Denise Napoli

The in vitro gliadin challenge is not useful in diagnosing nonceliac gluten sensitivity, reported Dr. Cristina Bucci and her colleagues in the October issue of Clinical Gastroenterology and Hepatology.

"Even if a clinical form of gluten intolerance other than celiac disease [CD] seems to be recognized both by patients and clinicians, there is no clear evidence of a mucosal or serologic modification that can be used as stigmata of the disease in those individuals," the authors wrote.

Dr. Bucci of the University of Salerno (Italy) and her colleagues looked at 119 adult patients who were negative for wheat allergy by a skin prick test.

They were divided into four cohorts.

The first cohort was the nonceliac gluten-sensitive (NCGS) group, who had negative serology and histology for CD but reported irritable bowel symptoms after ingesting gluten (n = 16).

The second group comprised untreated celiac patients at the moment of diagnosis, who had not been on a gluten-free diet (n = 35).

The third group included treated celiac patients on a gluten-free diet (n = 34), and the fourth group was made up of healthy controls who were being worked up for reasons other than suspicion of CD (n = 34).

All participants underwent upper endoscopy for duodenal biopsies, and the investigators also assessed patients’ serum anti–tissue transglutaminase antibodies, antiendomysium antibodies, and total IgA, plus human leukocyte antigen (HLA), where appropriate.

Next, the researchers assembled duodenal biopsy specimens from each patient, and a blinded biologist challenged these specimens to a gliadin digest (1 mg/mL).

They then assessed both early markers of inflammation in these specimens, including PY99 (antiphosphotyrosine monoclonal antibody), HLA-DR (the major histocompatibility complex, class II, DR), as well as later markers, like CD3 (a marker of mature T lymphocytes), CD25 (the inducible interleukin-2 receptor in both lymphoid and myeloid cells), and CD69 (a marker of T-cell activation).

Two biopsy specimens from each patient were left untouched by gliadin, for comparison.

The authors found that the specimens from all CD patients, regardless of current diet, showed increased immunofluorescence intensity when stimulated with gliadin, both for early and late inflammation markers.

On the other hand, reported Dr. Bucci, "only three healthy controls and three NCGS patients showed a weak, inconsistent response to the gliadin challenge for some, but not all, inflammation markers, and the mucosa of the majority of them did not seem to be activated by those stimuli."

Furthermore, one of these NCGS patients and one control were positive for Helicobacter pylori.

In addition, the authors wrote that tissue transglutaminase deposits were present at variable intensity in CD patients, but were not seen in NCGS patients and healthy controls.

According to Dr. Bucci, "A few years ago, only one type of gluten intolerance, CD and its skin form, dermatitis herpetiformis, was recognized by the scientific community."

Now that clinical practice has identified gluten-sensitive individuals who are not celiac positive, however, "wheat components other than proteins, for example, carbohydrates that already had been associated with the appearance of gastrointestinal symptoms in patients with IBS, also should be investigated for their role in the pathogenesis of NCGS."

The authors disclosed no financial conflicts. They wrote that the study was funded by the regional public health department.

The in vitro gliadin challenge is not useful in diagnosing nonceliac gluten sensitivity, reported Dr. Cristina Bucci and her colleagues in the October issue of Clinical Gastroenterology and Hepatology.

"Even if a clinical form of gluten intolerance other than celiac disease [CD] seems to be recognized both by patients and clinicians, there is no clear evidence of a mucosal or serologic modification that can be used as stigmata of the disease in those individuals," the authors wrote.

Dr. Bucci of the University of Salerno (Italy) and her colleagues looked at 119 adult patients who were negative for wheat allergy by a skin prick test.

They were divided into four cohorts.

The first cohort was the nonceliac gluten-sensitive (NCGS) group, who had negative serology and histology for CD but reported irritable bowel symptoms after ingesting gluten (n = 16).

The second group comprised untreated celiac patients at the moment of diagnosis, who had not been on a gluten-free diet (n = 35).

The third group included treated celiac patients on a gluten-free diet (n = 34), and the fourth group was made up of healthy controls who were being worked up for reasons other than suspicion of CD (n = 34).

All participants underwent upper endoscopy for duodenal biopsies, and the investigators also assessed patients’ serum anti–tissue transglutaminase antibodies, antiendomysium antibodies, and total IgA, plus human leukocyte antigen (HLA), where appropriate.

Next, the researchers assembled duodenal biopsy specimens from each patient, and a blinded biologist challenged these specimens to a gliadin digest (1 mg/mL).

They then assessed both early markers of inflammation in these specimens, including PY99 (antiphosphotyrosine monoclonal antibody), HLA-DR (the major histocompatibility complex, class II, DR), as well as later markers, like CD3 (a marker of mature T lymphocytes), CD25 (the inducible interleukin-2 receptor in both lymphoid and myeloid cells), and CD69 (a marker of T-cell activation).

Two biopsy specimens from each patient were left untouched by gliadin, for comparison.

The authors found that the specimens from all CD patients, regardless of current diet, showed increased immunofluorescence intensity when stimulated with gliadin, both for early and late inflammation markers.

On the other hand, reported Dr. Bucci, "only three healthy controls and three NCGS patients showed a weak, inconsistent response to the gliadin challenge for some, but not all, inflammation markers, and the mucosa of the majority of them did not seem to be activated by those stimuli."

Furthermore, one of these NCGS patients and one control were positive for Helicobacter pylori.

In addition, the authors wrote that tissue transglutaminase deposits were present at variable intensity in CD patients, but were not seen in NCGS patients and healthy controls.

According to Dr. Bucci, "A few years ago, only one type of gluten intolerance, CD and its skin form, dermatitis herpetiformis, was recognized by the scientific community."

Now that clinical practice has identified gluten-sensitive individuals who are not celiac positive, however, "wheat components other than proteins, for example, carbohydrates that already had been associated with the appearance of gastrointestinal symptoms in patients with IBS, also should be investigated for their role in the pathogenesis of NCGS."

The authors disclosed no financial conflicts. They wrote that the study was funded by the regional public health department.

The in vitro gliadin challenge is not useful in diagnosing nonceliac gluten sensitivity, reported Dr. Cristina Bucci and her colleagues in the October issue of Clinical Gastroenterology and Hepatology.

"Even if a clinical form of gluten intolerance other than celiac disease [CD] seems to be recognized both by patients and clinicians, there is no clear evidence of a mucosal or serologic modification that can be used as stigmata of the disease in those individuals," the authors wrote.

Dr. Bucci of the University of Salerno (Italy) and her colleagues looked at 119 adult patients who were negative for wheat allergy by a skin prick test.

They were divided into four cohorts.

The first cohort was the nonceliac gluten-sensitive (NCGS) group, who had negative serology and histology for CD but reported irritable bowel symptoms after ingesting gluten (n = 16).

The second group comprised untreated celiac patients at the moment of diagnosis, who had not been on a gluten-free diet (n = 35).

The third group included treated celiac patients on a gluten-free diet (n = 34), and the fourth group was made up of healthy controls who were being worked up for reasons other than suspicion of CD (n = 34).

All participants underwent upper endoscopy for duodenal biopsies, and the investigators also assessed patients’ serum anti–tissue transglutaminase antibodies, antiendomysium antibodies, and total IgA, plus human leukocyte antigen (HLA), where appropriate.

Next, the researchers assembled duodenal biopsy specimens from each patient, and a blinded biologist challenged these specimens to a gliadin digest (1 mg/mL).

They then assessed both early markers of inflammation in these specimens, including PY99 (antiphosphotyrosine monoclonal antibody), HLA-DR (the major histocompatibility complex, class II, DR), as well as later markers, like CD3 (a marker of mature T lymphocytes), CD25 (the inducible interleukin-2 receptor in both lymphoid and myeloid cells), and CD69 (a marker of T-cell activation).

Two biopsy specimens from each patient were left untouched by gliadin, for comparison.

The authors found that the specimens from all CD patients, regardless of current diet, showed increased immunofluorescence intensity when stimulated with gliadin, both for early and late inflammation markers.

On the other hand, reported Dr. Bucci, "only three healthy controls and three NCGS patients showed a weak, inconsistent response to the gliadin challenge for some, but not all, inflammation markers, and the mucosa of the majority of them did not seem to be activated by those stimuli."

Furthermore, one of these NCGS patients and one control were positive for Helicobacter pylori.

In addition, the authors wrote that tissue transglutaminase deposits were present at variable intensity in CD patients, but were not seen in NCGS patients and healthy controls.

According to Dr. Bucci, "A few years ago, only one type of gluten intolerance, CD and its skin form, dermatitis herpetiformis, was recognized by the scientific community."

Now that clinical practice has identified gluten-sensitive individuals who are not celiac positive, however, "wheat components other than proteins, for example, carbohydrates that already had been associated with the appearance of gastrointestinal symptoms in patients with IBS, also should be investigated for their role in the pathogenesis of NCGS."

The authors disclosed no financial conflicts. They wrote that the study was funded by the regional public health department.

Rheumatoid arthritis patients were less likely than their physicians to score themselves as being in clinical remission on a widely used clinical composite index, based on a prospective, cross-sectional study.

Meanwhile, ultrasound assessments also showed variable correlation with both patient and physician assessments of tender and swollen joints in the study of 69 patients with RA who were judged to be in clinical remission by their rheumatologist, according to lead investigator Dr. Iustina Janta of the Hospital General Universitario Gregorio Marañón, Madrid, and her colleagues.

"Accurate assessment of RA activity in a nonactive state is of the utmost importance because therapeutic decisions should target sustained remission or, at a minimum, the lowest possible disease activity to improve RA outcomes," Dr. Janta and her coauthors wrote (Rheumatology 2013 Sept. 17 [doi:10.1093/rheumatology/ket297]).

The mean age of the cohort was 60 years, and most of the patients were women (77%). The patients’ mean disease duration was nearly 12 years, and overall, 70% were in treatment with synthetic disease-modifying antirheumatic drugs. Another 16% took biologics, and the remainder used both classes of drugs.

To assess concordance between patient and physician assessments of disease activity, patients first indicated to the investigators which joints on a mannequin corresponded to their own tender or swollen joints. They also ranked their global health assessment on a visual analogue scale from 0 to 10.

A physician blinded to each patient’s own assessment then recorded an assessment of each patient’s tender joint count and swollen joint count, as well as the physician’s perception of the patient’s global assessment of disease activity.

Dr. Janta and her associates found that the mean scores calculated on the Disease Activity Score 28 (DAS28) were significantly higher according to patients, at 3.34, compared with the physician tally, at 2.55 (P less than .0005).

Indeed, even though the attending rheumatologist had judged all 69 patients to be in clinical remission, DAS28 scores calculated from the patients’ assessments indicated that only 18 patients (26%) fit this bill. But according to the physician assessment, that number was 36 patients (52%) – another significant difference (P less than .0005).

Next, the researchers assessed concordance between doctors and patients on the simplified disease activity index (SDAI). Here, there was better agreement: The mean score assessment among patients was 12.33, compared with a physician mean assessment of 10.55 (P = .246). That translated to a statistically similar SDAI-based remission rate of 15% according to patients vs. 12% according to physicians (P = .172).

Finally, ultrasound examinations with B mode and power Doppler showed no significant correlations with patient- and physician-derived clinical assessments. The mean number of tender joints was 4.34 based on patient assessment, 3.12 by physician examination, and 4.09 based on B-mode ultrasound.

On the other hand, swollen joint counts (SJCs) were significantly lower in both patient (2.00) and physician (1.42) estimation, compared with B-mode ultrasound (4.09) (P less than .0005 for ultrasound vs. patient mean SJC; P = .033 for ultrasound vs. physician SJC).

The ultrasound results on power Doppler were reversed in comparison with B-mode assessment. Tender joint counts were much higher when estimated by patients (4.34) and physicians (3.12), compared with Doppler ultrasound (1.1, P less than .0005 for both).

But mean swollen joint counts on power Doppler ultrasound (1.1) correlated well with patient- and physician-assessed counts (2 and 1.42, respectively).

