John R. Bell

Researchers in joint and tissue repair have mastered the art and science of harvesting skeletal tissue in vitro.

The next challenges to be faced are developing the best repair strategies and making the technologies cost effective, according to Dr. Francesco Dell'Accio and colleagues, who spoke at a translational science session on joint and tissue repair at the annual European Congress of Rheumatology in Amsterdam.

“Cell-based tissue repair is progressively exiting the experimental, 'proof of principle' phase,” said Dr. Dell'Accio of King's College London in an interview.

“Obtaining skeletal tissues in vitro from a variety of mature or stem cell populations is not a big challenge anymore. However, for cell-based repair strategies to reach the routine clinical applicability, we should develop cell preparations that consistently and reproducibly differentiate into the desired tissues in the diseased microenvironment.” Another important issue is to make such technologies cost effective. Allogeneic stem cell technologies or in situ recruitment of resident cells are important opportunities.

“Finally, biodegradable matrices and scaffolds that allow at the same time delivery (ideally arthroscopically) and containment of the cell preparation and control on tissue formation, patterning and maturation may prove of crucial importance,” Dr. Dell'Accio said.

New technologies may soon allow rheumatologists to perform procedures that traditionally have been the exclusive realm of orthopedists, he noted. “For many years, skeletal tissue repair has been predominantly of orthopedic interest because the inflammatory environment of rheumatic joints has been an obstacle for effective tissue regeneration and for the difficulty of the surgery required. Recently, however, the development of potent tools to control inflammation and the potential of these technologies to be delivered arthroscopically may allow the clinical rheumatologist not only to control inflammation but also to achieve tissue repair and reduce the disability of many rheumatic patients.”

It was noted that major new trial data are coming soon, as well as important changes in the regulatory path in Europe to allow development of these treatments into products—notably, a central route through the European Medicines Agency's Committee for Advanced Therapies.

Cell-based tissue repair could relieve the pain of superficial osteochondral defects. Courtesy Dr. Frank P. Luyten

Researchers in joint and tissue repair have mastered the art and science of harvesting skeletal tissue in vitro.

The next challenges to be faced are developing the best repair strategies and making the technologies cost effective, according to Dr. Francesco Dell'Accio and colleagues, who spoke at a translational science session on joint and tissue repair at the annual European Congress of Rheumatology in Amsterdam.

“Cell-based tissue repair is progressively exiting the experimental, 'proof of principle' phase,” said Dr. Dell'Accio of King's College London in an interview.

“Obtaining skeletal tissues in vitro from a variety of mature or stem cell populations is not a big challenge anymore. However, for cell-based repair strategies to reach the routine clinical applicability, we should develop cell preparations that consistently and reproducibly differentiate into the desired tissues in the diseased microenvironment.” Another important issue is to make such technologies cost effective. Allogeneic stem cell technologies or in situ recruitment of resident cells are important opportunities.

“Finally, biodegradable matrices and scaffolds that allow at the same time delivery (ideally arthroscopically) and containment of the cell preparation and control on tissue formation, patterning and maturation may prove of crucial importance,” Dr. Dell'Accio said.

New technologies may soon allow rheumatologists to perform procedures that traditionally have been the exclusive realm of orthopedists, he noted. “For many years, skeletal tissue repair has been predominantly of orthopedic interest because the inflammatory environment of rheumatic joints has been an obstacle for effective tissue regeneration and for the difficulty of the surgery required. Recently, however, the development of potent tools to control inflammation and the potential of these technologies to be delivered arthroscopically may allow the clinical rheumatologist not only to control inflammation but also to achieve tissue repair and reduce the disability of many rheumatic patients.”

It was noted that major new trial data are coming soon, as well as important changes in the regulatory path in Europe to allow development of these treatments into products—notably, a central route through the European Medicines Agency's Committee for Advanced Therapies.

Cell-based tissue repair could relieve the pain of superficial osteochondral defects. Courtesy Dr. Frank P. Luyten

Researchers in joint and tissue repair have mastered the art and science of harvesting skeletal tissue in vitro.

The next challenges to be faced are developing the best repair strategies and making the technologies cost effective, according to Dr. Francesco Dell'Accio and colleagues, who spoke at a translational science session on joint and tissue repair at the annual European Congress of Rheumatology in Amsterdam.

“Cell-based tissue repair is progressively exiting the experimental, 'proof of principle' phase,” said Dr. Dell'Accio of King's College London in an interview.

“Obtaining skeletal tissues in vitro from a variety of mature or stem cell populations is not a big challenge anymore. However, for cell-based repair strategies to reach the routine clinical applicability, we should develop cell preparations that consistently and reproducibly differentiate into the desired tissues in the diseased microenvironment.” Another important issue is to make such technologies cost effective. Allogeneic stem cell technologies or in situ recruitment of resident cells are important opportunities.

“Finally, biodegradable matrices and scaffolds that allow at the same time delivery (ideally arthroscopically) and containment of the cell preparation and control on tissue formation, patterning and maturation may prove of crucial importance,” Dr. Dell'Accio said.

New technologies may soon allow rheumatologists to perform procedures that traditionally have been the exclusive realm of orthopedists, he noted. “For many years, skeletal tissue repair has been predominantly of orthopedic interest because the inflammatory environment of rheumatic joints has been an obstacle for effective tissue regeneration and for the difficulty of the surgery required. Recently, however, the development of potent tools to control inflammation and the potential of these technologies to be delivered arthroscopically may allow the clinical rheumatologist not only to control inflammation but also to achieve tissue repair and reduce the disability of many rheumatic patients.”

It was noted that major new trial data are coming soon, as well as important changes in the regulatory path in Europe to allow development of these treatments into products—notably, a central route through the European Medicines Agency's Committee for Advanced Therapies.

Cell-based tissue repair could relieve the pain of superficial osteochondral defects. Courtesy Dr. Frank P. Luyten

The likelihood of progression of primary angiitis of the central nervous system in children can be predicted by using a high-risk profile comprising clinical features seen at diagnosis and on follow-up, according to new findings.

Dr. Susanne M. Benseler of the Hospital for Sick Children in Toronto and her colleagues found that in their study's cohort of patients with childhood primary angiitis of the central nervous system (cPACNS), progressive disease was associated with neurocognitive dysfunction, multifocal lesions as seen on MRI, and angiographic evidence of distal stenoses at presentation. Thus, they devised a high-risk profile encompassing those factors; the profile for their cohort had a high predictive value of disease progression (predicted P = .002; odds ratio 3.47; 95% confidence interval 2.11–8.24).

The investigators retrospectively assessed data from a consecutive cohort of children younger than 18 years who had been diagnosed with cPACNS over a 12-year period (1990–2002). Cases came from the institution's rheumatology database, as well as from the Canadian Pediatric Ischemic Stroke Registry (Arthritis Rheum. 2006;54:1291–7).

Criteria for having cPACNS were a clinical diagnosis of PACNS vasculitis and conventional CNS angiography and/or magnetic resonance angiography (MRA) findings of arterial stenosis that were not explained by other causes. The investigators excluded neonates and children with any various confounding conditions, such as systemic vasculitis.

The study's primary outcome was the presence or absence of stenosis progression more than 3 months after initial angiography. The researchers defined progression as “a decrease of at least 25% in the diameter at sites of initial stenosis or the appearance of new areas of stenosis.”

Specialists in stroke, neurology, and rheumatology followed up on all patients, collecting data on clinical presentation, underlying disease, stroke risk, and treatments from the databases.

Antithrombotic treatment had been administered according to established protocols; immunosuppressive treatment had been given in some individual cases. There were three treatment categories: antithrombotic therapy (heparin, aspirin, or warfarin) alone; antithrombotic therapy plus steroids; and antithrombotic therapy with steroids and intravenous cyclophosphamide.

The investigators then prospectively assessed patients in the stroke clinic at 3–6 months, 12 months, and 24 months post diagnosis, using the Pediatric Stroke Outcome Measure, an examination with five neurocognitive domains. They defined complete recovery as a neurologic deficit severity score of 0, with any other score indicating incomplete recovery.

In addition, laboratory tests were conducted, comprising an assessment of inflammatory markers, blood testing, prothrombotic testing, antibody profiling, and detection of abnormalities in cerebrospinal fluid. All children received MRI, MRA, or conventional cerebral angiography at diagnosis and follow-up, with results analyzed by blinded neuroradiologists.

Of the 62 children included in the study (38 boys and 24 girls), 20 patients (32%) were deemed to have progressive cPACNS, with the remaining 42 classified as nonprogressive. Among the most common symptoms in both groups were focal neurologic deficits: Hemiparesis was experienced by 60% of patients with progressive disease and 88% of those with nonprogressive disease; hemifacial weakness by 60% and 57%, respectively; hemisensory loss by 95% and 71%; and deficits in fine motor skills by 75% and 71%.

The differences between the two groups were more pronounced in their incidence of diffuse neurologic deficit. For progressive-disease patients, incidence in all three categories ranged from 60% to 75%, whereas in the nonprogressive group, incidence in those categories ranged from 7% to 19%. Likewise, progressive-disease patients experienced far more headaches than did children with nonprogressive cPACNS (95% vs. 38%).

Lesions and especially stenoses were more common in the progressive-cPACNS group. The largest lesion disparity was seen in the incidence of gray-matter lesions (90% for progressive vs. 48% for nonprogressive). For stenoses, as assessed via MRA, incidence was much greater among patients with progressive disease in all stenosis categories, except for proximal stenoses, for which the groups were equal. For multiple, bilateral, and distal stenoses, however, the differences in incidence were 30%, 33%, and 59%, respectively, between the two patient groups.

The researchers called for future trials assessing immunosuppressive therapy in children with features of nonprogressive disease.

The likelihood of progression of primary angiitis of the central nervous system in children can be predicted by using a high-risk profile comprising clinical features seen at diagnosis and on follow-up, according to new findings.

Dr. Susanne M. Benseler of the Hospital for Sick Children in Toronto and her colleagues found that in their study's cohort of patients with childhood primary angiitis of the central nervous system (cPACNS), progressive disease was associated with neurocognitive dysfunction, multifocal lesions as seen on MRI, and angiographic evidence of distal stenoses at presentation. Thus, they devised a high-risk profile encompassing those factors; the profile for their cohort had a high predictive value of disease progression (predicted P = .002; odds ratio 3.47; 95% confidence interval 2.11–8.24).

The investigators retrospectively assessed data from a consecutive cohort of children younger than 18 years who had been diagnosed with cPACNS over a 12-year period (1990–2002). Cases came from the institution's rheumatology database, as well as from the Canadian Pediatric Ischemic Stroke Registry (Arthritis Rheum. 2006;54:1291–7).

Criteria for having cPACNS were a clinical diagnosis of PACNS vasculitis and conventional CNS angiography and/or magnetic resonance angiography (MRA) findings of arterial stenosis that were not explained by other causes. The investigators excluded neonates and children with any various confounding conditions, such as systemic vasculitis.

The study's primary outcome was the presence or absence of stenosis progression more than 3 months after initial angiography. The researchers defined progression as “a decrease of at least 25% in the diameter at sites of initial stenosis or the appearance of new areas of stenosis.”

Specialists in stroke, neurology, and rheumatology followed up on all patients, collecting data on clinical presentation, underlying disease, stroke risk, and treatments from the databases.

Antithrombotic treatment had been administered according to established protocols; immunosuppressive treatment had been given in some individual cases. There were three treatment categories: antithrombotic therapy (heparin, aspirin, or warfarin) alone; antithrombotic therapy plus steroids; and antithrombotic therapy with steroids and intravenous cyclophosphamide.

