Diana Mahoney

BOSTON— “Genital herpes is a recurrent, lifelong viral disease. This is the one thing that patients and clinicians don't like to say, but there's no way around” it, Laura J. Mulcahy said at a conference on contraceptive technology sponsored by Contemporary Forums.

Other difficult truths about infection with herpes simplex virus (HSV) type 2? The overwhelming majority of people infected with the virus don't know that they have it, and people with asymptomatic or unrecognized disease shed the virus intermittently in the genital tract, said Ms. Mulcahy, a certified family nurse practitioner who is assistant medical director of the STD Center for Excellence at Montefiore Medical Center in New York.

“When we ask patients prior to screening for HSV-2 if they have a history of genital herpes … about 90% of those who ultimately test positive for HSV-2 antibodies reported having no history or symptoms of the infection,” she said. This underrecognition can be attributed to the fact that the leading cause of HSV-2 infection is asymptomatic shedding of the virus.

“There is a misperception and some clinicians are still telling patients that the infection is spread only through [HSV-2] sores. This is absolutely not true. The virus can shed even when the skin looks normal, and that's when most infections occur,” she said.

Patient education about asymptomatic disease is critical to an effective screening protocol. “When patients come in and have no symptoms, it means nothing to us,” Ms. Mulcahy emphasized. Patients who come in for STD screening are told that, “from this day forward, the fact that you or your partner have no symptoms means nothing; the fact that you and your partner look fine means nothing; and the fact that you or your partner had a negative screen 6 months ago, if you've had partners in the interim, means nothing,” she said.

Another factor contributing to the high rate of unrecognized disease is that many patients who have been screened for STDs believe they have been tested for genital herpes. “A complete STD screen does not include testing for herpes. Clinicians don't always tell this to patients, so many patients believe they are being tested for everything. If their STD screen is negative, they assume that means they don't have herpes,” Ms. Mulcahy said.

For this reason, “clinicians who don't routinely screen for herpes [as part of an STD screening protocol] must inform patients that they are not being tested and chart that in the patient record so there is no confusion,” she added.

If a patient asks to be screened for HSV-2, there are several points that should be addressed before testing, Ms. Mulcahy advised:

▸ The absence of symptoms does not predict a negative screen.

▸ In patients with lesions, a herpes culture has low sensitivity, especially as lesions heal. As such, a negative culture does not rule out HSV-2.

▸ In the event of a positive HSV-2 test in an asymptomatic person, it is not possible to determine how long the virus has been present, when or whether they will have outbreaks, or whether they will ever have a problem with herpes.

▸ In the event of a positive HSV-2 test, patients in some states have a legal obligation to inform current and future sexual partners of their infection status before genital to skin contact. “It is a misdemeanor in New York state, for example, to knowingly pass on or put someone else at risk for a sexually transmitted disease,” Ms. Mulcahy said.

Counseling patients on these points before testing is imperative. “If you wait until after a positive screen, I can guarantee patients will no longer be listening. They need to know what to expect before they hear the word positive,” she said.

Among the tools used to screen for HSV-2, clinical examination and history are insensitive and nonspecific. “Symptoms are easily confused with other conditions or may present atypically, for example, as redness rather than sores,” Ms. Mulcahy said. Viral culture is the most valid test available, despite the high rate of false negatives.

Polymerase chain reaction assays are another diagnostic option. They have increased sensitivity but are not approved by the Food and Drug Administration, nor are they available in all laboratories. Cellular detection methods, including Tzanck test and Pap smear, are not recommended for HSV detection because of their low sensitivity, she said.

Many type-specific serology tests, such as the older enzyme-lined immunoabsorbent assay tests, can result in false-positive results because of problems with cross reactivity. The newer type-specific HSV glycoprotein G1 (HSV-1) and G2 (HSV-2) tests are more reliable, but their sensitivities vary, she said, noting that a positive test should be confirmed with another test to reduce the risk of false-positive diagnoses. The Western blot is the reference standard serology test, but it is not approved and is only available from one laboratory at the University of Washington, Seattle.

“Do not underestimate the impact of this diagnosis on your patients. They will require extensive, thoughtful counseling [because] the physical impact of genital herpes is nothing compared to the psychological one,” Ms. Mulcahy said.

Such counseling should include information about the natural history of disease, the ability to bear children, the transmission risk to sexual partners, and the variations in severity of primary vs. recurrent episodes. It also is important to dispel cancer myths, reiterate the fact that the virus can be transmitted in the absence of symptoms or lesions, remind patients of their obligation to inform current and future partners, and recommend counseling and testing for sexual partners, she said.

Risk-reduction strategies also should be discussed, including avoiding sexual contact when symptoms or lesions are present and using latex barrier protection and suppressive therapy. There are three oral antiviral drugs—acyclovir, valacyclovir, and famciclovir—approved for the treatment of genital herpes. Topical treatments, she stressed, “absolutely do not work and have no role in the treatment of genital herpes.”

BOSTON— “Genital herpes is a recurrent, lifelong viral disease. This is the one thing that patients and clinicians don't like to say, but there's no way around” it, Laura J. Mulcahy said at a conference on contraceptive technology sponsored by Contemporary Forums.

Other difficult truths about infection with herpes simplex virus (HSV) type 2? The overwhelming majority of people infected with the virus don't know that they have it, and people with asymptomatic or unrecognized disease shed the virus intermittently in the genital tract, said Ms. Mulcahy, a certified family nurse practitioner who is assistant medical director of the STD Center for Excellence at Montefiore Medical Center in New York.

“When we ask patients prior to screening for HSV-2 if they have a history of genital herpes … about 90% of those who ultimately test positive for HSV-2 antibodies reported having no history or symptoms of the infection,” she said. This underrecognition can be attributed to the fact that the leading cause of HSV-2 infection is asymptomatic shedding of the virus.

“There is a misperception and some clinicians are still telling patients that the infection is spread only through [HSV-2] sores. This is absolutely not true. The virus can shed even when the skin looks normal, and that's when most infections occur,” she said.

Patient education about asymptomatic disease is critical to an effective screening protocol. “When patients come in and have no symptoms, it means nothing to us,” Ms. Mulcahy emphasized. Patients who come in for STD screening are told that, “from this day forward, the fact that you or your partner have no symptoms means nothing; the fact that you and your partner look fine means nothing; and the fact that you or your partner had a negative screen 6 months ago, if you've had partners in the interim, means nothing,” she said.

Another factor contributing to the high rate of unrecognized disease is that many patients who have been screened for STDs believe they have been tested for genital herpes. “A complete STD screen does not include testing for herpes. Clinicians don't always tell this to patients, so many patients believe they are being tested for everything. If their STD screen is negative, they assume that means they don't have herpes,” Ms. Mulcahy said.

For this reason, “clinicians who don't routinely screen for herpes [as part of an STD screening protocol] must inform patients that they are not being tested and chart that in the patient record so there is no confusion,” she added.

If a patient asks to be screened for HSV-2, there are several points that should be addressed before testing, Ms. Mulcahy advised:

▸ The absence of symptoms does not predict a negative screen.

▸ In patients with lesions, a herpes culture has low sensitivity, especially as lesions heal. As such, a negative culture does not rule out HSV-2.

▸ In the event of a positive HSV-2 test in an asymptomatic person, it is not possible to determine how long the virus has been present, when or whether they will have outbreaks, or whether they will ever have a problem with herpes.

▸ In the event of a positive HSV-2 test, patients in some states have a legal obligation to inform current and future sexual partners of their infection status before genital to skin contact. “It is a misdemeanor in New York state, for example, to knowingly pass on or put someone else at risk for a sexually transmitted disease,” Ms. Mulcahy said.

Counseling patients on these points before testing is imperative. “If you wait until after a positive screen, I can guarantee patients will no longer be listening. They need to know what to expect before they hear the word positive,” she said.

Among the tools used to screen for HSV-2, clinical examination and history are insensitive and nonspecific. “Symptoms are easily confused with other conditions or may present atypically, for example, as redness rather than sores,” Ms. Mulcahy said. Viral culture is the most valid test available, despite the high rate of false negatives.

Polymerase chain reaction assays are another diagnostic option. They have increased sensitivity but are not approved by the Food and Drug Administration, nor are they available in all laboratories. Cellular detection methods, including Tzanck test and Pap smear, are not recommended for HSV detection because of their low sensitivity, she said.

Many type-specific serology tests, such as the older enzyme-lined immunoabsorbent assay tests, can result in false-positive results because of problems with cross reactivity. The newer type-specific HSV glycoprotein G1 (HSV-1) and G2 (HSV-2) tests are more reliable, but their sensitivities vary, she said, noting that a positive test should be confirmed with another test to reduce the risk of false-positive diagnoses. The Western blot is the reference standard serology test, but it is not approved and is only available from one laboratory at the University of Washington, Seattle.

“Do not underestimate the impact of this diagnosis on your patients. They will require extensive, thoughtful counseling [because] the physical impact of genital herpes is nothing compared to the psychological one,” Ms. Mulcahy said.

Such counseling should include information about the natural history of disease, the ability to bear children, the transmission risk to sexual partners, and the variations in severity of primary vs. recurrent episodes. It also is important to dispel cancer myths, reiterate the fact that the virus can be transmitted in the absence of symptoms or lesions, remind patients of their obligation to inform current and future partners, and recommend counseling and testing for sexual partners, she said.

Risk-reduction strategies also should be discussed, including avoiding sexual contact when symptoms or lesions are present and using latex barrier protection and suppressive therapy. There are three oral antiviral drugs—acyclovir, valacyclovir, and famciclovir—approved for the treatment of genital herpes. Topical treatments, she stressed, “absolutely do not work and have no role in the treatment of genital herpes.”

BOSTON— “Genital herpes is a recurrent, lifelong viral disease. This is the one thing that patients and clinicians don't like to say, but there's no way around” it, Laura J. Mulcahy said at a conference on contraceptive technology sponsored by Contemporary Forums.

Other difficult truths about infection with herpes simplex virus (HSV) type 2? The overwhelming majority of people infected with the virus don't know that they have it, and people with asymptomatic or unrecognized disease shed the virus intermittently in the genital tract, said Ms. Mulcahy, a certified family nurse practitioner who is assistant medical director of the STD Center for Excellence at Montefiore Medical Center in New York.

“When we ask patients prior to screening for HSV-2 if they have a history of genital herpes … about 90% of those who ultimately test positive for HSV-2 antibodies reported having no history or symptoms of the infection,” she said. This underrecognition can be attributed to the fact that the leading cause of HSV-2 infection is asymptomatic shedding of the virus.

“There is a misperception and some clinicians are still telling patients that the infection is spread only through [HSV-2] sores. This is absolutely not true. The virus can shed even when the skin looks normal, and that's when most infections occur,” she said.

Patient education about asymptomatic disease is critical to an effective screening protocol. “When patients come in and have no symptoms, it means nothing to us,” Ms. Mulcahy emphasized. Patients who come in for STD screening are told that, “from this day forward, the fact that you or your partner have no symptoms means nothing; the fact that you and your partner look fine means nothing; and the fact that you or your partner had a negative screen 6 months ago, if you've had partners in the interim, means nothing,” she said.

Another factor contributing to the high rate of unrecognized disease is that many patients who have been screened for STDs believe they have been tested for genital herpes. “A complete STD screen does not include testing for herpes. Clinicians don't always tell this to patients, so many patients believe they are being tested for everything. If their STD screen is negative, they assume that means they don't have herpes,” Ms. Mulcahy said.

For this reason, “clinicians who don't routinely screen for herpes [as part of an STD screening protocol] must inform patients that they are not being tested and chart that in the patient record so there is no confusion,” she added.

If a patient asks to be screened for HSV-2, there are several points that should be addressed before testing, Ms. Mulcahy advised:

▸ The absence of symptoms does not predict a negative screen.

▸ In patients with lesions, a herpes culture has low sensitivity, especially as lesions heal. As such, a negative culture does not rule out HSV-2.

▸ In the event of a positive HSV-2 test in an asymptomatic person, it is not possible to determine how long the virus has been present, when or whether they will have outbreaks, or whether they will ever have a problem with herpes.

▸ In the event of a positive HSV-2 test, patients in some states have a legal obligation to inform current and future sexual partners of their infection status before genital to skin contact. “It is a misdemeanor in New York state, for example, to knowingly pass on or put someone else at risk for a sexually transmitted disease,” Ms. Mulcahy said.

Counseling patients on these points before testing is imperative. “If you wait until after a positive screen, I can guarantee patients will no longer be listening. They need to know what to expect before they hear the word positive,” she said.

Among the tools used to screen for HSV-2, clinical examination and history are insensitive and nonspecific. “Symptoms are easily confused with other conditions or may present atypically, for example, as redness rather than sores,” Ms. Mulcahy said. Viral culture is the most valid test available, despite the high rate of false negatives.

Polymerase chain reaction assays are another diagnostic option. They have increased sensitivity but are not approved by the Food and Drug Administration, nor are they available in all laboratories. Cellular detection methods, including Tzanck test and Pap smear, are not recommended for HSV detection because of their low sensitivity, she said.

Many type-specific serology tests, such as the older enzyme-lined immunoabsorbent assay tests, can result in false-positive results because of problems with cross reactivity. The newer type-specific HSV glycoprotein G1 (HSV-1) and G2 (HSV-2) tests are more reliable, but their sensitivities vary, she said, noting that a positive test should be confirmed with another test to reduce the risk of false-positive diagnoses. The Western blot is the reference standard serology test, but it is not approved and is only available from one laboratory at the University of Washington, Seattle.

“Do not underestimate the impact of this diagnosis on your patients. They will require extensive, thoughtful counseling [because] the physical impact of genital herpes is nothing compared to the psychological one,” Ms. Mulcahy said.

Such counseling should include information about the natural history of disease, the ability to bear children, the transmission risk to sexual partners, and the variations in severity of primary vs. recurrent episodes. It also is important to dispel cancer myths, reiterate the fact that the virus can be transmitted in the absence of symptoms or lesions, remind patients of their obligation to inform current and future partners, and recommend counseling and testing for sexual partners, she said.

Risk-reduction strategies also should be discussed, including avoiding sexual contact when symptoms or lesions are present and using latex barrier protection and suppressive therapy. There are three oral antiviral drugs—acyclovir, valacyclovir, and famciclovir—approved for the treatment of genital herpes. Topical treatments, she stressed, “absolutely do not work and have no role in the treatment of genital herpes.”

The rate of hospitalizations for kidney disease has risen sharply over the past 25 years, and the elevation has been driven primarily by a significant increase in the proportion of hospitalizations associated with acute renal failure relative to chronic kidney disease, particularly among older Americans, according to the Centers for Disease Control and Prevention.

An analysis of data from a national probability survey showed that the number of patients hospitalized with a diagnosis of either chronic or acute kidney disease rose from 416,000 in 1980 to 1.6 million in 2005, reported Dr. Nicole T. Flowers, a medical epidemiologist at the CDC, and her colleagues. Consistent increases in the rate of acute renal failure over the 25-year period, with smaller increases in the rate of chronic kidney failure, led to the shift in type of kidney disease most commonly associated with hospitalizations. The age-adjusted rate per 10,000 population for hospitalization for acute renal failure increased from 1.8 in 1980 to 36.5 in 2005. During the same period, the rate of chronic kidney failure rose from 7.4 to 13.8 per 10,000 population, they wrote (MMWR 2008;57:309–12).

