Jennie Smith

A large, retrospective cohort study published Nov. 12 in the British Medical Journal is the latest to look at the association between isotretinoin and attempted suicide. Concerns about a link between isotretinoin and suicidal behavior have abounded for years, although previous studies have failed to show a conclusive link.

By studying when (before, during, or up to 15 years after treatment) suicidal behavior is most likely to occur in relation to treatment, researchers found that although the risk is increased during and up to 1 year after treatment, such risk is more likely related to the psychological effects associated with the disease – severe acne – than with the isotretinoin, and may be affected by treatment failure.

Pharmacoepidemiologist Anders Sundström of the Karolinska Institute in Stockholm and colleagues examined named records for 5,756 Swedish patients (aged 15-49 years) who were prescribed isotretinoin in 1980-1989. The men had a mean age of 22.3 years (women, 27.1 years) at first prescription, and were taking mean daily doses of 44.5-mg and 39.2-mg isotretinoin, respectively, for severe acne. Mean length of treatment was 4 months for men and 3.9 months for women. The patients’ clinical records were compared with hospital-discharge and cause-of-death registers for the 1980-2001 period.

In all, 128 patients in the cohort were hospitalized for attempted suicide on 210 occasions during the study period; there were 24 completed suicides during this time. When the study cohort was compared with the general population, the standardized incidence ratios for suicide attempts rose from 0.89 (95% confidence interval, 0.54-1.37) at 3 years before treatment to 1.36 (95% CI, 0.65-2.50) in the year before treatment for first attempts, and from 0.99 (95% CI, 0.65-1.44) at 3 years before treatment to 1.57 (95% CI, 0.86-2.63) in the year before treatment for all attempts.

The risks were shown to be highest within 6 months after the start of treatment: 1.93 (95% CI, 1.08-3.18) for first attempts and 1.78 (95% CI, 1.04-2.85) for all attempts. The investigators also found that women who made suicide attempts received two or three treatments more often than did women who did not attempt suicide, suggesting treatment failure as a possible contributor.

After treatment, the standardized incidence ratio declined to 0.97 (95% CI, 0.64-1.40) for first attempts and 1.04 (95% CI, 0.74-1.43) for all attempts within 3 years. After 3 years and for the duration of follow-up, the rate remained on par with the background rate for the population.

The investigators concluded that "an increased risk of attempted suicide was apparent up to six months after the end of treatment with isotretinoin." However, they wrote, "the risk of attempted suicide was already rising before treatment, so an additional risk due to the isotretinoin treatment cannot be established." Patients with a history of suicide attempts need not be denied treatment with isotretinoin, they wrote, but "close monitoring of patients for suicidal behavior for up to a year after treatment has ended" would be advisable (BMJ 2010 Nov. 12 [doi:10/1136/bmj.c5812]).

The investigators acknowledged some limitations of their study, including a lack of data on potential confounding factors other than age, sex, and calendar year. Low statistical precision was also a limitation: Although standardized incidence ratios were clearly rising before treatment, they wrote, "we found no statistical significance until six months after treatment. In the internal cohort crossover analysis – that is, analyzing outcomes before and after treatment in the same population – the differences in incidence did not reach statistical significance, making the estimated number needed to harm uncertain."

Also, they wrote, "we had no information on the effect of treatment. A bias would exist if the patients who made suicide attempts had a poorer effect of treatment than did those who did not make such attempts. In that case, the suicidal behavior should be attributed to the treatment resistant acne and not to the treatment. However, such bias would only strengthen the assumed association between severe acne and suicidal behavior."

In an editorial comment, Dr. Parker Magin of the University of Newcastle in Callaghan, New South Wales, Australia, and Dr. John Sullivan of the University of New South Wales in Sydney, said that clinicians could draw important practical conclusions from the study – namely, that during and after treatment with isotretinoin (and especially when treatment is unsuccessful), "patients should be carefully monitored for depression and suicidal thoughts. Patients probably have an increased risk before treatment, however, so all patients with acne of a severity for which isotretinoin is indicated should have psychosocial factors and suicidal intent monitored."

As for who should perform the monitoring, Dr. Magin said that although dermatologists generally take on that role, general practitioners "have more appropriate training and experience in psychological medicine ... and could add invaluable expertise in the psychological aspects of management in a shared care model with dermatologists." Families of patients, Dr. Magin added, may also help with monitoring. (BMJ 2010 Nov. 12 [doi:10.1136/bmj.c5866])

The study was funded by the Swedish Research Council. Mr. Sundström and his coauthors declared that they had no conflicts of interest. Dr. Magin and Dr. Sullivan have been members of All About Acne, an organization supported by unrestricted educational grants from drug companies. Neither Dr. Magin nor Dr. Sullivan received payment from the organization, and the drug companies that provide support do not manufacture isotretinoin.

A large, retrospective cohort study published Nov. 12 in the British Medical Journal is the latest to look at the association between isotretinoin and attempted suicide. Concerns about a link between isotretinoin and suicidal behavior have abounded for years, although previous studies have failed to show a conclusive link.

By studying when (before, during, or up to 15 years after treatment) suicidal behavior is most likely to occur in relation to treatment, researchers found that although the risk is increased during and up to 1 year after treatment, such risk is more likely related to the psychological effects associated with the disease – severe acne – than with the isotretinoin, and may be affected by treatment failure.

Pharmacoepidemiologist Anders Sundström of the Karolinska Institute in Stockholm and colleagues examined named records for 5,756 Swedish patients (aged 15-49 years) who were prescribed isotretinoin in 1980-1989. The men had a mean age of 22.3 years (women, 27.1 years) at first prescription, and were taking mean daily doses of 44.5-mg and 39.2-mg isotretinoin, respectively, for severe acne. Mean length of treatment was 4 months for men and 3.9 months for women. The patients’ clinical records were compared with hospital-discharge and cause-of-death registers for the 1980-2001 period.

In all, 128 patients in the cohort were hospitalized for attempted suicide on 210 occasions during the study period; there were 24 completed suicides during this time. When the study cohort was compared with the general population, the standardized incidence ratios for suicide attempts rose from 0.89 (95% confidence interval, 0.54-1.37) at 3 years before treatment to 1.36 (95% CI, 0.65-2.50) in the year before treatment for first attempts, and from 0.99 (95% CI, 0.65-1.44) at 3 years before treatment to 1.57 (95% CI, 0.86-2.63) in the year before treatment for all attempts.

The risks were shown to be highest within 6 months after the start of treatment: 1.93 (95% CI, 1.08-3.18) for first attempts and 1.78 (95% CI, 1.04-2.85) for all attempts. The investigators also found that women who made suicide attempts received two or three treatments more often than did women who did not attempt suicide, suggesting treatment failure as a possible contributor.

After treatment, the standardized incidence ratio declined to 0.97 (95% CI, 0.64-1.40) for first attempts and 1.04 (95% CI, 0.74-1.43) for all attempts within 3 years. After 3 years and for the duration of follow-up, the rate remained on par with the background rate for the population.

The investigators concluded that "an increased risk of attempted suicide was apparent up to six months after the end of treatment with isotretinoin." However, they wrote, "the risk of attempted suicide was already rising before treatment, so an additional risk due to the isotretinoin treatment cannot be established." Patients with a history of suicide attempts need not be denied treatment with isotretinoin, they wrote, but "close monitoring of patients for suicidal behavior for up to a year after treatment has ended" would be advisable (BMJ 2010 Nov. 12 [doi:10/1136/bmj.c5812]).

The investigators acknowledged some limitations of their study, including a lack of data on potential confounding factors other than age, sex, and calendar year. Low statistical precision was also a limitation: Although standardized incidence ratios were clearly rising before treatment, they wrote, "we found no statistical significance until six months after treatment. In the internal cohort crossover analysis – that is, analyzing outcomes before and after treatment in the same population – the differences in incidence did not reach statistical significance, making the estimated number needed to harm uncertain."

Also, they wrote, "we had no information on the effect of treatment. A bias would exist if the patients who made suicide attempts had a poorer effect of treatment than did those who did not make such attempts. In that case, the suicidal behavior should be attributed to the treatment resistant acne and not to the treatment. However, such bias would only strengthen the assumed association between severe acne and suicidal behavior."

In an editorial comment, Dr. Parker Magin of the University of Newcastle in Callaghan, New South Wales, Australia, and Dr. John Sullivan of the University of New South Wales in Sydney, said that clinicians could draw important practical conclusions from the study – namely, that during and after treatment with isotretinoin (and especially when treatment is unsuccessful), "patients should be carefully monitored for depression and suicidal thoughts. Patients probably have an increased risk before treatment, however, so all patients with acne of a severity for which isotretinoin is indicated should have psychosocial factors and suicidal intent monitored."

As for who should perform the monitoring, Dr. Magin said that although dermatologists generally take on that role, general practitioners "have more appropriate training and experience in psychological medicine ... and could add invaluable expertise in the psychological aspects of management in a shared care model with dermatologists." Families of patients, Dr. Magin added, may also help with monitoring. (BMJ 2010 Nov. 12 [doi:10.1136/bmj.c5866])

The study was funded by the Swedish Research Council. Mr. Sundström and his coauthors declared that they had no conflicts of interest. Dr. Magin and Dr. Sullivan have been members of All About Acne, an organization supported by unrestricted educational grants from drug companies. Neither Dr. Magin nor Dr. Sullivan received payment from the organization, and the drug companies that provide support do not manufacture isotretinoin.

A large, retrospective cohort study published Nov. 12 in the British Medical Journal is the latest to look at the association between isotretinoin and attempted suicide. Concerns about a link between isotretinoin and suicidal behavior have abounded for years, although previous studies have failed to show a conclusive link.

By studying when (before, during, or up to 15 years after treatment) suicidal behavior is most likely to occur in relation to treatment, researchers found that although the risk is increased during and up to 1 year after treatment, such risk is more likely related to the psychological effects associated with the disease – severe acne – than with the isotretinoin, and may be affected by treatment failure.

Pharmacoepidemiologist Anders Sundström of the Karolinska Institute in Stockholm and colleagues examined named records for 5,756 Swedish patients (aged 15-49 years) who were prescribed isotretinoin in 1980-1989. The men had a mean age of 22.3 years (women, 27.1 years) at first prescription, and were taking mean daily doses of 44.5-mg and 39.2-mg isotretinoin, respectively, for severe acne. Mean length of treatment was 4 months for men and 3.9 months for women. The patients’ clinical records were compared with hospital-discharge and cause-of-death registers for the 1980-2001 period.

In all, 128 patients in the cohort were hospitalized for attempted suicide on 210 occasions during the study period; there were 24 completed suicides during this time. When the study cohort was compared with the general population, the standardized incidence ratios for suicide attempts rose from 0.89 (95% confidence interval, 0.54-1.37) at 3 years before treatment to 1.36 (95% CI, 0.65-2.50) in the year before treatment for first attempts, and from 0.99 (95% CI, 0.65-1.44) at 3 years before treatment to 1.57 (95% CI, 0.86-2.63) in the year before treatment for all attempts.

The risks were shown to be highest within 6 months after the start of treatment: 1.93 (95% CI, 1.08-3.18) for first attempts and 1.78 (95% CI, 1.04-2.85) for all attempts. The investigators also found that women who made suicide attempts received two or three treatments more often than did women who did not attempt suicide, suggesting treatment failure as a possible contributor.

After treatment, the standardized incidence ratio declined to 0.97 (95% CI, 0.64-1.40) for first attempts and 1.04 (95% CI, 0.74-1.43) for all attempts within 3 years. After 3 years and for the duration of follow-up, the rate remained on par with the background rate for the population.

The investigators concluded that "an increased risk of attempted suicide was apparent up to six months after the end of treatment with isotretinoin." However, they wrote, "the risk of attempted suicide was already rising before treatment, so an additional risk due to the isotretinoin treatment cannot be established." Patients with a history of suicide attempts need not be denied treatment with isotretinoin, they wrote, but "close monitoring of patients for suicidal behavior for up to a year after treatment has ended" would be advisable (BMJ 2010 Nov. 12 [doi:10/1136/bmj.c5812]).

The investigators acknowledged some limitations of their study, including a lack of data on potential confounding factors other than age, sex, and calendar year. Low statistical precision was also a limitation: Although standardized incidence ratios were clearly rising before treatment, they wrote, "we found no statistical significance until six months after treatment. In the internal cohort crossover analysis – that is, analyzing outcomes before and after treatment in the same population – the differences in incidence did not reach statistical significance, making the estimated number needed to harm uncertain."