The investigators then prospectively assessed patients in the stroke clinic at 3–6 months, 12 months, and 24 months post diagnosis, using the Pediatric Stroke Outcome Measure, an examination with five neurocognitive domains. They defined complete recovery as a neurologic deficit severity score of 0, with any other score indicating incomplete recovery.

In addition, laboratory tests were conducted, comprising an assessment of inflammatory markers, blood testing, prothrombotic testing, antibody profiling, and detection of abnormalities in cerebrospinal fluid. All children received MRI, MRA, or conventional cerebral angiography at diagnosis and follow-up, with results analyzed by blinded neuroradiologists.

Of the 62 children included in the study (38 boys and 24 girls), 20 patients (32%) were deemed to have progressive cPACNS, with the remaining 42 classified as nonprogressive. Among the most common symptoms in both groups were focal neurologic deficits: Hemiparesis was experienced by 60% of patients with progressive disease and 88% of those with nonprogressive disease; hemifacial weakness by 60% and 57%, respectively; hemisensory loss by 95% and 71%; and deficits in fine motor skills by 75% and 71%.

The differences between the two groups were more pronounced in their incidence of diffuse neurologic deficit. For progressive-disease patients, incidence in all three categories ranged from 60% to 75%, whereas in the nonprogressive group, incidence in those categories ranged from 7% to 19%. Likewise, progressive-disease patients experienced far more headaches than did children with nonprogressive cPACNS (95% vs. 38%).

Lesions and especially stenoses were more common in the progressive-cPACNS group. The largest lesion disparity was seen in the incidence of gray-matter lesions (90% for progressive vs. 48% for nonprogressive). For stenoses, as assessed via MRA, incidence was much greater among patients with progressive disease in all stenosis categories, except for proximal stenoses, for which the groups were equal. For multiple, bilateral, and distal stenoses, however, the differences in incidence were 30%, 33%, and 59%, respectively, between the two patient groups.

The researchers called for future trials assessing immunosuppressive therapy in children with features of nonprogressive disease.

The likelihood of progression of primary angiitis of the central nervous system in children can be predicted by using a high-risk profile comprising clinical features seen at diagnosis and on follow-up, according to new findings.

Dr. Susanne M. Benseler of the Hospital for Sick Children in Toronto and her colleagues found that in their study's cohort of patients with childhood primary angiitis of the central nervous system (cPACNS), progressive disease was associated with neurocognitive dysfunction, multifocal lesions as seen on MRI, and angiographic evidence of distal stenoses at presentation. Thus, they devised a high-risk profile encompassing those factors; the profile for their cohort had a high predictive value of disease progression (predicted P = .002; odds ratio 3.47; 95% confidence interval 2.11–8.24).

The investigators retrospectively assessed data from a consecutive cohort of children younger than 18 years who had been diagnosed with cPACNS over a 12-year period (1990–2002). Cases came from the institution's rheumatology database, as well as from the Canadian Pediatric Ischemic Stroke Registry (Arthritis Rheum. 2006;54:1291–7).

Criteria for having cPACNS were a clinical diagnosis of PACNS vasculitis and conventional CNS angiography and/or magnetic resonance angiography (MRA) findings of arterial stenosis that were not explained by other causes. The investigators excluded neonates and children with any various confounding conditions, such as systemic vasculitis.

The study's primary outcome was the presence or absence of stenosis progression more than 3 months after initial angiography. The researchers defined progression as “a decrease of at least 25% in the diameter at sites of initial stenosis or the appearance of new areas of stenosis.”

Specialists in stroke, neurology, and rheumatology followed up on all patients, collecting data on clinical presentation, underlying disease, stroke risk, and treatments from the databases.

Antithrombotic treatment had been administered according to established protocols; immunosuppressive treatment had been given in some individual cases. There were three treatment categories: antithrombotic therapy (heparin, aspirin, or warfarin) alone; antithrombotic therapy plus steroids; and antithrombotic therapy with steroids and intravenous cyclophosphamide.

The investigators then prospectively assessed patients in the stroke clinic at 3–6 months, 12 months, and 24 months post diagnosis, using the Pediatric Stroke Outcome Measure, an examination with five neurocognitive domains. They defined complete recovery as a neurologic deficit severity score of 0, with any other score indicating incomplete recovery.

In addition, laboratory tests were conducted, comprising an assessment of inflammatory markers, blood testing, prothrombotic testing, antibody profiling, and detection of abnormalities in cerebrospinal fluid. All children received MRI, MRA, or conventional cerebral angiography at diagnosis and follow-up, with results analyzed by blinded neuroradiologists.

Of the 62 children included in the study (38 boys and 24 girls), 20 patients (32%) were deemed to have progressive cPACNS, with the remaining 42 classified as nonprogressive. Among the most common symptoms in both groups were focal neurologic deficits: Hemiparesis was experienced by 60% of patients with progressive disease and 88% of those with nonprogressive disease; hemifacial weakness by 60% and 57%, respectively; hemisensory loss by 95% and 71%; and deficits in fine motor skills by 75% and 71%.

The differences between the two groups were more pronounced in their incidence of diffuse neurologic deficit. For progressive-disease patients, incidence in all three categories ranged from 60% to 75%, whereas in the nonprogressive group, incidence in those categories ranged from 7% to 19%. Likewise, progressive-disease patients experienced far more headaches than did children with nonprogressive cPACNS (95% vs. 38%).

Lesions and especially stenoses were more common in the progressive-cPACNS group. The largest lesion disparity was seen in the incidence of gray-matter lesions (90% for progressive vs. 48% for nonprogressive). For stenoses, as assessed via MRA, incidence was much greater among patients with progressive disease in all stenosis categories, except for proximal stenoses, for which the groups were equal. For multiple, bilateral, and distal stenoses, however, the differences in incidence were 30%, 33%, and 59%, respectively, between the two patient groups.

The researchers called for future trials assessing immunosuppressive therapy in children with features of nonprogressive disease.

BETHESDA, MD. — Children with sickle cell disease who were hospitalized for frequent recurrent painful episodes were given significantly less than the prescribed amount of morphine, Eufemia Jacob, Ph.D., reported in a poster presented at a meeting sponsored by the National Institutes of Health's Pain Consortium.

The mean dosages delivered during prolonged hospitalizations were 0.5–1.5 mg/kg per day, which represented, on average, only 37% of the prescribed amount of morphine. The prescribed amount consisted of a lower-than-recommended “background” infusion and additional higher doses the patients could get by pressing a button. Dr. Jacob and her colleagues concluded that the children were given “suboptimal” regimens, but she cautioned that “suboptimal” does not necessarily mean “undertreatment.”

Dr. Jacob of the department of pediatrics at Baylor College of Medicine, Houston, offered several possible reasons for the observed dosage difference: Children might not have pushed the button because they were asleep or too exhausted from the pain, did not like the side effects, or might not have understood the self-delivery system. The inherent processes involved in the biology of sickle cell disease may not be responsive to morphine. She is currently conducting a study to compare different methods of programming the morphine delivery system and to assess the contributions of genes and other biology markers. She hopes to customize regimens to shorten hospital stays for acute, painful episodes in patients with sickle cell disease.

BETHESDA, MD. — Children with sickle cell disease who were hospitalized for frequent recurrent painful episodes were given significantly less than the prescribed amount of morphine, Eufemia Jacob, Ph.D., reported in a poster presented at a meeting sponsored by the National Institutes of Health's Pain Consortium.

The mean dosages delivered during prolonged hospitalizations were 0.5–1.5 mg/kg per day, which represented, on average, only 37% of the prescribed amount of morphine. The prescribed amount consisted of a lower-than-recommended “background” infusion and additional higher doses the patients could get by pressing a button. Dr. Jacob and her colleagues concluded that the children were given “suboptimal” regimens, but she cautioned that “suboptimal” does not necessarily mean “undertreatment.”

Dr. Jacob of the department of pediatrics at Baylor College of Medicine, Houston, offered several possible reasons for the observed dosage difference: Children might not have pushed the button because they were asleep or too exhausted from the pain, did not like the side effects, or might not have understood the self-delivery system. The inherent processes involved in the biology of sickle cell disease may not be responsive to morphine. She is currently conducting a study to compare different methods of programming the morphine delivery system and to assess the contributions of genes and other biology markers. She hopes to customize regimens to shorten hospital stays for acute, painful episodes in patients with sickle cell disease.

BETHESDA, MD. — Children with sickle cell disease who were hospitalized for frequent recurrent painful episodes were given significantly less than the prescribed amount of morphine, Eufemia Jacob, Ph.D., reported in a poster presented at a meeting sponsored by the National Institutes of Health's Pain Consortium.

The mean dosages delivered during prolonged hospitalizations were 0.5–1.5 mg/kg per day, which represented, on average, only 37% of the prescribed amount of morphine. The prescribed amount consisted of a lower-than-recommended “background” infusion and additional higher doses the patients could get by pressing a button. Dr. Jacob and her colleagues concluded that the children were given “suboptimal” regimens, but she cautioned that “suboptimal” does not necessarily mean “undertreatment.”

Dr. Jacob of the department of pediatrics at Baylor College of Medicine, Houston, offered several possible reasons for the observed dosage difference: Children might not have pushed the button because they were asleep or too exhausted from the pain, did not like the side effects, or might not have understood the self-delivery system. The inherent processes involved in the biology of sickle cell disease may not be responsive to morphine. She is currently conducting a study to compare different methods of programming the morphine delivery system and to assess the contributions of genes and other biology markers. She hopes to customize regimens to shorten hospital stays for acute, painful episodes in patients with sickle cell disease.

BETHESDA, MD. – Pain perception, far from being the simple one-directional process first proposed by Descartes in 1664, appears to be modulated by several psychological, genetic, and other factors specific to the individual experiencing it, several presenters said at a meeting sponsored by the National Institutes of Health's Pain Consortium.

Robert C. Coghill, Ph.D., of Wake Forest University, Winston-Salem, N.C., noted that subjective factors influencing pain perception include the environment in which the pain is experienced, as well as the person's memories of past experiences with the particular stimulus and future implications associated with it.

“It's a complex combination of afferent information with who the person really is–what they're thinking about, what that stimulus means to them,” Dr. Coghill said.

As evidence of this subjectivity, he noted a “tremendous” variability among 17 normal, healthy individuals' perceived intensity of a pain stimulus in a functional MRI study that he and his colleagues conducted.

He noted that brain activity in the highly sensitive participants was greater than in the less-sensitive subjects as assessed on fMRI; the highly sensitive subjects also had activity in brain areas different from those in the less-sensitive subjects. These findings show that the subjects had a physical difference in the way they experienced pain, correlating with their self-reported sensitivity to the stimulus.

However, the investigators were surprised to note no such differences in activity within the thalamus. The fact that there were statistically significant differences in activity beyond the thalamus but not within it led his team to theorize that many differences in pain are not attributable to a bottom-up process but to a top-down process.

“Maybe these individuals are getting a generally similar input from their peripheral nerves through their spinal cord up into their thalamus,” he said. “Then, once it gets to the thalamus, and gets beyond and starts to get integrated into who that person really is–maybe that's where the individual differences are emerging.”

This idea led Dr. Coghill and his colleagues to investigate expectations as the source of such differences, by using a previously devised expectation model he called the “the stew-in-your-own-juices paradigm.”

Expectations, along with desire, he noted, “are a fundamental component of the placebo response” and are easy to manipulate and control. Moreover, they result from a person's experience with a particular stimulus to form an expectation for future experiences.