Other trends emerging from the National Hospital Discharge Survey for 1980–2005 include consistently higher kidney disease hospitalization rates among men compared with women, a rise in the number of patients aged 65 years and older requiring hospitalization for kidney disease, and an increase in the number of kidney disease hospital discharges associated with a concomitant diagnosis of diabetes mellitus or hypertension.

Although the rates of kidney disease for both sexes increased significantly over the 25-year period, “the rates were consistently 30%-40% higher among men than among women,” the authors reported. Hospitalizations increased in all age groups except for individuals younger than 18 years, they wrote, noting: “An increase of approximately 300% (from 56.2 to 179.3 per 10,000 population) occurred among persons aged 65–74 years, and an increase of approximately 350% (from 119.0 to 393.2 per 10,000 population) occurred among persons aged 75 years and older.”

With respect to concomitant diagnoses, diabetes mellitus was reported as an additional discharge diagnosis for 23.4% of hospitalized kidney disease patients in 1980 and for 27.0% in 2005.

“This proportion peaked at 39.0% in 1996,” the authors wrote. The percentage of hospitalized kidney disease patients with a discharge diagnosis of hypertension rose from 19.6% in 1980 to 41.1% in 2005.

In an accompanying editorial, the CDC suggested that the unexplained increase in hospitalizations associated with acute renal failure “might be attributed to actual increases in [acute renal failure] among hospitalized patients or to changes in the way it is diagnosed, defined, or reflected in hospital discharge codes.” It might also be a function, in part, of the aging of the U.S. population, “with greater numbers of older adults having diabetes and hypertension, both of which are major factors and comorbidities for kidney disease.”

The study findings are limited by their basis in medical records, which precludes the assessment of classification validity, particularly for the diagnosis of acute renal failure, because no standardized diagnostic criterion exists, the authors noted. Additionally, the study data are subject to sampling variability and do not allow for race- or ethnicity-based analyses, they said.

Limitations notwithstanding, the findings underscore the need for screening and early detection of kidney disease, as well as the need for standardized diagnostic criteria for acute renal failure, the authors wrote.

The rate of hospitalizations for kidney disease has risen sharply over the past 25 years, and the elevation has been driven primarily by a significant increase in the proportion of hospitalizations associated with acute renal failure relative to chronic kidney disease, particularly among older Americans, according to the Centers for Disease Control and Prevention.

An analysis of data from a national probability survey showed that the number of patients hospitalized with a diagnosis of either chronic or acute kidney disease rose from 416,000 in 1980 to 1.6 million in 2005, reported Dr. Nicole T. Flowers, a medical epidemiologist at the CDC, and her colleagues. Consistent increases in the rate of acute renal failure over the 25-year period, with smaller increases in the rate of chronic kidney failure, led to the shift in type of kidney disease most commonly associated with hospitalizations. The age-adjusted rate per 10,000 population for hospitalization for acute renal failure increased from 1.8 in 1980 to 36.5 in 2005. During the same period, the rate of chronic kidney failure rose from 7.4 to 13.8 per 10,000 population, they wrote (MMWR 2008;57:309–12).

Other trends emerging from the National Hospital Discharge Survey for 1980–2005 include consistently higher kidney disease hospitalization rates among men compared with women, a rise in the number of patients aged 65 years and older requiring hospitalization for kidney disease, and an increase in the number of kidney disease hospital discharges associated with a concomitant diagnosis of diabetes mellitus or hypertension.

Although the rates of kidney disease for both sexes increased significantly over the 25-year period, “the rates were consistently 30%-40% higher among men than among women,” the authors reported. Hospitalizations increased in all age groups except for individuals younger than 18 years, they wrote, noting: “An increase of approximately 300% (from 56.2 to 179.3 per 10,000 population) occurred among persons aged 65–74 years, and an increase of approximately 350% (from 119.0 to 393.2 per 10,000 population) occurred among persons aged 75 years and older.”

With respect to concomitant diagnoses, diabetes mellitus was reported as an additional discharge diagnosis for 23.4% of hospitalized kidney disease patients in 1980 and for 27.0% in 2005.

“This proportion peaked at 39.0% in 1996,” the authors wrote. The percentage of hospitalized kidney disease patients with a discharge diagnosis of hypertension rose from 19.6% in 1980 to 41.1% in 2005.

In an accompanying editorial, the CDC suggested that the unexplained increase in hospitalizations associated with acute renal failure “might be attributed to actual increases in [acute renal failure] among hospitalized patients or to changes in the way it is diagnosed, defined, or reflected in hospital discharge codes.” It might also be a function, in part, of the aging of the U.S. population, “with greater numbers of older adults having diabetes and hypertension, both of which are major factors and comorbidities for kidney disease.”

The study findings are limited by their basis in medical records, which precludes the assessment of classification validity, particularly for the diagnosis of acute renal failure, because no standardized diagnostic criterion exists, the authors noted. Additionally, the study data are subject to sampling variability and do not allow for race- or ethnicity-based analyses, they said.

Limitations notwithstanding, the findings underscore the need for screening and early detection of kidney disease, as well as the need for standardized diagnostic criteria for acute renal failure, the authors wrote.

The rate of hospitalizations for kidney disease has risen sharply over the past 25 years, and the elevation has been driven primarily by a significant increase in the proportion of hospitalizations associated with acute renal failure relative to chronic kidney disease, particularly among older Americans, according to the Centers for Disease Control and Prevention.

An analysis of data from a national probability survey showed that the number of patients hospitalized with a diagnosis of either chronic or acute kidney disease rose from 416,000 in 1980 to 1.6 million in 2005, reported Dr. Nicole T. Flowers, a medical epidemiologist at the CDC, and her colleagues. Consistent increases in the rate of acute renal failure over the 25-year period, with smaller increases in the rate of chronic kidney failure, led to the shift in type of kidney disease most commonly associated with hospitalizations. The age-adjusted rate per 10,000 population for hospitalization for acute renal failure increased from 1.8 in 1980 to 36.5 in 2005. During the same period, the rate of chronic kidney failure rose from 7.4 to 13.8 per 10,000 population, they wrote (MMWR 2008;57:309–12).

Other trends emerging from the National Hospital Discharge Survey for 1980–2005 include consistently higher kidney disease hospitalization rates among men compared with women, a rise in the number of patients aged 65 years and older requiring hospitalization for kidney disease, and an increase in the number of kidney disease hospital discharges associated with a concomitant diagnosis of diabetes mellitus or hypertension.

Although the rates of kidney disease for both sexes increased significantly over the 25-year period, “the rates were consistently 30%-40% higher among men than among women,” the authors reported. Hospitalizations increased in all age groups except for individuals younger than 18 years, they wrote, noting: “An increase of approximately 300% (from 56.2 to 179.3 per 10,000 population) occurred among persons aged 65–74 years, and an increase of approximately 350% (from 119.0 to 393.2 per 10,000 population) occurred among persons aged 75 years and older.”

With respect to concomitant diagnoses, diabetes mellitus was reported as an additional discharge diagnosis for 23.4% of hospitalized kidney disease patients in 1980 and for 27.0% in 2005.

“This proportion peaked at 39.0% in 1996,” the authors wrote. The percentage of hospitalized kidney disease patients with a discharge diagnosis of hypertension rose from 19.6% in 1980 to 41.1% in 2005.

In an accompanying editorial, the CDC suggested that the unexplained increase in hospitalizations associated with acute renal failure “might be attributed to actual increases in [acute renal failure] among hospitalized patients or to changes in the way it is diagnosed, defined, or reflected in hospital discharge codes.” It might also be a function, in part, of the aging of the U.S. population, “with greater numbers of older adults having diabetes and hypertension, both of which are major factors and comorbidities for kidney disease.”

The study findings are limited by their basis in medical records, which precludes the assessment of classification validity, particularly for the diagnosis of acute renal failure, because no standardized diagnostic criterion exists, the authors noted. Additionally, the study data are subject to sampling variability and do not allow for race- or ethnicity-based analyses, they said.

Limitations notwithstanding, the findings underscore the need for screening and early detection of kidney disease, as well as the need for standardized diagnostic criteria for acute renal failure, the authors wrote.

CHICAGO — Temporomandibular joint involvement is highly prevalent in children with new-onset juvenile idiopathic arthritis, but the absence of clinical symptoms or detectable swelling associated with the jaw condition in its early stages can delay diagnosis and timely treatment.

Recent studies have shown that as many as half, and possibly more, of all children with JIA have imaging evidence of temporomandibular joint (TMJ) arthritis, although few display clinical signs, such as impaired chewing ability, limited maximal mouth opening, pain, or crepitation, said Dr. Randy Q. Cron of the University of Alabama at Birmingham. “Usually we catch [TMJ arthritis] late, when we do some imaging because a patient's jaw looks smaller or is off center. Even though these kids have previously had normal findings on jaw examination, we see on MRI that they're pretty far gone in terms of effusions and condylar erosions.”

To minimize the potential for micrognathia and malocclusion—and the associated aesthetic and functional sequelae of both—“screening for jaw involvement should be undertaken at the time of JIA diagnosis,” Dr. Cron recommended. And because a history review and physical examination are insufficient screening measures, “medical imaging (specifically MRI, when possible) is required for an accurate diagnosis,” he said.

Although there has been some suggestion that ultrasound might be a reasonable screening tool, a prospective study by Dr. Pamela F. Weiss at the Children's Hospital of Philadelphia, Dr. Cron, and colleagues suggests that ultrasound is not up to the task. The study was designed to determine the point prevalence of TMJ arthritis at disease onset in children with JIA using both MRI and ultrasound, said Dr. Cron. A secondary aim “was to compare MRI versus ultrasound for diagnosing TMJ arthritis,” he said.

The study included 32 children (median age, 8.6 years) diagnosed with JIA between January 2005 and April 2007 who were prospectively evaluated for TMJ arthritis via questionnaires and physical examination to assess jaw pain and disability. The TMJs of all of the patients were imaged with both MRI and ultrasound within 8 weeks of diagnosis (Arthritis Rheum. 2008;58:1189-96).

Of the 32 patients, 75% were diagnosed with acute TMJ arthritis by MRI; none of the cases was identified by ultrasound, said Dr. Cron. Chronic TMJ arthritis was detected by MRI in 69% of the children, whereas ultrasound picked up chronic TMJ in only 28% of them, he said. Of the patients with acute TMJ arthritis, “more than 70% were asymptomatic and more than [60%] had normal findings on jaw examination, he noted.

The investigators also evaluated response to treatment with CT-guided intra-articular steroid injections among patients with TMJ arthritis identified on MRI, and determined that 56% of patients with acute disease—more than half of whom had been asymptomatic at baseline—had an improved maximal incisal opening after corticosteroid injection, said Dr. Cron.

In a previous retrospective study by the same research group, intra-articular corticosteroid injection was associated with increased mouth opening, decreased TMJ pain, and decreased TMJ effusions as detected by MRI in 23 patients in whom preinjection evidence of effusions (13 patients), bony erosions (19 patients), and condylar flattening (17 patients) was observed, Dr. Cron noted (Arthritis. Rheum, 2005;52:3563-9). Similarly, in a clinical review of a CT-guided percutaneous steroid injection technique in 15 JIA patients with TMJ arthropathy, the treatment resulted in substantial relief of clinical symptoms, when present, as well as resolution of related imaging abnormalities (AJR Am. J. Roentgenol. 2007;188:182-6).

These findings suggest that treating TMJ arthritis before the onset of obvious bone changes, facial asymmetry, and limited mobility can preserve normal jaw structure and function of JIA patients until they achieve disease remission, Dr. Cron said at a symposium sponsored by the American College of Rheumatology. Doing so, however, requires an awareness of the high prevalence of the condition as well as the implementation of a routine screening protocol in all new-onset JIA patients. “As clinicians, we see these patients every day. We have to remember that just because they're not complaining about pain or problems [in their jaw], it does not mean there's not inflammation that continues to rage on. Most likely, there is, and we have to be ready to treat it,” he said.

Intra-Articular Injection Pearls

For optimal safety and efficacy, CT-guided intra-articular corticosteroid injection of the TMJ of children with juvenile idiopathic arthritis should be performed in conjunction with an experienced pediatric interventional radiologist, stressed Dr. Randy Q. Cron.

The following technique, which was evaluated in a recently published study by radiologist Dr. Anne Marie Cahill of the Children's Hospital of Philadelphia, Dr. Cron, and colleagues, “is safe and technically successful, even in patients with joint space deformities,” according to Dr. Cron.

▸ Position the child supine in CT scanner with head rotated 45 degrees away from the TMJ to be injected.

▸ Perform axial CT scan through the area of interest.

▸ Prepare access site anterior to tragus with povidone-iodine and alcohol and anesthetize it with 1% lidocaine using a 30-gauge needle.

▸ Use CT to confirm needle placement for steroid injection in mandibular fossa.

▸ Inject long-acting steroid (1 mL triamcinolone acetonide) into TMJ with an 18- or 21-gauge needle.

In the aforementioned investigation, all of the procedures were performed on an outpatient basis, and none of the known potential immediate reactions to intra-articular steroid injection—such as pain, headache, joint infection, or loss of subcutaneous fat—was observed, according to the authors.

CHICAGO — Temporomandibular joint involvement is highly prevalent in children with new-onset juvenile idiopathic arthritis, but the absence of clinical symptoms or detectable swelling associated with the jaw condition in its early stages can delay diagnosis and timely treatment.

Recent studies have shown that as many as half, and possibly more, of all children with JIA have imaging evidence of temporomandibular joint (TMJ) arthritis, although few display clinical signs, such as impaired chewing ability, limited maximal mouth opening, pain, or crepitation, said Dr. Randy Q. Cron of the University of Alabama at Birmingham. “Usually we catch [TMJ arthritis] late, when we do some imaging because a patient's jaw looks smaller or is off center. Even though these kids have previously had normal findings on jaw examination, we see on MRI that they're pretty far gone in terms of effusions and condylar erosions.”

To minimize the potential for micrognathia and malocclusion—and the associated aesthetic and functional sequelae of both—“screening for jaw involvement should be undertaken at the time of JIA diagnosis,” Dr. Cron recommended. And because a history review and physical examination are insufficient screening measures, “medical imaging (specifically MRI, when possible) is required for an accurate diagnosis,” he said.

Although there has been some suggestion that ultrasound might be a reasonable screening tool, a prospective study by Dr. Pamela F. Weiss at the Children's Hospital of Philadelphia, Dr. Cron, and colleagues suggests that ultrasound is not up to the task. The study was designed to determine the point prevalence of TMJ arthritis at disease onset in children with JIA using both MRI and ultrasound, said Dr. Cron. A secondary aim “was to compare MRI versus ultrasound for diagnosing TMJ arthritis,” he said.

The study included 32 children (median age, 8.6 years) diagnosed with JIA between January 2005 and April 2007 who were prospectively evaluated for TMJ arthritis via questionnaires and physical examination to assess jaw pain and disability. The TMJs of all of the patients were imaged with both MRI and ultrasound within 8 weeks of diagnosis (Arthritis Rheum. 2008;58:1189-96).

Of the 32 patients, 75% were diagnosed with acute TMJ arthritis by MRI; none of the cases was identified by ultrasound, said Dr. Cron. Chronic TMJ arthritis was detected by MRI in 69% of the children, whereas ultrasound picked up chronic TMJ in only 28% of them, he said. Of the patients with acute TMJ arthritis, “more than 70% were asymptomatic and more than [60%] had normal findings on jaw examination, he noted.

The investigators also evaluated response to treatment with CT-guided intra-articular steroid injections among patients with TMJ arthritis identified on MRI, and determined that 56% of patients with acute disease—more than half of whom had been asymptomatic at baseline—had an improved maximal incisal opening after corticosteroid injection, said Dr. Cron.

