Denise Napoli

Investigational new drugs, including biologic drugs, will face new safety reporting requirements designed to increase timeliness as well as decrease unnecessary reporting of events not likely to be causal.

The changes bring the Food and Drug Administration’s reporting policies in line with international agencies, including the World Health Organization, in an effort to “help ensure harmonized reporting of globally conducted clinical trials.”

The requirements are the result of a final rule issued by the FDA and published in the Federal Register on Sept. 29.

The rule represents the culmination of work on a proposed rule, issued in 2003, and will go into effect 180 days from its publication, according to Karen Riley, an FDA spokeswoman.

Investigational new drug (IND) applications are submitted to the FDA prior to the onset of clinical trials. IND must be filed for any approval request, regardless of whether it is an application for a wholly novel compound or an application for a new indication of existing drugs, according to the agency.

Safety reports on these INDs must be submitted to the FDA and assessed by institutional review boards before clinical trials can begin.

Under the former rule, “sponsors investigating a drug ... were required to notify FDA and all participating investigators, in a written IND safety report, of any adverse experience associated with the use of the drug that was both serious and unexpected, and any finding from tests in laboratory animals that suggested a significant risk for human subjects.”

This requirement often resulted in reporting of events not likely to be associated with the drug, bogging down the agency and leading to slower recognition of truly causal effects, according to the draft guidance.

According to the new rule, rather than submitting details about all adverse events, applicants may submit only “suspected adverse reactions,” defined as events for which there is “evidence to suggest a causal relationship between the drug and the adverse event,” according to a FDA draft guidance for investigators.

For example, any “single occurrence of an event that is uncommon and known to be strongly associated with drug exposure (e.g., angioedema, hepatic injury, Stevens-Johnson syndrome)” would meet this definition, as well as “one or more occurrences of an event that is not commonly associated with drug exposure, but is otherwise uncommon in the population exposed to the drug (e.g., tendon rupture),” according to the guidance.

Other reportable findings include data concerning bioequivalence of generic biologic drugs, compared with their name-brand counterparts – for example, differing rates of absorption into the bloodstream.

Another change concerns timeliness of reporting. The new rules clarify that “expedited” reporting must occur within 15 days of the drug sponsor determining that given data meet the qualifications for reporting.

“For a serious and unexpected suspected adverse reaction from a clinical trial, this would be the day the sponsor receives information from the clinical investigator,” states the rule.

Moreover, it clarifies that “If any information necessary to evaluate and report the suspected adverse reaction is missing or unknown, the sponsor should actively seek such information.”

In a press release, Dr. Rachel E. Behrman, the associate director for medical policy at the FDA’s Center for Drug Evaluation and Research (CDER), said, “This final rule will expedite FDA’s review of critical safety information and help the agency monitor the safety of investigational drugs and biologics.”

“These changes will better protect people who are enrolled in clinical trials.”

Disclosures: None was reported.

Investigational new drugs, including biologic drugs, will face new safety reporting requirements designed to increase timeliness as well as decrease unnecessary reporting of events not likely to be causal.

The changes bring the Food and Drug Administration’s reporting policies in line with international agencies, including the World Health Organization, in an effort to “help ensure harmonized reporting of globally conducted clinical trials.”

The requirements are the result of a final rule issued by the FDA and published in the Federal Register on Sept. 29.

The rule represents the culmination of work on a proposed rule, issued in 2003, and will go into effect 180 days from its publication, according to Karen Riley, an FDA spokeswoman.

Investigational new drug (IND) applications are submitted to the FDA prior to the onset of clinical trials. IND must be filed for any approval request, regardless of whether it is an application for a wholly novel compound or an application for a new indication of existing drugs, according to the agency.

Safety reports on these INDs must be submitted to the FDA and assessed by institutional review boards before clinical trials can begin.

Under the former rule, “sponsors investigating a drug ... were required to notify FDA and all participating investigators, in a written IND safety report, of any adverse experience associated with the use of the drug that was both serious and unexpected, and any finding from tests in laboratory animals that suggested a significant risk for human subjects.”

This requirement often resulted in reporting of events not likely to be associated with the drug, bogging down the agency and leading to slower recognition of truly causal effects, according to the draft guidance.

According to the new rule, rather than submitting details about all adverse events, applicants may submit only “suspected adverse reactions,” defined as events for which there is “evidence to suggest a causal relationship between the drug and the adverse event,” according to a FDA draft guidance for investigators.

For example, any “single occurrence of an event that is uncommon and known to be strongly associated with drug exposure (e.g., angioedema, hepatic injury, Stevens-Johnson syndrome)” would meet this definition, as well as “one or more occurrences of an event that is not commonly associated with drug exposure, but is otherwise uncommon in the population exposed to the drug (e.g., tendon rupture),” according to the guidance.

Other reportable findings include data concerning bioequivalence of generic biologic drugs, compared with their name-brand counterparts – for example, differing rates of absorption into the bloodstream.

Another change concerns timeliness of reporting. The new rules clarify that “expedited” reporting must occur within 15 days of the drug sponsor determining that given data meet the qualifications for reporting.

“For a serious and unexpected suspected adverse reaction from a clinical trial, this would be the day the sponsor receives information from the clinical investigator,” states the rule.

Moreover, it clarifies that “If any information necessary to evaluate and report the suspected adverse reaction is missing or unknown, the sponsor should actively seek such information.”

In a press release, Dr. Rachel E. Behrman, the associate director for medical policy at the FDA’s Center for Drug Evaluation and Research (CDER), said, “This final rule will expedite FDA’s review of critical safety information and help the agency monitor the safety of investigational drugs and biologics.”

“These changes will better protect people who are enrolled in clinical trials.”

Disclosures: None was reported.

Investigational new drugs, including biologic drugs, will face new safety reporting requirements designed to increase timeliness as well as decrease unnecessary reporting of events not likely to be causal.

The changes bring the Food and Drug Administration’s reporting policies in line with international agencies, including the World Health Organization, in an effort to “help ensure harmonized reporting of globally conducted clinical trials.”

The requirements are the result of a final rule issued by the FDA and published in the Federal Register on Sept. 29.

The rule represents the culmination of work on a proposed rule, issued in 2003, and will go into effect 180 days from its publication, according to Karen Riley, an FDA spokeswoman.

Investigational new drug (IND) applications are submitted to the FDA prior to the onset of clinical trials. IND must be filed for any approval request, regardless of whether it is an application for a wholly novel compound or an application for a new indication of existing drugs, according to the agency.

Safety reports on these INDs must be submitted to the FDA and assessed by institutional review boards before clinical trials can begin.

Under the former rule, “sponsors investigating a drug ... were required to notify FDA and all participating investigators, in a written IND safety report, of any adverse experience associated with the use of the drug that was both serious and unexpected, and any finding from tests in laboratory animals that suggested a significant risk for human subjects.”

This requirement often resulted in reporting of events not likely to be associated with the drug, bogging down the agency and leading to slower recognition of truly causal effects, according to the draft guidance.

According to the new rule, rather than submitting details about all adverse events, applicants may submit only “suspected adverse reactions,” defined as events for which there is “evidence to suggest a causal relationship between the drug and the adverse event,” according to a FDA draft guidance for investigators.

For example, any “single occurrence of an event that is uncommon and known to be strongly associated with drug exposure (e.g., angioedema, hepatic injury, Stevens-Johnson syndrome)” would meet this definition, as well as “one or more occurrences of an event that is not commonly associated with drug exposure, but is otherwise uncommon in the population exposed to the drug (e.g., tendon rupture),” according to the guidance.

Other reportable findings include data concerning bioequivalence of generic biologic drugs, compared with their name-brand counterparts – for example, differing rates of absorption into the bloodstream.

Another change concerns timeliness of reporting. The new rules clarify that “expedited” reporting must occur within 15 days of the drug sponsor determining that given data meet the qualifications for reporting.

“For a serious and unexpected suspected adverse reaction from a clinical trial, this would be the day the sponsor receives information from the clinical investigator,” states the rule.

Moreover, it clarifies that “If any information necessary to evaluate and report the suspected adverse reaction is missing or unknown, the sponsor should actively seek such information.”

In a press release, Dr. Rachel E. Behrman, the associate director for medical policy at the FDA’s Center for Drug Evaluation and Research (CDER), said, “This final rule will expedite FDA’s review of critical safety information and help the agency monitor the safety of investigational drugs and biologics.”

“These changes will better protect people who are enrolled in clinical trials.”

Disclosures: None was reported.

Adding an oral, spleen tyrosine kinase inhibitor to an existing methotrexate regimen significantly lessened rheumatoid arthritis symptoms in patients with active disease, compared with placebo.

The results, though, were not without side effects, including hypertension, neutropenia, and diarrhea.

The phase II, double-blind, placebo-controlled study was sponsored by the drug’s maker, Rigel Pharmaceuticals, and published online Sept. 22 in the New England Journal of Medicine.

Spleen tyrosine kinase (Syk) is an intracellular cytoplasmic tyrosine kinase that is present in the synovium. It is an important mediator for “immunoreceptor signaling in macrophages, neutrophils, mast cells, and B cells,” the investigators noted. Syk inhibitors have previously been studied as therapeutic agents in cancers, including breast cancer and lymphoma.

The authors of the current study, led by Dr. Michael E. Weinblatt, codirector of the division of clinical rheumatology at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, looked at 457 patients at 64 sites around the world, specifically Bulgaria, Colombia, Mexico, Poland, Romania, and the United States. All patients met the American College of Rheumatology’s 1987 criteria for rheumatoid arthritis and had had active RA for at least 6 months prior to enrolling in the trial. The 1987 ACR criteria define “active” RA as involving six swollen joints, plus six tender joints, plus either an elevated erythrocyte sedimentation rate or an elevated C-reactive protein level.

Patients also had been receiving a “stable dose” of methotrexate for at least 3 months (between 7.5 mg and 25 mg/week), plus folic acid or folinic acid supplements.

Patients were randomized to four groups. The first group (n = 152) received the Syk inhibitor known as R788, in twice-daily doses of 100 mg. The second group (n = 152) received once-daily, 150-mg doses of the drug. The third group received placebo twice daily, and the fourth received once-daily placebo (total number of placebo patients = 153).

The majority of patients in all groups were female, and the mean age was 52 years in all groups.

Overall, 67% of patients in the R788 twice-daily, 100-mg dose group registered an ACR 20 response at 6 months; in the once-daily, 150-mg group, the response rate was 57%. Both numbers were significantly higher than among placebo patients, who had a response rate of 35% (P less than .001 for both comparisons).

The authors also found that patients taking the twice-daily Syk inhibitor responded sooner than those on the once-daily regimen or placebo. By the end of the first week, 36% of twice-daily patients had an ACR 20 response, compared with 23% in the once-daily R788 group and 14% in the placebo group (P less than .001 for the twice-daily group and P = .04 for the once-daily group, compared with placebo).

Moreover, by 6 months, 31% of the twice-daily R788 group had achieved RA remission (as defined by a Disease Activity Score–28 less than 2.6), compared with 21% in the once-daily group and 7% in the placebo group (P less than .001 for the twice-daily group, and P = .003 for the once-daily group, compared with placebo).

The therapy did have adverse events. Ten patients in the once-daily group and five in the twice-daily group withdrew, mostly because of nausea and diarrhea. There were also two serious infections in the once-daily group and five in the twice-daily group, as well as neutropenia and hypertension.

“Overall, the mean difference in the change in systolic pressure from baseline to month 1 between the combined R788 group and the placebo group was an increase of approximately 5 mm Hg in the R788 group,” wrote the authors (N. Engl. J. Med. 2010 [doi:10.1056/NEJMoa1000500]).

However, after either a reduction in R788 dose or addition of hypertensive medications, all patients experienced a drop in pressure, such that by 6 months each R788 group had less than a 1-mm Hg increase in systolic pressure over baseline.

In addition to disclosing that the study was supported by Rigel, the maker of R788, Dr. Weinblatt also reported having numerous financial relationships to pharmaceutical makers, including Rigel, as did his coauthors, three of whom are employees of Rigel and hold stock or stock options in the company.

Adding an oral, spleen tyrosine kinase inhibitor to an existing methotrexate regimen significantly lessened rheumatoid arthritis symptoms in patients with active disease, compared with placebo.

The results, though, were not without side effects, including hypertension, neutropenia, and diarrhea.

The phase II, double-blind, placebo-controlled study was sponsored by the drug’s maker, Rigel Pharmaceuticals, and published online Sept. 22 in the New England Journal of Medicine.

Spleen tyrosine kinase (Syk) is an intracellular cytoplasmic tyrosine kinase that is present in the synovium. It is an important mediator for “immunoreceptor signaling in macrophages, neutrophils, mast cells, and B cells,” the investigators noted. Syk inhibitors have previously been studied as therapeutic agents in cancers, including breast cancer and lymphoma.

