Bianca Nogrady

Lead exposure during childhood appears tied to a significant increase in the risk of psychopathology in adulthood, results of a multidecade, prospective cohort study show.

“These results suggest that early life lead exposure in the era of leaded gasoline experienced by individuals who are currently adults may have contributed to subtle, lifelong differences in emotion and behavior that are detectable at least up to 38 years of age,” Aaron Reuben and his coauthors wrote in JAMA Psychiatry.

The ongoing Dunedin longitudinal cohort study in New Zealand has followed 1,037 individuals born during 1972-1973. Of these individuals, 579 were tested for lead exposure at 11 years of age. The study assessed their mental health at 18, 21, 26, 32, and 38 years of age.

“Although follow-up studies of lead-tested children have reported the persistence of lead-related cognitive deficits well into adulthood, apart from antisocial outcomes, the long-term mental and behavioral health consequences of early life lead exposure have not been fully characterized,” wrote Mr. Reuben, a PhD student in the department of psychology and neuroscience at Duke University in Durham, N.C., and his coauthors.

Researchers saw that, for each 5-mcg/dL increase in childhood blood lead level, there was a significant 1.34-point increase in general psychopathology (P = 0.03), which was largely driven by a 1.41-point increase in internalizing (P = 0.02) and 1.30-point increase in thought-disorder symptoms (P = 0.04). Those associations were seen after adjustment for covariates, such as family socioeconomic status, maternal IQ, and family history of mental illness.

Adults who had higher lead exposure during childhood also were described by their informants – close friends or family members – as being significantly more neurotic, less agreeable, and less conscientious. However, they showed no significant differences in extroversion or in openness to experience, compared with those with less lead exposure.

“These results suggest that early-life lead exposure in the era of leaded gasoline experienced by individuals who are currently adults may have contributed to subtle, lifelong differences in emotion and behavior that are detectable at least up to 38 years of age,” the authors wrote.

They noted that the size of the effect was around one-third the size of the associations seen between psychopathology and other risk factors, such as family history of mental illness and childhood maltreatment. However, the effects of lead exposure on adult psychopathology were similar to its effects on IQ and stronger than the associations seen between lead exposure and criminal offending.

The researchers also examined how early these psychopathology symptoms could be detected with use of parent- and teacher-reported measures of antisocial behavior, hyperactivity, and internalizing from 11 years of age. This showed that individuals with higher lead exposure scored higher on these measures even at 11 years of age, “suggesting that the association between lead exposure and psychopathology may begin to manifest broadly well before adulthood.”

Mr. Reuben and his associates cited several limitations. One is that the study used a cohort that was predominantly white and born in the 1970s. Also, as an observational study, it does not establish causality between lead exposure and psychopathology.

Nevertheless, they wrote, the study results suggest that adult patients who were exposed to high levels of lead as children might benefit from increased screening and access to mental health services.

The Dunedin study is supported by the New Zealand Health Research Council and the New Zealand Ministry of Business, Innovation, and Employment. This study was supported by several entities, including the National Institute on Aging, the U.K. Medical Research Council, the National Institute of Child Health and Human Development, and the National Institute of Environmental Health Sciences. The authors reported no conflicts of interest.

SOURCE: Reuben A et al. JAMA Psychiatry. 2019 Jan 23. doi: 10.1001/jamapsychiatry.2018.4192.
 

Lead exposure during childhood appears tied to a significant increase in the risk of psychopathology in adulthood, results of a multidecade, prospective cohort study show.

“These results suggest that early life lead exposure in the era of leaded gasoline experienced by individuals who are currently adults may have contributed to subtle, lifelong differences in emotion and behavior that are detectable at least up to 38 years of age,” Aaron Reuben and his coauthors wrote in JAMA Psychiatry.

The ongoing Dunedin longitudinal cohort study in New Zealand has followed 1,037 individuals born during 1972-1973. Of these individuals, 579 were tested for lead exposure at 11 years of age. The study assessed their mental health at 18, 21, 26, 32, and 38 years of age.

“Although follow-up studies of lead-tested children have reported the persistence of lead-related cognitive deficits well into adulthood, apart from antisocial outcomes, the long-term mental and behavioral health consequences of early life lead exposure have not been fully characterized,” wrote Mr. Reuben, a PhD student in the department of psychology and neuroscience at Duke University in Durham, N.C., and his coauthors.

Researchers saw that, for each 5-mcg/dL increase in childhood blood lead level, there was a significant 1.34-point increase in general psychopathology (P = 0.03), which was largely driven by a 1.41-point increase in internalizing (P = 0.02) and 1.30-point increase in thought-disorder symptoms (P = 0.04). Those associations were seen after adjustment for covariates, such as family socioeconomic status, maternal IQ, and family history of mental illness.

Adults who had higher lead exposure during childhood also were described by their informants – close friends or family members – as being significantly more neurotic, less agreeable, and less conscientious. However, they showed no significant differences in extroversion or in openness to experience, compared with those with less lead exposure.

“These results suggest that early-life lead exposure in the era of leaded gasoline experienced by individuals who are currently adults may have contributed to subtle, lifelong differences in emotion and behavior that are detectable at least up to 38 years of age,” the authors wrote.

They noted that the size of the effect was around one-third the size of the associations seen between psychopathology and other risk factors, such as family history of mental illness and childhood maltreatment. However, the effects of lead exposure on adult psychopathology were similar to its effects on IQ and stronger than the associations seen between lead exposure and criminal offending.

The researchers also examined how early these psychopathology symptoms could be detected with use of parent- and teacher-reported measures of antisocial behavior, hyperactivity, and internalizing from 11 years of age. This showed that individuals with higher lead exposure scored higher on these measures even at 11 years of age, “suggesting that the association between lead exposure and psychopathology may begin to manifest broadly well before adulthood.”

Mr. Reuben and his associates cited several limitations. One is that the study used a cohort that was predominantly white and born in the 1970s. Also, as an observational study, it does not establish causality between lead exposure and psychopathology.

Nevertheless, they wrote, the study results suggest that adult patients who were exposed to high levels of lead as children might benefit from increased screening and access to mental health services.

The Dunedin study is supported by the New Zealand Health Research Council and the New Zealand Ministry of Business, Innovation, and Employment. This study was supported by several entities, including the National Institute on Aging, the U.K. Medical Research Council, the National Institute of Child Health and Human Development, and the National Institute of Environmental Health Sciences. The authors reported no conflicts of interest.

SOURCE: Reuben A et al. JAMA Psychiatry. 2019 Jan 23. doi: 10.1001/jamapsychiatry.2018.4192.
 

Lead exposure during childhood appears tied to a significant increase in the risk of psychopathology in adulthood, results of a multidecade, prospective cohort study show.

“These results suggest that early life lead exposure in the era of leaded gasoline experienced by individuals who are currently adults may have contributed to subtle, lifelong differences in emotion and behavior that are detectable at least up to 38 years of age,” Aaron Reuben and his coauthors wrote in JAMA Psychiatry.

The ongoing Dunedin longitudinal cohort study in New Zealand has followed 1,037 individuals born during 1972-1973. Of these individuals, 579 were tested for lead exposure at 11 years of age. The study assessed their mental health at 18, 21, 26, 32, and 38 years of age.

“Although follow-up studies of lead-tested children have reported the persistence of lead-related cognitive deficits well into adulthood, apart from antisocial outcomes, the long-term mental and behavioral health consequences of early life lead exposure have not been fully characterized,” wrote Mr. Reuben, a PhD student in the department of psychology and neuroscience at Duke University in Durham, N.C., and his coauthors.

Researchers saw that, for each 5-mcg/dL increase in childhood blood lead level, there was a significant 1.34-point increase in general psychopathology (P = 0.03), which was largely driven by a 1.41-point increase in internalizing (P = 0.02) and 1.30-point increase in thought-disorder symptoms (P = 0.04). Those associations were seen after adjustment for covariates, such as family socioeconomic status, maternal IQ, and family history of mental illness.

Adults who had higher lead exposure during childhood also were described by their informants – close friends or family members – as being significantly more neurotic, less agreeable, and less conscientious. However, they showed no significant differences in extroversion or in openness to experience, compared with those with less lead exposure.

“These results suggest that early-life lead exposure in the era of leaded gasoline experienced by individuals who are currently adults may have contributed to subtle, lifelong differences in emotion and behavior that are detectable at least up to 38 years of age,” the authors wrote.

They noted that the size of the effect was around one-third the size of the associations seen between psychopathology and other risk factors, such as family history of mental illness and childhood maltreatment. However, the effects of lead exposure on adult psychopathology were similar to its effects on IQ and stronger than the associations seen between lead exposure and criminal offending.

The researchers also examined how early these psychopathology symptoms could be detected with use of parent- and teacher-reported measures of antisocial behavior, hyperactivity, and internalizing from 11 years of age. This showed that individuals with higher lead exposure scored higher on these measures even at 11 years of age, “suggesting that the association between lead exposure and psychopathology may begin to manifest broadly well before adulthood.”

Mr. Reuben and his associates cited several limitations. One is that the study used a cohort that was predominantly white and born in the 1970s. Also, as an observational study, it does not establish causality between lead exposure and psychopathology.

