Mary Ann Moon

The use of DHA-rich fish oil supplements during pregnancy did not reduce the rate of postpartum depression in mothers or improve neurodevelopment in their children, according to a report.

“Current recommendations suggest that pregnant women increase their dietary DHA [docosahexaenoic acid] to improve their health outcomes as well as those of their children,” and the industry “successfully markets prenatal supplements with DHA to optimize brain function of mother and infant,” noted Maria Makrides, Ph.D., of Women's and Children's Hospital at Flinders Medical Centre in Adelaide, Australia, and her associates.

However, intervention trials with open-label designs, small sample sizes, high attrition rates, or poor statistical power have produced inconclusive results. Dr. Makrides and her colleagues performed the DOMINO (DHA to Optimize Mother Infant Outcome) trial to assess the efficacy and safety of DHA supplements.

In the double-blind trial, 2,320 women with singleton pregnancies who were attending five Australian perinatal centers were randomly assigned to take three fish oil capsules (1,197 women) or placebo capsules containing vegetable oil (1,202 women) daily. The fish oil capsules contained 800 mg/day of DHA and 100 mg/day of eicosapentaenoic acid. The study subjects were enrolled before they reached 21 weeks' gestation and took the supplements until delivery (JAMA 2010;304:1675-83).

The primary maternal outcome was a high level of depressive symptoms during the first 6 months post partum, as assessed by a score of more than 12 on the self-administered Edinburgh Postnatal Depression Scale. The incidence of that outcome was not significantly different between women who took fish oil capsules (9.7%) and the control subjects (11.2%).

In addition, the percentage of women who received a medical diagnosis of depression during the study did not differ significantly between the two groups.

The primary childhood outcome was neurodevelopment at age 18 months, as assessed by scores on the Cognitive and Language Composite Scales of the BSID-III (Bayley Scales of Infant and Toddler Development, third edition). Neither the mean cognitive scores nor the mean language scores differed significantly between children of mothers who took fish oil supplements and children of the control mothers. Similarly, scores on measures of motor development, social-emotional behavior, and adaptive behavior were not significantly different.

The women who took fish oil supplements had a lower rate of very preterm birth (1.1%) compared with the control group (2.3%). However, that was offset by their higher rate of postterm births requiring obstetric intervention (17.6% vs. 13.7%).

Adverse effects, including rates of hemorrhage and antenatal hospitalization, did not differ between the two study groups. The only adverse event that occurred more often in the DHA group than in the controls was eructation.

The Australian National Health and Medical Research Council funded the DOMINO study. Dr. Makrides reported serving on scientific advisory boards for Nestle, Fonterrra, and Nutricia.

DHA-rich fish oil supplements during pregnancy did not reduce the rate of postpartum depression or improve neurodevelopment in children.

Source ©Clayton Hansen/iStockphoto

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A Noteworthy Finding

One noteworthy finding of the DOMINO trial is that women who took fish oil supplements had a significantly lower risk of very preterm birth (defined as delivery before 34 weeks' gestation) than did women in the control group, said Dr. Emily Oken and Dr. Mandy B. Belfort.

The rate of very preterm birth was 1.1% with DHA-rich supplements (13 such births), compared with 2.3% with placebo (27 such births). The downstream benefits of that difference included lower rates of low birth weight, fewer admissions to the neonatal intensive care unit, and a nonsignificant 30% reduction in infant mortality.“

“Although the absolute numbers of these outcomes were small, the relative benefits were large,” they noted.

“For now, pregnant women should take care to get the recommended intake of 200 mg/day of DHA, either by including low-mercury, high-DHA fish in their diets or by taking a daily n-3 PUFA (polyunsaturated fatty acid) supplement. The benefit of higher intakes remains unclear,” Dr. Oken and Dr. Belfort concluded.

DR.OKEN is at Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston. DR. BELFORT is at Children's Hospital Boston. Neither Dr. Oken nor Dr. Belfort reported any financial disclosures. The comments were taken from their editorial accompanying the report (JAMA 2010;304:1717-8).

The use of DHA-rich fish oil supplements during pregnancy did not reduce the rate of postpartum depression in mothers or improve neurodevelopment in their children, according to a report.

“Current recommendations suggest that pregnant women increase their dietary DHA [docosahexaenoic acid] to improve their health outcomes as well as those of their children,” and the industry “successfully markets prenatal supplements with DHA to optimize brain function of mother and infant,” noted Maria Makrides, Ph.D., of Women's and Children's Hospital at Flinders Medical Centre in Adelaide, Australia, and her associates.

However, intervention trials with open-label designs, small sample sizes, high attrition rates, or poor statistical power have produced inconclusive results. Dr. Makrides and her colleagues performed the DOMINO (DHA to Optimize Mother Infant Outcome) trial to assess the efficacy and safety of DHA supplements.

In the double-blind trial, 2,320 women with singleton pregnancies who were attending five Australian perinatal centers were randomly assigned to take three fish oil capsules (1,197 women) or placebo capsules containing vegetable oil (1,202 women) daily. The fish oil capsules contained 800 mg/day of DHA and 100 mg/day of eicosapentaenoic acid. The study subjects were enrolled before they reached 21 weeks' gestation and took the supplements until delivery (JAMA 2010;304:1675-83).

The primary maternal outcome was a high level of depressive symptoms during the first 6 months post partum, as assessed by a score of more than 12 on the self-administered Edinburgh Postnatal Depression Scale. The incidence of that outcome was not significantly different between women who took fish oil capsules (9.7%) and the control subjects (11.2%).

In addition, the percentage of women who received a medical diagnosis of depression during the study did not differ significantly between the two groups.

The primary childhood outcome was neurodevelopment at age 18 months, as assessed by scores on the Cognitive and Language Composite Scales of the BSID-III (Bayley Scales of Infant and Toddler Development, third edition). Neither the mean cognitive scores nor the mean language scores differed significantly between children of mothers who took fish oil supplements and children of the control mothers. Similarly, scores on measures of motor development, social-emotional behavior, and adaptive behavior were not significantly different.

The women who took fish oil supplements had a lower rate of very preterm birth (1.1%) compared with the control group (2.3%). However, that was offset by their higher rate of postterm births requiring obstetric intervention (17.6% vs. 13.7%).

Adverse effects, including rates of hemorrhage and antenatal hospitalization, did not differ between the two study groups. The only adverse event that occurred more often in the DHA group than in the controls was eructation.

The Australian National Health and Medical Research Council funded the DOMINO study. Dr. Makrides reported serving on scientific advisory boards for Nestle, Fonterrra, and Nutricia.

DHA-rich fish oil supplements during pregnancy did not reduce the rate of postpartum depression or improve neurodevelopment in children.

Source ©Clayton Hansen/iStockphoto

View on the News

A Noteworthy Finding

One noteworthy finding of the DOMINO trial is that women who took fish oil supplements had a significantly lower risk of very preterm birth (defined as delivery before 34 weeks' gestation) than did women in the control group, said Dr. Emily Oken and Dr. Mandy B. Belfort.

The rate of very preterm birth was 1.1% with DHA-rich supplements (13 such births), compared with 2.3% with placebo (27 such births). The downstream benefits of that difference included lower rates of low birth weight, fewer admissions to the neonatal intensive care unit, and a nonsignificant 30% reduction in infant mortality.“

“Although the absolute numbers of these outcomes were small, the relative benefits were large,” they noted.

“For now, pregnant women should take care to get the recommended intake of 200 mg/day of DHA, either by including low-mercury, high-DHA fish in their diets or by taking a daily n-3 PUFA (polyunsaturated fatty acid) supplement. The benefit of higher intakes remains unclear,” Dr. Oken and Dr. Belfort concluded.

DR.OKEN is at Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston. DR. BELFORT is at Children's Hospital Boston. Neither Dr. Oken nor Dr. Belfort reported any financial disclosures. The comments were taken from their editorial accompanying the report (JAMA 2010;304:1717-8).

The use of DHA-rich fish oil supplements during pregnancy did not reduce the rate of postpartum depression in mothers or improve neurodevelopment in their children, according to a report.

“Current recommendations suggest that pregnant women increase their dietary DHA [docosahexaenoic acid] to improve their health outcomes as well as those of their children,” and the industry “successfully markets prenatal supplements with DHA to optimize brain function of mother and infant,” noted Maria Makrides, Ph.D., of Women's and Children's Hospital at Flinders Medical Centre in Adelaide, Australia, and her associates.

However, intervention trials with open-label designs, small sample sizes, high attrition rates, or poor statistical power have produced inconclusive results. Dr. Makrides and her colleagues performed the DOMINO (DHA to Optimize Mother Infant Outcome) trial to assess the efficacy and safety of DHA supplements.

In the double-blind trial, 2,320 women with singleton pregnancies who were attending five Australian perinatal centers were randomly assigned to take three fish oil capsules (1,197 women) or placebo capsules containing vegetable oil (1,202 women) daily. The fish oil capsules contained 800 mg/day of DHA and 100 mg/day of eicosapentaenoic acid. The study subjects were enrolled before they reached 21 weeks' gestation and took the supplements until delivery (JAMA 2010;304:1675-83).

The primary maternal outcome was a high level of depressive symptoms during the first 6 months post partum, as assessed by a score of more than 12 on the self-administered Edinburgh Postnatal Depression Scale. The incidence of that outcome was not significantly different between women who took fish oil capsules (9.7%) and the control subjects (11.2%).

In addition, the percentage of women who received a medical diagnosis of depression during the study did not differ significantly between the two groups.

The primary childhood outcome was neurodevelopment at age 18 months, as assessed by scores on the Cognitive and Language Composite Scales of the BSID-III (Bayley Scales of Infant and Toddler Development, third edition). Neither the mean cognitive scores nor the mean language scores differed significantly between children of mothers who took fish oil supplements and children of the control mothers. Similarly, scores on measures of motor development, social-emotional behavior, and adaptive behavior were not significantly different.

The women who took fish oil supplements had a lower rate of very preterm birth (1.1%) compared with the control group (2.3%). However, that was offset by their higher rate of postterm births requiring obstetric intervention (17.6% vs. 13.7%).

Adverse effects, including rates of hemorrhage and antenatal hospitalization, did not differ between the two study groups. The only adverse event that occurred more often in the DHA group than in the controls was eructation.

The Australian National Health and Medical Research Council funded the DOMINO study. Dr. Makrides reported serving on scientific advisory boards for Nestle, Fonterrra, and Nutricia.

DHA-rich fish oil supplements during pregnancy did not reduce the rate of postpartum depression or improve neurodevelopment in children.

Source ©Clayton Hansen/iStockphoto

View on the News

A Noteworthy Finding

One noteworthy finding of the DOMINO trial is that women who took fish oil supplements had a significantly lower risk of very preterm birth (defined as delivery before 34 weeks' gestation) than did women in the control group, said Dr. Emily Oken and Dr. Mandy B. Belfort.

The rate of very preterm birth was 1.1% with DHA-rich supplements (13 such births), compared with 2.3% with placebo (27 such births). The downstream benefits of that difference included lower rates of low birth weight, fewer admissions to the neonatal intensive care unit, and a nonsignificant 30% reduction in infant mortality.“

“Although the absolute numbers of these outcomes were small, the relative benefits were large,” they noted.

“For now, pregnant women should take care to get the recommended intake of 200 mg/day of DHA, either by including low-mercury, high-DHA fish in their diets or by taking a daily n-3 PUFA (polyunsaturated fatty acid) supplement. The benefit of higher intakes remains unclear,” Dr. Oken and Dr. Belfort concluded.

DR.OKEN is at Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston. DR. BELFORT is at Children's Hospital Boston. Neither Dr. Oken nor Dr. Belfort reported any financial disclosures. The comments were taken from their editorial accompanying the report (JAMA 2010;304:1717-8).

MRI remains strongly superior to mammography over the long term in screening women who are at increased risk of developing breast cancer, according to one study.

The advantage in sensitivity was highly significant for BRCA1 mutation carriers, but not for those who carried BRCA2 mutations and were more likely to present with ductal carcinoma in situ (DCIS).

Previous research showed that in the short term, MRI was approximately twice as sensitive as mammography in detecting breast cancer among women susceptible to the disease, and most guidelines now recommend MRI screening in those who carry BRCA1 or BRCA2 mutations. However, there is no consensus on the screening protocol for other risk groups, few studies have assessed BRCA1 carriers separately from BRCA2 carriers, and until now no studies have evaluated longer-term screening results, said Dr. Adriana J. Rijnsburger of Erasmus University Medical Center, Rotterdam, the Netherlands, and her associates.

To address these issues, the investigators enlarged and extended the Dutch MRI Screening Study (MRISC) and report their findings after following 2,157 women at six cancer or academic centers for 5 years.