The investigators played an audio tone for the participants before subjecting them to a thermal pain stimulus; the longer the interval between the tone and the stimulus, the hotter the stimulus was. Thus participants were trained to expect pain based on the length of the interval. The investigators then gave subjects a tone/stimulus interval leading them to expect less pain–but instead gave them the most severe stimulus. All 10 subjects, true to their training, reported less pain, and their pain-related brain activation also declined.

“The experience of pain is really unique from one individual to the next,” Dr. Coghill said. “Our sensory reality is highly subjective; it's shaped very much by what we think it's going to be.”

When asked what physicians should say to patients before administering a potentially painful procedure, he responded, “Certainly, the nurse with the big, huge needle full of tetanus immunization or whatever, saying, 'This won't hurt a bit' is a problem, because … expectations are created, and immediately you realize that they're not valid.”

Dr. Coghill suggested telling patients honestly that pain might be forthcoming–but also giving them a projected duration of the pain.

The differences in pain perception may also be a function of attention and emotion, M. Catherine Bushnell, Ph.D., of McGill University, Montreal, said in her presentation. She noted clinical and anecdotal evidence showing the effect of attention on pain perception–including human and animal studies that, like Dr. Coghill's, presented subjects with a pair of painful heat stimuli and a pair of sounds.

Subjects were asked to detect subtle differences in one stimulus or the other. By making the task more difficult, the researchers increased the subjects' level of attention on the task. They found that when subjects were more focused on the painful stimuli, there was more activity in corresponding regions of the brain, she said.

Dr. Bushnell also explained that some experiments can arouse a sympathetic reaction, which involves the cardiovascular system as well as emotions, as manipulation of subjects by tension tasks often does, she noted.

To separately examine the effects of mood and attention on pain perception, she and her colleagues performed an experiment that, instead of an auditory stimulus, used an olfactory stimulus, because smells “have strong emotional impact on people,” she said.

The investigators determined odors each patient did not like and then performed essentially the same comparison test as before, but using two odors with the two painful heat stimuli.

They found that regardless of where the subjects' attention was focused, if the odor was pleasant, they were in a good mood, but a bad odor always put them in a bad mood.

Attention significantly affected subjects' ratings of pain intensity but not of pain unpleasantness, whereas odor, the more emotionally fraught stimulus, had a strong and significant effect on unpleasantness and thus mood but no such effect on intensity.

She concluded that psychological factors might contribute to many pain states–for example, allodynia, in which a light touch can elicit severe pain. In such cases–including in experiments conducted by her pain clinic–the patient's perception is borne out by what is happening in the brain.

When asked in a panel discussion whether the ability to divert attention from one's pain could be affected by cognitive factors, she alluded to research findings that chronic-pain patients with more solicitous spouses reported more pain and had more activation of the pain region in the brain than did those with less solicitous spouses.

“By constantly asking a patient about their pain, you're focusing their attention on their pain,” Dr. Bushnell said.

Roger B. Fillingim, Ph.D., of the University of Florida, Gainesville, presented a discussion of the individual factors affecting pain perception, which can include gender, ethnicity, physiological and psychological states, and genetics. He cited previous research from his laboratory showing that men were able to tolerate ischemic pain longer than women could.

Dr. Fillingim also discussed an analysis showing that for ischemic pain, heat, pressure, and temporal summation of heat pain, the group with the highest pain sensitivity was more heavily populated by women and ethnic minorities. He cautioned, however, that such studies rely on self-reported pain thresholds.

To avoid this limitation, his group performed a study in which they induced a leg-muscle reflex normally correlated with pain. They found that African Americans responded to a lower stimulus intensity than whites did.

In the area of gender differences, Dr. Fillingim's group found that for all pain measures (heat, cold, ischemic, and pressure pain), men had greater-than-average self-reported tolerance, whereas women had less than the mean. This may be influenced by attitudes toward pain, such as catastrophizing, he noted.

But interestingly, positive affect was correlated with decreased pain sensitivity only in men. Analgesic responses were less consistent; morphine or pentazocine showed only insignificant sex differences in a study by his group. However, negative affect in men predicted less analgesia but had no effect on women's responses to pain medication. The same was true for catastrophizing.

There are also genetic factors that research has shown might influence pain and analgesia, Dr. Fillingim said. In particular, an allele of the OPRM1 gene predicts lower pressure-pain sensitivity in men. This allele is rare in African Americans but more common in whites and Hispanics, he noted. But only in whites did this allele seem to confer less pain sensitivity; the opposite was true in Hispanic subjects.

It's important to determine which factors predict individual differences in pain response, he emphasized, so that future treatment approaches can be tailored to each patient.

Activation (yellow) is visible during pain stimulation; the subject expected the administered 50° C stimulus.

There was less pain-related activation during the same stimulation when the subject expected a reduced stimulus. Images courtesy Dr. Robert C. Coghill/Wake Forest University School of Medicine

BETHESDA, MD. – Pain perception, far from being the simple one-directional process first proposed by Descartes in 1664, appears to be modulated by several psychological, genetic, and other factors specific to the individual experiencing it, several presenters said at a meeting sponsored by the National Institutes of Health's Pain Consortium.

Robert C. Coghill, Ph.D., of Wake Forest University, Winston-Salem, N.C., noted that subjective factors influencing pain perception include the environment in which the pain is experienced, as well as the person's memories of past experiences with the particular stimulus and future implications associated with it.

“It's a complex combination of afferent information with who the person really is–what they're thinking about, what that stimulus means to them,” Dr. Coghill said.

As evidence of this subjectivity, he noted a “tremendous” variability among 17 normal, healthy individuals' perceived intensity of a pain stimulus in a functional MRI study that he and his colleagues conducted.

He noted that brain activity in the highly sensitive participants was greater than in the less-sensitive subjects as assessed on fMRI; the highly sensitive subjects also had activity in brain areas different from those in the less-sensitive subjects. These findings show that the subjects had a physical difference in the way they experienced pain, correlating with their self-reported sensitivity to the stimulus.

However, the investigators were surprised to note no such differences in activity within the thalamus. The fact that there were statistically significant differences in activity beyond the thalamus but not within it led his team to theorize that many differences in pain are not attributable to a bottom-up process but to a top-down process.

“Maybe these individuals are getting a generally similar input from their peripheral nerves through their spinal cord up into their thalamus,” he said. “Then, once it gets to the thalamus, and gets beyond and starts to get integrated into who that person really is–maybe that's where the individual differences are emerging.”

This idea led Dr. Coghill and his colleagues to investigate expectations as the source of such differences, by using a previously devised expectation model he called the “the stew-in-your-own-juices paradigm.”

Expectations, along with desire, he noted, “are a fundamental component of the placebo response” and are easy to manipulate and control. Moreover, they result from a person's experience with a particular stimulus to form an expectation for future experiences.

The investigators played an audio tone for the participants before subjecting them to a thermal pain stimulus; the longer the interval between the tone and the stimulus, the hotter the stimulus was. Thus participants were trained to expect pain based on the length of the interval. The investigators then gave subjects a tone/stimulus interval leading them to expect less pain–but instead gave them the most severe stimulus. All 10 subjects, true to their training, reported less pain, and their pain-related brain activation also declined.

“The experience of pain is really unique from one individual to the next,” Dr. Coghill said. “Our sensory reality is highly subjective; it's shaped very much by what we think it's going to be.”

When asked what physicians should say to patients before administering a potentially painful procedure, he responded, “Certainly, the nurse with the big, huge needle full of tetanus immunization or whatever, saying, 'This won't hurt a bit' is a problem, because … expectations are created, and immediately you realize that they're not valid.”

Dr. Coghill suggested telling patients honestly that pain might be forthcoming–but also giving them a projected duration of the pain.

The differences in pain perception may also be a function of attention and emotion, M. Catherine Bushnell, Ph.D., of McGill University, Montreal, said in her presentation. She noted clinical and anecdotal evidence showing the effect of attention on pain perception–including human and animal studies that, like Dr. Coghill's, presented subjects with a pair of painful heat stimuli and a pair of sounds.

Subjects were asked to detect subtle differences in one stimulus or the other. By making the task more difficult, the researchers increased the subjects' level of attention on the task. They found that when subjects were more focused on the painful stimuli, there was more activity in corresponding regions of the brain, she said.

Dr. Bushnell also explained that some experiments can arouse a sympathetic reaction, which involves the cardiovascular system as well as emotions, as manipulation of subjects by tension tasks often does, she noted.

To separately examine the effects of mood and attention on pain perception, she and her colleagues performed an experiment that, instead of an auditory stimulus, used an olfactory stimulus, because smells “have strong emotional impact on people,” she said.

The investigators determined odors each patient did not like and then performed essentially the same comparison test as before, but using two odors with the two painful heat stimuli.

They found that regardless of where the subjects' attention was focused, if the odor was pleasant, they were in a good mood, but a bad odor always put them in a bad mood.

Attention significantly affected subjects' ratings of pain intensity but not of pain unpleasantness, whereas odor, the more emotionally fraught stimulus, had a strong and significant effect on unpleasantness and thus mood but no such effect on intensity.

She concluded that psychological factors might contribute to many pain states–for example, allodynia, in which a light touch can elicit severe pain. In such cases–including in experiments conducted by her pain clinic–the patient's perception is borne out by what is happening in the brain.

When asked in a panel discussion whether the ability to divert attention from one's pain could be affected by cognitive factors, she alluded to research findings that chronic-pain patients with more solicitous spouses reported more pain and had more activation of the pain region in the brain than did those with less solicitous spouses.

“By constantly asking a patient about their pain, you're focusing their attention on their pain,” Dr. Bushnell said.

Roger B. Fillingim, Ph.D., of the University of Florida, Gainesville, presented a discussion of the individual factors affecting pain perception, which can include gender, ethnicity, physiological and psychological states, and genetics. He cited previous research from his laboratory showing that men were able to tolerate ischemic pain longer than women could.

Dr. Fillingim also discussed an analysis showing that for ischemic pain, heat, pressure, and temporal summation of heat pain, the group with the highest pain sensitivity was more heavily populated by women and ethnic minorities. He cautioned, however, that such studies rely on self-reported pain thresholds.

To avoid this limitation, his group performed a study in which they induced a leg-muscle reflex normally correlated with pain. They found that African Americans responded to a lower stimulus intensity than whites did.

In the area of gender differences, Dr. Fillingim's group found that for all pain measures (heat, cold, ischemic, and pressure pain), men had greater-than-average self-reported tolerance, whereas women had less than the mean. This may be influenced by attitudes toward pain, such as catastrophizing, he noted.

But interestingly, positive affect was correlated with decreased pain sensitivity only in men. Analgesic responses were less consistent; morphine or pentazocine showed only insignificant sex differences in a study by his group. However, negative affect in men predicted less analgesia but had no effect on women's responses to pain medication. The same was true for catastrophizing.

There are also genetic factors that research has shown might influence pain and analgesia, Dr. Fillingim said. In particular, an allele of the OPRM1 gene predicts lower pressure-pain sensitivity in men. This allele is rare in African Americans but more common in whites and Hispanics, he noted. But only in whites did this allele seem to confer less pain sensitivity; the opposite was true in Hispanic subjects.

It's important to determine which factors predict individual differences in pain response, he emphasized, so that future treatment approaches can be tailored to each patient.

Activation (yellow) is visible during pain stimulation; the subject expected the administered 50° C stimulus.

There was less pain-related activation during the same stimulation when the subject expected a reduced stimulus. Images courtesy Dr. Robert C. Coghill/Wake Forest University School of Medicine

BETHESDA, MD. – Pain perception, far from being the simple one-directional process first proposed by Descartes in 1664, appears to be modulated by several psychological, genetic, and other factors specific to the individual experiencing it, several presenters said at a meeting sponsored by the National Institutes of Health's Pain Consortium.