Nevertheless, they wrote, the study results suggest that adult patients who were exposed to high levels of lead as children might benefit from increased screening and access to mental health services.

The Dunedin study is supported by the New Zealand Health Research Council and the New Zealand Ministry of Business, Innovation, and Employment. This study was supported by several entities, including the National Institute on Aging, the U.K. Medical Research Council, the National Institute of Child Health and Human Development, and the National Institute of Environmental Health Sciences. The authors reported no conflicts of interest.

SOURCE: Reuben A et al. JAMA Psychiatry. 2019 Jan 23. doi: 10.1001/jamapsychiatry.2018.4192.
 

Introduction of the quadrivalent human papillomavirus (HPV) vaccine was associated with significant declines in the incidence of vaccine-type virus both in vaccinated and unvaccinated young women, according to a study published in Pediatrics.

copyright itsmejust/Thinkstock

Four surveillance studies, conducted between 2006 and 2017, examined the rate of positive tests for vaccine-type HPV among 1,580 vaccinated and unvaccinated women aged 13-26 years. The majority of participants identified as African American or multiracial.

Overall, 97% of study participants received the quadrivalent vaccine, with vaccination rates increasing from 0% to 84% over the four waves of vaccination. Vaccine effectiveness – representing the relative risk of infection in vaccinated individuals, compared with unvaccinated risk before introduction of the vaccine – increased by 72% from wave 1 to wave 2, 91% from wave 1 to wave 3, and 80% from wave 1 to wave 4.

Among women who were vaccinated, rates of the quadrivalent vaccine–type HPV decreased by 81%, from 35% to 7%. But even among women who were unvaccinated, detection of the vaccine-targeted strains of HPV decreased by 40%, from 32% to 19%.

Chelse Spinner of the University of Cincinnati and her coauthors wrote that the decline in the quadrivalent vaccine–type HPV provided evidence of direct protection and high vaccine effectiveness in this real-world setting.

“This degree of effectiveness is remarkable given the fact that vaccination was defined as having received one or more doses (i.e., was not defined as having completed the vaccination series) and that women in this study were likely at a substantially higher risk for preexisting HPV infection than [were] those in the HPV vaccine clinical trials because of their reported sexual behaviors,” they wrote. “As noted in a recent review, evidence about herd protection will be a key component of cost-effectiveness analysis evaluating cervical cancer screening strategies.”

Twelve percent of women in the studies received the nine-valent HPV vaccine, and among these women, the rate of infection with the nine-valent vaccine-type HPV decreased from 47% in the first wave of vaccination to 14% in the last wave, representing a 71% decline.

The proportion of vaccinated women in the study who were infected with one or more of the five viral subtypes included in the nine-valent but not in the quadrivalent vaccine decreased significantly by 69%, from 23% to 7%.

However, these data also suggested a nonsignificant 58% increase among unvaccinated women in infections with one of the five subtypes covered by the nine-valent vaccine but not the quadrivalent vaccine.

Ms. Spinner and her associates noted this increase was unexpected and suggested the increase may be caused by the differences between vaccinated and unvaccinated women.

“For example, if women who are unvaccinated versus women who are vaccinated are more likely to practice riskier behaviors that would increase their risk of acquiring HPV, they would be more likely to acquire non–vaccine-type HPV,” they wrote.

Ms. Spinner graduated from the University of Cincinnati and now is a graduate student at the University of South Florida, Tampa. The study was funded by the National Institutes of Health. Darron R. Brown declared shares of Merck, but the other coauthors declared no other relevant financial disclosures.

SOURCE: Spinner C et al. Pediatrics. 2019, Jan 22. doi: 10.1542/peds.2018-1902.
 

Introduction of the quadrivalent human papillomavirus (HPV) vaccine was associated with significant declines in the incidence of vaccine-type virus both in vaccinated and unvaccinated young women, according to a study published in Pediatrics.

copyright itsmejust/Thinkstock

Four surveillance studies, conducted between 2006 and 2017, examined the rate of positive tests for vaccine-type HPV among 1,580 vaccinated and unvaccinated women aged 13-26 years. The majority of participants identified as African American or multiracial.

Overall, 97% of study participants received the quadrivalent vaccine, with vaccination rates increasing from 0% to 84% over the four waves of vaccination. Vaccine effectiveness – representing the relative risk of infection in vaccinated individuals, compared with unvaccinated risk before introduction of the vaccine – increased by 72% from wave 1 to wave 2, 91% from wave 1 to wave 3, and 80% from wave 1 to wave 4.

Among women who were vaccinated, rates of the quadrivalent vaccine–type HPV decreased by 81%, from 35% to 7%. But even among women who were unvaccinated, detection of the vaccine-targeted strains of HPV decreased by 40%, from 32% to 19%.

Chelse Spinner of the University of Cincinnati and her coauthors wrote that the decline in the quadrivalent vaccine–type HPV provided evidence of direct protection and high vaccine effectiveness in this real-world setting.

“This degree of effectiveness is remarkable given the fact that vaccination was defined as having received one or more doses (i.e., was not defined as having completed the vaccination series) and that women in this study were likely at a substantially higher risk for preexisting HPV infection than [were] those in the HPV vaccine clinical trials because of their reported sexual behaviors,” they wrote. “As noted in a recent review, evidence about herd protection will be a key component of cost-effectiveness analysis evaluating cervical cancer screening strategies.”

Twelve percent of women in the studies received the nine-valent HPV vaccine, and among these women, the rate of infection with the nine-valent vaccine-type HPV decreased from 47% in the first wave of vaccination to 14% in the last wave, representing a 71% decline.

The proportion of vaccinated women in the study who were infected with one or more of the five viral subtypes included in the nine-valent but not in the quadrivalent vaccine decreased significantly by 69%, from 23% to 7%.

However, these data also suggested a nonsignificant 58% increase among unvaccinated women in infections with one of the five subtypes covered by the nine-valent vaccine but not the quadrivalent vaccine.

Ms. Spinner and her associates noted this increase was unexpected and suggested the increase may be caused by the differences between vaccinated and unvaccinated women.

“For example, if women who are unvaccinated versus women who are vaccinated are more likely to practice riskier behaviors that would increase their risk of acquiring HPV, they would be more likely to acquire non–vaccine-type HPV,” they wrote.

Ms. Spinner graduated from the University of Cincinnati and now is a graduate student at the University of South Florida, Tampa. The study was funded by the National Institutes of Health. Darron R. Brown declared shares of Merck, but the other coauthors declared no other relevant financial disclosures.

SOURCE: Spinner C et al. Pediatrics. 2019, Jan 22. doi: 10.1542/peds.2018-1902.
 

Introduction of the quadrivalent human papillomavirus (HPV) vaccine was associated with significant declines in the incidence of vaccine-type virus both in vaccinated and unvaccinated young women, according to a study published in Pediatrics.

copyright itsmejust/Thinkstock

Four surveillance studies, conducted between 2006 and 2017, examined the rate of positive tests for vaccine-type HPV among 1,580 vaccinated and unvaccinated women aged 13-26 years. The majority of participants identified as African American or multiracial.

Overall, 97% of study participants received the quadrivalent vaccine, with vaccination rates increasing from 0% to 84% over the four waves of vaccination. Vaccine effectiveness – representing the relative risk of infection in vaccinated individuals, compared with unvaccinated risk before introduction of the vaccine – increased by 72% from wave 1 to wave 2, 91% from wave 1 to wave 3, and 80% from wave 1 to wave 4.

Among women who were vaccinated, rates of the quadrivalent vaccine–type HPV decreased by 81%, from 35% to 7%. But even among women who were unvaccinated, detection of the vaccine-targeted strains of HPV decreased by 40%, from 32% to 19%.

Chelse Spinner of the University of Cincinnati and her coauthors wrote that the decline in the quadrivalent vaccine–type HPV provided evidence of direct protection and high vaccine effectiveness in this real-world setting.

“This degree of effectiveness is remarkable given the fact that vaccination was defined as having received one or more doses (i.e., was not defined as having completed the vaccination series) and that women in this study were likely at a substantially higher risk for preexisting HPV infection than [were] those in the HPV vaccine clinical trials because of their reported sexual behaviors,” they wrote. “As noted in a recent review, evidence about herd protection will be a key component of cost-effectiveness analysis evaluating cervical cancer screening strategies.”

Twelve percent of women in the studies received the nine-valent HPV vaccine, and among these women, the rate of infection with the nine-valent vaccine-type HPV decreased from 47% in the first wave of vaccination to 14% in the last wave, representing a 71% decline.

The proportion of vaccinated women in the study who were infected with one or more of the five viral subtypes included in the nine-valent but not in the quadrivalent vaccine decreased significantly by 69%, from 23% to 7%.

However, these data also suggested a nonsignificant 58% increase among unvaccinated women in infections with one of the five subtypes covered by the nine-valent vaccine but not the quadrivalent vaccine.

Ms. Spinner and her associates noted this increase was unexpected and suggested the increase may be caused by the differences between vaccinated and unvaccinated women.

“For example, if women who are unvaccinated versus women who are vaccinated are more likely to practice riskier behaviors that would increase their risk of acquiring HPV, they would be more likely to acquire non–vaccine-type HPV,” they wrote.