The study subjects, aged 25–75 years at enrollment, had never had breast cancer but were at increased risk because they carried either the BRCA1 or BRCA2 mutation (raising their cumulative lifetime risk of developing breast cancer to 50%–85%), had a high-risk family history (raising their cumulative lifetime risk of developing breast cancer to 30%–50%), or had a moderate-risk family history (raising their cumulative lifetime risk of developing breast cancer to 15%–30%). They underwent biannual clinical breast examination and annual mammography and MRI.

During 5 years of follow-up, 97 breast cancers developed in 94 women, including 78 (80%) invasive tumors and 19 (20%) cases of DCIS.

Sensitivity at detecting breast cancer was 71% with MRI, significantly greater than the 41% sensitivity of mammography. When only invasive breast cancers were considered, MRI sensitivity increased to 78%, while mammography's sensitivity decreased to 36%. When the analysis was restricted only to women who carried genetic mutations, the sensitivity of MRI (67%) was “strikingly” higher than that of mammography (25%) for BRCA1 carriers. In contrast, MRI sensitivity (69%) was only slightly higher than mammography's sensitivity (62%) in BRCA2 carriers.

This difference can be explained, at least in part, by the higher proportion of DCIS in BRCA2 than in BRCA1 carriers; mammography was much more sensitive in detecting DCIS (69%) than in detecting invasive tumors (36%).

The specificity of the two screening methods was not significantly different.

Overall, 43% of breast cancers were detected by MRI only. This included 46% of the cancers in BRCA1 carriers, 31% in BRCA2 carriers, 41% in women with a high-risk family history, and 47% in the women with a moderate-risk family history, Dr. Rijnsburger and her colleagues said (J. Clin. Oncol. 2010; doi:10.1200/JCO.2009.27.2294).

These findings “support the recommendation of the American Cancer Society to use annual MRI screening not only for BRCA1/2 mutation carriers, but for all women with an approximately 20%–25% or greater cumulative lifetime risk of breast cancer due to a familial predisposition,” they noted.

Five women, all BRCA1/2 mutation carriers, developed distant metastases, and four of them died during follow-up. Two of the women who died had had a favorable tumor stage at diagnosis. This finding underscores the need for clinicians to avoid guaranteeing that all breast cancer deaths can be prevented by early detection via screening, the researchers said.

BRCA1-associated tumors “behaved completely differently” from BRCA2-associated tumors. They developed at a younger patient age, were not detected as well on mammography, were more likely to develop during the interval between screenings, were more likely to be invasive, and were larger at diagnosis. This indicates that the current screening schedule for BRCA1 carriers may need to be modified, perhaps by increasing MRI screening to twice rather than once yearly, they said.

This study was supported by the Dutch government and the Cancer Genomics Center in the Netherlands. The investigators reported having no financial conflicts of interest.

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Findings May Alter Routine Practice

“The investigators have conducted the largest such trial of MRI screening in high-risk individuals, and their new report that MRI screening appears to be preferentially useful in BRCA1 mutation carriers as compared to BRCA2 has potentially practice-changing implications,” said Dr. Andrew D. Seidman.

“The favorable overall survival in all high-risk groups reported suggests that careful MRI screening is not only superior to mammography alone, but may be an attractive alternative to risk-reducing prophylactic mastectomy for some women.”

ANDREW D. SEIDMAN, M.D., is on the American Society of Clinical Oncology communications committee and is an oncologist at Memorial Sloan-Kettering Cancer Center, New York. These comments were taken from an ASCO press statement accompanying the online report of Dr. Rijnsburger's study.

MRI remains strongly superior to mammography over the long term in screening women who are at increased risk of developing breast cancer, according to one study.

The advantage in sensitivity was highly significant for BRCA1 mutation carriers, but not for those who carried BRCA2 mutations and were more likely to present with ductal carcinoma in situ (DCIS).

Previous research showed that in the short term, MRI was approximately twice as sensitive as mammography in detecting breast cancer among women susceptible to the disease, and most guidelines now recommend MRI screening in those who carry BRCA1 or BRCA2 mutations. However, there is no consensus on the screening protocol for other risk groups, few studies have assessed BRCA1 carriers separately from BRCA2 carriers, and until now no studies have evaluated longer-term screening results, said Dr. Adriana J. Rijnsburger of Erasmus University Medical Center, Rotterdam, the Netherlands, and her associates.

To address these issues, the investigators enlarged and extended the Dutch MRI Screening Study (MRISC) and report their findings after following 2,157 women at six cancer or academic centers for 5 years.

The study subjects, aged 25–75 years at enrollment, had never had breast cancer but were at increased risk because they carried either the BRCA1 or BRCA2 mutation (raising their cumulative lifetime risk of developing breast cancer to 50%–85%), had a high-risk family history (raising their cumulative lifetime risk of developing breast cancer to 30%–50%), or had a moderate-risk family history (raising their cumulative lifetime risk of developing breast cancer to 15%–30%). They underwent biannual clinical breast examination and annual mammography and MRI.

During 5 years of follow-up, 97 breast cancers developed in 94 women, including 78 (80%) invasive tumors and 19 (20%) cases of DCIS.

Sensitivity at detecting breast cancer was 71% with MRI, significantly greater than the 41% sensitivity of mammography. When only invasive breast cancers were considered, MRI sensitivity increased to 78%, while mammography's sensitivity decreased to 36%. When the analysis was restricted only to women who carried genetic mutations, the sensitivity of MRI (67%) was “strikingly” higher than that of mammography (25%) for BRCA1 carriers. In contrast, MRI sensitivity (69%) was only slightly higher than mammography's sensitivity (62%) in BRCA2 carriers.

This difference can be explained, at least in part, by the higher proportion of DCIS in BRCA2 than in BRCA1 carriers; mammography was much more sensitive in detecting DCIS (69%) than in detecting invasive tumors (36%).

The specificity of the two screening methods was not significantly different.

Overall, 43% of breast cancers were detected by MRI only. This included 46% of the cancers in BRCA1 carriers, 31% in BRCA2 carriers, 41% in women with a high-risk family history, and 47% in the women with a moderate-risk family history, Dr. Rijnsburger and her colleagues said (J. Clin. Oncol. 2010; doi:10.1200/JCO.2009.27.2294).

These findings “support the recommendation of the American Cancer Society to use annual MRI screening not only for BRCA1/2 mutation carriers, but for all women with an approximately 20%–25% or greater cumulative lifetime risk of breast cancer due to a familial predisposition,” they noted.

Five women, all BRCA1/2 mutation carriers, developed distant metastases, and four of them died during follow-up. Two of the women who died had had a favorable tumor stage at diagnosis. This finding underscores the need for clinicians to avoid guaranteeing that all breast cancer deaths can be prevented by early detection via screening, the researchers said.

BRCA1-associated tumors “behaved completely differently” from BRCA2-associated tumors. They developed at a younger patient age, were not detected as well on mammography, were more likely to develop during the interval between screenings, were more likely to be invasive, and were larger at diagnosis. This indicates that the current screening schedule for BRCA1 carriers may need to be modified, perhaps by increasing MRI screening to twice rather than once yearly, they said.

This study was supported by the Dutch government and the Cancer Genomics Center in the Netherlands. The investigators reported having no financial conflicts of interest.

View on the News

Findings May Alter Routine Practice

“The investigators have conducted the largest such trial of MRI screening in high-risk individuals, and their new report that MRI screening appears to be preferentially useful in BRCA1 mutation carriers as compared to BRCA2 has potentially practice-changing implications,” said Dr. Andrew D. Seidman.

“The favorable overall survival in all high-risk groups reported suggests that careful MRI screening is not only superior to mammography alone, but may be an attractive alternative to risk-reducing prophylactic mastectomy for some women.”

ANDREW D. SEIDMAN, M.D., is on the American Society of Clinical Oncology communications committee and is an oncologist at Memorial Sloan-Kettering Cancer Center, New York. These comments were taken from an ASCO press statement accompanying the online report of Dr. Rijnsburger's study.

MRI remains strongly superior to mammography over the long term in screening women who are at increased risk of developing breast cancer, according to one study.

The advantage in sensitivity was highly significant for BRCA1 mutation carriers, but not for those who carried BRCA2 mutations and were more likely to present with ductal carcinoma in situ (DCIS).

Previous research showed that in the short term, MRI was approximately twice as sensitive as mammography in detecting breast cancer among women susceptible to the disease, and most guidelines now recommend MRI screening in those who carry BRCA1 or BRCA2 mutations. However, there is no consensus on the screening protocol for other risk groups, few studies have assessed BRCA1 carriers separately from BRCA2 carriers, and until now no studies have evaluated longer-term screening results, said Dr. Adriana J. Rijnsburger of Erasmus University Medical Center, Rotterdam, the Netherlands, and her associates.

To address these issues, the investigators enlarged and extended the Dutch MRI Screening Study (MRISC) and report their findings after following 2,157 women at six cancer or academic centers for 5 years.

The study subjects, aged 25–75 years at enrollment, had never had breast cancer but were at increased risk because they carried either the BRCA1 or BRCA2 mutation (raising their cumulative lifetime risk of developing breast cancer to 50%–85%), had a high-risk family history (raising their cumulative lifetime risk of developing breast cancer to 30%–50%), or had a moderate-risk family history (raising their cumulative lifetime risk of developing breast cancer to 15%–30%). They underwent biannual clinical breast examination and annual mammography and MRI.

During 5 years of follow-up, 97 breast cancers developed in 94 women, including 78 (80%) invasive tumors and 19 (20%) cases of DCIS.

Sensitivity at detecting breast cancer was 71% with MRI, significantly greater than the 41% sensitivity of mammography. When only invasive breast cancers were considered, MRI sensitivity increased to 78%, while mammography's sensitivity decreased to 36%. When the analysis was restricted only to women who carried genetic mutations, the sensitivity of MRI (67%) was “strikingly” higher than that of mammography (25%) for BRCA1 carriers. In contrast, MRI sensitivity (69%) was only slightly higher than mammography's sensitivity (62%) in BRCA2 carriers.

This difference can be explained, at least in part, by the higher proportion of DCIS in BRCA2 than in BRCA1 carriers; mammography was much more sensitive in detecting DCIS (69%) than in detecting invasive tumors (36%).

The specificity of the two screening methods was not significantly different.

Overall, 43% of breast cancers were detected by MRI only. This included 46% of the cancers in BRCA1 carriers, 31% in BRCA2 carriers, 41% in women with a high-risk family history, and 47% in the women with a moderate-risk family history, Dr. Rijnsburger and her colleagues said (J. Clin. Oncol. 2010; doi:10.1200/JCO.2009.27.2294).

These findings “support the recommendation of the American Cancer Society to use annual MRI screening not only for BRCA1/2 mutation carriers, but for all women with an approximately 20%–25% or greater cumulative lifetime risk of breast cancer due to a familial predisposition,” they noted.

Five women, all BRCA1/2 mutation carriers, developed distant metastases, and four of them died during follow-up. Two of the women who died had had a favorable tumor stage at diagnosis. This finding underscores the need for clinicians to avoid guaranteeing that all breast cancer deaths can be prevented by early detection via screening, the researchers said.

BRCA1-associated tumors “behaved completely differently” from BRCA2-associated tumors. They developed at a younger patient age, were not detected as well on mammography, were more likely to develop during the interval between screenings, were more likely to be invasive, and were larger at diagnosis. This indicates that the current screening schedule for BRCA1 carriers may need to be modified, perhaps by increasing MRI screening to twice rather than once yearly, they said.

This study was supported by the Dutch government and the Cancer Genomics Center in the Netherlands. The investigators reported having no financial conflicts of interest.

View on the News

Findings May Alter Routine Practice

“The investigators have conducted the largest such trial of MRI screening in high-risk individuals, and their new report that MRI screening appears to be preferentially useful in BRCA1 mutation carriers as compared to BRCA2 has potentially practice-changing implications,” said Dr. Andrew D. Seidman.

“The favorable overall survival in all high-risk groups reported suggests that careful MRI screening is not only superior to mammography alone, but may be an attractive alternative to risk-reducing prophylactic mastectomy for some women.”

ANDREW D. SEIDMAN, M.D., is on the American Society of Clinical Oncology communications committee and is an oncologist at Memorial Sloan-Kettering Cancer Center, New York. These comments were taken from an ASCO press statement accompanying the online report of Dr. Rijnsburger's study.

Major Finding: Opioid users had higher rates of overall adverse events, severe adverse events, cardiovascular events, fractures, and all-cause mortality than did NSAID users or coxib users.

Data Source: A propensity score–matched cohort analysis involving 12,840 elderly patients taking opioids, NSAIDs, or coxibs for rheumatoid arthritis or osteoarthritis pain.

Disclosures: The study was supported by the Agency for Healthcare Research and Quality. Dr. Solomon reported being an unpaid member of a celecoxib trial executive committee sponsored by Pfizer and an unpaid member of the data safety monitoring board for an analgesic trial sponsored by Pfizer.

Opioids were associated with more risks than were other analgesics in elderly patients taking the drugs for arthritis pain.

