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Jeff Evans has been editor of Rheumatology News/MDedge Rheumatology and the EULAR Congress News since 2013. He started at Frontline Medical Communications in 2001 and was a reporter for 8 years before serving as editor of Clinical Neurology News and World Neurology, and briefly as editor of GI & Hepatology News. He graduated cum laude from Cornell University (New York) with a BA in biological sciences, concentrating in neurobiology and behavior.
Postop PTH Test Unnecessary When Calcium Is Normal
LOUISVILLE, KY. — Patients who have undergone surgery for primary hyperparathyroidism do not benefit from routine measures of parathyroid hormone unless they have elevated calcium levels, according to a review presented by Dr. Tina Wei-Fang Yen at the annual meeting of the Central Surgical Association.
“We propose that calcium levels be obtained postoperatively at 1–2 weeks. If normal, they should be repeated at 6 months and then yearly. If the calcium level is elevated at any time point, we recommend checking the [parathyroid hormone] level,” said Dr. Yen.
Her advice is based on the findings of a review that found routine postoperative parathyroid hormone (PTH) testing of questionable benefit, even among the 20%–40% of patients with elevated PTH levels and normal serum calcium levels after curative parathyroidectomy. Furthermore, this additional testing adds cost and can make patients anxious, commented Dr. Yen of the general surgery department at the Medical College of Wisconsin, Milwaukee.
Dr. Yen and her associates compared the utility of postoperative and intraoperative PTH testing with that of intraoperative PTH testing alone.
The investigators used a prospective database of 328 consecutive patients who had PTH levels measured during and after 330 parathyroidectomies performed in 1999–2004.
In the study, the intraoperative PTH testing criteria used to conclude each operation included a measurement of the PTH level at 10 minutes after resection of the last parathyroid gland. This PTH level was at least 50% lower than the baseline value and was in the normal range of the intraoperative PTH assay.
Patients' calcium levels were measured at 1 week, 3 months, and 6 or more months after the operation. Normocalcemia at 6 or more months follow-up was considered to be a cure, Dr. Yen said.
In surgeries that met the intraoperative PTH testing criteria, the cure rate was 98.2%, which is similar to values reported in the literature, Dr. Yen said. A normal postoperative PTH level predicted cure, with a positive predictive value of 97.1% at 1 week, 97.3% at 3 months, and 96.5% at 6 months.
However, operative failure was not predicted with much success by failure to meet the intraoperative PTH testing criteria or by elevated PTH levels after surgery. Only 23.2% of the cases that failed to meet intraoperative PTH testing criteria proved to be actual failures. Furthermore, an elevated postoperative PTH level predicted operative failure in 13.7% at 1 week, in 14.3% at 3 months, and in 14% at 6 months. Most patients with elevated postoperative PTH levels were normocalcemic at follow-up of 6 months or longer, Dr. Yen said.
The percentage of cured patients who had an elevated postoperative PTH level ranged from 16% at 1 week after surgery to 25% at 6 months after surgery. Among the 315 patients who were cured, postoperative PTH measurements followed no distinct trend, regardless of whether the postoperative PTH level was initially normal or elevated at 1 week after surgery. Postoperative PTH values also fluctuated between elevated and normal values among the 15 patients whose operations failed.
“Although we do not have postoperative PTH values for every patient at every time point, our data demonstrate that postoperative PTH values fluctuate over time and do not predict failure well,” Dr. Yen said.
LOUISVILLE, KY. — Patients who have undergone surgery for primary hyperparathyroidism do not benefit from routine measures of parathyroid hormone unless they have elevated calcium levels, according to a review presented by Dr. Tina Wei-Fang Yen at the annual meeting of the Central Surgical Association.
“We propose that calcium levels be obtained postoperatively at 1–2 weeks. If normal, they should be repeated at 6 months and then yearly. If the calcium level is elevated at any time point, we recommend checking the [parathyroid hormone] level,” said Dr. Yen.
Her advice is based on the findings of a review that found routine postoperative parathyroid hormone (PTH) testing of questionable benefit, even among the 20%–40% of patients with elevated PTH levels and normal serum calcium levels after curative parathyroidectomy. Furthermore, this additional testing adds cost and can make patients anxious, commented Dr. Yen of the general surgery department at the Medical College of Wisconsin, Milwaukee.
Dr. Yen and her associates compared the utility of postoperative and intraoperative PTH testing with that of intraoperative PTH testing alone.
The investigators used a prospective database of 328 consecutive patients who had PTH levels measured during and after 330 parathyroidectomies performed in 1999–2004.
In the study, the intraoperative PTH testing criteria used to conclude each operation included a measurement of the PTH level at 10 minutes after resection of the last parathyroid gland. This PTH level was at least 50% lower than the baseline value and was in the normal range of the intraoperative PTH assay.
Patients' calcium levels were measured at 1 week, 3 months, and 6 or more months after the operation. Normocalcemia at 6 or more months follow-up was considered to be a cure, Dr. Yen said.
In surgeries that met the intraoperative PTH testing criteria, the cure rate was 98.2%, which is similar to values reported in the literature, Dr. Yen said. A normal postoperative PTH level predicted cure, with a positive predictive value of 97.1% at 1 week, 97.3% at 3 months, and 96.5% at 6 months.
However, operative failure was not predicted with much success by failure to meet the intraoperative PTH testing criteria or by elevated PTH levels after surgery. Only 23.2% of the cases that failed to meet intraoperative PTH testing criteria proved to be actual failures. Furthermore, an elevated postoperative PTH level predicted operative failure in 13.7% at 1 week, in 14.3% at 3 months, and in 14% at 6 months. Most patients with elevated postoperative PTH levels were normocalcemic at follow-up of 6 months or longer, Dr. Yen said.
The percentage of cured patients who had an elevated postoperative PTH level ranged from 16% at 1 week after surgery to 25% at 6 months after surgery. Among the 315 patients who were cured, postoperative PTH measurements followed no distinct trend, regardless of whether the postoperative PTH level was initially normal or elevated at 1 week after surgery. Postoperative PTH values also fluctuated between elevated and normal values among the 15 patients whose operations failed.
“Although we do not have postoperative PTH values for every patient at every time point, our data demonstrate that postoperative PTH values fluctuate over time and do not predict failure well,” Dr. Yen said.
LOUISVILLE, KY. — Patients who have undergone surgery for primary hyperparathyroidism do not benefit from routine measures of parathyroid hormone unless they have elevated calcium levels, according to a review presented by Dr. Tina Wei-Fang Yen at the annual meeting of the Central Surgical Association.
“We propose that calcium levels be obtained postoperatively at 1–2 weeks. If normal, they should be repeated at 6 months and then yearly. If the calcium level is elevated at any time point, we recommend checking the [parathyroid hormone] level,” said Dr. Yen.
Her advice is based on the findings of a review that found routine postoperative parathyroid hormone (PTH) testing of questionable benefit, even among the 20%–40% of patients with elevated PTH levels and normal serum calcium levels after curative parathyroidectomy. Furthermore, this additional testing adds cost and can make patients anxious, commented Dr. Yen of the general surgery department at the Medical College of Wisconsin, Milwaukee.
Dr. Yen and her associates compared the utility of postoperative and intraoperative PTH testing with that of intraoperative PTH testing alone.
The investigators used a prospective database of 328 consecutive patients who had PTH levels measured during and after 330 parathyroidectomies performed in 1999–2004.
In the study, the intraoperative PTH testing criteria used to conclude each operation included a measurement of the PTH level at 10 minutes after resection of the last parathyroid gland. This PTH level was at least 50% lower than the baseline value and was in the normal range of the intraoperative PTH assay.
Patients' calcium levels were measured at 1 week, 3 months, and 6 or more months after the operation. Normocalcemia at 6 or more months follow-up was considered to be a cure, Dr. Yen said.
In surgeries that met the intraoperative PTH testing criteria, the cure rate was 98.2%, which is similar to values reported in the literature, Dr. Yen said. A normal postoperative PTH level predicted cure, with a positive predictive value of 97.1% at 1 week, 97.3% at 3 months, and 96.5% at 6 months.
However, operative failure was not predicted with much success by failure to meet the intraoperative PTH testing criteria or by elevated PTH levels after surgery. Only 23.2% of the cases that failed to meet intraoperative PTH testing criteria proved to be actual failures. Furthermore, an elevated postoperative PTH level predicted operative failure in 13.7% at 1 week, in 14.3% at 3 months, and in 14% at 6 months. Most patients with elevated postoperative PTH levels were normocalcemic at follow-up of 6 months or longer, Dr. Yen said.
The percentage of cured patients who had an elevated postoperative PTH level ranged from 16% at 1 week after surgery to 25% at 6 months after surgery. Among the 315 patients who were cured, postoperative PTH measurements followed no distinct trend, regardless of whether the postoperative PTH level was initially normal or elevated at 1 week after surgery. Postoperative PTH values also fluctuated between elevated and normal values among the 15 patients whose operations failed.
“Although we do not have postoperative PTH values for every patient at every time point, our data demonstrate that postoperative PTH values fluctuate over time and do not predict failure well,” Dr. Yen said.
Study Reinterpreted: OCD Responds to Skilled Therapy
NEW YORK – Cognitive-behavioral therapy, when provided by a skilled therapist, can be just as effective as an SSRI or combined treatment for children with obsessive-compulsive disorder, Dr. Daniel S. Pine said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.
To reach that conclusion, Dr. Pine interpreted data from the Pediatric OCD Treatment Study differently than did the study's investigators.
The Pediatric OCD Treatment Study is the only published trial that compares cognitive-behavioral therapy (CBT) with an SSRI for the treatment of pediatric OCD, said Dr. Pine, chief of the section on development and affective neuroscience in the mood and anxiety disorders program at the National Institute of Mental Health.
In the study, 112 patients were randomized to receive sertraline (Zoloft), cognitive-behavioral therapy (CBT), a combination of the two modalities, or placebo for 12 weeks. Patients were treated at one of three sites, and were enrolled primarily at two of the sites (JAMA 2004;292:1969–76).
“There were robust site differences in the response to treatment,” he said. “When you look very carefully at the data that are published, what you see was that one site had a massive response to CBT and there was no benefit of adding an SSRI to CBT.” The other site had a “very weak” response to CBT, an “okay” response to an SSRI, and a “robust” response to the combination treatment, he noted.
The averaged data for the three sites showed a statistically significant benefit of combination therapy over CBT alone, sertraline alone, and placebo. The investigators concluded that pediatric patients with OCD should receive combination therapy.
“Personally, I think that's a misreading of the study,” Dr. Pine said. “I think what the study really tells us is that really well-executed CBT in kids with OCD is every bit as good as monotherapy [with an SSRI] and is every bit as good as combination therapy; however, not-so-great CBT really needs an SSRI to work.”
“It would be wonderful if CBT was always the same across therapists, patients, and cities, but it's not, and this study really shows it,” he added.
CBT might be the preferred method for treating pediatric OCD, especially in patients without a history of attention-deficit hyperactivity disorder or major depression, because the availability of a CBT therapist will vary depending on geographic location and the fact that there are “tremendous site differences in CBT,” he said.