Ms. Spinner graduated from the University of Cincinnati and now is a graduate student at the University of South Florida, Tampa. The study was funded by the National Institutes of Health. Darron R. Brown declared shares of Merck, but the other coauthors declared no other relevant financial disclosures.

SOURCE: Spinner C et al. Pediatrics. 2019, Jan 22. doi: 10.1542/peds.2018-1902.
 

Parents were much more confident about vaccinating their children against the human papillomavirus (HPV) when they were told about the diseases that the vaccine prevents rather than about safety, new research found.

Stuart Jenner/Thinkstock

In Pediatrics, researchers reported the outcomes of an online video-messaging study that attempted to address the most common parental questions and concerns about the HPV vaccine. They surveyed a national sample of 1,196 parents of children (aged 9-17 years) who watched four brief videos of a pediatrician talking about one of seven common concerns regarding HPV vaccination. The parents then were asked how each video affected them.

Parents who were exposed to messages about the diseases that the HPV vaccine prevented had the highest confidence in the HPV vaccine (46%). These messages included “HPV is a common virus that millions of people get every year. The HPV vaccine will protect your child from some cancers and genital warts” and “HPV infection can cause cancer in both men and women. The HPV vaccine will protect your child from many of these cancers.”

Similarly, parents exposed to messages about the need for HPV vaccination for both boys and girls also had the highest levels of confidence about HPV vaccination (44%).

Confidence was lower in parents exposed to messages about safety and side effects (30%)

“As such, reiterating vaccination benefits (including cancer prevention) when addressing concerns may also improve the impact of messages,” wrote Parth D. Shah, PhD, from the Fred Hutchinson Cancer Research Center, Seattle, and his coauthors.

Parents who received messages that expressed urgency about vaccination had lower confidence in the HPV vaccine.

“One reason may be that parents who are hesitant feel inappropriately rushed or that their concerns are not being treated with appropriate care,” the authors wrote.

However, messages that required a higher reading grade level and messages that were longer also seemed to inspire more confidence among parents. Parents who were exposed to messages about cancer prevention additionally were even more confident in HPV vaccine, Dr. Shah and his associates reported.

The study also found that 84% of parents wanted to talk to their children’s doctor about the diseases that the HPV vaccine prevented, while 68% wanted to talk about safety and side effects.

The study was funded by the Centers for Disease Control and Prevention and the National Cancer Institute. Dr. Shah was partially supported by an Agency for Healthcare Research and Quality grant. Another author declared being on paid advisory boards of research grants from Merck, Pfizer, and GlaxoSmithKline. No other conflicts of interest were declared.

SOURCE: Shah PD et al. Pediatrics. 2019 Feb. doi: 10.1542/peds.2018-1872.
 

Parents were much more confident about vaccinating their children against the human papillomavirus (HPV) when they were told about the diseases that the vaccine prevents rather than about safety, new research found.

Stuart Jenner/Thinkstock

In Pediatrics, researchers reported the outcomes of an online video-messaging study that attempted to address the most common parental questions and concerns about the HPV vaccine. They surveyed a national sample of 1,196 parents of children (aged 9-17 years) who watched four brief videos of a pediatrician talking about one of seven common concerns regarding HPV vaccination. The parents then were asked how each video affected them.

Parents who were exposed to messages about the diseases that the HPV vaccine prevented had the highest confidence in the HPV vaccine (46%). These messages included “HPV is a common virus that millions of people get every year. The HPV vaccine will protect your child from some cancers and genital warts” and “HPV infection can cause cancer in both men and women. The HPV vaccine will protect your child from many of these cancers.”

Similarly, parents exposed to messages about the need for HPV vaccination for both boys and girls also had the highest levels of confidence about HPV vaccination (44%).

Confidence was lower in parents exposed to messages about safety and side effects (30%)

“As such, reiterating vaccination benefits (including cancer prevention) when addressing concerns may also improve the impact of messages,” wrote Parth D. Shah, PhD, from the Fred Hutchinson Cancer Research Center, Seattle, and his coauthors.

Parents who received messages that expressed urgency about vaccination had lower confidence in the HPV vaccine.

“One reason may be that parents who are hesitant feel inappropriately rushed or that their concerns are not being treated with appropriate care,” the authors wrote.

However, messages that required a higher reading grade level and messages that were longer also seemed to inspire more confidence among parents. Parents who were exposed to messages about cancer prevention additionally were even more confident in HPV vaccine, Dr. Shah and his associates reported.

The study also found that 84% of parents wanted to talk to their children’s doctor about the diseases that the HPV vaccine prevented, while 68% wanted to talk about safety and side effects.

The study was funded by the Centers for Disease Control and Prevention and the National Cancer Institute. Dr. Shah was partially supported by an Agency for Healthcare Research and Quality grant. Another author declared being on paid advisory boards of research grants from Merck, Pfizer, and GlaxoSmithKline. No other conflicts of interest were declared.

SOURCE: Shah PD et al. Pediatrics. 2019 Feb. doi: 10.1542/peds.2018-1872.
 

Parents were much more confident about vaccinating their children against the human papillomavirus (HPV) when they were told about the diseases that the vaccine prevents rather than about safety, new research found.

Stuart Jenner/Thinkstock

In Pediatrics, researchers reported the outcomes of an online video-messaging study that attempted to address the most common parental questions and concerns about the HPV vaccine. They surveyed a national sample of 1,196 parents of children (aged 9-17 years) who watched four brief videos of a pediatrician talking about one of seven common concerns regarding HPV vaccination. The parents then were asked how each video affected them.

Parents who were exposed to messages about the diseases that the HPV vaccine prevented had the highest confidence in the HPV vaccine (46%). These messages included “HPV is a common virus that millions of people get every year. The HPV vaccine will protect your child from some cancers and genital warts” and “HPV infection can cause cancer in both men and women. The HPV vaccine will protect your child from many of these cancers.”

Similarly, parents exposed to messages about the need for HPV vaccination for both boys and girls also had the highest levels of confidence about HPV vaccination (44%).

Confidence was lower in parents exposed to messages about safety and side effects (30%)

“As such, reiterating vaccination benefits (including cancer prevention) when addressing concerns may also improve the impact of messages,” wrote Parth D. Shah, PhD, from the Fred Hutchinson Cancer Research Center, Seattle, and his coauthors.

Parents who received messages that expressed urgency about vaccination had lower confidence in the HPV vaccine.

“One reason may be that parents who are hesitant feel inappropriately rushed or that their concerns are not being treated with appropriate care,” the authors wrote.

However, messages that required a higher reading grade level and messages that were longer also seemed to inspire more confidence among parents. Parents who were exposed to messages about cancer prevention additionally were even more confident in HPV vaccine, Dr. Shah and his associates reported.

The study also found that 84% of parents wanted to talk to their children’s doctor about the diseases that the HPV vaccine prevented, while 68% wanted to talk about safety and side effects.

The study was funded by the Centers for Disease Control and Prevention and the National Cancer Institute. Dr. Shah was partially supported by an Agency for Healthcare Research and Quality grant. Another author declared being on paid advisory boards of research grants from Merck, Pfizer, and GlaxoSmithKline. No other conflicts of interest were declared.

SOURCE: Shah PD et al. Pediatrics. 2019 Feb. doi: 10.1542/peds.2018-1872.
 

Transdermal hormone replacement therapy is associated with the lowest risk of venous thromboembolism, yet still is relatively underused compared to oral preparations, researchers say.

Alexander Raths/Fotolia

Writing in the BMJ, Yana Vinogradova, PhD, of the University of Nottingham (England) and her associates reported the results of two nested case-control studies of hormone replacement therapy (HRT) and venous thromboembolism (VTE) from Jan. 1998 to Feb. 2017 that altogether included 80,396 women aged 40-79 years with a primary diagnosis of VTE matched to 391,494 female controls.

Overall, 7% of the women with VTE had been exposed to HRT in the 90 days before the index date versus 5.5% of controls.

The greatest increase in risk of VTE, compared with no exposure, was seen with oral conjugated equine estrogen with medroxyprogesterone acetate, which was associated with a more than twofold increase in risk (odds ratio, 2.10; 95% confidence interval, 1.92-2.31; P less than .01).

However transdermal HRT use was not associated with any increase in risk, compared with no HRT exposure. The data even pointed to a slight decrease in risk, which the authors suggested may be the result of some residual confounding or indication bias.

Oral HRT generally was associated with a 58% increased risk of VTE, which amounted to a number needed to harm of 1,076 and nine extra cases of VTE per 10,000 women taking oral HRT.

Dr. Vinogradova and her colleagues noted that the vast majority of women in the study were being prescribed oral HRT for menopausal symptoms despite previous studies showing transdermal HRT has much lower risk.

“When women with menopausal symptoms already have an increased VTE risk because of comorbidities or obesity, these women and their doctors should give greater consideration to transdermal HRT,” they wrote.