Robert C. Coghill, Ph.D., of Wake Forest University, Winston-Salem, N.C., noted that subjective factors influencing pain perception include the environment in which the pain is experienced, as well as the person's memories of past experiences with the particular stimulus and future implications associated with it.

“It's a complex combination of afferent information with who the person really is–what they're thinking about, what that stimulus means to them,” Dr. Coghill said.

As evidence of this subjectivity, he noted a “tremendous” variability among 17 normal, healthy individuals' perceived intensity of a pain stimulus in a functional MRI study that he and his colleagues conducted.

He noted that brain activity in the highly sensitive participants was greater than in the less-sensitive subjects as assessed on fMRI; the highly sensitive subjects also had activity in brain areas different from those in the less-sensitive subjects. These findings show that the subjects had a physical difference in the way they experienced pain, correlating with their self-reported sensitivity to the stimulus.

However, the investigators were surprised to note no such differences in activity within the thalamus. The fact that there were statistically significant differences in activity beyond the thalamus but not within it led his team to theorize that many differences in pain are not attributable to a bottom-up process but to a top-down process.

“Maybe these individuals are getting a generally similar input from their peripheral nerves through their spinal cord up into their thalamus,” he said. “Then, once it gets to the thalamus, and gets beyond and starts to get integrated into who that person really is–maybe that's where the individual differences are emerging.”

This idea led Dr. Coghill and his colleagues to investigate expectations as the source of such differences, by using a previously devised expectation model he called the “the stew-in-your-own-juices paradigm.”

Expectations, along with desire, he noted, “are a fundamental component of the placebo response” and are easy to manipulate and control. Moreover, they result from a person's experience with a particular stimulus to form an expectation for future experiences.

The investigators played an audio tone for the participants before subjecting them to a thermal pain stimulus; the longer the interval between the tone and the stimulus, the hotter the stimulus was. Thus participants were trained to expect pain based on the length of the interval. The investigators then gave subjects a tone/stimulus interval leading them to expect less pain–but instead gave them the most severe stimulus. All 10 subjects, true to their training, reported less pain, and their pain-related brain activation also declined.

“The experience of pain is really unique from one individual to the next,” Dr. Coghill said. “Our sensory reality is highly subjective; it's shaped very much by what we think it's going to be.”

When asked what physicians should say to patients before administering a potentially painful procedure, he responded, “Certainly, the nurse with the big, huge needle full of tetanus immunization or whatever, saying, 'This won't hurt a bit' is a problem, because … expectations are created, and immediately you realize that they're not valid.”

Dr. Coghill suggested telling patients honestly that pain might be forthcoming–but also giving them a projected duration of the pain.

The differences in pain perception may also be a function of attention and emotion, M. Catherine Bushnell, Ph.D., of McGill University, Montreal, said in her presentation. She noted clinical and anecdotal evidence showing the effect of attention on pain perception–including human and animal studies that, like Dr. Coghill's, presented subjects with a pair of painful heat stimuli and a pair of sounds.

Subjects were asked to detect subtle differences in one stimulus or the other. By making the task more difficult, the researchers increased the subjects' level of attention on the task. They found that when subjects were more focused on the painful stimuli, there was more activity in corresponding regions of the brain, she said.

Dr. Bushnell also explained that some experiments can arouse a sympathetic reaction, which involves the cardiovascular system as well as emotions, as manipulation of subjects by tension tasks often does, she noted.

To separately examine the effects of mood and attention on pain perception, she and her colleagues performed an experiment that, instead of an auditory stimulus, used an olfactory stimulus, because smells “have strong emotional impact on people,” she said.

The investigators determined odors each patient did not like and then performed essentially the same comparison test as before, but using two odors with the two painful heat stimuli.

They found that regardless of where the subjects' attention was focused, if the odor was pleasant, they were in a good mood, but a bad odor always put them in a bad mood.

Attention significantly affected subjects' ratings of pain intensity but not of pain unpleasantness, whereas odor, the more emotionally fraught stimulus, had a strong and significant effect on unpleasantness and thus mood but no such effect on intensity.

She concluded that psychological factors might contribute to many pain states–for example, allodynia, in which a light touch can elicit severe pain. In such cases–including in experiments conducted by her pain clinic–the patient's perception is borne out by what is happening in the brain.

When asked in a panel discussion whether the ability to divert attention from one's pain could be affected by cognitive factors, she alluded to research findings that chronic-pain patients with more solicitous spouses reported more pain and had more activation of the pain region in the brain than did those with less solicitous spouses.

“By constantly asking a patient about their pain, you're focusing their attention on their pain,” Dr. Bushnell said.

Roger B. Fillingim, Ph.D., of the University of Florida, Gainesville, presented a discussion of the individual factors affecting pain perception, which can include gender, ethnicity, physiological and psychological states, and genetics. He cited previous research from his laboratory showing that men were able to tolerate ischemic pain longer than women could.

Dr. Fillingim also discussed an analysis showing that for ischemic pain, heat, pressure, and temporal summation of heat pain, the group with the highest pain sensitivity was more heavily populated by women and ethnic minorities. He cautioned, however, that such studies rely on self-reported pain thresholds.

To avoid this limitation, his group performed a study in which they induced a leg-muscle reflex normally correlated with pain. They found that African Americans responded to a lower stimulus intensity than whites did.

In the area of gender differences, Dr. Fillingim's group found that for all pain measures (heat, cold, ischemic, and pressure pain), men had greater-than-average self-reported tolerance, whereas women had less than the mean. This may be influenced by attitudes toward pain, such as catastrophizing, he noted.

But interestingly, positive affect was correlated with decreased pain sensitivity only in men. Analgesic responses were less consistent; morphine or pentazocine showed only insignificant sex differences in a study by his group. However, negative affect in men predicted less analgesia but had no effect on women's responses to pain medication. The same was true for catastrophizing.

There are also genetic factors that research has shown might influence pain and analgesia, Dr. Fillingim said. In particular, an allele of the OPRM1 gene predicts lower pressure-pain sensitivity in men. This allele is rare in African Americans but more common in whites and Hispanics, he noted. But only in whites did this allele seem to confer less pain sensitivity; the opposite was true in Hispanic subjects.

It's important to determine which factors predict individual differences in pain response, he emphasized, so that future treatment approaches can be tailored to each patient.

Activation (yellow) is visible during pain stimulation; the subject expected the administered 50° C stimulus.

There was less pain-related activation during the same stimulation when the subject expected a reduced stimulus. Images courtesy Dr. Robert C. Coghill/Wake Forest University School of Medicine

Human papillomavirus testing alone was more sensitive than conventional cytology for detecting cervical intraepithelial neoplasia, and adding liquid-based cytology to HPV testing only increased the rate of false positives, according to a phase I report from a two-phase randomized controlled trial.

Dr. Guglielmo Ronco of the Centro per la Prevenzione Oncologica, Turin, Italy, and his colleagues from the New Technologies for Cervical Cancer Working Group enrolled more than 33,000 women from nine Italian cancer-screening programs. The primary end point of the analysis was cervical intraepithelial neoplasia grade 2 (CIN2) or higher (as confirmed by histology) or cervical cancer found via the screening test.

One group (16,658 women) was screened via conventional cytology; the experimental group (16,706) was screened by using the ThinPrep liquid-based cytology system (Cytyc Corp., Boxborough, Mass.) and tested for HPV with the Hybrid Capture 2 assay (Digene Corp., Gaithersburg, Md.). Mean patient age was 45 years. Exclusion criteria were pregnancy, prior hysterectomy, or CIN testing within the last 5 years. (J. Natl. Cancer Inst. 2006;98:765–74).

Referral to colposcopy was triggered by a finding of atypical squamous cells of undetermined significance (ASCUS) in the conventional arm and by either findings of ASCUS or a positive (at least 1 pg/mL) HPV test in the experimental arm.

CIN2 or a more severe histology was found in 75 of the women in the experimental arm, 54 of whom had ASCUS or more severe cytology and 73 of whom tested positive for HPV. Among women in the conventional arm, there were 51 women with CIN2 histology or worse.

When compared with the conventional cytology arm, the experimental screening group had higher relative sensitivity (1.47) for detecting CIN2 or greater but the decrease in positive predictive value (11.4% vs. 4.5%) was substantial. ASCUS was the cutoff for colposcopy.

By contrast, HPV testing alone, with 1- and 2-pg/mL cutoffs, increased sensitivity over conventional cytology by 43% and 41%, respectively.

In addition, HPV testing alone, again with 1- and 2-pg/mL cutoffs, avoided the loss of positive predictive value seen when liquid-based cytology was added, 6.6% and 8.5%, respectively.

“Our data strongly suggest that supplementing HPV testing with cytology provides little advantage and mainly increases costs and anxiety,” the authors concluded. They added that the absence of any high-grade lesions among 845 HPV-negative women with ASCUS cytology “strongly supports the use of HPV in triaging ASCUS when cytology is performed first, as previously reported.”

Human papillomavirus testing alone was more sensitive than conventional cytology for detecting cervical intraepithelial neoplasia, and adding liquid-based cytology to HPV testing only increased the rate of false positives, according to a phase I report from a two-phase randomized controlled trial.

Dr. Guglielmo Ronco of the Centro per la Prevenzione Oncologica, Turin, Italy, and his colleagues from the New Technologies for Cervical Cancer Working Group enrolled more than 33,000 women from nine Italian cancer-screening programs. The primary end point of the analysis was cervical intraepithelial neoplasia grade 2 (CIN2) or higher (as confirmed by histology) or cervical cancer found via the screening test.

One group (16,658 women) was screened via conventional cytology; the experimental group (16,706) was screened by using the ThinPrep liquid-based cytology system (Cytyc Corp., Boxborough, Mass.) and tested for HPV with the Hybrid Capture 2 assay (Digene Corp., Gaithersburg, Md.). Mean patient age was 45 years. Exclusion criteria were pregnancy, prior hysterectomy, or CIN testing within the last 5 years. (J. Natl. Cancer Inst. 2006;98:765–74).

Referral to colposcopy was triggered by a finding of atypical squamous cells of undetermined significance (ASCUS) in the conventional arm and by either findings of ASCUS or a positive (at least 1 pg/mL) HPV test in the experimental arm.

CIN2 or a more severe histology was found in 75 of the women in the experimental arm, 54 of whom had ASCUS or more severe cytology and 73 of whom tested positive for HPV. Among women in the conventional arm, there were 51 women with CIN2 histology or worse.

When compared with the conventional cytology arm, the experimental screening group had higher relative sensitivity (1.47) for detecting CIN2 or greater but the decrease in positive predictive value (11.4% vs. 4.5%) was substantial. ASCUS was the cutoff for colposcopy.

By contrast, HPV testing alone, with 1- and 2-pg/mL cutoffs, increased sensitivity over conventional cytology by 43% and 41%, respectively.

In addition, HPV testing alone, again with 1- and 2-pg/mL cutoffs, avoided the loss of positive predictive value seen when liquid-based cytology was added, 6.6% and 8.5%, respectively.

“Our data strongly suggest that supplementing HPV testing with cytology provides little advantage and mainly increases costs and anxiety,” the authors concluded. They added that the absence of any high-grade lesions among 845 HPV-negative women with ASCUS cytology “strongly supports the use of HPV in triaging ASCUS when cytology is performed first, as previously reported.”