Also, they wrote, "we had no information on the effect of treatment. A bias would exist if the patients who made suicide attempts had a poorer effect of treatment than did those who did not make such attempts. In that case, the suicidal behavior should be attributed to the treatment resistant acne and not to the treatment. However, such bias would only strengthen the assumed association between severe acne and suicidal behavior."

In an editorial comment, Dr. Parker Magin of the University of Newcastle in Callaghan, New South Wales, Australia, and Dr. John Sullivan of the University of New South Wales in Sydney, said that clinicians could draw important practical conclusions from the study – namely, that during and after treatment with isotretinoin (and especially when treatment is unsuccessful), "patients should be carefully monitored for depression and suicidal thoughts. Patients probably have an increased risk before treatment, however, so all patients with acne of a severity for which isotretinoin is indicated should have psychosocial factors and suicidal intent monitored."

As for who should perform the monitoring, Dr. Magin said that although dermatologists generally take on that role, general practitioners "have more appropriate training and experience in psychological medicine ... and could add invaluable expertise in the psychological aspects of management in a shared care model with dermatologists." Families of patients, Dr. Magin added, may also help with monitoring. (BMJ 2010 Nov. 12 [doi:10.1136/bmj.c5866])

The study was funded by the Swedish Research Council. Mr. Sundström and his coauthors declared that they had no conflicts of interest. Dr. Magin and Dr. Sullivan have been members of All About Acne, an organization supported by unrestricted educational grants from drug companies. Neither Dr. Magin nor Dr. Sullivan received payment from the organization, and the drug companies that provide support do not manufacture isotretinoin.

While England’s national death rate from coronary heart disease has been dropping steadily for nearly 2 decades – and by two-fifths in the last decade alone – stubborn disparities have remained along local lines, with some areas proving consistently worse off relative to others.

Findings published online Nov. 10 in JAMA suggest that although most factors associated with coronary heart disease (CHD) deaths lay in locally varying population characteristics such as smoking, ethnicity, and socioeconomic deprivation, areas that recorded a lower prevalence of hypertension saw higher CHD mortality rates, too – possibly because health services were being underused or some local primary care trusts were diagnosing and managing this CHD risk factor more effectively than others.

In short, "your post code may affect your chances of dying of coronary heart disease," the study’s lead author Dr. Louis S. Levene of the University of Leicester (England) said in an interview. The study, which examined publically available data for 2006, 2007, and 2008, covered England’s total population of about 54 million (JAMA 2010;304:2028-34).

Using a hierarchical regression model, Dr. Levene and his colleagues sought to examine the relationship between variations in coronary heart disease mortality among England’s 152 local primary care trusts and differences in any potentially explanatory factors associated with the populations they served and the delivery of health services. In 2008, the national age-standardized CHD mortality rate was 88.4/100,000 population in England (down from 97.9 in 2006 and 93.5 in 2007). Among individual local trusts, the age-standardized CHD mortality varied between 45.3 and 147.1/100,000.

The final model derived from the analysis explained about two-thirds of the variation in CHD mortality, consistent across the 3 years studied. In this model four of the five factors shown to correlate with higher local CHD mortality were population based: trusts with more white people (when examined independently of other risk factors), greater socioeconomic deprivation, more smokers, and more people with diabetes. This, Dr. Levene said, was not entirely a surprise.

The investigators also identified, however, an important service-related factor in trusts with higher CHD mortality, also consistent in the 3 years: less diagnosis of hypertension. This explained about 10% of the variation.

For example, while the Health Survey for England, an annual population study designed to measure health and health-related behaviors, saw rates of diagnosed and expected prevalence levels of diabetes that were very close in 2008, Dr. Levene and his colleagues saw a significant disparity the same year with hypertension. Only 13% of England’s population was recorded on practice registers as having hypertension, they noted, "although the Health Survey for England found a prevalence of hypertension of 30.1% among adults."

Dr. Levene said he did not know whether to ascribe the gap to underutilization of health services or a failure of the trusts to deliver preventive care. "A standard GP appointment lasts 10 minutes," he said in an interview, which may mean blood pressure checks are not done even though they are recommended by guidelines. "In my practice we have 13,000 patients – if someone comes in to see you for depression, we may try and remember to do [blood pressure]," he said. "People are getting better at doing it, since rates of diagnosis are going up."

Dr. Levene and his colleagues noted some of the limitations of their study, which included the possibility of having omitted or neglected potentially relevant factors, such as access to or continuity of health services. One missing potential population variable was sex, they wrote, "because the age-standardized CHD mortality rates are higher in men than in women." No other variables used were sex specific, so the effect of sex could not be analyzed.

Nonetheless, the investigators wrote, the findings had several policy implications. "Programs to reduce [CHD] mortality should address those characteristics of populations amenable to intervention, including smoking and deprivation. The importance of paying attention to population characteristics is emphasized by the finding that better detection of hypertension in the population was associated with reduced CHD mortality at the population level."

"My personal view," Dr. Levene told this news organization, "is that if collectively we become more interested in primary prevention in the wider population, this rate of decline should continue and the gaps should narrow."

The study was funded through the National Institute for Health Research. One of Dr. Levene’s coauthors, Dr. Kamlesh Khunti, reported being an adviser to the National Screening Committee and a clinical adviser for the Diabetes National Institute for Clinical Excellence-led Quality and Outcomes Framework Panel. No other authors reported any financial disclosures.

While England’s national death rate from coronary heart disease has been dropping steadily for nearly 2 decades – and by two-fifths in the last decade alone – stubborn disparities have remained along local lines, with some areas proving consistently worse off relative to others.

Findings published online Nov. 10 in JAMA suggest that although most factors associated with coronary heart disease (CHD) deaths lay in locally varying population characteristics such as smoking, ethnicity, and socioeconomic deprivation, areas that recorded a lower prevalence of hypertension saw higher CHD mortality rates, too – possibly because health services were being underused or some local primary care trusts were diagnosing and managing this CHD risk factor more effectively than others.

In short, "your post code may affect your chances of dying of coronary heart disease," the study’s lead author Dr. Louis S. Levene of the University of Leicester (England) said in an interview. The study, which examined publically available data for 2006, 2007, and 2008, covered England’s total population of about 54 million (JAMA 2010;304:2028-34).

Using a hierarchical regression model, Dr. Levene and his colleagues sought to examine the relationship between variations in coronary heart disease mortality among England’s 152 local primary care trusts and differences in any potentially explanatory factors associated with the populations they served and the delivery of health services. In 2008, the national age-standardized CHD mortality rate was 88.4/100,000 population in England (down from 97.9 in 2006 and 93.5 in 2007). Among individual local trusts, the age-standardized CHD mortality varied between 45.3 and 147.1/100,000.

The final model derived from the analysis explained about two-thirds of the variation in CHD mortality, consistent across the 3 years studied. In this model four of the five factors shown to correlate with higher local CHD mortality were population based: trusts with more white people (when examined independently of other risk factors), greater socioeconomic deprivation, more smokers, and more people with diabetes. This, Dr. Levene said, was not entirely a surprise.

The investigators also identified, however, an important service-related factor in trusts with higher CHD mortality, also consistent in the 3 years: less diagnosis of hypertension. This explained about 10% of the variation.

For example, while the Health Survey for England, an annual population study designed to measure health and health-related behaviors, saw rates of diagnosed and expected prevalence levels of diabetes that were very close in 2008, Dr. Levene and his colleagues saw a significant disparity the same year with hypertension. Only 13% of England’s population was recorded on practice registers as having hypertension, they noted, "although the Health Survey for England found a prevalence of hypertension of 30.1% among adults."

Dr. Levene said he did not know whether to ascribe the gap to underutilization of health services or a failure of the trusts to deliver preventive care. "A standard GP appointment lasts 10 minutes," he said in an interview, which may mean blood pressure checks are not done even though they are recommended by guidelines. "In my practice we have 13,000 patients – if someone comes in to see you for depression, we may try and remember to do [blood pressure]," he said. "People are getting better at doing it, since rates of diagnosis are going up."

Dr. Levene and his colleagues noted some of the limitations of their study, which included the possibility of having omitted or neglected potentially relevant factors, such as access to or continuity of health services. One missing potential population variable was sex, they wrote, "because the age-standardized CHD mortality rates are higher in men than in women." No other variables used were sex specific, so the effect of sex could not be analyzed.

Nonetheless, the investigators wrote, the findings had several policy implications. "Programs to reduce [CHD] mortality should address those characteristics of populations amenable to intervention, including smoking and deprivation. The importance of paying attention to population characteristics is emphasized by the finding that better detection of hypertension in the population was associated with reduced CHD mortality at the population level."

"My personal view," Dr. Levene told this news organization, "is that if collectively we become more interested in primary prevention in the wider population, this rate of decline should continue and the gaps should narrow."

The study was funded through the National Institute for Health Research. One of Dr. Levene’s coauthors, Dr. Kamlesh Khunti, reported being an adviser to the National Screening Committee and a clinical adviser for the Diabetes National Institute for Clinical Excellence-led Quality and Outcomes Framework Panel. No other authors reported any financial disclosures.

While England’s national death rate from coronary heart disease has been dropping steadily for nearly 2 decades – and by two-fifths in the last decade alone – stubborn disparities have remained along local lines, with some areas proving consistently worse off relative to others.

Findings published online Nov. 10 in JAMA suggest that although most factors associated with coronary heart disease (CHD) deaths lay in locally varying population characteristics such as smoking, ethnicity, and socioeconomic deprivation, areas that recorded a lower prevalence of hypertension saw higher CHD mortality rates, too – possibly because health services were being underused or some local primary care trusts were diagnosing and managing this CHD risk factor more effectively than others.

In short, "your post code may affect your chances of dying of coronary heart disease," the study’s lead author Dr. Louis S. Levene of the University of Leicester (England) said in an interview. The study, which examined publically available data for 2006, 2007, and 2008, covered England’s total population of about 54 million (JAMA 2010;304:2028-34).

Using a hierarchical regression model, Dr. Levene and his colleagues sought to examine the relationship between variations in coronary heart disease mortality among England’s 152 local primary care trusts and differences in any potentially explanatory factors associated with the populations they served and the delivery of health services. In 2008, the national age-standardized CHD mortality rate was 88.4/100,000 population in England (down from 97.9 in 2006 and 93.5 in 2007). Among individual local trusts, the age-standardized CHD mortality varied between 45.3 and 147.1/100,000.

The final model derived from the analysis explained about two-thirds of the variation in CHD mortality, consistent across the 3 years studied. In this model four of the five factors shown to correlate with higher local CHD mortality were population based: trusts with more white people (when examined independently of other risk factors), greater socioeconomic deprivation, more smokers, and more people with diabetes. This, Dr. Levene said, was not entirely a surprise.

The investigators also identified, however, an important service-related factor in trusts with higher CHD mortality, also consistent in the 3 years: less diagnosis of hypertension. This explained about 10% of the variation.

For example, while the Health Survey for England, an annual population study designed to measure health and health-related behaviors, saw rates of diagnosed and expected prevalence levels of diabetes that were very close in 2008, Dr. Levene and his colleagues saw a significant disparity the same year with hypertension. Only 13% of England’s population was recorded on practice registers as having hypertension, they noted, "although the Health Survey for England found a prevalence of hypertension of 30.1% among adults."

Dr. Levene said he did not know whether to ascribe the gap to underutilization of health services or a failure of the trusts to deliver preventive care. "A standard GP appointment lasts 10 minutes," he said in an interview, which may mean blood pressure checks are not done even though they are recommended by guidelines. "In my practice we have 13,000 patients – if someone comes in to see you for depression, we may try and remember to do [blood pressure]," he said. "People are getting better at doing it, since rates of diagnosis are going up."

Dr. Levene and his colleagues noted some of the limitations of their study, which included the possibility of having omitted or neglected potentially relevant factors, such as access to or continuity of health services. One missing potential population variable was sex, they wrote, "because the age-standardized CHD mortality rates are higher in men than in women." No other variables used were sex specific, so the effect of sex could not be analyzed.

Nonetheless, the investigators wrote, the findings had several policy implications. "Programs to reduce [CHD] mortality should address those characteristics of populations amenable to intervention, including smoking and deprivation. The importance of paying attention to population characteristics is emphasized by the finding that better detection of hypertension in the population was associated with reduced CHD mortality at the population level."

"My personal view," Dr. Levene told this news organization, "is that if collectively we become more interested in primary prevention in the wider population, this rate of decline should continue and the gaps should narrow."