Lubna Pal, MBBS, director of the menopause program and professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., commented in an interview, “These data are tremendously reassuring. The reported findings are: 1) reaffirm what we have already known , i.e. that advancing age, higher body mass index, and higher doses of exogenous systemic estrogen therapy are associated with increased risk for VTE; 2) offer greater granularity in risk for VTE with different formulations of estrogens and progestins and different regimens than understood thus far, 3) reaffirm that, unlike oral estrogen, transdermal estrogen formulations in doses commonly utilized in clinical practice are not associated with VTE risk, and 4) provide reassurance that the absolute risk, while exaggerated with oral estrogen or combination estrogen and progestin use, is nonetheless small as reflected in the number needed to harm with oral hormone therapy being 1,076, and the number of extra VTE cases attributable to oral HT being 9 per 10,000 woman years. 

“The authors are to be commended on this massive analytic undertaking that allows an improved understanding of HRT-related risk for VTE and offers meaningful guidance to the practitioner,” said Dr. Pal, who was not involved in the study.*

Estrogen-only preparations had a 40% higher risk and combined preparations had a 73% higher risk, compared with no exposure.

In estrogen-only preparations, the lowest risk was seen with estradiol, compared with conjugated equine estrogens or combined preparations.

The lowest risk of VTE among oral preparations was seen with estradiol plus dydrogesterone, which only showed a nonsignificant 18% increase in risk.

In an attempt to account for possible increased risk of VTE, the authors conducted a sensitivity analysis in a subgroup of women who had not previously used anticoagulants, but they found similar results to the main analysis.

“This sensitivity analysis indicates that most of the excluded women had probably used anticoagulants because of atrial fibrillation or hip replacement operations rather than an earlier unrecorded VTE,” they wrote.

One author declared directorship of a clinical software company, but no other conflicts of interest were declared. There was no external funding. Dr. Pal reported that she was a coinvestigator in the Kronos Early Estrogen Prevention Study and on an AMAG Pharmaceuticals advisory board and member of their speaker’s bureau. 

SOURCE: Vinogradova Y et al. BMJ. 2019 Jan 9. doi: 10.1136/bmj.k4810.

*This article was updated 1/11/19.
 

Transdermal hormone replacement therapy is associated with the lowest risk of venous thromboembolism, yet still is relatively underused compared to oral preparations, researchers say.

Alexander Raths/Fotolia

Writing in the BMJ, Yana Vinogradova, PhD, of the University of Nottingham (England) and her associates reported the results of two nested case-control studies of hormone replacement therapy (HRT) and venous thromboembolism (VTE) from Jan. 1998 to Feb. 2017 that altogether included 80,396 women aged 40-79 years with a primary diagnosis of VTE matched to 391,494 female controls.

Overall, 7% of the women with VTE had been exposed to HRT in the 90 days before the index date versus 5.5% of controls.

The greatest increase in risk of VTE, compared with no exposure, was seen with oral conjugated equine estrogen with medroxyprogesterone acetate, which was associated with a more than twofold increase in risk (odds ratio, 2.10; 95% confidence interval, 1.92-2.31; P less than .01).

However transdermal HRT use was not associated with any increase in risk, compared with no HRT exposure. The data even pointed to a slight decrease in risk, which the authors suggested may be the result of some residual confounding or indication bias.

Oral HRT generally was associated with a 58% increased risk of VTE, which amounted to a number needed to harm of 1,076 and nine extra cases of VTE per 10,000 women taking oral HRT.

Dr. Vinogradova and her colleagues noted that the vast majority of women in the study were being prescribed oral HRT for menopausal symptoms despite previous studies showing transdermal HRT has much lower risk.

“When women with menopausal symptoms already have an increased VTE risk because of comorbidities or obesity, these women and their doctors should give greater consideration to transdermal HRT,” they wrote.

Lubna Pal, MBBS, director of the menopause program and professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., commented in an interview, “These data are tremendously reassuring. The reported findings are: 1) reaffirm what we have already known , i.e. that advancing age, higher body mass index, and higher doses of exogenous systemic estrogen therapy are associated with increased risk for VTE; 2) offer greater granularity in risk for VTE with different formulations of estrogens and progestins and different regimens than understood thus far, 3) reaffirm that, unlike oral estrogen, transdermal estrogen formulations in doses commonly utilized in clinical practice are not associated with VTE risk, and 4) provide reassurance that the absolute risk, while exaggerated with oral estrogen or combination estrogen and progestin use, is nonetheless small as reflected in the number needed to harm with oral hormone therapy being 1,076, and the number of extra VTE cases attributable to oral HT being 9 per 10,000 woman years. 

“The authors are to be commended on this massive analytic undertaking that allows an improved understanding of HRT-related risk for VTE and offers meaningful guidance to the practitioner,” said Dr. Pal, who was not involved in the study.*

Estrogen-only preparations had a 40% higher risk and combined preparations had a 73% higher risk, compared with no exposure.

In estrogen-only preparations, the lowest risk was seen with estradiol, compared with conjugated equine estrogens or combined preparations.

The lowest risk of VTE among oral preparations was seen with estradiol plus dydrogesterone, which only showed a nonsignificant 18% increase in risk.

In an attempt to account for possible increased risk of VTE, the authors conducted a sensitivity analysis in a subgroup of women who had not previously used anticoagulants, but they found similar results to the main analysis.

“This sensitivity analysis indicates that most of the excluded women had probably used anticoagulants because of atrial fibrillation or hip replacement operations rather than an earlier unrecorded VTE,” they wrote.

One author declared directorship of a clinical software company, but no other conflicts of interest were declared. There was no external funding. Dr. Pal reported that she was a coinvestigator in the Kronos Early Estrogen Prevention Study and on an AMAG Pharmaceuticals advisory board and member of their speaker’s bureau. 

SOURCE: Vinogradova Y et al. BMJ. 2019 Jan 9. doi: 10.1136/bmj.k4810.

*This article was updated 1/11/19.
 

Transdermal hormone replacement therapy is associated with the lowest risk of venous thromboembolism, yet still is relatively underused compared to oral preparations, researchers say.

Alexander Raths/Fotolia

Writing in the BMJ, Yana Vinogradova, PhD, of the University of Nottingham (England) and her associates reported the results of two nested case-control studies of hormone replacement therapy (HRT) and venous thromboembolism (VTE) from Jan. 1998 to Feb. 2017 that altogether included 80,396 women aged 40-79 years with a primary diagnosis of VTE matched to 391,494 female controls.

Overall, 7% of the women with VTE had been exposed to HRT in the 90 days before the index date versus 5.5% of controls.

The greatest increase in risk of VTE, compared with no exposure, was seen with oral conjugated equine estrogen with medroxyprogesterone acetate, which was associated with a more than twofold increase in risk (odds ratio, 2.10; 95% confidence interval, 1.92-2.31; P less than .01).

However transdermal HRT use was not associated with any increase in risk, compared with no HRT exposure. The data even pointed to a slight decrease in risk, which the authors suggested may be the result of some residual confounding or indication bias.

Oral HRT generally was associated with a 58% increased risk of VTE, which amounted to a number needed to harm of 1,076 and nine extra cases of VTE per 10,000 women taking oral HRT.

Dr. Vinogradova and her colleagues noted that the vast majority of women in the study were being prescribed oral HRT for menopausal symptoms despite previous studies showing transdermal HRT has much lower risk.

“When women with menopausal symptoms already have an increased VTE risk because of comorbidities or obesity, these women and their doctors should give greater consideration to transdermal HRT,” they wrote.

Lubna Pal, MBBS, director of the menopause program and professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., commented in an interview, “These data are tremendously reassuring. The reported findings are: 1) reaffirm what we have already known , i.e. that advancing age, higher body mass index, and higher doses of exogenous systemic estrogen therapy are associated with increased risk for VTE; 2) offer greater granularity in risk for VTE with different formulations of estrogens and progestins and different regimens than understood thus far, 3) reaffirm that, unlike oral estrogen, transdermal estrogen formulations in doses commonly utilized in clinical practice are not associated with VTE risk, and 4) provide reassurance that the absolute risk, while exaggerated with oral estrogen or combination estrogen and progestin use, is nonetheless small as reflected in the number needed to harm with oral hormone therapy being 1,076, and the number of extra VTE cases attributable to oral HT being 9 per 10,000 woman years. 

“The authors are to be commended on this massive analytic undertaking that allows an improved understanding of HRT-related risk for VTE and offers meaningful guidance to the practitioner,” said Dr. Pal, who was not involved in the study.*

Estrogen-only preparations had a 40% higher risk and combined preparations had a 73% higher risk, compared with no exposure.

In estrogen-only preparations, the lowest risk was seen with estradiol, compared with conjugated equine estrogens or combined preparations.

The lowest risk of VTE among oral preparations was seen with estradiol plus dydrogesterone, which only showed a nonsignificant 18% increase in risk.

In an attempt to account for possible increased risk of VTE, the authors conducted a sensitivity analysis in a subgroup of women who had not previously used anticoagulants, but they found similar results to the main analysis.

“This sensitivity analysis indicates that most of the excluded women had probably used anticoagulants because of atrial fibrillation or hip replacement operations rather than an earlier unrecorded VTE,” they wrote.

One author declared directorship of a clinical software company, but no other conflicts of interest were declared. There was no external funding. Dr. Pal reported that she was a coinvestigator in the Kronos Early Estrogen Prevention Study and on an AMAG Pharmaceuticals advisory board and member of their speaker’s bureau. 