The authors of the current study, led by Dr. Michael E. Weinblatt, codirector of the division of clinical rheumatology at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, looked at 457 patients at 64 sites around the world, specifically Bulgaria, Colombia, Mexico, Poland, Romania, and the United States. All patients met the American College of Rheumatology’s 1987 criteria for rheumatoid arthritis and had had active RA for at least 6 months prior to enrolling in the trial. The 1987 ACR criteria define “active” RA as involving six swollen joints, plus six tender joints, plus either an elevated erythrocyte sedimentation rate or an elevated C-reactive protein level.

Patients also had been receiving a “stable dose” of methotrexate for at least 3 months (between 7.5 mg and 25 mg/week), plus folic acid or folinic acid supplements.

Patients were randomized to four groups. The first group (n = 152) received the Syk inhibitor known as R788, in twice-daily doses of 100 mg. The second group (n = 152) received once-daily, 150-mg doses of the drug. The third group received placebo twice daily, and the fourth received once-daily placebo (total number of placebo patients = 153).

The majority of patients in all groups were female, and the mean age was 52 years in all groups.

Overall, 67% of patients in the R788 twice-daily, 100-mg dose group registered an ACR 20 response at 6 months; in the once-daily, 150-mg group, the response rate was 57%. Both numbers were significantly higher than among placebo patients, who had a response rate of 35% (P less than .001 for both comparisons).

The authors also found that patients taking the twice-daily Syk inhibitor responded sooner than those on the once-daily regimen or placebo. By the end of the first week, 36% of twice-daily patients had an ACR 20 response, compared with 23% in the once-daily R788 group and 14% in the placebo group (P less than .001 for the twice-daily group and P = .04 for the once-daily group, compared with placebo).

Moreover, by 6 months, 31% of the twice-daily R788 group had achieved RA remission (as defined by a Disease Activity Score–28 less than 2.6), compared with 21% in the once-daily group and 7% in the placebo group (P less than .001 for the twice-daily group, and P = .003 for the once-daily group, compared with placebo).

The therapy did have adverse events. Ten patients in the once-daily group and five in the twice-daily group withdrew, mostly because of nausea and diarrhea. There were also two serious infections in the once-daily group and five in the twice-daily group, as well as neutropenia and hypertension.

“Overall, the mean difference in the change in systolic pressure from baseline to month 1 between the combined R788 group and the placebo group was an increase of approximately 5 mm Hg in the R788 group,” wrote the authors (N. Engl. J. Med. 2010 [doi:10.1056/NEJMoa1000500]).

However, after either a reduction in R788 dose or addition of hypertensive medications, all patients experienced a drop in pressure, such that by 6 months each R788 group had less than a 1-mm Hg increase in systolic pressure over baseline.

In addition to disclosing that the study was supported by Rigel, the maker of R788, Dr. Weinblatt also reported having numerous financial relationships to pharmaceutical makers, including Rigel, as did his coauthors, three of whom are employees of Rigel and hold stock or stock options in the company.

Adding an oral, spleen tyrosine kinase inhibitor to an existing methotrexate regimen significantly lessened rheumatoid arthritis symptoms in patients with active disease, compared with placebo.

The results, though, were not without side effects, including hypertension, neutropenia, and diarrhea.

The phase II, double-blind, placebo-controlled study was sponsored by the drug’s maker, Rigel Pharmaceuticals, and published online Sept. 22 in the New England Journal of Medicine.

Spleen tyrosine kinase (Syk) is an intracellular cytoplasmic tyrosine kinase that is present in the synovium. It is an important mediator for “immunoreceptor signaling in macrophages, neutrophils, mast cells, and B cells,” the investigators noted. Syk inhibitors have previously been studied as therapeutic agents in cancers, including breast cancer and lymphoma.

The authors of the current study, led by Dr. Michael E. Weinblatt, codirector of the division of clinical rheumatology at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston, looked at 457 patients at 64 sites around the world, specifically Bulgaria, Colombia, Mexico, Poland, Romania, and the United States. All patients met the American College of Rheumatology’s 1987 criteria for rheumatoid arthritis and had had active RA for at least 6 months prior to enrolling in the trial. The 1987 ACR criteria define “active” RA as involving six swollen joints, plus six tender joints, plus either an elevated erythrocyte sedimentation rate or an elevated C-reactive protein level.

Patients also had been receiving a “stable dose” of methotrexate for at least 3 months (between 7.5 mg and 25 mg/week), plus folic acid or folinic acid supplements.

Patients were randomized to four groups. The first group (n = 152) received the Syk inhibitor known as R788, in twice-daily doses of 100 mg. The second group (n = 152) received once-daily, 150-mg doses of the drug. The third group received placebo twice daily, and the fourth received once-daily placebo (total number of placebo patients = 153).

The majority of patients in all groups were female, and the mean age was 52 years in all groups.

Overall, 67% of patients in the R788 twice-daily, 100-mg dose group registered an ACR 20 response at 6 months; in the once-daily, 150-mg group, the response rate was 57%. Both numbers were significantly higher than among placebo patients, who had a response rate of 35% (P less than .001 for both comparisons).

The authors also found that patients taking the twice-daily Syk inhibitor responded sooner than those on the once-daily regimen or placebo. By the end of the first week, 36% of twice-daily patients had an ACR 20 response, compared with 23% in the once-daily R788 group and 14% in the placebo group (P less than .001 for the twice-daily group and P = .04 for the once-daily group, compared with placebo).

Moreover, by 6 months, 31% of the twice-daily R788 group had achieved RA remission (as defined by a Disease Activity Score–28 less than 2.6), compared with 21% in the once-daily group and 7% in the placebo group (P less than .001 for the twice-daily group, and P = .003 for the once-daily group, compared with placebo).

The therapy did have adverse events. Ten patients in the once-daily group and five in the twice-daily group withdrew, mostly because of nausea and diarrhea. There were also two serious infections in the once-daily group and five in the twice-daily group, as well as neutropenia and hypertension.

“Overall, the mean difference in the change in systolic pressure from baseline to month 1 between the combined R788 group and the placebo group was an increase of approximately 5 mm Hg in the R788 group,” wrote the authors (N. Engl. J. Med. 2010 [doi:10.1056/NEJMoa1000500]).

However, after either a reduction in R788 dose or addition of hypertensive medications, all patients experienced a drop in pressure, such that by 6 months each R788 group had less than a 1-mm Hg increase in systolic pressure over baseline.

In addition to disclosing that the study was supported by Rigel, the maker of R788, Dr. Weinblatt also reported having numerous financial relationships to pharmaceutical makers, including Rigel, as did his coauthors, three of whom are employees of Rigel and hold stock or stock options in the company.

Roughly 20% of 12- to 19-year-olds in the United States have some form of hearing loss, up from 15% of adolescents surveyed between 1988 and 1994, a study has shown.

That represents a significant 31% jump that is likely underestimated, according to Dr. Josef Shargorodsky of the Brigham and Women's Hospital in Boston and his associates.

Dr. Shargorodsky, who is also of the Massachusetts Eye and Ear Infirmary, Boston, and his associates looked at data from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 and compared them with data from NHANES III, conducted between 1988 and 1994. Both surveys provide nationally representative data on U.S. civilians aged 12-19 years, and both surveys included audiometry testing of both high- and low-frequency hearing (JAMA 2010;304:772-8).

A total of 2,928 NHANES III participants who had full data from a complete audiometry exam were included for analysis in the more recent study; there were 1,771 participants from NHANES 2005-2006 who had complete data.

There were no differences between the groups in terms of age, race, sex, or poverty-income ratio, although NHANES III participants were more likely to have had a history of three or more ear infections.

Dr. Shargorodsky and his associates found that among NHANES III participants, surveyed between 1988 and 1994, the prevalence of any hearing loss greater than 15 dB among 12- to 19-year-olds was 15%. By the 2005-2006 survey, in contrast, that number had jumped to 20%, representing roughly 6.5 million individuals.

The increases persisted when the data were stratified by type of hearing loss. For example, 11% of NHANES III participants had unilateral hearing loss; by 2005-2006, that number had jumped to 14%. The same increase was repeated when looking only at bilateral hearing loss, with a prevalence of 4% during NHANES III and 5.5% in 2005-2006.

The investigators also found that high-frequency hearing loss (13% in 1988-1994, vs. 16% in 2005-2006) was more prevalent than low-frequency loss (6% in 1988-1994, vs. 9% in 2005-2006) in both time periods.

However, only the change in high-frequency loss was significant.

Even more significant—and more troubling—was the increased prevalence of mild or worse hearing loss (25 dB or greater) in the 2005-2006 survey (as opposed to “slight” hearing loss of between 15 and 25 dB). That figure jumped from 3.5% to 5%—or more than 1 in 20 adolescents.

Dr. Shargorodsky and his associates pointed out some limitations to their study. For one, they wrote, “children whose hearing aids could not be removed, who could not tolerate earphones, or who had cochlear implants were not tested,” although this likely contributed to underestimation of hearing loss, if anything.

Additionally, the study's cross-sectional design could not assess causality.

“Interval factors between surveys, such as vaccination against Haemophilus influenzae and Streptococcus pneumoniae, as well as greater awareness of music-induced hearing loss, may have led to the expectation of no change or a reduction in the prevalence of hearing loss, but this was not observed,” the researchers said.

Dr. Shargorodsky and his associates reported having no disclosures relevant to this study, which was funded by the Massachusetts Eye and Ear Infirmary Foundation and the Vanderbilt University.

Roughly 20% of U.S. teens have some form of hearing loss.

Source ©M&M/Fotolia.com

Roughly 20% of 12- to 19-year-olds in the United States have some form of hearing loss, up from 15% of adolescents surveyed between 1988 and 1994, a study has shown.

That represents a significant 31% jump that is likely underestimated, according to Dr. Josef Shargorodsky of the Brigham and Women's Hospital in Boston and his associates.

Dr. Shargorodsky, who is also of the Massachusetts Eye and Ear Infirmary, Boston, and his associates looked at data from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 and compared them with data from NHANES III, conducted between 1988 and 1994. Both surveys provide nationally representative data on U.S. civilians aged 12-19 years, and both surveys included audiometry testing of both high- and low-frequency hearing (JAMA 2010;304:772-8).

A total of 2,928 NHANES III participants who had full data from a complete audiometry exam were included for analysis in the more recent study; there were 1,771 participants from NHANES 2005-2006 who had complete data.

There were no differences between the groups in terms of age, race, sex, or poverty-income ratio, although NHANES III participants were more likely to have had a history of three or more ear infections.

Dr. Shargorodsky and his associates found that among NHANES III participants, surveyed between 1988 and 1994, the prevalence of any hearing loss greater than 15 dB among 12- to 19-year-olds was 15%. By the 2005-2006 survey, in contrast, that number had jumped to 20%, representing roughly 6.5 million individuals.

The increases persisted when the data were stratified by type of hearing loss. For example, 11% of NHANES III participants had unilateral hearing loss; by 2005-2006, that number had jumped to 14%. The same increase was repeated when looking only at bilateral hearing loss, with a prevalence of 4% during NHANES III and 5.5% in 2005-2006.

The investigators also found that high-frequency hearing loss (13% in 1988-1994, vs. 16% in 2005-2006) was more prevalent than low-frequency loss (6% in 1988-1994, vs. 9% in 2005-2006) in both time periods.

However, only the change in high-frequency loss was significant.

Even more significant—and more troubling—was the increased prevalence of mild or worse hearing loss (25 dB or greater) in the 2005-2006 survey (as opposed to “slight” hearing loss of between 15 and 25 dB). That figure jumped from 3.5% to 5%—or more than 1 in 20 adolescents.

Dr. Shargorodsky and his associates pointed out some limitations to their study. For one, they wrote, “children whose hearing aids could not be removed, who could not tolerate earphones, or who had cochlear implants were not tested,” although this likely contributed to underestimation of hearing loss, if anything.

Additionally, the study's cross-sectional design could not assess causality.

“Interval factors between surveys, such as vaccination against Haemophilus influenzae and Streptococcus pneumoniae, as well as greater awareness of music-induced hearing loss, may have led to the expectation of no change or a reduction in the prevalence of hearing loss, but this was not observed,” the researchers said.

Dr. Shargorodsky and his associates reported having no disclosures relevant to this study, which was funded by the Massachusetts Eye and Ear Infirmary Foundation and the Vanderbilt University.

Roughly 20% of U.S. teens have some form of hearing loss.

Source ©M&M/Fotolia.com

Roughly 20% of 12- to 19-year-olds in the United States have some form of hearing loss, up from 15% of adolescents surveyed between 1988 and 1994, a study has shown.

That represents a significant 31% jump that is likely underestimated, according to Dr. Josef Shargorodsky of the Brigham and Women's Hospital in Boston and his associates.

Dr. Shargorodsky, who is also of the Massachusetts Eye and Ear Infirmary, Boston, and his associates looked at data from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 and compared them with data from NHANES III, conducted between 1988 and 1994. Both surveys provide nationally representative data on U.S. civilians aged 12-19 years, and both surveys included audiometry testing of both high- and low-frequency hearing (JAMA 2010;304:772-8).