The study was funded through the National Institute for Health Research. One of Dr. Levene’s coauthors, Dr. Kamlesh Khunti, reported being an adviser to the National Screening Committee and a clinical adviser for the Diabetes National Institute for Clinical Excellence-led Quality and Outcomes Framework Panel. No other authors reported any financial disclosures.

While England’s national death rate from coronary heart disease has been dropping steadily for nearly 2 decades – and by two-fifths in the last decade alone – stubborn disparities have remained along local lines, with some areas proving consistently worse off relative to others.

Findings published online Nov. 10 in JAMA suggest that although most factors associated with coronary heart disease (CHD) deaths lay in locally varying population characteristics such as smoking, ethnicity, and socioeconomic deprivation, areas that recorded a lower prevalence of hypertension saw higher CHD mortality rates, too – possibly because health services were being underused or some local primary care trusts were diagnosing and managing this CHD risk factor more effectively than others.

In short, "your post code may affect your chances of dying of coronary heart disease," the study’s lead author Dr. Louis S. Levene of the University of Leicester (England) said in an interview. The study, which examined publically available data for 2006, 2007, and 2008, covered England’s total population of about 54 million (JAMA 2010;304:2028-34).

Using a hierarchical regression model, Dr. Levene and his colleagues sought to examine the relationship between variations in coronary heart disease mortality among England’s 152 local primary care trusts and differences in any potentially explanatory factors associated with the populations they served and the delivery of health services. In 2008, the national age-standardized CHD mortality rate was 88.4/100,000 population in England (down from 97.9 in 2006 and 93.5 in 2007). Among individual local trusts, the age-standardized CHD mortality varied between 45.3 and 147.1/100,000.

The final model derived from the analysis explained about two-thirds of the variation in CHD mortality, consistent across the 3 years studied. In this model four of the five factors shown to correlate with higher local CHD mortality were population based: trusts with more white people (when examined independently of other risk factors), greater socioeconomic deprivation, more smokers, and more people with diabetes. This, Dr. Levene said, was not entirely a surprise.

The investigators also identified, however, an important service-related factor in trusts with higher CHD mortality, also consistent in the 3 years: less diagnosis of hypertension. This explained about 10% of the variation.

For example, while the Health Survey for England, an annual population study designed to measure health and health-related behaviors, saw rates of diagnosed and expected prevalence levels of diabetes that were very close in 2008, Dr. Levene and his colleagues saw a significant disparity the same year with hypertension. Only 13% of England’s population was recorded on practice registers as having hypertension, they noted, "although the Health Survey for England found a prevalence of hypertension of 30.1% among adults."

Dr. Levene said he did not know whether to ascribe the gap to underutilization of health services or a failure of the trusts to deliver preventive care. "A standard GP appointment lasts 10 minutes," he said in an interview, which may mean blood pressure checks are not done even though they are recommended by guidelines. "In my practice we have 13,000 patients – if someone comes in to see you for depression, we may try and remember to do [blood pressure]," he said. "People are getting better at doing it, since rates of diagnosis are going up."

Dr. Levene and his colleagues noted some of the limitations of their study, which included the possibility of having omitted or neglected potentially relevant factors, such as access to or continuity of health services. One missing potential population variable was sex, they wrote, "because the age-standardized CHD mortality rates are higher in men than in women." No other variables used were sex specific, so the effect of sex could not be analyzed.

Nonetheless, the investigators wrote, the findings had several policy implications. "Programs to reduce [CHD] mortality should address those characteristics of populations amenable to intervention, including smoking and deprivation. The importance of paying attention to population characteristics is emphasized by the finding that better detection of hypertension in the population was associated with reduced CHD mortality at the population level."

"My personal view," Dr. Levene told this news organization, "is that if collectively we become more interested in primary prevention in the wider population, this rate of decline should continue and the gaps should narrow."

The study was funded through the National Institute for Health Research. One of Dr. Levene’s coauthors, Dr. Kamlesh Khunti, reported being an adviser to the National Screening Committee and a clinical adviser for the Diabetes National Institute for Clinical Excellence-led Quality and Outcomes Framework Panel. No other authors reported any financial disclosures.

While England’s national death rate from coronary heart disease has been dropping steadily for nearly 2 decades – and by two-fifths in the last decade alone – stubborn disparities have remained along local lines, with some areas proving consistently worse off relative to others.

Findings published online Nov. 10 in JAMA suggest that although most factors associated with coronary heart disease (CHD) deaths lay in locally varying population characteristics such as smoking, ethnicity, and socioeconomic deprivation, areas that recorded a lower prevalence of hypertension saw higher CHD mortality rates, too – possibly because health services were being underused or some local primary care trusts were diagnosing and managing this CHD risk factor more effectively than others.

In short, "your post code may affect your chances of dying of coronary heart disease," the study’s lead author Dr. Louis S. Levene of the University of Leicester (England) said in an interview. The study, which examined publically available data for 2006, 2007, and 2008, covered England’s total population of about 54 million (JAMA 2010;304:2028-34).

Using a hierarchical regression model, Dr. Levene and his colleagues sought to examine the relationship between variations in coronary heart disease mortality among England’s 152 local primary care trusts and differences in any potentially explanatory factors associated with the populations they served and the delivery of health services. In 2008, the national age-standardized CHD mortality rate was 88.4/100,000 population in England (down from 97.9 in 2006 and 93.5 in 2007). Among individual local trusts, the age-standardized CHD mortality varied between 45.3 and 147.1/100,000.

The final model derived from the analysis explained about two-thirds of the variation in CHD mortality, consistent across the 3 years studied. In this model four of the five factors shown to correlate with higher local CHD mortality were population based: trusts with more white people (when examined independently of other risk factors), greater socioeconomic deprivation, more smokers, and more people with diabetes. This, Dr. Levene said, was not entirely a surprise.

The investigators also identified, however, an important service-related factor in trusts with higher CHD mortality, also consistent in the 3 years: less diagnosis of hypertension. This explained about 10% of the variation.

For example, while the Health Survey for England, an annual population study designed to measure health and health-related behaviors, saw rates of diagnosed and expected prevalence levels of diabetes that were very close in 2008, Dr. Levene and his colleagues saw a significant disparity the same year with hypertension. Only 13% of England’s population was recorded on practice registers as having hypertension, they noted, "although the Health Survey for England found a prevalence of hypertension of 30.1% among adults."

Dr. Levene said he did not know whether to ascribe the gap to underutilization of health services or a failure of the trusts to deliver preventive care. "A standard GP appointment lasts 10 minutes," he said in an interview, which may mean blood pressure checks are not done even though they are recommended by guidelines. "In my practice we have 13,000 patients – if someone comes in to see you for depression, we may try and remember to do [blood pressure]," he said. "People are getting better at doing it, since rates of diagnosis are going up."

Dr. Levene and his colleagues noted some of the limitations of their study, which included the possibility of having omitted or neglected potentially relevant factors, such as access to or continuity of health services. One missing potential population variable was sex, they wrote, "because the age-standardized CHD mortality rates are higher in men than in women." No other variables used were sex specific, so the effect of sex could not be analyzed.

Nonetheless, the investigators wrote, the findings had several policy implications. "Programs to reduce [CHD] mortality should address those characteristics of populations amenable to intervention, including smoking and deprivation. The importance of paying attention to population characteristics is emphasized by the finding that better detection of hypertension in the population was associated with reduced CHD mortality at the population level."

"My personal view," Dr. Levene told this news organization, "is that if collectively we become more interested in primary prevention in the wider population, this rate of decline should continue and the gaps should narrow."

The study was funded through the National Institute for Health Research. One of Dr. Levene’s coauthors, Dr. Kamlesh Khunti, reported being an adviser to the National Screening Committee and a clinical adviser for the Diabetes National Institute for Clinical Excellence-led Quality and Outcomes Framework Panel. No other authors reported any financial disclosures.

While England’s national death rate from coronary heart disease has been dropping steadily for nearly 2 decades – and by two-fifths in the last decade alone – stubborn disparities have remained along local lines, with some areas proving consistently worse off relative to others.

Findings published online Nov. 10 in JAMA suggest that although most factors associated with coronary heart disease (CHD) deaths lay in locally varying population characteristics such as smoking, ethnicity, and socioeconomic deprivation, areas that recorded a lower prevalence of hypertension saw higher CHD mortality rates, too – possibly because health services were being underused or some local primary care trusts were diagnosing and managing this CHD risk factor more effectively than others.

In short, "your post code may affect your chances of dying of coronary heart disease," the study’s lead author Dr. Louis S. Levene of the University of Leicester (England) said in an interview. The study, which examined publically available data for 2006, 2007, and 2008, covered England’s total population of about 54 million (JAMA 2010;304:2028-34).

Using a hierarchical regression model, Dr. Levene and his colleagues sought to examine the relationship between variations in coronary heart disease mortality among England’s 152 local primary care trusts and differences in any potentially explanatory factors associated with the populations they served and the delivery of health services. In 2008, the national age-standardized CHD mortality rate was 88.4/100,000 population in England (down from 97.9 in 2006 and 93.5 in 2007). Among individual local trusts, the age-standardized CHD mortality varied between 45.3 and 147.1/100,000.

The final model derived from the analysis explained about two-thirds of the variation in CHD mortality, consistent across the 3 years studied. In this model four of the five factors shown to correlate with higher local CHD mortality were population based: trusts with more white people (when examined independently of other risk factors), greater socioeconomic deprivation, more smokers, and more people with diabetes. This, Dr. Levene said, was not entirely a surprise.

The investigators also identified, however, an important service-related factor in trusts with higher CHD mortality, also consistent in the 3 years: less diagnosis of hypertension. This explained about 10% of the variation.

For example, while the Health Survey for England, an annual population study designed to measure health and health-related behaviors, saw rates of diagnosed and expected prevalence levels of diabetes that were very close in 2008, Dr. Levene and his colleagues saw a significant disparity the same year with hypertension. Only 13% of England’s population was recorded on practice registers as having hypertension, they noted, "although the Health Survey for England found a prevalence of hypertension of 30.1% among adults."

Dr. Levene said he did not know whether to ascribe the gap to underutilization of health services or a failure of the trusts to deliver preventive care. "A standard GP appointment lasts 10 minutes," he said in an interview, which may mean blood pressure checks are not done even though they are recommended by guidelines. "In my practice we have 13,000 patients – if someone comes in to see you for depression, we may try and remember to do [blood pressure]," he said. "People are getting better at doing it, since rates of diagnosis are going up."

Dr. Levene and his colleagues noted some of the limitations of their study, which included the possibility of having omitted or neglected potentially relevant factors, such as access to or continuity of health services. One missing potential population variable was sex, they wrote, "because the age-standardized CHD mortality rates are higher in men than in women." No other variables used were sex specific, so the effect of sex could not be analyzed.

Nonetheless, the investigators wrote, the findings had several policy implications. "Programs to reduce [CHD] mortality should address those characteristics of populations amenable to intervention, including smoking and deprivation. The importance of paying attention to population characteristics is emphasized by the finding that better detection of hypertension in the population was associated with reduced CHD mortality at the population level."

"My personal view," Dr. Levene told this news organization, "is that if collectively we become more interested in primary prevention in the wider population, this rate of decline should continue and the gaps should narrow."

The study was funded through the National Institute for Health Research. One of Dr. Levene’s coauthors, Dr. Kamlesh Khunti, reported being an adviser to the National Screening Committee and a clinical adviser for the Diabetes National Institute for Clinical Excellence-led Quality and Outcomes Framework Panel. No other authors reported any financial disclosures.

Women taking over-the-counter painkillers during pregnancy have an increased risk of having sons born with undescended testes, according to a study that also incorporates rat models to show why this might be.

Using data from a birth cohort study of singleton sons born to 1,463 women in Finland and 834 in Denmark, all of whom either completed written questionnaires or telephone interviews or both, the researchers, led by Henrik Leffers, Ph.D., of Rigshospitalet in Copenhagen, found the risk of cryptorchidism to increase sevenfold in boys born to women who used more then one of three over-the-counter painkillers – aspirin (acetylsalicylic acid), acetaminophen (paracetamol), or ibuprofen – simultaneously during their pregnancies. Exact doses of the painkillers were not recorded.

The findings, published online Nov. 8 in the journal Human Reproduction (doi:10.1093/humrep/deq323), also showed that any of these painkillers used for any duration during the second trimester more than doubled the risk of cryptorchidism, though the association for acetaminophen did not reach statistical significance.