SOURCE: Vinogradova Y et al. BMJ. 2019 Jan 9. doi: 10.1136/bmj.k4810.

*This article was updated 1/11/19.
 

Patients with hypertension who show substantial progression of cerebral small vessel disease over time have sixfold higher odds of developing mild cognitive impairment than do those without signs of progression on brain MRI, new research has found.

American Heart Association

The results, published online Jan. 4 in Hypertension, come from a longitudinal, population-based study of 976 patients with hypertension but with no history of dementia or clinical stroke. Participants underwent a vascular risk assessment, brain MRI, cognitive evaluation, and blood sampling at baseline, and 345 patients were also retested after a mean of nearly 4 years.

Researchers saw significant sixfold higher odds of developing incident mild cognitive impairment (MCI) among individuals who showed marked progression of periventricular white matter hyperintensities – an imaging hallmark of cerebral small vessel disease – compared with individuals who did not show any progression (odds ratio = 6.184; 95% confidence interval, 1.506-25.370; P = .011).

Patients with greater progression of periventricular white matter hyperintensities also showed significantly greater decreases in global cognition scores – both in total DRS-2 Z-score and executive function Z-score – when compared against individuals without white matter hyperintensity progression.

“As MCI is one of the most important risk factors in the development of dementia, future research should investigate the mechanisms by which PVH [periventricular white matter hyperintensities] trigger cognitive impairment and the clinical utility of its assessment,” wrote Joan Jiménez-Balado of Vall d’Hebron Research Institute, Barcelona, and his associates.

However, deep white matter hyperintensity progression – as opposed to periventricular – was not linked to cognitive changes, except in the case of bilateral occipital deep white matter hyperintensity changes, which were linked to a significant worsening in the attention Z-score.

The authors noted that the different impacts of periventricular versus deep white matter hyperintensities may relate to a number of factors. The first was that deep white matter hyperintensities disrupt cortico-cortical connections but periventricular ones are more likely to affect long cortico-subcortical association fibers, which “would be an important variable to determine the impaired networks involved in cognition.”

They also suggested that periventricular and deep white matter hyperintensities may affect different neuromodulator systems; the periventricular white matter could be closer to ascending cholinergic bundles that may play a role in vascular cognitive impairment.

Periventricular white matter hyperintensities may also accelerate the deposition of amyloid because of their association with venous collagenosis, which is linked to ischemia and disruptions of the interstitial fluid circulation.

“On the other hand, [deep white matter hyperintensity] may be more related to hypoperfusion, as deep areas are particularly vulnerable to low [blood pressure],” the authors wrote, while stressing that the pathophysiology of white matter hyperintensities is not fully understood, so further research is needed.

Overall, the 345 patients with follow-up data had a median age of 65 years at baseline and mean blood pressure of 143/78.2 mm Hg at baseline and 146.5/75 mm Hg at follow-up. White matter hyperintensity changes occurred periventricularly in 22% and in deep white matter in 48%. The researchers saw new infarcts in 6.1% of patients, and 5.5% had incident cerebral microbleeds. While incident cerebral microbleeds were significantly associated with declines in the attention Z-score, they did not affect other cognitive functions, and incidental infarcts were also not associated with cognitive changes.

Baseline blood pressure and average blood pressure during follow-up were not associated with changes in cardiac small vessel disease lesions. However, diastolic – but not systolic – blood pressure at baseline and follow-up was positively correlated with total, attention, and executive function DRS-2 Z-scores at follow-up.

Three-quarters of patients showed cognitive changes associated with normal aging both at baseline and follow-up, 9.1% had stable MCI, and 9.1% of patients had incident MCI. However, 6.6% of subjects reverted back to normal aging after having MCI at baseline.

The authors noted that they did not examine markers of neurodegeneration, such as tau or amyloid-beta, which could also be linked to hypertension and cerebral small vessel disease lesions.

The study was supported by Instituto de Salud Carlos III, AGAUR (Agency for Management of University and Research Grants), the Secretary of Universities and Research of the Department of Economy and Knowledge, and the European Regional Development Fund. The authors said they have no conflicts of interest.

SOURCE: Jiménez-Balado J et al. Hypertension. 2019 Jan 4. doi: 10.1161/HYPERTENSIONAHA.118.12090

Patients with hypertension who show substantial progression of cerebral small vessel disease over time have sixfold higher odds of developing mild cognitive impairment than do those without signs of progression on brain MRI, new research has found.

American Heart Association

The results, published online Jan. 4 in Hypertension, come from a longitudinal, population-based study of 976 patients with hypertension but with no history of dementia or clinical stroke. Participants underwent a vascular risk assessment, brain MRI, cognitive evaluation, and blood sampling at baseline, and 345 patients were also retested after a mean of nearly 4 years.

Researchers saw significant sixfold higher odds of developing incident mild cognitive impairment (MCI) among individuals who showed marked progression of periventricular white matter hyperintensities – an imaging hallmark of cerebral small vessel disease – compared with individuals who did not show any progression (odds ratio = 6.184; 95% confidence interval, 1.506-25.370; P = .011).

Patients with greater progression of periventricular white matter hyperintensities also showed significantly greater decreases in global cognition scores – both in total DRS-2 Z-score and executive function Z-score – when compared against individuals without white matter hyperintensity progression.

“As MCI is one of the most important risk factors in the development of dementia, future research should investigate the mechanisms by which PVH [periventricular white matter hyperintensities] trigger cognitive impairment and the clinical utility of its assessment,” wrote Joan Jiménez-Balado of Vall d’Hebron Research Institute, Barcelona, and his associates.

However, deep white matter hyperintensity progression – as opposed to periventricular – was not linked to cognitive changes, except in the case of bilateral occipital deep white matter hyperintensity changes, which were linked to a significant worsening in the attention Z-score.

The authors noted that the different impacts of periventricular versus deep white matter hyperintensities may relate to a number of factors. The first was that deep white matter hyperintensities disrupt cortico-cortical connections but periventricular ones are more likely to affect long cortico-subcortical association fibers, which “would be an important variable to determine the impaired networks involved in cognition.”

They also suggested that periventricular and deep white matter hyperintensities may affect different neuromodulator systems; the periventricular white matter could be closer to ascending cholinergic bundles that may play a role in vascular cognitive impairment.

Periventricular white matter hyperintensities may also accelerate the deposition of amyloid because of their association with venous collagenosis, which is linked to ischemia and disruptions of the interstitial fluid circulation.

“On the other hand, [deep white matter hyperintensity] may be more related to hypoperfusion, as deep areas are particularly vulnerable to low [blood pressure],” the authors wrote, while stressing that the pathophysiology of white matter hyperintensities is not fully understood, so further research is needed.

Overall, the 345 patients with follow-up data had a median age of 65 years at baseline and mean blood pressure of 143/78.2 mm Hg at baseline and 146.5/75 mm Hg at follow-up. White matter hyperintensity changes occurred periventricularly in 22% and in deep white matter in 48%. The researchers saw new infarcts in 6.1% of patients, and 5.5% had incident cerebral microbleeds. While incident cerebral microbleeds were significantly associated with declines in the attention Z-score, they did not affect other cognitive functions, and incidental infarcts were also not associated with cognitive changes.

Baseline blood pressure and average blood pressure during follow-up were not associated with changes in cardiac small vessel disease lesions. However, diastolic – but not systolic – blood pressure at baseline and follow-up was positively correlated with total, attention, and executive function DRS-2 Z-scores at follow-up.

Three-quarters of patients showed cognitive changes associated with normal aging both at baseline and follow-up, 9.1% had stable MCI, and 9.1% of patients had incident MCI. However, 6.6% of subjects reverted back to normal aging after having MCI at baseline.

The authors noted that they did not examine markers of neurodegeneration, such as tau or amyloid-beta, which could also be linked to hypertension and cerebral small vessel disease lesions.

The study was supported by Instituto de Salud Carlos III, AGAUR (Agency for Management of University and Research Grants), the Secretary of Universities and Research of the Department of Economy and Knowledge, and the European Regional Development Fund. The authors said they have no conflicts of interest.

SOURCE: Jiménez-Balado J et al. Hypertension. 2019 Jan 4. doi: 10.1161/HYPERTENSIONAHA.118.12090

Patients with hypertension who show substantial progression of cerebral small vessel disease over time have sixfold higher odds of developing mild cognitive impairment than do those without signs of progression on brain MRI, new research has found.

American Heart Association

The results, published online Jan. 4 in Hypertension, come from a longitudinal, population-based study of 976 patients with hypertension but with no history of dementia or clinical stroke. Participants underwent a vascular risk assessment, brain MRI, cognitive evaluation, and blood sampling at baseline, and 345 patients were also retested after a mean of nearly 4 years.

Researchers saw significant sixfold higher odds of developing incident mild cognitive impairment (MCI) among individuals who showed marked progression of periventricular white matter hyperintensities – an imaging hallmark of cerebral small vessel disease – compared with individuals who did not show any progression (odds ratio = 6.184; 95% confidence interval, 1.506-25.370; P = .011).

Patients with greater progression of periventricular white matter hyperintensities also showed significantly greater decreases in global cognition scores – both in total DRS-2 Z-score and executive function Z-score – when compared against individuals without white matter hyperintensity progression.