In a previous retrospective study by the same research group, intra-articular corticosteroid injection was associated with increased mouth opening, decreased TMJ pain, and decreased TMJ effusions as detected by MRI in 23 patients in whom preinjection evidence of effusions (13 patients), bony erosions (19 patients), and condylar flattening (17 patients) was observed, Dr. Cron noted (Arthritis. Rheum, 2005;52:3563-9). Similarly, in a clinical review of a CT-guided percutaneous steroid injection technique in 15 JIA patients with TMJ arthropathy, the treatment resulted in substantial relief of clinical symptoms, when present, as well as resolution of related imaging abnormalities (AJR Am. J. Roentgenol. 2007;188:182-6).

These findings suggest that treating TMJ arthritis before the onset of obvious bone changes, facial asymmetry, and limited mobility can preserve normal jaw structure and function of JIA patients until they achieve disease remission, Dr. Cron said at a symposium sponsored by the American College of Rheumatology. Doing so, however, requires an awareness of the high prevalence of the condition as well as the implementation of a routine screening protocol in all new-onset JIA patients. “As clinicians, we see these patients every day. We have to remember that just because they're not complaining about pain or problems [in their jaw], it does not mean there's not inflammation that continues to rage on. Most likely, there is, and we have to be ready to treat it,” he said.

Intra-Articular Injection Pearls

For optimal safety and efficacy, CT-guided intra-articular corticosteroid injection of the TMJ of children with juvenile idiopathic arthritis should be performed in conjunction with an experienced pediatric interventional radiologist, stressed Dr. Randy Q. Cron.

The following technique, which was evaluated in a recently published study by radiologist Dr. Anne Marie Cahill of the Children's Hospital of Philadelphia, Dr. Cron, and colleagues, “is safe and technically successful, even in patients with joint space deformities,” according to Dr. Cron.

▸ Position the child supine in CT scanner with head rotated 45 degrees away from the TMJ to be injected.

▸ Perform axial CT scan through the area of interest.

▸ Prepare access site anterior to tragus with povidone-iodine and alcohol and anesthetize it with 1% lidocaine using a 30-gauge needle.

▸ Use CT to confirm needle placement for steroid injection in mandibular fossa.

▸ Inject long-acting steroid (1 mL triamcinolone acetonide) into TMJ with an 18- or 21-gauge needle.

In the aforementioned investigation, all of the procedures were performed on an outpatient basis, and none of the known potential immediate reactions to intra-articular steroid injection—such as pain, headache, joint infection, or loss of subcutaneous fat—was observed, according to the authors.

CHICAGO — Temporomandibular joint involvement is highly prevalent in children with new-onset juvenile idiopathic arthritis, but the absence of clinical symptoms or detectable swelling associated with the jaw condition in its early stages can delay diagnosis and timely treatment.

Recent studies have shown that as many as half, and possibly more, of all children with JIA have imaging evidence of temporomandibular joint (TMJ) arthritis, although few display clinical signs, such as impaired chewing ability, limited maximal mouth opening, pain, or crepitation, said Dr. Randy Q. Cron of the University of Alabama at Birmingham. “Usually we catch [TMJ arthritis] late, when we do some imaging because a patient's jaw looks smaller or is off center. Even though these kids have previously had normal findings on jaw examination, we see on MRI that they're pretty far gone in terms of effusions and condylar erosions.”

To minimize the potential for micrognathia and malocclusion—and the associated aesthetic and functional sequelae of both—“screening for jaw involvement should be undertaken at the time of JIA diagnosis,” Dr. Cron recommended. And because a history review and physical examination are insufficient screening measures, “medical imaging (specifically MRI, when possible) is required for an accurate diagnosis,” he said.

Although there has been some suggestion that ultrasound might be a reasonable screening tool, a prospective study by Dr. Pamela F. Weiss at the Children's Hospital of Philadelphia, Dr. Cron, and colleagues suggests that ultrasound is not up to the task. The study was designed to determine the point prevalence of TMJ arthritis at disease onset in children with JIA using both MRI and ultrasound, said Dr. Cron. A secondary aim “was to compare MRI versus ultrasound for diagnosing TMJ arthritis,” he said.

The study included 32 children (median age, 8.6 years) diagnosed with JIA between January 2005 and April 2007 who were prospectively evaluated for TMJ arthritis via questionnaires and physical examination to assess jaw pain and disability. The TMJs of all of the patients were imaged with both MRI and ultrasound within 8 weeks of diagnosis (Arthritis Rheum. 2008;58:1189-96).

Of the 32 patients, 75% were diagnosed with acute TMJ arthritis by MRI; none of the cases was identified by ultrasound, said Dr. Cron. Chronic TMJ arthritis was detected by MRI in 69% of the children, whereas ultrasound picked up chronic TMJ in only 28% of them, he said. Of the patients with acute TMJ arthritis, “more than 70% were asymptomatic and more than [60%] had normal findings on jaw examination, he noted.

The investigators also evaluated response to treatment with CT-guided intra-articular steroid injections among patients with TMJ arthritis identified on MRI, and determined that 56% of patients with acute disease—more than half of whom had been asymptomatic at baseline—had an improved maximal incisal opening after corticosteroid injection, said Dr. Cron.

In a previous retrospective study by the same research group, intra-articular corticosteroid injection was associated with increased mouth opening, decreased TMJ pain, and decreased TMJ effusions as detected by MRI in 23 patients in whom preinjection evidence of effusions (13 patients), bony erosions (19 patients), and condylar flattening (17 patients) was observed, Dr. Cron noted (Arthritis. Rheum, 2005;52:3563-9). Similarly, in a clinical review of a CT-guided percutaneous steroid injection technique in 15 JIA patients with TMJ arthropathy, the treatment resulted in substantial relief of clinical symptoms, when present, as well as resolution of related imaging abnormalities (AJR Am. J. Roentgenol. 2007;188:182-6).

These findings suggest that treating TMJ arthritis before the onset of obvious bone changes, facial asymmetry, and limited mobility can preserve normal jaw structure and function of JIA patients until they achieve disease remission, Dr. Cron said at a symposium sponsored by the American College of Rheumatology. Doing so, however, requires an awareness of the high prevalence of the condition as well as the implementation of a routine screening protocol in all new-onset JIA patients. “As clinicians, we see these patients every day. We have to remember that just because they're not complaining about pain or problems [in their jaw], it does not mean there's not inflammation that continues to rage on. Most likely, there is, and we have to be ready to treat it,” he said.

Intra-Articular Injection Pearls

For optimal safety and efficacy, CT-guided intra-articular corticosteroid injection of the TMJ of children with juvenile idiopathic arthritis should be performed in conjunction with an experienced pediatric interventional radiologist, stressed Dr. Randy Q. Cron.

The following technique, which was evaluated in a recently published study by radiologist Dr. Anne Marie Cahill of the Children's Hospital of Philadelphia, Dr. Cron, and colleagues, “is safe and technically successful, even in patients with joint space deformities,” according to Dr. Cron.

▸ Position the child supine in CT scanner with head rotated 45 degrees away from the TMJ to be injected.

▸ Perform axial CT scan through the area of interest.

▸ Prepare access site anterior to tragus with povidone-iodine and alcohol and anesthetize it with 1% lidocaine using a 30-gauge needle.

▸ Use CT to confirm needle placement for steroid injection in mandibular fossa.

▸ Inject long-acting steroid (1 mL triamcinolone acetonide) into TMJ with an 18- or 21-gauge needle.

In the aforementioned investigation, all of the procedures were performed on an outpatient basis, and none of the known potential immediate reactions to intra-articular steroid injection—such as pain, headache, joint infection, or loss of subcutaneous fat—was observed, according to the authors.

BOSTON — Long-term exposure to antiretroviral therapy appears to convey substantial metabolic risk to adolescents and young adults with HIV infection, according to a National Institutes of Health study.

In a cross-sectional investigation of 40 HIV-infected patients aged 11–27 years who acquired HIV in infancy or childhood and had been exposed to antiretroviral therapy (ART), a majority of study participants had impaired glucose tolerance and other metabolic abnormalities, said Dr. Colleen M. Hadigan of the National Institute of Allergy and Infectious Diseases and her colleagues.

Whereas the medical literature is replete with studies linking such metabolic complications as dyslipidemia, lipodystrophy, and insulin resistance to long-term ART in HIV-infected adults, the pediatric literature is relatively sparse, and comprehensive reviews of metabolic consequences of ART in children are rare, Dr. Hadigan reported at the 15th Conference on Retroviruses and Opportunistic Infections.

The current study was designed to characterize the extent of metabolic abnormalities in a cohort of adolescents who acquired HIV infection perinatally or in childhood, she said.

All study subjects were ART experienced, with a mean treatment duration of 14 years, and all had current or past protease inhibitor and stavudine exposure. At the time of the investigation, 88% of the patients were receiving a protease inhibitor. At enrollment, approximately half of the patients had an HIV RNA of fewer than 50 copies per milliliter; the mean CD4 count was 665.

According to the study protocol, all of the subjects completed oral glucose tolerance testing and fasting insulin and lipid studies, and all underwent anthropometric assessments including whole body dual-energy x-ray absorptiometry (DXA) scans.

An analysis of the results showed impaired glucose tolerance in 20% of the subjects. The mean fasting insulin level for the group was 18 IU/mL, the mean glucose level was 86 mg/dL, and the mean homeostatic model for assessment of insulin resistance (HOMA) was 3.9, Dr. Hadigan reported at the conference, which was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

Approximately 38% of the subjects had a HOMA value greater than 4.0, and thus met the criteria for insulin resistance, Dr. Hadigan said. In addition, 50% had elevated triglyceride levels (greater than 150 mg/dL), 53% had low levels of HDL cholesterol (less than 50 mg/dL for females and less than 40 mg/dL for males), and 24% had an elevated total cholesterol level (greater than 200 mg/dL).

With respect to body mass index (BMI) and body fat, the mean BMI was 22 kg/m

Although none of the subjects had type 2 diabetes, the results suggest that long-term exposure to ART may substantially increase their risk for that outcome as well as for cardiovascular disease, Dr. Hadigan warned. As such, “these findings warrant careful monitoring in this population, as well as further research.”

BOSTON — Long-term exposure to antiretroviral therapy appears to convey substantial metabolic risk to adolescents and young adults with HIV infection, according to a National Institutes of Health study.

In a cross-sectional investigation of 40 HIV-infected patients aged 11–27 years who acquired HIV in infancy or childhood and had been exposed to antiretroviral therapy (ART), a majority of study participants had impaired glucose tolerance and other metabolic abnormalities, said Dr. Colleen M. Hadigan of the National Institute of Allergy and Infectious Diseases and her colleagues.

Whereas the medical literature is replete with studies linking such metabolic complications as dyslipidemia, lipodystrophy, and insulin resistance to long-term ART in HIV-infected adults, the pediatric literature is relatively sparse, and comprehensive reviews of metabolic consequences of ART in children are rare, Dr. Hadigan reported at the 15th Conference on Retroviruses and Opportunistic Infections.

The current study was designed to characterize the extent of metabolic abnormalities in a cohort of adolescents who acquired HIV infection perinatally or in childhood, she said.

All study subjects were ART experienced, with a mean treatment duration of 14 years, and all had current or past protease inhibitor and stavudine exposure. At the time of the investigation, 88% of the patients were receiving a protease inhibitor. At enrollment, approximately half of the patients had an HIV RNA of fewer than 50 copies per milliliter; the mean CD4 count was 665.

According to the study protocol, all of the subjects completed oral glucose tolerance testing and fasting insulin and lipid studies, and all underwent anthropometric assessments including whole body dual-energy x-ray absorptiometry (DXA) scans.

An analysis of the results showed impaired glucose tolerance in 20% of the subjects. The mean fasting insulin level for the group was 18 IU/mL, the mean glucose level was 86 mg/dL, and the mean homeostatic model for assessment of insulin resistance (HOMA) was 3.9, Dr. Hadigan reported at the conference, which was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

Approximately 38% of the subjects had a HOMA value greater than 4.0, and thus met the criteria for insulin resistance, Dr. Hadigan said. In addition, 50% had elevated triglyceride levels (greater than 150 mg/dL), 53% had low levels of HDL cholesterol (less than 50 mg/dL for females and less than 40 mg/dL for males), and 24% had an elevated total cholesterol level (greater than 200 mg/dL).

With respect to body mass index (BMI) and body fat, the mean BMI was 22 kg/m

Although none of the subjects had type 2 diabetes, the results suggest that long-term exposure to ART may substantially increase their risk for that outcome as well as for cardiovascular disease, Dr. Hadigan warned. As such, “these findings warrant careful monitoring in this population, as well as further research.”

BOSTON — Long-term exposure to antiretroviral therapy appears to convey substantial metabolic risk to adolescents and young adults with HIV infection, according to a National Institutes of Health study.

In a cross-sectional investigation of 40 HIV-infected patients aged 11–27 years who acquired HIV in infancy or childhood and had been exposed to antiretroviral therapy (ART), a majority of study participants had impaired glucose tolerance and other metabolic abnormalities, said Dr. Colleen M. Hadigan of the National Institute of Allergy and Infectious Diseases and her colleagues.

Whereas the medical literature is replete with studies linking such metabolic complications as dyslipidemia, lipodystrophy, and insulin resistance to long-term ART in HIV-infected adults, the pediatric literature is relatively sparse, and comprehensive reviews of metabolic consequences of ART in children are rare, Dr. Hadigan reported at the 15th Conference on Retroviruses and Opportunistic Infections.

The current study was designed to characterize the extent of metabolic abnormalities in a cohort of adolescents who acquired HIV infection perinatally or in childhood, she said.

All study subjects were ART experienced, with a mean treatment duration of 14 years, and all had current or past protease inhibitor and stavudine exposure. At the time of the investigation, 88% of the patients were receiving a protease inhibitor. At enrollment, approximately half of the patients had an HIV RNA of fewer than 50 copies per milliliter; the mean CD4 count was 665.

According to the study protocol, all of the subjects completed oral glucose tolerance testing and fasting insulin and lipid studies, and all underwent anthropometric assessments including whole body dual-energy x-ray absorptiometry (DXA) scans.

An analysis of the results showed impaired glucose tolerance in 20% of the subjects. The mean fasting insulin level for the group was 18 IU/mL, the mean glucose level was 86 mg/dL, and the mean homeostatic model for assessment of insulin resistance (HOMA) was 3.9, Dr. Hadigan reported at the conference, which was sponsored by the Foundation for Retrovirology and Human Health and the Centers for Disease Control and Prevention.

Approximately 38% of the subjects had a HOMA value greater than 4.0, and thus met the criteria for insulin resistance, Dr. Hadigan said. In addition, 50% had elevated triglyceride levels (greater than 150 mg/dL), 53% had low levels of HDL cholesterol (less than 50 mg/dL for females and less than 40 mg/dL for males), and 24% had an elevated total cholesterol level (greater than 200 mg/dL).

With respect to body mass index (BMI) and body fat, the mean BMI was 22 kg/m

Although none of the subjects had type 2 diabetes, the results suggest that long-term exposure to ART may substantially increase their risk for that outcome as well as for cardiovascular disease, Dr. Hadigan warned. As such, “these findings warrant careful monitoring in this population, as well as further research.”

BOSTON – The risk of suicide in older adults is higher among patients with cancer than among those with other medical illnesses, even after controlling for psychiatric illness and the risk of dying within 1 year, Dr. Matthew Miller reported at the annual meeting of the American Association of Suicidology.