Human papillomavirus testing alone was more sensitive than conventional cytology for detecting cervical intraepithelial neoplasia, and adding liquid-based cytology to HPV testing only increased the rate of false positives, according to a phase I report from a two-phase randomized controlled trial.

Dr. Guglielmo Ronco of the Centro per la Prevenzione Oncologica, Turin, Italy, and his colleagues from the New Technologies for Cervical Cancer Working Group enrolled more than 33,000 women from nine Italian cancer-screening programs. The primary end point of the analysis was cervical intraepithelial neoplasia grade 2 (CIN2) or higher (as confirmed by histology) or cervical cancer found via the screening test.

One group (16,658 women) was screened via conventional cytology; the experimental group (16,706) was screened by using the ThinPrep liquid-based cytology system (Cytyc Corp., Boxborough, Mass.) and tested for HPV with the Hybrid Capture 2 assay (Digene Corp., Gaithersburg, Md.). Mean patient age was 45 years. Exclusion criteria were pregnancy, prior hysterectomy, or CIN testing within the last 5 years. (J. Natl. Cancer Inst. 2006;98:765–74).

Referral to colposcopy was triggered by a finding of atypical squamous cells of undetermined significance (ASCUS) in the conventional arm and by either findings of ASCUS or a positive (at least 1 pg/mL) HPV test in the experimental arm.

CIN2 or a more severe histology was found in 75 of the women in the experimental arm, 54 of whom had ASCUS or more severe cytology and 73 of whom tested positive for HPV. Among women in the conventional arm, there were 51 women with CIN2 histology or worse.

When compared with the conventional cytology arm, the experimental screening group had higher relative sensitivity (1.47) for detecting CIN2 or greater but the decrease in positive predictive value (11.4% vs. 4.5%) was substantial. ASCUS was the cutoff for colposcopy.

By contrast, HPV testing alone, with 1- and 2-pg/mL cutoffs, increased sensitivity over conventional cytology by 43% and 41%, respectively.

In addition, HPV testing alone, again with 1- and 2-pg/mL cutoffs, avoided the loss of positive predictive value seen when liquid-based cytology was added, 6.6% and 8.5%, respectively.

“Our data strongly suggest that supplementing HPV testing with cytology provides little advantage and mainly increases costs and anxiety,” the authors concluded. They added that the absence of any high-grade lesions among 845 HPV-negative women with ASCUS cytology “strongly supports the use of HPV in triaging ASCUS when cytology is performed first, as previously reported.”

In juvenile idiopathic arthritis, health-related quality of life is “less than optimal”—especially in terms of gross motor and systemic functioning, both of which are related to pain, disease activity, and functional disability, reported K.L. Shaw, Ph.D., and colleagues.

Improving JIA patients' quality of life is thus “inextricably linked with managing these key aspects of care,” Dr. Shaw, of the University of Birmingham (England), and colleagues reported.

Adolescents with juvenile idiopathic arthritis, aged 11, 14, and 17 years, were recruited from 10 rheumatology centers in the United Kingdom to assess health-related quality of life using the Juvenile Arthritis Quality of Life Questionnaire (JAQQ), the investigators reported. They received complete responses from 308 participants (Arthritis Rheum. 2006;55:199–207).

The JAQQ was composed of 74 statements. Patients responded to the questionnaire statements by using a seven-point scale, with one representing “none of the time/never” and seven representing “all of the time/always.” (A “does not apply to me” option was also available for each question.)

The questions covered four categories: gross motor function, fine motor function, psychosocial function, and systemic symptoms. The respondents were also asked to list their five biggest problems in each of the four categories.

Results were similar across all age groups. The large-motor-skills category received a mean JAQQ score of 3.0 among all three age groups.

Activities reported as most problematic were “kneeling or sitting on heels for several minutes,” “standing for half an hour,” and “running two blocks,” the investigators reported.

Fine motor function received the lowest score from patients (median score 1.6). The most difficult reported tasks were “twisting off a bottle/jar top (previously opened)” and “opening a soft drink can.”

Psychosocial complaints were also of concern to the investigators, who suggested that, to reduce frustration, cognitive techniques be used to teach patients to have realistic expectations and emotional responses.

Psychosocial function had a median score of 2.6. The most common problems reported were “felt frustrated,” identified by nearly one-third of participants, and “felt depressed” reported by nearly one-fourth of the patients. Systemic problems included “stiffness,” “joint tenderness,” and “tires easily.”

Dr. Shaw and colleagues noted that their study was the largest to date in the United Kingdom and the only study to focus on JIA in adolescents.

They, however, cautioned that their study used only one questionnaire (the JAQQ), which was not calibrated, and that their study patient cohort was largely white and predominantly female, perhaps limiting its applicability to other patient groups.

ELSEVIER GLOBAL MEDICAL NEWS

In juvenile idiopathic arthritis, health-related quality of life is “less than optimal”—especially in terms of gross motor and systemic functioning, both of which are related to pain, disease activity, and functional disability, reported K.L. Shaw, Ph.D., and colleagues.

Improving JIA patients' quality of life is thus “inextricably linked with managing these key aspects of care,” Dr. Shaw, of the University of Birmingham (England), and colleagues reported.

Adolescents with juvenile idiopathic arthritis, aged 11, 14, and 17 years, were recruited from 10 rheumatology centers in the United Kingdom to assess health-related quality of life using the Juvenile Arthritis Quality of Life Questionnaire (JAQQ), the investigators reported. They received complete responses from 308 participants (Arthritis Rheum. 2006;55:199–207).

The JAQQ was composed of 74 statements. Patients responded to the questionnaire statements by using a seven-point scale, with one representing “none of the time/never” and seven representing “all of the time/always.” (A “does not apply to me” option was also available for each question.)

The questions covered four categories: gross motor function, fine motor function, psychosocial function, and systemic symptoms. The respondents were also asked to list their five biggest problems in each of the four categories.

Results were similar across all age groups. The large-motor-skills category received a mean JAQQ score of 3.0 among all three age groups.

Activities reported as most problematic were “kneeling or sitting on heels for several minutes,” “standing for half an hour,” and “running two blocks,” the investigators reported.

Fine motor function received the lowest score from patients (median score 1.6). The most difficult reported tasks were “twisting off a bottle/jar top (previously opened)” and “opening a soft drink can.”

Psychosocial complaints were also of concern to the investigators, who suggested that, to reduce frustration, cognitive techniques be used to teach patients to have realistic expectations and emotional responses.

Psychosocial function had a median score of 2.6. The most common problems reported were “felt frustrated,” identified by nearly one-third of participants, and “felt depressed” reported by nearly one-fourth of the patients. Systemic problems included “stiffness,” “joint tenderness,” and “tires easily.”

Dr. Shaw and colleagues noted that their study was the largest to date in the United Kingdom and the only study to focus on JIA in adolescents.

They, however, cautioned that their study used only one questionnaire (the JAQQ), which was not calibrated, and that their study patient cohort was largely white and predominantly female, perhaps limiting its applicability to other patient groups.

ELSEVIER GLOBAL MEDICAL NEWS

In juvenile idiopathic arthritis, health-related quality of life is “less than optimal”—especially in terms of gross motor and systemic functioning, both of which are related to pain, disease activity, and functional disability, reported K.L. Shaw, Ph.D., and colleagues.

Improving JIA patients' quality of life is thus “inextricably linked with managing these key aspects of care,” Dr. Shaw, of the University of Birmingham (England), and colleagues reported.

Adolescents with juvenile idiopathic arthritis, aged 11, 14, and 17 years, were recruited from 10 rheumatology centers in the United Kingdom to assess health-related quality of life using the Juvenile Arthritis Quality of Life Questionnaire (JAQQ), the investigators reported. They received complete responses from 308 participants (Arthritis Rheum. 2006;55:199–207).

The JAQQ was composed of 74 statements. Patients responded to the questionnaire statements by using a seven-point scale, with one representing “none of the time/never” and seven representing “all of the time/always.” (A “does not apply to me” option was also available for each question.)

The questions covered four categories: gross motor function, fine motor function, psychosocial function, and systemic symptoms. The respondents were also asked to list their five biggest problems in each of the four categories.

Results were similar across all age groups. The large-motor-skills category received a mean JAQQ score of 3.0 among all three age groups.

Activities reported as most problematic were “kneeling or sitting on heels for several minutes,” “standing for half an hour,” and “running two blocks,” the investigators reported.

Fine motor function received the lowest score from patients (median score 1.6). The most difficult reported tasks were “twisting off a bottle/jar top (previously opened)” and “opening a soft drink can.”

Psychosocial complaints were also of concern to the investigators, who suggested that, to reduce frustration, cognitive techniques be used to teach patients to have realistic expectations and emotional responses.

Psychosocial function had a median score of 2.6. The most common problems reported were “felt frustrated,” identified by nearly one-third of participants, and “felt depressed” reported by nearly one-fourth of the patients. Systemic problems included “stiffness,” “joint tenderness,” and “tires easily.”

Dr. Shaw and colleagues noted that their study was the largest to date in the United Kingdom and the only study to focus on JIA in adolescents.

They, however, cautioned that their study used only one questionnaire (the JAQQ), which was not calibrated, and that their study patient cohort was largely white and predominantly female, perhaps limiting its applicability to other patient groups.

ELSEVIER GLOBAL MEDICAL NEWS

In children younger than 6 years but older than 6 months, the influenza C virus is a significant cause of upper respiratory tract illness and is probably contracted in many cases from a preschool-aged child in the same home, Japanese researchers reported.

Dr. Yoko Matsuzaki of the department of infectious diseases at Yamagata (Japan) University and colleagues developed a tissue-culture method to test for the virus, and then examined roughly 85,000 respiratory tract specimens collected over a 14-year period from asymptomatic children who were no older than 15 years and had been seen at any of seven Japanese pediatric clinics and hospitals. In total, 187 specimens (0.22%) were positive for influenza C; 17 were excluded because of respiratory coinfection or incomplete medical records. The investigators obtained clinical data on the 170 remaining children and performed nucleotide sequencing to look at intrafamily transmission (J. Infect. Dis. 2006;193:1229–35).

There was a strong association between influenza C upper respiratory tract (URT) infection and the preschool age range. Indeed, 92% of the children found to have influenza C virus were between 6 months and 6 years old—a fact likely explained, they noted, by prior studies' findings that most humans acquire antibodies to influenza C by age 7–10 years and that newborns receive maternal antibodies against the virus that vanish by 6 months—leaving an open window of virus vulnerability in the intervening age group.

In the study, the infection incidence among 1-year-old children was more than three times that of children aged 7–12 months. Although only 17% of the total were hospitalized, this rate was nearly doubled (30%) in children younger than 2 years. The incidence among girls and boys was similar.

As to the transmission vector, “households are important sites for the transmission of the influenza viruses,” the researchers said—but for influenza C, they noted that “preschool children might play a significant role” in bringing the virus into the home.

Influenza C causes symptoms similar to those of other influenza strains. The most common symptoms in the study were fever, cough, and runny nose. This was true for children both younger and older than 6 years, regardless of whether the child was hospitalized. More than three-fourths (79%) of children who were not hospitalized were diagnosed with upper respiratory tract infection or influenza.

The authors found that most influenza C infections occurred in the winter and spring, but especially in the period from April through June. However, they noted that this seasonal association is not evident in regions of the world that—unlike snowy north central Japan—have mild winters. Thus, wintertime influenza C likely often coexists with influenza A and B in temperate areas, making differential diagnosis important.

In children younger than 6 years but older than 6 months, the influenza C virus is a significant cause of upper respiratory tract illness and is probably contracted in many cases from a preschool-aged child in the same home, Japanese researchers reported.