“This recommendation only applies to the case where you have access to a very skilled CBT therapist who has worked with pediatric anxiety disorders,” Dr. Pine explained.
An SSRI should be used if a skilled CBT therapist is not available or if a child has a severe anxiety disorder and will not undergo the crucial part of CBT that involves exposure to the feared stimulus, he advised.
NEW YORK – Cognitive-behavioral therapy, when provided by a skilled therapist, can be just as effective as an SSRI or combined treatment for children with obsessive-compulsive disorder, Dr. Daniel S. Pine said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.
To reach that conclusion, Dr. Pine interpreted data from the Pediatric OCD Treatment Study differently than did the study's investigators.
The Pediatric OCD Treatment Study is the only published trial that compares cognitive-behavioral therapy (CBT) with an SSRI for the treatment of pediatric OCD, said Dr. Pine, chief of the section on development and affective neuroscience in the mood and anxiety disorders program at the National Institute of Mental Health.
In the study, 112 patients were randomized to receive sertraline (Zoloft), cognitive-behavioral therapy (CBT), a combination of the two modalities, or placebo for 12 weeks. Patients were treated at one of three sites, and were enrolled primarily at two of the sites (JAMA 2004;292:1969–76).
“There were robust site differences in the response to treatment,” he said. “When you look very carefully at the data that are published, what you see was that one site had a massive response to CBT and there was no benefit of adding an SSRI to CBT.” The other site had a “very weak” response to CBT, an “okay” response to an SSRI, and a “robust” response to the combination treatment, he noted.
The averaged data for the three sites showed a statistically significant benefit of combination therapy over CBT alone, sertraline alone, and placebo. The investigators concluded that pediatric patients with OCD should receive combination therapy.
“Personally, I think that's a misreading of the study,” Dr. Pine said. “I think what the study really tells us is that really well-executed CBT in kids with OCD is every bit as good as monotherapy [with an SSRI] and is every bit as good as combination therapy; however, not-so-great CBT really needs an SSRI to work.”
“It would be wonderful if CBT was always the same across therapists, patients, and cities, but it's not, and this study really shows it,” he added.
CBT might be the preferred method for treating pediatric OCD, especially in patients without a history of attention-deficit hyperactivity disorder or major depression, because the availability of a CBT therapist will vary depending on geographic location and the fact that there are “tremendous site differences in CBT,” he said.
“This recommendation only applies to the case where you have access to a very skilled CBT therapist who has worked with pediatric anxiety disorders,” Dr. Pine explained.
An SSRI should be used if a skilled CBT therapist is not available or if a child has a severe anxiety disorder and will not undergo the crucial part of CBT that involves exposure to the feared stimulus, he advised.
NEW YORK – Cognitive-behavioral therapy, when provided by a skilled therapist, can be just as effective as an SSRI or combined treatment for children with obsessive-compulsive disorder, Dr. Daniel S. Pine said at a psychopharmacology update sponsored by the American Academy of Child and Adolescent Psychiatry.
To reach that conclusion, Dr. Pine interpreted data from the Pediatric OCD Treatment Study differently than did the study's investigators.
The Pediatric OCD Treatment Study is the only published trial that compares cognitive-behavioral therapy (CBT) with an SSRI for the treatment of pediatric OCD, said Dr. Pine, chief of the section on development and affective neuroscience in the mood and anxiety disorders program at the National Institute of Mental Health.
In the study, 112 patients were randomized to receive sertraline (Zoloft), cognitive-behavioral therapy (CBT), a combination of the two modalities, or placebo for 12 weeks. Patients were treated at one of three sites, and were enrolled primarily at two of the sites (JAMA 2004;292:1969–76).
“There were robust site differences in the response to treatment,” he said. “When you look very carefully at the data that are published, what you see was that one site had a massive response to CBT and there was no benefit of adding an SSRI to CBT.” The other site had a “very weak” response to CBT, an “okay” response to an SSRI, and a “robust” response to the combination treatment, he noted.
The averaged data for the three sites showed a statistically significant benefit of combination therapy over CBT alone, sertraline alone, and placebo. The investigators concluded that pediatric patients with OCD should receive combination therapy.
“Personally, I think that's a misreading of the study,” Dr. Pine said. “I think what the study really tells us is that really well-executed CBT in kids with OCD is every bit as good as monotherapy [with an SSRI] and is every bit as good as combination therapy; however, not-so-great CBT really needs an SSRI to work.”
“It would be wonderful if CBT was always the same across therapists, patients, and cities, but it's not, and this study really shows it,” he added.
CBT might be the preferred method for treating pediatric OCD, especially in patients without a history of attention-deficit hyperactivity disorder or major depression, because the availability of a CBT therapist will vary depending on geographic location and the fact that there are “tremendous site differences in CBT,” he said.
“This recommendation only applies to the case where you have access to a very skilled CBT therapist who has worked with pediatric anxiety disorders,” Dr. Pine explained.
An SSRI should be used if a skilled CBT therapist is not available or if a child has a severe anxiety disorder and will not undergo the crucial part of CBT that involves exposure to the feared stimulus, he advised.
Immigrants in Need of Comprehensive Care
WASHINGTON — Health care for U.S. immigrants needs to go beyond screening for a few specific infectious diseases by providing care addressing the long-term needs of individuals as well as public health concerns, Dr. Elizabeth D. Barnett said at the annual meeting of the American Society of Tropical Medicine and Hygiene.
“We need to talk about a comprehensive health assessment and move away from the idea of a one-time screening,” said Dr. Barnett, director of the International Clinic at Boston Medical Center.
Adequate comprehensive health assessments would focus not only on diseases of public health significance, but also diseases and conditions that affect the health of individuals and their families over decades. Such assessments would include:
▸ History and physical examination.
▸ Screening for infectious diseases such as tuberculosis and hepatitis B, and other standard tests of vision, hearing, and dental health.
▸ Routine immunizations, and other immunizations when indicated.
▸ Identification of risk factors for chronic diseases such as hepatitis B infection leading to liver disease, Helicobacter pylori infection leading to gastric cancer, and human papillomavirus infection leading to cervical cancer.
▸ Health risks related to lifestyle, such as obesity, inactivity, smoking, and dental caries.
▸ Primary care visits and subspecialty follow-up.
In addition to using a universal screening panel for certain diseases, clinicians could perform targeted screening tests related to risk groups, Dr. Barnett said.
Universal screening programs use easily applied protocols that don't leave any patients out, but they are not responsive to differences in immigrant groups. Targeted screening programs could change according to the immigrant group, provided that clinicians stay up to date on health risks, she said.
Physicians who care for undocumented or migrant populations may think that they cannot do extensive screening because many such immigrants do not have health insurance and cannot pay for the services. “We need to keep in mind that there will be benefits in the long run if we address the most important health needs right up front,” she said.
A system of screening for new immigrants could combine standard tests for diseases that pose significant burdens but that have readily available interventions—such as TB, hepatitis B, and anemia—with other screening tests that focus on risk factors.
Foreign-born persons accounted for 53% of TB cases in 2003; foreign-born persons had a rate of about 24 per 100,000 people, compared with 3 per 100,000 in U.S.-born individuals. Positive results on tuberculin skin tests have ranged in some immigrant and refugee groups from 25% to 70% in different years.
In immigrant populations with specific risk factors, targeted screening tests could look for diseases or conditions with proven interventions—lead levels in refugee and adopted children, schistosomiasis and strongyloides in Sudanese refugees, treponemiasis (syphilis) in refugee children, and Varicella antibody testing.
The increased prevalences of both H. pylori infection and cervical cancer in developing countries are two examples of health disparities in immigrant populations. No one knows for sure how immigrants with an H. pylori infection, many of whom are children, may fare 10 or 20 years from now, Dr. Barnett said.
Cervical cancer occurs at higher rates in Southeast Asian nations, but one report showed that a lower percentage of immigrant women aged 65 years or older from Cambodia and Vietnam had received a Pap smear in the preceding 3 years (64%–66%) than had women in the U.S. general population (86%) (MMWR 2004;53:760–7).
WASHINGTON — Health care for U.S. immigrants needs to go beyond screening for a few specific infectious diseases by providing care addressing the long-term needs of individuals as well as public health concerns, Dr. Elizabeth D. Barnett said at the annual meeting of the American Society of Tropical Medicine and Hygiene.
“We need to talk about a comprehensive health assessment and move away from the idea of a one-time screening,” said Dr. Barnett, director of the International Clinic at Boston Medical Center.
Adequate comprehensive health assessments would focus not only on diseases of public health significance, but also diseases and conditions that affect the health of individuals and their families over decades. Such assessments would include:
▸ History and physical examination.
▸ Screening for infectious diseases such as tuberculosis and hepatitis B, and other standard tests of vision, hearing, and dental health.
▸ Routine immunizations, and other immunizations when indicated.
▸ Identification of risk factors for chronic diseases such as hepatitis B infection leading to liver disease, Helicobacter pylori infection leading to gastric cancer, and human papillomavirus infection leading to cervical cancer.
▸ Health risks related to lifestyle, such as obesity, inactivity, smoking, and dental caries.
▸ Primary care visits and subspecialty follow-up.
In addition to using a universal screening panel for certain diseases, clinicians could perform targeted screening tests related to risk groups, Dr. Barnett said.
Universal screening programs use easily applied protocols that don't leave any patients out, but they are not responsive to differences in immigrant groups. Targeted screening programs could change according to the immigrant group, provided that clinicians stay up to date on health risks, she said.
Physicians who care for undocumented or migrant populations may think that they cannot do extensive screening because many such immigrants do not have health insurance and cannot pay for the services. “We need to keep in mind that there will be benefits in the long run if we address the most important health needs right up front,” she said.
A system of screening for new immigrants could combine standard tests for diseases that pose significant burdens but that have readily available interventions—such as TB, hepatitis B, and anemia—with other screening tests that focus on risk factors.
Foreign-born persons accounted for 53% of TB cases in 2003; foreign-born persons had a rate of about 24 per 100,000 people, compared with 3 per 100,000 in U.S.-born individuals. Positive results on tuberculin skin tests have ranged in some immigrant and refugee groups from 25% to 70% in different years.
In immigrant populations with specific risk factors, targeted screening tests could look for diseases or conditions with proven interventions—lead levels in refugee and adopted children, schistosomiasis and strongyloides in Sudanese refugees, treponemiasis (syphilis) in refugee children, and Varicella antibody testing.
The increased prevalences of both H. pylori infection and cervical cancer in developing countries are two examples of health disparities in immigrant populations. No one knows for sure how immigrants with an H. pylori infection, many of whom are children, may fare 10 or 20 years from now, Dr. Barnett said.
Cervical cancer occurs at higher rates in Southeast Asian nations, but one report showed that a lower percentage of immigrant women aged 65 years or older from Cambodia and Vietnam had received a Pap smear in the preceding 3 years (64%–66%) than had women in the U.S. general population (86%) (MMWR 2004;53:760–7).
