical implications of subjective memory complaints among elderly patients in general practice.

Methods

Recruiting the subjects

Seventeen general medical practices with 24 GPs located in the central district of Copenhagen, Denmark, participated in this study. These practices served a total of 40,865 patients, 2934 of whom were 65 years of age or older.

We asked all patients 65 years of age or older who consulted their GP in October and November 2002 to participate in the study, regardless of the reason for the encounter. We excluded patients who were not able to read Danish or not able to sign an informed consent form. We also excluded those with severe acute or terminal illness or a diagnosis of dementia.

Assessment of the patients

Participant questionnaire. Before the visit with their GP, we asked all qualifying patients to complete a questionnaire with items about self-reported health and memory status, as well as demographic questions. The item regarding memory status was phrased: “How would you evaluate your memory?” The categories were “excellent,” “good,” “less good,” “poor,” and “miserable.” Patients rating their memory as “less good,” “poor,” or “miserable” were classified as patients with subjective memory complaints, whereas patients rating their memory as “excellent” or “good” were defined as patients without subjective memory complaints.

Quality-of-life assessment. During their visit, the patients also completed the Danish Validated Version of EuroQoL-5D, which includes a visual analogue scale (VAS). EuroQoL-5D is a standardized instrument for use as a measure of health outcomes.⁹ Patients are asked to assess their health—in regards to mobility, self-care, everyday activities, pain, and anxiety—by checking 1 of 3 boxes. They are then asked to assess their general state of health on a VAS ranging from 0 to 100.

GP questionnaire. A questionnaire dealing with the GP’s clinical impression of dementia was developed together with 2 of the GPs and tested in a pilot survey. This questionnaire was completed by the GP for each patient before they administered the Mini Mental State Examination (MMSE), with no information from the completed participant questionnaire. The GPs could complete the questionnaire before or during the office visit.

MMSE. The MMSE, recommended in GP guidelines as a cognitive screening test, was given to the patients after the GPs completed their own questionnaires.¹⁰ The test is a 30-point questionnaire that assesses cognition; it includes simple questions and problems in a number of areas: time and place of the test, repeating lists of words, math problems, language use and comprehension, and copying a drawing. An MMSE score <24 has been widely used as an indication of the presence of cognitive impairment in population-based studies.

Registry data and ethics

The Danish National Health Register provided the information regarding the physicians and their practices.¹¹ The municipality of Copenhagen provided information regarding the nursing home status of patients.

The Scientific Ethical Committee for Copenhagen and Frederiksberg Municipalities evaluated the project. The Danish Data Protection Agency and the Danish College of General Practitioners Study Committee approved the project.

How we analyzed the data

All statistical analyses were performed using SAS, version 9.1 (SAS Institute Inc, Cary, NC). To avoid a possible cluster effect between the 17 practices, probabilities and corresponding 95% confidence intervals were estimated using a Generalized Estimating Equation (GEE) regression model. We used this method so that we could compare participants to nonparticipants, as well as to patients with subjective memory complaints and those without them. A backward elimination and a significance level of 5% to stay in model were used. Pearson’s chi-square was used to evaluate Goodness of Fit for the reduced model.

In the hypothesis-generating analysis, the following variables were included: age, gender, living with partner, receiving home care, school education, MMSE score, and EuroQoL-5D-VAS score. The EuroQoL-5D results were categorized into 3 groups: severe impairment (0 to 49 points), mild to moderate impairment (50 to 74), and normal (75 to 100). The MMSE was adjusted for age and education.

Results

Only quality-of-life scores predicted memory complaints

A total of 1180 patients 65 years of age and older consulted their GPs in the study period. From this group, we excluded 133 patients. Of the eligible 1047 patients, 775 (74.0%) patients agreed to participate in the study. These patents had a mean age of 74.8 years (standard deviation [SD], 7.1), and an average relationship with their GP of 11 years. Those who refused to participate in the study were more likely to be female and were less likely to complain about memory problems, according to the GP surveys.

The average MMSE score for these 775 patients was 28.2 (SD, 2.0), and the average EuroQoL-5D-VAS score was 70.9 (SD, 18.9). A total of 758 patients responded to the patient questionnaire regarding memory. Of these 758 patients, 177 (23.4%) reported memory complaints (that is, indicated their memory was “less good,” “poor,” or “miserable”). Only 33 (18.6%) of these 177 patients had previously consulted their GP regarding memory problems. The TABLE shows the characteristics of participants based on self-reported memory complaints.