Multiple studies have demonstrated that physical illness is a common antecedent to suicide in elderly people, and it has been proposed that elderly cancer patients are especially vulnerable, possibly because of an increased risk of depression, according to Dr. Miller of the Harvard School of Public Health, Boston.

To determine whether the risk of suicide is greater among elderly patients with cancer than among those with other medical illnesses, Dr. Miller and his colleagues evaluated the suicide risk associated with medical illness among older Americans in a case control study.

The investigators used health care utilization data linked to prescription and mortality files for a cohort of New Jersey Medicare recipients who received prescription medication for any medical illness during the period of study, and determined that, of 1,408 Medicare recipients aged 65 years and older who were receiving pharmaceutical assistance from 1994 to 2002, 128 died by suicide, predominantly by firearm. For comparative analysis, the remaining 1,280 patients were frequency-matched to case patients for age, gender, and race, Dr. Miller said.

In a multivariate model adjusted for age, sex, race, medical and psychiatric comorbidity, and the use of prescription medications, “the only medical condition associated with suicide was cancer,” Dr. Miller said, noting that cancer patients had a more than twofold greater risk of suicide.

Diagnoses of affective disorder and anxiety/personality disorder were similarly associated with suicide in the adjusted model, with respective odds ratios of 2.3 and 2.2, as were treatment with antidepressants and treatment with opioid analgesics, with respective odds ratios of 2.0 and 1.6, he said.

The reasons behind the increased risk of suicide among cancer patients require further empirical assessment, Dr. Miller said in an interview. “I suspect, based on work by other investigators, that hopelessness plays a large role, and that functional limitations and social support contribute as well.”

It's possible, he continued, “that some insight can be found in Susan Sontag's provocative musings in “Illness as Metaphor and AIDS and Its Metaphors” (New York: St. Martin's Press, 2001), which suggest that a component of the disproportionate risk of suicide in cancer patients is related to the premium placed on the prospect of a life lived free of cancer, a notion epitomized and reinforced by the words commonly used to describe the goals of cancer therapy, such as “cure” and “disease-free survival.”

It is also possible that the cancer itself or the chemotherapy used to treat the cancer could result in mental status changes that are risk factors for suicide; “unfortunately, our data are too sparse to address this speculation,” he stated.

With respect to prevention, “because hopelessness and depression are not identical, clinical interventions may need to address both of these dimensions of psychic conflict,” Dr. Miller said. “Certainly, addressing underlying depression is important, and a first step would be to rigorously screen for depression among patients diagnosed with cancer, especially soon after the diagnosis and at critical clinical junctures.”

And although interventions aimed at addressing hopelessness in cancer patients have not been studied in any detail, “psychotherapeutic interventions that focus on existential issues and focus on attenuating pessimistic cognitions or even spirituality centered interventions to address existential conflicts may help decrease hopelessness,” he said.

Finally, given the established link between access to firearms and suicide, both in this cohort and in the United States as a whole (J. Trauma 2007;62:1029-34), lethal-means counseling should be considered for at-risk patients, according to Dr. Miller.

“Lethal-means counseling refers to speaking with patients at heightened risk for suicide and their families about reducing their access to firearms,” he said.

“The goal of such counseling is to reduce the odds that a suicide attempt ends in death.”

BOSTON – The risk of suicide in older adults is higher among patients with cancer than among those with other medical illnesses, even after controlling for psychiatric illness and the risk of dying within 1 year, Dr. Matthew Miller reported at the annual meeting of the American Association of Suicidology.

Multiple studies have demonstrated that physical illness is a common antecedent to suicide in elderly people, and it has been proposed that elderly cancer patients are especially vulnerable, possibly because of an increased risk of depression, according to Dr. Miller of the Harvard School of Public Health, Boston.

To determine whether the risk of suicide is greater among elderly patients with cancer than among those with other medical illnesses, Dr. Miller and his colleagues evaluated the suicide risk associated with medical illness among older Americans in a case control study.

The investigators used health care utilization data linked to prescription and mortality files for a cohort of New Jersey Medicare recipients who received prescription medication for any medical illness during the period of study, and determined that, of 1,408 Medicare recipients aged 65 years and older who were receiving pharmaceutical assistance from 1994 to 2002, 128 died by suicide, predominantly by firearm. For comparative analysis, the remaining 1,280 patients were frequency-matched to case patients for age, gender, and race, Dr. Miller said.

In a multivariate model adjusted for age, sex, race, medical and psychiatric comorbidity, and the use of prescription medications, “the only medical condition associated with suicide was cancer,” Dr. Miller said, noting that cancer patients had a more than twofold greater risk of suicide.

Diagnoses of affective disorder and anxiety/personality disorder were similarly associated with suicide in the adjusted model, with respective odds ratios of 2.3 and 2.2, as were treatment with antidepressants and treatment with opioid analgesics, with respective odds ratios of 2.0 and 1.6, he said.

The reasons behind the increased risk of suicide among cancer patients require further empirical assessment, Dr. Miller said in an interview. “I suspect, based on work by other investigators, that hopelessness plays a large role, and that functional limitations and social support contribute as well.”

It's possible, he continued, “that some insight can be found in Susan Sontag's provocative musings in “Illness as Metaphor and AIDS and Its Metaphors” (New York: St. Martin's Press, 2001), which suggest that a component of the disproportionate risk of suicide in cancer patients is related to the premium placed on the prospect of a life lived free of cancer, a notion epitomized and reinforced by the words commonly used to describe the goals of cancer therapy, such as “cure” and “disease-free survival.”

It is also possible that the cancer itself or the chemotherapy used to treat the cancer could result in mental status changes that are risk factors for suicide; “unfortunately, our data are too sparse to address this speculation,” he stated.

With respect to prevention, “because hopelessness and depression are not identical, clinical interventions may need to address both of these dimensions of psychic conflict,” Dr. Miller said. “Certainly, addressing underlying depression is important, and a first step would be to rigorously screen for depression among patients diagnosed with cancer, especially soon after the diagnosis and at critical clinical junctures.”

And although interventions aimed at addressing hopelessness in cancer patients have not been studied in any detail, “psychotherapeutic interventions that focus on existential issues and focus on attenuating pessimistic cognitions or even spirituality centered interventions to address existential conflicts may help decrease hopelessness,” he said.

Finally, given the established link between access to firearms and suicide, both in this cohort and in the United States as a whole (J. Trauma 2007;62:1029-34), lethal-means counseling should be considered for at-risk patients, according to Dr. Miller.

“Lethal-means counseling refers to speaking with patients at heightened risk for suicide and their families about reducing their access to firearms,” he said.

“The goal of such counseling is to reduce the odds that a suicide attempt ends in death.”

BOSTON – The risk of suicide in older adults is higher among patients with cancer than among those with other medical illnesses, even after controlling for psychiatric illness and the risk of dying within 1 year, Dr. Matthew Miller reported at the annual meeting of the American Association of Suicidology.

Multiple studies have demonstrated that physical illness is a common antecedent to suicide in elderly people, and it has been proposed that elderly cancer patients are especially vulnerable, possibly because of an increased risk of depression, according to Dr. Miller of the Harvard School of Public Health, Boston.

To determine whether the risk of suicide is greater among elderly patients with cancer than among those with other medical illnesses, Dr. Miller and his colleagues evaluated the suicide risk associated with medical illness among older Americans in a case control study.

The investigators used health care utilization data linked to prescription and mortality files for a cohort of New Jersey Medicare recipients who received prescription medication for any medical illness during the period of study, and determined that, of 1,408 Medicare recipients aged 65 years and older who were receiving pharmaceutical assistance from 1994 to 2002, 128 died by suicide, predominantly by firearm. For comparative analysis, the remaining 1,280 patients were frequency-matched to case patients for age, gender, and race, Dr. Miller said.

In a multivariate model adjusted for age, sex, race, medical and psychiatric comorbidity, and the use of prescription medications, “the only medical condition associated with suicide was cancer,” Dr. Miller said, noting that cancer patients had a more than twofold greater risk of suicide.

Diagnoses of affective disorder and anxiety/personality disorder were similarly associated with suicide in the adjusted model, with respective odds ratios of 2.3 and 2.2, as were treatment with antidepressants and treatment with opioid analgesics, with respective odds ratios of 2.0 and 1.6, he said.

The reasons behind the increased risk of suicide among cancer patients require further empirical assessment, Dr. Miller said in an interview. “I suspect, based on work by other investigators, that hopelessness plays a large role, and that functional limitations and social support contribute as well.”

It's possible, he continued, “that some insight can be found in Susan Sontag's provocative musings in “Illness as Metaphor and AIDS and Its Metaphors” (New York: St. Martin's Press, 2001), which suggest that a component of the disproportionate risk of suicide in cancer patients is related to the premium placed on the prospect of a life lived free of cancer, a notion epitomized and reinforced by the words commonly used to describe the goals of cancer therapy, such as “cure” and “disease-free survival.”

It is also possible that the cancer itself or the chemotherapy used to treat the cancer could result in mental status changes that are risk factors for suicide; “unfortunately, our data are too sparse to address this speculation,” he stated.

With respect to prevention, “because hopelessness and depression are not identical, clinical interventions may need to address both of these dimensions of psychic conflict,” Dr. Miller said. “Certainly, addressing underlying depression is important, and a first step would be to rigorously screen for depression among patients diagnosed with cancer, especially soon after the diagnosis and at critical clinical junctures.”

And although interventions aimed at addressing hopelessness in cancer patients have not been studied in any detail, “psychotherapeutic interventions that focus on existential issues and focus on attenuating pessimistic cognitions or even spirituality centered interventions to address existential conflicts may help decrease hopelessness,” he said.

Finally, given the established link between access to firearms and suicide, both in this cohort and in the United States as a whole (J. Trauma 2007;62:1029-34), lethal-means counseling should be considered for at-risk patients, according to Dr. Miller.

“Lethal-means counseling refers to speaking with patients at heightened risk for suicide and their families about reducing their access to firearms,” he said.

“The goal of such counseling is to reduce the odds that a suicide attempt ends in death.”

BOSTON – Failure to use a developmental framework when assessing mental illness in children and adolescents with intellectual disabilities can hinder the accurate diagnosis of psychiatric disorders, and lead to inappropriate and possibly dangerous treatment, according to Lauren R. Charlot, Ph.D.

“It's important to consider the ways in which an individual's developmental stage affects his or her behavior and thoughts,” Dr. Charlot said at the annual meeting of the American Society for Adolescent Psychiatry.

“Some symptoms or behaviors that would seem pathologic for a typically developing individual may be 'typical' for a person with a particular set of skills and challenges, especially when under stress,” said Dr. Charlot, of the department of psychiatry at the University of Massachusetts, Worcester.

For example, she said, an adolescent with similar cognitive features to a typically developing preschool-age child might engage in self-talk–talking out loud to himself or herself–under stress. “Developmentally, this behavior is appropriate, but if you don't apply a developmental perspective, it seems abnormal and could easily be mistaken for psychotic ideation.”

The most important consideration when evaluating individuals with intellectual delays is the link between developmental stage and cognitive processes. Studies have identified multiple developmental effects on psychopathology in people with intellectual disabilities, Dr. Charlot noted. Among the developmental effects most likely to have an impact on psychiatric evaluation in this patient population are:

▸ Magical thinking, characterized by poor distinctions between fantasy and reality. “These kids may be talking to people who are not present, and they may be expressing wishes as beliefs,” Dr. Charlot said. Unfortunately, she added, “this behavior is often misconstrued as hallucinations or delusions,” even though it is a consequence of cognitive development rather than psychotic thinking.

▸ Prelogical thinking, which is characterized by primitive, incomplete thought processes and may present as seemingly tangential rambling. Normal among preschoolers, this mode of thought can be symptomatic of mental illness–particularly schizophrenia–in typically developing adolescents and adults, Dr. Charlot said. “This type of prelogical thinking is common at baseline in people with intellectual delays, and it tends to get exaggerated when they're under stress, which is often reported as 'racing thoughts.' But it's not a consequence of psychosis. It relates to an inability to understand logical relationships between subjects,” she said.

▸ Concrete thinking, whereby language and perceptions are interpreted literally. The limited ability to understand abstract language and ideas can lead individuals to misinterpret questions that are asked of them, which could be perceived as an indication of disturbed thought, Dr. Charlot said.

▸ Egocentrism, or the tendency to assume that everyone shares one's own thoughts and the inability to understand the consequences of one's own behavior on others. In normally developing children, egocentric behavior begins to wane after toddler and preschool stages. Therefore, when it presents in adolescents, it can be misconstrued as narcissistic or oppositional behavior, according to Dr. Charlot.

To avoid the “trap” of perceiving developmentally driven behaviors as symptomatic of mental illness in individuals with intellectual disabilities, “You need to ask the question: 'what is usual behavior for this patient?'” Dr. Charlot stressed. “Because the clinical population is highly heterogenous, you need to know what the individual person's baseline [behavior] is. You cannot use general population reference group [data] to determine that a symptom or symptoms are evidence of psychosis or other psychopathology.”

Additionally, Dr. Charlot continued, “ask yourself if the behaviors and symptoms are pathologic for a person functioning at this developmental level.” For example, if you are assessing an adolescent who appears labile and “all over the place,” she said, “that's not that unusual for an intellectually disabled individual who is experiencing stress.”

Before assuming that alterations in mood and behavior are indicative of a psychiatric disorder in adolescents with intellectual impairment, “hunt for possible sources of physical distress,” Dr. Charlot said.

Among the many medical problems that can manifest as behavioral issues are constipation, gastroesophageal reflux disease, seizure disorder, hypothyroidism, hypertension, anemia, candidiasis, urinary tract infection, diabetes, hypercholesterolemia, and obesity, she said, adding, “I can't tell you how many cases of adolescents with reported severe, aggressive behavior turned out to be constipated.”

Often, because of poor language skills, these individuals are unable to articulate physical complaints, resulting in agitation, which may then be attributed to a psychiatric disorder, she said at the meeting cosponsored by the University of Texas at Dallas.

Finally, if and when a psychiatric syndrome is identified, “be careful not to automatically attribute any future alterations in mental status or behavior as being secondary to the psychiatric problem,” Dr. Charlot said.

Under all circumstances, “comprehensive treatment should be directly derived from comprehensive assessment.”

BOSTON – Failure to use a developmental framework when assessing mental illness in children and adolescents with intellectual disabilities can hinder the accurate diagnosis of psychiatric disorders, and lead to inappropriate and possibly dangerous treatment, according to Lauren R. Charlot, Ph.D.

“It's important to consider the ways in which an individual's developmental stage affects his or her behavior and thoughts,” Dr. Charlot said at the annual meeting of the American Society for Adolescent Psychiatry.

“Some symptoms or behaviors that would seem pathologic for a typically developing individual may be 'typical' for a person with a particular set of skills and challenges, especially when under stress,” said Dr. Charlot, of the department of psychiatry at the University of Massachusetts, Worcester.

For example, she said, an adolescent with similar cognitive features to a typically developing preschool-age child might engage in self-talk–talking out loud to himself or herself–under stress. “Developmentally, this behavior is appropriate, but if you don't apply a developmental perspective, it seems abnormal and could easily be mistaken for psychotic ideation.”