Dr. Janta and her associates wrote that in the future, given the current trend in patient involvement in disease activity assessments throughout the field, "longitudinal studies should investigate the predictive capability of patient self-assessment of RA activity in relation to relevant disease outcomes, which will address the real value of the discrepancies between patient-assessed and physician-assessed RA activity."

They also noted that "studies on the optimal weight of power Doppler findings in global RA activity assessment are needed."

The authors stated that they had no relevant financial conflicts. They did not report any outside funding for this study.

Rheumatoid arthritis patients were less likely than their physicians to score themselves as being in clinical remission on a widely used clinical composite index, based on a prospective, cross-sectional study.

Meanwhile, ultrasound assessments also showed variable correlation with both patient and physician assessments of tender and swollen joints in the study of 69 patients with RA who were judged to be in clinical remission by their rheumatologist, according to lead investigator Dr. Iustina Janta of the Hospital General Universitario Gregorio Marañón, Madrid, and her colleagues.

"Accurate assessment of RA activity in a nonactive state is of the utmost importance because therapeutic decisions should target sustained remission or, at a minimum, the lowest possible disease activity to improve RA outcomes," Dr. Janta and her coauthors wrote (Rheumatology 2013 Sept. 17 [doi:10.1093/rheumatology/ket297]).

The mean age of the cohort was 60 years, and most of the patients were women (77%). The patients’ mean disease duration was nearly 12 years, and overall, 70% were in treatment with synthetic disease-modifying antirheumatic drugs. Another 16% took biologics, and the remainder used both classes of drugs.

To assess concordance between patient and physician assessments of disease activity, patients first indicated to the investigators which joints on a mannequin corresponded to their own tender or swollen joints. They also ranked their global health assessment on a visual analogue scale from 0 to 10.

A physician blinded to each patient’s own assessment then recorded an assessment of each patient’s tender joint count and swollen joint count, as well as the physician’s perception of the patient’s global assessment of disease activity.

Dr. Janta and her associates found that the mean scores calculated on the Disease Activity Score 28 (DAS28) were significantly higher according to patients, at 3.34, compared with the physician tally, at 2.55 (P less than .0005).

Indeed, even though the attending rheumatologist had judged all 69 patients to be in clinical remission, DAS28 scores calculated from the patients’ assessments indicated that only 18 patients (26%) fit this bill. But according to the physician assessment, that number was 36 patients (52%) – another significant difference (P less than .0005).

Next, the researchers assessed concordance between doctors and patients on the simplified disease activity index (SDAI). Here, there was better agreement: The mean score assessment among patients was 12.33, compared with a physician mean assessment of 10.55 (P = .246). That translated to a statistically similar SDAI-based remission rate of 15% according to patients vs. 12% according to physicians (P = .172).

Finally, ultrasound examinations with B mode and power Doppler showed no significant correlations with patient- and physician-derived clinical assessments. The mean number of tender joints was 4.34 based on patient assessment, 3.12 by physician examination, and 4.09 based on B-mode ultrasound.

On the other hand, swollen joint counts (SJCs) were significantly lower in both patient (2.00) and physician (1.42) estimation, compared with B-mode ultrasound (4.09) (P less than .0005 for ultrasound vs. patient mean SJC; P = .033 for ultrasound vs. physician SJC).

The ultrasound results on power Doppler were reversed in comparison with B-mode assessment. Tender joint counts were much higher when estimated by patients (4.34) and physicians (3.12), compared with Doppler ultrasound (1.1, P less than .0005 for both).

But mean swollen joint counts on power Doppler ultrasound (1.1) correlated well with patient- and physician-assessed counts (2 and 1.42, respectively).

Dr. Janta and her associates wrote that in the future, given the current trend in patient involvement in disease activity assessments throughout the field, "longitudinal studies should investigate the predictive capability of patient self-assessment of RA activity in relation to relevant disease outcomes, which will address the real value of the discrepancies between patient-assessed and physician-assessed RA activity."

They also noted that "studies on the optimal weight of power Doppler findings in global RA activity assessment are needed."

The authors stated that they had no relevant financial conflicts. They did not report any outside funding for this study.

Rheumatoid arthritis patients were less likely than their physicians to score themselves as being in clinical remission on a widely used clinical composite index, based on a prospective, cross-sectional study.

Meanwhile, ultrasound assessments also showed variable correlation with both patient and physician assessments of tender and swollen joints in the study of 69 patients with RA who were judged to be in clinical remission by their rheumatologist, according to lead investigator Dr. Iustina Janta of the Hospital General Universitario Gregorio Marañón, Madrid, and her colleagues.

"Accurate assessment of RA activity in a nonactive state is of the utmost importance because therapeutic decisions should target sustained remission or, at a minimum, the lowest possible disease activity to improve RA outcomes," Dr. Janta and her coauthors wrote (Rheumatology 2013 Sept. 17 [doi:10.1093/rheumatology/ket297]).

The mean age of the cohort was 60 years, and most of the patients were women (77%). The patients’ mean disease duration was nearly 12 years, and overall, 70% were in treatment with synthetic disease-modifying antirheumatic drugs. Another 16% took biologics, and the remainder used both classes of drugs.

To assess concordance between patient and physician assessments of disease activity, patients first indicated to the investigators which joints on a mannequin corresponded to their own tender or swollen joints. They also ranked their global health assessment on a visual analogue scale from 0 to 10.

A physician blinded to each patient’s own assessment then recorded an assessment of each patient’s tender joint count and swollen joint count, as well as the physician’s perception of the patient’s global assessment of disease activity.

Dr. Janta and her associates found that the mean scores calculated on the Disease Activity Score 28 (DAS28) were significantly higher according to patients, at 3.34, compared with the physician tally, at 2.55 (P less than .0005).

Indeed, even though the attending rheumatologist had judged all 69 patients to be in clinical remission, DAS28 scores calculated from the patients’ assessments indicated that only 18 patients (26%) fit this bill. But according to the physician assessment, that number was 36 patients (52%) – another significant difference (P less than .0005).

Next, the researchers assessed concordance between doctors and patients on the simplified disease activity index (SDAI). Here, there was better agreement: The mean score assessment among patients was 12.33, compared with a physician mean assessment of 10.55 (P = .246). That translated to a statistically similar SDAI-based remission rate of 15% according to patients vs. 12% according to physicians (P = .172).

Finally, ultrasound examinations with B mode and power Doppler showed no significant correlations with patient- and physician-derived clinical assessments. The mean number of tender joints was 4.34 based on patient assessment, 3.12 by physician examination, and 4.09 based on B-mode ultrasound.

On the other hand, swollen joint counts (SJCs) were significantly lower in both patient (2.00) and physician (1.42) estimation, compared with B-mode ultrasound (4.09) (P less than .0005 for ultrasound vs. patient mean SJC; P = .033 for ultrasound vs. physician SJC).

The ultrasound results on power Doppler were reversed in comparison with B-mode assessment. Tender joint counts were much higher when estimated by patients (4.34) and physicians (3.12), compared with Doppler ultrasound (1.1, P less than .0005 for both).

But mean swollen joint counts on power Doppler ultrasound (1.1) correlated well with patient- and physician-assessed counts (2 and 1.42, respectively).

Dr. Janta and her associates wrote that in the future, given the current trend in patient involvement in disease activity assessments throughout the field, "longitudinal studies should investigate the predictive capability of patient self-assessment of RA activity in relation to relevant disease outcomes, which will address the real value of the discrepancies between patient-assessed and physician-assessed RA activity."

They also noted that "studies on the optimal weight of power Doppler findings in global RA activity assessment are needed."

The authors stated that they had no relevant financial conflicts. They did not report any outside funding for this study.

Children who suffer bullying are more than twice as likely to have psychosomatic complaints as are their peers who are not bullied, according to a study published online Sept. 16 in the journal Pediatrics.

"Consider bullying as a possible risk factor in any patient with recurrent headaches, breathing problems, poor appetite, sleeping problems, and so on," advised coauthors Gianluca Gini, Ph.D., and Tiziana Pozzoli, Ph.D.

Indeed, "Any recurrent and unexplained somatic symptom can be a warning sign of bullying victimization," they added.

In the new meta-analysis, a follow-up to their 2009 effort (which included 11 studies), Dr. Gini and Dr. Pozzoli, of the University of Padua, Italy, looked at 30 studies of bullying and psychosomatic problems from around the world (Pediatrics 2013 [doi:10.1542/peds.2013-0614]).

©Mikael Damkier/Thinkstockphotos.com

A total of 219,560 children and adolescents were included, with about 50% female.

All studies had to include both reports of bullying and of psychosomatic complaints, as well as a control group of children or adolescents who were not bullied.

In total, the authors included six longitudinal studies and 24 cross-sectional designs in their meta-analysis.

Looking first at the longitudinal data only, Dr. Gini and Dr. Pozzoli found that bullied children had a significantly greater likelihood of experiencing psychosomatic problems, with an odds ratio of 2.39 (95% confidence interval, 1.76-3.24; P less than .0001).

The authors then calculated the risk for subjects enrolled in the remaining 24 cross-sectional studies.

Similarly, in this subset, bullied students were more than twice as likely to have psychosomatic complaints (OR, 2.17; 95% CI, 1.91-2.46; P less than .0001).

Next, the authors looked to see whether any factors such as the type of informant (the bullied child himself, vs. the parents, vs. another child), the geographic location, or the gender ratio of a particular cohort moderated the results.

Among these, only an increase in the number of female participants was found to have a significant moderating effect on the result, weakening the relationship somewhat; neither of the other two factors tested had any significant effect on the results.

When asked about the study, Dr. David Fassler said the findings contribute to the growing body of research on the adverse and lasting effects of bullying on both physical and emotional health.

"Despite increased awareness and sensitivity, bullying remains a common experience for many children and adolescents," Dr. Fassler, clinical professor of psychiatry at the University of Vermont in Burlington, said in an interview. "Surveys indicate that as many as half of all children are bullied at some time during their school years, and at least 10% are bullied on a regular basis."

For their part, the researchers conceded several important limitations in their study.

For one, they wrote, "Much variability exists in the methods and instruments used to assess the prevalence of symptoms and peer victimization experiences."

Future studies ought to use validated instruments to assess both experiences of bullying and psychosomatic complaints.

They also pointed out that none of the studies assessed different forms of victimization separately – for example, physical victimization vs. relational victimization – and the authors were therefore unable to analyze how these different forms might affect children in different ways.

Nevertheless, "Since the former meta-analysis, the number of studies testing the association between bullying experiences and psychosomatic problems has tripled," wrote the authors.

"We can reasonably conclude that this association is established, and we call for new research efforts aimed at elucidating the mechanisms through which bullying affects children’s health."

The authors stated that they had no financial relationships to disclose and that they received no outside funding.

Children who suffer bullying are more than twice as likely to have psychosomatic complaints as are their peers who are not bullied, according to a study published online Sept. 16 in the journal Pediatrics.

"Consider bullying as a possible risk factor in any patient with recurrent headaches, breathing problems, poor appetite, sleeping problems, and so on," advised coauthors Gianluca Gini, Ph.D., and Tiziana Pozzoli, Ph.D.

Indeed, "Any recurrent and unexplained somatic symptom can be a warning sign of bullying victimization," they added.

In the new meta-analysis, a follow-up to their 2009 effort (which included 11 studies), Dr. Gini and Dr. Pozzoli, of the University of Padua, Italy, looked at 30 studies of bullying and psychosomatic problems from around the world (Pediatrics 2013 [doi:10.1542/peds.2013-0614]).

©Mikael Damkier/Thinkstockphotos.com

A total of 219,560 children and adolescents were included, with about 50% female.

All studies had to include both reports of bullying and of psychosomatic complaints, as well as a control group of children or adolescents who were not bullied.

In total, the authors included six longitudinal studies and 24 cross-sectional designs in their meta-analysis.

Looking first at the longitudinal data only, Dr. Gini and Dr. Pozzoli found that bullied children had a significantly greater likelihood of experiencing psychosomatic problems, with an odds ratio of 2.39 (95% confidence interval, 1.76-3.24; P less than .0001).

The authors then calculated the risk for subjects enrolled in the remaining 24 cross-sectional studies.