Dr. Yoko Matsuzaki of the department of infectious diseases at Yamagata (Japan) University and colleagues developed a tissue-culture method to test for the virus, and then examined roughly 85,000 respiratory tract specimens collected over a 14-year period from asymptomatic children who were no older than 15 years and had been seen at any of seven Japanese pediatric clinics and hospitals. In total, 187 specimens (0.22%) were positive for influenza C; 17 were excluded because of respiratory coinfection or incomplete medical records. The investigators obtained clinical data on the 170 remaining children and performed nucleotide sequencing to look at intrafamily transmission (J. Infect. Dis. 2006;193:1229–35).

There was a strong association between influenza C upper respiratory tract (URT) infection and the preschool age range. Indeed, 92% of the children found to have influenza C virus were between 6 months and 6 years old—a fact likely explained, they noted, by prior studies' findings that most humans acquire antibodies to influenza C by age 7–10 years and that newborns receive maternal antibodies against the virus that vanish by 6 months—leaving an open window of virus vulnerability in the intervening age group.

In the study, the infection incidence among 1-year-old children was more than three times that of children aged 7–12 months. Although only 17% of the total were hospitalized, this rate was nearly doubled (30%) in children younger than 2 years. The incidence among girls and boys was similar.

As to the transmission vector, “households are important sites for the transmission of the influenza viruses,” the researchers said—but for influenza C, they noted that “preschool children might play a significant role” in bringing the virus into the home.

Influenza C causes symptoms similar to those of other influenza strains. The most common symptoms in the study were fever, cough, and runny nose. This was true for children both younger and older than 6 years, regardless of whether the child was hospitalized. More than three-fourths (79%) of children who were not hospitalized were diagnosed with upper respiratory tract infection or influenza.

The authors found that most influenza C infections occurred in the winter and spring, but especially in the period from April through June. However, they noted that this seasonal association is not evident in regions of the world that—unlike snowy north central Japan—have mild winters. Thus, wintertime influenza C likely often coexists with influenza A and B in temperate areas, making differential diagnosis important.

In children younger than 6 years but older than 6 months, the influenza C virus is a significant cause of upper respiratory tract illness and is probably contracted in many cases from a preschool-aged child in the same home, Japanese researchers reported.

Dr. Yoko Matsuzaki of the department of infectious diseases at Yamagata (Japan) University and colleagues developed a tissue-culture method to test for the virus, and then examined roughly 85,000 respiratory tract specimens collected over a 14-year period from asymptomatic children who were no older than 15 years and had been seen at any of seven Japanese pediatric clinics and hospitals. In total, 187 specimens (0.22%) were positive for influenza C; 17 were excluded because of respiratory coinfection or incomplete medical records. The investigators obtained clinical data on the 170 remaining children and performed nucleotide sequencing to look at intrafamily transmission (J. Infect. Dis. 2006;193:1229–35).

There was a strong association between influenza C upper respiratory tract (URT) infection and the preschool age range. Indeed, 92% of the children found to have influenza C virus were between 6 months and 6 years old—a fact likely explained, they noted, by prior studies' findings that most humans acquire antibodies to influenza C by age 7–10 years and that newborns receive maternal antibodies against the virus that vanish by 6 months—leaving an open window of virus vulnerability in the intervening age group.

In the study, the infection incidence among 1-year-old children was more than three times that of children aged 7–12 months. Although only 17% of the total were hospitalized, this rate was nearly doubled (30%) in children younger than 2 years. The incidence among girls and boys was similar.

As to the transmission vector, “households are important sites for the transmission of the influenza viruses,” the researchers said—but for influenza C, they noted that “preschool children might play a significant role” in bringing the virus into the home.

Influenza C causes symptoms similar to those of other influenza strains. The most common symptoms in the study were fever, cough, and runny nose. This was true for children both younger and older than 6 years, regardless of whether the child was hospitalized. More than three-fourths (79%) of children who were not hospitalized were diagnosed with upper respiratory tract infection or influenza.

The authors found that most influenza C infections occurred in the winter and spring, but especially in the period from April through June. However, they noted that this seasonal association is not evident in regions of the world that—unlike snowy north central Japan—have mild winters. Thus, wintertime influenza C likely often coexists with influenza A and B in temperate areas, making differential diagnosis important.

A prostate cancer-screening strategy using complexed prostate-specific antigen rather than total PSA would reduce the occurrence of needless biopsies without compromising sensitivity, according to a series of analyses that compared the detection accuracy of various cutoff values of the two biomarkers.

More accurate markers for detecting prostate cancer are needed, given that the current total PSA (tPSA) cutoff value of 4.0 ng/mL (the threshold at which prostate biopsy is recommended) misses the roughly 30% of cancers that occur in men with tPSA levels below that cutoff.

Dr. R. Joseph Babaian, of the University of Texas M.D. Anderson Cancer Center, Houston, and his coinvestigators compared biopsy findings with tPSA and complexed PSA (cPSA) in 467 men. Of that total, cancer was confirmed by biopsy in 147 (31.5%). Men with cancer had a mean age of 64 years, and those without cancer had a mean age of 62 years.

Using the Mann-Whitney U test, the investigators compared the number of men who had and did not have cancer in each tPSA and cPSA range.

They found that among men with tPSA scores in the broad range of 2.5–6.0 ng/mL, the cancer-detection rate was 31.5%. The cancer-detection rate was similarly 32.6% among men with cPSA values in the range of 2.2–5.1 ng/mL (J. Urol. 2006;175:897–901).

They concluded that among men with tPSA in the range of 2.5–6.0 ng/mL, determining biopsy decisions based on a cPSA cutoff value of 2.2 ng/mL—rather than a tPSA level of 2.5 ng/mL—would have eliminated 12% of needless biopsies but missed 2% of cancer cases. Using the same cPSA cutoff among men with tPSA of 2.5–4.0 ng/mL would have spared 20% of the patients unnecessary biopsies.

In a separate analysis involving 2,807 men who participated in a free cancer-detection program at M.D. Anderson, the investigators concluded that using a 2.2- ng/mL cutoff value for cPSA—rather than a tPSA cutoff of 2.5 ng/mL—would save roughly 3% of this population from undergoing unnecessary biopsies, or 32,000 biopsies per 1 million men.

Avoiding unnecessary biopsies would provide a significant money-saving opportunity for the health care industry. “The direct biopsy charges saved would be about $38 million per 1 million men undergoing a PSA test in the United States,” the investigators wrote. They estimated that nationally, $190 million in direct, annual biopsy charges would be saved.

These study results confirm findings from previous investigations suggesting that cPSA might be a better initial diagnostic tool than tPSA, they wrote.

Their analyses, however, were limited by the fact that some participants came from referrals. A population-based study would, they said, provide stronger evidence of cPSA's superior accuracy.

In an editorial comment, Dr. J. Kellogg Parsons of the University of California, San Diego, wrote that “compared to tPSA, cPSA has increased specificity for prostate cancer detection at all clinically relevant sensitivities. Superior specificity decreases the number of false-positive results, which in turn potentially decreases unnecessary biopsies, health care expenditures, and patient anxiety.”

The study was supported by Bayer Diagnostics. Dr. Babaian disclosed a financial interest and/or other relationship with Bayer and AstraZeneca.

A prostate cancer-screening strategy using complexed prostate-specific antigen rather than total PSA would reduce the occurrence of needless biopsies without compromising sensitivity, according to a series of analyses that compared the detection accuracy of various cutoff values of the two biomarkers.

More accurate markers for detecting prostate cancer are needed, given that the current total PSA (tPSA) cutoff value of 4.0 ng/mL (the threshold at which prostate biopsy is recommended) misses the roughly 30% of cancers that occur in men with tPSA levels below that cutoff.

Dr. R. Joseph Babaian, of the University of Texas M.D. Anderson Cancer Center, Houston, and his coinvestigators compared biopsy findings with tPSA and complexed PSA (cPSA) in 467 men. Of that total, cancer was confirmed by biopsy in 147 (31.5%). Men with cancer had a mean age of 64 years, and those without cancer had a mean age of 62 years.

Using the Mann-Whitney U test, the investigators compared the number of men who had and did not have cancer in each tPSA and cPSA range.

They found that among men with tPSA scores in the broad range of 2.5–6.0 ng/mL, the cancer-detection rate was 31.5%. The cancer-detection rate was similarly 32.6% among men with cPSA values in the range of 2.2–5.1 ng/mL (J. Urol. 2006;175:897–901).

They concluded that among men with tPSA in the range of 2.5–6.0 ng/mL, determining biopsy decisions based on a cPSA cutoff value of 2.2 ng/mL—rather than a tPSA level of 2.5 ng/mL—would have eliminated 12% of needless biopsies but missed 2% of cancer cases. Using the same cPSA cutoff among men with tPSA of 2.5–4.0 ng/mL would have spared 20% of the patients unnecessary biopsies.

In a separate analysis involving 2,807 men who participated in a free cancer-detection program at M.D. Anderson, the investigators concluded that using a 2.2- ng/mL cutoff value for cPSA—rather than a tPSA cutoff of 2.5 ng/mL—would save roughly 3% of this population from undergoing unnecessary biopsies, or 32,000 biopsies per 1 million men.

Avoiding unnecessary biopsies would provide a significant money-saving opportunity for the health care industry. “The direct biopsy charges saved would be about $38 million per 1 million men undergoing a PSA test in the United States,” the investigators wrote. They estimated that nationally, $190 million in direct, annual biopsy charges would be saved.

These study results confirm findings from previous investigations suggesting that cPSA might be a better initial diagnostic tool than tPSA, they wrote.

Their analyses, however, were limited by the fact that some participants came from referrals. A population-based study would, they said, provide stronger evidence of cPSA's superior accuracy.

In an editorial comment, Dr. J. Kellogg Parsons of the University of California, San Diego, wrote that “compared to tPSA, cPSA has increased specificity for prostate cancer detection at all clinically relevant sensitivities. Superior specificity decreases the number of false-positive results, which in turn potentially decreases unnecessary biopsies, health care expenditures, and patient anxiety.”

The study was supported by Bayer Diagnostics. Dr. Babaian disclosed a financial interest and/or other relationship with Bayer and AstraZeneca.

A prostate cancer-screening strategy using complexed prostate-specific antigen rather than total PSA would reduce the occurrence of needless biopsies without compromising sensitivity, according to a series of analyses that compared the detection accuracy of various cutoff values of the two biomarkers.

More accurate markers for detecting prostate cancer are needed, given that the current total PSA (tPSA) cutoff value of 4.0 ng/mL (the threshold at which prostate biopsy is recommended) misses the roughly 30% of cancers that occur in men with tPSA levels below that cutoff.

Dr. R. Joseph Babaian, of the University of Texas M.D. Anderson Cancer Center, Houston, and his coinvestigators compared biopsy findings with tPSA and complexed PSA (cPSA) in 467 men. Of that total, cancer was confirmed by biopsy in 147 (31.5%). Men with cancer had a mean age of 64 years, and those without cancer had a mean age of 62 years.

Using the Mann-Whitney U test, the investigators compared the number of men who had and did not have cancer in each tPSA and cPSA range.

They found that among men with tPSA scores in the broad range of 2.5–6.0 ng/mL, the cancer-detection rate was 31.5%. The cancer-detection rate was similarly 32.6% among men with cPSA values in the range of 2.2–5.1 ng/mL (J. Urol. 2006;175:897–901).