WASHINGTON — Health care for U.S. immigrants needs to go beyond screening for a few specific infectious diseases by providing care addressing the long-term needs of individuals as well as public health concerns, Dr. Elizabeth D. Barnett said at the annual meeting of the American Society of Tropical Medicine and Hygiene.
“We need to talk about a comprehensive health assessment and move away from the idea of a one-time screening,” said Dr. Barnett, director of the International Clinic at Boston Medical Center.
Adequate comprehensive health assessments would focus not only on diseases of public health significance, but also diseases and conditions that affect the health of individuals and their families over decades. Such assessments would include:
▸ History and physical examination.
▸ Screening for infectious diseases such as tuberculosis and hepatitis B, and other standard tests of vision, hearing, and dental health.
▸ Routine immunizations, and other immunizations when indicated.
▸ Identification of risk factors for chronic diseases such as hepatitis B infection leading to liver disease, Helicobacter pylori infection leading to gastric cancer, and human papillomavirus infection leading to cervical cancer.
▸ Health risks related to lifestyle, such as obesity, inactivity, smoking, and dental caries.
▸ Primary care visits and subspecialty follow-up.
In addition to using a universal screening panel for certain diseases, clinicians could perform targeted screening tests related to risk groups, Dr. Barnett said.
Universal screening programs use easily applied protocols that don't leave any patients out, but they are not responsive to differences in immigrant groups. Targeted screening programs could change according to the immigrant group, provided that clinicians stay up to date on health risks, she said.
Physicians who care for undocumented or migrant populations may think that they cannot do extensive screening because many such immigrants do not have health insurance and cannot pay for the services. “We need to keep in mind that there will be benefits in the long run if we address the most important health needs right up front,” she said.
A system of screening for new immigrants could combine standard tests for diseases that pose significant burdens but that have readily available interventions—such as TB, hepatitis B, and anemia—with other screening tests that focus on risk factors.
Foreign-born persons accounted for 53% of TB cases in 2003; foreign-born persons had a rate of about 24 per 100,000 people, compared with 3 per 100,000 in U.S.-born individuals. Positive results on tuberculin skin tests have ranged in some immigrant and refugee groups from 25% to 70% in different years.
In immigrant populations with specific risk factors, targeted screening tests could look for diseases or conditions with proven interventions—lead levels in refugee and adopted children, schistosomiasis and strongyloides in Sudanese refugees, treponemiasis (syphilis) in refugee children, and Varicella antibody testing.
The increased prevalences of both H. pylori infection and cervical cancer in developing countries are two examples of health disparities in immigrant populations. No one knows for sure how immigrants with an H. pylori infection, many of whom are children, may fare 10 or 20 years from now, Dr. Barnett said.
Cervical cancer occurs at higher rates in Southeast Asian nations, but one report showed that a lower percentage of immigrant women aged 65 years or older from Cambodia and Vietnam had received a Pap smear in the preceding 3 years (64%–66%) than had women in the U.S. general population (86%) (MMWR 2004;53:760–7).
Proxy Clinical Markers for Shiga Toxin Disease Identified
WASHINGTON — The severity of disease caused by Shiga toxin-producing bacteria may be tracked with a new scale in development that uses clinical markers of disease rather than direct measurement of toxin load, Dr. Martin M. Bitzan reported at a biodefense research meeting sponsored by the American Society for Microbiology.
“While the clinical diagnosis of hemolytic uremic syndrome appears straightforward, there are no defined criteria to describe and grade the severity of hemolytic uremic syndrome or of the preceding gastrointestinal disease,” Dr. Bitzan of the department of nephrology, Montreal Children's Hospital, said in a poster.
Measurement of Shiga toxin in body fluids or tissue is currently not feasible, which makes it necessary to develop proxy markers of Shiga toxinemia, he and his colleague noted.
Sporadic cases or outbreaks of infections involving Shiga toxin-producing bacteria mostly occur in children in community settings. The majority of these infections in North America are caused by Escherichia coli serotype O157:H7.
The researchers developed a disease severity scale comprising four distinct facets of Shiga toxin-producing E. coli infections: enteropathy, inflammation and vasculopathy, thrombotic microangiopathy, and nephropathy.
They tested the scale on a database of 146 consecutive patients aged 1–16 years with Shiga toxin-producing E. coli who had bloody (85%) or nonbloody (15%) diarrhea that resulted in partial (5%) or complete (13%) hemolytic uremic syndrome (HUS). The scores of patients with HUS on all of the scale's components except enteropathy became significantly worse 3–5 days after disease onset than those without the syndrome. The scale is being validated in another study.
WASHINGTON — The severity of disease caused by Shiga toxin-producing bacteria may be tracked with a new scale in development that uses clinical markers of disease rather than direct measurement of toxin load, Dr. Martin M. Bitzan reported at a biodefense research meeting sponsored by the American Society for Microbiology.
“While the clinical diagnosis of hemolytic uremic syndrome appears straightforward, there are no defined criteria to describe and grade the severity of hemolytic uremic syndrome or of the preceding gastrointestinal disease,” Dr. Bitzan of the department of nephrology, Montreal Children's Hospital, said in a poster.
Measurement of Shiga toxin in body fluids or tissue is currently not feasible, which makes it necessary to develop proxy markers of Shiga toxinemia, he and his colleague noted.
Sporadic cases or outbreaks of infections involving Shiga toxin-producing bacteria mostly occur in children in community settings. The majority of these infections in North America are caused by Escherichia coli serotype O157:H7.
The researchers developed a disease severity scale comprising four distinct facets of Shiga toxin-producing E. coli infections: enteropathy, inflammation and vasculopathy, thrombotic microangiopathy, and nephropathy.
They tested the scale on a database of 146 consecutive patients aged 1–16 years with Shiga toxin-producing E. coli who had bloody (85%) or nonbloody (15%) diarrhea that resulted in partial (5%) or complete (13%) hemolytic uremic syndrome (HUS). The scores of patients with HUS on all of the scale's components except enteropathy became significantly worse 3–5 days after disease onset than those without the syndrome. The scale is being validated in another study.
WASHINGTON — The severity of disease caused by Shiga toxin-producing bacteria may be tracked with a new scale in development that uses clinical markers of disease rather than direct measurement of toxin load, Dr. Martin M. Bitzan reported at a biodefense research meeting sponsored by the American Society for Microbiology.
“While the clinical diagnosis of hemolytic uremic syndrome appears straightforward, there are no defined criteria to describe and grade the severity of hemolytic uremic syndrome or of the preceding gastrointestinal disease,” Dr. Bitzan of the department of nephrology, Montreal Children's Hospital, said in a poster.
Measurement of Shiga toxin in body fluids or tissue is currently not feasible, which makes it necessary to develop proxy markers of Shiga toxinemia, he and his colleague noted.
Sporadic cases or outbreaks of infections involving Shiga toxin-producing bacteria mostly occur in children in community settings. The majority of these infections in North America are caused by Escherichia coli serotype O157:H7.
The researchers developed a disease severity scale comprising four distinct facets of Shiga toxin-producing E. coli infections: enteropathy, inflammation and vasculopathy, thrombotic microangiopathy, and nephropathy.
They tested the scale on a database of 146 consecutive patients aged 1–16 years with Shiga toxin-producing E. coli who had bloody (85%) or nonbloody (15%) diarrhea that resulted in partial (5%) or complete (13%) hemolytic uremic syndrome (HUS). The scores of patients with HUS on all of the scale's components except enteropathy became significantly worse 3–5 days after disease onset than those without the syndrome. The scale is being validated in another study.
High BMI, Blood Glucose Tied to Blood Ca Deaths
BETHESDA, MD. — High body mass index and high plasma glucose levels after an oral glucose challenge are independently associated with an increased risk of dying of hematopoietic cancer, Dr. Brian Chiu reported at the annual meeting of the American Society of Preventive Oncology.
In some instances, those two factors showed a strong, dose-response relationship in increasing the risk of dying of hematopoietic cancer, particularly non-Hodgkin lymphoma (NHL) or leukemia.
“We are particularly focusing on non-Hodgkin lymphoma because according to Surveillance, Epidemiology, and End Results (SEER) data, the incidence of non-Hodgkin lymphoma in the United States has been increasing dramatically during the past 30 years” from about 10 cases per 100,000 person-years in 1973 to 20 per 100,000 in 2002, said Dr. Chiu of the department of preventive medicine at Northwestern University, Chicago. The increase has occurred in both men and women.
The prevalence of obesity has also increased at the same time, rising by 60% from 1970 to 1990 and by 74% from 1990 to 2002, according to data from the first three National Health and Nutrition Examination Surveys. The prevalence of diagnosed diabetes increased by about 60% during 1990–2004.
The current prospective study involved 35,420 people (average age 40 years) who participated in the Chicago Heart Association Detection Project in Industry during 1967–1973. The study was originally designed to screen for cardiovascular disease risk factors.
At baseline, participants' height and weight were assessed, as was blood glucose level 1 hour after they received an oral 50-g dose of glucose.
Dr. Chiu found that by the end of 2002, 129 study participants had died of NHL, 151 of leukemia, and 66 of multiple myeloma.
Men in the highest quartile of BMI (28.7 kg/m
Both men and women in the highest quartile of BMI also were 2–2.4 times more likely to die from leukemia than were those in the lowest quartile. Women, but not men, in the highest quartile of postload plasma glucose were significantly more likely to die of multiple myeloma than were women in the lowest quartile. The comparisons were adjusted for age, education, smoking status, race, and BMI or postload plasma glucose (depending on the comparison).
Dr. Chiu collected data on participant mortality, but not on the prevalence of hematopoietic cancers at baseline. He excluded people who died of a hematopoietic cancer within the first 5 years of the follow-up.
BETHESDA, MD. — High body mass index and high plasma glucose levels after an oral glucose challenge are independently associated with an increased risk of dying of hematopoietic cancer, Dr. Brian Chiu reported at the annual meeting of the American Society of Preventive Oncology.
In some instances, those two factors showed a strong, dose-response relationship in increasing the risk of dying of hematopoietic cancer, particularly non-Hodgkin lymphoma (NHL) or leukemia.
“We are particularly focusing on non-Hodgkin lymphoma because according to Surveillance, Epidemiology, and End Results (SEER) data, the incidence of non-Hodgkin lymphoma in the United States has been increasing dramatically during the past 30 years” from about 10 cases per 100,000 person-years in 1973 to 20 per 100,000 in 2002, said Dr. Chiu of the department of preventive medicine at Northwestern University, Chicago. The increase has occurred in both men and women.
The prevalence of obesity has also increased at the same time, rising by 60% from 1970 to 1990 and by 74% from 1990 to 2002, according to data from the first three National Health and Nutrition Examination Surveys. The prevalence of diagnosed diabetes increased by about 60% during 1990–2004.
The current prospective study involved 35,420 people (average age 40 years) who participated in the Chicago Heart Association Detection Project in Industry during 1967–1973. The study was originally designed to screen for cardiovascular disease risk factors.
At baseline, participants' height and weight were assessed, as was blood glucose level 1 hour after they received an oral 50-g dose of glucose.