The most important consideration when evaluating individuals with intellectual delays is the link between developmental stage and cognitive processes. Studies have identified multiple developmental effects on psychopathology in people with intellectual disabilities, Dr. Charlot noted. Among the developmental effects most likely to have an impact on psychiatric evaluation in this patient population are:

▸ Magical thinking, characterized by poor distinctions between fantasy and reality. “These kids may be talking to people who are not present, and they may be expressing wishes as beliefs,” Dr. Charlot said. Unfortunately, she added, “this behavior is often misconstrued as hallucinations or delusions,” even though it is a consequence of cognitive development rather than psychotic thinking.

▸ Prelogical thinking, which is characterized by primitive, incomplete thought processes and may present as seemingly tangential rambling. Normal among preschoolers, this mode of thought can be symptomatic of mental illness–particularly schizophrenia–in typically developing adolescents and adults, Dr. Charlot said. “This type of prelogical thinking is common at baseline in people with intellectual delays, and it tends to get exaggerated when they're under stress, which is often reported as 'racing thoughts.' But it's not a consequence of psychosis. It relates to an inability to understand logical relationships between subjects,” she said.

▸ Concrete thinking, whereby language and perceptions are interpreted literally. The limited ability to understand abstract language and ideas can lead individuals to misinterpret questions that are asked of them, which could be perceived as an indication of disturbed thought, Dr. Charlot said.

▸ Egocentrism, or the tendency to assume that everyone shares one's own thoughts and the inability to understand the consequences of one's own behavior on others. In normally developing children, egocentric behavior begins to wane after toddler and preschool stages. Therefore, when it presents in adolescents, it can be misconstrued as narcissistic or oppositional behavior, according to Dr. Charlot.

To avoid the “trap” of perceiving developmentally driven behaviors as symptomatic of mental illness in individuals with intellectual disabilities, “You need to ask the question: 'what is usual behavior for this patient?'” Dr. Charlot stressed. “Because the clinical population is highly heterogenous, you need to know what the individual person's baseline [behavior] is. You cannot use general population reference group [data] to determine that a symptom or symptoms are evidence of psychosis or other psychopathology.”

Additionally, Dr. Charlot continued, “ask yourself if the behaviors and symptoms are pathologic for a person functioning at this developmental level.” For example, if you are assessing an adolescent who appears labile and “all over the place,” she said, “that's not that unusual for an intellectually disabled individual who is experiencing stress.”

Before assuming that alterations in mood and behavior are indicative of a psychiatric disorder in adolescents with intellectual impairment, “hunt for possible sources of physical distress,” Dr. Charlot said.

Among the many medical problems that can manifest as behavioral issues are constipation, gastroesophageal reflux disease, seizure disorder, hypothyroidism, hypertension, anemia, candidiasis, urinary tract infection, diabetes, hypercholesterolemia, and obesity, she said, adding, “I can't tell you how many cases of adolescents with reported severe, aggressive behavior turned out to be constipated.”

Often, because of poor language skills, these individuals are unable to articulate physical complaints, resulting in agitation, which may then be attributed to a psychiatric disorder, she said at the meeting cosponsored by the University of Texas at Dallas.

Finally, if and when a psychiatric syndrome is identified, “be careful not to automatically attribute any future alterations in mental status or behavior as being secondary to the psychiatric problem,” Dr. Charlot said.

Under all circumstances, “comprehensive treatment should be directly derived from comprehensive assessment.”

BOSTON – Failure to use a developmental framework when assessing mental illness in children and adolescents with intellectual disabilities can hinder the accurate diagnosis of psychiatric disorders, and lead to inappropriate and possibly dangerous treatment, according to Lauren R. Charlot, Ph.D.

“It's important to consider the ways in which an individual's developmental stage affects his or her behavior and thoughts,” Dr. Charlot said at the annual meeting of the American Society for Adolescent Psychiatry.

“Some symptoms or behaviors that would seem pathologic for a typically developing individual may be 'typical' for a person with a particular set of skills and challenges, especially when under stress,” said Dr. Charlot, of the department of psychiatry at the University of Massachusetts, Worcester.

For example, she said, an adolescent with similar cognitive features to a typically developing preschool-age child might engage in self-talk–talking out loud to himself or herself–under stress. “Developmentally, this behavior is appropriate, but if you don't apply a developmental perspective, it seems abnormal and could easily be mistaken for psychotic ideation.”

The most important consideration when evaluating individuals with intellectual delays is the link between developmental stage and cognitive processes. Studies have identified multiple developmental effects on psychopathology in people with intellectual disabilities, Dr. Charlot noted. Among the developmental effects most likely to have an impact on psychiatric evaluation in this patient population are:

▸ Magical thinking, characterized by poor distinctions between fantasy and reality. “These kids may be talking to people who are not present, and they may be expressing wishes as beliefs,” Dr. Charlot said. Unfortunately, she added, “this behavior is often misconstrued as hallucinations or delusions,” even though it is a consequence of cognitive development rather than psychotic thinking.

▸ Prelogical thinking, which is characterized by primitive, incomplete thought processes and may present as seemingly tangential rambling. Normal among preschoolers, this mode of thought can be symptomatic of mental illness–particularly schizophrenia–in typically developing adolescents and adults, Dr. Charlot said. “This type of prelogical thinking is common at baseline in people with intellectual delays, and it tends to get exaggerated when they're under stress, which is often reported as 'racing thoughts.' But it's not a consequence of psychosis. It relates to an inability to understand logical relationships between subjects,” she said.

▸ Concrete thinking, whereby language and perceptions are interpreted literally. The limited ability to understand abstract language and ideas can lead individuals to misinterpret questions that are asked of them, which could be perceived as an indication of disturbed thought, Dr. Charlot said.

▸ Egocentrism, or the tendency to assume that everyone shares one's own thoughts and the inability to understand the consequences of one's own behavior on others. In normally developing children, egocentric behavior begins to wane after toddler and preschool stages. Therefore, when it presents in adolescents, it can be misconstrued as narcissistic or oppositional behavior, according to Dr. Charlot.

To avoid the “trap” of perceiving developmentally driven behaviors as symptomatic of mental illness in individuals with intellectual disabilities, “You need to ask the question: 'what is usual behavior for this patient?'” Dr. Charlot stressed. “Because the clinical population is highly heterogenous, you need to know what the individual person's baseline [behavior] is. You cannot use general population reference group [data] to determine that a symptom or symptoms are evidence of psychosis or other psychopathology.”

Additionally, Dr. Charlot continued, “ask yourself if the behaviors and symptoms are pathologic for a person functioning at this developmental level.” For example, if you are assessing an adolescent who appears labile and “all over the place,” she said, “that's not that unusual for an intellectually disabled individual who is experiencing stress.”

Before assuming that alterations in mood and behavior are indicative of a psychiatric disorder in adolescents with intellectual impairment, “hunt for possible sources of physical distress,” Dr. Charlot said.

Among the many medical problems that can manifest as behavioral issues are constipation, gastroesophageal reflux disease, seizure disorder, hypothyroidism, hypertension, anemia, candidiasis, urinary tract infection, diabetes, hypercholesterolemia, and obesity, she said, adding, “I can't tell you how many cases of adolescents with reported severe, aggressive behavior turned out to be constipated.”

Often, because of poor language skills, these individuals are unable to articulate physical complaints, resulting in agitation, which may then be attributed to a psychiatric disorder, she said at the meeting cosponsored by the University of Texas at Dallas.

Finally, if and when a psychiatric syndrome is identified, “be careful not to automatically attribute any future alterations in mental status or behavior as being secondary to the psychiatric problem,” Dr. Charlot said.

Under all circumstances, “comprehensive treatment should be directly derived from comprehensive assessment.”

A sharp rise in the number of adult hospitalizations and deaths attributable to Clostridium difficile infection over a 6-year period has investigators calling for increased allocation of public health resources aimed at the prevention of disease caused by the GI pathogen.

In a population-based analysis of adult hospitalizations related to C. difficile-associated disease (CDAD) between 2000 and 2005, Dr. Marya D. Zilberberg of the University of Massachusetts School of Public Health and Health Sciences, Amherst, and colleagues determined that the incidence of adult CDAD hospitalizations rose from 5.5 cases per 10,000 population in 2000 to 11.2 per 10,000 population in 2005. Furthermore, the investigators reported that the CDAD-related, age-adjusted case fatality rate rose from 1.2% in 2000 to 2.2% in 2004.

“In our analysis, we detected a 23% annual increase in CDAD hospitalizations in the 6-year period from 2000 through 2005,” the investigators wrote. “Moreover, the absolute number of CDAD hospitalizations more than doubled in all age groups except the youngest, for whom they increased by 74.1% over the study period.” The rate of increase in the incidence of CDAD was steepest in the group aged 85 years and older, followed by the group aged 65–84 years, the group aged 45–64 years, and the group aged 18–44 years (Emerg. Infect. Dis. 2008;14:929–31).

The numbers help explain the increasing mortality rates related to CDAD, the authors wrote, referring specifically to a recent report documenting a 35% per year increase in the number of CDAD deaths from 1999 through 2004 (Emerg. Infect. Dis. 2007;13:1417–9). “By observing a 23% per year increase in the volume of hospitalizations with CDAD in the period 2000–2005, we demonstrate that at least half of the reported mortality increase with CDAD is due to an increase in the incidence of hospitalizations with this severe infection,” they stated, noting that the increased hospitalization likely represents the effects of increased virulence of the organism as well as growing resistance to some antibiotic treatments.

Data for the current analysis were obtained from the National Inpatient Sample, which is a 20% sample of U.S. community hospitals, weighted to provide national estimates. The investigators identified CDAD by ICD-9-CM code 8.45 for intestinal infection with C. difficile, and age-stratified the number of discharges per year.

“The rapid rate of growth of CDAD-related hospitalizations and mortality is alarming, particularly in view of the aging U.S. population,” the authors wrote. “If this rate of rise, along with the increase in virulence and diminished susceptibility to antimicrobial drug treatments, persists, C. difficile-associated disease will result not only in a considerable strain on the U.S. health care system but also in rising numbers of deaths related to this disease.” For this reason, they stressed, “research into the best preventive strategies, such as limiting the use of antimicrobial agents in both human disease and the food supply, is a public health imperative.”

A sharp rise in the number of adult hospitalizations and deaths attributable to Clostridium difficile infection over a 6-year period has investigators calling for increased allocation of public health resources aimed at the prevention of disease caused by the GI pathogen.

In a population-based analysis of adult hospitalizations related to C. difficile-associated disease (CDAD) between 2000 and 2005, Dr. Marya D. Zilberberg of the University of Massachusetts School of Public Health and Health Sciences, Amherst, and colleagues determined that the incidence of adult CDAD hospitalizations rose from 5.5 cases per 10,000 population in 2000 to 11.2 per 10,000 population in 2005. Furthermore, the investigators reported that the CDAD-related, age-adjusted case fatality rate rose from 1.2% in 2000 to 2.2% in 2004.

“In our analysis, we detected a 23% annual increase in CDAD hospitalizations in the 6-year period from 2000 through 2005,” the investigators wrote. “Moreover, the absolute number of CDAD hospitalizations more than doubled in all age groups except the youngest, for whom they increased by 74.1% over the study period.” The rate of increase in the incidence of CDAD was steepest in the group aged 85 years and older, followed by the group aged 65–84 years, the group aged 45–64 years, and the group aged 18–44 years (Emerg. Infect. Dis. 2008;14:929–31).

The numbers help explain the increasing mortality rates related to CDAD, the authors wrote, referring specifically to a recent report documenting a 35% per year increase in the number of CDAD deaths from 1999 through 2004 (Emerg. Infect. Dis. 2007;13:1417–9). “By observing a 23% per year increase in the volume of hospitalizations with CDAD in the period 2000–2005, we demonstrate that at least half of the reported mortality increase with CDAD is due to an increase in the incidence of hospitalizations with this severe infection,” they stated, noting that the increased hospitalization likely represents the effects of increased virulence of the organism as well as growing resistance to some antibiotic treatments.

Data for the current analysis were obtained from the National Inpatient Sample, which is a 20% sample of U.S. community hospitals, weighted to provide national estimates. The investigators identified CDAD by ICD-9-CM code 8.45 for intestinal infection with C. difficile, and age-stratified the number of discharges per year.

“The rapid rate of growth of CDAD-related hospitalizations and mortality is alarming, particularly in view of the aging U.S. population,” the authors wrote. “If this rate of rise, along with the increase in virulence and diminished susceptibility to antimicrobial drug treatments, persists, C. difficile-associated disease will result not only in a considerable strain on the U.S. health care system but also in rising numbers of deaths related to this disease.” For this reason, they stressed, “research into the best preventive strategies, such as limiting the use of antimicrobial agents in both human disease and the food supply, is a public health imperative.”

A sharp rise in the number of adult hospitalizations and deaths attributable to Clostridium difficile infection over a 6-year period has investigators calling for increased allocation of public health resources aimed at the prevention of disease caused by the GI pathogen.

In a population-based analysis of adult hospitalizations related to C. difficile-associated disease (CDAD) between 2000 and 2005, Dr. Marya D. Zilberberg of the University of Massachusetts School of Public Health and Health Sciences, Amherst, and colleagues determined that the incidence of adult CDAD hospitalizations rose from 5.5 cases per 10,000 population in 2000 to 11.2 per 10,000 population in 2005. Furthermore, the investigators reported that the CDAD-related, age-adjusted case fatality rate rose from 1.2% in 2000 to 2.2% in 2004.

“In our analysis, we detected a 23% annual increase in CDAD hospitalizations in the 6-year period from 2000 through 2005,” the investigators wrote. “Moreover, the absolute number of CDAD hospitalizations more than doubled in all age groups except the youngest, for whom they increased by 74.1% over the study period.” The rate of increase in the incidence of CDAD was steepest in the group aged 85 years and older, followed by the group aged 65–84 years, the group aged 45–64 years, and the group aged 18–44 years (Emerg. Infect. Dis. 2008;14:929–31).

The numbers help explain the increasing mortality rates related to CDAD, the authors wrote, referring specifically to a recent report documenting a 35% per year increase in the number of CDAD deaths from 1999 through 2004 (Emerg. Infect. Dis. 2007;13:1417–9). “By observing a 23% per year increase in the volume of hospitalizations with CDAD in the period 2000–2005, we demonstrate that at least half of the reported mortality increase with CDAD is due to an increase in the incidence of hospitalizations with this severe infection,” they stated, noting that the increased hospitalization likely represents the effects of increased virulence of the organism as well as growing resistance to some antibiotic treatments.

Data for the current analysis were obtained from the National Inpatient Sample, which is a 20% sample of U.S. community hospitals, weighted to provide national estimates. The investigators identified CDAD by ICD-9-CM code 8.45 for intestinal infection with C. difficile, and age-stratified the number of discharges per year.

“The rapid rate of growth of CDAD-related hospitalizations and mortality is alarming, particularly in view of the aging U.S. population,” the authors wrote. “If this rate of rise, along with the increase in virulence and diminished susceptibility to antimicrobial drug treatments, persists, C. difficile-associated disease will result not only in a considerable strain on the U.S. health care system but also in rising numbers of deaths related to this disease.” For this reason, they stressed, “research into the best preventive strategies, such as limiting the use of antimicrobial agents in both human disease and the food supply, is a public health imperative.”

BOSTON — The presence of naturally occurring Lactobacillus in the vaginal flora of HIV-positive women is associated with a reduced amount of HIV in the vagina, while the absence of the “good bacteria” is associated with an increased vaginal viral load, researchers found in a prospective observational cohort study of 57 HIV-positive women.

As a key regulator of the vaginal ecosystem, hydrogen peroxide (H₂O₂)-producing Lactobacillus may decrease HIV-1 replication through direct effects as well as through the suppression of pathogenic bacteria, explained Dr. Jane Hitti of the University of Washington, Seattle.