Similarly, in this subset, bullied students were more than twice as likely to have psychosomatic complaints (OR, 2.17; 95% CI, 1.91-2.46; P less than .0001).

Next, the authors looked to see whether any factors such as the type of informant (the bullied child himself, vs. the parents, vs. another child), the geographic location, or the gender ratio of a particular cohort moderated the results.

Among these, only an increase in the number of female participants was found to have a significant moderating effect on the result, weakening the relationship somewhat; neither of the other two factors tested had any significant effect on the results.

When asked about the study, Dr. David Fassler said the findings contribute to the growing body of research on the adverse and lasting effects of bullying on both physical and emotional health.

"Despite increased awareness and sensitivity, bullying remains a common experience for many children and adolescents," Dr. Fassler, clinical professor of psychiatry at the University of Vermont in Burlington, said in an interview. "Surveys indicate that as many as half of all children are bullied at some time during their school years, and at least 10% are bullied on a regular basis."

For their part, the researchers conceded several important limitations in their study.

For one, they wrote, "Much variability exists in the methods and instruments used to assess the prevalence of symptoms and peer victimization experiences."

Future studies ought to use validated instruments to assess both experiences of bullying and psychosomatic complaints.

They also pointed out that none of the studies assessed different forms of victimization separately – for example, physical victimization vs. relational victimization – and the authors were therefore unable to analyze how these different forms might affect children in different ways.

Nevertheless, "Since the former meta-analysis, the number of studies testing the association between bullying experiences and psychosomatic problems has tripled," wrote the authors.

"We can reasonably conclude that this association is established, and we call for new research efforts aimed at elucidating the mechanisms through which bullying affects children’s health."

The authors stated that they had no financial relationships to disclose and that they received no outside funding.

Children who suffer bullying are more than twice as likely to have psychosomatic complaints as are their peers who are not bullied, according to a study published online Sept. 16 in the journal Pediatrics.

"Consider bullying as a possible risk factor in any patient with recurrent headaches, breathing problems, poor appetite, sleeping problems, and so on," advised coauthors Gianluca Gini, Ph.D., and Tiziana Pozzoli, Ph.D.

Indeed, "Any recurrent and unexplained somatic symptom can be a warning sign of bullying victimization," they added.

In the new meta-analysis, a follow-up to their 2009 effort (which included 11 studies), Dr. Gini and Dr. Pozzoli, of the University of Padua, Italy, looked at 30 studies of bullying and psychosomatic problems from around the world (Pediatrics 2013 [doi:10.1542/peds.2013-0614]).

©Mikael Damkier/Thinkstockphotos.com

A total of 219,560 children and adolescents were included, with about 50% female.

All studies had to include both reports of bullying and of psychosomatic complaints, as well as a control group of children or adolescents who were not bullied.

In total, the authors included six longitudinal studies and 24 cross-sectional designs in their meta-analysis.

Looking first at the longitudinal data only, Dr. Gini and Dr. Pozzoli found that bullied children had a significantly greater likelihood of experiencing psychosomatic problems, with an odds ratio of 2.39 (95% confidence interval, 1.76-3.24; P less than .0001).

The authors then calculated the risk for subjects enrolled in the remaining 24 cross-sectional studies.

Similarly, in this subset, bullied students were more than twice as likely to have psychosomatic complaints (OR, 2.17; 95% CI, 1.91-2.46; P less than .0001).

Next, the authors looked to see whether any factors such as the type of informant (the bullied child himself, vs. the parents, vs. another child), the geographic location, or the gender ratio of a particular cohort moderated the results.

Among these, only an increase in the number of female participants was found to have a significant moderating effect on the result, weakening the relationship somewhat; neither of the other two factors tested had any significant effect on the results.

When asked about the study, Dr. David Fassler said the findings contribute to the growing body of research on the adverse and lasting effects of bullying on both physical and emotional health.

"Despite increased awareness and sensitivity, bullying remains a common experience for many children and adolescents," Dr. Fassler, clinical professor of psychiatry at the University of Vermont in Burlington, said in an interview. "Surveys indicate that as many as half of all children are bullied at some time during their school years, and at least 10% are bullied on a regular basis."

For their part, the researchers conceded several important limitations in their study.

For one, they wrote, "Much variability exists in the methods and instruments used to assess the prevalence of symptoms and peer victimization experiences."

Future studies ought to use validated instruments to assess both experiences of bullying and psychosomatic complaints.

They also pointed out that none of the studies assessed different forms of victimization separately – for example, physical victimization vs. relational victimization – and the authors were therefore unable to analyze how these different forms might affect children in different ways.

Nevertheless, "Since the former meta-analysis, the number of studies testing the association between bullying experiences and psychosomatic problems has tripled," wrote the authors.

"We can reasonably conclude that this association is established, and we call for new research efforts aimed at elucidating the mechanisms through which bullying affects children’s health."

The authors stated that they had no financial relationships to disclose and that they received no outside funding.

Treatment with the nonpathogenic probiotic yeast Saccharomyces boulardii does not prevent relapse in Crohn’s disease.

The finding – which nevertheless does "not allow the exclusion of the potential therapeutic efficacy of probiotics" – comes from the third study to assess S. boulardii in Crohn’s, wrote Dr. Arnaud Bourreille and colleagues. The results are in the August issue of Clinical Gastroenterology and Hepatology.

In a yearlong, randomized, double-blind, placebo-controlled study, Dr. Bourreille, of the CHU de Nantes, France, and colleagues looked at 159 adult patients enrolled at 32 centers during the acute phase of Crohn’s disease.

Patients were treated for 4 weeks with corticosteroids, budesonide, and/or aminosalicylates, according to the preference of each investigator, until remission. They were then randomized to receive either oral S. boulardii at 1 g daily or a placebo until the end of the study at week 52 or earlier, in the case of relapse, with follow-up conducted every 12 weeks.

Relapse was defined as registering a Crohn’s disease activity index (CDAI) higher than 220 points on follow-up; registering a CDAI between 150 and 220 with an increase of at least 70 points over the baseline value; or requiring a surgical procedure or medical treatment specifically for CD.

The authors found that by 1 year, 80 patients had experienced relapse of Crohn’s: 38 in the S. boulardii group (47.5%) and 42 in the placebo group (52.5%), a nonsignificant difference (P less than .05).

The authors also found that the median time to relapse was not statistically different between groups, at 40.7 weeks for the treatment group (range, 2.6-56.0) and 39.0 weeks for patients taking placebo (range, 0.1-55.0) weeks (P = .78).

Indeed, the only finding that did reach statistical significance was among treatment group and smoking status, where nonsmokers given placebo had more relapses (72.0%) than did those treated with S. boulardii (34.5%; P = .016 for the difference between cohorts).

"However, in smokers and former smokers, the proportion of relapse was not significantly different," added the authors.

Looking at safety, Dr. Bourreille reported that just over half of patients in each group complained of adverse events, including diarrhea, arthralgia, constipation, and abdominal pain.

"One oral fungal infection occurred in one patient treated with S. boulardii," he added. "None of the drug-related AEs was serious."

Compliance was greater than 90% in both the treatment and placebo groups.

Dr. Bourreille conceded that the study was limited by the use of clinical relapse as an endpoint, versus relapse defined by endoscopic findings.

"Clinical recurrence was chosen as the primary endpoint because endoscopic evaluation was not deemed necessary for the surveillance of nonsevere CD," wrote the investigators. "Moreover, at the time the study was designed, the concept of mucosal healing was not considered to be as relevant as it now is."

They added, however, that biological parameters of inflammation "were measured at each visit to ensure that clinical recurrence was associated with objective inflammation."

Dr. Bourreille and several coauthors disclosed ties with multiple pharmaceutical companies, including Biocodex, the maker of S. boulardii. Two coauthors were Biocodex employees.

Treatment with the nonpathogenic probiotic yeast Saccharomyces boulardii does not prevent relapse in Crohn’s disease.

The finding – which nevertheless does "not allow the exclusion of the potential therapeutic efficacy of probiotics" – comes from the third study to assess S. boulardii in Crohn’s, wrote Dr. Arnaud Bourreille and colleagues. The results are in the August issue of Clinical Gastroenterology and Hepatology.

In a yearlong, randomized, double-blind, placebo-controlled study, Dr. Bourreille, of the CHU de Nantes, France, and colleagues looked at 159 adult patients enrolled at 32 centers during the acute phase of Crohn’s disease.

Patients were treated for 4 weeks with corticosteroids, budesonide, and/or aminosalicylates, according to the preference of each investigator, until remission. They were then randomized to receive either oral S. boulardii at 1 g daily or a placebo until the end of the study at week 52 or earlier, in the case of relapse, with follow-up conducted every 12 weeks.

Relapse was defined as registering a Crohn’s disease activity index (CDAI) higher than 220 points on follow-up; registering a CDAI between 150 and 220 with an increase of at least 70 points over the baseline value; or requiring a surgical procedure or medical treatment specifically for CD.

The authors found that by 1 year, 80 patients had experienced relapse of Crohn’s: 38 in the S. boulardii group (47.5%) and 42 in the placebo group (52.5%), a nonsignificant difference (P less than .05).

The authors also found that the median time to relapse was not statistically different between groups, at 40.7 weeks for the treatment group (range, 2.6-56.0) and 39.0 weeks for patients taking placebo (range, 0.1-55.0) weeks (P = .78).

Indeed, the only finding that did reach statistical significance was among treatment group and smoking status, where nonsmokers given placebo had more relapses (72.0%) than did those treated with S. boulardii (34.5%; P = .016 for the difference between cohorts).

"However, in smokers and former smokers, the proportion of relapse was not significantly different," added the authors.

Looking at safety, Dr. Bourreille reported that just over half of patients in each group complained of adverse events, including diarrhea, arthralgia, constipation, and abdominal pain.

"One oral fungal infection occurred in one patient treated with S. boulardii," he added. "None of the drug-related AEs was serious."

Compliance was greater than 90% in both the treatment and placebo groups.

Dr. Bourreille conceded that the study was limited by the use of clinical relapse as an endpoint, versus relapse defined by endoscopic findings.

"Clinical recurrence was chosen as the primary endpoint because endoscopic evaluation was not deemed necessary for the surveillance of nonsevere CD," wrote the investigators. "Moreover, at the time the study was designed, the concept of mucosal healing was not considered to be as relevant as it now is."

They added, however, that biological parameters of inflammation "were measured at each visit to ensure that clinical recurrence was associated with objective inflammation."

Dr. Bourreille and several coauthors disclosed ties with multiple pharmaceutical companies, including Biocodex, the maker of S. boulardii. Two coauthors were Biocodex employees.

Treatment with the nonpathogenic probiotic yeast Saccharomyces boulardii does not prevent relapse in Crohn’s disease.

The finding – which nevertheless does "not allow the exclusion of the potential therapeutic efficacy of probiotics" – comes from the third study to assess S. boulardii in Crohn’s, wrote Dr. Arnaud Bourreille and colleagues. The results are in the August issue of Clinical Gastroenterology and Hepatology.

In a yearlong, randomized, double-blind, placebo-controlled study, Dr. Bourreille, of the CHU de Nantes, France, and colleagues looked at 159 adult patients enrolled at 32 centers during the acute phase of Crohn’s disease.

Patients were treated for 4 weeks with corticosteroids, budesonide, and/or aminosalicylates, according to the preference of each investigator, until remission. They were then randomized to receive either oral S. boulardii at 1 g daily or a placebo until the end of the study at week 52 or earlier, in the case of relapse, with follow-up conducted every 12 weeks.

Relapse was defined as registering a Crohn’s disease activity index (CDAI) higher than 220 points on follow-up; registering a CDAI between 150 and 220 with an increase of at least 70 points over the baseline value; or requiring a surgical procedure or medical treatment specifically for CD.

The authors found that by 1 year, 80 patients had experienced relapse of Crohn’s: 38 in the S. boulardii group (47.5%) and 42 in the placebo group (52.5%), a nonsignificant difference (P less than .05).

The authors also found that the median time to relapse was not statistically different between groups, at 40.7 weeks for the treatment group (range, 2.6-56.0) and 39.0 weeks for patients taking placebo (range, 0.1-55.0) weeks (P = .78).