Although NSAIDs are known to pose certain risks, the results of the study “support the safety of [NSAIDs] compared with other analgesics,” said Dr. Daniel H. Solomon and his associates at Brigham and Women's Hospital, Boston.

Few studies have examined the relative risks of the three major analgesic groups: NSAIDs, opioids, and coxibs (selective cyclooxygenase-2 inhibitors). “Postmarketing surveillance data from usual care cohorts provide an opportunity to examine comparative safety across a wid-range of events and can complement safety data from randomized controlled trials. However, imbalance in baseline population characteristics confounds many postmarketing surveillance studies,” Dr. Solomon and his colleagues noted (Arch. Intern. Med. 2010;170:1968-78).

“Propensity score–matched analyses may provide better balance of confounders and facilitate relatively straightforward comparative safety analyses,” they added.

To compare safety, the researchers performed a propensity-matched cohort analysis using information from a Medicare database of pharmaceutical coverage for low-income elderly residents of Pennsylvania and New Jersey in 1999-2005. The study population included 12,840 adults with rheumatoid arthritis or osteoarthritis who began using one of the three types of analgesics during the study period and were followed for at least 1 year.

Overall, adverse safety event rates were high for all three groups, with the rate of adverse events leading to hospitalization being greater than 100 per 1,000 person-years for all three types of analgesics. Opioid users had the highest rates of serious adverse events. In particular, the rate of hip, pelvis, wrist, or humerus fractures was 101 per 1,000 person-years in the opioid group, compared with 19 per 1,000 person-years in the coxib group and 26 per 1,000 person-years in the NSAID group.

Even though a link between opioids and fractures has been reported previously, “the strength of the association we observed is larger than in previous reports,” Dr. Solomon and his associates said.

Compared with NSAIDs, opioids (hazard ratio, 1.77) and coxibs (HR, 1.28) were associated with elevated risk for cardiovascular events such as MI, stroke, heart failure, revascularization, and cardiac death. That “unexpected” finding regarding such severe events warrants further study, the investigators noted.

Compared with NSAIDs, risk for upper GI bleeding, lower GI bleeding, or bowel obstruction was similarly high for opioid users (HR, 1.07) but was lower for coxib users (HR, 0.60).

In general, opioid users experienced the most adverse events over time, while NSAID users experienced the fewest.

In addition, “opioid users experienced moderate risk early in treatment,” the investigators noted, while the other groups did not.

Opioid users had significantly higher all-cause mortality (75 deaths per 1,000 person-years) than did either NSAID users (48 deaths per 1,000 person-years) or coxib users (47 deaths per 1,000 person-years).

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Oversight in the Statistical Methods

The propensity matching was meticulous in this study, leading to well-balanced baseline characteristics among the three treatment groups.

This reassures readers that the observational study design is as robust as possible, and that treatment effects alone account for the observed differences among opioid, NSAID, and coxib users.

However, there is a single unmeasured confounder that calls into question the validity of some of the study findings: the use of over-the-counter NSAIDs, said Dr. William C. Becker and Dr. Patrick G. O'Connor.

It is likely that “a significant proportion” of patients in the opioid group were also taking NSAIDs, because “physicians routinely recommend antiinflammatory medication in addition to opioids to achieve therapeutic synergy in the treatment of arthritis,” they noted.

“It seems implausible that a group of 'opioid-only' elderly patients” who were actually taking supplemental NSAIDs would have a higher risk of adverse cardiovascular events, GI bleeding, and acute kidney injury than would a group taking NSAIDs alone, because these are all known effects of NSAID therapy.

Despite this limitation, “the data on falls and fracture from this … study are nonetheless compelling and carry important clinical implications,” Dr. Becker and Dr. O'Connor said.

DR. BECKER and DR. O'CONNOR are in general internal medicine at Yale University, New Haven, Conn. They reported no financial disclosures. These comments were taken from their invited commentary accompanying Dr. Solomon's report (Arch. Intern. Med. 2010;170:1986-8).

Major Finding: Opioid users had higher rates of overall adverse events, severe adverse events, cardiovascular events, fractures, and all-cause mortality than did NSAID users or coxib users.

Data Source: A propensity score–matched cohort analysis involving 12,840 elderly patients taking opioids, NSAIDs, or coxibs for rheumatoid arthritis or osteoarthritis pain.

Disclosures: The study was supported by the Agency for Healthcare Research and Quality. Dr. Solomon reported being an unpaid member of a celecoxib trial executive committee sponsored by Pfizer and an unpaid member of the data safety monitoring board for an analgesic trial sponsored by Pfizer.

Opioids were associated with more risks than were other analgesics in elderly patients taking the drugs for arthritis pain.

Although NSAIDs are known to pose certain risks, the results of the study “support the safety of [NSAIDs] compared with other analgesics,” said Dr. Daniel H. Solomon and his associates at Brigham and Women's Hospital, Boston.

Few studies have examined the relative risks of the three major analgesic groups: NSAIDs, opioids, and coxibs (selective cyclooxygenase-2 inhibitors). “Postmarketing surveillance data from usual care cohorts provide an opportunity to examine comparative safety across a wid-range of events and can complement safety data from randomized controlled trials. However, imbalance in baseline population characteristics confounds many postmarketing surveillance studies,” Dr. Solomon and his colleagues noted (Arch. Intern. Med. 2010;170:1968-78).

“Propensity score–matched analyses may provide better balance of confounders and facilitate relatively straightforward comparative safety analyses,” they added.

To compare safety, the researchers performed a propensity-matched cohort analysis using information from a Medicare database of pharmaceutical coverage for low-income elderly residents of Pennsylvania and New Jersey in 1999-2005. The study population included 12,840 adults with rheumatoid arthritis or osteoarthritis who began using one of the three types of analgesics during the study period and were followed for at least 1 year.

Overall, adverse safety event rates were high for all three groups, with the rate of adverse events leading to hospitalization being greater than 100 per 1,000 person-years for all three types of analgesics. Opioid users had the highest rates of serious adverse events. In particular, the rate of hip, pelvis, wrist, or humerus fractures was 101 per 1,000 person-years in the opioid group, compared with 19 per 1,000 person-years in the coxib group and 26 per 1,000 person-years in the NSAID group.

Even though a link between opioids and fractures has been reported previously, “the strength of the association we observed is larger than in previous reports,” Dr. Solomon and his associates said.

Compared with NSAIDs, opioids (hazard ratio, 1.77) and coxibs (HR, 1.28) were associated with elevated risk for cardiovascular events such as MI, stroke, heart failure, revascularization, and cardiac death. That “unexpected” finding regarding such severe events warrants further study, the investigators noted.

Compared with NSAIDs, risk for upper GI bleeding, lower GI bleeding, or bowel obstruction was similarly high for opioid users (HR, 1.07) but was lower for coxib users (HR, 0.60).

In general, opioid users experienced the most adverse events over time, while NSAID users experienced the fewest.

In addition, “opioid users experienced moderate risk early in treatment,” the investigators noted, while the other groups did not.

Opioid users had significantly higher all-cause mortality (75 deaths per 1,000 person-years) than did either NSAID users (48 deaths per 1,000 person-years) or coxib users (47 deaths per 1,000 person-years).

View on the news

Oversight in the Statistical Methods

The propensity matching was meticulous in this study, leading to well-balanced baseline characteristics among the three treatment groups.

This reassures readers that the observational study design is as robust as possible, and that treatment effects alone account for the observed differences among opioid, NSAID, and coxib users.

However, there is a single unmeasured confounder that calls into question the validity of some of the study findings: the use of over-the-counter NSAIDs, said Dr. William C. Becker and Dr. Patrick G. O'Connor.

It is likely that “a significant proportion” of patients in the opioid group were also taking NSAIDs, because “physicians routinely recommend antiinflammatory medication in addition to opioids to achieve therapeutic synergy in the treatment of arthritis,” they noted.

“It seems implausible that a group of 'opioid-only' elderly patients” who were actually taking supplemental NSAIDs would have a higher risk of adverse cardiovascular events, GI bleeding, and acute kidney injury than would a group taking NSAIDs alone, because these are all known effects of NSAID therapy.

Despite this limitation, “the data on falls and fracture from this … study are nonetheless compelling and carry important clinical implications,” Dr. Becker and Dr. O'Connor said.

DR. BECKER and DR. O'CONNOR are in general internal medicine at Yale University, New Haven, Conn. They reported no financial disclosures. These comments were taken from their invited commentary accompanying Dr. Solomon's report (Arch. Intern. Med. 2010;170:1986-8).

Major Finding: Opioid users had higher rates of overall adverse events, severe adverse events, cardiovascular events, fractures, and all-cause mortality than did NSAID users or coxib users.

Data Source: A propensity score–matched cohort analysis involving 12,840 elderly patients taking opioids, NSAIDs, or coxibs for rheumatoid arthritis or osteoarthritis pain.

Disclosures: The study was supported by the Agency for Healthcare Research and Quality. Dr. Solomon reported being an unpaid member of a celecoxib trial executive committee sponsored by Pfizer and an unpaid member of the data safety monitoring board for an analgesic trial sponsored by Pfizer.

Opioids were associated with more risks than were other analgesics in elderly patients taking the drugs for arthritis pain.

Although NSAIDs are known to pose certain risks, the results of the study “support the safety of [NSAIDs] compared with other analgesics,” said Dr. Daniel H. Solomon and his associates at Brigham and Women's Hospital, Boston.

Few studies have examined the relative risks of the three major analgesic groups: NSAIDs, opioids, and coxibs (selective cyclooxygenase-2 inhibitors). “Postmarketing surveillance data from usual care cohorts provide an opportunity to examine comparative safety across a wid-range of events and can complement safety data from randomized controlled trials. However, imbalance in baseline population characteristics confounds many postmarketing surveillance studies,” Dr. Solomon and his colleagues noted (Arch. Intern. Med. 2010;170:1968-78).

“Propensity score–matched analyses may provide better balance of confounders and facilitate relatively straightforward comparative safety analyses,” they added.

To compare safety, the researchers performed a propensity-matched cohort analysis using information from a Medicare database of pharmaceutical coverage for low-income elderly residents of Pennsylvania and New Jersey in 1999-2005. The study population included 12,840 adults with rheumatoid arthritis or osteoarthritis who began using one of the three types of analgesics during the study period and were followed for at least 1 year.

Overall, adverse safety event rates were high for all three groups, with the rate of adverse events leading to hospitalization being greater than 100 per 1,000 person-years for all three types of analgesics. Opioid users had the highest rates of serious adverse events. In particular, the rate of hip, pelvis, wrist, or humerus fractures was 101 per 1,000 person-years in the opioid group, compared with 19 per 1,000 person-years in the coxib group and 26 per 1,000 person-years in the NSAID group.

Even though a link between opioids and fractures has been reported previously, “the strength of the association we observed is larger than in previous reports,” Dr. Solomon and his associates said.

Compared with NSAIDs, opioids (hazard ratio, 1.77) and coxibs (HR, 1.28) were associated with elevated risk for cardiovascular events such as MI, stroke, heart failure, revascularization, and cardiac death. That “unexpected” finding regarding such severe events warrants further study, the investigators noted.

Compared with NSAIDs, risk for upper GI bleeding, lower GI bleeding, or bowel obstruction was similarly high for opioid users (HR, 1.07) but was lower for coxib users (HR, 0.60).

In general, opioid users experienced the most adverse events over time, while NSAID users experienced the fewest.

In addition, “opioid users experienced moderate risk early in treatment,” the investigators noted, while the other groups did not.

Opioid users had significantly higher all-cause mortality (75 deaths per 1,000 person-years) than did either NSAID users (48 deaths per 1,000 person-years) or coxib users (47 deaths per 1,000 person-years).

View on the news

Oversight in the Statistical Methods

The propensity matching was meticulous in this study, leading to well-balanced baseline characteristics among the three treatment groups.

This reassures readers that the observational study design is as robust as possible, and that treatment effects alone account for the observed differences among opioid, NSAID, and coxib users.

However, there is a single unmeasured confounder that calls into question the validity of some of the study findings: the use of over-the-counter NSAIDs, said Dr. William C. Becker and Dr. Patrick G. O'Connor.

It is likely that “a significant proportion” of patients in the opioid group were also taking NSAIDs, because “physicians routinely recommend antiinflammatory medication in addition to opioids to achieve therapeutic synergy in the treatment of arthritis,” they noted.

“It seems implausible that a group of 'opioid-only' elderly patients” who were actually taking supplemental NSAIDs would have a higher risk of adverse cardiovascular events, GI bleeding, and acute kidney injury than would a group taking NSAIDs alone, because these are all known effects of NSAID therapy.

Despite this limitation, “the data on falls and fracture from this … study are nonetheless compelling and carry important clinical implications,” Dr. Becker and Dr. O'Connor said.