The highest risk was observed, Dr. Leffers and his colleagues reported, among women who used more than one compound simultaneously for more than 2 weeks in the second trimester (adjusted odds ratio, 21.7 [1.83–258])."

A possible mechanism for this effect, Dr. Leffers and his colleagues hypothesized, was demonstrated by some of the study’s coauthors, who found in a linked investigation that intrauterine exposure to acetaminophen, at three times the recommended dose for humans, led to a reduction in anogenital distance among fetal rats, and also reduced testosterone production by about half in fetal rat testes.

Aspirin was also tested in rats, but the results were not conclusive. "A particular strength of this study is the use of two complementary rat models to support the contention that the association between analgesic use and cryptorchidism seen in our cohort study may result from a reduction in androgen production," Dr. Leffers and his colleagues wrote.

Their study adds to findings published earlier this month (Epidemiology 2010;21:779-85) from a cohort of 47,000 boys born in Denmark, 980 of whom were identified in childhood as having cryptorchidism. That study, which also looked at acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy through telephone interviews and questionnaires with mothers, saw exposure to acetaminophen during both the first and second trimesters associated with increased cryptorchidism (hazard ratio = 1.33). Acetaminophen exposure of more than 4 weeks between the 8th and 14th gestational weeks was associated with an HR of 1.38. However no association was found for either ibuprofen or aspirin.

Dr. Leffers and his colleagues’ study found all but one of their statistically significant associations in the Danish part of their cohort and speculated that differences in design of the Finnish and Danish cohort studies may have been partly responsible.

Although the Finnish questionnaire asked respondents to list only which medications were taken and when, the Danish telephone interviews asked the most pointed questions about over-the-counter and prescription pain medications, including which products were used in which weeks of pregnancy. Though just more than a quarter (26%) of the Danish mothers responding to the written questionnaire said they had used mild analgesics, more than half (56%) of those interviewed by telephone said the same.

"These findings indicated that many mothers did not consider mild analgesics as medication and hence strongly underreported their use unless specifically asked. We therefore only included the data from the computer-assisted telephone interview from the Danish part of the study," the investigators wrote.

In a press release accompanying the study, Dr. Leffers said: "A single paracetamol tablet (500 mg) contains more endocrine disruptor potency than the combined exposure to the 10 most prevalent of the currently known environmental endocrine disruptors during the whole pregnancy."

Men born with cryptorchidism, the researchers noted, see an increased risk of having poor semen quality and testicular germ cell cancer.

Dr. Leffers and his colleagues’ study was funded by European Commission and French government grants, the Villum Kann Rasmussen Foundation, and Novo Nordisk. None of its authors declared conflicts of interest.

Women taking over-the-counter painkillers during pregnancy have an increased risk of having sons born with undescended testes, according to a study that also incorporates rat models to show why this might be.

Using data from a birth cohort study of singleton sons born to 1,463 women in Finland and 834 in Denmark, all of whom either completed written questionnaires or telephone interviews or both, the researchers, led by Henrik Leffers, Ph.D., of Rigshospitalet in Copenhagen, found the risk of cryptorchidism to increase sevenfold in boys born to women who used more then one of three over-the-counter painkillers – aspirin (acetylsalicylic acid), acetaminophen (paracetamol), or ibuprofen – simultaneously during their pregnancies. Exact doses of the painkillers were not recorded.

The findings, published online Nov. 8 in the journal Human Reproduction (doi:10.1093/humrep/deq323), also showed that any of these painkillers used for any duration during the second trimester more than doubled the risk of cryptorchidism, though the association for acetaminophen did not reach statistical significance.

The highest risk was observed, Dr. Leffers and his colleagues reported, among women who used more than one compound simultaneously for more than 2 weeks in the second trimester (adjusted odds ratio, 21.7 [1.83–258])."

A possible mechanism for this effect, Dr. Leffers and his colleagues hypothesized, was demonstrated by some of the study’s coauthors, who found in a linked investigation that intrauterine exposure to acetaminophen, at three times the recommended dose for humans, led to a reduction in anogenital distance among fetal rats, and also reduced testosterone production by about half in fetal rat testes.

Aspirin was also tested in rats, but the results were not conclusive. "A particular strength of this study is the use of two complementary rat models to support the contention that the association between analgesic use and cryptorchidism seen in our cohort study may result from a reduction in androgen production," Dr. Leffers and his colleagues wrote.

Their study adds to findings published earlier this month (Epidemiology 2010;21:779-85) from a cohort of 47,000 boys born in Denmark, 980 of whom were identified in childhood as having cryptorchidism. That study, which also looked at acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy through telephone interviews and questionnaires with mothers, saw exposure to acetaminophen during both the first and second trimesters associated with increased cryptorchidism (hazard ratio = 1.33). Acetaminophen exposure of more than 4 weeks between the 8th and 14th gestational weeks was associated with an HR of 1.38. However no association was found for either ibuprofen or aspirin.

Dr. Leffers and his colleagues’ study found all but one of their statistically significant associations in the Danish part of their cohort and speculated that differences in design of the Finnish and Danish cohort studies may have been partly responsible.

Although the Finnish questionnaire asked respondents to list only which medications were taken and when, the Danish telephone interviews asked the most pointed questions about over-the-counter and prescription pain medications, including which products were used in which weeks of pregnancy. Though just more than a quarter (26%) of the Danish mothers responding to the written questionnaire said they had used mild analgesics, more than half (56%) of those interviewed by telephone said the same.

"These findings indicated that many mothers did not consider mild analgesics as medication and hence strongly underreported their use unless specifically asked. We therefore only included the data from the computer-assisted telephone interview from the Danish part of the study," the investigators wrote.

In a press release accompanying the study, Dr. Leffers said: "A single paracetamol tablet (500 mg) contains more endocrine disruptor potency than the combined exposure to the 10 most prevalent of the currently known environmental endocrine disruptors during the whole pregnancy."

Men born with cryptorchidism, the researchers noted, see an increased risk of having poor semen quality and testicular germ cell cancer.

Dr. Leffers and his colleagues’ study was funded by European Commission and French government grants, the Villum Kann Rasmussen Foundation, and Novo Nordisk. None of its authors declared conflicts of interest.

Women taking over-the-counter painkillers during pregnancy have an increased risk of having sons born with undescended testes, according to a study that also incorporates rat models to show why this might be.

Using data from a birth cohort study of singleton sons born to 1,463 women in Finland and 834 in Denmark, all of whom either completed written questionnaires or telephone interviews or both, the researchers, led by Henrik Leffers, Ph.D., of Rigshospitalet in Copenhagen, found the risk of cryptorchidism to increase sevenfold in boys born to women who used more then one of three over-the-counter painkillers – aspirin (acetylsalicylic acid), acetaminophen (paracetamol), or ibuprofen – simultaneously during their pregnancies. Exact doses of the painkillers were not recorded.

The findings, published online Nov. 8 in the journal Human Reproduction (doi:10.1093/humrep/deq323), also showed that any of these painkillers used for any duration during the second trimester more than doubled the risk of cryptorchidism, though the association for acetaminophen did not reach statistical significance.

The highest risk was observed, Dr. Leffers and his colleagues reported, among women who used more than one compound simultaneously for more than 2 weeks in the second trimester (adjusted odds ratio, 21.7 [1.83–258])."

A possible mechanism for this effect, Dr. Leffers and his colleagues hypothesized, was demonstrated by some of the study’s coauthors, who found in a linked investigation that intrauterine exposure to acetaminophen, at three times the recommended dose for humans, led to a reduction in anogenital distance among fetal rats, and also reduced testosterone production by about half in fetal rat testes.

Aspirin was also tested in rats, but the results were not conclusive. "A particular strength of this study is the use of two complementary rat models to support the contention that the association between analgesic use and cryptorchidism seen in our cohort study may result from a reduction in androgen production," Dr. Leffers and his colleagues wrote.

Their study adds to findings published earlier this month (Epidemiology 2010;21:779-85) from a cohort of 47,000 boys born in Denmark, 980 of whom were identified in childhood as having cryptorchidism. That study, which also looked at acetaminophen, ibuprofen, and acetylsalicylic acid during pregnancy through telephone interviews and questionnaires with mothers, saw exposure to acetaminophen during both the first and second trimesters associated with increased cryptorchidism (hazard ratio = 1.33). Acetaminophen exposure of more than 4 weeks between the 8th and 14th gestational weeks was associated with an HR of 1.38. However no association was found for either ibuprofen or aspirin.

Dr. Leffers and his colleagues’ study found all but one of their statistically significant associations in the Danish part of their cohort and speculated that differences in design of the Finnish and Danish cohort studies may have been partly responsible.

Although the Finnish questionnaire asked respondents to list only which medications were taken and when, the Danish telephone interviews asked the most pointed questions about over-the-counter and prescription pain medications, including which products were used in which weeks of pregnancy. Though just more than a quarter (26%) of the Danish mothers responding to the written questionnaire said they had used mild analgesics, more than half (56%) of those interviewed by telephone said the same.

"These findings indicated that many mothers did not consider mild analgesics as medication and hence strongly underreported their use unless specifically asked. We therefore only included the data from the computer-assisted telephone interview from the Danish part of the study," the investigators wrote.

In a press release accompanying the study, Dr. Leffers said: "A single paracetamol tablet (500 mg) contains more endocrine disruptor potency than the combined exposure to the 10 most prevalent of the currently known environmental endocrine disruptors during the whole pregnancy."

Men born with cryptorchidism, the researchers noted, see an increased risk of having poor semen quality and testicular germ cell cancer.

Dr. Leffers and his colleagues’ study was funded by European Commission and French government grants, the Villum Kann Rasmussen Foundation, and Novo Nordisk. None of its authors declared conflicts of interest.

The Food and Drug Administration has approved the antidepressant duloxetine for the management of chronic musculoskeletal pain in adults, the agency announced Nov. 4

The approval marks the fifth of duloxetine’s U.S. licensed indications to date and its third for treatment of pain. Duloxetine, marketed as Cymbalta, was first approved in 2004 to treat depression, and later the drug gained indications for generalized anxiety disorder, diabetic neuropathy, and fibromyalgia. All of the indications are for people aged 18 years and older. The drug has received European Union marketing authorization for depression, anxiety, and diabetic neuropathy only.

The mechanism by which duloxetine, a serotonin and norepinephrine reuptake inhibitor, works on pain is uncertain, Eli Lilly said in a press statement accompanying the announcement. However, it is believed to increase the availability of both neurotransmitters, enhancing the body’ natural pain-suppressing system.

In August the FDA’s Anesthetic and Life Support Drugs Advisory Committee had voted 8 to 6 to recommend the extension of indication for duloxetine, a vote that was considered too narrow to predict what the agency would ultimately decide. The drug’s effectiveness was not well agreed upon, either, with an 8 to 5 vote in favor, and one member abstaining.

Evidence from two studies submitted to the agency by the manufacturer (n = 236 and n = 401) showed that duloxetine at oral doses of 60-120 mg daily reduced chronic lower back pain better than placebo after 12 and 13 weeks. Evidence from a third study (n = 404) showed no benefit. For osteoarthritis, one study (n = 256) showed a statistically significant reduction in pain after 13 weeks in people taking between 60 and 120 mg, and another study (n = 231) did not.

The maximum dosage for the musculoskeletal pain indication, which includes osteoarthritis and lower back pain, is 60 mg/day, the same as the maximum recommended dosage for depression.

Adverse events observed in the musculoskeletal pain studies included nausea, dry mouth, insomnia, sleepiness, constipation, dizziness, fatigue, and constipation.

Osteoarthritis affects 27 million American adults, the company said. An estimated 70%-85% experience low back pain at some time, with some reports estimating that up to a tenth of these will go on to have chronic back pain.

The Food and Drug Administration has approved the antidepressant duloxetine for the management of chronic musculoskeletal pain in adults, the agency announced Nov. 4

The approval marks the fifth of duloxetine’s U.S. licensed indications to date and its third for treatment of pain. Duloxetine, marketed as Cymbalta, was first approved in 2004 to treat depression, and later the drug gained indications for generalized anxiety disorder, diabetic neuropathy, and fibromyalgia. All of the indications are for people aged 18 years and older. The drug has received European Union marketing authorization for depression, anxiety, and diabetic neuropathy only.

The mechanism by which duloxetine, a serotonin and norepinephrine reuptake inhibitor, works on pain is uncertain, Eli Lilly said in a press statement accompanying the announcement. However, it is believed to increase the availability of both neurotransmitters, enhancing the body’ natural pain-suppressing system.