A total of 2,928 NHANES III participants who had full data from a complete audiometry exam were included for analysis in the more recent study; there were 1,771 participants from NHANES 2005-2006 who had complete data.

There were no differences between the groups in terms of age, race, sex, or poverty-income ratio, although NHANES III participants were more likely to have had a history of three or more ear infections.

Dr. Shargorodsky and his associates found that among NHANES III participants, surveyed between 1988 and 1994, the prevalence of any hearing loss greater than 15 dB among 12- to 19-year-olds was 15%. By the 2005-2006 survey, in contrast, that number had jumped to 20%, representing roughly 6.5 million individuals.

The increases persisted when the data were stratified by type of hearing loss. For example, 11% of NHANES III participants had unilateral hearing loss; by 2005-2006, that number had jumped to 14%. The same increase was repeated when looking only at bilateral hearing loss, with a prevalence of 4% during NHANES III and 5.5% in 2005-2006.

The investigators also found that high-frequency hearing loss (13% in 1988-1994, vs. 16% in 2005-2006) was more prevalent than low-frequency loss (6% in 1988-1994, vs. 9% in 2005-2006) in both time periods.

However, only the change in high-frequency loss was significant.

Even more significant—and more troubling—was the increased prevalence of mild or worse hearing loss (25 dB or greater) in the 2005-2006 survey (as opposed to “slight” hearing loss of between 15 and 25 dB). That figure jumped from 3.5% to 5%—or more than 1 in 20 adolescents.

Dr. Shargorodsky and his associates pointed out some limitations to their study. For one, they wrote, “children whose hearing aids could not be removed, who could not tolerate earphones, or who had cochlear implants were not tested,” although this likely contributed to underestimation of hearing loss, if anything.

Additionally, the study's cross-sectional design could not assess causality.

“Interval factors between surveys, such as vaccination against Haemophilus influenzae and Streptococcus pneumoniae, as well as greater awareness of music-induced hearing loss, may have led to the expectation of no change or a reduction in the prevalence of hearing loss, but this was not observed,” the researchers said.

Dr. Shargorodsky and his associates reported having no disclosures relevant to this study, which was funded by the Massachusetts Eye and Ear Infirmary Foundation and the Vanderbilt University.

Roughly 20% of U.S. teens have some form of hearing loss.

Source ©M&M/Fotolia.com

The median age at the time of death for white patients with muscular dystrophy is 10-12 years older than it is for black patients with the disease, according an analysis of data from all death certificates in the United States.

Moreover, in the 5 most recent years of the study’s 20-year time period, 24.5% of black males with muscular dystrophy (MD) had cardiomyopathy, compared with 12.8% of white males with the disease.

The findings, published online in the Sept. 14 issue of the journal Neurology, “might have been related to different prevalences of the various types of MD, different natural histories, or differences in environmental, genetic, or behavioral risk factors,” wrote Aileen Kenneson, Ph.D., of the Centers for Disease Control and Prevention’s National Center on Birth Defects and Developmental Disabilities, and her colleagues.

“However, it is possible that the use of corticosteroids and [noninvasive ventilation] was less common among black than white patients,” the investigators added.

Dr. Kenneson, who is currently affiliated with consulting firm McKing Consulting Corporation in Atlanta, and her associates looked at records from the National Center for Health Statistics’ Multiple Cause Mortality Files, which contain data from all death certificates in the United States, including immediate and underlying causes of death coded with the International Classification of Diseases.

The group confined their search to the period between 1986 and 2005; they excluded congenital MD from their analysis, since “the distribution of age at death [among these patients] indicated that they were clinically distinct” from other MD patient types.

Overall, there were 18,315 MD-associated deaths from 1986 through 2005; roughly three-quarters were male. The overwhelming majority (90.6%) were white, while 7.7% of deaths occurred among black patients. The remaining 1.7% were among patients identified as being from other races (Neurology 2010;75:982-9).

The authors found a significantly lower median age at death among black females with MD, compared with white females (51 years vs. 63 years, respectively).

They also noted that among white women, the proportion who were 45 years or older at death increased, from 78.7% in the first decade of the study period to 83.8% in the second decade.

“In comparison, only about 63% of black females were 45 years or older at death, and this proportion did not change over time,” the investigators wrote.

Among males, the median age at death was significantly lower among blacks than whites (23 years vs. 33 years, respectively).

The median age at death during the 20-year time span of the study increased significantly by 1.3 years annually for white males without cardiomyopathy and 0.2 years annually for those with cardiomyopathy. In contrast, the median age at death increased just 0.33 years annually for black patients without cardiomyopathy. Black patients with cardiomyopathy showed no significant gain in life expectancy at all.

The authors pointed out that although cardiomyopathy was more often reported among blacks than whites, this finding was true “even early in the study period before the widespread use of corticosteroids and [noninvasive ventilation] were likely to have had an effect.” Cardiomyopathy is a major contributor to morbidity and mortality in various types of MD.

That could mean that the increased incidence of cardiomyopathy among nonwhite patients is due to simple racial differences the course of MD, or to the higher frequency of cardiomyopathy among blacks in general, rather than a disparity in treatment.

Dr. Kenneson and her coauthors pointed out several limitations of this study. For one, she wrote, the database “did not include information about quality of life, so increases in age at death do not necessarily equate with improvements in quality of life.”

Secondly, “While the database contains some possible social effect modifiers, such as education and marital status, it does not include information to assess sufficiently other sociocultural variables, such as health insurance and family structure.”

The investigators acknowledged the potential for inaccurate data to be recorded on death certificates, although they thought the chance of this was likely remote.

Dr. Kenneson disclosed receiving research support from the CDC. Another investigator reported receiving advisory fees and research support from several pharmaceutical companies and muscular dystrophy-related support and research foundations.

The median age at the time of death for white patients with muscular dystrophy is 10-12 years older than it is for black patients with the disease, according an analysis of data from all death certificates in the United States.

Moreover, in the 5 most recent years of the study’s 20-year time period, 24.5% of black males with muscular dystrophy (MD) had cardiomyopathy, compared with 12.8% of white males with the disease.

The findings, published online in the Sept. 14 issue of the journal Neurology, “might have been related to different prevalences of the various types of MD, different natural histories, or differences in environmental, genetic, or behavioral risk factors,” wrote Aileen Kenneson, Ph.D., of the Centers for Disease Control and Prevention’s National Center on Birth Defects and Developmental Disabilities, and her colleagues.

“However, it is possible that the use of corticosteroids and [noninvasive ventilation] was less common among black than white patients,” the investigators added.

Dr. Kenneson, who is currently affiliated with consulting firm McKing Consulting Corporation in Atlanta, and her associates looked at records from the National Center for Health Statistics’ Multiple Cause Mortality Files, which contain data from all death certificates in the United States, including immediate and underlying causes of death coded with the International Classification of Diseases.

The group confined their search to the period between 1986 and 2005; they excluded congenital MD from their analysis, since “the distribution of age at death [among these patients] indicated that they were clinically distinct” from other MD patient types.

Overall, there were 18,315 MD-associated deaths from 1986 through 2005; roughly three-quarters were male. The overwhelming majority (90.6%) were white, while 7.7% of deaths occurred among black patients. The remaining 1.7% were among patients identified as being from other races (Neurology 2010;75:982-9).

The authors found a significantly lower median age at death among black females with MD, compared with white females (51 years vs. 63 years, respectively).

They also noted that among white women, the proportion who were 45 years or older at death increased, from 78.7% in the first decade of the study period to 83.8% in the second decade.

“In comparison, only about 63% of black females were 45 years or older at death, and this proportion did not change over time,” the investigators wrote.

Among males, the median age at death was significantly lower among blacks than whites (23 years vs. 33 years, respectively).

The median age at death during the 20-year time span of the study increased significantly by 1.3 years annually for white males without cardiomyopathy and 0.2 years annually for those with cardiomyopathy. In contrast, the median age at death increased just 0.33 years annually for black patients without cardiomyopathy. Black patients with cardiomyopathy showed no significant gain in life expectancy at all.

The authors pointed out that although cardiomyopathy was more often reported among blacks than whites, this finding was true “even early in the study period before the widespread use of corticosteroids and [noninvasive ventilation] were likely to have had an effect.” Cardiomyopathy is a major contributor to morbidity and mortality in various types of MD.

That could mean that the increased incidence of cardiomyopathy among nonwhite patients is due to simple racial differences the course of MD, or to the higher frequency of cardiomyopathy among blacks in general, rather than a disparity in treatment.

Dr. Kenneson and her coauthors pointed out several limitations of this study. For one, she wrote, the database “did not include information about quality of life, so increases in age at death do not necessarily equate with improvements in quality of life.”

Secondly, “While the database contains some possible social effect modifiers, such as education and marital status, it does not include information to assess sufficiently other sociocultural variables, such as health insurance and family structure.”

The investigators acknowledged the potential for inaccurate data to be recorded on death certificates, although they thought the chance of this was likely remote.

Dr. Kenneson disclosed receiving research support from the CDC. Another investigator reported receiving advisory fees and research support from several pharmaceutical companies and muscular dystrophy-related support and research foundations.

The median age at the time of death for white patients with muscular dystrophy is 10-12 years older than it is for black patients with the disease, according an analysis of data from all death certificates in the United States.

Moreover, in the 5 most recent years of the study’s 20-year time period, 24.5% of black males with muscular dystrophy (MD) had cardiomyopathy, compared with 12.8% of white males with the disease.

The findings, published online in the Sept. 14 issue of the journal Neurology, “might have been related to different prevalences of the various types of MD, different natural histories, or differences in environmental, genetic, or behavioral risk factors,” wrote Aileen Kenneson, Ph.D., of the Centers for Disease Control and Prevention’s National Center on Birth Defects and Developmental Disabilities, and her colleagues.

“However, it is possible that the use of corticosteroids and [noninvasive ventilation] was less common among black than white patients,” the investigators added.

Dr. Kenneson, who is currently affiliated with consulting firm McKing Consulting Corporation in Atlanta, and her associates looked at records from the National Center for Health Statistics’ Multiple Cause Mortality Files, which contain data from all death certificates in the United States, including immediate and underlying causes of death coded with the International Classification of Diseases.

The group confined their search to the period between 1986 and 2005; they excluded congenital MD from their analysis, since “the distribution of age at death [among these patients] indicated that they were clinically distinct” from other MD patient types.

Overall, there were 18,315 MD-associated deaths from 1986 through 2005; roughly three-quarters were male. The overwhelming majority (90.6%) were white, while 7.7% of deaths occurred among black patients. The remaining 1.7% were among patients identified as being from other races (Neurology 2010;75:982-9).

The authors found a significantly lower median age at death among black females with MD, compared with white females (51 years vs. 63 years, respectively).

They also noted that among white women, the proportion who were 45 years or older at death increased, from 78.7% in the first decade of the study period to 83.8% in the second decade.

“In comparison, only about 63% of black females were 45 years or older at death, and this proportion did not change over time,” the investigators wrote.

Among males, the median age at death was significantly lower among blacks than whites (23 years vs. 33 years, respectively).

The median age at death during the 20-year time span of the study increased significantly by 1.3 years annually for white males without cardiomyopathy and 0.2 years annually for those with cardiomyopathy. In contrast, the median age at death increased just 0.33 years annually for black patients without cardiomyopathy. Black patients with cardiomyopathy showed no significant gain in life expectancy at all.

The authors pointed out that although cardiomyopathy was more often reported among blacks than whites, this finding was true “even early in the study period before the widespread use of corticosteroids and [noninvasive ventilation] were likely to have had an effect.” Cardiomyopathy is a major contributor to morbidity and mortality in various types of MD.

That could mean that the increased incidence of cardiomyopathy among nonwhite patients is due to simple racial differences the course of MD, or to the higher frequency of cardiomyopathy among blacks in general, rather than a disparity in treatment.

Dr. Kenneson and her coauthors pointed out several limitations of this study. For one, she wrote, the database “did not include information about quality of life, so increases in age at death do not necessarily equate with improvements in quality of life.”

Secondly, “While the database contains some possible social effect modifiers, such as education and marital status, it does not include information to assess sufficiently other sociocultural variables, such as health insurance and family structure.”

The investigators acknowledged the potential for inaccurate data to be recorded on death certificates, although they thought the chance of this was likely remote.

Dr. Kenneson disclosed receiving research support from the CDC. Another investigator reported receiving advisory fees and research support from several pharmaceutical companies and muscular dystrophy-related support and research foundations.

The median age at the time of death for white patients with muscular dystrophy is 10-12 years older than it is for black patients with the disease, according an analysis of data from all death certificates in the United States.

Moreover, in the 5 most recent years of the study’s 20-year time period, 24.5% of black males with muscular dystrophy (MD) had cardiomyopathy, compared with 12.8% of white males with the disease.