DR. BECKER and DR. O'CONNOR are in general internal medicine at Yale University, New Haven, Conn. They reported no financial disclosures. These comments were taken from their invited commentary accompanying Dr. Solomon's report (Arch. Intern. Med. 2010;170:1986-8).

For symptomatic patients who undergo cardiac computed tomography angiography to evaluate suspected coronary artery disease, a finding of no CAD conveys an excellent prognosis, according to a meta-analysis of 18 studies of diagnostic cardiac computed tomography angiography (CCTA).

The meta-analysis clearly showed that the low (0.16%) annualized event rate that follows such negative test results is comparable to the background event rate among healthy, low-risk individuals in the general population. It is also comparable to the event rates observed after risk-stratification modalities such as stress echocardiography and myocardial perfusion scanning, said Dr. Edward A. Hulten of the cardiology service at Walter Reed Army Medical Center, Washington, and his associates.

The diagnostic accuracy of CCTA has been reported in more than 50 studies, but the technology's prognostic value has been less well established, the investigators observed. This meta-analysis shows that “the concept that CCTA offers anatomic but not prognostic value compared with widely used functional stress testing is no longer accurate,” they wrote.

Dr. Hulten and his colleagues performed a meta-analysis of prospective and retrospective observational studies in which 9,592 patients suspected of having CAD were evaluated using CCTA and followed for a median of 20 months. Seventeen of these studies were rated as good quality.

For the patients whose CCTA results indicated no CAD, the annualized rate of major adverse cardiovascular events (MACE) was 0.16%. There were no coronary revascularizations, myocardial infarctions, or admissions for unstable angina; the only events were from all-cause mortality.

“Considered in concert with the wealth of data regarding the high anatomic accuracy for CCTA, these results are convincing for CCTA to effectively diagnose CAD and convey risk strata for future adverse cardiovascular events,” the researchers said (J. Am. Coll. Cardiol. 2010;57 [doi:10.1016/jacc.2010.10.011]).

Positive results on CCTA correlated with major adverse cardiovascular events. The average annualized MACE rate for a finding of CAD was 8.8% per year (vs. 0.17% per year for negative findings). Revascularization procedures accounted for most of these events; the annualized rate of death or MI was 3.2% vs. 0.15 for positive vs. negative scans. Moreover, the rate of adverse events increased as the severity of coronary artery disease on CCTA exam increased.

Although a negative CCTA scan can be considered strongly predictive of an excellent outcome, the reverse is not true: A positive CCTA scan cannot be considered strongly predictive of future adverse events. With the annualized MACE rate at only 8.8%, the great majority of patients found on CCTA to have coronary disease also have good outcomes in the 20 months' follow-up, Dr. Hulten and his associates pointed out.

They also noted that many of the authors of studies included in the meta-analysis “reported prognosis based on a relatively simple classification of CAD luminal stenosis, specifically, no CAD, nonobstructive CAD, or potentially obstructive CAD (greater than 50% stenosis).” With studies defining “normal” CCTA in slightly different ways, it was not possible to have stratification details that would be clinically informative, the authors wrote. They also noted that their research included data from “different generations of CT scanning technology” the newer of which are known to have improved image quality and accuracy.

As in many other many studies of noninvasive coronary risk stratification tests, the investigators wrote, a limitation of their study is verification bias: “The observed increase in MACE is driven in part by coronary revascularization, demonstrating evidence of a work-up or verification bias. That is, patients with CCTA evidence of a greater than 50% stenosis are more likely to undergo catheterization and subsequent revascularization.”

For symptomatic patients who undergo cardiac computed tomography angiography to evaluate suspected coronary artery disease, a finding of no CAD conveys an excellent prognosis, according to a meta-analysis of 18 studies of diagnostic cardiac computed tomography angiography (CCTA).

The meta-analysis clearly showed that the low (0.16%) annualized event rate that follows such negative test results is comparable to the background event rate among healthy, low-risk individuals in the general population. It is also comparable to the event rates observed after risk-stratification modalities such as stress echocardiography and myocardial perfusion scanning, said Dr. Edward A. Hulten of the cardiology service at Walter Reed Army Medical Center, Washington, and his associates.

The diagnostic accuracy of CCTA has been reported in more than 50 studies, but the technology's prognostic value has been less well established, the investigators observed. This meta-analysis shows that “the concept that CCTA offers anatomic but not prognostic value compared with widely used functional stress testing is no longer accurate,” they wrote.

Dr. Hulten and his colleagues performed a meta-analysis of prospective and retrospective observational studies in which 9,592 patients suspected of having CAD were evaluated using CCTA and followed for a median of 20 months. Seventeen of these studies were rated as good quality.

For the patients whose CCTA results indicated no CAD, the annualized rate of major adverse cardiovascular events (MACE) was 0.16%. There were no coronary revascularizations, myocardial infarctions, or admissions for unstable angina; the only events were from all-cause mortality.

“Considered in concert with the wealth of data regarding the high anatomic accuracy for CCTA, these results are convincing for CCTA to effectively diagnose CAD and convey risk strata for future adverse cardiovascular events,” the researchers said (J. Am. Coll. Cardiol. 2010;57 [doi:10.1016/jacc.2010.10.011]).

Positive results on CCTA correlated with major adverse cardiovascular events. The average annualized MACE rate for a finding of CAD was 8.8% per year (vs. 0.17% per year for negative findings). Revascularization procedures accounted for most of these events; the annualized rate of death or MI was 3.2% vs. 0.15 for positive vs. negative scans. Moreover, the rate of adverse events increased as the severity of coronary artery disease on CCTA exam increased.

Although a negative CCTA scan can be considered strongly predictive of an excellent outcome, the reverse is not true: A positive CCTA scan cannot be considered strongly predictive of future adverse events. With the annualized MACE rate at only 8.8%, the great majority of patients found on CCTA to have coronary disease also have good outcomes in the 20 months' follow-up, Dr. Hulten and his associates pointed out.

They also noted that many of the authors of studies included in the meta-analysis “reported prognosis based on a relatively simple classification of CAD luminal stenosis, specifically, no CAD, nonobstructive CAD, or potentially obstructive CAD (greater than 50% stenosis).” With studies defining “normal” CCTA in slightly different ways, it was not possible to have stratification details that would be clinically informative, the authors wrote. They also noted that their research included data from “different generations of CT scanning technology” the newer of which are known to have improved image quality and accuracy.

As in many other many studies of noninvasive coronary risk stratification tests, the investigators wrote, a limitation of their study is verification bias: “The observed increase in MACE is driven in part by coronary revascularization, demonstrating evidence of a work-up or verification bias. That is, patients with CCTA evidence of a greater than 50% stenosis are more likely to undergo catheterization and subsequent revascularization.”

For symptomatic patients who undergo cardiac computed tomography angiography to evaluate suspected coronary artery disease, a finding of no CAD conveys an excellent prognosis, according to a meta-analysis of 18 studies of diagnostic cardiac computed tomography angiography (CCTA).

The meta-analysis clearly showed that the low (0.16%) annualized event rate that follows such negative test results is comparable to the background event rate among healthy, low-risk individuals in the general population. It is also comparable to the event rates observed after risk-stratification modalities such as stress echocardiography and myocardial perfusion scanning, said Dr. Edward A. Hulten of the cardiology service at Walter Reed Army Medical Center, Washington, and his associates.

The diagnostic accuracy of CCTA has been reported in more than 50 studies, but the technology's prognostic value has been less well established, the investigators observed. This meta-analysis shows that “the concept that CCTA offers anatomic but not prognostic value compared with widely used functional stress testing is no longer accurate,” they wrote.

Dr. Hulten and his colleagues performed a meta-analysis of prospective and retrospective observational studies in which 9,592 patients suspected of having CAD were evaluated using CCTA and followed for a median of 20 months. Seventeen of these studies were rated as good quality.

For the patients whose CCTA results indicated no CAD, the annualized rate of major adverse cardiovascular events (MACE) was 0.16%. There were no coronary revascularizations, myocardial infarctions, or admissions for unstable angina; the only events were from all-cause mortality.

“Considered in concert with the wealth of data regarding the high anatomic accuracy for CCTA, these results are convincing for CCTA to effectively diagnose CAD and convey risk strata for future adverse cardiovascular events,” the researchers said (J. Am. Coll. Cardiol. 2010;57 [doi:10.1016/jacc.2010.10.011]).

Positive results on CCTA correlated with major adverse cardiovascular events. The average annualized MACE rate for a finding of CAD was 8.8% per year (vs. 0.17% per year for negative findings). Revascularization procedures accounted for most of these events; the annualized rate of death or MI was 3.2% vs. 0.15 for positive vs. negative scans. Moreover, the rate of adverse events increased as the severity of coronary artery disease on CCTA exam increased.

Although a negative CCTA scan can be considered strongly predictive of an excellent outcome, the reverse is not true: A positive CCTA scan cannot be considered strongly predictive of future adverse events. With the annualized MACE rate at only 8.8%, the great majority of patients found on CCTA to have coronary disease also have good outcomes in the 20 months' follow-up, Dr. Hulten and his associates pointed out.

They also noted that many of the authors of studies included in the meta-analysis “reported prognosis based on a relatively simple classification of CAD luminal stenosis, specifically, no CAD, nonobstructive CAD, or potentially obstructive CAD (greater than 50% stenosis).” With studies defining “normal” CCTA in slightly different ways, it was not possible to have stratification details that would be clinically informative, the authors wrote. They also noted that their research included data from “different generations of CT scanning technology” the newer of which are known to have improved image quality and accuracy.

As in many other many studies of noninvasive coronary risk stratification tests, the investigators wrote, a limitation of their study is verification bias: “The observed increase in MACE is driven in part by coronary revascularization, demonstrating evidence of a work-up or verification bias. That is, patients with CCTA evidence of a greater than 50% stenosis are more likely to undergo catheterization and subsequent revascularization.”

Both markers of rheumatoid arthritis severity and traditional markers of cardiovascular risk are important and independent predictors of future CV events in RA patients.

Dr. Daniel H. Solomon, chief of the section of clinical sciences in the division of rheumatology, immunology, and allergy at the Brigham and Women's Hospital, Boston, and his associates examined the relative importance of the two types of markers in predicting CV events using a large, longitudinal cohort of RA patients, CORRONA (Consortium of Rheumatology Researchers of North America). Enrollment began in 2002, and patients were followed through 2006. For this analysis, 10,156 subjects were followed for a median of 22 months for the development of incident MI, stroke, or transient ischemic attack.

The study subjects' mean age was 59 years, and 75% were women. Median disease duration at baseline was 7 years. There were 29 MIs and 47 strokes or TIAs during follow-up, for an event rate of about 4 per 1,000 person-years.

Six traditional markers of CV risk – hypertension, diabetes, hyperlipidemia, current tobacco use, known cardiovascular disease, and a family history of premature CV events – were important predictors of CV events during follow-up. In addition, seven markers of RA severity were strong, independent predictors of CV risk.

Moreover, the incidence of CV events escalated as the number of either type of risk factor increased. The incidence was 0 in patients with no CV risk factors and no markers of RA severity, and it rose to 7.5 per 1,000 person-years in patients with two or more CV risk factors and three or more markers of RA severity, the researchers wrote (Ann. Rheum. Dis. 2010;69:1920-5).

There was no specific support for this analysis. Dr. Solomon receives support from the National Institutes of Health, the Agency for Healthcare Quality and Research, the Arthritis Foundation, Abbott, and Amgen.

Both markers of rheumatoid arthritis severity and traditional markers of cardiovascular risk are important and independent predictors of future CV events in RA patients.

Dr. Daniel H. Solomon, chief of the section of clinical sciences in the division of rheumatology, immunology, and allergy at the Brigham and Women's Hospital, Boston, and his associates examined the relative importance of the two types of markers in predicting CV events using a large, longitudinal cohort of RA patients, CORRONA (Consortium of Rheumatology Researchers of North America). Enrollment began in 2002, and patients were followed through 2006. For this analysis, 10,156 subjects were followed for a median of 22 months for the development of incident MI, stroke, or transient ischemic attack.

The study subjects' mean age was 59 years, and 75% were women. Median disease duration at baseline was 7 years. There were 29 MIs and 47 strokes or TIAs during follow-up, for an event rate of about 4 per 1,000 person-years.

Six traditional markers of CV risk – hypertension, diabetes, hyperlipidemia, current tobacco use, known cardiovascular disease, and a family history of premature CV events – were important predictors of CV events during follow-up. In addition, seven markers of RA severity were strong, independent predictors of CV risk.

Moreover, the incidence of CV events escalated as the number of either type of risk factor increased. The incidence was 0 in patients with no CV risk factors and no markers of RA severity, and it rose to 7.5 per 1,000 person-years in patients with two or more CV risk factors and three or more markers of RA severity, the researchers wrote (Ann. Rheum. Dis. 2010;69:1920-5).