In a hypothesis-generating analysis, we found that the only predictor for subjective memory complaints, as compared with those patients with good memory (stated as “excellent” or “good”), was an impairment of EuroQoL-5D-VAS: for a score of 0–49 points, the odds ratio (OR) for subjective memory complaints was 4.8; for a score of 50–74 points, the OR was 4.1. The patients’ gender, education, MMSE score, whether they lived alone or with a partner, and whether they were receiving home care did not seem to be independent predictors.

TABLE
Quality-of-life score was the only predictor of self-reported memory problems

Discussion

Other predictors of memory problems remain to be discovered

Depression,¹² other psychiatric conditions,^3,4 as well as certain medications may be associated with self-reported memory problems in elderly patients. These associations may explain why we found a correlation between reports of a lower quality of life and subjective memory complaints. Advanced age, female gender, and a low level of education have also been associated with a higher prevalence of memory complaints in other studies, but our study did not confirm any of these findings.

Limitations of this study

This study had several limitations. It had some selection bias, which may decrease its generalizability. In addition, this study was not designed to clarify whether memory complaints could be an early indicator for onset of dementia, or whether these complaints are associated with mild cognitive impairment or existing dementia.

The collection of data was monitored on a weekly basis by site visits from a study nurse. However, we did not monitor the actual exams.

An MMSE score of <24 has been widely used as an indication of the presence of cognitive impairment in population-based studies.¹² However, research has shown that MMSE scores are affected by age, education, and cultural background; this may explain why the MMSE by itself is not sufficient to diagnose dementia.¹²

Future studies should focus on clinically relevant outcomes

Further prospective studies in GP settings are needed to examine the potential implications of subjective memory complaints. We suggest that in future studies, clinically relevant outcomes—such as death, nursing home placement, medication usage, or health care usage—be used as possible correlating factors.

Correspondence
Frans Boch Waldorff, MD, PhD, Research Unit of General Practice, Kommunehospitalet, Øster Farimagsgade 5, DK-1014 Copenhagen, Denmark; fbw@gpract.ku.dk

The varicella vaccine has had tremendous success over the last few years, but its success has stalled.

The widespread use of the varicella vaccine has led to a coverage rate of 88%, and the vaccine has proven to be 85% effective. As a result, between 1995 and 2001 there was an 87% decline in hospitalizations, 66% decline in deaths, and an 87% decline in costs attributed to varicella.

However, the number of varicella cases has remained at a constant level over the past few years and sporadic outbreaks continue to occur in schools—even where high rates of immunization are achieved.^1,2

Varicella outbreaks involve both infections in unvaccinated children and “breakthrough disease” in those who have been vaccinated. If a vaccinated person is exposed to varicella, the risk of suffering a breakthrough infection is about 15%.² A 2-dose series of varicella vaccine reduces the risk by about 75%¹ (Figure).

Breakthrough disease is usually milder than infection in the unvaccinated, with fewer skin lesions, milder symptoms, and fewer complications. Those affected, though, are still infectious to others.

It was this ongoing risk of varicella that prompted the Advisory Committee on Immunization Practices (ACIP) to recommend new control measures, reported on in 2007.¹

FIGURE
2 doses of varicella vaccine reduce risk of breakthrough infection by about 75%¹

ACIP now recommends 2 doses of the vaccine

ACIP recommends the following:

• Universal administration of 2 doses of varicella vaccine; the first at ages 12 to 15 months and the second at age 4 to 6 years. (This is the same schedule as immunization against mumps, measles, and rubella.)
• Two doses of varicella vaccine, 4 to 8 weeks apart, for all adolescents and adults without evidence of immunity. (See “New criteria to prove immunity” at right.)
• A catch-up second dose for everyone who received one dose previously.
• Screening for varicella immunity in pregnant women and postpartum vaccination for those who are not immune, with 2 doses 4 to 8 weeks apart. The first dose should be administered before discharge.

Which HIV patients can get the vaccine?

ACIP has also clarified when HIV patients can be vaccinated, noting that single antigen varicella vaccine can be administered to HIV positive children if their CD4+ Tlymphocyte % is ≥15%. HIV positive adolescents and adults can be vaccinated if their CD4+ T-lymphocyte count ≥200/μL and, if 2 doses are indicated, they should be separated by at least 3 months.

2 options: Varivax and ProQuad

Two varicella vaccines contain modified live varicella virus antigen. Varivax, a single antigen vaccine, is approved for use in adults, adolescents, and children ≥12 months of age. The second vaccine, ProQuad, is approved for use in patients who are between 12 months and 12 years of age, and contains 4 viral antigens: mumps, measles, rubella, and varicella.

The quadrivalent MMRV vaccine is currently unavailable, however, and isn’t expected to be available until early 2009.³ Once the supply is stabilized, though, it will facilitate vaccination of children by decreasing the number of injections needed to achieve full immunization status.