The findings, published online in the Sept. 14 issue of the journal Neurology, “might have been related to different prevalences of the various types of MD, different natural histories, or differences in environmental, genetic, or behavioral risk factors,” wrote Aileen Kenneson, Ph.D., of the Centers for Disease Control and Prevention’s National Center on Birth Defects and Developmental Disabilities, and her colleagues.

“However, it is possible that the use of corticosteroids and [noninvasive ventilation] was less common among black than white patients,” the investigators added.

Dr. Kenneson, who is currently affiliated with consulting firm McKing Consulting Corporation in Atlanta, and her associates looked at records from the National Center for Health Statistics’ Multiple Cause Mortality Files, which contain data from all death certificates in the United States, including immediate and underlying causes of death coded with the International Classification of Diseases.

The group confined their search to the period between 1986 and 2005; they excluded congenital MD from their analysis, since “the distribution of age at death [among these patients] indicated that they were clinically distinct” from other MD patient types.

Overall, there were 18,315 MD-associated deaths from 1986 through 2005; roughly three-quarters were male. The overwhelming majority (90.6%) were white, while 7.7% of deaths occurred among black patients. The remaining 1.7% were among patients identified as being from other races (Neurology 2010;75:982-9).

The authors found a significantly lower median age at death among black females with MD, compared with white females (51 years vs. 63 years, respectively).

They also noted that among white women, the proportion who were 45 years or older at death increased, from 78.7% in the first decade of the study period to 83.8% in the second decade.

“In comparison, only about 63% of black females were 45 years or older at death, and this proportion did not change over time,” the investigators wrote.

Among males, the median age at death was significantly lower among blacks than whites (23 years vs. 33 years, respectively).

The median age at death during the 20-year time span of the study increased significantly by 1.3 years annually for white males without cardiomyopathy and 0.2 years annually for those with cardiomyopathy. In contrast, the median age at death increased just 0.33 years annually for black patients without cardiomyopathy. Black patients with cardiomyopathy showed no significant gain in life expectancy at all.

The authors pointed out that although cardiomyopathy was more often reported among blacks than whites, this finding was true “even early in the study period before the widespread use of corticosteroids and [noninvasive ventilation] were likely to have had an effect.” Cardiomyopathy is a major contributor to morbidity and mortality in various types of MD.

That could mean that the increased incidence of cardiomyopathy among nonwhite patients is due to simple racial differences the course of MD, or to the higher frequency of cardiomyopathy among blacks in general, rather than a disparity in treatment.

Dr. Kenneson and her coauthors pointed out several limitations of this study. For one, she wrote, the database “did not include information about quality of life, so increases in age at death do not necessarily equate with improvements in quality of life.”

Secondly, “While the database contains some possible social effect modifiers, such as education and marital status, it does not include information to assess sufficiently other sociocultural variables, such as health insurance and family structure.”

The investigators acknowledged the potential for inaccurate data to be recorded on death certificates, although they thought the chance of this was likely remote.

Dr. Kenneson disclosed receiving research support from the CDC. Another investigator reported receiving advisory fees and research support from several pharmaceutical companies and muscular dystrophy-related support and research foundations.

The median age at the time of death for white patients with muscular dystrophy is 10-12 years older than it is for black patients with the disease, according an analysis of data from all death certificates in the United States.

Moreover, in the 5 most recent years of the study’s 20-year time period, 24.5% of black males with muscular dystrophy (MD) had cardiomyopathy, compared with 12.8% of white males with the disease.

The findings, published online in the Sept. 14 issue of the journal Neurology, “might have been related to different prevalences of the various types of MD, different natural histories, or differences in environmental, genetic, or behavioral risk factors,” wrote Aileen Kenneson, Ph.D., of the Centers for Disease Control and Prevention’s National Center on Birth Defects and Developmental Disabilities, and her colleagues.

“However, it is possible that the use of corticosteroids and [noninvasive ventilation] was less common among black than white patients,” the investigators added.

Dr. Kenneson, who is currently affiliated with consulting firm McKing Consulting Corporation in Atlanta, and her associates looked at records from the National Center for Health Statistics’ Multiple Cause Mortality Files, which contain data from all death certificates in the United States, including immediate and underlying causes of death coded with the International Classification of Diseases.

The group confined their search to the period between 1986 and 2005; they excluded congenital MD from their analysis, since “the distribution of age at death [among these patients] indicated that they were clinically distinct” from other MD patient types.

Overall, there were 18,315 MD-associated deaths from 1986 through 2005; roughly three-quarters were male. The overwhelming majority (90.6%) were white, while 7.7% of deaths occurred among black patients. The remaining 1.7% were among patients identified as being from other races (Neurology 2010;75:982-9).

The authors found a significantly lower median age at death among black females with MD, compared with white females (51 years vs. 63 years, respectively).

They also noted that among white women, the proportion who were 45 years or older at death increased, from 78.7% in the first decade of the study period to 83.8% in the second decade.

“In comparison, only about 63% of black females were 45 years or older at death, and this proportion did not change over time,” the investigators wrote.

Among males, the median age at death was significantly lower among blacks than whites (23 years vs. 33 years, respectively).

The median age at death during the 20-year time span of the study increased significantly by 1.3 years annually for white males without cardiomyopathy and 0.2 years annually for those with cardiomyopathy. In contrast, the median age at death increased just 0.33 years annually for black patients without cardiomyopathy. Black patients with cardiomyopathy showed no significant gain in life expectancy at all.

The authors pointed out that although cardiomyopathy was more often reported among blacks than whites, this finding was true “even early in the study period before the widespread use of corticosteroids and [noninvasive ventilation] were likely to have had an effect.” Cardiomyopathy is a major contributor to morbidity and mortality in various types of MD.

That could mean that the increased incidence of cardiomyopathy among nonwhite patients is due to simple racial differences the course of MD, or to the higher frequency of cardiomyopathy among blacks in general, rather than a disparity in treatment.

Dr. Kenneson and her coauthors pointed out several limitations of this study. For one, she wrote, the database “did not include information about quality of life, so increases in age at death do not necessarily equate with improvements in quality of life.”

Secondly, “While the database contains some possible social effect modifiers, such as education and marital status, it does not include information to assess sufficiently other sociocultural variables, such as health insurance and family structure.”

The investigators acknowledged the potential for inaccurate data to be recorded on death certificates, although they thought the chance of this was likely remote.

Dr. Kenneson disclosed receiving research support from the CDC. Another investigator reported receiving advisory fees and research support from several pharmaceutical companies and muscular dystrophy-related support and research foundations.

The median age at the time of death for white patients with muscular dystrophy is 10-12 years older than it is for black patients with the disease, according an analysis of data from all death certificates in the United States.

Moreover, in the 5 most recent years of the study’s 20-year time period, 24.5% of black males with muscular dystrophy (MD) had cardiomyopathy, compared with 12.8% of white males with the disease.

The findings, published online in the Sept. 14 issue of the journal Neurology, “might have been related to different prevalences of the various types of MD, different natural histories, or differences in environmental, genetic, or behavioral risk factors,” wrote Aileen Kenneson, Ph.D., of the Centers for Disease Control and Prevention’s National Center on Birth Defects and Developmental Disabilities, and her colleagues.

“However, it is possible that the use of corticosteroids and [noninvasive ventilation] was less common among black than white patients,” the investigators added.

Dr. Kenneson, who is currently affiliated with consulting firm McKing Consulting Corporation in Atlanta, and her associates looked at records from the National Center for Health Statistics’ Multiple Cause Mortality Files, which contain data from all death certificates in the United States, including immediate and underlying causes of death coded with the International Classification of Diseases.

The group confined their search to the period between 1986 and 2005; they excluded congenital MD from their analysis, since “the distribution of age at death [among these patients] indicated that they were clinically distinct” from other MD patient types.

Overall, there were 18,315 MD-associated deaths from 1986 through 2005; roughly three-quarters were male. The overwhelming majority (90.6%) were white, while 7.7% of deaths occurred among black patients. The remaining 1.7% were among patients identified as being from other races (Neurology 2010;75:982-9).

The authors found a significantly lower median age at death among black females with MD, compared with white females (51 years vs. 63 years, respectively).

They also noted that among white women, the proportion who were 45 years or older at death increased, from 78.7% in the first decade of the study period to 83.8% in the second decade.

“In comparison, only about 63% of black females were 45 years or older at death, and this proportion did not change over time,” the investigators wrote.

Among males, the median age at death was significantly lower among blacks than whites (23 years vs. 33 years, respectively).

The median age at death during the 20-year time span of the study increased significantly by 1.3 years annually for white males without cardiomyopathy and 0.2 years annually for those with cardiomyopathy. In contrast, the median age at death increased just 0.33 years annually for black patients without cardiomyopathy. Black patients with cardiomyopathy showed no significant gain in life expectancy at all.

The authors pointed out that although cardiomyopathy was more often reported among blacks than whites, this finding was true “even early in the study period before the widespread use of corticosteroids and [noninvasive ventilation] were likely to have had an effect.” Cardiomyopathy is a major contributor to morbidity and mortality in various types of MD.

That could mean that the increased incidence of cardiomyopathy among nonwhite patients is due to simple racial differences the course of MD, or to the higher frequency of cardiomyopathy among blacks in general, rather than a disparity in treatment.

Dr. Kenneson and her coauthors pointed out several limitations of this study. For one, she wrote, the database “did not include information about quality of life, so increases in age at death do not necessarily equate with improvements in quality of life.”

Secondly, “While the database contains some possible social effect modifiers, such as education and marital status, it does not include information to assess sufficiently other sociocultural variables, such as health insurance and family structure.”

The investigators acknowledged the potential for inaccurate data to be recorded on death certificates, although they thought the chance of this was likely remote.

Dr. Kenneson disclosed receiving research support from the CDC. Another investigator reported receiving advisory fees and research support from several pharmaceutical companies and muscular dystrophy-related support and research foundations.

Acute pancreatitis patients with both organ failure and infected pancreatic necrosis have a risk of death that is twice as high as that of patients with one or the other complication alone, Dr. Maxim S. Petrov and colleagues reported in the September issue of Gastroenterology.

The finding, from a meta-analysis that included nearly 1,500 patients, could provide “strong justification” for revision of the Atlanta system of pancreatic disease severity, “with this worst-prognosis group being termed ‘critical’ acute pancreatitis,” wrote the authors.

Dr. Petrov and his colleagues, of the surgery department at the University of Auckland in New Zealand, searched the Medline, Scopus, and Embase databases for studies published between Jan. 1, 1993, and Aug. 1, 2009, that examined either organ failure or necrotic infection in acute pancreatitis patients. Studies that did not specifically assess in-hospital mortality were excluded.

The start date of the search, in 1993, corresponds with the publication of the Atlanta system of pancreatic disease classification, which considers local pancreatic complications and extrapancreatic organ failure to be the major determinants of severity and divides patients into “mild” and “severe” categories.

A total of 513 abstracts were identified for further investigation, and ultimately 14 papers, representing 1,478 patients with acute pancreatitis, were included. Seven of the studies were conducted in Europe, three in North America, two in Asia, and two in Central and South America (Gastroenterology 2010 Sept.1 [doi:10.1053/j.gastro.2010.06.010]).

Among the entire cohort of acute pancreatitis patients, 600 had organ failure (OF, for a prevalence of 41%), and 314 had infected pancreatic necrosis (IPN, prevalence of 21%).

Overall in-hospital mortality among the entire patient population was 13% (191 patients), according to Dr. Petrov and his colleagues. The deaths included 87 of 387 patients with OF only (mortality of 22% in this group) and 10 of 93 patients with IPN only (mortality of 11%).

However, when the researchers looked at all patients who had OF, irrespective of their IPN status, the mortality crept up to 30% (179 out of 600 total patients with OF). A similar scenario occurred among all IPN patients, including those with both IPN and OF, where the mortality hit 32% (102 out of 314 total IPN patients).

These findings are “consistent with the Atlanta classification that admits that the presence of OF and/or IPN determines severity,” wrote the authors. However, “the present study takes this further by demonstrating that both OF and IPN are equivalent determinants of severity,” a point of controversy among studies that have found OF to be the primary determinant, regardless of whether local pancreatic complications are present.

However, in patients who had both OF and IPN, mortality jumped to 43% (92 deaths out of 213 total patients with OF and IPN). This finding amounted to a highly significant relative risk of death of 1.94, compared with OF patients who did not have IPN (95% confidence interval 1.32-2.85, P = .0007).

The outcome “did not appear to depend on the number of failed distant organs, definition of OF, indications for surgery, type of study, year of publication, and study setting,” wrote the authors, although the risk was significant only in English-language studies, versus papers included in the meta-analysis that were published in other languages. Most of the 14 papers were written in English, but there was one study each written in Russian, Spanish, and Turkish.