To evaluate the effects of the bacteria on cervicovaginal lavage (CVL) HIV-1 RNA concentrations over time, she and her colleagues followed 57 HIV-positive women from Seattle and Rochester, N.Y., for up to 5 years, looking at changes in their vaginal bacteria as well as changes in the vaginal viral load and their plasma viral load.

For each woman in the study, plasma and CVL samples were collected for HIV quantitation every 3–4 months, as were vaginal cultures to identify H₂O₂Lactobacillus. The investigators conducted longitudinal analyses using linear regression to examine the change in log-transformed CVL HIV RNA between two consecutive visits for the same woman as a function of Lactobacillus colonization, adjusting for plasma HIV RNA and antiretroviral therapy.

At the start of the study, 31 women were on antiretroviral therapy and 22 had an undetectable viral load. Lactobacillus was present in 32 of the 57 women. During the study, plasma viral load was detectable at 64% of visits and vaginal viral load was detectable at 17% of visits. While viral load was highly correlated with plasma viral load, it was not significantly correlated with antiretroviral therapy, Dr. Hitti reported at the 15th Conference on Retroviruses and Opportunistic Infections.

“What we found, first of all, was that only about half of the women at any given time were carrying the [H₂O₂Lactobacillus], and that some women switched back and forth between carrying the good bacteria and not having it,” Dr. Hitti said. “When these women had the healthy Lactobacillus in the vagina, they tended to have a lower viral load in the vagina.” The finding remained statistically significant after adjusting for plasma HIV and antiretroviral therapy, she noted.

In looking at visit pairs—two consecutive visits for the same woman—”we found that women who acquired the healthy bacteria had a 0.7 log10 decrease in their vaginal viral load, compared with women who were stable the whole time,” Dr. Hitti said. “Conversely, women who lost the healthy bacteria had a 0.5 log10 increase in their viral load.”

In addition to stressing the importance of maintaining a healthy Lactobacillus vaginal flora for HIV-infected women, the findings may have relevance for secondary prevention strategies, according to Dr. Hitti. “One of the logical next steps is to think about whether it might be possible to develop strategies for increasing the likelihood that women would carry these healthy vaginal bacteria as a way to decrease the amount of HIV in the vagina, which could be helpful in terms of preventing the spread of HIV in the future.”

One possible preventive strategy might be Lactobacillus supplementation, but not with the type of Lactobacillus that is found in yogurt, “which is kind of a cousin, but doesn't really feel at home in the vagina,” Dr. Hitti said. “The ideal approach would be to use the kind of Lactobacillus that specifically likes to live in the vagina. The optimal strategy would be to take a well characterized preparation of that type of Lactobacillus and conduct trials to look at whether it's possible to achieve colonization in the vagina.”

A few such studies have been conducted among HIV-negative women to look at colonization, but “I don't think any similar trials have as yet been done in HIV-positive women, and that's a direction I hope we can go in,” she said.

BOSTON — The presence of naturally occurring Lactobacillus in the vaginal flora of HIV-positive women is associated with a reduced amount of HIV in the vagina, while the absence of the “good bacteria” is associated with an increased vaginal viral load, researchers found in a prospective observational cohort study of 57 HIV-positive women.

As a key regulator of the vaginal ecosystem, hydrogen peroxide (H₂O₂)-producing Lactobacillus may decrease HIV-1 replication through direct effects as well as through the suppression of pathogenic bacteria, explained Dr. Jane Hitti of the University of Washington, Seattle.

To evaluate the effects of the bacteria on cervicovaginal lavage (CVL) HIV-1 RNA concentrations over time, she and her colleagues followed 57 HIV-positive women from Seattle and Rochester, N.Y., for up to 5 years, looking at changes in their vaginal bacteria as well as changes in the vaginal viral load and their plasma viral load.

For each woman in the study, plasma and CVL samples were collected for HIV quantitation every 3–4 months, as were vaginal cultures to identify H₂O₂Lactobacillus. The investigators conducted longitudinal analyses using linear regression to examine the change in log-transformed CVL HIV RNA between two consecutive visits for the same woman as a function of Lactobacillus colonization, adjusting for plasma HIV RNA and antiretroviral therapy.

At the start of the study, 31 women were on antiretroviral therapy and 22 had an undetectable viral load. Lactobacillus was present in 32 of the 57 women. During the study, plasma viral load was detectable at 64% of visits and vaginal viral load was detectable at 17% of visits. While viral load was highly correlated with plasma viral load, it was not significantly correlated with antiretroviral therapy, Dr. Hitti reported at the 15th Conference on Retroviruses and Opportunistic Infections.

“What we found, first of all, was that only about half of the women at any given time were carrying the [H₂O₂Lactobacillus], and that some women switched back and forth between carrying the good bacteria and not having it,” Dr. Hitti said. “When these women had the healthy Lactobacillus in the vagina, they tended to have a lower viral load in the vagina.” The finding remained statistically significant after adjusting for plasma HIV and antiretroviral therapy, she noted.

In looking at visit pairs—two consecutive visits for the same woman—”we found that women who acquired the healthy bacteria had a 0.7 log10 decrease in their vaginal viral load, compared with women who were stable the whole time,” Dr. Hitti said. “Conversely, women who lost the healthy bacteria had a 0.5 log10 increase in their viral load.”

In addition to stressing the importance of maintaining a healthy Lactobacillus vaginal flora for HIV-infected women, the findings may have relevance for secondary prevention strategies, according to Dr. Hitti. “One of the logical next steps is to think about whether it might be possible to develop strategies for increasing the likelihood that women would carry these healthy vaginal bacteria as a way to decrease the amount of HIV in the vagina, which could be helpful in terms of preventing the spread of HIV in the future.”

One possible preventive strategy might be Lactobacillus supplementation, but not with the type of Lactobacillus that is found in yogurt, “which is kind of a cousin, but doesn't really feel at home in the vagina,” Dr. Hitti said. “The ideal approach would be to use the kind of Lactobacillus that specifically likes to live in the vagina. The optimal strategy would be to take a well characterized preparation of that type of Lactobacillus and conduct trials to look at whether it's possible to achieve colonization in the vagina.”

A few such studies have been conducted among HIV-negative women to look at colonization, but “I don't think any similar trials have as yet been done in HIV-positive women, and that's a direction I hope we can go in,” she said.

BOSTON — The presence of naturally occurring Lactobacillus in the vaginal flora of HIV-positive women is associated with a reduced amount of HIV in the vagina, while the absence of the “good bacteria” is associated with an increased vaginal viral load, researchers found in a prospective observational cohort study of 57 HIV-positive women.

As a key regulator of the vaginal ecosystem, hydrogen peroxide (H₂O₂)-producing Lactobacillus may decrease HIV-1 replication through direct effects as well as through the suppression of pathogenic bacteria, explained Dr. Jane Hitti of the University of Washington, Seattle.

To evaluate the effects of the bacteria on cervicovaginal lavage (CVL) HIV-1 RNA concentrations over time, she and her colleagues followed 57 HIV-positive women from Seattle and Rochester, N.Y., for up to 5 years, looking at changes in their vaginal bacteria as well as changes in the vaginal viral load and their plasma viral load.

For each woman in the study, plasma and CVL samples were collected for HIV quantitation every 3–4 months, as were vaginal cultures to identify H₂O₂Lactobacillus. The investigators conducted longitudinal analyses using linear regression to examine the change in log-transformed CVL HIV RNA between two consecutive visits for the same woman as a function of Lactobacillus colonization, adjusting for plasma HIV RNA and antiretroviral therapy.

At the start of the study, 31 women were on antiretroviral therapy and 22 had an undetectable viral load. Lactobacillus was present in 32 of the 57 women. During the study, plasma viral load was detectable at 64% of visits and vaginal viral load was detectable at 17% of visits. While viral load was highly correlated with plasma viral load, it was not significantly correlated with antiretroviral therapy, Dr. Hitti reported at the 15th Conference on Retroviruses and Opportunistic Infections.

“What we found, first of all, was that only about half of the women at any given time were carrying the [H₂O₂Lactobacillus], and that some women switched back and forth between carrying the good bacteria and not having it,” Dr. Hitti said. “When these women had the healthy Lactobacillus in the vagina, they tended to have a lower viral load in the vagina.” The finding remained statistically significant after adjusting for plasma HIV and antiretroviral therapy, she noted.

In looking at visit pairs—two consecutive visits for the same woman—”we found that women who acquired the healthy bacteria had a 0.7 log10 decrease in their vaginal viral load, compared with women who were stable the whole time,” Dr. Hitti said. “Conversely, women who lost the healthy bacteria had a 0.5 log10 increase in their viral load.”

In addition to stressing the importance of maintaining a healthy Lactobacillus vaginal flora for HIV-infected women, the findings may have relevance for secondary prevention strategies, according to Dr. Hitti. “One of the logical next steps is to think about whether it might be possible to develop strategies for increasing the likelihood that women would carry these healthy vaginal bacteria as a way to decrease the amount of HIV in the vagina, which could be helpful in terms of preventing the spread of HIV in the future.”

One possible preventive strategy might be Lactobacillus supplementation, but not with the type of Lactobacillus that is found in yogurt, “which is kind of a cousin, but doesn't really feel at home in the vagina,” Dr. Hitti said. “The ideal approach would be to use the kind of Lactobacillus that specifically likes to live in the vagina. The optimal strategy would be to take a well characterized preparation of that type of Lactobacillus and conduct trials to look at whether it's possible to achieve colonization in the vagina.”

A few such studies have been conducted among HIV-negative women to look at colonization, but “I don't think any similar trials have as yet been done in HIV-positive women, and that's a direction I hope we can go in,” she said.

CHICAGO — The only “sure thing” about the medical management of pregnant women who have a rheumatic disease is that there are no sure things, advises a rheumatologist with particular expertise in lupus.

“In an ideal world, pregnancy in these women would always be planned; the rheumatic disease would have been in remission for at least 6 months at the time of conception, and there would be a plan for treatment if the disease flares. Unfortunately, clinical medicine isn't an ideal world,” said Dr. Bonnie L. Bermas, director of the Center for Lupus and Antiphospholipid Antibody at Brigham and Women's Hospital, Boston.

Exacerbating the challenge is the absence of any one-size-fits-all management formula, Dr. Bermas said, noting that the interplay among the individual patient, disease, and treatment variables—all of which are unpredictable—drives therapeutic decisions.

With rheumatoid arthritis (RA), for example, “the literature supports that about 70%-80% of patients will go into remission during pregnancy, though most will flare post partum,” said Dr. Bermas at a symposium sponsored by the American College of Rheumatology (ACR). Even though this knowledge provides clinicians with some flexibility with respect to medication during pregnancy, “we really can't predict who's going to go into remission, so we can't say up front, 'I guarantee you'll be able to go off treatment once you become pregnant,'” she said.

Systemic lupus erythematosus (SLE), on the other hand, is thought to be associated with a slightly increased risk of flare during pregnancy, said Dr. Bermas. “This means that we will approach a lupus patient differently than a rheumatoid arthritis patient in terms of our management plan, and the answers to the critical questions—'Will the disease flare? Will the baby be affected by the disease? What medications are safe to take during pregnancy?'—will be different.”

Although the Food and Drug Administration's use-in-pregnancy ratings for the mainstays of rheumatic disease therapies provide a management framework, there is often a discrepancy between what the FDA says is allowable during pregnancy and what clinicians feel comfortable prescribing, Dr. Bermas said.

NSAIDs, Cyclooxygenase-2 Inhibitors

Although animal studies have shown an increased risk of congenital anomalies with these agents, “when you get to the human studies, there really is no increased risk of congenital anomalies,” said Dr. Bermas. “There is an increased risk of premature closure of the ductus arteriosus in patients exposed to nonsteroidals late in pregnancy, so we counsel patients that they can use nonsteroidals up to 24 weeks' gestation. We could probably protract this out to 30 weeks, but it's easier to say, 'stop the NSAIDS in the third trimester.'”

For patients trying to conceive, “we advise that they avoid using COX-2s and NSAIDs during the conception cycle because both can have an impact on implantation,” Dr. Bermas noted.

Antimalarials

A single case report of congenital defects in three of four babies born to one mother who took 250 mg of chloroquine two times a day during each of her four pregnancies earned antimalarials an FDA category C rating, “which is sort of representative of how the literature about medication in pregnancy has been interpreted over the years,” said Dr. Bermas. In the meantime, she said, there have been several case series in which no increased risk of congenital anomalies has been seen, and the literature on the use of these drugs as malarial prophylaxis (at higher doses than are used to treat rheumatic disease) has identified no untoward effects in pregnant women.

“For many years, we didn't use any of these drugs during pregnancy, but a recent ACR survey showed that most rheumatologists today are comfortable leaving patients on antimalarials during pregnancy,” said Dr. Berman. “Having said that, if I have an RA patient whose main medication is hydroxychloroquine, that patient probably has fairly mild disease. Considering that most RA patients go into remission during pregnancy, I usually recommend stopping the drug during gestation.”

But for a patient with SLE who is well maintained on hydroxychloroquine, “I'd probably keep the medication on board,” because additional data show that patients with lupus who remain on therapy have better outcomes.

Steroids

For flares of most rheumatic diseases, steroids are considered “the ace in the hole,” said Dr. Bermas.

“During pregnancy, if rheumatoid arthritis, for example, becomes active, most clinicians recommend starting treatment with the lowest dose possible of a glucocorticoid medication, most commonly prednisone.” Both prednisone and methylprednisolone cross the placenta, but only at low levels, she said.

The data on steroid safety during pregnancy are mixed. “Originally, there were some case reports of cleft palate formation in offspring, although no increased risk of fetal anomalies was found in a large series of asthma patients treated with steroids throughout pregnancy,” said Dr. Bermas. “In a meta-analysis of epidemiological studies, however, there was a 3.4-fold increase in the incidence of cleft palate formation associated with maternal exposure to corticosteroids [Teratology, 2000;62:385–92],” she said. “The key time frame seems to be between weeks 6 and 12, when the palate is forming.”

Corticosteroids during pregnancy are also associated with maternal comorbidities, including gestational diabetes, hypertension, and accelerated osteoporosis. “For this reason, the goal should always be to keep the dose as low as possible,” she said.

Azathioprine and 6-Mercaptopurine

The use of azathioprine, a nonbiologic disease-modifying antirheumatic drug, is generally limited to women with severe disease who have not responded to other treatments, Dr. Bermas stated. There are “conflicting data about the safety of this drug during pregnancy. Animal data [suggest that] the drug is teratogenic, and there have been case reports of fetal malformations, but transplant series indicate that the medication doesn't increase the rate of congenital anomalies,” she said. Small-for-gestational-age babies and premature rupture of membranes are associated with use of the drug during pregnancy.

As with azathioprine, the nucleoside analog 6-mercaptopurine is teratogenic in animals, and it is plagued by conflicting human data. Some of the human studies suggest that “there is an increased risk of congenital anomalies, but the gastrointestinal literature doesn't support this,” Dr. Bermas noted. “From a rheumatology perspective, this medication is rarely used, so I would suggest discontinuing it during pregnancy.”

Sulfasalazine

“Case reports of fetal malformations linked to sulfasalazine from the inflammatory bowel disease literature didn't pan out in larger studies,” said Dr. Bermas. “This drug can be used in pregnancy. It does cause azoospermia in men, however, so if you have a male patient who is interested in trying to get his partner pregnant, advise him to stop taking sulfasalazine for 3 months before conception for spermatogenesis.”