There was no specific support for this analysis. Dr. Solomon receives support from the National Institutes of Health, the Agency for Healthcare Quality and Research, the Arthritis Foundation, Abbott, and Amgen.

Both markers of rheumatoid arthritis severity and traditional markers of cardiovascular risk are important and independent predictors of future CV events in RA patients.

Dr. Daniel H. Solomon, chief of the section of clinical sciences in the division of rheumatology, immunology, and allergy at the Brigham and Women's Hospital, Boston, and his associates examined the relative importance of the two types of markers in predicting CV events using a large, longitudinal cohort of RA patients, CORRONA (Consortium of Rheumatology Researchers of North America). Enrollment began in 2002, and patients were followed through 2006. For this analysis, 10,156 subjects were followed for a median of 22 months for the development of incident MI, stroke, or transient ischemic attack.

The study subjects' mean age was 59 years, and 75% were women. Median disease duration at baseline was 7 years. There were 29 MIs and 47 strokes or TIAs during follow-up, for an event rate of about 4 per 1,000 person-years.

Six traditional markers of CV risk – hypertension, diabetes, hyperlipidemia, current tobacco use, known cardiovascular disease, and a family history of premature CV events – were important predictors of CV events during follow-up. In addition, seven markers of RA severity were strong, independent predictors of CV risk.

Moreover, the incidence of CV events escalated as the number of either type of risk factor increased. The incidence was 0 in patients with no CV risk factors and no markers of RA severity, and it rose to 7.5 per 1,000 person-years in patients with two or more CV risk factors and three or more markers of RA severity, the researchers wrote (Ann. Rheum. Dis. 2010;69:1920-5).

There was no specific support for this analysis. Dr. Solomon receives support from the National Institutes of Health, the Agency for Healthcare Quality and Research, the Arthritis Foundation, Abbott, and Amgen.

Gait speed correlated with expected years of life remaining to people aged 65 years and older, with increased walking speed predicting longer life expectancy, according to a report in the Jan. 5 issue of JAMA.

For both sexes and at any age older than 65 years, a gait speed of 0.8 meters per second correlated with the median life expectancy for a person's age and sex. Faster walking speeds consistently correlated with extended survival, said Dr. Stephanie Studenski of the division of geriatric medicine at the University of Pittsburgh and her associates.

They assessed the relationship between gait speed and survival in a pooled analysis using data from nine cohort studies of community-dwelling adults. Each study included at least 400 people, gait speed data at baseline, and follow-up for at least 5 years. All of the studies measured gait speed by having subjects walk at their usual pace from a standing start for 6-8 feet indoors.

There were 34,485 study subjects, including “substantial” numbers of African American and Hispanic patients, as well as 1,765 who were older than 85 years. Gait speed ranged widely, from less than 0.4 meters per second (in 1,247 people) to more than 1.4 meters per second (in 1,491 people). There were 17,528 deaths during follow-up.

Predicted years of life remaining correlated with gait speed for patients of both sexes and all ages.

A walking speed of approximately 0.8 meters per second was associated with the predicted median life expectancy for a subject's age and sex. Gait speeds faster than that rate predicted longer-than-average life expectancy, while slower gait speeds predicted shorter-than-average life expectancy. Gait speeds of 1.2 meters per second and faster predicted “exceptional” life expectancy, the investigators said (JAMA 2010;305:50-8).

Gait speed “was especially informative after age 75 years” in patients who had no, or only minor, functional limitations. It may be less helpful in predicting life expectancy for patients who already report functional impairments and dependency on others for performing the activities of daily living, the investigators noted.

The data allowed Dr. Studenski and her colleagues to calculate survival estimates for a broad range of gait speeds, and to calculate absolute rates and median years of survival. “Compared with prior studies that were too small to assess potential effect modification by age, sex, race/ethnicity, and other subgroups, we were able to assess multiple subgroup effects with substantial power,” the researchers said.

However, they emphasized that the survival estimates must be validated in additional data sets before being used in clinical practice.

“Because gait speed can be assessed by nonprofessional staff using a 4-meter walkway and a stopwatch, it is relatively simple to measure compared with many medical assessments,” they added.

In practice, gait speed can be used to identify elderly patients with a high probability of living 5-10 more years, who can then be targeted for preventive interventions that require a long time before benefits are realized. It can also identify patients at increased risk for early mortality, who can then be targeted for interventions to maximize health and survival, the researchers explained.

The study was supported by the National Institute on Aging and by Merck. Dr. Studenski also received support from Merck, Novartis, and GTX, and royalties from “Hazzard's Geriatric Medicine & Gerontology,” Sixth Edition (McGraw Hill, 2009).

Gait speed correlated with expected years of life remaining to people aged 65 years and older, with increased walking speed predicting longer life expectancy, according to a report in the Jan. 5 issue of JAMA.

For both sexes and at any age older than 65 years, a gait speed of 0.8 meters per second correlated with the median life expectancy for a person's age and sex. Faster walking speeds consistently correlated with extended survival, said Dr. Stephanie Studenski of the division of geriatric medicine at the University of Pittsburgh and her associates.

They assessed the relationship between gait speed and survival in a pooled analysis using data from nine cohort studies of community-dwelling adults. Each study included at least 400 people, gait speed data at baseline, and follow-up for at least 5 years. All of the studies measured gait speed by having subjects walk at their usual pace from a standing start for 6-8 feet indoors.

There were 34,485 study subjects, including “substantial” numbers of African American and Hispanic patients, as well as 1,765 who were older than 85 years. Gait speed ranged widely, from less than 0.4 meters per second (in 1,247 people) to more than 1.4 meters per second (in 1,491 people). There were 17,528 deaths during follow-up.

Predicted years of life remaining correlated with gait speed for patients of both sexes and all ages.

A walking speed of approximately 0.8 meters per second was associated with the predicted median life expectancy for a subject's age and sex. Gait speeds faster than that rate predicted longer-than-average life expectancy, while slower gait speeds predicted shorter-than-average life expectancy. Gait speeds of 1.2 meters per second and faster predicted “exceptional” life expectancy, the investigators said (JAMA 2010;305:50-8).

Gait speed “was especially informative after age 75 years” in patients who had no, or only minor, functional limitations. It may be less helpful in predicting life expectancy for patients who already report functional impairments and dependency on others for performing the activities of daily living, the investigators noted.

The data allowed Dr. Studenski and her colleagues to calculate survival estimates for a broad range of gait speeds, and to calculate absolute rates and median years of survival. “Compared with prior studies that were too small to assess potential effect modification by age, sex, race/ethnicity, and other subgroups, we were able to assess multiple subgroup effects with substantial power,” the researchers said.

However, they emphasized that the survival estimates must be validated in additional data sets before being used in clinical practice.

“Because gait speed can be assessed by nonprofessional staff using a 4-meter walkway and a stopwatch, it is relatively simple to measure compared with many medical assessments,” they added.

In practice, gait speed can be used to identify elderly patients with a high probability of living 5-10 more years, who can then be targeted for preventive interventions that require a long time before benefits are realized. It can also identify patients at increased risk for early mortality, who can then be targeted for interventions to maximize health and survival, the researchers explained.

The study was supported by the National Institute on Aging and by Merck. Dr. Studenski also received support from Merck, Novartis, and GTX, and royalties from “Hazzard's Geriatric Medicine & Gerontology,” Sixth Edition (McGraw Hill, 2009).

Gait speed correlated with expected years of life remaining to people aged 65 years and older, with increased walking speed predicting longer life expectancy, according to a report in the Jan. 5 issue of JAMA.

For both sexes and at any age older than 65 years, a gait speed of 0.8 meters per second correlated with the median life expectancy for a person's age and sex. Faster walking speeds consistently correlated with extended survival, said Dr. Stephanie Studenski of the division of geriatric medicine at the University of Pittsburgh and her associates.

They assessed the relationship between gait speed and survival in a pooled analysis using data from nine cohort studies of community-dwelling adults. Each study included at least 400 people, gait speed data at baseline, and follow-up for at least 5 years. All of the studies measured gait speed by having subjects walk at their usual pace from a standing start for 6-8 feet indoors.

There were 34,485 study subjects, including “substantial” numbers of African American and Hispanic patients, as well as 1,765 who were older than 85 years. Gait speed ranged widely, from less than 0.4 meters per second (in 1,247 people) to more than 1.4 meters per second (in 1,491 people). There were 17,528 deaths during follow-up.

Predicted years of life remaining correlated with gait speed for patients of both sexes and all ages.

A walking speed of approximately 0.8 meters per second was associated with the predicted median life expectancy for a subject's age and sex. Gait speeds faster than that rate predicted longer-than-average life expectancy, while slower gait speeds predicted shorter-than-average life expectancy. Gait speeds of 1.2 meters per second and faster predicted “exceptional” life expectancy, the investigators said (JAMA 2010;305:50-8).

Gait speed “was especially informative after age 75 years” in patients who had no, or only minor, functional limitations. It may be less helpful in predicting life expectancy for patients who already report functional impairments and dependency on others for performing the activities of daily living, the investigators noted.

The data allowed Dr. Studenski and her colleagues to calculate survival estimates for a broad range of gait speeds, and to calculate absolute rates and median years of survival. “Compared with prior studies that were too small to assess potential effect modification by age, sex, race/ethnicity, and other subgroups, we were able to assess multiple subgroup effects with substantial power,” the researchers said.

However, they emphasized that the survival estimates must be validated in additional data sets before being used in clinical practice.

“Because gait speed can be assessed by nonprofessional staff using a 4-meter walkway and a stopwatch, it is relatively simple to measure compared with many medical assessments,” they added.

In practice, gait speed can be used to identify elderly patients with a high probability of living 5-10 more years, who can then be targeted for preventive interventions that require a long time before benefits are realized. It can also identify patients at increased risk for early mortality, who can then be targeted for interventions to maximize health and survival, the researchers explained.

The study was supported by the National Institute on Aging and by Merck. Dr. Studenski also received support from Merck, Novartis, and GTX, and royalties from “Hazzard's Geriatric Medicine & Gerontology,” Sixth Edition (McGraw Hill, 2009).

Maintaining a high level of physical activity throughout young adulthood curbed both the weight gain and the expanding waistline characteristic of middle age, according to a report in JAMA.

That finding, from a longitudinal study that tracked men and women during the 20-year transition from young adulthood to middle age, “highlights the value of incorporating and maintaining at least 30 minutes of activity into daily life,” said Dr. Arlene L. Hankinson of the department of preventive medicine at Northwestern University, Chicago, and her associates (JAMA 2010;304:2603-10).

The investigators undertook their study because public health guidelines recommending regular exercise have been “largely based on cross-sectional observational and short-term clinical evidence that cannot account for the changing risk of weight gain with increasing age,” the study investigators noted.

Moreover, it had never been shown that federal guidelines advocating 30 minutes of moderate to vigorous daily activity are sufficient to prevent weight gain during the transition to middle age, “when the highest risk of weight gain occurs,” they said.

Dr. Hankinson and her colleagues examined the issue using data from CARDIA (Coronary Artery Risk Development in Young Adults), a multicenter, longitudinal, cohort study of the development of coronary risk factors in young adults.

They assessed data collected for 3,554 subjects who were 18-30 years of age at baseline in 1985-1986 regarding self-reported participation in 13 specific sports, exercise, home maintenance, and occupational activities.

At all activity levels, men and women alike showed gains in weight, body mass index, and waist circumference during the study's 20 years of follow-up.

“Some age-related weight gain may be unavoidable in our society, as it has been observed even among a population of vigorously active runners through middle age,” the researchers noted.

However, habitual daily vigorous physical activity was associated with smaller increases in mean weight, BMI, and waist circumference, compared with moderate, inconsistent, or low activity, the investigators added.

Men with high activity levels gained 2.6 fewer kilograms, and women with high activity levels gained 6.1 fewer kilograms per year than did men and women with low activity levels.

Similarly, men with high activity levels gained 3.1 fewer centimeters and women with high activity levels gained 3.8 fewer centimeters in waist circumference per year.

However, only a small proportion of the study subjects (11% of men and 12% of women) maintained that high level of vigorous activity over 20 years.

Approximately 37% of the study cohort participated in regular activity equivalent to the levels recommended by the U. S. Department of Health and Human Services.

At that level of activity, men gained 1.8 fewer kilograms and women gained 4.7 fewer kilograms during follow-up than did study subjects who had lower levels of activity.

The National Heart, Lung, and Blood Institute supported the study. No financial conflicts of interest were reported.

Maintaining a high level of physical activity throughout young adulthood curbed both the weight gain and the expanding waistline characteristic of middle age, according to a report in JAMA.

That finding, from a longitudinal study that tracked men and women during the 20-year transition from young adulthood to middle age, “highlights the value of incorporating and maintaining at least 30 minutes of activity into daily life,” said Dr. Arlene L. Hankinson of the department of preventive medicine at Northwestern University, Chicago, and her associates (JAMA 2010;304:2603-10).