“The determinants of disease severity in acute pancreatitis continue to be the subject of debate,” wrote Dr. Petrov. “From a practical perspective, this study identifies a subgroup of patients with acute pancreatitis with both OF and IPN who have a substantially higher mortality” than patients who have one complication or the other, or who have neither, wrote Dr. Petrov.

Acknowledgment of this special, critically ill category of patients “will improve clinical assessment of individual patients during the course of acute pancreatitis, communication between caregivers, and comparison between groups in clinical studies.”

Dr. Petrov and his colleagues reported no conflicts of interest related to this study.

Acute pancreatitis patients with both organ failure and infected pancreatic necrosis have a risk of death that is twice as high as that of patients with one or the other complication alone, Dr. Maxim S. Petrov and colleagues reported in the September issue of Gastroenterology.

The finding, from a meta-analysis that included nearly 1,500 patients, could provide “strong justification” for revision of the Atlanta system of pancreatic disease severity, “with this worst-prognosis group being termed ‘critical’ acute pancreatitis,” wrote the authors.

Dr. Petrov and his colleagues, of the surgery department at the University of Auckland in New Zealand, searched the Medline, Scopus, and Embase databases for studies published between Jan. 1, 1993, and Aug. 1, 2009, that examined either organ failure or necrotic infection in acute pancreatitis patients. Studies that did not specifically assess in-hospital mortality were excluded.

The start date of the search, in 1993, corresponds with the publication of the Atlanta system of pancreatic disease classification, which considers local pancreatic complications and extrapancreatic organ failure to be the major determinants of severity and divides patients into “mild” and “severe” categories.

A total of 513 abstracts were identified for further investigation, and ultimately 14 papers, representing 1,478 patients with acute pancreatitis, were included. Seven of the studies were conducted in Europe, three in North America, two in Asia, and two in Central and South America (Gastroenterology 2010 Sept.1 [doi:10.1053/j.gastro.2010.06.010]).

Among the entire cohort of acute pancreatitis patients, 600 had organ failure (OF, for a prevalence of 41%), and 314 had infected pancreatic necrosis (IPN, prevalence of 21%).

Overall in-hospital mortality among the entire patient population was 13% (191 patients), according to Dr. Petrov and his colleagues. The deaths included 87 of 387 patients with OF only (mortality of 22% in this group) and 10 of 93 patients with IPN only (mortality of 11%).

However, when the researchers looked at all patients who had OF, irrespective of their IPN status, the mortality crept up to 30% (179 out of 600 total patients with OF). A similar scenario occurred among all IPN patients, including those with both IPN and OF, where the mortality hit 32% (102 out of 314 total IPN patients).

These findings are “consistent with the Atlanta classification that admits that the presence of OF and/or IPN determines severity,” wrote the authors. However, “the present study takes this further by demonstrating that both OF and IPN are equivalent determinants of severity,” a point of controversy among studies that have found OF to be the primary determinant, regardless of whether local pancreatic complications are present.

However, in patients who had both OF and IPN, mortality jumped to 43% (92 deaths out of 213 total patients with OF and IPN). This finding amounted to a highly significant relative risk of death of 1.94, compared with OF patients who did not have IPN (95% confidence interval 1.32-2.85, P = .0007).

The outcome “did not appear to depend on the number of failed distant organs, definition of OF, indications for surgery, type of study, year of publication, and study setting,” wrote the authors, although the risk was significant only in English-language studies, versus papers included in the meta-analysis that were published in other languages. Most of the 14 papers were written in English, but there was one study each written in Russian, Spanish, and Turkish.

“The determinants of disease severity in acute pancreatitis continue to be the subject of debate,” wrote Dr. Petrov. “From a practical perspective, this study identifies a subgroup of patients with acute pancreatitis with both OF and IPN who have a substantially higher mortality” than patients who have one complication or the other, or who have neither, wrote Dr. Petrov.

Acknowledgment of this special, critically ill category of patients “will improve clinical assessment of individual patients during the course of acute pancreatitis, communication between caregivers, and comparison between groups in clinical studies.”

Dr. Petrov and his colleagues reported no conflicts of interest related to this study.

Acute pancreatitis patients with both organ failure and infected pancreatic necrosis have a risk of death that is twice as high as that of patients with one or the other complication alone, Dr. Maxim S. Petrov and colleagues reported in the September issue of Gastroenterology.

The finding, from a meta-analysis that included nearly 1,500 patients, could provide “strong justification” for revision of the Atlanta system of pancreatic disease severity, “with this worst-prognosis group being termed ‘critical’ acute pancreatitis,” wrote the authors.

Dr. Petrov and his colleagues, of the surgery department at the University of Auckland in New Zealand, searched the Medline, Scopus, and Embase databases for studies published between Jan. 1, 1993, and Aug. 1, 2009, that examined either organ failure or necrotic infection in acute pancreatitis patients. Studies that did not specifically assess in-hospital mortality were excluded.

The start date of the search, in 1993, corresponds with the publication of the Atlanta system of pancreatic disease classification, which considers local pancreatic complications and extrapancreatic organ failure to be the major determinants of severity and divides patients into “mild” and “severe” categories.

A total of 513 abstracts were identified for further investigation, and ultimately 14 papers, representing 1,478 patients with acute pancreatitis, were included. Seven of the studies were conducted in Europe, three in North America, two in Asia, and two in Central and South America (Gastroenterology 2010 Sept.1 [doi:10.1053/j.gastro.2010.06.010]).

Among the entire cohort of acute pancreatitis patients, 600 had organ failure (OF, for a prevalence of 41%), and 314 had infected pancreatic necrosis (IPN, prevalence of 21%).

Overall in-hospital mortality among the entire patient population was 13% (191 patients), according to Dr. Petrov and his colleagues. The deaths included 87 of 387 patients with OF only (mortality of 22% in this group) and 10 of 93 patients with IPN only (mortality of 11%).

However, when the researchers looked at all patients who had OF, irrespective of their IPN status, the mortality crept up to 30% (179 out of 600 total patients with OF). A similar scenario occurred among all IPN patients, including those with both IPN and OF, where the mortality hit 32% (102 out of 314 total IPN patients).

These findings are “consistent with the Atlanta classification that admits that the presence of OF and/or IPN determines severity,” wrote the authors. However, “the present study takes this further by demonstrating that both OF and IPN are equivalent determinants of severity,” a point of controversy among studies that have found OF to be the primary determinant, regardless of whether local pancreatic complications are present.

However, in patients who had both OF and IPN, mortality jumped to 43% (92 deaths out of 213 total patients with OF and IPN). This finding amounted to a highly significant relative risk of death of 1.94, compared with OF patients who did not have IPN (95% confidence interval 1.32-2.85, P = .0007).

The outcome “did not appear to depend on the number of failed distant organs, definition of OF, indications for surgery, type of study, year of publication, and study setting,” wrote the authors, although the risk was significant only in English-language studies, versus papers included in the meta-analysis that were published in other languages. Most of the 14 papers were written in English, but there was one study each written in Russian, Spanish, and Turkish.

“The determinants of disease severity in acute pancreatitis continue to be the subject of debate,” wrote Dr. Petrov. “From a practical perspective, this study identifies a subgroup of patients with acute pancreatitis with both OF and IPN who have a substantially higher mortality” than patients who have one complication or the other, or who have neither, wrote Dr. Petrov.

Acknowledgment of this special, critically ill category of patients “will improve clinical assessment of individual patients during the course of acute pancreatitis, communication between caregivers, and comparison between groups in clinical studies.”

Dr. Petrov and his colleagues reported no conflicts of interest related to this study.

Acute pancreatitis patients with both organ failure and infected pancreatic necrosis have a risk of death that is twice as high as that of patients with one or the other complication alone, Dr. Maxim S. Petrov and colleagues reported in the September issue of Gastroenterology.

The finding, from a meta-analysis that included nearly 1,500 patients, could provide “strong justification” for revision of the Atlanta system of pancreatic disease severity, “with this worst-prognosis group being termed ‘critical’ acute pancreatitis,” wrote the authors.

Dr. Petrov and his colleagues, of the surgery department at the University of Auckland in New Zealand, searched the Medline, Scopus, and Embase databases for studies published between Jan. 1, 1993, and Aug. 1, 2009, that examined either organ failure or necrotic infection in acute pancreatitis patients. Studies that did not specifically assess in-hospital mortality were excluded.

The start date of the search, in 1993, corresponds with the publication of the Atlanta system of pancreatic disease classification, which considers local pancreatic complications and extrapancreatic organ failure to be the major determinants of severity and divides patients into “mild” and “severe” categories.

A total of 513 abstracts were identified for further investigation, and ultimately 14 papers, representing 1,478 patients with acute pancreatitis, were included. Seven of the studies were conducted in Europe, three in North America, two in Asia, and two in Central and South America (Gastroenterology 2010 Sept.1 [doi:10.1053/j.gastro.2010.06.010]).

Among the entire cohort of acute pancreatitis patients, 600 had organ failure (OF, for a prevalence of 41%), and 314 had infected pancreatic necrosis (IPN, prevalence of 21%).

Overall in-hospital mortality among the entire patient population was 13% (191 patients), according to Dr. Petrov and his colleagues. The deaths included 87 of 387 patients with OF only (mortality of 22% in this group) and 10 of 93 patients with IPN only (mortality of 11%).

However, when the researchers looked at all patients who had OF, irrespective of their IPN status, the mortality crept up to 30% (179 out of 600 total patients with OF). A similar scenario occurred among all IPN patients, including those with both IPN and OF, where the mortality hit 32% (102 out of 314 total IPN patients).

These findings are “consistent with the Atlanta classification that admits that the presence of OF and/or IPN determines severity,” wrote the authors. However, “the present study takes this further by demonstrating that both OF and IPN are equivalent determinants of severity,” a point of controversy among studies that have found OF to be the primary determinant, regardless of whether local pancreatic complications are present.

However, in patients who had both OF and IPN, mortality jumped to 43% (92 deaths out of 213 total patients with OF and IPN). This finding amounted to a highly significant relative risk of death of 1.94, compared with OF patients who did not have IPN (95% confidence interval 1.32-2.85, P = .0007).

The outcome “did not appear to depend on the number of failed distant organs, definition of OF, indications for surgery, type of study, year of publication, and study setting,” wrote the authors, although the risk was significant only in English-language studies, versus papers included in the meta-analysis that were published in other languages. Most of the 14 papers were written in English, but there was one study each written in Russian, Spanish, and Turkish.

“The determinants of disease severity in acute pancreatitis continue to be the subject of debate,” wrote Dr. Petrov. “From a practical perspective, this study identifies a subgroup of patients with acute pancreatitis with both OF and IPN who have a substantially higher mortality” than patients who have one complication or the other, or who have neither, wrote Dr. Petrov.

Acknowledgment of this special, critically ill category of patients “will improve clinical assessment of individual patients during the course of acute pancreatitis, communication between caregivers, and comparison between groups in clinical studies.”

Dr. Petrov and his colleagues reported no conflicts of interest related to this study.

Acute pancreatitis patients with both organ failure and infected pancreatic necrosis have a risk of death that is twice as high as that of patients with one or the other complication alone, Dr. Maxim S. Petrov and colleagues reported in the September issue of Gastroenterology.

The finding, from a meta-analysis that included nearly 1,500 patients, could provide “strong justification” for revision of the Atlanta system of pancreatic disease severity, “with this worst-prognosis group being termed ‘critical’ acute pancreatitis,” wrote the authors.

Dr. Petrov and his colleagues, of the surgery department at the University of Auckland in New Zealand, searched the Medline, Scopus, and Embase databases for studies published between Jan. 1, 1993, and Aug. 1, 2009, that examined either organ failure or necrotic infection in acute pancreatitis patients. Studies that did not specifically assess in-hospital mortality were excluded.

The start date of the search, in 1993, corresponds with the publication of the Atlanta system of pancreatic disease classification, which considers local pancreatic complications and extrapancreatic organ failure to be the major determinants of severity and divides patients into “mild” and “severe” categories.

A total of 513 abstracts were identified for further investigation, and ultimately 14 papers, representing 1,478 patients with acute pancreatitis, were included. Seven of the studies were conducted in Europe, three in North America, two in Asia, and two in Central and South America (Gastroenterology 2010 Sept.1 [doi:10.1053/j.gastro.2010.06.010]).

Among the entire cohort of acute pancreatitis patients, 600 had organ failure (OF, for a prevalence of 41%), and 314 had infected pancreatic necrosis (IPN, prevalence of 21%).

Overall in-hospital mortality among the entire patient population was 13% (191 patients), according to Dr. Petrov and his colleagues. The deaths included 87 of 387 patients with OF only (mortality of 22% in this group) and 10 of 93 patients with IPN only (mortality of 11%).

However, when the researchers looked at all patients who had OF, irrespective of their IPN status, the mortality crept up to 30% (179 out of 600 total patients with OF). A similar scenario occurred among all IPN patients, including those with both IPN and OF, where the mortality hit 32% (102 out of 314 total IPN patients).