Penicillamine

Occasionally used in the treatment of progressive systemic sclerosis, penicillamine has been shown to interfere with collagen biosynthesis and to cause malformations in animal studies, according to Dr. Bermas. “In humans, cases of cutis laxa and connective tissue disorders have been reported with exposure to this medication,” she said. As such, “this medication should not be used during pregnancy.”

Mycophenolate Mofetil

“We had such high hopes for mycophenolate mofetil. We thought this would be one of those medications that could be safely used during pregnancy,” said Dr. Bermas. “Unfortunately, there are increased case reports of congenital anomalies, including one report of the drug being used during pregnancy in a renal transplant patient. The baby was born prematurely and was noted to have hypoplastic nails and short fifth fingers.” Although there is not a rich body of literature yet, “this medication should be avoided during pregnancy,” she said.

IVIG

Intravenous immunoglobulin is not a common drug for rheumatologic disorders, and the literature on its use in pregnancy is limited. “In one case report of an individual with steroid-resistant idiopathic thrombocytopenic purpura, IVIG was used with no adverse effects on the offspring,” said Dr. Bermas. “The medication has also been used to manage the obstetrical complications of the antiphospholipid antibody syndrome without inducing congenital malformations.” Based on the available data, IVIG, when warranted, is acceptable for use in pregnancy, she said.

Cyclosporin A

The large body of data regarding the use of cyclosporin A during pregnancy comes from the transplant literature. “These medications are not teratogenic, although they are associated with small-for-gestational-age infants and hypertension of pregnancy,” said Dr. Bermas. The drug is not widely used, but in individual cases, if the potential benefit outweighs the possible risk, clinicians may choose to continue treatment with it, she noted.

Chlorambucil and Cyclophosphamide

Both of these cytotoxic agents are teratogenic and should be avoided during pregnancy, Dr. Bermas stressed. “In life-or-death situations, cyclophosphosamide has been used in the third trimester,” she said.

Methotrexate

Because of the high risk of congenital anomalies, methotrexate is an FDA category X drug for use in pregnancy. In addition to being teratogenic, it is also abortifacient, said Dr. Bermas, noting that, in terms of gestation, the use of methotrexate during weeks 6–8 at dosages greater than 10 mg/day substantially increases the risk of fetal harm. “I recommend that patients, both men and women, discontinue methotrexate for at least 3 months prior to conception,” she said.

Leflunomide

Another FDA category X drug for use in pregnancy because of its high teratogenicity, leflunomide “has an extremely long half-life, so either you need to wash out with cholestyramine or discontinue for 2 years before conception,” said Dr. Bermas. “As a general rule, I avoid using this in women of childbearing potential.”

Anti-TNF-α Agents

Limited data exist regarding the safety of the tumor necrosis factor-? inhibitors during pregnancy, “although case reports of two infants exposed to these drugs in utero being born with anomalies potentially consistent with VACTERL [vertebral, anal, cardiac, tracheal, esophageal, renal, and limb] syndrome give clinicians pause,” said Dr. Bermas. On the other hand, animal studies reported no teratogenic or fetotoxic effects, and some reports on human pregnancy in patients taking these drugs did not show an increase in birth defects or adverse pregnancy outcomes, she said. In one large study comprising 131 patients with inflammatory chronic diseases—including 8 patients with RA—who were directly exposed to inifliximab, drug exposure during pregnancy resulted in outcomes similar to those seen in the general population of pregnant women (Am. J. Gastroenterol, 2004;99:2385–92).

Rituximab

More commonly used for the treatment of non-Hodgkin's lymphoma, rituximab is also used for patients with refractory RA. Although as of yet there are no reports of congenital anomalies associated with this anti-CD20 monoclonal antibody, “there are insufficient data regarding the safety of the drug in animal or human pregnancy,” said Dr. Bermas. Two case reports of successful outcomes in women treated with rituximab for non-Hodgkin's lymphoma during pregnancy are promising, but not yet representative, she said. In fact, given the availability of safer alternative medications for pregnant RA patients, along with the possibility of remission during pregnancy, rituximab should probably be avoided unless there's a compelling reason to use it, she said.

Drug Treatment Considerations

The treatment of rheumatic diseases in pregnant women should be based on disease severity and drug safety, according to Dr. Bermas, who suggested the following general guide to treatment options:

Mild Disease

▸ For inflammatory arthritis, Dr. Bermas recommends stopping drug therapy before pregnancy or when pregnancy is discovered.

▸ For SLE, maintain these patients on hydroxychloroquine.

▸ NSAIDS are acceptable up to week 24.

Moderate Disease

▸ Steroids should be used at the lowest possible dose.

▸ Azathioprine should be used with caution.

▸ Cyclosporin A should be used with caution.

▸ Sulfasalazine should be used with caution.

Severe Disease

▸ High-dose steroids should be used with caution.

▸ Azathioprine should be used with caution.

▸ Cyclosporin A should be used with caution.

▸ Cyclophosphamide should be used only in life-or-death situations.

CHICAGO — The only “sure thing” about the medical management of pregnant women who have a rheumatic disease is that there are no sure things, advises a rheumatologist with particular expertise in lupus.

“In an ideal world, pregnancy in these women would always be planned; the rheumatic disease would have been in remission for at least 6 months at the time of conception, and there would be a plan for treatment if the disease flares. Unfortunately, clinical medicine isn't an ideal world,” said Dr. Bonnie L. Bermas, director of the Center for Lupus and Antiphospholipid Antibody at Brigham and Women's Hospital, Boston.

Exacerbating the challenge is the absence of any one-size-fits-all management formula, Dr. Bermas said, noting that the interplay among the individual patient, disease, and treatment variables—all of which are unpredictable—drives therapeutic decisions.

With rheumatoid arthritis (RA), for example, “the literature supports that about 70%-80% of patients will go into remission during pregnancy, though most will flare post partum,” said Dr. Bermas at a symposium sponsored by the American College of Rheumatology (ACR). Even though this knowledge provides clinicians with some flexibility with respect to medication during pregnancy, “we really can't predict who's going to go into remission, so we can't say up front, 'I guarantee you'll be able to go off treatment once you become pregnant,'” she said.

Systemic lupus erythematosus (SLE), on the other hand, is thought to be associated with a slightly increased risk of flare during pregnancy, said Dr. Bermas. “This means that we will approach a lupus patient differently than a rheumatoid arthritis patient in terms of our management plan, and the answers to the critical questions—'Will the disease flare? Will the baby be affected by the disease? What medications are safe to take during pregnancy?'—will be different.”

Although the Food and Drug Administration's use-in-pregnancy ratings for the mainstays of rheumatic disease therapies provide a management framework, there is often a discrepancy between what the FDA says is allowable during pregnancy and what clinicians feel comfortable prescribing, Dr. Bermas said.

NSAIDs, Cyclooxygenase-2 Inhibitors

Although animal studies have shown an increased risk of congenital anomalies with these agents, “when you get to the human studies, there really is no increased risk of congenital anomalies,” said Dr. Bermas. “There is an increased risk of premature closure of the ductus arteriosus in patients exposed to nonsteroidals late in pregnancy, so we counsel patients that they can use nonsteroidals up to 24 weeks' gestation. We could probably protract this out to 30 weeks, but it's easier to say, 'stop the NSAIDS in the third trimester.'”

For patients trying to conceive, “we advise that they avoid using COX-2s and NSAIDs during the conception cycle because both can have an impact on implantation,” Dr. Bermas noted.

Antimalarials

A single case report of congenital defects in three of four babies born to one mother who took 250 mg of chloroquine two times a day during each of her four pregnancies earned antimalarials an FDA category C rating, “which is sort of representative of how the literature about medication in pregnancy has been interpreted over the years,” said Dr. Bermas. In the meantime, she said, there have been several case series in which no increased risk of congenital anomalies has been seen, and the literature on the use of these drugs as malarial prophylaxis (at higher doses than are used to treat rheumatic disease) has identified no untoward effects in pregnant women.

“For many years, we didn't use any of these drugs during pregnancy, but a recent ACR survey showed that most rheumatologists today are comfortable leaving patients on antimalarials during pregnancy,” said Dr. Berman. “Having said that, if I have an RA patient whose main medication is hydroxychloroquine, that patient probably has fairly mild disease. Considering that most RA patients go into remission during pregnancy, I usually recommend stopping the drug during gestation.”

But for a patient with SLE who is well maintained on hydroxychloroquine, “I'd probably keep the medication on board,” because additional data show that patients with lupus who remain on therapy have better outcomes.

Steroids

For flares of most rheumatic diseases, steroids are considered “the ace in the hole,” said Dr. Bermas.

“During pregnancy, if rheumatoid arthritis, for example, becomes active, most clinicians recommend starting treatment with the lowest dose possible of a glucocorticoid medication, most commonly prednisone.” Both prednisone and methylprednisolone cross the placenta, but only at low levels, she said.

The data on steroid safety during pregnancy are mixed. “Originally, there were some case reports of cleft palate formation in offspring, although no increased risk of fetal anomalies was found in a large series of asthma patients treated with steroids throughout pregnancy,” said Dr. Bermas. “In a meta-analysis of epidemiological studies, however, there was a 3.4-fold increase in the incidence of cleft palate formation associated with maternal exposure to corticosteroids [Teratology, 2000;62:385–92],” she said. “The key time frame seems to be between weeks 6 and 12, when the palate is forming.”

Corticosteroids during pregnancy are also associated with maternal comorbidities, including gestational diabetes, hypertension, and accelerated osteoporosis. “For this reason, the goal should always be to keep the dose as low as possible,” she said.

Azathioprine and 6-Mercaptopurine

The use of azathioprine, a nonbiologic disease-modifying antirheumatic drug, is generally limited to women with severe disease who have not responded to other treatments, Dr. Bermas stated. There are “conflicting data about the safety of this drug during pregnancy. Animal data [suggest that] the drug is teratogenic, and there have been case reports of fetal malformations, but transplant series indicate that the medication doesn't increase the rate of congenital anomalies,” she said. Small-for-gestational-age babies and premature rupture of membranes are associated with use of the drug during pregnancy.

As with azathioprine, the nucleoside analog 6-mercaptopurine is teratogenic in animals, and it is plagued by conflicting human data. Some of the human studies suggest that “there is an increased risk of congenital anomalies, but the gastrointestinal literature doesn't support this,” Dr. Bermas noted. “From a rheumatology perspective, this medication is rarely used, so I would suggest discontinuing it during pregnancy.”

Sulfasalazine

“Case reports of fetal malformations linked to sulfasalazine from the inflammatory bowel disease literature didn't pan out in larger studies,” said Dr. Bermas. “This drug can be used in pregnancy. It does cause azoospermia in men, however, so if you have a male patient who is interested in trying to get his partner pregnant, advise him to stop taking sulfasalazine for 3 months before conception for spermatogenesis.”

Penicillamine

Occasionally used in the treatment of progressive systemic sclerosis, penicillamine has been shown to interfere with collagen biosynthesis and to cause malformations in animal studies, according to Dr. Bermas. “In humans, cases of cutis laxa and connective tissue disorders have been reported with exposure to this medication,” she said. As such, “this medication should not be used during pregnancy.”

Mycophenolate Mofetil

“We had such high hopes for mycophenolate mofetil. We thought this would be one of those medications that could be safely used during pregnancy,” said Dr. Bermas. “Unfortunately, there are increased case reports of congenital anomalies, including one report of the drug being used during pregnancy in a renal transplant patient. The baby was born prematurely and was noted to have hypoplastic nails and short fifth fingers.” Although there is not a rich body of literature yet, “this medication should be avoided during pregnancy,” she said.

IVIG

Intravenous immunoglobulin is not a common drug for rheumatologic disorders, and the literature on its use in pregnancy is limited. “In one case report of an individual with steroid-resistant idiopathic thrombocytopenic purpura, IVIG was used with no adverse effects on the offspring,” said Dr. Bermas. “The medication has also been used to manage the obstetrical complications of the antiphospholipid antibody syndrome without inducing congenital malformations.” Based on the available data, IVIG, when warranted, is acceptable for use in pregnancy, she said.

Cyclosporin A

The large body of data regarding the use of cyclosporin A during pregnancy comes from the transplant literature. “These medications are not teratogenic, although they are associated with small-for-gestational-age infants and hypertension of pregnancy,” said Dr. Bermas. The drug is not widely used, but in individual cases, if the potential benefit outweighs the possible risk, clinicians may choose to continue treatment with it, she noted.

Chlorambucil and Cyclophosphamide

Both of these cytotoxic agents are teratogenic and should be avoided during pregnancy, Dr. Bermas stressed. “In life-or-death situations, cyclophosphosamide has been used in the third trimester,” she said.

Methotrexate

Because of the high risk of congenital anomalies, methotrexate is an FDA category X drug for use in pregnancy. In addition to being teratogenic, it is also abortifacient, said Dr. Bermas, noting that, in terms of gestation, the use of methotrexate during weeks 6–8 at dosages greater than 10 mg/day substantially increases the risk of fetal harm. “I recommend that patients, both men and women, discontinue methotrexate for at least 3 months prior to conception,” she said.

Leflunomide

Another FDA category X drug for use in pregnancy because of its high teratogenicity, leflunomide “has an extremely long half-life, so either you need to wash out with cholestyramine or discontinue for 2 years before conception,” said Dr. Bermas. “As a general rule, I avoid using this in women of childbearing potential.”

Anti-TNF-α Agents

Limited data exist regarding the safety of the tumor necrosis factor-? inhibitors during pregnancy, “although case reports of two infants exposed to these drugs in utero being born with anomalies potentially consistent with VACTERL [vertebral, anal, cardiac, tracheal, esophageal, renal, and limb] syndrome give clinicians pause,” said Dr. Bermas. On the other hand, animal studies reported no teratogenic or fetotoxic effects, and some reports on human pregnancy in patients taking these drugs did not show an increase in birth defects or adverse pregnancy outcomes, she said. In one large study comprising 131 patients with inflammatory chronic diseases—including 8 patients with RA—who were directly exposed to inifliximab, drug exposure during pregnancy resulted in outcomes similar to those seen in the general population of pregnant women (Am. J. Gastroenterol, 2004;99:2385–92).

Rituximab

More commonly used for the treatment of non-Hodgkin's lymphoma, rituximab is also used for patients with refractory RA. Although as of yet there are no reports of congenital anomalies associated with this anti-CD20 monoclonal antibody, “there are insufficient data regarding the safety of the drug in animal or human pregnancy,” said Dr. Bermas. Two case reports of successful outcomes in women treated with rituximab for non-Hodgkin's lymphoma during pregnancy are promising, but not yet representative, she said. In fact, given the availability of safer alternative medications for pregnant RA patients, along with the possibility of remission during pregnancy, rituximab should probably be avoided unless there's a compelling reason to use it, she said.

Drug Treatment Considerations

The treatment of rheumatic diseases in pregnant women should be based on disease severity and drug safety, according to Dr. Bermas, who suggested the following general guide to treatment options:

Mild Disease

▸ For inflammatory arthritis, Dr. Bermas recommends stopping drug therapy before pregnancy or when pregnancy is discovered.

▸ For SLE, maintain these patients on hydroxychloroquine.

▸ NSAIDS are acceptable up to week 24.

Moderate Disease

▸ Steroids should be used at the lowest possible dose.

▸ Azathioprine should be used with caution.

▸ Cyclosporin A should be used with caution.

▸ Sulfasalazine should be used with caution.

Severe Disease

▸ High-dose steroids should be used with caution.