In August the FDA’s Anesthetic and Life Support Drugs Advisory Committee had voted 8 to 6 to recommend the extension of indication for duloxetine, a vote that was considered too narrow to predict what the agency would ultimately decide. The drug’s effectiveness was not well agreed upon, either, with an 8 to 5 vote in favor, and one member abstaining.

Evidence from two studies submitted to the agency by the manufacturer (n = 236 and n = 401) showed that duloxetine at oral doses of 60-120 mg daily reduced chronic lower back pain better than placebo after 12 and 13 weeks. Evidence from a third study (n = 404) showed no benefit. For osteoarthritis, one study (n = 256) showed a statistically significant reduction in pain after 13 weeks in people taking between 60 and 120 mg, and another study (n = 231) did not.

The maximum dosage for the musculoskeletal pain indication, which includes osteoarthritis and lower back pain, is 60 mg/day, the same as the maximum recommended dosage for depression.

Adverse events observed in the musculoskeletal pain studies included nausea, dry mouth, insomnia, sleepiness, constipation, dizziness, fatigue, and constipation.

Osteoarthritis affects 27 million American adults, the company said. An estimated 70%-85% experience low back pain at some time, with some reports estimating that up to a tenth of these will go on to have chronic back pain.

The Food and Drug Administration has approved the antidepressant duloxetine for the management of chronic musculoskeletal pain in adults, the agency announced Nov. 4

The approval marks the fifth of duloxetine’s U.S. licensed indications to date and its third for treatment of pain. Duloxetine, marketed as Cymbalta, was first approved in 2004 to treat depression, and later the drug gained indications for generalized anxiety disorder, diabetic neuropathy, and fibromyalgia. All of the indications are for people aged 18 years and older. The drug has received European Union marketing authorization for depression, anxiety, and diabetic neuropathy only.

The mechanism by which duloxetine, a serotonin and norepinephrine reuptake inhibitor, works on pain is uncertain, Eli Lilly said in a press statement accompanying the announcement. However, it is believed to increase the availability of both neurotransmitters, enhancing the body’ natural pain-suppressing system.

In August the FDA’s Anesthetic and Life Support Drugs Advisory Committee had voted 8 to 6 to recommend the extension of indication for duloxetine, a vote that was considered too narrow to predict what the agency would ultimately decide. The drug’s effectiveness was not well agreed upon, either, with an 8 to 5 vote in favor, and one member abstaining.

Evidence from two studies submitted to the agency by the manufacturer (n = 236 and n = 401) showed that duloxetine at oral doses of 60-120 mg daily reduced chronic lower back pain better than placebo after 12 and 13 weeks. Evidence from a third study (n = 404) showed no benefit. For osteoarthritis, one study (n = 256) showed a statistically significant reduction in pain after 13 weeks in people taking between 60 and 120 mg, and another study (n = 231) did not.

The maximum dosage for the musculoskeletal pain indication, which includes osteoarthritis and lower back pain, is 60 mg/day, the same as the maximum recommended dosage for depression.

Adverse events observed in the musculoskeletal pain studies included nausea, dry mouth, insomnia, sleepiness, constipation, dizziness, fatigue, and constipation.

Osteoarthritis affects 27 million American adults, the company said. An estimated 70%-85% experience low back pain at some time, with some reports estimating that up to a tenth of these will go on to have chronic back pain.

The Food and Drug Administration has approved the antidepressant duloxetine for the management of chronic musculoskeletal pain in adults, the agency announced Nov. 4

The approval marks the fifth of duloxetine’s U.S. licensed indications to date and its third for treatment of pain. Duloxetine, marketed as Cymbalta, was first approved in 2004 to treat depression, and later the drug gained indications for generalized anxiety disorder, diabetic neuropathy, and fibromyalgia. All of the indications are for people aged 18 years and older. The drug has received European Union marketing authorization for depression, anxiety, and diabetic neuropathy only.

The mechanism by which duloxetine, a serotonin and norepinephrine reuptake inhibitor, works on pain is uncertain, Eli Lilly said in a press statement accompanying the announcement. However, it is believed to increase the availability of both neurotransmitters, enhancing the body’ natural pain-suppressing system.

In August the FDA’s Anesthetic and Life Support Drugs Advisory Committee had voted 8 to 6 to recommend the extension of indication for duloxetine, a vote that was considered too narrow to predict what the agency would ultimately decide. The drug’s effectiveness was not well agreed upon, either, with an 8 to 5 vote in favor, and one member abstaining.

Evidence from two studies submitted to the agency by the manufacturer (n = 236 and n = 401) showed that duloxetine at oral doses of 60-120 mg daily reduced chronic lower back pain better than placebo after 12 and 13 weeks. Evidence from a third study (n = 404) showed no benefit. For osteoarthritis, one study (n = 256) showed a statistically significant reduction in pain after 13 weeks in people taking between 60 and 120 mg, and another study (n = 231) did not.

The maximum dosage for the musculoskeletal pain indication, which includes osteoarthritis and lower back pain, is 60 mg/day, the same as the maximum recommended dosage for depression.

Adverse events observed in the musculoskeletal pain studies included nausea, dry mouth, insomnia, sleepiness, constipation, dizziness, fatigue, and constipation.

Osteoarthritis affects 27 million American adults, the company said. An estimated 70%-85% experience low back pain at some time, with some reports estimating that up to a tenth of these will go on to have chronic back pain.

The Food and Drug Administration has approved the antidepressant duloxetine for the management of chronic musculoskeletal pain in adults, the agency announced Nov. 4

The approval marks the fifth of duloxetine’s U.S. licensed indications to date and its third for treatment of pain. Duloxetine, marketed as Cymbalta, was first approved in 2004 to treat depression, and later the drug gained indications for generalized anxiety disorder, diabetic neuropathy, and fibromyalgia. All of the indications are for people aged 18 years and older. The drug has received European Union marketing authorization for depression, anxiety, and diabetic neuropathy only.

The mechanism by which duloxetine, a serotonin and norepinephrine reuptake inhibitor, works on pain is uncertain, Eli Lilly said in a press statement accompanying the announcement. However, it is believed to increase the availability of both neurotransmitters, enhancing the body’ natural pain-suppressing system.

In August the FDA’s Anesthetic and Life Support Drugs Advisory Committee had voted 8 to 6 to recommend the extension of indication for duloxetine, a vote that was considered too narrow to predict what the agency would ultimately decide. The drug’s effectiveness was not well agreed upon, either, with an 8 to 5 vote in favor, and one member abstaining.

Evidence from two studies submitted to the agency by the manufacturer (n = 236 and n = 401) showed that duloxetine at oral doses of 60-120 mg daily reduced chronic lower back pain better than placebo after 12 and 13 weeks. Evidence from a third study (n = 404) showed no benefit. For osteoarthritis, one study (n = 256) showed a statistically significant reduction in pain after 13 weeks in people taking between 60 and 120 mg, and another study (n = 231) did not.

The maximum dosage for the musculoskeletal pain indication, which includes osteoarthritis and lower back pain, is 60 mg/day, the same as the maximum recommended dosage for depression.

Adverse events observed in the musculoskeletal pain studies included nausea, dry mouth, insomnia, sleepiness, constipation, dizziness, fatigue, and constipation.

Osteoarthritis affects 27 million American adults, the company said. An estimated 70%-85% experience low back pain at some time, with some reports estimating that up to a tenth of these will go on to have chronic back pain.

The Food and Drug Administration has approved the antidepressant duloxetine for the management of chronic musculoskeletal pain in adults, the agency announced Nov. 4

The approval marks the fifth of duloxetine’s U.S. licensed indications to date and its third for treatment of pain. Duloxetine, marketed as Cymbalta, was first approved in 2004 to treat depression, and later the drug gained indications for generalized anxiety disorder, diabetic neuropathy, and fibromyalgia. All of the indications are for people aged 18 years and older. The drug has received European Union marketing authorization for depression, anxiety, and diabetic neuropathy only.

The mechanism by which duloxetine, a serotonin and norepinephrine reuptake inhibitor, works on pain is uncertain, Eli Lilly said in a press statement accompanying the announcement. However, it is believed to increase the availability of both neurotransmitters, enhancing the body’ natural pain-suppressing system.

In August the FDA’s Anesthetic and Life Support Drugs Advisory Committee had voted 8 to 6 to recommend the extension of indication for duloxetine, a vote that was considered too narrow to predict what the agency would ultimately decide. The drug’s effectiveness was not well agreed upon, either, with an 8 to 5 vote in favor, and one member abstaining.

Evidence from two studies submitted to the agency by the manufacturer (n = 236 and n = 401) showed that duloxetine at oral doses of 60-120 mg daily reduced chronic lower back pain better than placebo after 12 and 13 weeks. Evidence from a third study (n = 404) showed no benefit. For osteoarthritis, one study (n = 256) showed a statistically significant reduction in pain after 13 weeks in people taking between 60 and 120 mg, and another study (n = 231) did not.

The maximum dosage for the musculoskeletal pain indication, which includes osteoarthritis and lower back pain, is 60 mg/day, the same as the maximum recommended dosage for depression.

Adverse events observed in the musculoskeletal pain studies included nausea, dry mouth, insomnia, sleepiness, constipation, dizziness, fatigue, and constipation.

Osteoarthritis affects 27 million American adults, the company said. An estimated 70%-85% experience low back pain at some time, with some reports estimating that up to a tenth of these will go on to have chronic back pain.

The U.K. National Institute for Health and Clinical Excellence said in September that it would recommend the osteoporosis drug denosumab for older women at risk of fractures who cannot take oral bisphosphonates.

NICE's standard treatment recommendation for this patient group is alendronate and either risedronate or etidronate.

All of these agents are oral medications associated with adverse upper-GI effects if not taken according to instructions. Patients must take the medicines before meals and should not lie down for at least half an hour afterward. Denosumab, by contrast, is an injection administered twice annually.

Denosumab (Prolia, Amgen) is a monoclonal antibody that reduces osteoclast activity, limiting bone breakdown.

The NICE reviewers, in deciding to recommend denosumab, considered results from a manufacturer-sponsored phase III randomized controlled trial of denosumab 60 mg subcutaneously every 6 months in 7,868 osteoporotic women aged 60–90 years.

After 3 years, 7.2% of the placebo patients sustained a new vertebral fracture, compared with 2.3% of those who were taking denosumab, a 68% reduction. Nonvertebral fractures were 6.5% with denosumab versus 8% with placebo, and hip fractures were reduced by 40% to 2.3% in the treatment arm.

The drug was also shown to increase bone mineral density at the lumbar spine by 9% over the 3 years compared with placebo, and by 6% at the hip.

The NICE reviewers, while acknowledging denosumab's effectiveness, nonetheless noted that it was not being considered as a replacement for the cheap and widely available oral bisphosphonates, but as an alternative only where these were unsuitable.

Denosumab costs approximately $290.00 for a 1-mL prefilled syringe (60 mg per mL solution), and about $580.00 for 1 year of treatment.

Women eligible for treatment with denosumab must be intolerant of, have contraindications to, or be unable to comply with manufacturer instructions for taking alendronate and risedronate or etidronate.

They must also have bone density scores indicative of fracture risk. Other clinical risk factors for fracture that may be considered are alcohol consumption of more than 4 units per day, parental history of hip fracture, and rheumatoid arthritis.

NICE's guidance on denosumab, which is in final appraisal stage, mirrors its guidance on strontium ranelate, another treatment option for postmenopausal women at risk of fracture who cannot take bisphosphonates.

The U.K. National Institute for Health and Clinical Excellence said in September that it would recommend the osteoporosis drug denosumab for older women at risk of fractures who cannot take oral bisphosphonates.

NICE's standard treatment recommendation for this patient group is alendronate and either risedronate or etidronate.

All of these agents are oral medications associated with adverse upper-GI effects if not taken according to instructions. Patients must take the medicines before meals and should not lie down for at least half an hour afterward. Denosumab, by contrast, is an injection administered twice annually.

Denosumab (Prolia, Amgen) is a monoclonal antibody that reduces osteoclast activity, limiting bone breakdown.

The NICE reviewers, in deciding to recommend denosumab, considered results from a manufacturer-sponsored phase III randomized controlled trial of denosumab 60 mg subcutaneously every 6 months in 7,868 osteoporotic women aged 60–90 years.

After 3 years, 7.2% of the placebo patients sustained a new vertebral fracture, compared with 2.3% of those who were taking denosumab, a 68% reduction. Nonvertebral fractures were 6.5% with denosumab versus 8% with placebo, and hip fractures were reduced by 40% to 2.3% in the treatment arm.