Indeed, the only finding that did reach statistical significance was among treatment group and smoking status, where nonsmokers given placebo had more relapses (72.0%) than did those treated with S. boulardii (34.5%; P = .016 for the difference between cohorts).

"However, in smokers and former smokers, the proportion of relapse was not significantly different," added the authors.

Looking at safety, Dr. Bourreille reported that just over half of patients in each group complained of adverse events, including diarrhea, arthralgia, constipation, and abdominal pain.

"One oral fungal infection occurred in one patient treated with S. boulardii," he added. "None of the drug-related AEs was serious."

Compliance was greater than 90% in both the treatment and placebo groups.

Dr. Bourreille conceded that the study was limited by the use of clinical relapse as an endpoint, versus relapse defined by endoscopic findings.

"Clinical recurrence was chosen as the primary endpoint because endoscopic evaluation was not deemed necessary for the surveillance of nonsevere CD," wrote the investigators. "Moreover, at the time the study was designed, the concept of mucosal healing was not considered to be as relevant as it now is."

They added, however, that biological parameters of inflammation "were measured at each visit to ensure that clinical recurrence was associated with objective inflammation."

Dr. Bourreille and several coauthors disclosed ties with multiple pharmaceutical companies, including Biocodex, the maker of S. boulardii. Two coauthors were Biocodex employees.

Deaths from liver-related causes remained static between 1979 and 2008, according to updated estimates from the Rochester Epidemiology Project and the National Death Index.

The finding represents a dramatic correction to previous estimates from the National Center for Health Statistics (NCHS) at the Centers for Disease Control and Prevention, which used a very narrow definition of liver-related mortality, Dr. Sumeet K. Asrani and colleagues reported. The results were published in the August issue of Gastroenterology.

Courtesy: American Gastroenterological Association

According to Dr. Asrani of the Mayo Clinic, Rochester, Minn., "current estimates [from the NCHS] are solely based on one diagnostic category, namely chronic liver disease and cirrhosis, which fails to capture deaths attributed to other uniquely liver-related descriptors, such as hepatic encephalopathy or hepatorenal syndrome."

Deaths due to viral hepatitis or liver cancer are also not included.

"For example, the current estimates of liver-related deaths might not include the demise of a person with hepatitis C cirrhosis who died of hepatorenal syndrome."

In their updated assessment, the researchers looked at data from the Rochester Epidemiology Project, in which death records of Olmsted County residents are tracked from multiple sources, including county and state vital records, as well as individual medical charts.

The researchers found that when the CDC definition was used, which includes causes attributable to a single ICD-9 code of 571 and ICD-10 codes of K70, K73, and K74, there were 71 liver-related deaths among Olmsted County residents between 1999 and 2008.

In contrast, when the updated definition was applied, which included additional diagnoses specific to liver disease yet excluded in the CDC definition, as well as viral hepatitis and malignant neoplasm of the liver and intrahepatic bile ducts, there were 261 liver-related deaths in the county between 1999 and 2008.

That included 85 deaths (32.6%) from viral hepatitis and 70 deaths (26.8%) from hepatobiliary malignancies.

The researchers then looked at national mortality rates.

According to the restrictive CDC estimates, in 2008, there were 29,951 deaths due to liver disease in the United States, for a death rate of 11.7 per 100,000 persons (16.2 for men and 7.6 for women).

Using the updated definition, however, Dr. Asrani tallied 66,007 deaths, including 10,256 from the expanded liver disease diagnosis, 7,625 from viral hepatitis, and 18,175 from hepatobiliary malignancies, for a death rate of 25.7 per 100,000 persons (35.7 for men and 16.8 for women).

Finally, the investigators compared longitudinal trends in death rates.

They found that when the CDC definition was used, deaths due to liver disease (per 100,000 persons) decreased from 16.5 in the era encompassing the years 1979 to 1988 to 11.7 in the years between 1999 and 2008, a reduction of 38%.

"However, when the updated definition was applied, the downward trend disappeared," they wrote.

Indeed, liver-related mortality per 100,000 persons was basically unchanged over 30 years: 23.9 for the era between 1979 and1988 and 24.4 for the period from 1999 to 2008.

"This discrepancy was accounted for by deaths due to viral hepatitis, which increased from 0.5 to 2.5 per 100,000 and hepatobiliary cancer, which increased from 3.1 to 6.4 per 100,000," wrote the authors.

"These data support that deaths due to viral hepatitis and hepatobiliary cancers should be included in the enumeration of liver-related deaths to accurately represent the burden of chronic liver disease."

"Underappreciation of the prevalence and natural history of liver disease can lead to suboptimal care," they concluded.

The authors disclosed no conflicts of interest related to this study, which was partially supported by grants from the National Institutes of Health.

Deaths from liver-related causes remained static between 1979 and 2008, according to updated estimates from the Rochester Epidemiology Project and the National Death Index.

The finding represents a dramatic correction to previous estimates from the National Center for Health Statistics (NCHS) at the Centers for Disease Control and Prevention, which used a very narrow definition of liver-related mortality, Dr. Sumeet K. Asrani and colleagues reported. The results were published in the August issue of Gastroenterology.

Courtesy: American Gastroenterological Association

According to Dr. Asrani of the Mayo Clinic, Rochester, Minn., "current estimates [from the NCHS] are solely based on one diagnostic category, namely chronic liver disease and cirrhosis, which fails to capture deaths attributed to other uniquely liver-related descriptors, such as hepatic encephalopathy or hepatorenal syndrome."

Deaths due to viral hepatitis or liver cancer are also not included.

"For example, the current estimates of liver-related deaths might not include the demise of a person with hepatitis C cirrhosis who died of hepatorenal syndrome."

In their updated assessment, the researchers looked at data from the Rochester Epidemiology Project, in which death records of Olmsted County residents are tracked from multiple sources, including county and state vital records, as well as individual medical charts.

The researchers found that when the CDC definition was used, which includes causes attributable to a single ICD-9 code of 571 and ICD-10 codes of K70, K73, and K74, there were 71 liver-related deaths among Olmsted County residents between 1999 and 2008.

In contrast, when the updated definition was applied, which included additional diagnoses specific to liver disease yet excluded in the CDC definition, as well as viral hepatitis and malignant neoplasm of the liver and intrahepatic bile ducts, there were 261 liver-related deaths in the county between 1999 and 2008.

That included 85 deaths (32.6%) from viral hepatitis and 70 deaths (26.8%) from hepatobiliary malignancies.

The researchers then looked at national mortality rates.

According to the restrictive CDC estimates, in 2008, there were 29,951 deaths due to liver disease in the United States, for a death rate of 11.7 per 100,000 persons (16.2 for men and 7.6 for women).

Using the updated definition, however, Dr. Asrani tallied 66,007 deaths, including 10,256 from the expanded liver disease diagnosis, 7,625 from viral hepatitis, and 18,175 from hepatobiliary malignancies, for a death rate of 25.7 per 100,000 persons (35.7 for men and 16.8 for women).

Finally, the investigators compared longitudinal trends in death rates.

They found that when the CDC definition was used, deaths due to liver disease (per 100,000 persons) decreased from 16.5 in the era encompassing the years 1979 to 1988 to 11.7 in the years between 1999 and 2008, a reduction of 38%.

"However, when the updated definition was applied, the downward trend disappeared," they wrote.

Indeed, liver-related mortality per 100,000 persons was basically unchanged over 30 years: 23.9 for the era between 1979 and1988 and 24.4 for the period from 1999 to 2008.

"This discrepancy was accounted for by deaths due to viral hepatitis, which increased from 0.5 to 2.5 per 100,000 and hepatobiliary cancer, which increased from 3.1 to 6.4 per 100,000," wrote the authors.

"These data support that deaths due to viral hepatitis and hepatobiliary cancers should be included in the enumeration of liver-related deaths to accurately represent the burden of chronic liver disease."

"Underappreciation of the prevalence and natural history of liver disease can lead to suboptimal care," they concluded.

The authors disclosed no conflicts of interest related to this study, which was partially supported by grants from the National Institutes of Health.

Deaths from liver-related causes remained static between 1979 and 2008, according to updated estimates from the Rochester Epidemiology Project and the National Death Index.

The finding represents a dramatic correction to previous estimates from the National Center for Health Statistics (NCHS) at the Centers for Disease Control and Prevention, which used a very narrow definition of liver-related mortality, Dr. Sumeet K. Asrani and colleagues reported. The results were published in the August issue of Gastroenterology.

Courtesy: American Gastroenterological Association

According to Dr. Asrani of the Mayo Clinic, Rochester, Minn., "current estimates [from the NCHS] are solely based on one diagnostic category, namely chronic liver disease and cirrhosis, which fails to capture deaths attributed to other uniquely liver-related descriptors, such as hepatic encephalopathy or hepatorenal syndrome."

Deaths due to viral hepatitis or liver cancer are also not included.

"For example, the current estimates of liver-related deaths might not include the demise of a person with hepatitis C cirrhosis who died of hepatorenal syndrome."

In their updated assessment, the researchers looked at data from the Rochester Epidemiology Project, in which death records of Olmsted County residents are tracked from multiple sources, including county and state vital records, as well as individual medical charts.

The researchers found that when the CDC definition was used, which includes causes attributable to a single ICD-9 code of 571 and ICD-10 codes of K70, K73, and K74, there were 71 liver-related deaths among Olmsted County residents between 1999 and 2008.

In contrast, when the updated definition was applied, which included additional diagnoses specific to liver disease yet excluded in the CDC definition, as well as viral hepatitis and malignant neoplasm of the liver and intrahepatic bile ducts, there were 261 liver-related deaths in the county between 1999 and 2008.

That included 85 deaths (32.6%) from viral hepatitis and 70 deaths (26.8%) from hepatobiliary malignancies.

The researchers then looked at national mortality rates.

According to the restrictive CDC estimates, in 2008, there were 29,951 deaths due to liver disease in the United States, for a death rate of 11.7 per 100,000 persons (16.2 for men and 7.6 for women).

Using the updated definition, however, Dr. Asrani tallied 66,007 deaths, including 10,256 from the expanded liver disease diagnosis, 7,625 from viral hepatitis, and 18,175 from hepatobiliary malignancies, for a death rate of 25.7 per 100,000 persons (35.7 for men and 16.8 for women).

Finally, the investigators compared longitudinal trends in death rates.

They found that when the CDC definition was used, deaths due to liver disease (per 100,000 persons) decreased from 16.5 in the era encompassing the years 1979 to 1988 to 11.7 in the years between 1999 and 2008, a reduction of 38%.

"However, when the updated definition was applied, the downward trend disappeared," they wrote.

Indeed, liver-related mortality per 100,000 persons was basically unchanged over 30 years: 23.9 for the era between 1979 and1988 and 24.4 for the period from 1999 to 2008.

"This discrepancy was accounted for by deaths due to viral hepatitis, which increased from 0.5 to 2.5 per 100,000 and hepatobiliary cancer, which increased from 3.1 to 6.4 per 100,000," wrote the authors.

"These data support that deaths due to viral hepatitis and hepatobiliary cancers should be included in the enumeration of liver-related deaths to accurately represent the burden of chronic liver disease."

"Underappreciation of the prevalence and natural history of liver disease can lead to suboptimal care," they concluded.

The authors disclosed no conflicts of interest related to this study, which was partially supported by grants from the National Institutes of Health.

Peroral endoscopic myotomy is a safe and effective therapy for achalasia, with 82% of patients in symptom remission at 12 months post treatment.

"With [peroral endoscopic myotomy] it seems possible to emulate the surgical principles of laparoscopic Heller myotomy without the need for skin incisions and to reduce the procedural trauma," reported Dr. Daniel Von Renteln and colleagues. The findings are in the August issue of Gastroenterology.

According to Dr. Von Renteln of the University Hospital Hamburg-Eppendorf in Hamburg, Germany, peroral endoscopic myotomy (POEM) is a novel alternative achalasia treatment.

As described previously (Endoscopy 2010;42:265-71), under general anesthesia and following endoscopy to visualize the gastroesophageal junction, a mucosal incision is made to create entry to the submucosal space. A submucosal tunnel is then created, extending downward, allowing myotomy of the esophageal sphincter. The mucosal entry site is then closed with hemostatic clips.