“As MCI is one of the most important risk factors in the development of dementia, future research should investigate the mechanisms by which PVH [periventricular white matter hyperintensities] trigger cognitive impairment and the clinical utility of its assessment,” wrote Joan Jiménez-Balado of Vall d’Hebron Research Institute, Barcelona, and his associates.

However, deep white matter hyperintensity progression – as opposed to periventricular – was not linked to cognitive changes, except in the case of bilateral occipital deep white matter hyperintensity changes, which were linked to a significant worsening in the attention Z-score.

The authors noted that the different impacts of periventricular versus deep white matter hyperintensities may relate to a number of factors. The first was that deep white matter hyperintensities disrupt cortico-cortical connections but periventricular ones are more likely to affect long cortico-subcortical association fibers, which “would be an important variable to determine the impaired networks involved in cognition.”

They also suggested that periventricular and deep white matter hyperintensities may affect different neuromodulator systems; the periventricular white matter could be closer to ascending cholinergic bundles that may play a role in vascular cognitive impairment.

Periventricular white matter hyperintensities may also accelerate the deposition of amyloid because of their association with venous collagenosis, which is linked to ischemia and disruptions of the interstitial fluid circulation.

“On the other hand, [deep white matter hyperintensity] may be more related to hypoperfusion, as deep areas are particularly vulnerable to low [blood pressure],” the authors wrote, while stressing that the pathophysiology of white matter hyperintensities is not fully understood, so further research is needed.

Overall, the 345 patients with follow-up data had a median age of 65 years at baseline and mean blood pressure of 143/78.2 mm Hg at baseline and 146.5/75 mm Hg at follow-up. White matter hyperintensity changes occurred periventricularly in 22% and in deep white matter in 48%. The researchers saw new infarcts in 6.1% of patients, and 5.5% had incident cerebral microbleeds. While incident cerebral microbleeds were significantly associated with declines in the attention Z-score, they did not affect other cognitive functions, and incidental infarcts were also not associated with cognitive changes.

Baseline blood pressure and average blood pressure during follow-up were not associated with changes in cardiac small vessel disease lesions. However, diastolic – but not systolic – blood pressure at baseline and follow-up was positively correlated with total, attention, and executive function DRS-2 Z-scores at follow-up.

Three-quarters of patients showed cognitive changes associated with normal aging both at baseline and follow-up, 9.1% had stable MCI, and 9.1% of patients had incident MCI. However, 6.6% of subjects reverted back to normal aging after having MCI at baseline.

The authors noted that they did not examine markers of neurodegeneration, such as tau or amyloid-beta, which could also be linked to hypertension and cerebral small vessel disease lesions.

The study was supported by Instituto de Salud Carlos III, AGAUR (Agency for Management of University and Research Grants), the Secretary of Universities and Research of the Department of Economy and Knowledge, and the European Regional Development Fund. The authors said they have no conflicts of interest.

SOURCE: Jiménez-Balado J et al. Hypertension. 2019 Jan 4. doi: 10.1161/HYPERTENSIONAHA.118.12090

Opioid prescriptions after gynecologic surgery can be significantly reduced without impacting postoperative pain scores or complication rates, according to a paper published in JAMA Network Open.

A tertiary care comprehensive care center implemented an ultrarestrictive opioid prescription protocol (UROPP) then evaluated the outcomes in a case-control study involving 605 women undergoing gynecologic surgery, compared with 626 controls treated before implementation of the new protocol.

The ultrarestrictive protocol was prompted by frequent inquiries from patients who had used very little of their prescribed opioids after surgery and wanted to know what to do with the unused pills.

The new protocol involved a short preoperative counseling session about postoperative pain management. Following that, ambulatory surgery, minimally invasive surgery, or laparotomy patients were prescribed a 7-day supply of nonopioid pain relief. Laparotomy patients were also prescribed a 3-day supply of an oral opioid.

Any patients who required more than five opioid doses in the 24 hours before discharge were also prescribed a 3-day supply of opioid pain medication as needed, and all patients had the option of requesting an additional 3-day opioid refill.

Researchers saw no significant differences between the two groups in mean postoperative pain scores 2 weeks after surgery, and a similar number of patients in each group requested an opioid refill. There was also no significant difference in the number of postoperative complications between groups.

Implementation of the ultrarestrictive protocol was associated with significant declines in the mean number of opioid pills prescribed dropped from 31.7 to 3.5 in all surgical cases, from 43.6 to 12.1 in the laparotomy group, from 38.4 to 1.3 in the minimally invasive surgery group, and from 13.9 to 0.2 in patients who underwent ambulatory surgery.

“These data suggest that the implementation of a UROPP in a large surgical service is feasible and safe and was associated with a significantly decreased number of opioids dispensed during the perioperative period, particularly among opioid-naive patients,” wrote Jaron Mark, MD, of the department of gynecologic oncology at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and his coauthors. “The opioid-sparing effect was also marked and statistically significant in the laparotomy group, where most patients remained physically active and recovered well with no negative sequelae or elevated pain score after surgery.”

The researchers also noted that patients who were discharged home with an opioid prescription were more likely to call and request a refill within 30 days, compared with patients who did not receive opioids at discharge.

The study was supported by the Roswell Park Comprehensive Cancer Center, the National Cancer Institute and the Roswell Park Alliance Foundation. Two authors reported receiving fees and nonfinancial support from the private sector unrelated to the study.

SOURCE: Mark J et al. JAMA Netw Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5452.
 

Opioid prescriptions after gynecologic surgery can be significantly reduced without impacting postoperative pain scores or complication rates, according to a paper published in JAMA Network Open.

A tertiary care comprehensive care center implemented an ultrarestrictive opioid prescription protocol (UROPP) then evaluated the outcomes in a case-control study involving 605 women undergoing gynecologic surgery, compared with 626 controls treated before implementation of the new protocol.

The ultrarestrictive protocol was prompted by frequent inquiries from patients who had used very little of their prescribed opioids after surgery and wanted to know what to do with the unused pills.

The new protocol involved a short preoperative counseling session about postoperative pain management. Following that, ambulatory surgery, minimally invasive surgery, or laparotomy patients were prescribed a 7-day supply of nonopioid pain relief. Laparotomy patients were also prescribed a 3-day supply of an oral opioid.

Any patients who required more than five opioid doses in the 24 hours before discharge were also prescribed a 3-day supply of opioid pain medication as needed, and all patients had the option of requesting an additional 3-day opioid refill.

Researchers saw no significant differences between the two groups in mean postoperative pain scores 2 weeks after surgery, and a similar number of patients in each group requested an opioid refill. There was also no significant difference in the number of postoperative complications between groups.

Implementation of the ultrarestrictive protocol was associated with significant declines in the mean number of opioid pills prescribed dropped from 31.7 to 3.5 in all surgical cases, from 43.6 to 12.1 in the laparotomy group, from 38.4 to 1.3 in the minimally invasive surgery group, and from 13.9 to 0.2 in patients who underwent ambulatory surgery.

“These data suggest that the implementation of a UROPP in a large surgical service is feasible and safe and was associated with a significantly decreased number of opioids dispensed during the perioperative period, particularly among opioid-naive patients,” wrote Jaron Mark, MD, of the department of gynecologic oncology at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and his coauthors. “The opioid-sparing effect was also marked and statistically significant in the laparotomy group, where most patients remained physically active and recovered well with no negative sequelae or elevated pain score after surgery.”

The researchers also noted that patients who were discharged home with an opioid prescription were more likely to call and request a refill within 30 days, compared with patients who did not receive opioids at discharge.

The study was supported by the Roswell Park Comprehensive Cancer Center, the National Cancer Institute and the Roswell Park Alliance Foundation. Two authors reported receiving fees and nonfinancial support from the private sector unrelated to the study.

SOURCE: Mark J et al. JAMA Netw Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5452.
 

Opioid prescriptions after gynecologic surgery can be significantly reduced without impacting postoperative pain scores or complication rates, according to a paper published in JAMA Network Open.

A tertiary care comprehensive care center implemented an ultrarestrictive opioid prescription protocol (UROPP) then evaluated the outcomes in a case-control study involving 605 women undergoing gynecologic surgery, compared with 626 controls treated before implementation of the new protocol.

The ultrarestrictive protocol was prompted by frequent inquiries from patients who had used very little of their prescribed opioids after surgery and wanted to know what to do with the unused pills.

The new protocol involved a short preoperative counseling session about postoperative pain management. Following that, ambulatory surgery, minimally invasive surgery, or laparotomy patients were prescribed a 7-day supply of nonopioid pain relief. Laparotomy patients were also prescribed a 3-day supply of an oral opioid.

Any patients who required more than five opioid doses in the 24 hours before discharge were also prescribed a 3-day supply of opioid pain medication as needed, and all patients had the option of requesting an additional 3-day opioid refill.

Researchers saw no significant differences between the two groups in mean postoperative pain scores 2 weeks after surgery, and a similar number of patients in each group requested an opioid refill. There was also no significant difference in the number of postoperative complications between groups.

Implementation of the ultrarestrictive protocol was associated with significant declines in the mean number of opioid pills prescribed dropped from 31.7 to 3.5 in all surgical cases, from 43.6 to 12.1 in the laparotomy group, from 38.4 to 1.3 in the minimally invasive surgery group, and from 13.9 to 0.2 in patients who underwent ambulatory surgery.