They concluded that among men with tPSA in the range of 2.5–6.0 ng/mL, determining biopsy decisions based on a cPSA cutoff value of 2.2 ng/mL—rather than a tPSA level of 2.5 ng/mL—would have eliminated 12% of needless biopsies but missed 2% of cancer cases. Using the same cPSA cutoff among men with tPSA of 2.5–4.0 ng/mL would have spared 20% of the patients unnecessary biopsies.

In a separate analysis involving 2,807 men who participated in a free cancer-detection program at M.D. Anderson, the investigators concluded that using a 2.2- ng/mL cutoff value for cPSA—rather than a tPSA cutoff of 2.5 ng/mL—would save roughly 3% of this population from undergoing unnecessary biopsies, or 32,000 biopsies per 1 million men.

Avoiding unnecessary biopsies would provide a significant money-saving opportunity for the health care industry. “The direct biopsy charges saved would be about $38 million per 1 million men undergoing a PSA test in the United States,” the investigators wrote. They estimated that nationally, $190 million in direct, annual biopsy charges would be saved.

These study results confirm findings from previous investigations suggesting that cPSA might be a better initial diagnostic tool than tPSA, they wrote.

Their analyses, however, were limited by the fact that some participants came from referrals. A population-based study would, they said, provide stronger evidence of cPSA's superior accuracy.

In an editorial comment, Dr. J. Kellogg Parsons of the University of California, San Diego, wrote that “compared to tPSA, cPSA has increased specificity for prostate cancer detection at all clinically relevant sensitivities. Superior specificity decreases the number of false-positive results, which in turn potentially decreases unnecessary biopsies, health care expenditures, and patient anxiety.”

The study was supported by Bayer Diagnostics. Dr. Babaian disclosed a financial interest and/or other relationship with Bayer and AstraZeneca.

The American Academy of Otolaryngology's first-ever guidelines for the diagnosis and treatment of acute otitis externa—commonly known as swimmer's ear—include a recommendation to treat pain and to use antimicrobial drops, rather than oral antibiotics, as first-line treatment.

The clinical practice guidelines were derived from a metaanalysis of nearly 3,000 published reports and were written by a panel of otolaryngologists from various subspecialties.

The document notes that starting treatment of acute otitis externa (AOE) with drops can help prevent bacterial resistance—even though many drops contain antibiotics themselves. “It's a concentration issue,” explained Dr. Richard Rosenfeld, who led the AAO guidelines writing committee. “You can achieve a concentration with a topical drop that's about 1,000 times higher [at the infection site] than with a systemic drug. Topical [medication] is so incredibly potent that it overwhelms any ability of resistance. … Dead bugs don't mutate—especially if you wipe them all out with a Scud missile of a drop.”

But drops don't have to even contain antibiotics to be effective, he noted. “We tested many types of topical therapy out there—antiseptics, various types of antibiotics, and also steroid-containing preparations. And they all seemed to have very comparable efficacy. We saw only minor, clinically irrelevant differences in efficacy. That doesn't mean that it's at all irrelevant what you use—for example, quinolone drops are perhaps most suitable for severe infections, because they're the most potent—but that's only anecdotal,” added Dr. Rosenfeld, director of pediatric otolaryngology at Long Island College Hospital in New York.

As to prevention of swimmer's ear, Dr. Rosenfeld said that although there's no specific policy statement, in his opinion, the key is to avoid the things that trigger AOE. Those include trauma or scratching of the ear canal and allowing excess water to build up in the ear canal and get trapped there. Trauma can be caused by cotton swabs or other objects inserted to remove wax or to scratch, or even by inserting foam ear plugs for swimming. Such earplugs are fine for preventing noise exposure because there is no water involved, he said. “But for swimming, just stuffing [foam] earplugs into your ears just doesn't work” and can lead to trauma, he said.

When water does get in the ear, Dr. Rosenfeld recommended eliminating it with a hair dryer on a low setting. Administering a few drops of isopropyl alcohol also works, and it is considerably less expensive than over-the-counter swimmer's ear drops. Alternatively, a few drops of white vinegar and rubbing alcohol combined in a 50/50 ratio also can prevent swimmer's ear if applied after swimming or bathing. This combination is similar to some of the commercially available preparations. Vinegar is 5% acetic acid, and mixing it with the alcohol gets it down to 2.5% acetic acid. The alcohol helps kill bacteria and is a drying agent.

“It's a poor man's version of some of the rather expensive prescription drops. I wouldn't recommend it as a mainstay of treatment, but for people who are prone to AOE, it should help prevent it,” he said.

“It's a lot simpler to use drops,” commented Dr. Roland Eavey, professor of otology and laryngology at Harvard University, Boston. “Drops don't cause systemic side effects, such as diarrhea—and by using drops, you help keep down bacterial resistance.”

Dr. Eavey, who also is director of pediatric otolaryngology at Massachusetts Eye and Ear Infirmary in Boston, and who served on the AAO's guidelines panel for acute otitis media, agreed with the strong recommendation in favor of assessing and treating pain. “Otitis externa can be very painful. On the assessment, when a child comes in with really bad external otitis externa, they first of all need pain relief.”

He also shared the AAO's recommendation regarding differential diagnosis. “For example, although rare in childhood, malignant external otitis is a serious bone infection which mimics acute external otitis and can occur in insulin-dependent diabetics,” he said.

He added his own specific recommendation: “You need to differentiate between a child with acute otitis and one with acute mastoiditis if there is swelling behind the ear. In that case, you need a clinical view of the eardrum and possibly a CT scan to make sure it's not mastoiditis. But for garden-variety otitis externa, go with the ear drops, and the patient should get better—if they're not much improved in 2–3 days, the patient should be reassessed.

Dr. Eavey also shared a treatment pearl. “My recommendation is also to have Mom or Dad warm up the drops up in their hand or carry them in their pocket, because drops are often colder than the ear canal—and so to a child, it can feel like having ice water poured into their ear.” He echoed a tip advocated in the guidelines that putting a wick in a severely swollen ear can help deliver the drops into the canal.

Dr. Seth Pransky, a pediatric otolaryngologist at Children's Hospital in San Diego, observed that although the guidelines are new, their advice is familiar to many physicians. “Perhaps this might be considered new for primary care physicians, but the vast majority of otolaryngologists understand that this is a disease treated with topical rather than oral antibiotics. There are cases where orals are necessary, and the guidelines point that out—but they're a lot less common than garden variety, run-of-the-mill swimmer's ear, which is very painful.”

Dr. Michael Pichichero, professor of microbiology and immunology at the University of Rochester (N.Y.) Medical Center, also approved of the recommendations. “I think the guidelines are very well written and comprehensive and appear to be evidence based—on as much evidence as we do have,” he said in an interview.

In particular Dr. Pichichero noted that distinguishing between patients who have an intact eardrum and those who don't has a sizeable impact on the antibiotic choice—because if the eardrum is not intact, “we really should move to preference for the chloroquinolone antibiotic preparations, which are not ototoxic.”

The document gave various treatment recommendations for specific AOE etiologies and advised against the use of alternative therapies such as ear candles.

The guidelines, which were published as a supplement to the journal, Otolaryngology-Head and Neck Surgery, will be available free of charge at www.entnet.org

The American Academy of Otolaryngology's first-ever guidelines for the diagnosis and treatment of acute otitis externa—commonly known as swimmer's ear—include a recommendation to treat pain and to use antimicrobial drops, rather than oral antibiotics, as first-line treatment.

The clinical practice guidelines were derived from a metaanalysis of nearly 3,000 published reports and were written by a panel of otolaryngologists from various subspecialties.

The document notes that starting treatment of acute otitis externa (AOE) with drops can help prevent bacterial resistance—even though many drops contain antibiotics themselves. “It's a concentration issue,” explained Dr. Richard Rosenfeld, who led the AAO guidelines writing committee. “You can achieve a concentration with a topical drop that's about 1,000 times higher [at the infection site] than with a systemic drug. Topical [medication] is so incredibly potent that it overwhelms any ability of resistance. … Dead bugs don't mutate—especially if you wipe them all out with a Scud missile of a drop.”

But drops don't have to even contain antibiotics to be effective, he noted. “We tested many types of topical therapy out there—antiseptics, various types of antibiotics, and also steroid-containing preparations. And they all seemed to have very comparable efficacy. We saw only minor, clinically irrelevant differences in efficacy. That doesn't mean that it's at all irrelevant what you use—for example, quinolone drops are perhaps most suitable for severe infections, because they're the most potent—but that's only anecdotal,” added Dr. Rosenfeld, director of pediatric otolaryngology at Long Island College Hospital in New York.

As to prevention of swimmer's ear, Dr. Rosenfeld said that although there's no specific policy statement, in his opinion, the key is to avoid the things that trigger AOE. Those include trauma or scratching of the ear canal and allowing excess water to build up in the ear canal and get trapped there. Trauma can be caused by cotton swabs or other objects inserted to remove wax or to scratch, or even by inserting foam ear plugs for swimming. Such earplugs are fine for preventing noise exposure because there is no water involved, he said. “But for swimming, just stuffing [foam] earplugs into your ears just doesn't work” and can lead to trauma, he said.

When water does get in the ear, Dr. Rosenfeld recommended eliminating it with a hair dryer on a low setting. Administering a few drops of isopropyl alcohol also works, and it is considerably less expensive than over-the-counter swimmer's ear drops. Alternatively, a few drops of white vinegar and rubbing alcohol combined in a 50/50 ratio also can prevent swimmer's ear if applied after swimming or bathing. This combination is similar to some of the commercially available preparations. Vinegar is 5% acetic acid, and mixing it with the alcohol gets it down to 2.5% acetic acid. The alcohol helps kill bacteria and is a drying agent.

“It's a poor man's version of some of the rather expensive prescription drops. I wouldn't recommend it as a mainstay of treatment, but for people who are prone to AOE, it should help prevent it,” he said.

“It's a lot simpler to use drops,” commented Dr. Roland Eavey, professor of otology and laryngology at Harvard University, Boston. “Drops don't cause systemic side effects, such as diarrhea—and by using drops, you help keep down bacterial resistance.”

Dr. Eavey, who also is director of pediatric otolaryngology at Massachusetts Eye and Ear Infirmary in Boston, and who served on the AAO's guidelines panel for acute otitis media, agreed with the strong recommendation in favor of assessing and treating pain. “Otitis externa can be very painful. On the assessment, when a child comes in with really bad external otitis externa, they first of all need pain relief.”

He also shared the AAO's recommendation regarding differential diagnosis. “For example, although rare in childhood, malignant external otitis is a serious bone infection which mimics acute external otitis and can occur in insulin-dependent diabetics,” he said.

He added his own specific recommendation: “You need to differentiate between a child with acute otitis and one with acute mastoiditis if there is swelling behind the ear. In that case, you need a clinical view of the eardrum and possibly a CT scan to make sure it's not mastoiditis. But for garden-variety otitis externa, go with the ear drops, and the patient should get better—if they're not much improved in 2–3 days, the patient should be reassessed.

Dr. Eavey also shared a treatment pearl. “My recommendation is also to have Mom or Dad warm up the drops up in their hand or carry them in their pocket, because drops are often colder than the ear canal—and so to a child, it can feel like having ice water poured into their ear.” He echoed a tip advocated in the guidelines that putting a wick in a severely swollen ear can help deliver the drops into the canal.

Dr. Seth Pransky, a pediatric otolaryngologist at Children's Hospital in San Diego, observed that although the guidelines are new, their advice is familiar to many physicians. “Perhaps this might be considered new for primary care physicians, but the vast majority of otolaryngologists understand that this is a disease treated with topical rather than oral antibiotics. There are cases where orals are necessary, and the guidelines point that out—but they're a lot less common than garden variety, run-of-the-mill swimmer's ear, which is very painful.”