In the present study, the researchers looked at 70 patients who underwent the procedure at five centers in Europe and North America.

The mean procedure time for POEM was 105 minutes and the mean length of myotomy was 13 cm. Patients experienced a small but significant drop in hemoglobin post procedure (from 13 to 12 g/dL, P less than .001) as well as small but significant increases in leukocyte count and C-reactive protein levels.

At 3 months post procedure, treatment success was achieved in 97% of cases, with mean Eckhardt scores decreasing from 7 pre procedure to 1 post procedure (P less than .001).

Of the 61 patients who underwent manometry at 3 months, the researchers found that the mean pretreatment and posttreatment lower esophageal sphincter pressures were 28 mm Hg versus 9 mm Hg, respectively (P less than .001).

Results at 6 months and 12 months were comparable, with treatment success of 88.5% and 82.4%, respectively, and mean Eckhardt scores of 1.3 and 1.7, respectively (P less than .001 for both).

Patients who failed treatment subsequently underwent laparoscopic Heller myotomy (n = 3) or balloon dilatation (n = 5), with safe and effective outcomes, reported the authors.

"Because the target area for the myotomy during POEM is lateral (on the lesser curvature side) and the myotomy during LHM is anterior, subsequent LHM seems to be a feasible second-line treatment if POEM fails."

Moreover, roughly half of the patients in the current study had previously undergone endoscopic balloon dilatation or botulinum toxin injection before POEM, the researchers wrote. "This shows that POEM is safe and efficient after previous treatments."

Nevertheless, the procedure is not without risk. "Visible complete transmural openings into the mediastinum and into the peritoneal cavity occurred in the majority of patients," they pointed out. "Therefore, POEM potentially carries the risk of mediastinitis/peritonitis and/or damage to surrounding organs."

Clip dislocation at mucosal closure (n = 3), mucosal injury through electrocautery or laceration (n = 3), and bleeding requiring intervention also occurred (n = 1).

Finally, looking at postprocedure reflux rates, at 12 months, roughly 37% of patients complained of gastroesophageal reflux, with just under 8% of these patients reporting reflux symptoms daily.

Overall, 29% were prescribed a proton pump inhibitor; 19.6% of these used a PPI daily.

The authors disclosed no conflicts of interest. The study was supported by EURO-NOTES Foundation – a partnership between the European Association for Endoscopic Surgery and the European Society of Gastrointestinal Endoscopy – and Olympus, maker of endotherapeutic supplies.

Peroral endoscopic myotomy is a safe and effective therapy for achalasia, with 82% of patients in symptom remission at 12 months post treatment.

"With [peroral endoscopic myotomy] it seems possible to emulate the surgical principles of laparoscopic Heller myotomy without the need for skin incisions and to reduce the procedural trauma," reported Dr. Daniel Von Renteln and colleagues. The findings are in the August issue of Gastroenterology.

According to Dr. Von Renteln of the University Hospital Hamburg-Eppendorf in Hamburg, Germany, peroral endoscopic myotomy (POEM) is a novel alternative achalasia treatment.

As described previously (Endoscopy 2010;42:265-71), under general anesthesia and following endoscopy to visualize the gastroesophageal junction, a mucosal incision is made to create entry to the submucosal space. A submucosal tunnel is then created, extending downward, allowing myotomy of the esophageal sphincter. The mucosal entry site is then closed with hemostatic clips.

In the present study, the researchers looked at 70 patients who underwent the procedure at five centers in Europe and North America.

The mean procedure time for POEM was 105 minutes and the mean length of myotomy was 13 cm. Patients experienced a small but significant drop in hemoglobin post procedure (from 13 to 12 g/dL, P less than .001) as well as small but significant increases in leukocyte count and C-reactive protein levels.

At 3 months post procedure, treatment success was achieved in 97% of cases, with mean Eckhardt scores decreasing from 7 pre procedure to 1 post procedure (P less than .001).

Of the 61 patients who underwent manometry at 3 months, the researchers found that the mean pretreatment and posttreatment lower esophageal sphincter pressures were 28 mm Hg versus 9 mm Hg, respectively (P less than .001).

Results at 6 months and 12 months were comparable, with treatment success of 88.5% and 82.4%, respectively, and mean Eckhardt scores of 1.3 and 1.7, respectively (P less than .001 for both).

Patients who failed treatment subsequently underwent laparoscopic Heller myotomy (n = 3) or balloon dilatation (n = 5), with safe and effective outcomes, reported the authors.

"Because the target area for the myotomy during POEM is lateral (on the lesser curvature side) and the myotomy during LHM is anterior, subsequent LHM seems to be a feasible second-line treatment if POEM fails."

Moreover, roughly half of the patients in the current study had previously undergone endoscopic balloon dilatation or botulinum toxin injection before POEM, the researchers wrote. "This shows that POEM is safe and efficient after previous treatments."

Nevertheless, the procedure is not without risk. "Visible complete transmural openings into the mediastinum and into the peritoneal cavity occurred in the majority of patients," they pointed out. "Therefore, POEM potentially carries the risk of mediastinitis/peritonitis and/or damage to surrounding organs."

Clip dislocation at mucosal closure (n = 3), mucosal injury through electrocautery or laceration (n = 3), and bleeding requiring intervention also occurred (n = 1).

Finally, looking at postprocedure reflux rates, at 12 months, roughly 37% of patients complained of gastroesophageal reflux, with just under 8% of these patients reporting reflux symptoms daily.

Overall, 29% were prescribed a proton pump inhibitor; 19.6% of these used a PPI daily.

The authors disclosed no conflicts of interest. The study was supported by EURO-NOTES Foundation – a partnership between the European Association for Endoscopic Surgery and the European Society of Gastrointestinal Endoscopy – and Olympus, maker of endotherapeutic supplies.

Peroral endoscopic myotomy is a safe and effective therapy for achalasia, with 82% of patients in symptom remission at 12 months post treatment.

"With [peroral endoscopic myotomy] it seems possible to emulate the surgical principles of laparoscopic Heller myotomy without the need for skin incisions and to reduce the procedural trauma," reported Dr. Daniel Von Renteln and colleagues. The findings are in the August issue of Gastroenterology.

According to Dr. Von Renteln of the University Hospital Hamburg-Eppendorf in Hamburg, Germany, peroral endoscopic myotomy (POEM) is a novel alternative achalasia treatment.

As described previously (Endoscopy 2010;42:265-71), under general anesthesia and following endoscopy to visualize the gastroesophageal junction, a mucosal incision is made to create entry to the submucosal space. A submucosal tunnel is then created, extending downward, allowing myotomy of the esophageal sphincter. The mucosal entry site is then closed with hemostatic clips.

In the present study, the researchers looked at 70 patients who underwent the procedure at five centers in Europe and North America.

The mean procedure time for POEM was 105 minutes and the mean length of myotomy was 13 cm. Patients experienced a small but significant drop in hemoglobin post procedure (from 13 to 12 g/dL, P less than .001) as well as small but significant increases in leukocyte count and C-reactive protein levels.

At 3 months post procedure, treatment success was achieved in 97% of cases, with mean Eckhardt scores decreasing from 7 pre procedure to 1 post procedure (P less than .001).

Of the 61 patients who underwent manometry at 3 months, the researchers found that the mean pretreatment and posttreatment lower esophageal sphincter pressures were 28 mm Hg versus 9 mm Hg, respectively (P less than .001).

Results at 6 months and 12 months were comparable, with treatment success of 88.5% and 82.4%, respectively, and mean Eckhardt scores of 1.3 and 1.7, respectively (P less than .001 for both).

Patients who failed treatment subsequently underwent laparoscopic Heller myotomy (n = 3) or balloon dilatation (n = 5), with safe and effective outcomes, reported the authors.

"Because the target area for the myotomy during POEM is lateral (on the lesser curvature side) and the myotomy during LHM is anterior, subsequent LHM seems to be a feasible second-line treatment if POEM fails."

Moreover, roughly half of the patients in the current study had previously undergone endoscopic balloon dilatation or botulinum toxin injection before POEM, the researchers wrote. "This shows that POEM is safe and efficient after previous treatments."

Nevertheless, the procedure is not without risk. "Visible complete transmural openings into the mediastinum and into the peritoneal cavity occurred in the majority of patients," they pointed out. "Therefore, POEM potentially carries the risk of mediastinitis/peritonitis and/or damage to surrounding organs."

Clip dislocation at mucosal closure (n = 3), mucosal injury through electrocautery or laceration (n = 3), and bleeding requiring intervention also occurred (n = 1).

Finally, looking at postprocedure reflux rates, at 12 months, roughly 37% of patients complained of gastroesophageal reflux, with just under 8% of these patients reporting reflux symptoms daily.

Overall, 29% were prescribed a proton pump inhibitor; 19.6% of these used a PPI daily.

The authors disclosed no conflicts of interest. The study was supported by EURO-NOTES Foundation – a partnership between the European Association for Endoscopic Surgery and the European Society of Gastrointestinal Endoscopy – and Olympus, maker of endotherapeutic supplies.

Fewer than 20% of patients with hepatitis C virus genotype 1 receive triple therapy with boceprevir or telaprevir, according to Dr. Emerson Y. Chen and colleagues. The results are in the August issue of Clinical Gastroenterology and Hepatology.

The "disappointingly low use of the new therapies, even after a decade without novel medications," suggests that real-world use of these drugs is hampered by factors including safety and the low predicted response rates in prior nonresponders, they wrote.

Dr. Chen of the University of Texas Southwestern Medical School, Dallas, looked at 487 patients with HCV genotype 1 presenting to one of two academic outpatient hepatology practices in Dallas and Miami.

The majority of patients were between 50 and 60 years of age, male, and white. More than two-thirds had private insurance, and half of the patients were treatment naive.

Overall, the authors found that 91 patients (18.7%) were started on triple therapy (boceprevir or telaprevir plus pegylated interferon and ribavirin) while the remaining 396 patients remained untreated.

Dr. Chen then assessed the reasons for treatment deferral. The most common, he found, was contraindication (50.5%), including complications of liver disease and medical comorbidities. The next biggest reason cited for treatment deferral was "patient choice" (22.5%), which included concerns about side effects, limited success rates, financial issues, or inability to commit time for treatment. Finally, the presence of less advanced liver disease (17.4%) and the anticipation (among providers and patients alike) of better future therapies (9.6%) were also factors in triple therapy refusal.

"Although several expert panels for treatment recommendations are available, there exists an uncertainty among providers regarding selecting patients without major contraindications for triple therapy now over newer direct-acting antiviral therapy later," they added.

Next, the researchers compared the triple therapy patients with therapy deferrals.

In univariate analysis, they found that about three-fourths of patients who chose to initiate triple therapy had fibrosis stage 3 or were cirrhotic, although less than 10% had a history of overt decompensation.

"In contrast, among those who deferred treatment, more than 20% had decompensated liver disease, and 46% had early [an] fibrosis stage," they wrote.

Looking at patients’ mean Model for End-Stage Liver Disease scores, cirrhotic patients who deferred treatment registered a 9.3, compared with 7.3 for patients who elected to undergo triple therapy treatment (P less than .001). Additionally, 90% of cirrhotic patients on treatment were Child-Pugh class A compared with 63% in the nontreatment group (P = .003).

Commenting on the findings, Dr. Chen wrote that "although patients with mild fibrosis or persistently normal liver function tests have often not been recommended for repeat biopsy or treatment, they would likely benefit from treatment before they become older or develop contraindications.

"Nevertheless, many hepatologists appear to be recommending deferral of treatment for patients with mild to moderate fibrosis, waiting for the second-generation direct-acting antivirals with even higher sustained virologic response rates" and fewer side effects.

"Newly diagnosed treatment-naive patients along with those with less advanced liver disease will benefit from society-wide consensus regarding therapy initiation now or at a later time."

The authors disclosed funding from the Doris Duke Charitable Foundation and the University of Miami. Two authors disclosed ties to Merck, maker of boceprevir and ribavirin, and Vertex, which makes telaprevir.