Dr. Chiu found that by the end of 2002, 129 study participants had died of NHL, 151 of leukemia, and 66 of multiple myeloma.
Men in the highest quartile of BMI (28.7 kg/m
Both men and women in the highest quartile of BMI also were 2–2.4 times more likely to die from leukemia than were those in the lowest quartile. Women, but not men, in the highest quartile of postload plasma glucose were significantly more likely to die of multiple myeloma than were women in the lowest quartile. The comparisons were adjusted for age, education, smoking status, race, and BMI or postload plasma glucose (depending on the comparison).
Dr. Chiu collected data on participant mortality, but not on the prevalence of hematopoietic cancers at baseline. He excluded people who died of a hematopoietic cancer within the first 5 years of the follow-up.
BETHESDA, MD. — High body mass index and high plasma glucose levels after an oral glucose challenge are independently associated with an increased risk of dying of hematopoietic cancer, Dr. Brian Chiu reported at the annual meeting of the American Society of Preventive Oncology.
In some instances, those two factors showed a strong, dose-response relationship in increasing the risk of dying of hematopoietic cancer, particularly non-Hodgkin lymphoma (NHL) or leukemia.
“We are particularly focusing on non-Hodgkin lymphoma because according to Surveillance, Epidemiology, and End Results (SEER) data, the incidence of non-Hodgkin lymphoma in the United States has been increasing dramatically during the past 30 years” from about 10 cases per 100,000 person-years in 1973 to 20 per 100,000 in 2002, said Dr. Chiu of the department of preventive medicine at Northwestern University, Chicago. The increase has occurred in both men and women.
The prevalence of obesity has also increased at the same time, rising by 60% from 1970 to 1990 and by 74% from 1990 to 2002, according to data from the first three National Health and Nutrition Examination Surveys. The prevalence of diagnosed diabetes increased by about 60% during 1990–2004.
The current prospective study involved 35,420 people (average age 40 years) who participated in the Chicago Heart Association Detection Project in Industry during 1967–1973. The study was originally designed to screen for cardiovascular disease risk factors.
At baseline, participants' height and weight were assessed, as was blood glucose level 1 hour after they received an oral 50-g dose of glucose.
Dr. Chiu found that by the end of 2002, 129 study participants had died of NHL, 151 of leukemia, and 66 of multiple myeloma.
Men in the highest quartile of BMI (28.7 kg/m
Both men and women in the highest quartile of BMI also were 2–2.4 times more likely to die from leukemia than were those in the lowest quartile. Women, but not men, in the highest quartile of postload plasma glucose were significantly more likely to die of multiple myeloma than were women in the lowest quartile. The comparisons were adjusted for age, education, smoking status, race, and BMI or postload plasma glucose (depending on the comparison).
Dr. Chiu collected data on participant mortality, but not on the prevalence of hematopoietic cancers at baseline. He excluded people who died of a hematopoietic cancer within the first 5 years of the follow-up.
Clinical Capsules
Dietary Calcium Cuts Polyp Risk
Calcium obtained from dietary sources, but not calcium supplements, may protect against the development of colon polyps, Janet A. Tooze, Ph.D., reported in a poster presentation at the annual meeting of the American Society of Preventive Oncology.
In a retrospective study, 598 participants aged 40–69 years completed a food frequency questionnaire in 1992–1994 when they were participating in the Insulin Resistance Arteriosclerosis Study. They later underwent colonoscopy during 2002–2004.
Overall, people in the three highest quartiles of dietary calcium intake were about two to almost three times more likely to be free of colon polyps than were people in the lowest quartile. Supplemental calcium use did not significantly affect the risk for colon polyps. The cutoff for the lowest quartile of calcium intake was about 500 mg per day, said Dr. Tooze of Wake Forest University, Winston-Salem, N.C.
One or more polyps were found in 49% of the participants, including 32% with an adenoma or hyperplastic polyp, 23% with any adenoma, and 6% with an advanced adenoma.
The prevalence of supplemental calcium use was not high—only 15%, according to the researchers. “The source of calcium may be related to the protective effect for polyp development and adenoma development,” the researchers wrote.
Americans Avoid Colon Ca Screening
Aversion to colonoscopy and lack of physician communication are major reasons Americans avoid colon cancer screening, according to a survey of 1,200 people aged 50 to 70 years.
The survey, conducted in February by Harris Interactive, suggests that three out of four eligible Americans are not being screened regularly for this second leading cause of cancer death, a screening rate far lower than rates reported for breast, cervical, and prostate cancers. Only one-third of respondents said they had been screened at least once for colon cancer.
The primary reasons for not being screened included, “don't want to have a colonoscopy” (28%), “doctor did not discuss screening with them” (26%), “did not have any symptoms” (24%), “did not feel they were at risk” (17%), “did not follow through on MD [doctor] recommendations” (9%), “did not know they should be screened” (8%), “did not have time” (5%), and “embarrassed to discuss screening with MD” (4%). Respondents were able to select from more than one category.
Screening rates were highest among those who claimed to be the most knowledgeable about colon cancer. Only 35% of those who considered themselves lacking knowledge about colon cancer had ever been screened, but 79% of respondents who felt they were “knowledgeable” or “very knowledgeable” had been screened.
However, only half of respondents considered themselves knowledgeable about the disease, and far fewer understood the need for, and benefits of, screening.
A personal or family history of the disease was reported by one in five people. Over a third of adults said they were in “excellent” or “very good” health, and three-quarters felt they were doing a good job of managing their own health.
Entecavir vs. Lamivudine for HBV
Two head-to-head phase III trials have shown that the new drug entecavir may be superior to lamivudine for treating chronic hepatitis B.
The two nucleoside drugs were pitted against each other in double-blind trials that involved more than 1,300 patients with HBeAg-positive and HBeAg-negative chronic hepatitis B.
At 48 weeks into the antigen-positive study, histologic improvement was seen in 72% of the entecavir group and 62% of the lamivudine group. Target DNA levels were measured in 21% of patients in the entecavir group and 19% of those taking lamivudine. Significant virologic response occurred in 70% and 46%, respectively. There was no evidence of emerging resistant variants to entecavir, and the frequency of adverse events was similar for the two drugs (N. Engl. J. Med. 2006;354:1001–10).
Of the entecavir patients, 67% had undetectable levels of HBV DNA at 48 weeks. “The efficacy of entecavir appears to result from its potent suppression of HBV replication,” the authors explained.
In the study of HBeAg-negative patients, entecavir produced histologic improvement in 70% of patients, while lamivudine came in at 61%. Among patients not previously treated with a nucleoside analogue, the rates of histologic improvement, serologic response, and normalization of alanine aminotransferase levels were significantly higher at 48 weeks with entecavir than with lamivudine.
Again, the safety profiles of the two drugs were similar, and there was no evidence of viral resistance to entecavir, the investigators reported (N. Engl. J. Med. 2006;354:1011–20).
Dietary Calcium Cuts Polyp Risk
Calcium obtained from dietary sources, but not calcium supplements, may protect against the development of colon polyps, Janet A. Tooze, Ph.D., reported in a poster presentation at the annual meeting of the American Society of Preventive Oncology.
In a retrospective study, 598 participants aged 40–69 years completed a food frequency questionnaire in 1992–1994 when they were participating in the Insulin Resistance Arteriosclerosis Study. They later underwent colonoscopy during 2002–2004.
Overall, people in the three highest quartiles of dietary calcium intake were about two to almost three times more likely to be free of colon polyps than were people in the lowest quartile. Supplemental calcium use did not significantly affect the risk for colon polyps. The cutoff for the lowest quartile of calcium intake was about 500 mg per day, said Dr. Tooze of Wake Forest University, Winston-Salem, N.C.
One or more polyps were found in 49% of the participants, including 32% with an adenoma or hyperplastic polyp, 23% with any adenoma, and 6% with an advanced adenoma.
The prevalence of supplemental calcium use was not high—only 15%, according to the researchers. “The source of calcium may be related to the protective effect for polyp development and adenoma development,” the researchers wrote.
Americans Avoid Colon Ca Screening
Aversion to colonoscopy and lack of physician communication are major reasons Americans avoid colon cancer screening, according to a survey of 1,200 people aged 50 to 70 years.
The survey, conducted in February by Harris Interactive, suggests that three out of four eligible Americans are not being screened regularly for this second leading cause of cancer death, a screening rate far lower than rates reported for breast, cervical, and prostate cancers. Only one-third of respondents said they had been screened at least once for colon cancer.
The primary reasons for not being screened included, “don't want to have a colonoscopy” (28%), “doctor did not discuss screening with them” (26%), “did not have any symptoms” (24%), “did not feel they were at risk” (17%), “did not follow through on MD [doctor] recommendations” (9%), “did not know they should be screened” (8%), “did not have time” (5%), and “embarrassed to discuss screening with MD” (4%). Respondents were able to select from more than one category.
Screening rates were highest among those who claimed to be the most knowledgeable about colon cancer. Only 35% of those who considered themselves lacking knowledge about colon cancer had ever been screened, but 79% of respondents who felt they were “knowledgeable” or “very knowledgeable” had been screened.
However, only half of respondents considered themselves knowledgeable about the disease, and far fewer understood the need for, and benefits of, screening.
A personal or family history of the disease was reported by one in five people. Over a third of adults said they were in “excellent” or “very good” health, and three-quarters felt they were doing a good job of managing their own health.
Entecavir vs. Lamivudine for HBV
Two head-to-head phase III trials have shown that the new drug entecavir may be superior to lamivudine for treating chronic hepatitis B.
The two nucleoside drugs were pitted against each other in double-blind trials that involved more than 1,300 patients with HBeAg-positive and HBeAg-negative chronic hepatitis B.
At 48 weeks into the antigen-positive study, histologic improvement was seen in 72% of the entecavir group and 62% of the lamivudine group. Target DNA levels were measured in 21% of patients in the entecavir group and 19% of those taking lamivudine. Significant virologic response occurred in 70% and 46%, respectively. There was no evidence of emerging resistant variants to entecavir, and the frequency of adverse events was similar for the two drugs (N. Engl. J. Med. 2006;354:1001–10).
Of the entecavir patients, 67% had undetectable levels of HBV DNA at 48 weeks. “The efficacy of entecavir appears to result from its potent suppression of HBV replication,” the authors explained.
In the study of HBeAg-negative patients, entecavir produced histologic improvement in 70% of patients, while lamivudine came in at 61%. Among patients not previously treated with a nucleoside analogue, the rates of histologic improvement, serologic response, and normalization of alanine aminotransferase levels were significantly higher at 48 weeks with entecavir than with lamivudine.
Again, the safety profiles of the two drugs were similar, and there was no evidence of viral resistance to entecavir, the investigators reported (N. Engl. J. Med. 2006;354:1011–20).
Dietary Calcium Cuts Polyp Risk
Calcium obtained from dietary sources, but not calcium supplements, may protect against the development of colon polyps, Janet A. Tooze, Ph.D., reported in a poster presentation at the annual meeting of the American Society of Preventive Oncology.