These findings are “consistent with the Atlanta classification that admits that the presence of OF and/or IPN determines severity,” wrote the authors. However, “the present study takes this further by demonstrating that both OF and IPN are equivalent determinants of severity,” a point of controversy among studies that have found OF to be the primary determinant, regardless of whether local pancreatic complications are present.

However, in patients who had both OF and IPN, mortality jumped to 43% (92 deaths out of 213 total patients with OF and IPN). This finding amounted to a highly significant relative risk of death of 1.94, compared with OF patients who did not have IPN (95% confidence interval 1.32-2.85, P = .0007).

The outcome “did not appear to depend on the number of failed distant organs, definition of OF, indications for surgery, type of study, year of publication, and study setting,” wrote the authors, although the risk was significant only in English-language studies, versus papers included in the meta-analysis that were published in other languages. Most of the 14 papers were written in English, but there was one study each written in Russian, Spanish, and Turkish.

“The determinants of disease severity in acute pancreatitis continue to be the subject of debate,” wrote Dr. Petrov. “From a practical perspective, this study identifies a subgroup of patients with acute pancreatitis with both OF and IPN who have a substantially higher mortality” than patients who have one complication or the other, or who have neither, wrote Dr. Petrov.

Acknowledgment of this special, critically ill category of patients “will improve clinical assessment of individual patients during the course of acute pancreatitis, communication between caregivers, and comparison between groups in clinical studies.”

Dr. Petrov and his colleagues reported no conflicts of interest related to this study.

Acute pancreatitis patients with both organ failure and infected pancreatic necrosis have a risk of death that is twice as high as that of patients with one or the other complication alone, Dr. Maxim S. Petrov and colleagues reported in the September issue of Gastroenterology.

The finding, from a meta-analysis that included nearly 1,500 patients, could provide “strong justification” for revision of the Atlanta system of pancreatic disease severity, “with this worst-prognosis group being termed ‘critical’ acute pancreatitis,” wrote the authors.

Dr. Petrov and his colleagues, of the surgery department at the University of Auckland in New Zealand, searched the Medline, Scopus, and Embase databases for studies published between Jan. 1, 1993, and Aug. 1, 2009, that examined either organ failure or necrotic infection in acute pancreatitis patients. Studies that did not specifically assess in-hospital mortality were excluded.

The start date of the search, in 1993, corresponds with the publication of the Atlanta system of pancreatic disease classification, which considers local pancreatic complications and extrapancreatic organ failure to be the major determinants of severity and divides patients into “mild” and “severe” categories.

A total of 513 abstracts were identified for further investigation, and ultimately 14 papers, representing 1,478 patients with acute pancreatitis, were included. Seven of the studies were conducted in Europe, three in North America, two in Asia, and two in Central and South America (Gastroenterology 2010 Sept.1 [doi:10.1053/j.gastro.2010.06.010]).

Among the entire cohort of acute pancreatitis patients, 600 had organ failure (OF, for a prevalence of 41%), and 314 had infected pancreatic necrosis (IPN, prevalence of 21%).

Overall in-hospital mortality among the entire patient population was 13% (191 patients), according to Dr. Petrov and his colleagues. The deaths included 87 of 387 patients with OF only (mortality of 22% in this group) and 10 of 93 patients with IPN only (mortality of 11%).

However, when the researchers looked at all patients who had OF, irrespective of their IPN status, the mortality crept up to 30% (179 out of 600 total patients with OF). A similar scenario occurred among all IPN patients, including those with both IPN and OF, where the mortality hit 32% (102 out of 314 total IPN patients).

These findings are “consistent with the Atlanta classification that admits that the presence of OF and/or IPN determines severity,” wrote the authors. However, “the present study takes this further by demonstrating that both OF and IPN are equivalent determinants of severity,” a point of controversy among studies that have found OF to be the primary determinant, regardless of whether local pancreatic complications are present.

However, in patients who had both OF and IPN, mortality jumped to 43% (92 deaths out of 213 total patients with OF and IPN). This finding amounted to a highly significant relative risk of death of 1.94, compared with OF patients who did not have IPN (95% confidence interval 1.32-2.85, P = .0007).

The outcome “did not appear to depend on the number of failed distant organs, definition of OF, indications for surgery, type of study, year of publication, and study setting,” wrote the authors, although the risk was significant only in English-language studies, versus papers included in the meta-analysis that were published in other languages. Most of the 14 papers were written in English, but there was one study each written in Russian, Spanish, and Turkish.

“The determinants of disease severity in acute pancreatitis continue to be the subject of debate,” wrote Dr. Petrov. “From a practical perspective, this study identifies a subgroup of patients with acute pancreatitis with both OF and IPN who have a substantially higher mortality” than patients who have one complication or the other, or who have neither, wrote Dr. Petrov.

Acknowledgment of this special, critically ill category of patients “will improve clinical assessment of individual patients during the course of acute pancreatitis, communication between caregivers, and comparison between groups in clinical studies.”

Dr. Petrov and his colleagues reported no conflicts of interest related to this study.

The proton pump inhibitor rabeprazole had a small, but significant effect in reducing laryngopharyngeal reflux symptoms after 12 weeks of treatment, Dr. Paul K.Y. Lam and colleagues reported in an article appearing in the September issue of Clinical Gastroenterology and Hepatology.

The results are in contrast to those of previous, smaller studies that did not find PPIs to be of benefit in laryngopharyngeal reflux (LPR), wrote the authors.

This study also was one of the first to use both the nine-item Reflux Symptom Index questionnaire (J. Voice 2002;16:274-7) and the Reflux Finding Score to measure both laryngopharyngeal reflux (LPR) symptoms and physical findings.

According to Dr. Lam, of the department of surgery at the University of Hong Kong, the researchers looked at patients referred to the Voice & Laryngeal Pathology Laboratory at his institution between November 2004 and June 2007. To be included in the prospective, double-blind, placebo-controlled, randomized study, patients needed to have either hoarseness, globus (a feeling of a lump in the throat), persistent throat discomfort, or frequent throat clearing for at least 1 month in the preceding year, as well as videostroboscopic evidence of LPR with a corresponding “reflux finding score” above 7.

The reflux finding score, or RFS, is “an 8-item clinical severity scale based on findings during fiberoptic laryngoscopy” that ranges from 0, indicating no abnormal findings, to 26 (Laryngoscope 2001;111:1313-7).

Participants also had to have a negative history for any upper respiratory tract infection or allergic laryngitis in the 4 weeks prior to evaluation, and could not be younger than age 18 years, have any other laryngeal pathology, or have a history of gastroesophageal x-ray or surgery. Patients who had been taking an acid suppressive drug any time during the month prior to enrollment were also excluded.

A total of 82 patients were randomized and completed the study at 6, 12, and 18 weeks follow-up. Overall, 42 patients took rabeprazole 20 mg twice daily for 12 weeks, 30 minutes prior to lunch and dinner (mean age, 46 years; 15 males), while the remaining 40 subjects were given placebo (mean age, 47 years; 8 males).

All patients also were taught to abstain from caffeine, alcohol, smoking, spicy food, and other potential triggers of reflux. They were advised to avoid eating less than 3 hours before bedtime and to drink plenty of water.

“Patients in the rabeprazole group had a significantly reduced total RSI score at week 6 (-3.03 +/-1.05, p = 0.003) and at week 12 (-3.73 +/- 1.18, p = 0.002) compared to the placebo group,” wrote the authors.

However, the improvement on the RSI did not persist at week 18, which was 6 weeks following conclusion of the PPI regimen (-1.48 +/- 1.26, p = 0.124).

In contrast, when looking at physical improvement as measured on the RFS, there was no significant difference between groups at weeks 6, 12, or 18, with significance set at the 0.01 level.

Rather, both groups showed improvement, possibly due to the effects of education regarding abstinence from smoking, alcohol, and caffeine, although “this did not translate into significant improvement in RSI in the placebo patient group.”

Indeed, within the rabeprazole group, Dr. Lam did find improvement from baseline at both week 12 (-2.21 +/- 0.64. p = 0.002) and week 18 (-3.21 +/- 0.57, p = 0.0001), especially relating to laryngeal and vocal cord edema.

Dr. Lam and colleagues conceded that “Despite the improvement in both RSI and RFS in the rabeprazole group at week 12, the actual change was not much (only 2.81 and 2.21, respectively).”

Furthermore, total average scores for both the RSI and the RFS were still high even after 12 weeks of therapy with rabeprazole, “with RSI score well above 10 and RFS more than 7” which was positive for a laryngopharyngeal reflux condition.

The authors disclosed that the study was partially sponsored by the developer of rabeprazole, Esai Co. Ltd. The researchers reported having no conflicts to disclose in relation to the study.

The proton pump inhibitor rabeprazole had a small, but significant effect in reducing laryngopharyngeal reflux symptoms after 12 weeks of treatment, Dr. Paul K.Y. Lam and colleagues reported in an article appearing in the September issue of Clinical Gastroenterology and Hepatology.

The results are in contrast to those of previous, smaller studies that did not find PPIs to be of benefit in laryngopharyngeal reflux (LPR), wrote the authors.

This study also was one of the first to use both the nine-item Reflux Symptom Index questionnaire (J. Voice 2002;16:274-7) and the Reflux Finding Score to measure both laryngopharyngeal reflux (LPR) symptoms and physical findings.

According to Dr. Lam, of the department of surgery at the University of Hong Kong, the researchers looked at patients referred to the Voice & Laryngeal Pathology Laboratory at his institution between November 2004 and June 2007. To be included in the prospective, double-blind, placebo-controlled, randomized study, patients needed to have either hoarseness, globus (a feeling of a lump in the throat), persistent throat discomfort, or frequent throat clearing for at least 1 month in the preceding year, as well as videostroboscopic evidence of LPR with a corresponding “reflux finding score” above 7.

The reflux finding score, or RFS, is “an 8-item clinical severity scale based on findings during fiberoptic laryngoscopy” that ranges from 0, indicating no abnormal findings, to 26 (Laryngoscope 2001;111:1313-7).

Participants also had to have a negative history for any upper respiratory tract infection or allergic laryngitis in the 4 weeks prior to evaluation, and could not be younger than age 18 years, have any other laryngeal pathology, or have a history of gastroesophageal x-ray or surgery. Patients who had been taking an acid suppressive drug any time during the month prior to enrollment were also excluded.

A total of 82 patients were randomized and completed the study at 6, 12, and 18 weeks follow-up. Overall, 42 patients took rabeprazole 20 mg twice daily for 12 weeks, 30 minutes prior to lunch and dinner (mean age, 46 years; 15 males), while the remaining 40 subjects were given placebo (mean age, 47 years; 8 males).

All patients also were taught to abstain from caffeine, alcohol, smoking, spicy food, and other potential triggers of reflux. They were advised to avoid eating less than 3 hours before bedtime and to drink plenty of water.

“Patients in the rabeprazole group had a significantly reduced total RSI score at week 6 (-3.03 +/-1.05, p = 0.003) and at week 12 (-3.73 +/- 1.18, p = 0.002) compared to the placebo group,” wrote the authors.

However, the improvement on the RSI did not persist at week 18, which was 6 weeks following conclusion of the PPI regimen (-1.48 +/- 1.26, p = 0.124).

In contrast, when looking at physical improvement as measured on the RFS, there was no significant difference between groups at weeks 6, 12, or 18, with significance set at the 0.01 level.

Rather, both groups showed improvement, possibly due to the effects of education regarding abstinence from smoking, alcohol, and caffeine, although “this did not translate into significant improvement in RSI in the placebo patient group.”

Indeed, within the rabeprazole group, Dr. Lam did find improvement from baseline at both week 12 (-2.21 +/- 0.64. p = 0.002) and week 18 (-3.21 +/- 0.57, p = 0.0001), especially relating to laryngeal and vocal cord edema.

Dr. Lam and colleagues conceded that “Despite the improvement in both RSI and RFS in the rabeprazole group at week 12, the actual change was not much (only 2.81 and 2.21, respectively).”

Furthermore, total average scores for both the RSI and the RFS were still high even after 12 weeks of therapy with rabeprazole, “with RSI score well above 10 and RFS more than 7” which was positive for a laryngopharyngeal reflux condition.

The authors disclosed that the study was partially sponsored by the developer of rabeprazole, Esai Co. Ltd. The researchers reported having no conflicts to disclose in relation to the study.

The proton pump inhibitor rabeprazole had a small, but significant effect in reducing laryngopharyngeal reflux symptoms after 12 weeks of treatment, Dr. Paul K.Y. Lam and colleagues reported in an article appearing in the September issue of Clinical Gastroenterology and Hepatology.

The results are in contrast to those of previous, smaller studies that did not find PPIs to be of benefit in laryngopharyngeal reflux (LPR), wrote the authors.