29-year-old patient with varicellaThese 2 varicella vaccines should not be confused with the varicella zoster vaccine, Zostavax, which is approved for use in adults who are 60 years of age and older for the prevention of shingles and postherpetic neuralgia.⁴

Pregnancy precludes vaccination

Varicella vaccine is contraindicated during pregnancy and in those who have had a severe allergic reaction to any vaccine component, including gelatin; have a malignancy of the blood, bone marrow, or lymphatic system; have a congenital or hereditary immunodeficiency; or are receiving systemic immunosuppressive therapy including those on the equivalent of 2 mg/kg, or >20 mg/day, of prednisone.

You should delay giving the vaccine to patients with an acute, severe illness. There is a potential for immune globulin containing products to interfere with the effectiveness of live virus vaccines. As a result, if a patient has received blood, plasma, or immune globulin, you should wait 3 to 11 months before giving the varicella vaccine. These products should also be avoided, if possible, for 2 weeks after the vaccine has been administered.

Avoid using quadrivalent MMRV in patients with HIV infection because it contains a higher quantity of varicella antigen than the single antigen product.

One final precaution: Patients should avoid taking salicylates for 6 weeks following vaccination because of the theoretical risk of Reye’s syndrome.

The varicella vaccine has had tremendous success over the last few years, but its success has stalled.

The widespread use of the varicella vaccine has led to a coverage rate of 88%, and the vaccine has proven to be 85% effective. As a result, between 1995 and 2001 there was an 87% decline in hospitalizations, 66% decline in deaths, and an 87% decline in costs attributed to varicella.

However, the number of varicella cases has remained at a constant level over the past few years and sporadic outbreaks continue to occur in schools—even where high rates of immunization are achieved.^1,2

Varicella outbreaks involve both infections in unvaccinated children and “breakthrough disease” in those who have been vaccinated. If a vaccinated person is exposed to varicella, the risk of suffering a breakthrough infection is about 15%.² A 2-dose series of varicella vaccine reduces the risk by about 75%¹ (Figure).

Breakthrough disease is usually milder than infection in the unvaccinated, with fewer skin lesions, milder symptoms, and fewer complications. Those affected, though, are still infectious to others.

It was this ongoing risk of varicella that prompted the Advisory Committee on Immunization Practices (ACIP) to recommend new control measures, reported on in 2007.¹

FIGURE
2 doses of varicella vaccine reduce risk of breakthrough infection by about 75%¹

ACIP now recommends 2 doses of the vaccine

ACIP recommends the following:

• Universal administration of 2 doses of varicella vaccine; the first at ages 12 to 15 months and the second at age 4 to 6 years. (This is the same schedule as immunization against mumps, measles, and rubella.)
• Two doses of varicella vaccine, 4 to 8 weeks apart, for all adolescents and adults without evidence of immunity. (See “New criteria to prove immunity” at right.)
• A catch-up second dose for everyone who received one dose previously.
• Screening for varicella immunity in pregnant women and postpartum vaccination for those who are not immune, with 2 doses 4 to 8 weeks apart. The first dose should be administered before discharge.

Which HIV patients can get the vaccine?

ACIP has also clarified when HIV patients can be vaccinated, noting that single antigen varicella vaccine can be administered to HIV positive children if their CD4+ Tlymphocyte % is ≥15%. HIV positive adolescents and adults can be vaccinated if their CD4+ T-lymphocyte count ≥200/μL and, if 2 doses are indicated, they should be separated by at least 3 months.

2 options: Varivax and ProQuad

Two varicella vaccines contain modified live varicella virus antigen. Varivax, a single antigen vaccine, is approved for use in adults, adolescents, and children ≥12 months of age. The second vaccine, ProQuad, is approved for use in patients who are between 12 months and 12 years of age, and contains 4 viral antigens: mumps, measles, rubella, and varicella.

The quadrivalent MMRV vaccine is currently unavailable, however, and isn’t expected to be available until early 2009.³ Once the supply is stabilized, though, it will facilitate vaccination of children by decreasing the number of injections needed to achieve full immunization status.

29-year-old patient with varicellaThese 2 varicella vaccines should not be confused with the varicella zoster vaccine, Zostavax, which is approved for use in adults who are 60 years of age and older for the prevention of shingles and postherpetic neuralgia.⁴

Pregnancy precludes vaccination

Varicella vaccine is contraindicated during pregnancy and in those who have had a severe allergic reaction to any vaccine component, including gelatin; have a malignancy of the blood, bone marrow, or lymphatic system; have a congenital or hereditary immunodeficiency; or are receiving systemic immunosuppressive therapy including those on the equivalent of 2 mg/kg, or >20 mg/day, of prednisone.