In a retrospective study, 598 participants aged 40–69 years completed a food frequency questionnaire in 1992–1994 when they were participating in the Insulin Resistance Arteriosclerosis Study. They later underwent colonoscopy during 2002–2004.
Overall, people in the three highest quartiles of dietary calcium intake were about two to almost three times more likely to be free of colon polyps than were people in the lowest quartile. Supplemental calcium use did not significantly affect the risk for colon polyps. The cutoff for the lowest quartile of calcium intake was about 500 mg per day, said Dr. Tooze of Wake Forest University, Winston-Salem, N.C.
One or more polyps were found in 49% of the participants, including 32% with an adenoma or hyperplastic polyp, 23% with any adenoma, and 6% with an advanced adenoma.
The prevalence of supplemental calcium use was not high—only 15%, according to the researchers. “The source of calcium may be related to the protective effect for polyp development and adenoma development,” the researchers wrote.
Americans Avoid Colon Ca Screening
Aversion to colonoscopy and lack of physician communication are major reasons Americans avoid colon cancer screening, according to a survey of 1,200 people aged 50 to 70 years.
The survey, conducted in February by Harris Interactive, suggests that three out of four eligible Americans are not being screened regularly for this second leading cause of cancer death, a screening rate far lower than rates reported for breast, cervical, and prostate cancers. Only one-third of respondents said they had been screened at least once for colon cancer.
The primary reasons for not being screened included, “don't want to have a colonoscopy” (28%), “doctor did not discuss screening with them” (26%), “did not have any symptoms” (24%), “did not feel they were at risk” (17%), “did not follow through on MD [doctor] recommendations” (9%), “did not know they should be screened” (8%), “did not have time” (5%), and “embarrassed to discuss screening with MD” (4%). Respondents were able to select from more than one category.
Screening rates were highest among those who claimed to be the most knowledgeable about colon cancer. Only 35% of those who considered themselves lacking knowledge about colon cancer had ever been screened, but 79% of respondents who felt they were “knowledgeable” or “very knowledgeable” had been screened.
However, only half of respondents considered themselves knowledgeable about the disease, and far fewer understood the need for, and benefits of, screening.
A personal or family history of the disease was reported by one in five people. Over a third of adults said they were in “excellent” or “very good” health, and three-quarters felt they were doing a good job of managing their own health.
Entecavir vs. Lamivudine for HBV
Two head-to-head phase III trials have shown that the new drug entecavir may be superior to lamivudine for treating chronic hepatitis B.
The two nucleoside drugs were pitted against each other in double-blind trials that involved more than 1,300 patients with HBeAg-positive and HBeAg-negative chronic hepatitis B.
At 48 weeks into the antigen-positive study, histologic improvement was seen in 72% of the entecavir group and 62% of the lamivudine group. Target DNA levels were measured in 21% of patients in the entecavir group and 19% of those taking lamivudine. Significant virologic response occurred in 70% and 46%, respectively. There was no evidence of emerging resistant variants to entecavir, and the frequency of adverse events was similar for the two drugs (N. Engl. J. Med. 2006;354:1001–10).
Of the entecavir patients, 67% had undetectable levels of HBV DNA at 48 weeks. “The efficacy of entecavir appears to result from its potent suppression of HBV replication,” the authors explained.
In the study of HBeAg-negative patients, entecavir produced histologic improvement in 70% of patients, while lamivudine came in at 61%. Among patients not previously treated with a nucleoside analogue, the rates of histologic improvement, serologic response, and normalization of alanine aminotransferase levels were significantly higher at 48 weeks with entecavir than with lamivudine.
Again, the safety profiles of the two drugs were similar, and there was no evidence of viral resistance to entecavir, the investigators reported (N. Engl. J. Med. 2006;354:1011–20).
Rapid Diagnostics Coming For Bioterrorism Agents
WASHINGTON — Several rapid diagnostic tools for detecting the unique profiles of common pathogens as well as bioterrorism pathogens in exhaled breath and body fluids may soon be tested on patients in emergency departments, speakers said at a biodefense research meeting sponsored by the American Society for Microbiology.
In a real bioterrorism (BT) event, physicians in multiple disciplines will likely collaborate, but in particular, it will be emergency department, hospital, and research laboratory personnel who will use such diagnostic equipment in clinical settings, said Dr. Richard E. Rothman, of the emergency medicine department at Johns Hopkins University, Baltimore.
“The current diagnostic tools that we use in clinical practice are really limited” in terms of a prolonged wait time for results and sampling problems such as multiple blood draws and tedious steps, he said.
From the perspective of an emergency physician, he said, the key diagnostic questions that physicians need to ask routinely when patients come to the ED include, “Is there an infection? What is the organism? Is it uncommon? Could it be a BT agent?”
Dr. Rothman and his associates have developed several large-scale institutional review board protocols to sample breath condensates initially in animals, then in volunteers, and ultimately in ED patients.
Other protocols have been developed to collect excess sera, cerebrospinal fluid, or nasopharyngeal aspirates from large numbers of ED patients and compare the results of standard microbiologic assays with those of new assays under development.
The rationale for analyzing breath condensates is based on evidence that pathogens in the respiratory system may elicit a host response that can be detected in the breath of an infected patient. Analyses of the patient's immune response could potentially discriminate between bacterial and viral infections and possibly determine what microbe is causing the symptoms.
In vitro studies have shown that specific cytokines and other inflammatory mediators from murine macrophages are activated in a time-dependent manner in the presence of bacterial lipopolysaccharides.
Researchers collaborating with Dr. Rothman have used a mask device called the ECoScreen to hold condensate for analysis by a mass spectrometer. The investigators also have developed their own mask to collect exhaled breath condensate.
In one study, collections of breath condensates from a group of 60 piglets that were exposed to bacteria showed a peak in interleukin-2 as early as 1 hour after exposure to Staphylococcus aureus enterotoxin B—long before the onset of symptoms, Dr. Rothman said.
The work has already shown that animals have unique cytokine profiles to different pathogens, and “now we're moving on to try to define baseline mass spectrometry profiles in healthy humans” and choose an optimal device for sampling, he said. From there, Dr. Rothman and his colleagues plan on sampling ED patients who are healthy or have acute respiratory symptoms.
An ideal diagnostic assay for detecting microorganisms would be sensitive and specific, applicable to multiple types of specimens, able to detect common organisms and BT agents, and useful as a triage tool, Dr. Rothman said.
Several years ago, Dr. Rothman conducted a pilot study with Charlotte A. Gaydos, Dr.P.H., to determine if a group of 51 febrile intravenous drug users were bacteremic when they arrived at the ED. At the time, most of these patients were hospitalized while diagnostic tests were run.
The study findings suggested that it might be possible to detect bacteremia by running polymerase chain reaction (PCR) assays for 16S ribosomal RNA, which is highly conserved among bacteria. Different species of bacteria have differences in the 16S nucleotide sequence.
The PCR assay had 87% sensitivity and 87% specificity for bacteremia, compared with blood culture; all eight patients who had culture-positive infective endocarditis also were determined to be positive by PCR (J. Infect. Dis. 2002;186:1677–81).
Real-time PCR assays that detect single category BT agents already exist. But in real BT events the particular agent isn't known. It is better to be able to detect multiple pathogens in a single reaction, Dr. Rothman said.
Dr. Rothman and Dr. Gaydos have developed universal primers and probes to use in their quantitative, real-time PCR assay for 16S ribosomal RNA. They also designed species-specific primers and probes to detect agents commonly seen in ED and infectious disease settings or in BT events.
The assay was able to detect 25 common bacterial pathogens (such as Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, Streptococcus agalactiae, and Staphylococcus aureus) and inactivated BT agents (such as Bacillus anthracis, Francisella tularensis, Yersinia pestis, and Brucella species) in about 3 hours and 45 minutes, compared with 24 or more hours for detection by culture, said Dr. Gaydos, of the school of public health at Johns Hopkins.
In all cases, the probes for common bacterial pathogens picked up the intended target bacteria and did not cross-react with contaminants or other pathogens. The BT-specific probes detected all of the agents they were intended to find and did not cross-react with other BT pathogens, except in the cases of the B. anthracis probe picking up B. cereus and the Y. pestis probe picking up F. philomiragia and Y. pseudotuberculosis. In each of those cases, a confirmatory test is required to distinguish the species from each other, she said.
“This method could be used for spinal fluid or blood or any other sterile fluid or tissue,” Dr. Gaydos said. “This shows a lot of promise for being used in emergency departments.”
WASHINGTON — Several rapid diagnostic tools for detecting the unique profiles of common pathogens as well as bioterrorism pathogens in exhaled breath and body fluids may soon be tested on patients in emergency departments, speakers said at a biodefense research meeting sponsored by the American Society for Microbiology.
In a real bioterrorism (BT) event, physicians in multiple disciplines will likely collaborate, but in particular, it will be emergency department, hospital, and research laboratory personnel who will use such diagnostic equipment in clinical settings, said Dr. Richard E. Rothman, of the emergency medicine department at Johns Hopkins University, Baltimore.
“The current diagnostic tools that we use in clinical practice are really limited” in terms of a prolonged wait time for results and sampling problems such as multiple blood draws and tedious steps, he said.
From the perspective of an emergency physician, he said, the key diagnostic questions that physicians need to ask routinely when patients come to the ED include, “Is there an infection? What is the organism? Is it uncommon? Could it be a BT agent?”
Dr. Rothman and his associates have developed several large-scale institutional review board protocols to sample breath condensates initially in animals, then in volunteers, and ultimately in ED patients.
Other protocols have been developed to collect excess sera, cerebrospinal fluid, or nasopharyngeal aspirates from large numbers of ED patients and compare the results of standard microbiologic assays with those of new assays under development.
The rationale for analyzing breath condensates is based on evidence that pathogens in the respiratory system may elicit a host response that can be detected in the breath of an infected patient. Analyses of the patient's immune response could potentially discriminate between bacterial and viral infections and possibly determine what microbe is causing the symptoms.
In vitro studies have shown that specific cytokines and other inflammatory mediators from murine macrophages are activated in a time-dependent manner in the presence of bacterial lipopolysaccharides.
Researchers collaborating with Dr. Rothman have used a mask device called the ECoScreen to hold condensate for analysis by a mass spectrometer. The investigators also have developed their own mask to collect exhaled breath condensate.
In one study, collections of breath condensates from a group of 60 piglets that were exposed to bacteria showed a peak in interleukin-2 as early as 1 hour after exposure to Staphylococcus aureus enterotoxin B—long before the onset of symptoms, Dr. Rothman said.
The work has already shown that animals have unique cytokine profiles to different pathogens, and “now we're moving on to try to define baseline mass spectrometry profiles in healthy humans” and choose an optimal device for sampling, he said. From there, Dr. Rothman and his colleagues plan on sampling ED patients who are healthy or have acute respiratory symptoms.
An ideal diagnostic assay for detecting microorganisms would be sensitive and specific, applicable to multiple types of specimens, able to detect common organisms and BT agents, and useful as a triage tool, Dr. Rothman said.