“These data suggest that the implementation of a UROPP in a large surgical service is feasible and safe and was associated with a significantly decreased number of opioids dispensed during the perioperative period, particularly among opioid-naive patients,” wrote Jaron Mark, MD, of the department of gynecologic oncology at Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., and his coauthors. “The opioid-sparing effect was also marked and statistically significant in the laparotomy group, where most patients remained physically active and recovered well with no negative sequelae or elevated pain score after surgery.”

The researchers also noted that patients who were discharged home with an opioid prescription were more likely to call and request a refill within 30 days, compared with patients who did not receive opioids at discharge.

The study was supported by the Roswell Park Comprehensive Cancer Center, the National Cancer Institute and the Roswell Park Alliance Foundation. Two authors reported receiving fees and nonfinancial support from the private sector unrelated to the study.

SOURCE: Mark J et al. JAMA Netw Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5452.
 

A negative colonoscopy result is associated with a reduced risk of colorectal cancer for more than 12 years after the examination, compared with an unscreened population, new research has found.

In a retrospective cohort study published in JAMA Internal Medicine, researchers analyzed data from 1,251,318 individuals at average risk of colorectal cancer who were eligible to participate in screening over more than 9 million person-years of follow-up.

They found that screened individuals with a negative result had an adjusted 46%-95% lower risk of colorectal cancer and 29%-96% lower risk of colorectal cancer mortality than unscreened individuals across more than 12 years of follow-up.

At 10 years post colonoscopy, participants who had a negative colonoscopy result still had a significant 46% lower risk of colorectal cancer (hazard ratio [HR], 0.54; 95% [confidence interval] CI: 0.31-0.94) and 88% lower risk of colorectal cancer mortality (HR, 0.12; 95% CI: 0.02-0.82). After more than 12 years, there was still a nonsignificant trend toward a lower risk of colorectal cancer incidence and mortality.

Jeffrey K. Lee, MD, of Kaiser Permanente San Francisco, and his coauthors suggested that their findings have implications for the timing of rescreening after a negative colonoscopy result.

“The current guideline-recommended 10-year rescreening interval is not based on a predetermined risk threshold, and while we observed a reduced risk of colorectal cancer and related deaths throughout the more than 12-year follow-up period, an examination of absolute risk [incidence] could provide another justification for the timing for rescreening,” they wrote. “Additional research is needed to evaluate the costs and benefits of earlier versus later rescreening, optimal rescreening tests following a negative colonoscopy result [e.g., another colonoscopy versus annual fecal immunochemical testing], and whether the benefits of rescreening vary between subgroups.”

The study showed that the rate of repeat endoscopic procedures increased at year 10, largely because of screening colonoscopies which are recommended at 10-year intervals. However, in a separate analysis, the authors excluded colonoscopies for a screening indication and still found a similar reduction in the risk of colorectal cancer, compared with the unscreened group.

The data also showed a 22%-87% lower risk of proximal colorectal cancer, a 50%-99% lower risk of distal cancer, a 31%-95% lower risk of early-stage colorectal cancer, and a 56%-96% reduced risk of advanced-stage colorectal cancer among those who had a negative result, compared with those who did not undergo screening.

The authors wrote that this pattern of greater risk reductions in the distal versus proximal cancer had been seen in previous studies and could be the result of incomplete examinations, inadequate bowel cleansing, challenges in identifying right colon polyps and sessile serrated adenomas, or differences in polyp biology in the proximal versus distal colon.

The incidence rates of colorectal cancer among those who had a negative result from colonoscopy ranged from 16.6 per 100,000 person-years (95% CI: 8.2-12.8) at 1 year after screening to 133.2 per 100,000 person-years (95% CI: 70.9-227.8) at the 10-year mark. In comparison, the incidence rates among the unscreened population increased from 62.9 per 100,000 person-years (95% CI: 55.7-70.0) at year 1 to 224.8 per 100,000 person-years (95% CI: 202.5-247.0) after year 12.

Mortality rates from colorectal cancer at year 1 were 6.8 per 100,000 person-years (95% CI: 0.8-12.7) in the negative results group and 10.5 (95% CI: 8.2-12.8) in the unscreened cohort. At year 12, that figure was 92.2 per 100,000 person-years (95% CI: 19.0-165.4) in the negative results cohort, while after year 12 in the unscreened cohort, colorectal cancer mortality rates increased to 192 per 100,000 person years (95% CI: 7-214.3).

While the study made use of a validated cancer registry to ensure they accurately captured cancers and mortality, the authors acknowledged that they weren’t able to adjust for residual confounding factors such as red-meat intake or smoking.

The study was supported by the National Cancer Institute, the American Gastroenterological Association, and the Sylvia Allison Kaplan Foundation. No conflicts of interest were reported.

The AGA GI Patient Center provides education materials that can help your patients better understand their colorectal cancer risk and prepare for a colonoscopy. Visit patient.gastro.org to review and download.

SOURCE: Lee JK et al. JAMA Intern Med. 2018 Dec 17. doi: 10.1001/jamainternmed.2018.5565.

A negative colonoscopy result is associated with a reduced risk of colorectal cancer for more than 12 years after the examination, compared with an unscreened population, new research has found.

In a retrospective cohort study published in JAMA Internal Medicine, researchers analyzed data from 1,251,318 individuals at average risk of colorectal cancer who were eligible to participate in screening over more than 9 million person-years of follow-up.

They found that screened individuals with a negative result had an adjusted 46%-95% lower risk of colorectal cancer and 29%-96% lower risk of colorectal cancer mortality than unscreened individuals across more than 12 years of follow-up.

At 10 years post colonoscopy, participants who had a negative colonoscopy result still had a significant 46% lower risk of colorectal cancer (hazard ratio [HR], 0.54; 95% [confidence interval] CI: 0.31-0.94) and 88% lower risk of colorectal cancer mortality (HR, 0.12; 95% CI: 0.02-0.82). After more than 12 years, there was still a nonsignificant trend toward a lower risk of colorectal cancer incidence and mortality.

Jeffrey K. Lee, MD, of Kaiser Permanente San Francisco, and his coauthors suggested that their findings have implications for the timing of rescreening after a negative colonoscopy result.

“The current guideline-recommended 10-year rescreening interval is not based on a predetermined risk threshold, and while we observed a reduced risk of colorectal cancer and related deaths throughout the more than 12-year follow-up period, an examination of absolute risk [incidence] could provide another justification for the timing for rescreening,” they wrote. “Additional research is needed to evaluate the costs and benefits of earlier versus later rescreening, optimal rescreening tests following a negative colonoscopy result [e.g., another colonoscopy versus annual fecal immunochemical testing], and whether the benefits of rescreening vary between subgroups.”

The study showed that the rate of repeat endoscopic procedures increased at year 10, largely because of screening colonoscopies which are recommended at 10-year intervals. However, in a separate analysis, the authors excluded colonoscopies for a screening indication and still found a similar reduction in the risk of colorectal cancer, compared with the unscreened group.

The data also showed a 22%-87% lower risk of proximal colorectal cancer, a 50%-99% lower risk of distal cancer, a 31%-95% lower risk of early-stage colorectal cancer, and a 56%-96% reduced risk of advanced-stage colorectal cancer among those who had a negative result, compared with those who did not undergo screening.

The authors wrote that this pattern of greater risk reductions in the distal versus proximal cancer had been seen in previous studies and could be the result of incomplete examinations, inadequate bowel cleansing, challenges in identifying right colon polyps and sessile serrated adenomas, or differences in polyp biology in the proximal versus distal colon.

The incidence rates of colorectal cancer among those who had a negative result from colonoscopy ranged from 16.6 per 100,000 person-years (95% CI: 8.2-12.8) at 1 year after screening to 133.2 per 100,000 person-years (95% CI: 70.9-227.8) at the 10-year mark. In comparison, the incidence rates among the unscreened population increased from 62.9 per 100,000 person-years (95% CI: 55.7-70.0) at year 1 to 224.8 per 100,000 person-years (95% CI: 202.5-247.0) after year 12.

Mortality rates from colorectal cancer at year 1 were 6.8 per 100,000 person-years (95% CI: 0.8-12.7) in the negative results group and 10.5 (95% CI: 8.2-12.8) in the unscreened cohort. At year 12, that figure was 92.2 per 100,000 person-years (95% CI: 19.0-165.4) in the negative results cohort, while after year 12 in the unscreened cohort, colorectal cancer mortality rates increased to 192 per 100,000 person years (95% CI: 7-214.3).

While the study made use of a validated cancer registry to ensure they accurately captured cancers and mortality, the authors acknowledged that they weren’t able to adjust for residual confounding factors such as red-meat intake or smoking.

The study was supported by the National Cancer Institute, the American Gastroenterological Association, and the Sylvia Allison Kaplan Foundation. No conflicts of interest were reported.

The AGA GI Patient Center provides education materials that can help your patients better understand their colorectal cancer risk and prepare for a colonoscopy. Visit patient.gastro.org to review and download.

SOURCE: Lee JK et al. JAMA Intern Med. 2018 Dec 17. doi: 10.1001/jamainternmed.2018.5565.