Dr. Michael Pichichero, professor of microbiology and immunology at the University of Rochester (N.Y.) Medical Center, also approved of the recommendations. “I think the guidelines are very well written and comprehensive and appear to be evidence based—on as much evidence as we do have,” he said in an interview.

In particular Dr. Pichichero noted that distinguishing between patients who have an intact eardrum and those who don't has a sizeable impact on the antibiotic choice—because if the eardrum is not intact, “we really should move to preference for the chloroquinolone antibiotic preparations, which are not ototoxic.”

The document gave various treatment recommendations for specific AOE etiologies and advised against the use of alternative therapies such as ear candles.

The guidelines, which were published as a supplement to the journal, Otolaryngology-Head and Neck Surgery, will be available free of charge at www.entnet.org

The American Academy of Otolaryngology's first-ever guidelines for the diagnosis and treatment of acute otitis externa—commonly known as swimmer's ear—include a recommendation to treat pain and to use antimicrobial drops, rather than oral antibiotics, as first-line treatment.

The clinical practice guidelines were derived from a metaanalysis of nearly 3,000 published reports and were written by a panel of otolaryngologists from various subspecialties.

The document notes that starting treatment of acute otitis externa (AOE) with drops can help prevent bacterial resistance—even though many drops contain antibiotics themselves. “It's a concentration issue,” explained Dr. Richard Rosenfeld, who led the AAO guidelines writing committee. “You can achieve a concentration with a topical drop that's about 1,000 times higher [at the infection site] than with a systemic drug. Topical [medication] is so incredibly potent that it overwhelms any ability of resistance. … Dead bugs don't mutate—especially if you wipe them all out with a Scud missile of a drop.”

But drops don't have to even contain antibiotics to be effective, he noted. “We tested many types of topical therapy out there—antiseptics, various types of antibiotics, and also steroid-containing preparations. And they all seemed to have very comparable efficacy. We saw only minor, clinically irrelevant differences in efficacy. That doesn't mean that it's at all irrelevant what you use—for example, quinolone drops are perhaps most suitable for severe infections, because they're the most potent—but that's only anecdotal,” added Dr. Rosenfeld, director of pediatric otolaryngology at Long Island College Hospital in New York.

As to prevention of swimmer's ear, Dr. Rosenfeld said that although there's no specific policy statement, in his opinion, the key is to avoid the things that trigger AOE. Those include trauma or scratching of the ear canal and allowing excess water to build up in the ear canal and get trapped there. Trauma can be caused by cotton swabs or other objects inserted to remove wax or to scratch, or even by inserting foam ear plugs for swimming. Such earplugs are fine for preventing noise exposure because there is no water involved, he said. “But for swimming, just stuffing [foam] earplugs into your ears just doesn't work” and can lead to trauma, he said.

When water does get in the ear, Dr. Rosenfeld recommended eliminating it with a hair dryer on a low setting. Administering a few drops of isopropyl alcohol also works, and it is considerably less expensive than over-the-counter swimmer's ear drops. Alternatively, a few drops of white vinegar and rubbing alcohol combined in a 50/50 ratio also can prevent swimmer's ear if applied after swimming or bathing. This combination is similar to some of the commercially available preparations. Vinegar is 5% acetic acid, and mixing it with the alcohol gets it down to 2.5% acetic acid. The alcohol helps kill bacteria and is a drying agent.

“It's a poor man's version of some of the rather expensive prescription drops. I wouldn't recommend it as a mainstay of treatment, but for people who are prone to AOE, it should help prevent it,” he said.

“It's a lot simpler to use drops,” commented Dr. Roland Eavey, professor of otology and laryngology at Harvard University, Boston. “Drops don't cause systemic side effects, such as diarrhea—and by using drops, you help keep down bacterial resistance.”

Dr. Eavey, who also is director of pediatric otolaryngology at Massachusetts Eye and Ear Infirmary in Boston, and who served on the AAO's guidelines panel for acute otitis media, agreed with the strong recommendation in favor of assessing and treating pain. “Otitis externa can be very painful. On the assessment, when a child comes in with really bad external otitis externa, they first of all need pain relief.”

He also shared the AAO's recommendation regarding differential diagnosis. “For example, although rare in childhood, malignant external otitis is a serious bone infection which mimics acute external otitis and can occur in insulin-dependent diabetics,” he said.

He added his own specific recommendation: “You need to differentiate between a child with acute otitis and one with acute mastoiditis if there is swelling behind the ear. In that case, you need a clinical view of the eardrum and possibly a CT scan to make sure it's not mastoiditis. But for garden-variety otitis externa, go with the ear drops, and the patient should get better—if they're not much improved in 2–3 days, the patient should be reassessed.

Dr. Eavey also shared a treatment pearl. “My recommendation is also to have Mom or Dad warm up the drops up in their hand or carry them in their pocket, because drops are often colder than the ear canal—and so to a child, it can feel like having ice water poured into their ear.” He echoed a tip advocated in the guidelines that putting a wick in a severely swollen ear can help deliver the drops into the canal.

Dr. Seth Pransky, a pediatric otolaryngologist at Children's Hospital in San Diego, observed that although the guidelines are new, their advice is familiar to many physicians. “Perhaps this might be considered new for primary care physicians, but the vast majority of otolaryngologists understand that this is a disease treated with topical rather than oral antibiotics. There are cases where orals are necessary, and the guidelines point that out—but they're a lot less common than garden variety, run-of-the-mill swimmer's ear, which is very painful.”

Dr. Michael Pichichero, professor of microbiology and immunology at the University of Rochester (N.Y.) Medical Center, also approved of the recommendations. “I think the guidelines are very well written and comprehensive and appear to be evidence based—on as much evidence as we do have,” he said in an interview.

In particular Dr. Pichichero noted that distinguishing between patients who have an intact eardrum and those who don't has a sizeable impact on the antibiotic choice—because if the eardrum is not intact, “we really should move to preference for the chloroquinolone antibiotic preparations, which are not ototoxic.”

The document gave various treatment recommendations for specific AOE etiologies and advised against the use of alternative therapies such as ear candles.

The guidelines, which were published as a supplement to the journal, Otolaryngology-Head and Neck Surgery, will be available free of charge at www.entnet.org

Progesterone and estrogen may provoke allergic antibody reactions in some women, which might in turn help explain various menstrual disorders, according to a prospective study.

Dr. Russell R. Roby and colleagues from the Roby Institute in Austin, Tex., found increased reactions to both hormones in patients with menstruation-related symptoms compared with control women (Am. J. Reprod. Immunol. 2006;55:307–13).

“Our data presented in this paper are the first to show the presence of IgM and IgE against different steroid hormones,” they reported.

The investigators noted that acne, asthma, epilepsy, allergic rhinitis, and other disorders have been linked with menstrual cycle influences.

Their report “suggests the possibility of hormone allergy,” they wrote, citing earlier investigations linking hormone reactions to endocrine disorders and periodic rashes.

The researchers sampled the blood of 270 patients from their clinic who reported a change in their menstrual symptoms over the course of 2 years and tested for IgM and IgG antibodies to progesterone.

They also obtained blood samples from 288 unaffected women to serve as a control group.

When blood was tested via enzyme-linked immunosorbent assay, the test patients had a mean optical density (a measure of antibody levels) of 0.17 for IgG and 0.32 for IgM.

In the control population, the mean optical density was 0.08 for IgG and 0.13 for IgM—a statistically significant difference in both cases.

The investigators also tested another group of 98 patients for IgE antibodies against both progesterone and estrogen, using a control group of 320 patients (the same 288 from a commercial laboratory plus 32 from their clinic with possible hormone allergy).

For progesterone, test patients had a mean optical density of 0.42, compared with a mean optical density of 0.11 in the lab-based control group and 0.23 in the clinic-based control group—a highly significant increase, the investigators noted.

For estrogen, the test group's mean optical density was 0.69, compared with 0.15 for the lab-based controls and 0.24 for the local controls—also a highly significant difference.

Progesterone and estrogen may provoke allergic antibody reactions in some women, which might in turn help explain various menstrual disorders, according to a prospective study.

Dr. Russell R. Roby and colleagues from the Roby Institute in Austin, Tex., found increased reactions to both hormones in patients with menstruation-related symptoms compared with control women (Am. J. Reprod. Immunol. 2006;55:307–13).

“Our data presented in this paper are the first to show the presence of IgM and IgE against different steroid hormones,” they reported.

The investigators noted that acne, asthma, epilepsy, allergic rhinitis, and other disorders have been linked with menstrual cycle influences.

Their report “suggests the possibility of hormone allergy,” they wrote, citing earlier investigations linking hormone reactions to endocrine disorders and periodic rashes.

The researchers sampled the blood of 270 patients from their clinic who reported a change in their menstrual symptoms over the course of 2 years and tested for IgM and IgG antibodies to progesterone.

They also obtained blood samples from 288 unaffected women to serve as a control group.

When blood was tested via enzyme-linked immunosorbent assay, the test patients had a mean optical density (a measure of antibody levels) of 0.17 for IgG and 0.32 for IgM.

In the control population, the mean optical density was 0.08 for IgG and 0.13 for IgM—a statistically significant difference in both cases.

The investigators also tested another group of 98 patients for IgE antibodies against both progesterone and estrogen, using a control group of 320 patients (the same 288 from a commercial laboratory plus 32 from their clinic with possible hormone allergy).

For progesterone, test patients had a mean optical density of 0.42, compared with a mean optical density of 0.11 in the lab-based control group and 0.23 in the clinic-based control group—a highly significant increase, the investigators noted.

For estrogen, the test group's mean optical density was 0.69, compared with 0.15 for the lab-based controls and 0.24 for the local controls—also a highly significant difference.

Progesterone and estrogen may provoke allergic antibody reactions in some women, which might in turn help explain various menstrual disorders, according to a prospective study.

Dr. Russell R. Roby and colleagues from the Roby Institute in Austin, Tex., found increased reactions to both hormones in patients with menstruation-related symptoms compared with control women (Am. J. Reprod. Immunol. 2006;55:307–13).

“Our data presented in this paper are the first to show the presence of IgM and IgE against different steroid hormones,” they reported.

The investigators noted that acne, asthma, epilepsy, allergic rhinitis, and other disorders have been linked with menstrual cycle influences.

Their report “suggests the possibility of hormone allergy,” they wrote, citing earlier investigations linking hormone reactions to endocrine disorders and periodic rashes.

The researchers sampled the blood of 270 patients from their clinic who reported a change in their menstrual symptoms over the course of 2 years and tested for IgM and IgG antibodies to progesterone.

They also obtained blood samples from 288 unaffected women to serve as a control group.

When blood was tested via enzyme-linked immunosorbent assay, the test patients had a mean optical density (a measure of antibody levels) of 0.17 for IgG and 0.32 for IgM.

In the control population, the mean optical density was 0.08 for IgG and 0.13 for IgM—a statistically significant difference in both cases.

The investigators also tested another group of 98 patients for IgE antibodies against both progesterone and estrogen, using a control group of 320 patients (the same 288 from a commercial laboratory plus 32 from their clinic with possible hormone allergy).

For progesterone, test patients had a mean optical density of 0.42, compared with a mean optical density of 0.11 in the lab-based control group and 0.23 in the clinic-based control group—a highly significant increase, the investigators noted.

For estrogen, the test group's mean optical density was 0.69, compared with 0.15 for the lab-based controls and 0.24 for the local controls—also a highly significant difference.