Several years ago, Dr. Rothman conducted a pilot study with Charlotte A. Gaydos, Dr.P.H., to determine if a group of 51 febrile intravenous drug users were bacteremic when they arrived at the ED. At the time, most of these patients were hospitalized while diagnostic tests were run.
The study findings suggested that it might be possible to detect bacteremia by running polymerase chain reaction (PCR) assays for 16S ribosomal RNA, which is highly conserved among bacteria. Different species of bacteria have differences in the 16S nucleotide sequence.
The PCR assay had 87% sensitivity and 87% specificity for bacteremia, compared with blood culture; all eight patients who had culture-positive infective endocarditis also were determined to be positive by PCR (J. Infect. Dis. 2002;186:1677–81).
Real-time PCR assays that detect single category BT agents already exist. But in real BT events the particular agent isn't known. It is better to be able to detect multiple pathogens in a single reaction, Dr. Rothman said.
Dr. Rothman and Dr. Gaydos have developed universal primers and probes to use in their quantitative, real-time PCR assay for 16S ribosomal RNA. They also designed species-specific primers and probes to detect agents commonly seen in ED and infectious disease settings or in BT events.
The assay was able to detect 25 common bacterial pathogens (such as Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, Streptococcus agalactiae, and Staphylococcus aureus) and inactivated BT agents (such as Bacillus anthracis, Francisella tularensis, Yersinia pestis, and Brucella species) in about 3 hours and 45 minutes, compared with 24 or more hours for detection by culture, said Dr. Gaydos, of the school of public health at Johns Hopkins.
In all cases, the probes for common bacterial pathogens picked up the intended target bacteria and did not cross-react with contaminants or other pathogens. The BT-specific probes detected all of the agents they were intended to find and did not cross-react with other BT pathogens, except in the cases of the B. anthracis probe picking up B. cereus and the Y. pestis probe picking up F. philomiragia and Y. pseudotuberculosis. In each of those cases, a confirmatory test is required to distinguish the species from each other, she said.
“This method could be used for spinal fluid or blood or any other sterile fluid or tissue,” Dr. Gaydos said. “This shows a lot of promise for being used in emergency departments.”
WASHINGTON — Several rapid diagnostic tools for detecting the unique profiles of common pathogens as well as bioterrorism pathogens in exhaled breath and body fluids may soon be tested on patients in emergency departments, speakers said at a biodefense research meeting sponsored by the American Society for Microbiology.
In a real bioterrorism (BT) event, physicians in multiple disciplines will likely collaborate, but in particular, it will be emergency department, hospital, and research laboratory personnel who will use such diagnostic equipment in clinical settings, said Dr. Richard E. Rothman, of the emergency medicine department at Johns Hopkins University, Baltimore.
“The current diagnostic tools that we use in clinical practice are really limited” in terms of a prolonged wait time for results and sampling problems such as multiple blood draws and tedious steps, he said.
From the perspective of an emergency physician, he said, the key diagnostic questions that physicians need to ask routinely when patients come to the ED include, “Is there an infection? What is the organism? Is it uncommon? Could it be a BT agent?”
Dr. Rothman and his associates have developed several large-scale institutional review board protocols to sample breath condensates initially in animals, then in volunteers, and ultimately in ED patients.
Other protocols have been developed to collect excess sera, cerebrospinal fluid, or nasopharyngeal aspirates from large numbers of ED patients and compare the results of standard microbiologic assays with those of new assays under development.
The rationale for analyzing breath condensates is based on evidence that pathogens in the respiratory system may elicit a host response that can be detected in the breath of an infected patient. Analyses of the patient's immune response could potentially discriminate between bacterial and viral infections and possibly determine what microbe is causing the symptoms.
In vitro studies have shown that specific cytokines and other inflammatory mediators from murine macrophages are activated in a time-dependent manner in the presence of bacterial lipopolysaccharides.
Researchers collaborating with Dr. Rothman have used a mask device called the ECoScreen to hold condensate for analysis by a mass spectrometer. The investigators also have developed their own mask to collect exhaled breath condensate.
In one study, collections of breath condensates from a group of 60 piglets that were exposed to bacteria showed a peak in interleukin-2 as early as 1 hour after exposure to Staphylococcus aureus enterotoxin B—long before the onset of symptoms, Dr. Rothman said.
The work has already shown that animals have unique cytokine profiles to different pathogens, and “now we're moving on to try to define baseline mass spectrometry profiles in healthy humans” and choose an optimal device for sampling, he said. From there, Dr. Rothman and his colleagues plan on sampling ED patients who are healthy or have acute respiratory symptoms.
An ideal diagnostic assay for detecting microorganisms would be sensitive and specific, applicable to multiple types of specimens, able to detect common organisms and BT agents, and useful as a triage tool, Dr. Rothman said.
Several years ago, Dr. Rothman conducted a pilot study with Charlotte A. Gaydos, Dr.P.H., to determine if a group of 51 febrile intravenous drug users were bacteremic when they arrived at the ED. At the time, most of these patients were hospitalized while diagnostic tests were run.
The study findings suggested that it might be possible to detect bacteremia by running polymerase chain reaction (PCR) assays for 16S ribosomal RNA, which is highly conserved among bacteria. Different species of bacteria have differences in the 16S nucleotide sequence.
The PCR assay had 87% sensitivity and 87% specificity for bacteremia, compared with blood culture; all eight patients who had culture-positive infective endocarditis also were determined to be positive by PCR (J. Infect. Dis. 2002;186:1677–81).
Real-time PCR assays that detect single category BT agents already exist. But in real BT events the particular agent isn't known. It is better to be able to detect multiple pathogens in a single reaction, Dr. Rothman said.
Dr. Rothman and Dr. Gaydos have developed universal primers and probes to use in their quantitative, real-time PCR assay for 16S ribosomal RNA. They also designed species-specific primers and probes to detect agents commonly seen in ED and infectious disease settings or in BT events.
The assay was able to detect 25 common bacterial pathogens (such as Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, Streptococcus agalactiae, and Staphylococcus aureus) and inactivated BT agents (such as Bacillus anthracis, Francisella tularensis, Yersinia pestis, and Brucella species) in about 3 hours and 45 minutes, compared with 24 or more hours for detection by culture, said Dr. Gaydos, of the school of public health at Johns Hopkins.
In all cases, the probes for common bacterial pathogens picked up the intended target bacteria and did not cross-react with contaminants or other pathogens. The BT-specific probes detected all of the agents they were intended to find and did not cross-react with other BT pathogens, except in the cases of the B. anthracis probe picking up B. cereus and the Y. pestis probe picking up F. philomiragia and Y. pseudotuberculosis. In each of those cases, a confirmatory test is required to distinguish the species from each other, she said.
“This method could be used for spinal fluid or blood or any other sterile fluid or tissue,” Dr. Gaydos said. “This shows a lot of promise for being used in emergency departments.”
Laparoscopic Bypass Helps the 'Super-Super Obese'
LOUISVILLE, KY. — “Super-super obese” patients obtain nearly the same benefits from laparoscopic Roux-en-Y gastric bypass as do less obese patients without incurring unwarranted risks, Dr. Jon C. Gould reported at the annual meeting of the Central Surgical Association.
Surgeons have taken several different approaches in treating super-super obesity (a body mass index greater than 60 kg/m
Still others consider super-super obese patients to be nonoperative, said Dr. Gould of the bariatric program at the University of Wisconsin, Madison.
To study the results of laparoscopic surgery in these patients, he and his colleagues reviewed prospectively collected data on procedures performed on 28 patients with a BMI greater than 60 kg/m
The super-super obese patients were required to lose a specific amount of weight on a high-protein, low-calorie diet before the operation. The required amount of weight loss, determined at the discretion of the surgeon, was “somewhat subjectively” based on where a patient carried his or her weight, but the amount typically was 30–40 pounds, he said.
The surgery involved a circular stapled gastrojejunostomy with an antecolic, antegastric placement of a 150-cm Roux limb. A 50-cm biliopancreatic limb was used.
Few early complications developed in patients in either group. The group of less obese patients incurred one death, two staple-line leaks, four bleeding episodes, and six wound infections. One staple-line leak and one wound infection occurred among the 28 super-super obese patients.
Stenosis developed among significantly more of the super-super obese patients (29%) than among those with a lower BMI (9%). This difference persisted even after the investigators had switched from using a 21-mm stapler in the first 142 patients to a 25-mm stapler in the following 142 patients. Dr. Gould was unsure whether stenosis resulted from surgeons routinely oversewing the gastrojejunostomy in the super-super obese patients, from increased tension on the anastomosis, or from intraabdominal pressure. But all of the patients with stenosis responded well to endoscopic dilatation without any long-term comorbidity, he said.
Patients with lower BMI lost a significantly higher percentage of their excess weight at 1 and 2 years (69% and 75%, respectively) than did higher BMI patients (57% and 61%). But the super-super obese patients lost significantly more weight overall (about 150 vs. 120 pounds). Most of the super-super obese patients (92%) failed to achieve a BMI less than 35, compared with 17% of the less obese patients.
Resolution of preoperative medical conditions post surgery was similar among super-super obese and less obese patients: type 2 diabetes (100% vs. 80%, respectively), gastroesophageal reflux disease (80% vs. 96%), and hyperlipidemia (80% vs. 91%).
But hypertension resolved in significantly more of the less obese than in the super-super obese patients (89% vs. 63%). The super-super obese patients also reported a quality of life similar to that reported by the less obese patients after the operation.
“It's not clear to me why [super-super obese] patients respond somewhat differently to some of these procedures than our less obese patients do, and I think we do need to take a step back to assess and think about how we're going to define success in these patients,” Dr. Gould said. “To what lengths should we go to achieve a specific postoperative BMI, what morbidity should we accept to achieve that BMI, or should our end point—our definition of success—be more related to quality of life and health?”
LOUISVILLE, KY. — “Super-super obese” patients obtain nearly the same benefits from laparoscopic Roux-en-Y gastric bypass as do less obese patients without incurring unwarranted risks, Dr. Jon C. Gould reported at the annual meeting of the Central Surgical Association.
Surgeons have taken several different approaches in treating super-super obesity (a body mass index greater than 60 kg/m
Still others consider super-super obese patients to be nonoperative, said Dr. Gould of the bariatric program at the University of Wisconsin, Madison.
To study the results of laparoscopic surgery in these patients, he and his colleagues reviewed prospectively collected data on procedures performed on 28 patients with a BMI greater than 60 kg/m
The super-super obese patients were required to lose a specific amount of weight on a high-protein, low-calorie diet before the operation. The required amount of weight loss, determined at the discretion of the surgeon, was “somewhat subjectively” based on where a patient carried his or her weight, but the amount typically was 30–40 pounds, he said.
The surgery involved a circular stapled gastrojejunostomy with an antecolic, antegastric placement of a 150-cm Roux limb. A 50-cm biliopancreatic limb was used.
Few early complications developed in patients in either group. The group of less obese patients incurred one death, two staple-line leaks, four bleeding episodes, and six wound infections. One staple-line leak and one wound infection occurred among the 28 super-super obese patients.