The drug was also shown to increase bone mineral density at the lumbar spine by 9% over the 3 years compared with placebo, and by 6% at the hip.

The NICE reviewers, while acknowledging denosumab's effectiveness, nonetheless noted that it was not being considered as a replacement for the cheap and widely available oral bisphosphonates, but as an alternative only where these were unsuitable.

Denosumab costs approximately $290.00 for a 1-mL prefilled syringe (60 mg per mL solution), and about $580.00 for 1 year of treatment.

Women eligible for treatment with denosumab must be intolerant of, have contraindications to, or be unable to comply with manufacturer instructions for taking alendronate and risedronate or etidronate.

They must also have bone density scores indicative of fracture risk. Other clinical risk factors for fracture that may be considered are alcohol consumption of more than 4 units per day, parental history of hip fracture, and rheumatoid arthritis.

NICE's guidance on denosumab, which is in final appraisal stage, mirrors its guidance on strontium ranelate, another treatment option for postmenopausal women at risk of fracture who cannot take bisphosphonates.

The U.K. National Institute for Health and Clinical Excellence said in September that it would recommend the osteoporosis drug denosumab for older women at risk of fractures who cannot take oral bisphosphonates.

NICE's standard treatment recommendation for this patient group is alendronate and either risedronate or etidronate.

All of these agents are oral medications associated with adverse upper-GI effects if not taken according to instructions. Patients must take the medicines before meals and should not lie down for at least half an hour afterward. Denosumab, by contrast, is an injection administered twice annually.

Denosumab (Prolia, Amgen) is a monoclonal antibody that reduces osteoclast activity, limiting bone breakdown.

The NICE reviewers, in deciding to recommend denosumab, considered results from a manufacturer-sponsored phase III randomized controlled trial of denosumab 60 mg subcutaneously every 6 months in 7,868 osteoporotic women aged 60–90 years.

After 3 years, 7.2% of the placebo patients sustained a new vertebral fracture, compared with 2.3% of those who were taking denosumab, a 68% reduction. Nonvertebral fractures were 6.5% with denosumab versus 8% with placebo, and hip fractures were reduced by 40% to 2.3% in the treatment arm.

The drug was also shown to increase bone mineral density at the lumbar spine by 9% over the 3 years compared with placebo, and by 6% at the hip.

The NICE reviewers, while acknowledging denosumab's effectiveness, nonetheless noted that it was not being considered as a replacement for the cheap and widely available oral bisphosphonates, but as an alternative only where these were unsuitable.

Denosumab costs approximately $290.00 for a 1-mL prefilled syringe (60 mg per mL solution), and about $580.00 for 1 year of treatment.

Women eligible for treatment with denosumab must be intolerant of, have contraindications to, or be unable to comply with manufacturer instructions for taking alendronate and risedronate or etidronate.

They must also have bone density scores indicative of fracture risk. Other clinical risk factors for fracture that may be considered are alcohol consumption of more than 4 units per day, parental history of hip fracture, and rheumatoid arthritis.

NICE's guidance on denosumab, which is in final appraisal stage, mirrors its guidance on strontium ranelate, another treatment option for postmenopausal women at risk of fracture who cannot take bisphosphonates.

A survey-based study of oncologists and hematologists has shown that sperm banking is not routinely offered to U.K. men before potentially fertility-compromising cancer treatments.

Although U.S.-based studies have reported that as few as 50% of men are offered the opportunity to store sperm before cancer treatment (J. Clin. Oncol. 2002;20:1890-7), U.K. national guidelines state clearly that sperm cryostorage should be offered to all men and adolescents before undergoing such treatments. However, the study found, the decision to offer remains, in practice, largely a matter of clinician judgment, with a patient’s age, sexuality and chances of survival factored in.

For their research, published online Oct. 28 in the Annals of Oncology (doi:10.1093/annonc/mdq579), Geraldine Hartshorne, Ph.D., of the University of Warwick (England) and colleagues sent 2357 surveys to U.K. hematologists and oncologists from a national list, and 499 responses were received, 253 from hematologists and 246 from oncologists.

"The idea arose because I work in an IVF unit and we were aware of patients coming through who had had cancer treatment who did not have sperm banked," Dr. Hartshorne said in an interview. "Many had not been offered the opportunity."

Some 42% of oncologists and hematologists responding to Dr. Hartshorne and colleagues’ questionnaire said that they would offer sperm banking to patients whose cancer treatments had already begun, in direct contradiction of national clinical guidelines, the study found. And only 26% of oncologists and 38% of hematologists document their patients’ decisions on whether to have sperm stored.

About 11% of responding oncologists and hematologists said that they would "tend NOT to discuss sperm banking" with a patient who was homosexual, nearly 50% said they might not raise the issue with a patient unlikely to survive treatment, and 10% said they might hesitate with patients whom they would expect to take offense for religious reasons. Nearly 79% said they would tend not to talk about sperm storage with a terminally ill patient. Considerations of patients’ advanced age were also frequently cited as a factor in the decision whether to offer sperm banking (8% would tend not to discuss it with a person 40 or older; 36% would not do so with a patient 50 or older).

"We tried to analyze this in terms of whether doctors are making assumptions on their patients’ best interests, which of course doctors must do. But perhaps in this situation, this is not ideal practice," Dr. Hartshorne said, likening it to "unconscious discrimination."

Dr. Hartshorne and colleagues warned that clinicians who rely on their own judgments to ask patients about sperm banking could find themselves at risk of litigation. "Any set ‘cutoff’ age or personal criteria applied by clinicians could be challenged under human rights or equality legislation. Bearing in mind increasing social trends for second families, delaying parenthood and civil partnerships, an individualized approach is more appropriate. Moreover, posthumous use of banked sperm is legally accepted in the UK," they wrote.

Exacerbating the problem of uptake, Dr. Hartshorne and colleagues wrote, was the inconsistency of Primary Care Trusts in how they handle sperm banking. While most trusts fund sperm storage for cancer patients in some way or another, "there is no standard process," they wrote. "In some areas, sperm banking for cancer patients is not NHS funded, while in others, it is considered on a case-by-case basis. ... A further complexity is that even if PCTs fund the initial banking procedure, their policies then support sperm storage for different lengths of time." After a set period, 5 years, for example, the researchers wrote, patients may have to take on the costs of keeping sperm stored.

The researchers outlined a series of administrative and policy changes that would lessen obstacles to sperm storage and improve communication between sperm banks, PCTs, fertility centers and cancer doctors. While the bureaucratic changes toward improving uptake of sperm banking require some thought and planning, Dr. Hartshorne said, the remedy for clinicians is simple and can be put into place immediately: "Just, A: make the offer to everyone, and B: document that you did."

The study was funded by Cancer Research UK and the U.K. Department of Health; none of its authors declared conflicts of interest.

A survey-based study of oncologists and hematologists has shown that sperm banking is not routinely offered to U.K. men before potentially fertility-compromising cancer treatments.

Although U.S.-based studies have reported that as few as 50% of men are offered the opportunity to store sperm before cancer treatment (J. Clin. Oncol. 2002;20:1890-7), U.K. national guidelines state clearly that sperm cryostorage should be offered to all men and adolescents before undergoing such treatments. However, the study found, the decision to offer remains, in practice, largely a matter of clinician judgment, with a patient’s age, sexuality and chances of survival factored in.

For their research, published online Oct. 28 in the Annals of Oncology (doi:10.1093/annonc/mdq579), Geraldine Hartshorne, Ph.D., of the University of Warwick (England) and colleagues sent 2357 surveys to U.K. hematologists and oncologists from a national list, and 499 responses were received, 253 from hematologists and 246 from oncologists.

"The idea arose because I work in an IVF unit and we were aware of patients coming through who had had cancer treatment who did not have sperm banked," Dr. Hartshorne said in an interview. "Many had not been offered the opportunity."

Some 42% of oncologists and hematologists responding to Dr. Hartshorne and colleagues’ questionnaire said that they would offer sperm banking to patients whose cancer treatments had already begun, in direct contradiction of national clinical guidelines, the study found. And only 26% of oncologists and 38% of hematologists document their patients’ decisions on whether to have sperm stored.

About 11% of responding oncologists and hematologists said that they would "tend NOT to discuss sperm banking" with a patient who was homosexual, nearly 50% said they might not raise the issue with a patient unlikely to survive treatment, and 10% said they might hesitate with patients whom they would expect to take offense for religious reasons. Nearly 79% said they would tend not to talk about sperm storage with a terminally ill patient. Considerations of patients’ advanced age were also frequently cited as a factor in the decision whether to offer sperm banking (8% would tend not to discuss it with a person 40 or older; 36% would not do so with a patient 50 or older).

"We tried to analyze this in terms of whether doctors are making assumptions on their patients’ best interests, which of course doctors must do. But perhaps in this situation, this is not ideal practice," Dr. Hartshorne said, likening it to "unconscious discrimination."

Dr. Hartshorne and colleagues warned that clinicians who rely on their own judgments to ask patients about sperm banking could find themselves at risk of litigation. "Any set ‘cutoff’ age or personal criteria applied by clinicians could be challenged under human rights or equality legislation. Bearing in mind increasing social trends for second families, delaying parenthood and civil partnerships, an individualized approach is more appropriate. Moreover, posthumous use of banked sperm is legally accepted in the UK," they wrote.

Exacerbating the problem of uptake, Dr. Hartshorne and colleagues wrote, was the inconsistency of Primary Care Trusts in how they handle sperm banking. While most trusts fund sperm storage for cancer patients in some way or another, "there is no standard process," they wrote. "In some areas, sperm banking for cancer patients is not NHS funded, while in others, it is considered on a case-by-case basis. ... A further complexity is that even if PCTs fund the initial banking procedure, their policies then support sperm storage for different lengths of time." After a set period, 5 years, for example, the researchers wrote, patients may have to take on the costs of keeping sperm stored.

The researchers outlined a series of administrative and policy changes that would lessen obstacles to sperm storage and improve communication between sperm banks, PCTs, fertility centers and cancer doctors. While the bureaucratic changes toward improving uptake of sperm banking require some thought and planning, Dr. Hartshorne said, the remedy for clinicians is simple and can be put into place immediately: "Just, A: make the offer to everyone, and B: document that you did."

The study was funded by Cancer Research UK and the U.K. Department of Health; none of its authors declared conflicts of interest.

A survey-based study of oncologists and hematologists has shown that sperm banking is not routinely offered to U.K. men before potentially fertility-compromising cancer treatments.

Although U.S.-based studies have reported that as few as 50% of men are offered the opportunity to store sperm before cancer treatment (J. Clin. Oncol. 2002;20:1890-7), U.K. national guidelines state clearly that sperm cryostorage should be offered to all men and adolescents before undergoing such treatments. However, the study found, the decision to offer remains, in practice, largely a matter of clinician judgment, with a patient’s age, sexuality and chances of survival factored in.

For their research, published online Oct. 28 in the Annals of Oncology (doi:10.1093/annonc/mdq579), Geraldine Hartshorne, Ph.D., of the University of Warwick (England) and colleagues sent 2357 surveys to U.K. hematologists and oncologists from a national list, and 499 responses were received, 253 from hematologists and 246 from oncologists.

"The idea arose because I work in an IVF unit and we were aware of patients coming through who had had cancer treatment who did not have sperm banked," Dr. Hartshorne said in an interview. "Many had not been offered the opportunity."

Some 42% of oncologists and hematologists responding to Dr. Hartshorne and colleagues’ questionnaire said that they would offer sperm banking to patients whose cancer treatments had already begun, in direct contradiction of national clinical guidelines, the study found. And only 26% of oncologists and 38% of hematologists document their patients’ decisions on whether to have sperm stored.

About 11% of responding oncologists and hematologists said that they would "tend NOT to discuss sperm banking" with a patient who was homosexual, nearly 50% said they might not raise the issue with a patient unlikely to survive treatment, and 10% said they might hesitate with patients whom they would expect to take offense for religious reasons. Nearly 79% said they would tend not to talk about sperm storage with a terminally ill patient. Considerations of patients’ advanced age were also frequently cited as a factor in the decision whether to offer sperm banking (8% would tend not to discuss it with a person 40 or older; 36% would not do so with a patient 50 or older).

"We tried to analyze this in terms of whether doctors are making assumptions on their patients’ best interests, which of course doctors must do. But perhaps in this situation, this is not ideal practice," Dr. Hartshorne said, likening it to "unconscious discrimination."