The investigators undertook their study because public health guidelines recommending regular exercise have been “largely based on cross-sectional observational and short-term clinical evidence that cannot account for the changing risk of weight gain with increasing age,” the study investigators noted.

Moreover, it had never been shown that federal guidelines advocating 30 minutes of moderate to vigorous daily activity are sufficient to prevent weight gain during the transition to middle age, “when the highest risk of weight gain occurs,” they said.

Dr. Hankinson and her colleagues examined the issue using data from CARDIA (Coronary Artery Risk Development in Young Adults), a multicenter, longitudinal, cohort study of the development of coronary risk factors in young adults.

They assessed data collected for 3,554 subjects who were 18-30 years of age at baseline in 1985-1986 regarding self-reported participation in 13 specific sports, exercise, home maintenance, and occupational activities.

At all activity levels, men and women alike showed gains in weight, body mass index, and waist circumference during the study's 20 years of follow-up.

“Some age-related weight gain may be unavoidable in our society, as it has been observed even among a population of vigorously active runners through middle age,” the researchers noted.

However, habitual daily vigorous physical activity was associated with smaller increases in mean weight, BMI, and waist circumference, compared with moderate, inconsistent, or low activity, the investigators added.

Men with high activity levels gained 2.6 fewer kilograms, and women with high activity levels gained 6.1 fewer kilograms per year than did men and women with low activity levels.

Similarly, men with high activity levels gained 3.1 fewer centimeters and women with high activity levels gained 3.8 fewer centimeters in waist circumference per year.

However, only a small proportion of the study subjects (11% of men and 12% of women) maintained that high level of vigorous activity over 20 years.

Approximately 37% of the study cohort participated in regular activity equivalent to the levels recommended by the U. S. Department of Health and Human Services.

At that level of activity, men gained 1.8 fewer kilograms and women gained 4.7 fewer kilograms during follow-up than did study subjects who had lower levels of activity.

The National Heart, Lung, and Blood Institute supported the study. No financial conflicts of interest were reported.

Maintaining a high level of physical activity throughout young adulthood curbed both the weight gain and the expanding waistline characteristic of middle age, according to a report in JAMA.

That finding, from a longitudinal study that tracked men and women during the 20-year transition from young adulthood to middle age, “highlights the value of incorporating and maintaining at least 30 minutes of activity into daily life,” said Dr. Arlene L. Hankinson of the department of preventive medicine at Northwestern University, Chicago, and her associates (JAMA 2010;304:2603-10).

The investigators undertook their study because public health guidelines recommending regular exercise have been “largely based on cross-sectional observational and short-term clinical evidence that cannot account for the changing risk of weight gain with increasing age,” the study investigators noted.

Moreover, it had never been shown that federal guidelines advocating 30 minutes of moderate to vigorous daily activity are sufficient to prevent weight gain during the transition to middle age, “when the highest risk of weight gain occurs,” they said.

Dr. Hankinson and her colleagues examined the issue using data from CARDIA (Coronary Artery Risk Development in Young Adults), a multicenter, longitudinal, cohort study of the development of coronary risk factors in young adults.

They assessed data collected for 3,554 subjects who were 18-30 years of age at baseline in 1985-1986 regarding self-reported participation in 13 specific sports, exercise, home maintenance, and occupational activities.

At all activity levels, men and women alike showed gains in weight, body mass index, and waist circumference during the study's 20 years of follow-up.

“Some age-related weight gain may be unavoidable in our society, as it has been observed even among a population of vigorously active runners through middle age,” the researchers noted.

However, habitual daily vigorous physical activity was associated with smaller increases in mean weight, BMI, and waist circumference, compared with moderate, inconsistent, or low activity, the investigators added.

Men with high activity levels gained 2.6 fewer kilograms, and women with high activity levels gained 6.1 fewer kilograms per year than did men and women with low activity levels.

Similarly, men with high activity levels gained 3.1 fewer centimeters and women with high activity levels gained 3.8 fewer centimeters in waist circumference per year.

However, only a small proportion of the study subjects (11% of men and 12% of women) maintained that high level of vigorous activity over 20 years.

Approximately 37% of the study cohort participated in regular activity equivalent to the levels recommended by the U. S. Department of Health and Human Services.

At that level of activity, men gained 1.8 fewer kilograms and women gained 4.7 fewer kilograms during follow-up than did study subjects who had lower levels of activity.

The National Heart, Lung, and Blood Institute supported the study. No financial conflicts of interest were reported.

Opioids were associated with more risks than were other analgesics in elderly patients taking the drugs for arthritis pain, according to a report in the Archives of Internal Medicine.

Although NSAIDs are known to pose certain risks, the results of the study “support the safety of [NSAIDs] compared with other analgesics,” said Dr. Daniel H. Solomon and his associates at Brigham and Women's Hospital, Boston.

Few studies have examined the relative risks of the three major analgesic groups: NSAIDs, opioids, and coxibs (selective cyclooxygenase-2 inhibitors). “Postmarketing surveillance data from usual care cohorts provide an opportunity to examine comparative safety across a wide range of events and can complement safety data from randomized controlled trials. However, imbalance in baseline population characteristics confounds many postmarketing surveillance studies,” Dr. Solomon and his colleagues noted (Arch. Intern. Med. 2010;170:1968-78). “Propensity score-matched analyses may provide better balance of confounders and facilitate relatively straightforward comparative safety analyses,” they added.

To compare safety, the researchers performed a propensity-matched cohort analysis using information from a Medicare database of pharmaceutical coverage for low-income elderly residents of Pennsylvania and New Jersey in 1999-2005. The study population included 12,840 adults with rheumatoid arthritis or osteoarthritis who began using one of the three types of analgesics during the study period and were followed for at least 1 year.

Overall, adverse safety event rates were high for all three groups, with the rate of adverse-event hospitalization being greater than 100 per 1,000 person-years for all three types of analgesics.

Opioid users had the highest rates of serious adverse events. Their rate of hip, pelvis, wrist, or humerus fractures was 101 per 1,000 person-years, compared with 19 per 1,000 person-years in the coxib group and 26 per 1,000 person-years in the NSAID group. Even though a link between opioids and fractures has been reported previously, “the strength of the association we observed is larger than in previous reports,” the researchers said.

Compared with NSAIDs, opioids (hazard ratio, 1.77) and coxibs (HR, 1.28) were associated with elevated risk for cardiovascular events such as MI, stroke, heart failure, revascularization, and cardiac death. That “unexpected” finding regarding such severe events warrants further study, the investigators noted.

Compared with NSAIDs, risk for upper GI bleeding, lower GI bleeding, or bowel obstruction was similarly high for opioid users (HR, 1.07) but was lower for coxib users (HR, 0.60).

In general, opioid users experienced the most adverse events over time, and NSAID users experienced the fewest. In addition, “opioid users experienced moderate risk early in treatment,” the researchers noted, whereas the other groups did not. Opioid users had significantly higher all-cause mortality (75 deaths per 1,000 person-years) than did either NSAID users (48 deaths per 1,000 person-years) or coxib users (47 deaths per 1,000 person-years).

The study findings indicate that recent concerns that have been raised regarding the use of opioids for nonmalignant pain are warranted, the researchers said.

The study was supported by the Agency for Healthcare Research and Quality. Dr. Solomon reported being an unpaid member of a celecoxib trial executive committee sponsored by Pfizer and an unpaid member of the data safety monitoring board for an analgesic trial sponsored by Pfizer.

View on the News

An Oversight in Statistical Methods

The propensity matching was meticulous in this study, leading to well-balanced baseline characteristics among the three treatment groups. This reassures readers that the observational study design is as robust as possible, and that treatment effects alone account for the observed differences among opioid, NSAID, and coxib users.

However, there is a single unmeasured confounder that calls into question the validity of some of the study findings: the use of over-the-counter NSAIDs, noted Dr. William C. Becker and Dr. Patrick G. O'Connor.

It is likely that “a significant proportion” of patients in the opioid group were also taking NSAIDs, because “physicians routinely recommend antiinflammatory medication in addition to opioids to achieve therapeutic synergy in the treatment of arthritis,” they noted.

“It seems implausible that a group of 'opioid-only' elderly patients” who were actually taking supplemental NSAIDs would have a higher risk of adverse cardiovascular events, GI bleeding, and acute kidney injury than would a group taking NSAIDs alone, because these are all known effects of NSAID therapy.

Despite this limitation, “the data on falls and fracture from this … study are nonetheless compelling and carry important clinical implications,” Dr. Becker and Dr. O'Connor said.

DR. BECKER and DR. O'CONNOR are in general internal medicine at Yale University, New Haven, Conn. They reported no financial disclosures. These comments were taken from their invited commentary accompanying Dr. Solomon's report (Arch. Intern. Med. 2010;170:1986-8).

Opioids were associated with more risks than were other analgesics in elderly patients taking the drugs for arthritis pain, according to a report in the Archives of Internal Medicine.

Although NSAIDs are known to pose certain risks, the results of the study “support the safety of [NSAIDs] compared with other analgesics,” said Dr. Daniel H. Solomon and his associates at Brigham and Women's Hospital, Boston.

Few studies have examined the relative risks of the three major analgesic groups: NSAIDs, opioids, and coxibs (selective cyclooxygenase-2 inhibitors). “Postmarketing surveillance data from usual care cohorts provide an opportunity to examine comparative safety across a wide range of events and can complement safety data from randomized controlled trials. However, imbalance in baseline population characteristics confounds many postmarketing surveillance studies,” Dr. Solomon and his colleagues noted (Arch. Intern. Med. 2010;170:1968-78). “Propensity score-matched analyses may provide better balance of confounders and facilitate relatively straightforward comparative safety analyses,” they added.

To compare safety, the researchers performed a propensity-matched cohort analysis using information from a Medicare database of pharmaceutical coverage for low-income elderly residents of Pennsylvania and New Jersey in 1999-2005. The study population included 12,840 adults with rheumatoid arthritis or osteoarthritis who began using one of the three types of analgesics during the study period and were followed for at least 1 year.

Overall, adverse safety event rates were high for all three groups, with the rate of adverse-event hospitalization being greater than 100 per 1,000 person-years for all three types of analgesics.

Opioid users had the highest rates of serious adverse events. Their rate of hip, pelvis, wrist, or humerus fractures was 101 per 1,000 person-years, compared with 19 per 1,000 person-years in the coxib group and 26 per 1,000 person-years in the NSAID group. Even though a link between opioids and fractures has been reported previously, “the strength of the association we observed is larger than in previous reports,” the researchers said.

Compared with NSAIDs, opioids (hazard ratio, 1.77) and coxibs (HR, 1.28) were associated with elevated risk for cardiovascular events such as MI, stroke, heart failure, revascularization, and cardiac death. That “unexpected” finding regarding such severe events warrants further study, the investigators noted.

Compared with NSAIDs, risk for upper GI bleeding, lower GI bleeding, or bowel obstruction was similarly high for opioid users (HR, 1.07) but was lower for coxib users (HR, 0.60).

In general, opioid users experienced the most adverse events over time, and NSAID users experienced the fewest. In addition, “opioid users experienced moderate risk early in treatment,” the researchers noted, whereas the other groups did not. Opioid users had significantly higher all-cause mortality (75 deaths per 1,000 person-years) than did either NSAID users (48 deaths per 1,000 person-years) or coxib users (47 deaths per 1,000 person-years).

The study findings indicate that recent concerns that have been raised regarding the use of opioids for nonmalignant pain are warranted, the researchers said.

The study was supported by the Agency for Healthcare Research and Quality. Dr. Solomon reported being an unpaid member of a celecoxib trial executive committee sponsored by Pfizer and an unpaid member of the data safety monitoring board for an analgesic trial sponsored by Pfizer.

View on the News

An Oversight in Statistical Methods

The propensity matching was meticulous in this study, leading to well-balanced baseline characteristics among the three treatment groups. This reassures readers that the observational study design is as robust as possible, and that treatment effects alone account for the observed differences among opioid, NSAID, and coxib users.

However, there is a single unmeasured confounder that calls into question the validity of some of the study findings: the use of over-the-counter NSAIDs, noted Dr. William C. Becker and Dr. Patrick G. O'Connor.

It is likely that “a significant proportion” of patients in the opioid group were also taking NSAIDs, because “physicians routinely recommend antiinflammatory medication in addition to opioids to achieve therapeutic synergy in the treatment of arthritis,” they noted.

“It seems implausible that a group of 'opioid-only' elderly patients” who were actually taking supplemental NSAIDs would have a higher risk of adverse cardiovascular events, GI bleeding, and acute kidney injury than would a group taking NSAIDs alone, because these are all known effects of NSAID therapy.

Despite this limitation, “the data on falls and fracture from this … study are nonetheless compelling and carry important clinical implications,” Dr. Becker and Dr. O'Connor said.