Stenosis developed among significantly more of the super-super obese patients (29%) than among those with a lower BMI (9%). This difference persisted even after the investigators had switched from using a 21-mm stapler in the first 142 patients to a 25-mm stapler in the following 142 patients. Dr. Gould was unsure whether stenosis resulted from surgeons routinely oversewing the gastrojejunostomy in the super-super obese patients, from increased tension on the anastomosis, or from intraabdominal pressure. But all of the patients with stenosis responded well to endoscopic dilatation without any long-term comorbidity, he said.
Patients with lower BMI lost a significantly higher percentage of their excess weight at 1 and 2 years (69% and 75%, respectively) than did higher BMI patients (57% and 61%). But the super-super obese patients lost significantly more weight overall (about 150 vs. 120 pounds). Most of the super-super obese patients (92%) failed to achieve a BMI less than 35, compared with 17% of the less obese patients.
Resolution of preoperative medical conditions post surgery was similar among super-super obese and less obese patients: type 2 diabetes (100% vs. 80%, respectively), gastroesophageal reflux disease (80% vs. 96%), and hyperlipidemia (80% vs. 91%).
But hypertension resolved in significantly more of the less obese than in the super-super obese patients (89% vs. 63%). The super-super obese patients also reported a quality of life similar to that reported by the less obese patients after the operation.
“It's not clear to me why [super-super obese] patients respond somewhat differently to some of these procedures than our less obese patients do, and I think we do need to take a step back to assess and think about how we're going to define success in these patients,” Dr. Gould said. “To what lengths should we go to achieve a specific postoperative BMI, what morbidity should we accept to achieve that BMI, or should our end point—our definition of success—be more related to quality of life and health?”
LOUISVILLE, KY. — “Super-super obese” patients obtain nearly the same benefits from laparoscopic Roux-en-Y gastric bypass as do less obese patients without incurring unwarranted risks, Dr. Jon C. Gould reported at the annual meeting of the Central Surgical Association.
Surgeons have taken several different approaches in treating super-super obesity (a body mass index greater than 60 kg/m
Still others consider super-super obese patients to be nonoperative, said Dr. Gould of the bariatric program at the University of Wisconsin, Madison.
To study the results of laparoscopic surgery in these patients, he and his colleagues reviewed prospectively collected data on procedures performed on 28 patients with a BMI greater than 60 kg/m
The super-super obese patients were required to lose a specific amount of weight on a high-protein, low-calorie diet before the operation. The required amount of weight loss, determined at the discretion of the surgeon, was “somewhat subjectively” based on where a patient carried his or her weight, but the amount typically was 30–40 pounds, he said.
The surgery involved a circular stapled gastrojejunostomy with an antecolic, antegastric placement of a 150-cm Roux limb. A 50-cm biliopancreatic limb was used.
Few early complications developed in patients in either group. The group of less obese patients incurred one death, two staple-line leaks, four bleeding episodes, and six wound infections. One staple-line leak and one wound infection occurred among the 28 super-super obese patients.
Stenosis developed among significantly more of the super-super obese patients (29%) than among those with a lower BMI (9%). This difference persisted even after the investigators had switched from using a 21-mm stapler in the first 142 patients to a 25-mm stapler in the following 142 patients. Dr. Gould was unsure whether stenosis resulted from surgeons routinely oversewing the gastrojejunostomy in the super-super obese patients, from increased tension on the anastomosis, or from intraabdominal pressure. But all of the patients with stenosis responded well to endoscopic dilatation without any long-term comorbidity, he said.
Patients with lower BMI lost a significantly higher percentage of their excess weight at 1 and 2 years (69% and 75%, respectively) than did higher BMI patients (57% and 61%). But the super-super obese patients lost significantly more weight overall (about 150 vs. 120 pounds). Most of the super-super obese patients (92%) failed to achieve a BMI less than 35, compared with 17% of the less obese patients.
Resolution of preoperative medical conditions post surgery was similar among super-super obese and less obese patients: type 2 diabetes (100% vs. 80%, respectively), gastroesophageal reflux disease (80% vs. 96%), and hyperlipidemia (80% vs. 91%).
But hypertension resolved in significantly more of the less obese than in the super-super obese patients (89% vs. 63%). The super-super obese patients also reported a quality of life similar to that reported by the less obese patients after the operation.
“It's not clear to me why [super-super obese] patients respond somewhat differently to some of these procedures than our less obese patients do, and I think we do need to take a step back to assess and think about how we're going to define success in these patients,” Dr. Gould said. “To what lengths should we go to achieve a specific postoperative BMI, what morbidity should we accept to achieve that BMI, or should our end point—our definition of success—be more related to quality of life and health?”
Calcium in Diet, Not Supplements, Cuts Polyp Risk
BETHESDA, MD. — Calcium obtained from dietary sources, but not calcium supplements, may be associated with a protective effect against the development of colon polyps, Janet A. Tooze, Ph.D., reported at the annual meeting of the American Society of Preventive Oncology.
In a retrospective study, 598 participants aged 40–69 years completed a food frequency questionnaire in 1992–1994 when they were participating in the Insulin Resistance Arteriosclerosis Study. They later underwent colonoscopy during 2002–2004.
Overall, people in the three highest quartiles of dietary calcium intake were about 2–3 times more likely to be free of colon polyps than people in the lowest quartile. Supplemental calcium use did not significantly affect the risk for colon polyps. The cutoff for the lowest quartile of calcium intake was about 500 mg per day, according to Dr. Tooze, of Wake Forest University, Winston-Salem, N.C.
One or more polyps were found in 49% of subjects, including 32% with an adenoma or hyperplastic polyp, 23% with any adenoma, and 6% with an advanced adenoma (villous features or size larger than 1 cm).
The prevalence of supplemental calcium use was not high—only 15%, according to the researchers.
“The source of calcium may be related to the protective effect for polyp development and adenoma development,” they wrote in their poster presented at the meeting.
BETHESDA, MD. — Calcium obtained from dietary sources, but not calcium supplements, may be associated with a protective effect against the development of colon polyps, Janet A. Tooze, Ph.D., reported at the annual meeting of the American Society of Preventive Oncology.
In a retrospective study, 598 participants aged 40–69 years completed a food frequency questionnaire in 1992–1994 when they were participating in the Insulin Resistance Arteriosclerosis Study. They later underwent colonoscopy during 2002–2004.
Overall, people in the three highest quartiles of dietary calcium intake were about 2–3 times more likely to be free of colon polyps than people in the lowest quartile. Supplemental calcium use did not significantly affect the risk for colon polyps. The cutoff for the lowest quartile of calcium intake was about 500 mg per day, according to Dr. Tooze, of Wake Forest University, Winston-Salem, N.C.
One or more polyps were found in 49% of subjects, including 32% with an adenoma or hyperplastic polyp, 23% with any adenoma, and 6% with an advanced adenoma (villous features or size larger than 1 cm).
The prevalence of supplemental calcium use was not high—only 15%, according to the researchers.
“The source of calcium may be related to the protective effect for polyp development and adenoma development,” they wrote in their poster presented at the meeting.
BETHESDA, MD. — Calcium obtained from dietary sources, but not calcium supplements, may be associated with a protective effect against the development of colon polyps, Janet A. Tooze, Ph.D., reported at the annual meeting of the American Society of Preventive Oncology.
In a retrospective study, 598 participants aged 40–69 years completed a food frequency questionnaire in 1992–1994 when they were participating in the Insulin Resistance Arteriosclerosis Study. They later underwent colonoscopy during 2002–2004.
Overall, people in the three highest quartiles of dietary calcium intake were about 2–3 times more likely to be free of colon polyps than people in the lowest quartile. Supplemental calcium use did not significantly affect the risk for colon polyps. The cutoff for the lowest quartile of calcium intake was about 500 mg per day, according to Dr. Tooze, of Wake Forest University, Winston-Salem, N.C.
One or more polyps were found in 49% of subjects, including 32% with an adenoma or hyperplastic polyp, 23% with any adenoma, and 6% with an advanced adenoma (villous features or size larger than 1 cm).
The prevalence of supplemental calcium use was not high—only 15%, according to the researchers.
“The source of calcium may be related to the protective effect for polyp development and adenoma development,” they wrote in their poster presented at the meeting.
Diagnostics for Bioterrorism Agents on the Way
WASHINGTON — Several rapid diagnostic tools for detecting the unique profiles of both common pathogens and bioterrorism pathogens in exhaled breath and body fluids may soon be tested on patients in emergency departments, speakers said at a biodefense research meeting sponsored by the American Society for Microbiology.
In a real bioterrorism (BT) event, physicians in multiple disciplines will likely collaborate, but in particular, it will be emergency department, hospital, and research laboratory personnel who will use such diagnostic equipment in real clinical settings, said Dr. Richard E. Rothman, of the emergency medicine department at Johns Hopkins University, Baltimore.
“The current diagnostic tools that we use in clinical practice are really limited” in terms of a prolonged wait time for results and sampling problems such as multiple blood draws and tedious steps, he said.
From the perspective of an emergency physician, he said, the key diagnostic questions that physicians need to ask routinely when patients come to the ED include, “Is there an infection? What is the organism? Is it uncommon? Could it be a BT agent?”
Dr. Rothman and his associates have developed several large-scale institutional review board protocols to sample breath condensates initially in animals, then in volunteers, and ultimately in ED patients. Other protocols have been developed to collect excess sera, cerebrospinal fluid, or nasopharyngeal aspirates from large numbers of ED patients and compare the results of standard microbiologic assays with those of new assays under development.
The rationale for analyzing breath condensates is based on evidence that pathogens in the respiratory system may elicit a host response that can be detected in the breath of an infected patient. Analyses of the patient's immune response could potentially discriminate between bacterial and viral infections and possibly determine what microbe is causing the symptoms.
In vitro studies have shown that specific cytokines and other inflammatory mediators from murine macrophages are activated in a time-dependent manner in the presence of bacterial lipopolysaccharides.
Researchers collaborating with Dr. Rothman have used a mask device called the ECoScreen to hold condensate for analysis by a mass spectrometer. The investigators also have developed their own mask to collect exhaled breath condensate.
In one study, collections of breath condensates from a group of 60 piglets that were exposed to bacteria showed a peak in interleukin-2 as early as 1 hour after exposure to Staphylococcus aureus enterotoxin B—long before the onset of symptoms, Dr. Rothman said.
The work has already shown that animals have unique cytokine profiles to different pathogens, and “now we're moving on to try to define baseline mass spectrometry profiles in healthy humans” and choose an optimal device for sampling, he said. From there, Dr. Rothman and his colleagues plan on sampling ED patients who are healthy or have acute respiratory symptoms.
An ideal diagnostic assay for detecting microorganisms would be sensitive and specific, applicable to multiple types of specimens, able to detect common organisms and BT agents, and useful as a triage tool, Dr. Rothman said.
Several years ago, Dr. Rothman conducted a pilot study with Charlotte A. Gaydos, Dr.P.H., to determine if a group of 51 febrile intravenous drug users were bacteremic when they arrived at the ED. At the time, most of these patients were hospitalized while diagnostic tests were run. The study findings suggested that it might be possible to detect bacteremia by running polymerase chain reaction (PCR) assays for 16S ribosomal RNA, which is highly conserved among bacteria. Different species of bacteria have differences in the 16S nucleotide sequence.