Dr. Hartshorne and colleagues warned that clinicians who rely on their own judgments to ask patients about sperm banking could find themselves at risk of litigation. "Any set ‘cutoff’ age or personal criteria applied by clinicians could be challenged under human rights or equality legislation. Bearing in mind increasing social trends for second families, delaying parenthood and civil partnerships, an individualized approach is more appropriate. Moreover, posthumous use of banked sperm is legally accepted in the UK," they wrote.

Exacerbating the problem of uptake, Dr. Hartshorne and colleagues wrote, was the inconsistency of Primary Care Trusts in how they handle sperm banking. While most trusts fund sperm storage for cancer patients in some way or another, "there is no standard process," they wrote. "In some areas, sperm banking for cancer patients is not NHS funded, while in others, it is considered on a case-by-case basis. ... A further complexity is that even if PCTs fund the initial banking procedure, their policies then support sperm storage for different lengths of time." After a set period, 5 years, for example, the researchers wrote, patients may have to take on the costs of keeping sperm stored.

The researchers outlined a series of administrative and policy changes that would lessen obstacles to sperm storage and improve communication between sperm banks, PCTs, fertility centers and cancer doctors. While the bureaucratic changes toward improving uptake of sperm banking require some thought and planning, Dr. Hartshorne said, the remedy for clinicians is simple and can be put into place immediately: "Just, A: make the offer to everyone, and B: document that you did."

The study was funded by Cancer Research UK and the U.K. Department of Health; none of its authors declared conflicts of interest.

Ethnic minority children and children with severe chronic diseases died at a disproportionate rate during the H1N1 pandemic of 2009 and 2010, a U.K. government study has found, and the influenza pandemic proved deadlier to England’s children in general than did leukemia in any given year.

Photo credit: CDC

In their analysis of all 70 laboratory-confirmed H1N1 deaths in England for people younger than 18 years, published online Oct. 27 in the Lancet, Dr. Liam J. Donaldson of the U.K. National Patient Safety Agency and Dr. Nabihah Sachedina of the U.K. Department of Health showed overall pediatric mortality from pandemic influenza to have been 6 per million population. This rate is three times as high as England’s normal estimated pediatric death rate up to age 14 years for seasonal influenza, and slightly higher than the Netherlands death rate of 5 per million (in children under age 14) during the pandemic period (Lancet 2010 Oct. 27 [doi:10.1016/S0140-6736(10)61195-6]).

More prone to fatal pandemic H1N1 infection in England, the investigators found, were children born to Bangladeshi and Pakistani families – 47 and 36 per million, respectively, compared with 4 per million for white children. The authors said the finding “might be attributable to clustering of pandemic influenza A(H1N1) cases in areas of England with high ethnic minority populations,” although areas with lower ethnic minority populations were also affected, they noted. The authors allowed that more preexisting disorders might be present among ethnic minority children, but said there were few data to support the claim; among the 70 cases studied, preexisting health status did not differ among ethnic groups, they said.

Of the 70 fatal pediatric H1N1 cases recorded between June 26, 2009, and March 22, 2010, children with severe preexisting disease accounted for 45, or 64%, the investigators found; 15, or 21%, were healthy, and the rest had mild or moderate existing disease. Deaths occurred evenly between boys and girls (31 and 39, respectively), with the median age at death 7 years. Children under age 1 year also saw a higher rate than children as a whole (14 per 1 million population).

“Chronic neurological, gastrointestinal, or respiratory disease were all present in more than half of all deaths,” the authors wrote. Of the 35 children with neurological disorders who died, 19 had spastic quadriplegic cerebral palsy. Half of the school-age children who died had attended schools for children with special needs; nearly a quarter had been born prematurely. A prior diagnosis of asthma was present in 5 deaths, complex congenital cardiac disease was reported in 8, severe gastroesophageal reflux was reported in 11, and regular gastrostomy or nasogastric feeding took place in 41.

Some 27% of the deaths occurred before the child could be admitted to a hospital, the researchers said, and children in this group were likelier to have been healthy or to have only mild preexisting disorders than were those who died after admission.

In more than three-quarters of the deaths, primarily respiratory symptoms were reported at presentation; in two cases, mainly gastrointestinal symptoms were reported. Among hospital deaths, nearly a quarter of the children presented in cardiorespiratory arrest; only one presented with nonspecific symptoms, the investigators said.

Importantly, only two of the children who died had been vaccinated, and they had received vaccine too late – within 2 days before becoming sick – for it to be effective, they said.

The investigators concluded that children with the identified risk factors for death from influenza should be prioritized for vaccination.

The study was funded by the U.K. Department of Health. Dr. Donaldson was the chief medical officer for England from 1998 to May 2010. In this role he advised the government on the management of the pandemic. Dr. Sachedina supported him in this task from 2009 to 2010. They declared that they had no additional conflicts of interest.

In a comment accompanying the article, Dr. Robert A. Fowler and Dr. Philippe Jouvet of Sunnybrook Hospital, University of Toronto, said the fact that previously healthy children accounted for more than one-fifth of the deaths was a serious concern as well (Lancet 2010 Oct. 27 [doi:10.1016/S0140-6736(10)61385-2]).

“Although this finding is not more important than the identification of underlying medical risk factors, it represents a persistent message of the H1N1 pandemic – that children and young adults who were not expected to become severely ill because of influenza did so, and in greater numbers than with seasonal influenza,” they wrote.

Dr. Fowler and Dr. Jouvet declared they had no conflicts of interest.

Ethnic minority children and children with severe chronic diseases died at a disproportionate rate during the H1N1 pandemic of 2009 and 2010, a U.K. government study has found, and the influenza pandemic proved deadlier to England’s children in general than did leukemia in any given year.

Photo credit: CDC

In their analysis of all 70 laboratory-confirmed H1N1 deaths in England for people younger than 18 years, published online Oct. 27 in the Lancet, Dr. Liam J. Donaldson of the U.K. National Patient Safety Agency and Dr. Nabihah Sachedina of the U.K. Department of Health showed overall pediatric mortality from pandemic influenza to have been 6 per million population. This rate is three times as high as England’s normal estimated pediatric death rate up to age 14 years for seasonal influenza, and slightly higher than the Netherlands death rate of 5 per million (in children under age 14) during the pandemic period (Lancet 2010 Oct. 27 [doi:10.1016/S0140-6736(10)61195-6]).

More prone to fatal pandemic H1N1 infection in England, the investigators found, were children born to Bangladeshi and Pakistani families – 47 and 36 per million, respectively, compared with 4 per million for white children. The authors said the finding “might be attributable to clustering of pandemic influenza A(H1N1) cases in areas of England with high ethnic minority populations,” although areas with lower ethnic minority populations were also affected, they noted. The authors allowed that more preexisting disorders might be present among ethnic minority children, but said there were few data to support the claim; among the 70 cases studied, preexisting health status did not differ among ethnic groups, they said.

Of the 70 fatal pediatric H1N1 cases recorded between June 26, 2009, and March 22, 2010, children with severe preexisting disease accounted for 45, or 64%, the investigators found; 15, or 21%, were healthy, and the rest had mild or moderate existing disease. Deaths occurred evenly between boys and girls (31 and 39, respectively), with the median age at death 7 years. Children under age 1 year also saw a higher rate than children as a whole (14 per 1 million population).

“Chronic neurological, gastrointestinal, or respiratory disease were all present in more than half of all deaths,” the authors wrote. Of the 35 children with neurological disorders who died, 19 had spastic quadriplegic cerebral palsy. Half of the school-age children who died had attended schools for children with special needs; nearly a quarter had been born prematurely. A prior diagnosis of asthma was present in 5 deaths, complex congenital cardiac disease was reported in 8, severe gastroesophageal reflux was reported in 11, and regular gastrostomy or nasogastric feeding took place in 41.

Some 27% of the deaths occurred before the child could be admitted to a hospital, the researchers said, and children in this group were likelier to have been healthy or to have only mild preexisting disorders than were those who died after admission.

In more than three-quarters of the deaths, primarily respiratory symptoms were reported at presentation; in two cases, mainly gastrointestinal symptoms were reported. Among hospital deaths, nearly a quarter of the children presented in cardiorespiratory arrest; only one presented with nonspecific symptoms, the investigators said.

Importantly, only two of the children who died had been vaccinated, and they had received vaccine too late – within 2 days before becoming sick – for it to be effective, they said.

The investigators concluded that children with the identified risk factors for death from influenza should be prioritized for vaccination.

The study was funded by the U.K. Department of Health. Dr. Donaldson was the chief medical officer for England from 1998 to May 2010. In this role he advised the government on the management of the pandemic. Dr. Sachedina supported him in this task from 2009 to 2010. They declared that they had no additional conflicts of interest.

In a comment accompanying the article, Dr. Robert A. Fowler and Dr. Philippe Jouvet of Sunnybrook Hospital, University of Toronto, said the fact that previously healthy children accounted for more than one-fifth of the deaths was a serious concern as well (Lancet 2010 Oct. 27 [doi:10.1016/S0140-6736(10)61385-2]).

“Although this finding is not more important than the identification of underlying medical risk factors, it represents a persistent message of the H1N1 pandemic – that children and young adults who were not expected to become severely ill because of influenza did so, and in greater numbers than with seasonal influenza,” they wrote.

Dr. Fowler and Dr. Jouvet declared they had no conflicts of interest.

Ethnic minority children and children with severe chronic diseases died at a disproportionate rate during the H1N1 pandemic of 2009 and 2010, a U.K. government study has found, and the influenza pandemic proved deadlier to England’s children in general than did leukemia in any given year.

Photo credit: CDC

In their analysis of all 70 laboratory-confirmed H1N1 deaths in England for people younger than 18 years, published online Oct. 27 in the Lancet, Dr. Liam J. Donaldson of the U.K. National Patient Safety Agency and Dr. Nabihah Sachedina of the U.K. Department of Health showed overall pediatric mortality from pandemic influenza to have been 6 per million population. This rate is three times as high as England’s normal estimated pediatric death rate up to age 14 years for seasonal influenza, and slightly higher than the Netherlands death rate of 5 per million (in children under age 14) during the pandemic period (Lancet 2010 Oct. 27 [doi:10.1016/S0140-6736(10)61195-6]).

More prone to fatal pandemic H1N1 infection in England, the investigators found, were children born to Bangladeshi and Pakistani families – 47 and 36 per million, respectively, compared with 4 per million for white children. The authors said the finding “might be attributable to clustering of pandemic influenza A(H1N1) cases in areas of England with high ethnic minority populations,” although areas with lower ethnic minority populations were also affected, they noted. The authors allowed that more preexisting disorders might be present among ethnic minority children, but said there were few data to support the claim; among the 70 cases studied, preexisting health status did not differ among ethnic groups, they said.

Of the 70 fatal pediatric H1N1 cases recorded between June 26, 2009, and March 22, 2010, children with severe preexisting disease accounted for 45, or 64%, the investigators found; 15, or 21%, were healthy, and the rest had mild or moderate existing disease. Deaths occurred evenly between boys and girls (31 and 39, respectively), with the median age at death 7 years. Children under age 1 year also saw a higher rate than children as a whole (14 per 1 million population).

“Chronic neurological, gastrointestinal, or respiratory disease were all present in more than half of all deaths,” the authors wrote. Of the 35 children with neurological disorders who died, 19 had spastic quadriplegic cerebral palsy. Half of the school-age children who died had attended schools for children with special needs; nearly a quarter had been born prematurely. A prior diagnosis of asthma was present in 5 deaths, complex congenital cardiac disease was reported in 8, severe gastroesophageal reflux was reported in 11, and regular gastrostomy or nasogastric feeding took place in 41.

Some 27% of the deaths occurred before the child could be admitted to a hospital, the researchers said, and children in this group were likelier to have been healthy or to have only mild preexisting disorders than were those who died after admission.

In more than three-quarters of the deaths, primarily respiratory symptoms were reported at presentation; in two cases, mainly gastrointestinal symptoms were reported. Among hospital deaths, nearly a quarter of the children presented in cardiorespiratory arrest; only one presented with nonspecific symptoms, the investigators said.

Importantly, only two of the children who died had been vaccinated, and they had received vaccine too late – within 2 days before becoming sick – for it to be effective, they said.

The investigators concluded that children with the identified risk factors for death from influenza should be prioritized for vaccination.

The study was funded by the U.K. Department of Health. Dr. Donaldson was the chief medical officer for England from 1998 to May 2010. In this role he advised the government on the management of the pandemic. Dr. Sachedina supported him in this task from 2009 to 2010. They declared that they had no additional conflicts of interest.