DR. BECKER and DR. O'CONNOR are in general internal medicine at Yale University, New Haven, Conn. They reported no financial disclosures. These comments were taken from their invited commentary accompanying Dr. Solomon's report (Arch. Intern. Med. 2010;170:1986-8).

Opioids were associated with more risks than were other analgesics in elderly patients taking the drugs for arthritis pain, according to a report in the Archives of Internal Medicine.

Although NSAIDs are known to pose certain risks, the results of the study “support the safety of [NSAIDs] compared with other analgesics,” said Dr. Daniel H. Solomon and his associates at Brigham and Women's Hospital, Boston.

Few studies have examined the relative risks of the three major analgesic groups: NSAIDs, opioids, and coxibs (selective cyclooxygenase-2 inhibitors). “Postmarketing surveillance data from usual care cohorts provide an opportunity to examine comparative safety across a wide range of events and can complement safety data from randomized controlled trials. However, imbalance in baseline population characteristics confounds many postmarketing surveillance studies,” Dr. Solomon and his colleagues noted (Arch. Intern. Med. 2010;170:1968-78). “Propensity score-matched analyses may provide better balance of confounders and facilitate relatively straightforward comparative safety analyses,” they added.

To compare safety, the researchers performed a propensity-matched cohort analysis using information from a Medicare database of pharmaceutical coverage for low-income elderly residents of Pennsylvania and New Jersey in 1999-2005. The study population included 12,840 adults with rheumatoid arthritis or osteoarthritis who began using one of the three types of analgesics during the study period and were followed for at least 1 year.

Overall, adverse safety event rates were high for all three groups, with the rate of adverse-event hospitalization being greater than 100 per 1,000 person-years for all three types of analgesics.

Opioid users had the highest rates of serious adverse events. Their rate of hip, pelvis, wrist, or humerus fractures was 101 per 1,000 person-years, compared with 19 per 1,000 person-years in the coxib group and 26 per 1,000 person-years in the NSAID group. Even though a link between opioids and fractures has been reported previously, “the strength of the association we observed is larger than in previous reports,” the researchers said.

Compared with NSAIDs, opioids (hazard ratio, 1.77) and coxibs (HR, 1.28) were associated with elevated risk for cardiovascular events such as MI, stroke, heart failure, revascularization, and cardiac death. That “unexpected” finding regarding such severe events warrants further study, the investigators noted.

Compared with NSAIDs, risk for upper GI bleeding, lower GI bleeding, or bowel obstruction was similarly high for opioid users (HR, 1.07) but was lower for coxib users (HR, 0.60).

In general, opioid users experienced the most adverse events over time, and NSAID users experienced the fewest. In addition, “opioid users experienced moderate risk early in treatment,” the researchers noted, whereas the other groups did not. Opioid users had significantly higher all-cause mortality (75 deaths per 1,000 person-years) than did either NSAID users (48 deaths per 1,000 person-years) or coxib users (47 deaths per 1,000 person-years).

The study findings indicate that recent concerns that have been raised regarding the use of opioids for nonmalignant pain are warranted, the researchers said.

The study was supported by the Agency for Healthcare Research and Quality. Dr. Solomon reported being an unpaid member of a celecoxib trial executive committee sponsored by Pfizer and an unpaid member of the data safety monitoring board for an analgesic trial sponsored by Pfizer.

View on the News

An Oversight in Statistical Methods

The propensity matching was meticulous in this study, leading to well-balanced baseline characteristics among the three treatment groups. This reassures readers that the observational study design is as robust as possible, and that treatment effects alone account for the observed differences among opioid, NSAID, and coxib users.

However, there is a single unmeasured confounder that calls into question the validity of some of the study findings: the use of over-the-counter NSAIDs, noted Dr. William C. Becker and Dr. Patrick G. O'Connor.

It is likely that “a significant proportion” of patients in the opioid group were also taking NSAIDs, because “physicians routinely recommend antiinflammatory medication in addition to opioids to achieve therapeutic synergy in the treatment of arthritis,” they noted.

“It seems implausible that a group of 'opioid-only' elderly patients” who were actually taking supplemental NSAIDs would have a higher risk of adverse cardiovascular events, GI bleeding, and acute kidney injury than would a group taking NSAIDs alone, because these are all known effects of NSAID therapy.

Despite this limitation, “the data on falls and fracture from this … study are nonetheless compelling and carry important clinical implications,” Dr. Becker and Dr. O'Connor said.

DR. BECKER and DR. O'CONNOR are in general internal medicine at Yale University, New Haven, Conn. They reported no financial disclosures. These comments were taken from their invited commentary accompanying Dr. Solomon's report (Arch. Intern. Med. 2010;170:1986-8).

MRI remains strongly superior to mammography over the long term in screening women who are at increased risk of developing breast cancer, according to a study published online in the Journal of Clinical Oncology.

The advantage in sensitivity was highly significant for BRCA1 mutation carriers, but not for those who carried BRCA2 mutations and were more likely to present with ductal carcinoma in situ (DCIS).

Previous research showed that in the short term, MRI was approximately twice as sensitive as mammography in detecting breast cancer among women susceptible to the disease, and most guidelines now recommend MRI screening in those who carry BRCA1 or BRCA2 mutations.

However, there is no consensus on the screening protocol for other risk groups, few studies have assessed BRCA1 carriers separately from BRCA2 carriers, and until now no studies have evaluated longer-term screening results, said Dr. Adriana J. Rijnsburger of Erasmus University Medical Center, Rotterdam, the Netherlands, and her associates.

To address these issues, the investigators enlarged and extended the Dutch MRI Screening Study (MRISC) and report their findings after following 2,157 women at six cancer or academic centers for 5 years.

The study subjects, aged 25-75 years at enrollment, had never had breast cancer but were at increased risk because they carried either the BRCA1 or BRCA2 mutation (raising their cumulative lifetime risk of developing breast cancer to 50%-85%), had a high-risk family history (raising their cumulative lifetime risk of developing breast cancer to 30%-50%), or had a moderate-risk family history (raising their cumulative lifetime risk of developing breast cancer to 15%-30%).

They underwent biannual clinical breast examination and annual mammography and MRI.

During 5 years of follow-up, 97 breast cancers developed in 94 women, including 78 (80%) invasive tumors and 19 (20%) cases of DCIS.

Sensitivity at detecting breast cancer was 71% with MRI, significantly greater than the 41% sensitivity of mammography. When only invasive breast cancers were considered, MRI sensitivity increased to 78%, while mammography's sensitivity decreased to 36%.

When the analysis was restricted only to women who carried genetic mutations, the sensitivity of MRI (67%) was “strikingly” higher than that of mammography (25%) for BRCA1 carriers. In contrast, MRI sensitivity (69%) was only slightly higher than mammography's sensitivity (62%) in BRCA2 carriers.

This difference can be explained, at least in part, by the higher proportion of DCIS in BRCA2 than in BRCA1 carriers; mammography was much more sensitive in detecting DCIS (69%) than in detecting invasive tumors (36%).

The specificity of the two screening methods was not significantly different.

Overall, 43% of breast cancers were detected by MRI only. This included 46% of the cancers in BRCA1 carriers, 31% in BRCA2 carriers, 41% in women with a high-risk family history, and 47% in the women with a moderate-risk family history, Dr. Rijnsburger and her colleagues said (J. Clin. Oncol. 2010 Nov. 16; doi:10.1200/JCO.2009.27.2294).

These findings “support the recommendation of the American Cancer Society to use annual MRI screening not only for BRCA1/2 mutation carriers, but for all women with an approximately 20%-25% or greater cumulative lifetime risk of breast cancer due to a familial predisposition,” they noted, with the caveat that cost-effectiveness should be evaluated separately in all risk groups.

This also was the first prospective study of screening in this at-risk patient population to report mortality data, the researchers added.

Five women, all BRCA1/2 mutation carriers, developed distant metastases, and four of them died during follow-up. Two of the women who died had had a favorable tumor stage at diagnosis.

This finding underscores the need for clinicians to avoid guaranteeing that all breast cancer deaths can be prevented by early detection via screening, Dr. Rijnsburger and her associates said.

Survival was 84% in the women with BRCA1 mutations and invasive cancer, and 93% in those with BRCA2 mutations and invasive cancer. Survival was 100% in the other at-risk groups.

BRCA1-associated tumors “behaved completely differently” from BRCA2-associated tumors. They developed at a younger patient age, were not detected as well on mammography, were more likely to develop during the interval between screenings, were more likely to be invasive, and were larger at diagnosis, the investigators said.

This indicates that the current screening schedule for BRCA1 carriers may need to be modified, perhaps by increasing MRI screening to twice rather than once yearly, Dr. Rijnsburger and her colleagues said.

This study was supported by the Dutch government and the Cancer Genomics Center in the Netherlands. The investigators reported having no financial conflicts of interest.

MRI remains strongly superior to mammography over the long term in screening women who are at increased risk of developing breast cancer, according to a study published online in the Journal of Clinical Oncology.

The advantage in sensitivity was highly significant for BRCA1 mutation carriers, but not for those who carried BRCA2 mutations and were more likely to present with ductal carcinoma in situ (DCIS).

Previous research showed that in the short term, MRI was approximately twice as sensitive as mammography in detecting breast cancer among women susceptible to the disease, and most guidelines now recommend MRI screening in those who carry BRCA1 or BRCA2 mutations.

However, there is no consensus on the screening protocol for other risk groups, few studies have assessed BRCA1 carriers separately from BRCA2 carriers, and until now no studies have evaluated longer-term screening results, said Dr. Adriana J. Rijnsburger of Erasmus University Medical Center, Rotterdam, the Netherlands, and her associates.

To address these issues, the investigators enlarged and extended the Dutch MRI Screening Study (MRISC) and report their findings after following 2,157 women at six cancer or academic centers for 5 years.

The study subjects, aged 25-75 years at enrollment, had never had breast cancer but were at increased risk because they carried either the BRCA1 or BRCA2 mutation (raising their cumulative lifetime risk of developing breast cancer to 50%-85%), had a high-risk family history (raising their cumulative lifetime risk of developing breast cancer to 30%-50%), or had a moderate-risk family history (raising their cumulative lifetime risk of developing breast cancer to 15%-30%).

They underwent biannual clinical breast examination and annual mammography and MRI.

During 5 years of follow-up, 97 breast cancers developed in 94 women, including 78 (80%) invasive tumors and 19 (20%) cases of DCIS.

Sensitivity at detecting breast cancer was 71% with MRI, significantly greater than the 41% sensitivity of mammography. When only invasive breast cancers were considered, MRI sensitivity increased to 78%, while mammography's sensitivity decreased to 36%.

When the analysis was restricted only to women who carried genetic mutations, the sensitivity of MRI (67%) was “strikingly” higher than that of mammography (25%) for BRCA1 carriers. In contrast, MRI sensitivity (69%) was only slightly higher than mammography's sensitivity (62%) in BRCA2 carriers.

This difference can be explained, at least in part, by the higher proportion of DCIS in BRCA2 than in BRCA1 carriers; mammography was much more sensitive in detecting DCIS (69%) than in detecting invasive tumors (36%).

The specificity of the two screening methods was not significantly different.

Overall, 43% of breast cancers were detected by MRI only. This included 46% of the cancers in BRCA1 carriers, 31% in BRCA2 carriers, 41% in women with a high-risk family history, and 47% in the women with a moderate-risk family history, Dr. Rijnsburger and her colleagues said (J. Clin. Oncol. 2010 Nov. 16; doi:10.1200/JCO.2009.27.2294).

These findings “support the recommendation of the American Cancer Society to use annual MRI screening not only for BRCA1/2 mutation carriers, but for all women with an approximately 20%-25% or greater cumulative lifetime risk of breast cancer due to a familial predisposition,” they noted, with the caveat that cost-effectiveness should be evaluated separately in all risk groups.

This also was the first prospective study of screening in this at-risk patient population to report mortality data, the researchers added.

Five women, all BRCA1/2 mutation carriers, developed distant metastases, and four of them died during follow-up. Two of the women who died had had a favorable tumor stage at diagnosis.

This finding underscores the need for clinicians to avoid guaranteeing that all breast cancer deaths can be prevented by early detection via screening, Dr. Rijnsburger and her associates said.

Survival was 84% in the women with BRCA1 mutations and invasive cancer, and 93% in those with BRCA2 mutations and invasive cancer. Survival was 100% in the other at-risk groups.

BRCA1-associated tumors “behaved completely differently” from BRCA2-associated tumors. They developed at a younger patient age, were not detected as well on mammography, were more likely to develop during the interval between screenings, were more likely to be invasive, and were larger at diagnosis, the investigators said.

This indicates that the current screening schedule for BRCA1 carriers may need to be modified, perhaps by increasing MRI screening to twice rather than once yearly, Dr. Rijnsburger and her colleagues said.

This study was supported by the Dutch government and the Cancer Genomics Center in the Netherlands. The investigators reported having no financial conflicts of interest.