This study also was one of the first to use both the nine-item Reflux Symptom Index questionnaire (J. Voice 2002;16:274-7) and the Reflux Finding Score to measure both laryngopharyngeal reflux (LPR) symptoms and physical findings.

According to Dr. Lam, of the department of surgery at the University of Hong Kong, the researchers looked at patients referred to the Voice & Laryngeal Pathology Laboratory at his institution between November 2004 and June 2007. To be included in the prospective, double-blind, placebo-controlled, randomized study, patients needed to have either hoarseness, globus (a feeling of a lump in the throat), persistent throat discomfort, or frequent throat clearing for at least 1 month in the preceding year, as well as videostroboscopic evidence of LPR with a corresponding “reflux finding score” above 7.

The reflux finding score, or RFS, is “an 8-item clinical severity scale based on findings during fiberoptic laryngoscopy” that ranges from 0, indicating no abnormal findings, to 26 (Laryngoscope 2001;111:1313-7).

Participants also had to have a negative history for any upper respiratory tract infection or allergic laryngitis in the 4 weeks prior to evaluation, and could not be younger than age 18 years, have any other laryngeal pathology, or have a history of gastroesophageal x-ray or surgery. Patients who had been taking an acid suppressive drug any time during the month prior to enrollment were also excluded.

A total of 82 patients were randomized and completed the study at 6, 12, and 18 weeks follow-up. Overall, 42 patients took rabeprazole 20 mg twice daily for 12 weeks, 30 minutes prior to lunch and dinner (mean age, 46 years; 15 males), while the remaining 40 subjects were given placebo (mean age, 47 years; 8 males).

All patients also were taught to abstain from caffeine, alcohol, smoking, spicy food, and other potential triggers of reflux. They were advised to avoid eating less than 3 hours before bedtime and to drink plenty of water.

“Patients in the rabeprazole group had a significantly reduced total RSI score at week 6 (-3.03 +/-1.05, p = 0.003) and at week 12 (-3.73 +/- 1.18, p = 0.002) compared to the placebo group,” wrote the authors.

However, the improvement on the RSI did not persist at week 18, which was 6 weeks following conclusion of the PPI regimen (-1.48 +/- 1.26, p = 0.124).

In contrast, when looking at physical improvement as measured on the RFS, there was no significant difference between groups at weeks 6, 12, or 18, with significance set at the 0.01 level.

Rather, both groups showed improvement, possibly due to the effects of education regarding abstinence from smoking, alcohol, and caffeine, although “this did not translate into significant improvement in RSI in the placebo patient group.”

Indeed, within the rabeprazole group, Dr. Lam did find improvement from baseline at both week 12 (-2.21 +/- 0.64. p = 0.002) and week 18 (-3.21 +/- 0.57, p = 0.0001), especially relating to laryngeal and vocal cord edema.

Dr. Lam and colleagues conceded that “Despite the improvement in both RSI and RFS in the rabeprazole group at week 12, the actual change was not much (only 2.81 and 2.21, respectively).”

Furthermore, total average scores for both the RSI and the RFS were still high even after 12 weeks of therapy with rabeprazole, “with RSI score well above 10 and RFS more than 7” which was positive for a laryngopharyngeal reflux condition.

The authors disclosed that the study was partially sponsored by the developer of rabeprazole, Esai Co. Ltd. The researchers reported having no conflicts to disclose in relation to the study.

The proton pump inhibitor rabeprazole had a small, but significant effect in reducing laryngopharyngeal reflux symptoms after 12 weeks of treatment, Dr. Paul K.Y. Lam and colleagues reported in an article appearing in the September issue of Clinical Gastroenterology and Hepatology.

The results are in contrast to those of previous, smaller studies that did not find PPIs to be of benefit in laryngopharyngeal reflux (LPR), wrote the authors.

This study also was one of the first to use both the nine-item Reflux Symptom Index questionnaire (J. Voice 2002;16:274-7) and the Reflux Finding Score to measure both laryngopharyngeal reflux (LPR) symptoms and physical findings.

According to Dr. Lam, of the department of surgery at the University of Hong Kong, the researchers looked at patients referred to the Voice & Laryngeal Pathology Laboratory at his institution between November 2004 and June 2007. To be included in the prospective, double-blind, placebo-controlled, randomized study, patients needed to have either hoarseness, globus (a feeling of a lump in the throat), persistent throat discomfort, or frequent throat clearing for at least 1 month in the preceding year, as well as videostroboscopic evidence of LPR with a corresponding “reflux finding score” above 7.

The reflux finding score, or RFS, is “an 8-item clinical severity scale based on findings during fiberoptic laryngoscopy” that ranges from 0, indicating no abnormal findings, to 26 (Laryngoscope 2001;111:1313-7).

Participants also had to have a negative history for any upper respiratory tract infection or allergic laryngitis in the 4 weeks prior to evaluation, and could not be younger than age 18 years, have any other laryngeal pathology, or have a history of gastroesophageal x-ray or surgery. Patients who had been taking an acid suppressive drug any time during the month prior to enrollment were also excluded.

A total of 82 patients were randomized and completed the study at 6, 12, and 18 weeks follow-up. Overall, 42 patients took rabeprazole 20 mg twice daily for 12 weeks, 30 minutes prior to lunch and dinner (mean age, 46 years; 15 males), while the remaining 40 subjects were given placebo (mean age, 47 years; 8 males).

All patients also were taught to abstain from caffeine, alcohol, smoking, spicy food, and other potential triggers of reflux. They were advised to avoid eating less than 3 hours before bedtime and to drink plenty of water.

“Patients in the rabeprazole group had a significantly reduced total RSI score at week 6 (-3.03 +/-1.05, p = 0.003) and at week 12 (-3.73 +/- 1.18, p = 0.002) compared to the placebo group,” wrote the authors.

However, the improvement on the RSI did not persist at week 18, which was 6 weeks following conclusion of the PPI regimen (-1.48 +/- 1.26, p = 0.124).

In contrast, when looking at physical improvement as measured on the RFS, there was no significant difference between groups at weeks 6, 12, or 18, with significance set at the 0.01 level.

Rather, both groups showed improvement, possibly due to the effects of education regarding abstinence from smoking, alcohol, and caffeine, although “this did not translate into significant improvement in RSI in the placebo patient group.”

Indeed, within the rabeprazole group, Dr. Lam did find improvement from baseline at both week 12 (-2.21 +/- 0.64. p = 0.002) and week 18 (-3.21 +/- 0.57, p = 0.0001), especially relating to laryngeal and vocal cord edema.

Dr. Lam and colleagues conceded that “Despite the improvement in both RSI and RFS in the rabeprazole group at week 12, the actual change was not much (only 2.81 and 2.21, respectively).”

Furthermore, total average scores for both the RSI and the RFS were still high even after 12 weeks of therapy with rabeprazole, “with RSI score well above 10 and RFS more than 7” which was positive for a laryngopharyngeal reflux condition.

The authors disclosed that the study was partially sponsored by the developer of rabeprazole, Esai Co. Ltd. The researchers reported having no conflicts to disclose in relation to the study.

The proton pump inhibitor rabeprazole had a small, but significant effect in reducing laryngopharyngeal reflux symptoms after 12 weeks of treatment, Dr. Paul K.Y. Lam and colleagues reported in an article appearing in the September issue of Clinical Gastroenterology and Hepatology.

The results are in contrast to those of previous, smaller studies that did not find PPIs to be of benefit in laryngopharyngeal reflux (LPR), wrote the authors.

This study also was one of the first to use both the nine-item Reflux Symptom Index questionnaire (J. Voice 2002;16:274-7) and the Reflux Finding Score to measure both laryngopharyngeal reflux (LPR) symptoms and physical findings.

According to Dr. Lam, of the department of surgery at the University of Hong Kong, the researchers looked at patients referred to the Voice & Laryngeal Pathology Laboratory at his institution between November 2004 and June 2007. To be included in the prospective, double-blind, placebo-controlled, randomized study, patients needed to have either hoarseness, globus (a feeling of a lump in the throat), persistent throat discomfort, or frequent throat clearing for at least 1 month in the preceding year, as well as videostroboscopic evidence of LPR with a corresponding “reflux finding score” above 7.

The reflux finding score, or RFS, is “an 8-item clinical severity scale based on findings during fiberoptic laryngoscopy” that ranges from 0, indicating no abnormal findings, to 26 (Laryngoscope 2001;111:1313-7).

Participants also had to have a negative history for any upper respiratory tract infection or allergic laryngitis in the 4 weeks prior to evaluation, and could not be younger than age 18 years, have any other laryngeal pathology, or have a history of gastroesophageal x-ray or surgery. Patients who had been taking an acid suppressive drug any time during the month prior to enrollment were also excluded.

A total of 82 patients were randomized and completed the study at 6, 12, and 18 weeks follow-up. Overall, 42 patients took rabeprazole 20 mg twice daily for 12 weeks, 30 minutes prior to lunch and dinner (mean age, 46 years; 15 males), while the remaining 40 subjects were given placebo (mean age, 47 years; 8 males).

All patients also were taught to abstain from caffeine, alcohol, smoking, spicy food, and other potential triggers of reflux. They were advised to avoid eating less than 3 hours before bedtime and to drink plenty of water.

“Patients in the rabeprazole group had a significantly reduced total RSI score at week 6 (-3.03 +/-1.05, p = 0.003) and at week 12 (-3.73 +/- 1.18, p = 0.002) compared to the placebo group,” wrote the authors.

However, the improvement on the RSI did not persist at week 18, which was 6 weeks following conclusion of the PPI regimen (-1.48 +/- 1.26, p = 0.124).

In contrast, when looking at physical improvement as measured on the RFS, there was no significant difference between groups at weeks 6, 12, or 18, with significance set at the 0.01 level.

Rather, both groups showed improvement, possibly due to the effects of education regarding abstinence from smoking, alcohol, and caffeine, although “this did not translate into significant improvement in RSI in the placebo patient group.”

Indeed, within the rabeprazole group, Dr. Lam did find improvement from baseline at both week 12 (-2.21 +/- 0.64. p = 0.002) and week 18 (-3.21 +/- 0.57, p = 0.0001), especially relating to laryngeal and vocal cord edema.

Dr. Lam and colleagues conceded that “Despite the improvement in both RSI and RFS in the rabeprazole group at week 12, the actual change was not much (only 2.81 and 2.21, respectively).”

Furthermore, total average scores for both the RSI and the RFS were still high even after 12 weeks of therapy with rabeprazole, “with RSI score well above 10 and RFS more than 7” which was positive for a laryngopharyngeal reflux condition.

The authors disclosed that the study was partially sponsored by the developer of rabeprazole, Esai Co. Ltd. The researchers reported having no conflicts to disclose in relation to the study.

The proton pump inhibitor rabeprazole had a small, but significant effect in reducing laryngopharyngeal reflux symptoms after 12 weeks of treatment, Dr. Paul K.Y. Lam and colleagues reported in an article appearing in the September issue of Clinical Gastroenterology and Hepatology.

The results are in contrast to those of previous, smaller studies that did not find PPIs to be of benefit in laryngopharyngeal reflux (LPR), wrote the authors.

This study also was one of the first to use both the nine-item Reflux Symptom Index questionnaire (J. Voice 2002;16:274-7) and the Reflux Finding Score to measure both laryngopharyngeal reflux (LPR) symptoms and physical findings.

According to Dr. Lam, of the department of surgery at the University of Hong Kong, the researchers looked at patients referred to the Voice & Laryngeal Pathology Laboratory at his institution between November 2004 and June 2007. To be included in the prospective, double-blind, placebo-controlled, randomized study, patients needed to have either hoarseness, globus (a feeling of a lump in the throat), persistent throat discomfort, or frequent throat clearing for at least 1 month in the preceding year, as well as videostroboscopic evidence of LPR with a corresponding “reflux finding score” above 7.

The reflux finding score, or RFS, is “an 8-item clinical severity scale based on findings during fiberoptic laryngoscopy” that ranges from 0, indicating no abnormal findings, to 26 (Laryngoscope 2001;111:1313-7).

Participants also had to have a negative history for any upper respiratory tract infection or allergic laryngitis in the 4 weeks prior to evaluation, and could not be younger than age 18 years, have any other laryngeal pathology, or have a history of gastroesophageal x-ray or surgery. Patients who had been taking an acid suppressive drug any time during the month prior to enrollment were also excluded.

A total of 82 patients were randomized and completed the study at 6, 12, and 18 weeks follow-up. Overall, 42 patients took rabeprazole 20 mg twice daily for 12 weeks, 30 minutes prior to lunch and dinner (mean age, 46 years; 15 males), while the remaining 40 subjects were given placebo (mean age, 47 years; 8 males).

All patients also were taught to abstain from caffeine, alcohol, smoking, spicy food, and other potential triggers of reflux. They were advised to avoid eating less than 3 hours before bedtime and to drink plenty of water.