The PCR assay had 87% sensitivity and 87% specificity for bacteremia, compared with blood culture; all eight patients who had culture-positive infective endocarditis also were determined to be positive by PCR (J. Infect. Dis. 2002;186:1677–81).
Real-time PCR assays that detect single category A BT agents already exist. But in real BT events the particular agent isn't known. It is better to be able to detect multiple pathogens in a single reaction, Dr. Rothman said.
Dr. Rothman and Dr. Gaydos have developed universal primers and probes to use in their quantitative, real-time PCR assay for 16S ribosomal RNA. They also designed species-specific primers and probes to detect agents commonly seen in ED and infectious disease settings or in BT events.
The assay was able to detect 25 common bacterial pathogens (such as Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, Streptococcus agalactiae, and Staphylococcus aureus) and inactivated BT agents (such as Bacillus anthracis, Francisella tularensis, Yersinia pestis, and Brucella species) in about 3 hours and 45 minutes, compared with 24 or more hours for detection by culture, said Dr. Gaydos, of the school of public health at Johns Hopkins.
In all cases, the probes for common bacterial pathogens picked up the intended target bacteria and did not cross-react with contaminants or other pathogens. The BT-specific probes detected all of the agents they were intended to find and did not cross-react with other BT pathogens, except in the cases of the B. anthracis probe picking up B. cereus and the Y. pestis probe picking up F. philomiragia and Y. pseudotuberculosis. In each of those cases, a confirmatory test is required to distinguish the species from each other, she said. “This method could be used for spinal fluid or blood or any other sterile fluid or tissue. This shows a lot of promise for being used in emergency departments.”
WASHINGTON — Several rapid diagnostic tools for detecting the unique profiles of both common pathogens and bioterrorism pathogens in exhaled breath and body fluids may soon be tested on patients in emergency departments, speakers said at a biodefense research meeting sponsored by the American Society for Microbiology.
In a real bioterrorism (BT) event, physicians in multiple disciplines will likely collaborate, but in particular, it will be emergency department, hospital, and research laboratory personnel who will use such diagnostic equipment in real clinical settings, said Dr. Richard E. Rothman, of the emergency medicine department at Johns Hopkins University, Baltimore.
“The current diagnostic tools that we use in clinical practice are really limited” in terms of a prolonged wait time for results and sampling problems such as multiple blood draws and tedious steps, he said.
From the perspective of an emergency physician, he said, the key diagnostic questions that physicians need to ask routinely when patients come to the ED include, “Is there an infection? What is the organism? Is it uncommon? Could it be a BT agent?”
Dr. Rothman and his associates have developed several large-scale institutional review board protocols to sample breath condensates initially in animals, then in volunteers, and ultimately in ED patients. Other protocols have been developed to collect excess sera, cerebrospinal fluid, or nasopharyngeal aspirates from large numbers of ED patients and compare the results of standard microbiologic assays with those of new assays under development.
The rationale for analyzing breath condensates is based on evidence that pathogens in the respiratory system may elicit a host response that can be detected in the breath of an infected patient. Analyses of the patient's immune response could potentially discriminate between bacterial and viral infections and possibly determine what microbe is causing the symptoms.
In vitro studies have shown that specific cytokines and other inflammatory mediators from murine macrophages are activated in a time-dependent manner in the presence of bacterial lipopolysaccharides.
Researchers collaborating with Dr. Rothman have used a mask device called the ECoScreen to hold condensate for analysis by a mass spectrometer. The investigators also have developed their own mask to collect exhaled breath condensate.
In one study, collections of breath condensates from a group of 60 piglets that were exposed to bacteria showed a peak in interleukin-2 as early as 1 hour after exposure to Staphylococcus aureus enterotoxin B—long before the onset of symptoms, Dr. Rothman said.
The work has already shown that animals have unique cytokine profiles to different pathogens, and “now we're moving on to try to define baseline mass spectrometry profiles in healthy humans” and choose an optimal device for sampling, he said. From there, Dr. Rothman and his colleagues plan on sampling ED patients who are healthy or have acute respiratory symptoms.
An ideal diagnostic assay for detecting microorganisms would be sensitive and specific, applicable to multiple types of specimens, able to detect common organisms and BT agents, and useful as a triage tool, Dr. Rothman said.
Several years ago, Dr. Rothman conducted a pilot study with Charlotte A. Gaydos, Dr.P.H., to determine if a group of 51 febrile intravenous drug users were bacteremic when they arrived at the ED. At the time, most of these patients were hospitalized while diagnostic tests were run. The study findings suggested that it might be possible to detect bacteremia by running polymerase chain reaction (PCR) assays for 16S ribosomal RNA, which is highly conserved among bacteria. Different species of bacteria have differences in the 16S nucleotide sequence.
The PCR assay had 87% sensitivity and 87% specificity for bacteremia, compared with blood culture; all eight patients who had culture-positive infective endocarditis also were determined to be positive by PCR (J. Infect. Dis. 2002;186:1677–81).
Real-time PCR assays that detect single category A BT agents already exist. But in real BT events the particular agent isn't known. It is better to be able to detect multiple pathogens in a single reaction, Dr. Rothman said.
Dr. Rothman and Dr. Gaydos have developed universal primers and probes to use in their quantitative, real-time PCR assay for 16S ribosomal RNA. They also designed species-specific primers and probes to detect agents commonly seen in ED and infectious disease settings or in BT events.
The assay was able to detect 25 common bacterial pathogens (such as Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, Streptococcus agalactiae, and Staphylococcus aureus) and inactivated BT agents (such as Bacillus anthracis, Francisella tularensis, Yersinia pestis, and Brucella species) in about 3 hours and 45 minutes, compared with 24 or more hours for detection by culture, said Dr. Gaydos, of the school of public health at Johns Hopkins.
In all cases, the probes for common bacterial pathogens picked up the intended target bacteria and did not cross-react with contaminants or other pathogens. The BT-specific probes detected all of the agents they were intended to find and did not cross-react with other BT pathogens, except in the cases of the B. anthracis probe picking up B. cereus and the Y. pestis probe picking up F. philomiragia and Y. pseudotuberculosis. In each of those cases, a confirmatory test is required to distinguish the species from each other, she said. “This method could be used for spinal fluid or blood or any other sterile fluid or tissue. This shows a lot of promise for being used in emergency departments.”
WASHINGTON — Several rapid diagnostic tools for detecting the unique profiles of both common pathogens and bioterrorism pathogens in exhaled breath and body fluids may soon be tested on patients in emergency departments, speakers said at a biodefense research meeting sponsored by the American Society for Microbiology.
In a real bioterrorism (BT) event, physicians in multiple disciplines will likely collaborate, but in particular, it will be emergency department, hospital, and research laboratory personnel who will use such diagnostic equipment in real clinical settings, said Dr. Richard E. Rothman, of the emergency medicine department at Johns Hopkins University, Baltimore.
“The current diagnostic tools that we use in clinical practice are really limited” in terms of a prolonged wait time for results and sampling problems such as multiple blood draws and tedious steps, he said.
From the perspective of an emergency physician, he said, the key diagnostic questions that physicians need to ask routinely when patients come to the ED include, “Is there an infection? What is the organism? Is it uncommon? Could it be a BT agent?”
Dr. Rothman and his associates have developed several large-scale institutional review board protocols to sample breath condensates initially in animals, then in volunteers, and ultimately in ED patients. Other protocols have been developed to collect excess sera, cerebrospinal fluid, or nasopharyngeal aspirates from large numbers of ED patients and compare the results of standard microbiologic assays with those of new assays under development.
The rationale for analyzing breath condensates is based on evidence that pathogens in the respiratory system may elicit a host response that can be detected in the breath of an infected patient. Analyses of the patient's immune response could potentially discriminate between bacterial and viral infections and possibly determine what microbe is causing the symptoms.
In vitro studies have shown that specific cytokines and other inflammatory mediators from murine macrophages are activated in a time-dependent manner in the presence of bacterial lipopolysaccharides.
Researchers collaborating with Dr. Rothman have used a mask device called the ECoScreen to hold condensate for analysis by a mass spectrometer. The investigators also have developed their own mask to collect exhaled breath condensate.
In one study, collections of breath condensates from a group of 60 piglets that were exposed to bacteria showed a peak in interleukin-2 as early as 1 hour after exposure to Staphylococcus aureus enterotoxin B—long before the onset of symptoms, Dr. Rothman said.
The work has already shown that animals have unique cytokine profiles to different pathogens, and “now we're moving on to try to define baseline mass spectrometry profiles in healthy humans” and choose an optimal device for sampling, he said. From there, Dr. Rothman and his colleagues plan on sampling ED patients who are healthy or have acute respiratory symptoms.
An ideal diagnostic assay for detecting microorganisms would be sensitive and specific, applicable to multiple types of specimens, able to detect common organisms and BT agents, and useful as a triage tool, Dr. Rothman said.
Several years ago, Dr. Rothman conducted a pilot study with Charlotte A. Gaydos, Dr.P.H., to determine if a group of 51 febrile intravenous drug users were bacteremic when they arrived at the ED. At the time, most of these patients were hospitalized while diagnostic tests were run. The study findings suggested that it might be possible to detect bacteremia by running polymerase chain reaction (PCR) assays for 16S ribosomal RNA, which is highly conserved among bacteria. Different species of bacteria have differences in the 16S nucleotide sequence.
The PCR assay had 87% sensitivity and 87% specificity for bacteremia, compared with blood culture; all eight patients who had culture-positive infective endocarditis also were determined to be positive by PCR (J. Infect. Dis. 2002;186:1677–81).
Real-time PCR assays that detect single category A BT agents already exist. But in real BT events the particular agent isn't known. It is better to be able to detect multiple pathogens in a single reaction, Dr. Rothman said.
Dr. Rothman and Dr. Gaydos have developed universal primers and probes to use in their quantitative, real-time PCR assay for 16S ribosomal RNA. They also designed species-specific primers and probes to detect agents commonly seen in ED and infectious disease settings or in BT events.
The assay was able to detect 25 common bacterial pathogens (such as Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, Streptococcus agalactiae, and Staphylococcus aureus) and inactivated BT agents (such as Bacillus anthracis, Francisella tularensis, Yersinia pestis, and Brucella species) in about 3 hours and 45 minutes, compared with 24 or more hours for detection by culture, said Dr. Gaydos, of the school of public health at Johns Hopkins.
In all cases, the probes for common bacterial pathogens picked up the intended target bacteria and did not cross-react with contaminants or other pathogens. The BT-specific probes detected all of the agents they were intended to find and did not cross-react with other BT pathogens, except in the cases of the B. anthracis probe picking up B. cereus and the Y. pestis probe picking up F. philomiragia and Y. pseudotuberculosis. In each of those cases, a confirmatory test is required to distinguish the species from each other, she said. “This method could be used for spinal fluid or blood or any other sterile fluid or tissue. This shows a lot of promise for being used in emergency departments.”