▸ Azathioprine should be used with caution.

▸ Cyclosporin A should be used with caution.

▸ Cyclophosphamide should be used only in life-or-death situations.

CHICAGO — The only “sure thing” about the medical management of pregnant women who have a rheumatic disease is that there are no sure things, advises a rheumatologist with particular expertise in lupus.

“In an ideal world, pregnancy in these women would always be planned; the rheumatic disease would have been in remission for at least 6 months at the time of conception, and there would be a plan for treatment if the disease flares. Unfortunately, clinical medicine isn't an ideal world,” said Dr. Bonnie L. Bermas, director of the Center for Lupus and Antiphospholipid Antibody at Brigham and Women's Hospital, Boston.

Exacerbating the challenge is the absence of any one-size-fits-all management formula, Dr. Bermas said, noting that the interplay among the individual patient, disease, and treatment variables—all of which are unpredictable—drives therapeutic decisions.

With rheumatoid arthritis (RA), for example, “the literature supports that about 70%-80% of patients will go into remission during pregnancy, though most will flare post partum,” said Dr. Bermas at a symposium sponsored by the American College of Rheumatology (ACR). Even though this knowledge provides clinicians with some flexibility with respect to medication during pregnancy, “we really can't predict who's going to go into remission, so we can't say up front, 'I guarantee you'll be able to go off treatment once you become pregnant,'” she said.

Systemic lupus erythematosus (SLE), on the other hand, is thought to be associated with a slightly increased risk of flare during pregnancy, said Dr. Bermas. “This means that we will approach a lupus patient differently than a rheumatoid arthritis patient in terms of our management plan, and the answers to the critical questions—'Will the disease flare? Will the baby be affected by the disease? What medications are safe to take during pregnancy?'—will be different.”

Although the Food and Drug Administration's use-in-pregnancy ratings for the mainstays of rheumatic disease therapies provide a management framework, there is often a discrepancy between what the FDA says is allowable during pregnancy and what clinicians feel comfortable prescribing, Dr. Bermas said.

NSAIDs, Cyclooxygenase-2 Inhibitors

Although animal studies have shown an increased risk of congenital anomalies with these agents, “when you get to the human studies, there really is no increased risk of congenital anomalies,” said Dr. Bermas. “There is an increased risk of premature closure of the ductus arteriosus in patients exposed to nonsteroidals late in pregnancy, so we counsel patients that they can use nonsteroidals up to 24 weeks' gestation. We could probably protract this out to 30 weeks, but it's easier to say, 'stop the NSAIDS in the third trimester.'”

For patients trying to conceive, “we advise that they avoid using COX-2s and NSAIDs during the conception cycle because both can have an impact on implantation,” Dr. Bermas noted.

Antimalarials

A single case report of congenital defects in three of four babies born to one mother who took 250 mg of chloroquine two times a day during each of her four pregnancies earned antimalarials an FDA category C rating, “which is sort of representative of how the literature about medication in pregnancy has been interpreted over the years,” said Dr. Bermas. In the meantime, she said, there have been several case series in which no increased risk of congenital anomalies has been seen, and the literature on the use of these drugs as malarial prophylaxis (at higher doses than are used to treat rheumatic disease) has identified no untoward effects in pregnant women.

“For many years, we didn't use any of these drugs during pregnancy, but a recent ACR survey showed that most rheumatologists today are comfortable leaving patients on antimalarials during pregnancy,” said Dr. Berman. “Having said that, if I have an RA patient whose main medication is hydroxychloroquine, that patient probably has fairly mild disease. Considering that most RA patients go into remission during pregnancy, I usually recommend stopping the drug during gestation.”

But for a patient with SLE who is well maintained on hydroxychloroquine, “I'd probably keep the medication on board,” because additional data show that patients with lupus who remain on therapy have better outcomes.

Steroids

For flares of most rheumatic diseases, steroids are considered “the ace in the hole,” said Dr. Bermas.

“During pregnancy, if rheumatoid arthritis, for example, becomes active, most clinicians recommend starting treatment with the lowest dose possible of a glucocorticoid medication, most commonly prednisone.” Both prednisone and methylprednisolone cross the placenta, but only at low levels, she said.

The data on steroid safety during pregnancy are mixed. “Originally, there were some case reports of cleft palate formation in offspring, although no increased risk of fetal anomalies was found in a large series of asthma patients treated with steroids throughout pregnancy,” said Dr. Bermas. “In a meta-analysis of epidemiological studies, however, there was a 3.4-fold increase in the incidence of cleft palate formation associated with maternal exposure to corticosteroids [Teratology, 2000;62:385–92],” she said. “The key time frame seems to be between weeks 6 and 12, when the palate is forming.”

Corticosteroids during pregnancy are also associated with maternal comorbidities, including gestational diabetes, hypertension, and accelerated osteoporosis. “For this reason, the goal should always be to keep the dose as low as possible,” she said.

Azathioprine and 6-Mercaptopurine

The use of azathioprine, a nonbiologic disease-modifying antirheumatic drug, is generally limited to women with severe disease who have not responded to other treatments, Dr. Bermas stated. There are “conflicting data about the safety of this drug during pregnancy. Animal data [suggest that] the drug is teratogenic, and there have been case reports of fetal malformations, but transplant series indicate that the medication doesn't increase the rate of congenital anomalies,” she said. Small-for-gestational-age babies and premature rupture of membranes are associated with use of the drug during pregnancy.

As with azathioprine, the nucleoside analog 6-mercaptopurine is teratogenic in animals, and it is plagued by conflicting human data. Some of the human studies suggest that “there is an increased risk of congenital anomalies, but the gastrointestinal literature doesn't support this,” Dr. Bermas noted. “From a rheumatology perspective, this medication is rarely used, so I would suggest discontinuing it during pregnancy.”

Sulfasalazine

“Case reports of fetal malformations linked to sulfasalazine from the inflammatory bowel disease literature didn't pan out in larger studies,” said Dr. Bermas. “This drug can be used in pregnancy. It does cause azoospermia in men, however, so if you have a male patient who is interested in trying to get his partner pregnant, advise him to stop taking sulfasalazine for 3 months before conception for spermatogenesis.”

Penicillamine

Occasionally used in the treatment of progressive systemic sclerosis, penicillamine has been shown to interfere with collagen biosynthesis and to cause malformations in animal studies, according to Dr. Bermas. “In humans, cases of cutis laxa and connective tissue disorders have been reported with exposure to this medication,” she said. As such, “this medication should not be used during pregnancy.”

Mycophenolate Mofetil

“We had such high hopes for mycophenolate mofetil. We thought this would be one of those medications that could be safely used during pregnancy,” said Dr. Bermas. “Unfortunately, there are increased case reports of congenital anomalies, including one report of the drug being used during pregnancy in a renal transplant patient. The baby was born prematurely and was noted to have hypoplastic nails and short fifth fingers.” Although there is not a rich body of literature yet, “this medication should be avoided during pregnancy,” she said.

IVIG

Intravenous immunoglobulin is not a common drug for rheumatologic disorders, and the literature on its use in pregnancy is limited. “In one case report of an individual with steroid-resistant idiopathic thrombocytopenic purpura, IVIG was used with no adverse effects on the offspring,” said Dr. Bermas. “The medication has also been used to manage the obstetrical complications of the antiphospholipid antibody syndrome without inducing congenital malformations.” Based on the available data, IVIG, when warranted, is acceptable for use in pregnancy, she said.

Cyclosporin A

The large body of data regarding the use of cyclosporin A during pregnancy comes from the transplant literature. “These medications are not teratogenic, although they are associated with small-for-gestational-age infants and hypertension of pregnancy,” said Dr. Bermas. The drug is not widely used, but in individual cases, if the potential benefit outweighs the possible risk, clinicians may choose to continue treatment with it, she noted.

Chlorambucil and Cyclophosphamide

Both of these cytotoxic agents are teratogenic and should be avoided during pregnancy, Dr. Bermas stressed. “In life-or-death situations, cyclophosphosamide has been used in the third trimester,” she said.

Methotrexate

Because of the high risk of congenital anomalies, methotrexate is an FDA category X drug for use in pregnancy. In addition to being teratogenic, it is also abortifacient, said Dr. Bermas, noting that, in terms of gestation, the use of methotrexate during weeks 6–8 at dosages greater than 10 mg/day substantially increases the risk of fetal harm. “I recommend that patients, both men and women, discontinue methotrexate for at least 3 months prior to conception,” she said.

Leflunomide

Another FDA category X drug for use in pregnancy because of its high teratogenicity, leflunomide “has an extremely long half-life, so either you need to wash out with cholestyramine or discontinue for 2 years before conception,” said Dr. Bermas. “As a general rule, I avoid using this in women of childbearing potential.”

Anti-TNF-α Agents

Limited data exist regarding the safety of the tumor necrosis factor-? inhibitors during pregnancy, “although case reports of two infants exposed to these drugs in utero being born with anomalies potentially consistent with VACTERL [vertebral, anal, cardiac, tracheal, esophageal, renal, and limb] syndrome give clinicians pause,” said Dr. Bermas. On the other hand, animal studies reported no teratogenic or fetotoxic effects, and some reports on human pregnancy in patients taking these drugs did not show an increase in birth defects or adverse pregnancy outcomes, she said. In one large study comprising 131 patients with inflammatory chronic diseases—including 8 patients with RA—who were directly exposed to inifliximab, drug exposure during pregnancy resulted in outcomes similar to those seen in the general population of pregnant women (Am. J. Gastroenterol, 2004;99:2385–92).

Rituximab

More commonly used for the treatment of non-Hodgkin's lymphoma, rituximab is also used for patients with refractory RA. Although as of yet there are no reports of congenital anomalies associated with this anti-CD20 monoclonal antibody, “there are insufficient data regarding the safety of the drug in animal or human pregnancy,” said Dr. Bermas. Two case reports of successful outcomes in women treated with rituximab for non-Hodgkin's lymphoma during pregnancy are promising, but not yet representative, she said. In fact, given the availability of safer alternative medications for pregnant RA patients, along with the possibility of remission during pregnancy, rituximab should probably be avoided unless there's a compelling reason to use it, she said.

Drug Treatment Considerations

The treatment of rheumatic diseases in pregnant women should be based on disease severity and drug safety, according to Dr. Bermas, who suggested the following general guide to treatment options:

Mild Disease

▸ For inflammatory arthritis, Dr. Bermas recommends stopping drug therapy before pregnancy or when pregnancy is discovered.

▸ For SLE, maintain these patients on hydroxychloroquine.

▸ NSAIDS are acceptable up to week 24.

Moderate Disease

▸ Steroids should be used at the lowest possible dose.

▸ Azathioprine should be used with caution.

▸ Cyclosporin A should be used with caution.

▸ Sulfasalazine should be used with caution.

Severe Disease

▸ High-dose steroids should be used with caution.

▸ Azathioprine should be used with caution.

▸ Cyclosporin A should be used with caution.

▸ Cyclophosphamide should be used only in life-or-death situations.

BOSTON — Don't do Pap smears in adolescents under age 21 years or in the first 3 years after their sexual debut “because it can do more harm than good.”

“High-grade lesions are rare in teenagers … and they take years to develop,” Dr. Michael S. Policar stressed at a conference on contraceptive technology sponsored by Contemporary Forums. About “91% of low-grade lesions in teens, such as cervical intraepithelial neoplasia 1 [CIN 1] often resolve spontaneously, 6% remain stable, and only 3% progress to high-grade dysplasia.” Biopsy-proven CIN 2 lesions often also regress spontaneously, he added.

Recognition of these early cytologic abnormalities on Pap testing could lead to unnecessary intervention and consequent risks, said Dr. Policar of the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco. As such, the American College of Obstetricians and Gynecologists recommends Pap testing should not be initiated until age 21 or 3 years after first intercourse.

Restraint is also warranted in managing teens whose Pap tests show atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL). Consensus guidelines call for reflex human papillomavirus (HPV) testing for women with ASC-US and colposcopic examination of the cervix for HPV infection, LSIL, and high-grade squamous intraepithelial lesion (HSIL). But these no longer apply to adolescents and young women, he said, referring to the American Society for Colposcopy and Cervical Pathology guidelines for abnormal cervical screening tests (Am. J. Obstet. Gynecol. 2007; 197:346-55). Those adolescents should undergo a repeat Pap smear in 12 months.

Dr. Policar disclosed that he is a speaker for Graceway Pharmaceuticals LLC, Merck & Co., and TyRx Pharma Inc.

BOSTON — Don't do Pap smears in adolescents under age 21 years or in the first 3 years after their sexual debut “because it can do more harm than good.”

“High-grade lesions are rare in teenagers … and they take years to develop,” Dr. Michael S. Policar stressed at a conference on contraceptive technology sponsored by Contemporary Forums. About “91% of low-grade lesions in teens, such as cervical intraepithelial neoplasia 1 [CIN 1] often resolve spontaneously, 6% remain stable, and only 3% progress to high-grade dysplasia.” Biopsy-proven CIN 2 lesions often also regress spontaneously, he added.

Recognition of these early cytologic abnormalities on Pap testing could lead to unnecessary intervention and consequent risks, said Dr. Policar of the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco. As such, the American College of Obstetricians and Gynecologists recommends Pap testing should not be initiated until age 21 or 3 years after first intercourse.

Restraint is also warranted in managing teens whose Pap tests show atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL). Consensus guidelines call for reflex human papillomavirus (HPV) testing for women with ASC-US and colposcopic examination of the cervix for HPV infection, LSIL, and high-grade squamous intraepithelial lesion (HSIL). But these no longer apply to adolescents and young women, he said, referring to the American Society for Colposcopy and Cervical Pathology guidelines for abnormal cervical screening tests (Am. J. Obstet. Gynecol. 2007; 197:346-55). Those adolescents should undergo a repeat Pap smear in 12 months.

Dr. Policar disclosed that he is a speaker for Graceway Pharmaceuticals LLC, Merck & Co., and TyRx Pharma Inc.

BOSTON — Don't do Pap smears in adolescents under age 21 years or in the first 3 years after their sexual debut “because it can do more harm than good.”

“High-grade lesions are rare in teenagers … and they take years to develop,” Dr. Michael S. Policar stressed at a conference on contraceptive technology sponsored by Contemporary Forums. About “91% of low-grade lesions in teens, such as cervical intraepithelial neoplasia 1 [CIN 1] often resolve spontaneously, 6% remain stable, and only 3% progress to high-grade dysplasia.” Biopsy-proven CIN 2 lesions often also regress spontaneously, he added.

Recognition of these early cytologic abnormalities on Pap testing could lead to unnecessary intervention and consequent risks, said Dr. Policar of the department of obstetrics, gynecology, and reproductive sciences at the University of California, San Francisco. As such, the American College of Obstetricians and Gynecologists recommends Pap testing should not be initiated until age 21 or 3 years after first intercourse.

Restraint is also warranted in managing teens whose Pap tests show atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intraepithelial lesions (LSIL). Consensus guidelines call for reflex human papillomavirus (HPV) testing for women with ASC-US and colposcopic examination of the cervix for HPV infection, LSIL, and high-grade squamous intraepithelial lesion (HSIL). But these no longer apply to adolescents and young women, he said, referring to the American Society for Colposcopy and Cervical Pathology guidelines for abnormal cervical screening tests (Am. J. Obstet. Gynecol. 2007; 197:346-55). Those adolescents should undergo a repeat Pap smear in 12 months.

Dr. Policar disclosed that he is a speaker for Graceway Pharmaceuticals LLC, Merck & Co., and TyRx Pharma Inc.