Fewer than 20% of patients with hepatitis C virus genotype 1 receive triple therapy with boceprevir or telaprevir, according to Dr. Emerson Y. Chen and colleagues. The results are in the August issue of Clinical Gastroenterology and Hepatology.

The "disappointingly low use of the new therapies, even after a decade without novel medications," suggests that real-world use of these drugs is hampered by factors including safety and the low predicted response rates in prior nonresponders, they wrote.

Dr. Chen of the University of Texas Southwestern Medical School, Dallas, looked at 487 patients with HCV genotype 1 presenting to one of two academic outpatient hepatology practices in Dallas and Miami.

The majority of patients were between 50 and 60 years of age, male, and white. More than two-thirds had private insurance, and half of the patients were treatment naive.

Overall, the authors found that 91 patients (18.7%) were started on triple therapy (boceprevir or telaprevir plus pegylated interferon and ribavirin) while the remaining 396 patients remained untreated.

Dr. Chen then assessed the reasons for treatment deferral. The most common, he found, was contraindication (50.5%), including complications of liver disease and medical comorbidities. The next biggest reason cited for treatment deferral was "patient choice" (22.5%), which included concerns about side effects, limited success rates, financial issues, or inability to commit time for treatment. Finally, the presence of less advanced liver disease (17.4%) and the anticipation (among providers and patients alike) of better future therapies (9.6%) were also factors in triple therapy refusal.

"Although several expert panels for treatment recommendations are available, there exists an uncertainty among providers regarding selecting patients without major contraindications for triple therapy now over newer direct-acting antiviral therapy later," they added.

Next, the researchers compared the triple therapy patients with therapy deferrals.

In univariate analysis, they found that about three-fourths of patients who chose to initiate triple therapy had fibrosis stage 3 or were cirrhotic, although less than 10% had a history of overt decompensation.

"In contrast, among those who deferred treatment, more than 20% had decompensated liver disease, and 46% had early [an] fibrosis stage," they wrote.

Looking at patients’ mean Model for End-Stage Liver Disease scores, cirrhotic patients who deferred treatment registered a 9.3, compared with 7.3 for patients who elected to undergo triple therapy treatment (P less than .001). Additionally, 90% of cirrhotic patients on treatment were Child-Pugh class A compared with 63% in the nontreatment group (P = .003).

Commenting on the findings, Dr. Chen wrote that "although patients with mild fibrosis or persistently normal liver function tests have often not been recommended for repeat biopsy or treatment, they would likely benefit from treatment before they become older or develop contraindications.

"Nevertheless, many hepatologists appear to be recommending deferral of treatment for patients with mild to moderate fibrosis, waiting for the second-generation direct-acting antivirals with even higher sustained virologic response rates" and fewer side effects.

"Newly diagnosed treatment-naive patients along with those with less advanced liver disease will benefit from society-wide consensus regarding therapy initiation now or at a later time."

The authors disclosed funding from the Doris Duke Charitable Foundation and the University of Miami. Two authors disclosed ties to Merck, maker of boceprevir and ribavirin, and Vertex, which makes telaprevir.

Fewer than 20% of patients with hepatitis C virus genotype 1 receive triple therapy with boceprevir or telaprevir, according to Dr. Emerson Y. Chen and colleagues. The results are in the August issue of Clinical Gastroenterology and Hepatology.

The "disappointingly low use of the new therapies, even after a decade without novel medications," suggests that real-world use of these drugs is hampered by factors including safety and the low predicted response rates in prior nonresponders, they wrote.

Dr. Chen of the University of Texas Southwestern Medical School, Dallas, looked at 487 patients with HCV genotype 1 presenting to one of two academic outpatient hepatology practices in Dallas and Miami.

The majority of patients were between 50 and 60 years of age, male, and white. More than two-thirds had private insurance, and half of the patients were treatment naive.

Overall, the authors found that 91 patients (18.7%) were started on triple therapy (boceprevir or telaprevir plus pegylated interferon and ribavirin) while the remaining 396 patients remained untreated.

Dr. Chen then assessed the reasons for treatment deferral. The most common, he found, was contraindication (50.5%), including complications of liver disease and medical comorbidities. The next biggest reason cited for treatment deferral was "patient choice" (22.5%), which included concerns about side effects, limited success rates, financial issues, or inability to commit time for treatment. Finally, the presence of less advanced liver disease (17.4%) and the anticipation (among providers and patients alike) of better future therapies (9.6%) were also factors in triple therapy refusal.

"Although several expert panels for treatment recommendations are available, there exists an uncertainty among providers regarding selecting patients without major contraindications for triple therapy now over newer direct-acting antiviral therapy later," they added.

Next, the researchers compared the triple therapy patients with therapy deferrals.

In univariate analysis, they found that about three-fourths of patients who chose to initiate triple therapy had fibrosis stage 3 or were cirrhotic, although less than 10% had a history of overt decompensation.

"In contrast, among those who deferred treatment, more than 20% had decompensated liver disease, and 46% had early [an] fibrosis stage," they wrote.

Looking at patients’ mean Model for End-Stage Liver Disease scores, cirrhotic patients who deferred treatment registered a 9.3, compared with 7.3 for patients who elected to undergo triple therapy treatment (P less than .001). Additionally, 90% of cirrhotic patients on treatment were Child-Pugh class A compared with 63% in the nontreatment group (P = .003).

Commenting on the findings, Dr. Chen wrote that "although patients with mild fibrosis or persistently normal liver function tests have often not been recommended for repeat biopsy or treatment, they would likely benefit from treatment before they become older or develop contraindications.

"Nevertheless, many hepatologists appear to be recommending deferral of treatment for patients with mild to moderate fibrosis, waiting for the second-generation direct-acting antivirals with even higher sustained virologic response rates" and fewer side effects.

"Newly diagnosed treatment-naive patients along with those with less advanced liver disease will benefit from society-wide consensus regarding therapy initiation now or at a later time."

The authors disclosed funding from the Doris Duke Charitable Foundation and the University of Miami. Two authors disclosed ties to Merck, maker of boceprevir and ribavirin, and Vertex, which makes telaprevir.

Despite high rates of early clinical response, 30% of veterans taking direct-acting antivirals for hepatitis C discontinued treatment by week 24.

The findings highlight "the challenges associated with maintenance of these regimens" in a real-world cohort, wrote Pamela S. Belperio, Pharm.D., and colleagues. The study appears in the August issue of Clinical Gastroenterology and Hepatology.

Dr. Belperio of Veterans Affairs Palo Alto (Calif.) Health Care System, looked at 859 patients registered with the VA’s Clinical Case Registry for HCV who initiated triple therapy with pegylated interferon, ribavirin, and either boceprevir (n = 661) or telaprevir (n = 198) before Jan. 1, 2012, at 94 different VA facilities.

The authors determined how long the patient took the drug by looking at medication dispensed dates, and patients were classified as having response rates of "undetectable" if HCV RNA levels at their most recent assay were undetectable.

Patients’ mean age was 57 years; most of the patients were male. Patients with HIV or hepatitis B virus coinfection, hepatocellular carcinoma, or liver transplantation were excluded.

Even so, "Up to 13% of boceprevir-treated veterans and 24% of telaprevir-treated veterans would have been excluded from the phase III trials [of these therapies] based on hematologic exclusion criteria used in the telaprevir trials," Dr. Belperio wrote.

Despite this, the authors found that by week 12, 76% of all treatment-naive, noncirrhotic patients taking boceprevir had achieved undetectable viral loads, as had 78% of telaprevir patients.

By 24 weeks, those numbers were 74% for boceprevir patients and 60% for telaprevir patients.

However, the researchers also found that about one-third of patients discontinued treatment with either boceprevir or telaprevir before 24 weeks (30% and 34%, respectively; P = .37), with an incidence of hematologic adverse events that was both higher and more pronounced than has been reported in clinical trials of direct-acting antivirals (DAAs), wrote Dr. Belperio.

Indeed, anemia of at least grade 1 (hemoglobin below normal limits but greater than or equal to 10 g/dL) occurred in 50% of patients in both DAA groups, "which is up to a 15% increased incidence of anemia over what has been reported elsewhere."

There was also significant thrombocytopenia for both drugs, which Dr. Belperio said was four times higher than in clinical trials. In fact, her group reported that 66% of patients taking boceprevir had grade 1 thrombocytopenia. (platelets below normal limits but greater than or equal to 75,000/mm³), as did 59% of patients taking telaprevir.

"This may reflect the greater proportion of cirrhotic patients in our cohort compared with the clinical trials; however, it is concerning given the limited strategies currently available to manage thrombocytopenia and the unknown effect that PEG dose reductions may have on sustained virologic response in the context of DAA-based therapies," they wrote.

There also was a portion of patients for whom treatment was determined to be futile, according to Food and Drug Administration specifications: 9% of patients receiving boceprevir at week 12 and 5% at week 24, as well as 6% of telaprevir patients at week 4, 4% at week 12, and 7% at week 24.

The authors conceded several limitations to this study, including that they were unable to assess reasons for early treatment discontinuation.

Nevertheless, the data "offer clinicians a perspective on expectations of early response and safety of DAA regimens in routine clinical practice, allowing a more nuanced discussion between providers and patients regarding the risks and benefits of embarking on DAA-based treatment."

The authors disclosed that one coinvestigator has previously received grant support from Gilead Sciences, maker of HCV therapies. They disclosed no other conflicts of interest.

Despite high rates of early clinical response, 30% of veterans taking direct-acting antivirals for hepatitis C discontinued treatment by week 24.

The findings highlight "the challenges associated with maintenance of these regimens" in a real-world cohort, wrote Pamela S. Belperio, Pharm.D., and colleagues. The study appears in the August issue of Clinical Gastroenterology and Hepatology.

Dr. Belperio of Veterans Affairs Palo Alto (Calif.) Health Care System, looked at 859 patients registered with the VA’s Clinical Case Registry for HCV who initiated triple therapy with pegylated interferon, ribavirin, and either boceprevir (n = 661) or telaprevir (n = 198) before Jan. 1, 2012, at 94 different VA facilities.

The authors determined how long the patient took the drug by looking at medication dispensed dates, and patients were classified as having response rates of "undetectable" if HCV RNA levels at their most recent assay were undetectable.

Patients’ mean age was 57 years; most of the patients were male. Patients with HIV or hepatitis B virus coinfection, hepatocellular carcinoma, or liver transplantation were excluded.

Even so, "Up to 13% of boceprevir-treated veterans and 24% of telaprevir-treated veterans would have been excluded from the phase III trials [of these therapies] based on hematologic exclusion criteria used in the telaprevir trials," Dr. Belperio wrote.

Despite this, the authors found that by week 12, 76% of all treatment-naive, noncirrhotic patients taking boceprevir had achieved undetectable viral loads, as had 78% of telaprevir patients.

By 24 weeks, those numbers were 74% for boceprevir patients and 60% for telaprevir patients.

However, the researchers also found that about one-third of patients discontinued treatment with either boceprevir or telaprevir before 24 weeks (30% and 34%, respectively; P = .37), with an incidence of hematologic adverse events that was both higher and more pronounced than has been reported in clinical trials of direct-acting antivirals (DAAs), wrote Dr. Belperio.

Indeed, anemia of at least grade 1 (hemoglobin below normal limits but greater than or equal to 10 g/dL) occurred in 50% of patients in both DAA groups, "which is up to a 15% increased incidence of anemia over what has been reported elsewhere."

There was also significant thrombocytopenia for both drugs, which Dr. Belperio said was four times higher than in clinical trials. In fact, her group reported that 66% of patients taking boceprevir had grade 1 thrombocytopenia. (platelets below normal limits but greater than or equal to 75,000/mm³), as did 59% of patients taking telaprevir.

"This may reflect the greater proportion of cirrhotic patients in our cohort compared with the clinical trials; however, it is concerning given the limited strategies currently available to manage thrombocytopenia and the unknown effect that PEG dose reductions may have on sustained virologic response in the context of DAA-based therapies," they wrote.

There also was a portion of patients for whom treatment was determined to be futile, according to Food and Drug Administration specifications: 9% of patients receiving boceprevir at week 12 and 5% at week 24, as well as 6% of telaprevir patients at week 4, 4% at week 12, and 7% at week 24.