You should delay giving the vaccine to patients with an acute, severe illness. There is a potential for immune globulin containing products to interfere with the effectiveness of live virus vaccines. As a result, if a patient has received blood, plasma, or immune globulin, you should wait 3 to 11 months before giving the varicella vaccine. These products should also be avoided, if possible, for 2 weeks after the vaccine has been administered.

Avoid using quadrivalent MMRV in patients with HIV infection because it contains a higher quantity of varicella antigen than the single antigen product.

One final precaution: Patients should avoid taking salicylates for 6 weeks following vaccination because of the theoretical risk of Reye’s syndrome.

The varicella vaccine has had tremendous success over the last few years, but its success has stalled.

The widespread use of the varicella vaccine has led to a coverage rate of 88%, and the vaccine has proven to be 85% effective. As a result, between 1995 and 2001 there was an 87% decline in hospitalizations, 66% decline in deaths, and an 87% decline in costs attributed to varicella.

However, the number of varicella cases has remained at a constant level over the past few years and sporadic outbreaks continue to occur in schools—even where high rates of immunization are achieved.^1,2

Varicella outbreaks involve both infections in unvaccinated children and “breakthrough disease” in those who have been vaccinated. If a vaccinated person is exposed to varicella, the risk of suffering a breakthrough infection is about 15%.² A 2-dose series of varicella vaccine reduces the risk by about 75%¹ (Figure).

Breakthrough disease is usually milder than infection in the unvaccinated, with fewer skin lesions, milder symptoms, and fewer complications. Those affected, though, are still infectious to others.

It was this ongoing risk of varicella that prompted the Advisory Committee on Immunization Practices (ACIP) to recommend new control measures, reported on in 2007.¹

FIGURE
2 doses of varicella vaccine reduce risk of breakthrough infection by about 75%¹

ACIP now recommends 2 doses of the vaccine

ACIP recommends the following:

• Universal administration of 2 doses of varicella vaccine; the first at ages 12 to 15 months and the second at age 4 to 6 years. (This is the same schedule as immunization against mumps, measles, and rubella.)
• Two doses of varicella vaccine, 4 to 8 weeks apart, for all adolescents and adults without evidence of immunity. (See “New criteria to prove immunity” at right.)
• A catch-up second dose for everyone who received one dose previously.
• Screening for varicella immunity in pregnant women and postpartum vaccination for those who are not immune, with 2 doses 4 to 8 weeks apart. The first dose should be administered before discharge.

Which HIV patients can get the vaccine?

ACIP has also clarified when HIV patients can be vaccinated, noting that single antigen varicella vaccine can be administered to HIV positive children if their CD4+ Tlymphocyte % is ≥15%. HIV positive adolescents and adults can be vaccinated if their CD4+ T-lymphocyte count ≥200/μL and, if 2 doses are indicated, they should be separated by at least 3 months.

2 options: Varivax and ProQuad

Two varicella vaccines contain modified live varicella virus antigen. Varivax, a single antigen vaccine, is approved for use in adults, adolescents, and children ≥12 months of age. The second vaccine, ProQuad, is approved for use in patients who are between 12 months and 12 years of age, and contains 4 viral antigens: mumps, measles, rubella, and varicella.

The quadrivalent MMRV vaccine is currently unavailable, however, and isn’t expected to be available until early 2009.³ Once the supply is stabilized, though, it will facilitate vaccination of children by decreasing the number of injections needed to achieve full immunization status.

29-year-old patient with varicellaThese 2 varicella vaccines should not be confused with the varicella zoster vaccine, Zostavax, which is approved for use in adults who are 60 years of age and older for the prevention of shingles and postherpetic neuralgia.⁴

Pregnancy precludes vaccination

Varicella vaccine is contraindicated during pregnancy and in those who have had a severe allergic reaction to any vaccine component, including gelatin; have a malignancy of the blood, bone marrow, or lymphatic system; have a congenital or hereditary immunodeficiency; or are receiving systemic immunosuppressive therapy including those on the equivalent of 2 mg/kg, or >20 mg/day, of prednisone.

You should delay giving the vaccine to patients with an acute, severe illness. There is a potential for immune globulin containing products to interfere with the effectiveness of live virus vaccines. As a result, if a patient has received blood, plasma, or immune globulin, you should wait 3 to 11 months before giving the varicella vaccine. These products should also be avoided, if possible, for 2 weeks after the vaccine has been administered.

Avoid using quadrivalent MMRV in patients with HIV infection because it contains a higher quantity of varicella antigen than the single antigen product.

One final precaution: Patients should avoid taking salicylates for 6 weeks following vaccination because of the theoretical risk of Reye’s syndrome.