“Patients in the rabeprazole group had a significantly reduced total RSI score at week 6 (-3.03 +/-1.05, p = 0.003) and at week 12 (-3.73 +/- 1.18, p = 0.002) compared to the placebo group,” wrote the authors.

However, the improvement on the RSI did not persist at week 18, which was 6 weeks following conclusion of the PPI regimen (-1.48 +/- 1.26, p = 0.124).

In contrast, when looking at physical improvement as measured on the RFS, there was no significant difference between groups at weeks 6, 12, or 18, with significance set at the 0.01 level.

Rather, both groups showed improvement, possibly due to the effects of education regarding abstinence from smoking, alcohol, and caffeine, although “this did not translate into significant improvement in RSI in the placebo patient group.”

Indeed, within the rabeprazole group, Dr. Lam did find improvement from baseline at both week 12 (-2.21 +/- 0.64. p = 0.002) and week 18 (-3.21 +/- 0.57, p = 0.0001), especially relating to laryngeal and vocal cord edema.

Dr. Lam and colleagues conceded that “Despite the improvement in both RSI and RFS in the rabeprazole group at week 12, the actual change was not much (only 2.81 and 2.21, respectively).”

Furthermore, total average scores for both the RSI and the RFS were still high even after 12 weeks of therapy with rabeprazole, “with RSI score well above 10 and RFS more than 7” which was positive for a laryngopharyngeal reflux condition.

The authors disclosed that the study was partially sponsored by the developer of rabeprazole, Esai Co. Ltd. The researchers reported having no conflicts to disclose in relation to the study.

In patients with hepatitis C genotype 2 or 3, a polymorphism in the region of the interleukin 28B gene on chromosome 19 was associated with a sustained virologic response following treatment with peginterferon-alpha and ribavirin, Dr. Alessandra Mangia and her colleagues reported in the September issue of Gastroenterology.

The finding mirrors similar results among genotype 1 hepatitis C patients with the mutation, who are more than twice as likely to respond to prolonged treatment as patients without it, and could point to a “potential role for IL28B genotyping in selecting non-[rapid virologic response] patients for standard 24-week therapy or more prolonged therapy,” she and her colleagues wrote.

Dr. Mangia, of the liver unit at the IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy, studied 213 genotype 2 patients and 55 genotype 3 patients, for a total of 268 patients with hepatitis C, in a multicenter, randomized controlled trial (Gastroenterology 2010 Sept 1 [doi:10.1053/j.gastro.2010.05.079]).

Patients were randomly assigned to either standard 24-week therapy (68 patients) or “variable” treatment, which depended on their response (200 patients). The 122 patients in the variable treatment group who had a rapid virologic response at week 4 received treatment for 12 weeks, while the remaining 78 underwent 24 weeks of therapy. Rapid virologic response was defined as undetectable serum/plasma hepatitis C RNA, according to an assay that has a lower limit of detection of less than 50 IU/mL.

All patients received peginterferon alpha-2b, 1.0 mcg/kg/wk, plus ribavirin, 1,000 mg daily (1,200 mg if body weight was greater than 75 kg).

The researchers then determined the patient genotypes. “The genomic region associated with hepatitis C virus treatment response lies on chromosome 19 and contains multiple [single nucleotide polymorphisms, or SNPs] in linkage disequilibrium around the IL28B gene,” they wrote. “We selected the most strongly associated SNP, rs12979860, located 3 [kilobases] upstream of the IL28B gene, for genotyping in the cohorts.”

Patients could be either homozygous for the gene (CC), heterozygous (CT), or not have it at all (TT).

For all the genotypes combined, 201 patients (75%) attained a sustained virologic response: 51/68 (75%) in the standard treatment arm and 150/200 (75%) in the two variable treatment arms combined, they wrote.

Within the variable treatment arms, 98/122 (80%) of rapid response patients in the 12-week arm had a sustained response, and 52/78 (67%) of the non-rapid response patients in the 24-week arm attained a sustained virologic response (P = .1).

However, when patients were stratified according to genotype, Dr. Mangia found that 82% of those with the CC genotype had a sustained virologic response, compared with 75% with the CT genotype and 58% with the TT genotype (odds ratio 1.8, 95% confidence interval 1.2-2.7, P = .0046).

Moreover, although roughly equivalent proportions of each genotype had a rapid virologic response (165 patients total; 53%, 66%, and 59% for CC, CT, and TT patients, respectively), this effect was “largely driven” by those patients in the variable treatment arm who did not have a rapid response, wrote the authors.

Indeed, among those patients who did not have a rapid response, the link between CC genotype and sustained response was even stronger (87% of CC patients, vs. 67% of CT patients, vs. 29% of TT patients; OR 4.0, 95% CI 1.9-8.5, P = .0002).

The link was independent of whether the patient had hepatitis C genotype 2 or genotype 3.

Current guidelines recommend 12 weeks of therapy for all hepatitis C genotype 2 and 3 patients with a low viral load, irrespective of their IL28B status, according to the authors.

“It is tempting to speculate that such treatment would be most suitable for CC patients,” they said, but “prospective studies randomizing patients according to IL28B-type will be necessary.”

Several authors, not including Dr. Mangia, disclosed that they are coinventors of a patent application based on IL28B. The researchers also reported financial and research support from the Duke Clinical Research Institute, Richard B. Boebel Family Fund, National Health and Medical Research Council of Australia, Gastroenterology Society of Australia, and Royal Australasian College of Physicians.

In patients with hepatitis C genotype 2 or 3, a polymorphism in the region of the interleukin 28B gene on chromosome 19 was associated with a sustained virologic response following treatment with peginterferon-alpha and ribavirin, Dr. Alessandra Mangia and her colleagues reported in the September issue of Gastroenterology.

The finding mirrors similar results among genotype 1 hepatitis C patients with the mutation, who are more than twice as likely to respond to prolonged treatment as patients without it, and could point to a “potential role for IL28B genotyping in selecting non-[rapid virologic response] patients for standard 24-week therapy or more prolonged therapy,” she and her colleagues wrote.

Dr. Mangia, of the liver unit at the IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy, studied 213 genotype 2 patients and 55 genotype 3 patients, for a total of 268 patients with hepatitis C, in a multicenter, randomized controlled trial (Gastroenterology 2010 Sept 1 [doi:10.1053/j.gastro.2010.05.079]).

Patients were randomly assigned to either standard 24-week therapy (68 patients) or “variable” treatment, which depended on their response (200 patients). The 122 patients in the variable treatment group who had a rapid virologic response at week 4 received treatment for 12 weeks, while the remaining 78 underwent 24 weeks of therapy. Rapid virologic response was defined as undetectable serum/plasma hepatitis C RNA, according to an assay that has a lower limit of detection of less than 50 IU/mL.

All patients received peginterferon alpha-2b, 1.0 mcg/kg/wk, plus ribavirin, 1,000 mg daily (1,200 mg if body weight was greater than 75 kg).

The researchers then determined the patient genotypes. “The genomic region associated with hepatitis C virus treatment response lies on chromosome 19 and contains multiple [single nucleotide polymorphisms, or SNPs] in linkage disequilibrium around the IL28B gene,” they wrote. “We selected the most strongly associated SNP, rs12979860, located 3 [kilobases] upstream of the IL28B gene, for genotyping in the cohorts.”

Patients could be either homozygous for the gene (CC), heterozygous (CT), or not have it at all (TT).

For all the genotypes combined, 201 patients (75%) attained a sustained virologic response: 51/68 (75%) in the standard treatment arm and 150/200 (75%) in the two variable treatment arms combined, they wrote.

Within the variable treatment arms, 98/122 (80%) of rapid response patients in the 12-week arm had a sustained response, and 52/78 (67%) of the non-rapid response patients in the 24-week arm attained a sustained virologic response (P = .1).

However, when patients were stratified according to genotype, Dr. Mangia found that 82% of those with the CC genotype had a sustained virologic response, compared with 75% with the CT genotype and 58% with the TT genotype (odds ratio 1.8, 95% confidence interval 1.2-2.7, P = .0046).

Moreover, although roughly equivalent proportions of each genotype had a rapid virologic response (165 patients total; 53%, 66%, and 59% for CC, CT, and TT patients, respectively), this effect was “largely driven” by those patients in the variable treatment arm who did not have a rapid response, wrote the authors.

Indeed, among those patients who did not have a rapid response, the link between CC genotype and sustained response was even stronger (87% of CC patients, vs. 67% of CT patients, vs. 29% of TT patients; OR 4.0, 95% CI 1.9-8.5, P = .0002).

The link was independent of whether the patient had hepatitis C genotype 2 or genotype 3.

Current guidelines recommend 12 weeks of therapy for all hepatitis C genotype 2 and 3 patients with a low viral load, irrespective of their IL28B status, according to the authors.

“It is tempting to speculate that such treatment would be most suitable for CC patients,” they said, but “prospective studies randomizing patients according to IL28B-type will be necessary.”

Several authors, not including Dr. Mangia, disclosed that they are coinventors of a patent application based on IL28B. The researchers also reported financial and research support from the Duke Clinical Research Institute, Richard B. Boebel Family Fund, National Health and Medical Research Council of Australia, Gastroenterology Society of Australia, and Royal Australasian College of Physicians.

In patients with hepatitis C genotype 2 or 3, a polymorphism in the region of the interleukin 28B gene on chromosome 19 was associated with a sustained virologic response following treatment with peginterferon-alpha and ribavirin, Dr. Alessandra Mangia and her colleagues reported in the September issue of Gastroenterology.

The finding mirrors similar results among genotype 1 hepatitis C patients with the mutation, who are more than twice as likely to respond to prolonged treatment as patients without it, and could point to a “potential role for IL28B genotyping in selecting non-[rapid virologic response] patients for standard 24-week therapy or more prolonged therapy,” she and her colleagues wrote.

Dr. Mangia, of the liver unit at the IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy, studied 213 genotype 2 patients and 55 genotype 3 patients, for a total of 268 patients with hepatitis C, in a multicenter, randomized controlled trial (Gastroenterology 2010 Sept 1 [doi:10.1053/j.gastro.2010.05.079]).

Patients were randomly assigned to either standard 24-week therapy (68 patients) or “variable” treatment, which depended on their response (200 patients). The 122 patients in the variable treatment group who had a rapid virologic response at week 4 received treatment for 12 weeks, while the remaining 78 underwent 24 weeks of therapy. Rapid virologic response was defined as undetectable serum/plasma hepatitis C RNA, according to an assay that has a lower limit of detection of less than 50 IU/mL.

All patients received peginterferon alpha-2b, 1.0 mcg/kg/wk, plus ribavirin, 1,000 mg daily (1,200 mg if body weight was greater than 75 kg).

The researchers then determined the patient genotypes. “The genomic region associated with hepatitis C virus treatment response lies on chromosome 19 and contains multiple [single nucleotide polymorphisms, or SNPs] in linkage disequilibrium around the IL28B gene,” they wrote. “We selected the most strongly associated SNP, rs12979860, located 3 [kilobases] upstream of the IL28B gene, for genotyping in the cohorts.”

Patients could be either homozygous for the gene (CC), heterozygous (CT), or not have it at all (TT).

For all the genotypes combined, 201 patients (75%) attained a sustained virologic response: 51/68 (75%) in the standard treatment arm and 150/200 (75%) in the two variable treatment arms combined, they wrote.

Within the variable treatment arms, 98/122 (80%) of rapid response patients in the 12-week arm had a sustained response, and 52/78 (67%) of the non-rapid response patients in the 24-week arm attained a sustained virologic response (P = .1).

However, when patients were stratified according to genotype, Dr. Mangia found that 82% of those with the CC genotype had a sustained virologic response, compared with 75% with the CT genotype and 58% with the TT genotype (odds ratio 1.8, 95% confidence interval 1.2-2.7, P = .0046).

Moreover, although roughly equivalent proportions of each genotype had a rapid virologic response (165 patients total; 53%, 66%, and 59% for CC, CT, and TT patients, respectively), this effect was “largely driven” by those patients in the variable treatment arm who did not have a rapid response, wrote the authors.

Indeed, among those patients who did not have a rapid response, the link between CC genotype and sustained response was even stronger (87% of CC patients, vs. 67% of CT patients, vs. 29% of TT patients; OR 4.0, 95% CI 1.9-8.5, P = .0002).

The link was independent of whether the patient had hepatitis C genotype 2 or genotype 3.

Current guidelines recommend 12 weeks of therapy for all hepatitis C genotype 2 and 3 patients with a low viral load, irrespective of their IL28B status, according to the authors.

“It is tempting to speculate that such treatment would be most suitable for CC patients,” they said, but “prospective studies randomizing patients according to IL28B-type will be necessary.”

Several authors, not including Dr. Mangia, disclosed that they are coinventors of a patent application based on IL28B. The researchers also reported financial and research support from the Duke Clinical Research Institute, Richard B. Boebel Family Fund, National Health and Medical Research Council of Australia, Gastroenterology Society of Australia, and Royal Australasian College of Physicians.