The authors conceded several limitations to this study, including that they were unable to assess reasons for early treatment discontinuation.

Nevertheless, the data "offer clinicians a perspective on expectations of early response and safety of DAA regimens in routine clinical practice, allowing a more nuanced discussion between providers and patients regarding the risks and benefits of embarking on DAA-based treatment."

The authors disclosed that one coinvestigator has previously received grant support from Gilead Sciences, maker of HCV therapies. They disclosed no other conflicts of interest.

Despite high rates of early clinical response, 30% of veterans taking direct-acting antivirals for hepatitis C discontinued treatment by week 24.

The findings highlight "the challenges associated with maintenance of these regimens" in a real-world cohort, wrote Pamela S. Belperio, Pharm.D., and colleagues. The study appears in the August issue of Clinical Gastroenterology and Hepatology.

Dr. Belperio of Veterans Affairs Palo Alto (Calif.) Health Care System, looked at 859 patients registered with the VA’s Clinical Case Registry for HCV who initiated triple therapy with pegylated interferon, ribavirin, and either boceprevir (n = 661) or telaprevir (n = 198) before Jan. 1, 2012, at 94 different VA facilities.

The authors determined how long the patient took the drug by looking at medication dispensed dates, and patients were classified as having response rates of "undetectable" if HCV RNA levels at their most recent assay were undetectable.

Patients’ mean age was 57 years; most of the patients were male. Patients with HIV or hepatitis B virus coinfection, hepatocellular carcinoma, or liver transplantation were excluded.

Even so, "Up to 13% of boceprevir-treated veterans and 24% of telaprevir-treated veterans would have been excluded from the phase III trials [of these therapies] based on hematologic exclusion criteria used in the telaprevir trials," Dr. Belperio wrote.

Despite this, the authors found that by week 12, 76% of all treatment-naive, noncirrhotic patients taking boceprevir had achieved undetectable viral loads, as had 78% of telaprevir patients.

By 24 weeks, those numbers were 74% for boceprevir patients and 60% for telaprevir patients.

However, the researchers also found that about one-third of patients discontinued treatment with either boceprevir or telaprevir before 24 weeks (30% and 34%, respectively; P = .37), with an incidence of hematologic adverse events that was both higher and more pronounced than has been reported in clinical trials of direct-acting antivirals (DAAs), wrote Dr. Belperio.

Indeed, anemia of at least grade 1 (hemoglobin below normal limits but greater than or equal to 10 g/dL) occurred in 50% of patients in both DAA groups, "which is up to a 15% increased incidence of anemia over what has been reported elsewhere."

There was also significant thrombocytopenia for both drugs, which Dr. Belperio said was four times higher than in clinical trials. In fact, her group reported that 66% of patients taking boceprevir had grade 1 thrombocytopenia. (platelets below normal limits but greater than or equal to 75,000/mm³), as did 59% of patients taking telaprevir.

"This may reflect the greater proportion of cirrhotic patients in our cohort compared with the clinical trials; however, it is concerning given the limited strategies currently available to manage thrombocytopenia and the unknown effect that PEG dose reductions may have on sustained virologic response in the context of DAA-based therapies," they wrote.

There also was a portion of patients for whom treatment was determined to be futile, according to Food and Drug Administration specifications: 9% of patients receiving boceprevir at week 12 and 5% at week 24, as well as 6% of telaprevir patients at week 4, 4% at week 12, and 7% at week 24.

The authors conceded several limitations to this study, including that they were unable to assess reasons for early treatment discontinuation.

Nevertheless, the data "offer clinicians a perspective on expectations of early response and safety of DAA regimens in routine clinical practice, allowing a more nuanced discussion between providers and patients regarding the risks and benefits of embarking on DAA-based treatment."

The authors disclosed that one coinvestigator has previously received grant support from Gilead Sciences, maker of HCV therapies. They disclosed no other conflicts of interest.

Patients with autism, Williams syndrome, and Down syndrome are all socially vulnerable, but in "markedly different" ways. Understanding these differences might help tailor specific interventions to keep these populations safe from abuse and exploitation.

That’s the conclusion of a recent study by Marisa H. Fisher, Ph.D., and her colleagues, published in the August issue of Research in Autism Spectrum Disorders. The study looked at 103 parents or guardians who reported information on adolescents and adults with autism spectrum disorder (n = 29), Williams syndrome (n = 38), or Down syndrome (n = 36) (Res. Autism Spectr. Disord. 2013;7:931-7).

Patient ages averaged between 24-25 years across syndromes, and 67% of respondents were mothers, though no differences in responses was found based on the type of guardian or parent that was polled, wrote Dr. Fisher of the Vanderbilt Kennedy Center, in Nashville, Tenn.

All respondents completed a 30-item Social Vulnerability Questionnaire. Developed by Dr. Fisher, this scale assessed the degree of emotional bullying experienced by the patient (teasing, taunting); the patient’s risk awareness (for example, the ability to detect and avoid victimization); the degree of social protection (the existence or lack of a peer network); perceived vulnerability (physical traits that could make the patient a target); parental independence; and credulity (reasons why the patient might "fall for" certain types of victimization).

The respondents also answered an open-ended question, which simply asked for an example of a time that the patient had been victimized in the past, "to determine the percentage of individuals who had ever experienced some form of victimization in their lifetime and the different types of victimization experienced within each condition."

Based on answers to the last question, the authors found that fully 73% of respondents could detail at least one instance of victimization, including teasing or persuasion (35%), money or theft (32%), or physical or sexual abuse (21%).

All three groups experienced all of the above forms of victimization at roughly equal rates, according to the survey, wrote the authors, with many patients experiencing more than one form.

Next, the authors looked at results from the social vulnerability questionnaire.

Looking at risk awareness profiles, the investigators found that patients with autism and Down syndrome were less risk-aware than were their peers with Williams syndrome.

For example, "individuals with [autism spectrum disorder and [Down syndrome] were less likely to tell a parent or authority figure if something questionable happened and were less aware that they had a disability," they wrote.

In the realm of perceived vulnerability, the fact that Down syndrome patients were more likely to look different from and be smaller than same-age patients made them especially vulnerable.

However, in terms of social protection, it was the patients with autism who were less likely to have friends or to be considered a part of a social group, and therefore more vulnerable to the victimization that preyed upon this weakness.

Finally, when it came to parental independence, it was the parents of patients with Williams syndrome who were most likely to leave their children alone for an extended period of time and to allow them to be with members of the opposite sex unsupervised.

According to Dr. Fisher, the finding that all patients are victimized, but for different reasons, means that antivictimization interventions must be tailored to the specific needs of different groups.

For example, for individuals with autism spectrum disorders, "A strong peer network would seem an important protective factor for decreasing bullying and other interpersonal violence."

Perhaps one way to reduce vulnerability to victimization experienced by people with autism spectrum disorders might be to provide social skills interventions and ways to increase friendships.

"Conversely, the social vulnerability of individuals with Williams syndrome seemed related to increased independence from their parents," she wrote.

"Most successful, then, might be programs such as those designed to teach individuals with Williams syndrome how to appropriately respond to strangers."

She concluded, "By identifying different correlates relating to social vulnerability in these conditions, intervention research should now focus on improving programs aimed at reducing victimization and vulnerability for individuals with [autism spectrum disorders], [Williams syndrome], and [Down syndrome.]"

The authors cited several limitations, including the relatively small sample size. They disclosed no conflicts.

Patients with autism, Williams syndrome, and Down syndrome are all socially vulnerable, but in "markedly different" ways. Understanding these differences might help tailor specific interventions to keep these populations safe from abuse and exploitation.

That’s the conclusion of a recent study by Marisa H. Fisher, Ph.D., and her colleagues, published in the August issue of Research in Autism Spectrum Disorders. The study looked at 103 parents or guardians who reported information on adolescents and adults with autism spectrum disorder (n = 29), Williams syndrome (n = 38), or Down syndrome (n = 36) (Res. Autism Spectr. Disord. 2013;7:931-7).

Patient ages averaged between 24-25 years across syndromes, and 67% of respondents were mothers, though no differences in responses was found based on the type of guardian or parent that was polled, wrote Dr. Fisher of the Vanderbilt Kennedy Center, in Nashville, Tenn.

All respondents completed a 30-item Social Vulnerability Questionnaire. Developed by Dr. Fisher, this scale assessed the degree of emotional bullying experienced by the patient (teasing, taunting); the patient’s risk awareness (for example, the ability to detect and avoid victimization); the degree of social protection (the existence or lack of a peer network); perceived vulnerability (physical traits that could make the patient a target); parental independence; and credulity (reasons why the patient might "fall for" certain types of victimization).

The respondents also answered an open-ended question, which simply asked for an example of a time that the patient had been victimized in the past, "to determine the percentage of individuals who had ever experienced some form of victimization in their lifetime and the different types of victimization experienced within each condition."

Based on answers to the last question, the authors found that fully 73% of respondents could detail at least one instance of victimization, including teasing or persuasion (35%), money or theft (32%), or physical or sexual abuse (21%).

All three groups experienced all of the above forms of victimization at roughly equal rates, according to the survey, wrote the authors, with many patients experiencing more than one form.

Next, the authors looked at results from the social vulnerability questionnaire.

Looking at risk awareness profiles, the investigators found that patients with autism and Down syndrome were less risk-aware than were their peers with Williams syndrome.

For example, "individuals with [autism spectrum disorder and [Down syndrome] were less likely to tell a parent or authority figure if something questionable happened and were less aware that they had a disability," they wrote.

In the realm of perceived vulnerability, the fact that Down syndrome patients were more likely to look different from and be smaller than same-age patients made them especially vulnerable.

However, in terms of social protection, it was the patients with autism who were less likely to have friends or to be considered a part of a social group, and therefore more vulnerable to the victimization that preyed upon this weakness.

Finally, when it came to parental independence, it was the parents of patients with Williams syndrome who were most likely to leave their children alone for an extended period of time and to allow them to be with members of the opposite sex unsupervised.

According to Dr. Fisher, the finding that all patients are victimized, but for different reasons, means that antivictimization interventions must be tailored to the specific needs of different groups.

For example, for individuals with autism spectrum disorders, "A strong peer network would seem an important protective factor for decreasing bullying and other interpersonal violence."

Perhaps one way to reduce vulnerability to victimization experienced by people with autism spectrum disorders might be to provide social skills interventions and ways to increase friendships.

"Conversely, the social vulnerability of individuals with Williams syndrome seemed related to increased independence from their parents," she wrote.

"Most successful, then, might be programs such as those designed to teach individuals with Williams syndrome how to appropriately respond to strangers."

She concluded, "By identifying different correlates relating to social vulnerability in these conditions, intervention research should now focus on improving programs aimed at reducing victimization and vulnerability for individuals with [autism spectrum disorders], [Williams syndrome], and [Down syndrome.]"

The authors cited several limitations, including the relatively small sample size. They disclosed no conflicts.

Patients with autism, Williams syndrome, and Down syndrome are all socially vulnerable, but in "markedly different" ways. Understanding these differences might help tailor specific interventions to keep these populations safe from abuse and exploitation.

That’s the conclusion of a recent study by Marisa H. Fisher, Ph.D., and her colleagues, published in the August issue of Research in Autism Spectrum Disorders. The study looked at 103 parents or guardians who reported information on adolescents and adults with autism spectrum disorder (n = 29), Williams syndrome (n = 38), or Down syndrome (n = 36) (Res. Autism Spectr. Disord. 2013;7:931-7).

Patient ages averaged between 24-25 years across syndromes, and 67% of respondents were mothers, though no differences in responses was found based on the type of guardian or parent that was polled, wrote Dr. Fisher of the Vanderbilt Kennedy Center, in Nashville, Tenn.

All respondents completed a 30-item Social Vulnerability Questionnaire. Developed by Dr. Fisher, this scale assessed the degree of emotional bullying experienced by the patient (teasing, taunting); the patient’s risk awareness (for example, the ability to detect and avoid victimization); the degree of social protection (the existence or lack of a peer network); perceived vulnerability (physical traits that could make the patient a target); parental independence; and credulity (reasons why the patient might "fall for" certain types of victimization).