MRI remains strongly superior to mammography over the long term in screening women who are at increased risk of developing breast cancer, according to a study published online in the Journal of Clinical Oncology.

The advantage in sensitivity was highly significant for BRCA1 mutation carriers, but not for those who carried BRCA2 mutations and were more likely to present with ductal carcinoma in situ (DCIS).

Previous research showed that in the short term, MRI was approximately twice as sensitive as mammography in detecting breast cancer among women susceptible to the disease, and most guidelines now recommend MRI screening in those who carry BRCA1 or BRCA2 mutations.

However, there is no consensus on the screening protocol for other risk groups, few studies have assessed BRCA1 carriers separately from BRCA2 carriers, and until now no studies have evaluated longer-term screening results, said Dr. Adriana J. Rijnsburger of Erasmus University Medical Center, Rotterdam, the Netherlands, and her associates.

To address these issues, the investigators enlarged and extended the Dutch MRI Screening Study (MRISC) and report their findings after following 2,157 women at six cancer or academic centers for 5 years.

The study subjects, aged 25-75 years at enrollment, had never had breast cancer but were at increased risk because they carried either the BRCA1 or BRCA2 mutation (raising their cumulative lifetime risk of developing breast cancer to 50%-85%), had a high-risk family history (raising their cumulative lifetime risk of developing breast cancer to 30%-50%), or had a moderate-risk family history (raising their cumulative lifetime risk of developing breast cancer to 15%-30%).

They underwent biannual clinical breast examination and annual mammography and MRI.

During 5 years of follow-up, 97 breast cancers developed in 94 women, including 78 (80%) invasive tumors and 19 (20%) cases of DCIS.

Sensitivity at detecting breast cancer was 71% with MRI, significantly greater than the 41% sensitivity of mammography. When only invasive breast cancers were considered, MRI sensitivity increased to 78%, while mammography's sensitivity decreased to 36%.

When the analysis was restricted only to women who carried genetic mutations, the sensitivity of MRI (67%) was “strikingly” higher than that of mammography (25%) for BRCA1 carriers. In contrast, MRI sensitivity (69%) was only slightly higher than mammography's sensitivity (62%) in BRCA2 carriers.

This difference can be explained, at least in part, by the higher proportion of DCIS in BRCA2 than in BRCA1 carriers; mammography was much more sensitive in detecting DCIS (69%) than in detecting invasive tumors (36%).

The specificity of the two screening methods was not significantly different.

Overall, 43% of breast cancers were detected by MRI only. This included 46% of the cancers in BRCA1 carriers, 31% in BRCA2 carriers, 41% in women with a high-risk family history, and 47% in the women with a moderate-risk family history, Dr. Rijnsburger and her colleagues said (J. Clin. Oncol. 2010 Nov. 16; doi:10.1200/JCO.2009.27.2294).

These findings “support the recommendation of the American Cancer Society to use annual MRI screening not only for BRCA1/2 mutation carriers, but for all women with an approximately 20%-25% or greater cumulative lifetime risk of breast cancer due to a familial predisposition,” they noted, with the caveat that cost-effectiveness should be evaluated separately in all risk groups.

This also was the first prospective study of screening in this at-risk patient population to report mortality data, the researchers added.

Five women, all BRCA1/2 mutation carriers, developed distant metastases, and four of them died during follow-up. Two of the women who died had had a favorable tumor stage at diagnosis.

This finding underscores the need for clinicians to avoid guaranteeing that all breast cancer deaths can be prevented by early detection via screening, Dr. Rijnsburger and her associates said.

Survival was 84% in the women with BRCA1 mutations and invasive cancer, and 93% in those with BRCA2 mutations and invasive cancer. Survival was 100% in the other at-risk groups.

BRCA1-associated tumors “behaved completely differently” from BRCA2-associated tumors. They developed at a younger patient age, were not detected as well on mammography, were more likely to develop during the interval between screenings, were more likely to be invasive, and were larger at diagnosis, the investigators said.

This indicates that the current screening schedule for BRCA1 carriers may need to be modified, perhaps by increasing MRI screening to twice rather than once yearly, Dr. Rijnsburger and her colleagues said.

This study was supported by the Dutch government and the Cancer Genomics Center in the Netherlands. The investigators reported having no financial conflicts of interest.

Regular use of sunscreen during a clinical trial of basal cell and squamous cell carcinomas was found to reduce the incidence of a different skin malignancy – new primary melanomas – up to 10 years later, according to a study published online in the journal.

The number of invasive melanomas in particular decreased by 73%, but this was an exploratory finding “and should be interpreted cautiously,” said Dr. Adéle C. Green and her associates at the Queensland Institute of Medical Research, Royal Brisbane (Australia) Hospital.

The original clinical trial, conducted in 1992-1996 and involving 1,621 white Queensland residents aged 25-75 years at baseline, examined the effects of 5 years of sunscreen application and beta-carotene supplementation on the incidence of basal and squamous cell carcinoma.

The researchers' new report focuses on the incidence of melanoma as a secondary end point in the same population. “Despite the known etiologic role of sun exposure, the question regarding sunscreen use to prevent melanoma remains open and controversial,” they noted.

In all, 812 patients were given a free, unlimited supply of SPF-16 sunscreen and told to use it daily on their head, neck, arms, and hands, whereas 809 controls were randomly assigned to continue using sunscreen of any SPF at their own discretion, which included no use at all in 38% and infrequent use in another 35%.

The two groups were similar in established risk factors for skin cancer, degree of sun exposure, and use of sun protection measures other than sunscreen.

Between baseline in 1992 and the end of the extended follow-up in 2006, 36 study patients developed first primary melanomas. These were in situ malignancies in 22 subjects and invasive in 14; none was metastatic. Three patients who had melanoma diagnosed in 1992 were excluded.

Only 11 subjects in the sunscreen group developed melanoma, compared with 22 in the comparison group. “Risk of melanoma overall was reduced in those randomly assigned to daily sunscreen compared with discretionary use, although the result was of borderline statistical significance,” the investigators reported (J. Clin. Oncol. 2010 Dec. 6 [doi:10.1200/JCO.2010.28.7078]).

The average melanoma thickness was 0.53 mm in the sunscreen group, compared with 1.2 mm in the comparison group. The incidence of invasive melanoma was decreased by 73% with sunscreen, whereas the incidence of in situ lesions was not significantly different between the two groups.

Melanoma incidence was decreased at all sites on the body, not just on the sites assigned to protection by sunscreen. This is probably because many study patients in the sunscreen group applied sunscreen to their trunks and lower limbs regularly, even though they had not been instructed to do so, Dr. Green and her associates noted.

“Our findings provide reassurance in view of the widespread uncertainty to date about sunscreen's ability to prevent melanoma,” they reported.

“Although the results are directly relevant to people who live in sunny climates like Australia's and who receive relatively high levels of ambient sun exposure as a matter of course, they also have implications for white people living in temperate climates in North America and Europe who are at increased risk of melanoma because of increased solar UV exposure caused by the predilection for holidays in sunny places,” they concluded.

The application of sunscreen was found to decrease the risk of melanoma in study participants.

Source ©Joel Carillet/Istockphoto.com

Regular use of sunscreen during a clinical trial of basal cell and squamous cell carcinomas was found to reduce the incidence of a different skin malignancy – new primary melanomas – up to 10 years later, according to a study published online in the journal.

The number of invasive melanomas in particular decreased by 73%, but this was an exploratory finding “and should be interpreted cautiously,” said Dr. Adéle C. Green and her associates at the Queensland Institute of Medical Research, Royal Brisbane (Australia) Hospital.

The original clinical trial, conducted in 1992-1996 and involving 1,621 white Queensland residents aged 25-75 years at baseline, examined the effects of 5 years of sunscreen application and beta-carotene supplementation on the incidence of basal and squamous cell carcinoma.

The researchers' new report focuses on the incidence of melanoma as a secondary end point in the same population. “Despite the known etiologic role of sun exposure, the question regarding sunscreen use to prevent melanoma remains open and controversial,” they noted.

In all, 812 patients were given a free, unlimited supply of SPF-16 sunscreen and told to use it daily on their head, neck, arms, and hands, whereas 809 controls were randomly assigned to continue using sunscreen of any SPF at their own discretion, which included no use at all in 38% and infrequent use in another 35%.

The two groups were similar in established risk factors for skin cancer, degree of sun exposure, and use of sun protection measures other than sunscreen.

Between baseline in 1992 and the end of the extended follow-up in 2006, 36 study patients developed first primary melanomas. These were in situ malignancies in 22 subjects and invasive in 14; none was metastatic. Three patients who had melanoma diagnosed in 1992 were excluded.

Only 11 subjects in the sunscreen group developed melanoma, compared with 22 in the comparison group. “Risk of melanoma overall was reduced in those randomly assigned to daily sunscreen compared with discretionary use, although the result was of borderline statistical significance,” the investigators reported (J. Clin. Oncol. 2010 Dec. 6 [doi:10.1200/JCO.2010.28.7078]).

The average melanoma thickness was 0.53 mm in the sunscreen group, compared with 1.2 mm in the comparison group. The incidence of invasive melanoma was decreased by 73% with sunscreen, whereas the incidence of in situ lesions was not significantly different between the two groups.

Melanoma incidence was decreased at all sites on the body, not just on the sites assigned to protection by sunscreen. This is probably because many study patients in the sunscreen group applied sunscreen to their trunks and lower limbs regularly, even though they had not been instructed to do so, Dr. Green and her associates noted.

“Our findings provide reassurance in view of the widespread uncertainty to date about sunscreen's ability to prevent melanoma,” they reported.

“Although the results are directly relevant to people who live in sunny climates like Australia's and who receive relatively high levels of ambient sun exposure as a matter of course, they also have implications for white people living in temperate climates in North America and Europe who are at increased risk of melanoma because of increased solar UV exposure caused by the predilection for holidays in sunny places,” they concluded.

The application of sunscreen was found to decrease the risk of melanoma in study participants.

Source ©Joel Carillet/Istockphoto.com

Regular use of sunscreen during a clinical trial of basal cell and squamous cell carcinomas was found to reduce the incidence of a different skin malignancy – new primary melanomas – up to 10 years later, according to a study published online in the journal.

The number of invasive melanomas in particular decreased by 73%, but this was an exploratory finding “and should be interpreted cautiously,” said Dr. Adéle C. Green and her associates at the Queensland Institute of Medical Research, Royal Brisbane (Australia) Hospital.

The original clinical trial, conducted in 1992-1996 and involving 1,621 white Queensland residents aged 25-75 years at baseline, examined the effects of 5 years of sunscreen application and beta-carotene supplementation on the incidence of basal and squamous cell carcinoma.

The researchers' new report focuses on the incidence of melanoma as a secondary end point in the same population. “Despite the known etiologic role of sun exposure, the question regarding sunscreen use to prevent melanoma remains open and controversial,” they noted.

In all, 812 patients were given a free, unlimited supply of SPF-16 sunscreen and told to use it daily on their head, neck, arms, and hands, whereas 809 controls were randomly assigned to continue using sunscreen of any SPF at their own discretion, which included no use at all in 38% and infrequent use in another 35%.

The two groups were similar in established risk factors for skin cancer, degree of sun exposure, and use of sun protection measures other than sunscreen.

Between baseline in 1992 and the end of the extended follow-up in 2006, 36 study patients developed first primary melanomas. These were in situ malignancies in 22 subjects and invasive in 14; none was metastatic. Three patients who had melanoma diagnosed in 1992 were excluded.

Only 11 subjects in the sunscreen group developed melanoma, compared with 22 in the comparison group. “Risk of melanoma overall was reduced in those randomly assigned to daily sunscreen compared with discretionary use, although the result was of borderline statistical significance,” the investigators reported (J. Clin. Oncol. 2010 Dec. 6 [doi:10.1200/JCO.2010.28.7078]).

The average melanoma thickness was 0.53 mm in the sunscreen group, compared with 1.2 mm in the comparison group. The incidence of invasive melanoma was decreased by 73% with sunscreen, whereas the incidence of in situ lesions was not significantly different between the two groups.

Melanoma incidence was decreased at all sites on the body, not just on the sites assigned to protection by sunscreen. This is probably because many study patients in the sunscreen group applied sunscreen to their trunks and lower limbs regularly, even though they had not been instructed to do so, Dr. Green and her associates noted.

“Our findings provide reassurance in view of the widespread uncertainty to date about sunscreen's ability to prevent melanoma,” they reported.

“Although the results are directly relevant to people who live in sunny climates like Australia's and who receive relatively high levels of ambient sun exposure as a matter of course, they also have implications for white people living in temperate climates in North America and Europe who are at increased risk of melanoma because of increased solar UV exposure caused by the predilection for holidays in sunny places,” they concluded.

The application of sunscreen was found to decrease the risk of melanoma in study participants.

Source ©Joel Carillet/Istockphoto.com