In a comment accompanying the article, Dr. Robert A. Fowler and Dr. Philippe Jouvet of Sunnybrook Hospital, University of Toronto, said the fact that previously healthy children accounted for more than one-fifth of the deaths was a serious concern as well (Lancet 2010 Oct. 27 [doi:10.1016/S0140-6736(10)61385-2]).

“Although this finding is not more important than the identification of underlying medical risk factors, it represents a persistent message of the H1N1 pandemic – that children and young adults who were not expected to become severely ill because of influenza did so, and in greater numbers than with seasonal influenza,” they wrote.

Dr. Fowler and Dr. Jouvet declared they had no conflicts of interest.

Ethnic minority children and children with severe chronic diseases died at a disproportionate rate during the H1N1 pandemic of 2009 and 2010, a U.K. government study has found, and the influenza pandemic proved deadlier to England’s children in general than did leukemia in any given year.

Photo credit: CDC

In their analysis of all 70 laboratory-confirmed H1N1 deaths in England for people younger than 18 years, published online Oct. 27 in the Lancet, Dr. Liam J. Donaldson of the U.K. National Patient Safety Agency and Dr. Nabihah Sachedina of the U.K. Department of Health showed overall pediatric mortality from pandemic influenza to have been 6 per million population. This rate is three times as high as England’s normal estimated pediatric death rate up to age 14 years for seasonal influenza, and slightly higher than the Netherlands death rate of 5 per million (in children under age 14) during the pandemic period (Lancet 2010 Oct. 27 [doi:10.1016/S0140-6736(10)61195-6]).

More prone to fatal pandemic H1N1 infection in England, the investigators found, were children born to Bangladeshi and Pakistani families – 47 and 36 per million, respectively, compared with 4 per million for white children. The authors said the finding “might be attributable to clustering of pandemic influenza A(H1N1) cases in areas of England with high ethnic minority populations,” although areas with lower ethnic minority populations were also affected, they noted. The authors allowed that more preexisting disorders might be present among ethnic minority children, but said there were few data to support the claim; among the 70 cases studied, preexisting health status did not differ among ethnic groups, they said.

Of the 70 fatal pediatric H1N1 cases recorded between June 26, 2009, and March 22, 2010, children with severe preexisting disease accounted for 45, or 64%, the investigators found; 15, or 21%, were healthy, and the rest had mild or moderate existing disease. Deaths occurred evenly between boys and girls (31 and 39, respectively), with the median age at death 7 years. Children under age 1 year also saw a higher rate than children as a whole (14 per 1 million population).

“Chronic neurological, gastrointestinal, or respiratory disease were all present in more than half of all deaths,” the authors wrote. Of the 35 children with neurological disorders who died, 19 had spastic quadriplegic cerebral palsy. Half of the school-age children who died had attended schools for children with special needs; nearly a quarter had been born prematurely. A prior diagnosis of asthma was present in 5 deaths, complex congenital cardiac disease was reported in 8, severe gastroesophageal reflux was reported in 11, and regular gastrostomy or nasogastric feeding took place in 41.

Some 27% of the deaths occurred before the child could be admitted to a hospital, the researchers said, and children in this group were likelier to have been healthy or to have only mild preexisting disorders than were those who died after admission.

In more than three-quarters of the deaths, primarily respiratory symptoms were reported at presentation; in two cases, mainly gastrointestinal symptoms were reported. Among hospital deaths, nearly a quarter of the children presented in cardiorespiratory arrest; only one presented with nonspecific symptoms, the investigators said.

Importantly, only two of the children who died had been vaccinated, and they had received vaccine too late – within 2 days before becoming sick – for it to be effective, they said.

The investigators concluded that children with the identified risk factors for death from influenza should be prioritized for vaccination.

The study was funded by the U.K. Department of Health. Dr. Donaldson was the chief medical officer for England from 1998 to May 2010. In this role he advised the government on the management of the pandemic. Dr. Sachedina supported him in this task from 2009 to 2010. They declared that they had no additional conflicts of interest.

In a comment accompanying the article, Dr. Robert A. Fowler and Dr. Philippe Jouvet of Sunnybrook Hospital, University of Toronto, said the fact that previously healthy children accounted for more than one-fifth of the deaths was a serious concern as well (Lancet 2010 Oct. 27 [doi:10.1016/S0140-6736(10)61385-2]).

“Although this finding is not more important than the identification of underlying medical risk factors, it represents a persistent message of the H1N1 pandemic – that children and young adults who were not expected to become severely ill because of influenza did so, and in greater numbers than with seasonal influenza,” they wrote.

Dr. Fowler and Dr. Jouvet declared they had no conflicts of interest.

Ethnic minority children and children with severe chronic diseases died at a disproportionate rate during the H1N1 pandemic of 2009 and 2010, a U.K. government study has found, and the influenza pandemic proved deadlier to England’s children in general than did leukemia in any given year.

Photo credit: CDC

In their analysis of all 70 laboratory-confirmed H1N1 deaths in England for people younger than 18 years, published online Oct. 27 in the Lancet, Dr. Liam J. Donaldson of the U.K. National Patient Safety Agency and Dr. Nabihah Sachedina of the U.K. Department of Health showed overall pediatric mortality from pandemic influenza to have been 6 per million population. This rate is three times as high as England’s normal estimated pediatric death rate up to age 14 years for seasonal influenza, and slightly higher than the Netherlands death rate of 5 per million (in children under age 14) during the pandemic period (Lancet 2010 Oct. 27 [doi:10.1016/S0140-6736(10)61195-6]).

More prone to fatal pandemic H1N1 infection in England, the investigators found, were children born to Bangladeshi and Pakistani families – 47 and 36 per million, respectively, compared with 4 per million for white children. The authors said the finding “might be attributable to clustering of pandemic influenza A(H1N1) cases in areas of England with high ethnic minority populations,” although areas with lower ethnic minority populations were also affected, they noted. The authors allowed that more preexisting disorders might be present among ethnic minority children, but said there were few data to support the claim; among the 70 cases studied, preexisting health status did not differ among ethnic groups, they said.

Of the 70 fatal pediatric H1N1 cases recorded between June 26, 2009, and March 22, 2010, children with severe preexisting disease accounted for 45, or 64%, the investigators found; 15, or 21%, were healthy, and the rest had mild or moderate existing disease. Deaths occurred evenly between boys and girls (31 and 39, respectively), with the median age at death 7 years. Children under age 1 year also saw a higher rate than children as a whole (14 per 1 million population).

“Chronic neurological, gastrointestinal, or respiratory disease were all present in more than half of all deaths,” the authors wrote. Of the 35 children with neurological disorders who died, 19 had spastic quadriplegic cerebral palsy. Half of the school-age children who died had attended schools for children with special needs; nearly a quarter had been born prematurely. A prior diagnosis of asthma was present in 5 deaths, complex congenital cardiac disease was reported in 8, severe gastroesophageal reflux was reported in 11, and regular gastrostomy or nasogastric feeding took place in 41.

Some 27% of the deaths occurred before the child could be admitted to a hospital, the researchers said, and children in this group were likelier to have been healthy or to have only mild preexisting disorders than were those who died after admission.

In more than three-quarters of the deaths, primarily respiratory symptoms were reported at presentation; in two cases, mainly gastrointestinal symptoms were reported. Among hospital deaths, nearly a quarter of the children presented in cardiorespiratory arrest; only one presented with nonspecific symptoms, the investigators said.

Importantly, only two of the children who died had been vaccinated, and they had received vaccine too late – within 2 days before becoming sick – for it to be effective, they said.

The investigators concluded that children with the identified risk factors for death from influenza should be prioritized for vaccination.

The study was funded by the U.K. Department of Health. Dr. Donaldson was the chief medical officer for England from 1998 to May 2010. In this role he advised the government on the management of the pandemic. Dr. Sachedina supported him in this task from 2009 to 2010. They declared that they had no additional conflicts of interest.

In a comment accompanying the article, Dr. Robert A. Fowler and Dr. Philippe Jouvet of Sunnybrook Hospital, University of Toronto, said the fact that previously healthy children accounted for more than one-fifth of the deaths was a serious concern as well (Lancet 2010 Oct. 27 [doi:10.1016/S0140-6736(10)61385-2]).

“Although this finding is not more important than the identification of underlying medical risk factors, it represents a persistent message of the H1N1 pandemic – that children and young adults who were not expected to become severely ill because of influenza did so, and in greater numbers than with seasonal influenza,” they wrote.

Dr. Fowler and Dr. Jouvet declared they had no conflicts of interest.

Ethnic minority children and children with severe chronic diseases died at a disproportionate rate during the H1N1 pandemic of 2009 and 2010, a U.K. government study has found, and the influenza pandemic proved deadlier to England’s children in general than did leukemia in any given year.

Photo credit: CDC

In their analysis of all 70 laboratory-confirmed H1N1 deaths in England for people younger than 18 years, published online Oct. 27 in the Lancet, Dr. Liam J. Donaldson of the U.K. National Patient Safety Agency and Dr. Nabihah Sachedina of the U.K. Department of Health showed overall pediatric mortality from pandemic influenza to have been 6 per million population. This rate is three times as high as England’s normal estimated pediatric death rate up to age 14 years for seasonal influenza, and slightly higher than the Netherlands death rate of 5 per million (in children under age 14) during the pandemic period (Lancet 2010 Oct. 27 [doi:10.1016/S0140-6736(10)61195-6]).

More prone to fatal pandemic H1N1 infection in England, the investigators found, were children born to Bangladeshi and Pakistani families – 47 and 36 per million, respectively, compared with 4 per million for white children. The authors said the finding “might be attributable to clustering of pandemic influenza A(H1N1) cases in areas of England with high ethnic minority populations,” although areas with lower ethnic minority populations were also affected, they noted. The authors allowed that more preexisting disorders might be present among ethnic minority children, but said there were few data to support the claim; among the 70 cases studied, preexisting health status did not differ among ethnic groups, they said.

Of the 70 fatal pediatric H1N1 cases recorded between June 26, 2009, and March 22, 2010, children with severe preexisting disease accounted for 45, or 64%, the investigators found; 15, or 21%, were healthy, and the rest had mild or moderate existing disease. Deaths occurred evenly between boys and girls (31 and 39, respectively), with the median age at death 7 years. Children under age 1 year also saw a higher rate than children as a whole (14 per 1 million population).

“Chronic neurological, gastrointestinal, or respiratory disease were all present in more than half of all deaths,” the authors wrote. Of the 35 children with neurological disorders who died, 19 had spastic quadriplegic cerebral palsy. Half of the school-age children who died had attended schools for children with special needs; nearly a quarter had been born prematurely. A prior diagnosis of asthma was present in 5 deaths, complex congenital cardiac disease was reported in 8, severe gastroesophageal reflux was reported in 11, and regular gastrostomy or nasogastric feeding took place in 41.

Some 27% of the deaths occurred before the child could be admitted to a hospital, the researchers said, and children in this group were likelier to have been healthy or to have only mild preexisting disorders than were those who died after admission.

In more than three-quarters of the deaths, primarily respiratory symptoms were reported at presentation; in two cases, mainly gastrointestinal symptoms were reported. Among hospital deaths, nearly a quarter of the children presented in cardiorespiratory arrest; only one presented with nonspecific symptoms, the investigators said.

Importantly, only two of the children who died had been vaccinated, and they had received vaccine too late – within 2 days before becoming sick – for it to be effective, they said.

The investigators concluded that children with the identified risk factors for death from influenza should be prioritized for vaccination.

The study was funded by the U.K. Department of Health. Dr. Donaldson was the chief medical officer for England from 1998 to May 2010. In this role he advised the government on the management of the pandemic. Dr. Sachedina supported him in this task from 2009 to 2010. They declared that they had no additional conflicts of interest.

In a comment accompanying the article, Dr. Robert A. Fowler and Dr. Philippe Jouvet of Sunnybrook Hospital, University of Toronto, said the fact that previously healthy children accounted for more than one-fifth of the deaths was a serious concern as well (Lancet 2010 Oct. 27 [doi:10.1016/S0140-6736(10)61385-2]).

“Although this finding is not more important than the identification of underlying medical risk factors, it represents a persistent message of the H1N1 pandemic – that children and young adults who were not expected to become severely ill because of influenza did so, and in greater numbers than with seasonal influenza,” they wrote.

Dr. Fowler and Dr. Jouvet declared they had no conflicts of interest.