The respondents also answered an open-ended question, which simply asked for an example of a time that the patient had been victimized in the past, "to determine the percentage of individuals who had ever experienced some form of victimization in their lifetime and the different types of victimization experienced within each condition."

Based on answers to the last question, the authors found that fully 73% of respondents could detail at least one instance of victimization, including teasing or persuasion (35%), money or theft (32%), or physical or sexual abuse (21%).

All three groups experienced all of the above forms of victimization at roughly equal rates, according to the survey, wrote the authors, with many patients experiencing more than one form.

Next, the authors looked at results from the social vulnerability questionnaire.

Looking at risk awareness profiles, the investigators found that patients with autism and Down syndrome were less risk-aware than were their peers with Williams syndrome.

For example, "individuals with [autism spectrum disorder and [Down syndrome] were less likely to tell a parent or authority figure if something questionable happened and were less aware that they had a disability," they wrote.

In the realm of perceived vulnerability, the fact that Down syndrome patients were more likely to look different from and be smaller than same-age patients made them especially vulnerable.

However, in terms of social protection, it was the patients with autism who were less likely to have friends or to be considered a part of a social group, and therefore more vulnerable to the victimization that preyed upon this weakness.

Finally, when it came to parental independence, it was the parents of patients with Williams syndrome who were most likely to leave their children alone for an extended period of time and to allow them to be with members of the opposite sex unsupervised.

According to Dr. Fisher, the finding that all patients are victimized, but for different reasons, means that antivictimization interventions must be tailored to the specific needs of different groups.

For example, for individuals with autism spectrum disorders, "A strong peer network would seem an important protective factor for decreasing bullying and other interpersonal violence."

Perhaps one way to reduce vulnerability to victimization experienced by people with autism spectrum disorders might be to provide social skills interventions and ways to increase friendships.

"Conversely, the social vulnerability of individuals with Williams syndrome seemed related to increased independence from their parents," she wrote.

"Most successful, then, might be programs such as those designed to teach individuals with Williams syndrome how to appropriately respond to strangers."

She concluded, "By identifying different correlates relating to social vulnerability in these conditions, intervention research should now focus on improving programs aimed at reducing victimization and vulnerability for individuals with [autism spectrum disorders], [Williams syndrome], and [Down syndrome.]"

The authors cited several limitations, including the relatively small sample size. They disclosed no conflicts.

Autism spectrum disorder patients who attempt suicide are younger and more likely to have comorbid adjustment disorder, compared with suicidal patients without autism.

The findings come from what the investigators say is the "first study to compare suicide attempts in [autism spectrum disorder] and [non–autism spectrum disorder] patients in adults in the emergency department, according to Dr. Koji Kato and colleagues (Gen. Hosp. Psychiatry 2013;35:50-3).

Dr. Kato looked at 587 consecutive adult patients who attempted suicide and were hospitalized at the Advanced Critical Care Center of Tokai (Japan) University Hospital between April 2010 and December 2011.

Overall, 43 of the 587 subjects (7.3%) were found to have autism spectrum disorders, diagnosed by family history and also by administration of the Autism-Spectrum Quotient–Japanese version during hospitalization, wrote Dr. Kato of Tokai University, Kanagawa, Japan.

"Poor interpersonal problem-solving skills or impulsive behavior, which is characteristic of individuals with [autism spectrum disorders], had been linked with an increased risk of suicidal behavior among youth." -Dr. Kato, et. al. 

The researchers then began to characterize these patients in comparison with their nonautism counterparts. First, they found that patients with autism spectrum disorder were significantly younger than were their nonautism counterparts (33.7 years versus 42.5 years, respectively; P = .001) and also much more likely to be male (81.4% vs. 30.3%; P less than .001).

Similarly, more than three-quarters of the autism spectrum patients were unmarried, compared with just over one-third of nonautism patients (76.7% vs. 37.5%; P less than .001) and were in fact more likely to be living alone at the time of the attempt (41.9% vs. 18.9%; P less than .001).

Next, the authors looked at psychiatric diagnoses. They found that patients with an autism spectrum disorder were much less likely to have a diagnosis of a mood disorder, compared with their nonautism counterparts (18.6% vs. 34.2%, P = .043), although they were much more likely to have adjustment disorders (70.0% vs. 41.5%, P less than .001).

Commenting on the marked difference in age between autism spectrum disorder patients and the rest of the cohort, they wrote: "Poor interpersonal problem-solving skills or impulsive behavior, which is characteristic of individuals with [autism spectrum disorders], had been linked with an increased risk of suicidal behavior among youth."

Indeed, other research "suggests that suicidal acts are more frequent in adolescents with Asperger syndrome, perhaps due to bullying and feelings of inadequacy in coping with the social demands that occur during puberty."

Looking at the documented higher incidence of single individuals and individuals living alone in the autism spectrum disorders group "could be explained by autism spectrum disorder characteristics such as lack of social reciprocity and/or repeated failure to develop peer relationships since childhood or adolescence," they added.

Finally, they addressed the prevalence of mood and adjustment disorders among the cohort.

They conceded that the individuals with autism spectrum disorders in this study "were compared to control subjects who had also attempted suicide" versus patients in the general population, which likely skews the significance of the prevalence of psychiatric disorders as a risk factor for suicide.

Nevertheless, "not only mood disorders but also an adjustment disorder may contribute to suicidal behavior in individuals with autism spectrum disorders," they wrote.

Dr. Kato disclosed that the study was partly funded by grants from pharmaceutical companies, including the makers of antidepressant and antipsychotic medication, and to one of the coinvestigators. The investigators disclosed no other personal conflicts of interest.

cpnews@frontlinemedcom.com

Autism spectrum disorder patients who attempt suicide are younger and more likely to have comorbid adjustment disorder, compared with suicidal patients without autism.

The findings come from what the investigators say is the "first study to compare suicide attempts in [autism spectrum disorder] and [non–autism spectrum disorder] patients in adults in the emergency department, according to Dr. Koji Kato and colleagues (Gen. Hosp. Psychiatry 2013;35:50-3).

Dr. Kato looked at 587 consecutive adult patients who attempted suicide and were hospitalized at the Advanced Critical Care Center of Tokai (Japan) University Hospital between April 2010 and December 2011.

Overall, 43 of the 587 subjects (7.3%) were found to have autism spectrum disorders, diagnosed by family history and also by administration of the Autism-Spectrum Quotient–Japanese version during hospitalization, wrote Dr. Kato of Tokai University, Kanagawa, Japan.

"Poor interpersonal problem-solving skills or impulsive behavior, which is characteristic of individuals with [autism spectrum disorders], had been linked with an increased risk of suicidal behavior among youth." -Dr. Kato, et. al. 

The researchers then began to characterize these patients in comparison with their nonautism counterparts. First, they found that patients with autism spectrum disorder were significantly younger than were their nonautism counterparts (33.7 years versus 42.5 years, respectively; P = .001) and also much more likely to be male (81.4% vs. 30.3%; P less than .001).

Similarly, more than three-quarters of the autism spectrum patients were unmarried, compared with just over one-third of nonautism patients (76.7% vs. 37.5%; P less than .001) and were in fact more likely to be living alone at the time of the attempt (41.9% vs. 18.9%; P less than .001).

Next, the authors looked at psychiatric diagnoses. They found that patients with an autism spectrum disorder were much less likely to have a diagnosis of a mood disorder, compared with their nonautism counterparts (18.6% vs. 34.2%, P = .043), although they were much more likely to have adjustment disorders (70.0% vs. 41.5%, P less than .001).

Commenting on the marked difference in age between autism spectrum disorder patients and the rest of the cohort, they wrote: "Poor interpersonal problem-solving skills or impulsive behavior, which is characteristic of individuals with [autism spectrum disorders], had been linked with an increased risk of suicidal behavior among youth."

Indeed, other research "suggests that suicidal acts are more frequent in adolescents with Asperger syndrome, perhaps due to bullying and feelings of inadequacy in coping with the social demands that occur during puberty."

Looking at the documented higher incidence of single individuals and individuals living alone in the autism spectrum disorders group "could be explained by autism spectrum disorder characteristics such as lack of social reciprocity and/or repeated failure to develop peer relationships since childhood or adolescence," they added.

Finally, they addressed the prevalence of mood and adjustment disorders among the cohort.

They conceded that the individuals with autism spectrum disorders in this study "were compared to control subjects who had also attempted suicide" versus patients in the general population, which likely skews the significance of the prevalence of psychiatric disorders as a risk factor for suicide.

Nevertheless, "not only mood disorders but also an adjustment disorder may contribute to suicidal behavior in individuals with autism spectrum disorders," they wrote.

Dr. Kato disclosed that the study was partly funded by grants from pharmaceutical companies, including the makers of antidepressant and antipsychotic medication, and to one of the coinvestigators. The investigators disclosed no other personal conflicts of interest.

cpnews@frontlinemedcom.com

Autism spectrum disorder patients who attempt suicide are younger and more likely to have comorbid adjustment disorder, compared with suicidal patients without autism.

The findings come from what the investigators say is the "first study to compare suicide attempts in [autism spectrum disorder] and [non–autism spectrum disorder] patients in adults in the emergency department, according to Dr. Koji Kato and colleagues (Gen. Hosp. Psychiatry 2013;35:50-3).

Dr. Kato looked at 587 consecutive adult patients who attempted suicide and were hospitalized at the Advanced Critical Care Center of Tokai (Japan) University Hospital between April 2010 and December 2011.

Overall, 43 of the 587 subjects (7.3%) were found to have autism spectrum disorders, diagnosed by family history and also by administration of the Autism-Spectrum Quotient–Japanese version during hospitalization, wrote Dr. Kato of Tokai University, Kanagawa, Japan.

"Poor interpersonal problem-solving skills or impulsive behavior, which is characteristic of individuals with [autism spectrum disorders], had been linked with an increased risk of suicidal behavior among youth." -Dr. Kato, et. al. 

The researchers then began to characterize these patients in comparison with their nonautism counterparts. First, they found that patients with autism spectrum disorder were significantly younger than were their nonautism counterparts (33.7 years versus 42.5 years, respectively; P = .001) and also much more likely to be male (81.4% vs. 30.3%; P less than .001).

Similarly, more than three-quarters of the autism spectrum patients were unmarried, compared with just over one-third of nonautism patients (76.7% vs. 37.5%; P less than .001) and were in fact more likely to be living alone at the time of the attempt (41.9% vs. 18.9%; P less than .001).

Next, the authors looked at psychiatric diagnoses. They found that patients with an autism spectrum disorder were much less likely to have a diagnosis of a mood disorder, compared with their nonautism counterparts (18.6% vs. 34.2%, P = .043), although they were much more likely to have adjustment disorders (70.0% vs. 41.5%, P less than .001).

Commenting on the marked difference in age between autism spectrum disorder patients and the rest of the cohort, they wrote: "Poor interpersonal problem-solving skills or impulsive behavior, which is characteristic of individuals with [autism spectrum disorders], had been linked with an increased risk of suicidal behavior among youth."

Indeed, other research "suggests that suicidal acts are more frequent in adolescents with Asperger syndrome, perhaps due to bullying and feelings of inadequacy in coping with the social demands that occur during puberty."

Looking at the documented higher incidence of single individuals and individuals living alone in the autism spectrum disorders group "could be explained by autism spectrum disorder characteristics such as lack of social reciprocity and/or repeated failure to develop peer relationships since childhood or adolescence," they added.

Finally, they addressed the prevalence of mood and adjustment disorders among the cohort.

They conceded that the individuals with autism spectrum disorders in this study "were compared to control subjects who had also attempted suicide" versus patients in the general population, which likely skews the significance of the prevalence of psychiatric disorders as a risk factor for suicide.

Nevertheless, "not only mood disorders but also an adjustment disorder may contribute to suicidal behavior in individuals with autism spectrum disorders," they wrote.

Dr. Kato disclosed that the study was partly funded by grants from pharmaceutical companies, including the makers of antidepressant and antipsychotic medication, and to one of the coinvestigators. The investigators disclosed no other personal conflicts of interest.

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