A negative colonoscopy result is associated with a reduced risk of colorectal cancer for more than 12 years after the examination, compared with an unscreened population, new research has found.

In a retrospective cohort study published in JAMA Internal Medicine, researchers analyzed data from 1,251,318 individuals at average risk of colorectal cancer who were eligible to participate in screening over more than 9 million person-years of follow-up.

They found that screened individuals with a negative result had an adjusted 46%-95% lower risk of colorectal cancer and 29%-96% lower risk of colorectal cancer mortality than unscreened individuals across more than 12 years of follow-up.

At 10 years post colonoscopy, participants who had a negative colonoscopy result still had a significant 46% lower risk of colorectal cancer (hazard ratio [HR], 0.54; 95% [confidence interval] CI: 0.31-0.94) and 88% lower risk of colorectal cancer mortality (HR, 0.12; 95% CI: 0.02-0.82). After more than 12 years, there was still a nonsignificant trend toward a lower risk of colorectal cancer incidence and mortality.

Jeffrey K. Lee, MD, of Kaiser Permanente San Francisco, and his coauthors suggested that their findings have implications for the timing of rescreening after a negative colonoscopy result.

“The current guideline-recommended 10-year rescreening interval is not based on a predetermined risk threshold, and while we observed a reduced risk of colorectal cancer and related deaths throughout the more than 12-year follow-up period, an examination of absolute risk [incidence] could provide another justification for the timing for rescreening,” they wrote. “Additional research is needed to evaluate the costs and benefits of earlier versus later rescreening, optimal rescreening tests following a negative colonoscopy result [e.g., another colonoscopy versus annual fecal immunochemical testing], and whether the benefits of rescreening vary between subgroups.”

The study showed that the rate of repeat endoscopic procedures increased at year 10, largely because of screening colonoscopies which are recommended at 10-year intervals. However, in a separate analysis, the authors excluded colonoscopies for a screening indication and still found a similar reduction in the risk of colorectal cancer, compared with the unscreened group.

The data also showed a 22%-87% lower risk of proximal colorectal cancer, a 50%-99% lower risk of distal cancer, a 31%-95% lower risk of early-stage colorectal cancer, and a 56%-96% reduced risk of advanced-stage colorectal cancer among those who had a negative result, compared with those who did not undergo screening.

The authors wrote that this pattern of greater risk reductions in the distal versus proximal cancer had been seen in previous studies and could be the result of incomplete examinations, inadequate bowel cleansing, challenges in identifying right colon polyps and sessile serrated adenomas, or differences in polyp biology in the proximal versus distal colon.

The incidence rates of colorectal cancer among those who had a negative result from colonoscopy ranged from 16.6 per 100,000 person-years (95% CI: 8.2-12.8) at 1 year after screening to 133.2 per 100,000 person-years (95% CI: 70.9-227.8) at the 10-year mark. In comparison, the incidence rates among the unscreened population increased from 62.9 per 100,000 person-years (95% CI: 55.7-70.0) at year 1 to 224.8 per 100,000 person-years (95% CI: 202.5-247.0) after year 12.

Mortality rates from colorectal cancer at year 1 were 6.8 per 100,000 person-years (95% CI: 0.8-12.7) in the negative results group and 10.5 (95% CI: 8.2-12.8) in the unscreened cohort. At year 12, that figure was 92.2 per 100,000 person-years (95% CI: 19.0-165.4) in the negative results cohort, while after year 12 in the unscreened cohort, colorectal cancer mortality rates increased to 192 per 100,000 person years (95% CI: 7-214.3).

While the study made use of a validated cancer registry to ensure they accurately captured cancers and mortality, the authors acknowledged that they weren’t able to adjust for residual confounding factors such as red-meat intake or smoking.

The study was supported by the National Cancer Institute, the American Gastroenterological Association, and the Sylvia Allison Kaplan Foundation. No conflicts of interest were reported.

The AGA GI Patient Center provides education materials that can help your patients better understand their colorectal cancer risk and prepare for a colonoscopy. Visit patient.gastro.org to review and download.

SOURCE: Lee JK et al. JAMA Intern Med. 2018 Dec 17. doi: 10.1001/jamainternmed.2018.5565.

A negative colonoscopy result is associated with a reduced risk of colorectal cancer for more than 12 years after the examination, compared with an unscreened population, new research has found.

In a retrospective cohort study published in JAMA Internal Medicine, researchers analyzed data from 1,251,318 individuals at average risk of colorectal cancer who were eligible to participate in screening over more than 9 million person-years of follow-up.

They found that screened individuals with a negative result had an adjusted 46%-95% lower risk of colorectal cancer and 29%-96% lower risk of colorectal cancer mortality than unscreened individuals across more than 12 years of follow-up.

At 10 years post colonoscopy, participants who had a negative colonoscopy result still had a significant 46% lower risk of colorectal cancer and 88% lower risk of colorectal cancer mortality. After more than 12 years, there was still a nonsignificant trend towards a lower risk of colorectal cancer incidence and mortality.

Jeffrey K. Lee, MD, of Kaiser Permanente San Francisco, and his coauthors suggested that their findings have implications for the timing of rescreening after a negative colonoscopy result.

“The current guideline-recommended 10-year rescreening interval is not based on a predetermined risk threshold, and while we observed a reduced risk of colorectal cancer and related deaths throughout the more than 12-year follow-up period, an examination of absolute risk [incidence] could provide another justification for the timing for rescreening,” they wrote. “Additional research is needed to evaluate the costs and benefits of earlier versus later rescreening, optimal rescreening tests following a negative colonoscopy result [e.g., another colonoscopy versus annual fecal immunochemical testing], and whether the benefits of rescreening vary between subgroups.”

The study showed that the rate of repeat endoscopic procedures increased at year 10, largely because of screening colonoscopies which are recommended at 10-year intervals. However in a separate analysis, the authors excluded colonoscopies for a screening indication and still found a similar reduction in the risk of colorectal cancer, compared with the unscreened group.

The data also showed a 22%-87% lower risk of proximal colorectal cancer, a 50%-99% lower risk of distal cancer, a 31%-95% lower risk of early-stage colorectal cancer, and a 56%-96% reduced risk of advanced-stage colorectal cancer among those who had a negative result, compared with those who did not undergo screening.

The authors wrote that this pattern of greater risk reductions in the distal versus proximal cancer had been seen in previous studies and could be the result of incomplete examinations, inadequate bowel cleansing, challenges in identifying right colon polyps and sessile serrated adenomas, or differences in polyp biology in the proximal versus distal colon.

The incidence rates of colorectal cancer among those who had a negative result from colonoscopy ranged from 16.6 per 100,000 person-years at 1 year after screening to 133.2 per 100,000 person-years at the 10-year mark. In comparison, the incidence rates among the unscreened population increased from 62.9 per 100,000 person-years at year 1 to 224.8 after year 12.

Mortality rates from colorectal cancer at year 1 were 6.8 per 100,000 person-years in the negative results group and 10.5 in the unscreened cohort. At year 12, that figure was 92.2 per 100,000 person-years in the negative results cohort, while after year 12 in the unscreened cohort, colorectal cancer mortality rates increased to 192 per 100,000 person years.

While the study made use of a validated cancer registry to ensure they accurately captured cancers and mortality, the authors acknowledged that they weren’t able to adjust for residual confounding factors such as red-meat intake or smoking.

The study was supported by the National Cancer Institute, the American Gastroenterological Association, and the Sylvia Allison Kaplan Foundation. No conflicts of interest were reported.

SOURCE: Lee JK et al. JAMA Intern Med. 2018 Dec 17. doi: 10.1001/jamainternmed.2018.5565.

A negative colonoscopy result is associated with a reduced risk of colorectal cancer for more than 12 years after the examination, compared with an unscreened population, new research has found.

In a retrospective cohort study published in JAMA Internal Medicine, researchers analyzed data from 1,251,318 individuals at average risk of colorectal cancer who were eligible to participate in screening over more than 9 million person-years of follow-up.

They found that screened individuals with a negative result had an adjusted 46%-95% lower risk of colorectal cancer and 29%-96% lower risk of colorectal cancer mortality than unscreened individuals across more than 12 years of follow-up.

At 10 years post colonoscopy, participants who had a negative colonoscopy result still had a significant 46% lower risk of colorectal cancer and 88% lower risk of colorectal cancer mortality. After more than 12 years, there was still a nonsignificant trend towards a lower risk of colorectal cancer incidence and mortality.

Jeffrey K. Lee, MD, of Kaiser Permanente San Francisco, and his coauthors suggested that their findings have implications for the timing of rescreening after a negative colonoscopy result.

“The current guideline-recommended 10-year rescreening interval is not based on a predetermined risk threshold, and while we observed a reduced risk of colorectal cancer and related deaths throughout the more than 12-year follow-up period, an examination of absolute risk [incidence] could provide another justification for the timing for rescreening,” they wrote. “Additional research is needed to evaluate the costs and benefits of earlier versus later rescreening, optimal rescreening tests following a negative colonoscopy result [e.g., another colonoscopy versus annual fecal immunochemical testing], and whether the benefits of rescreening vary between subgroups.”

The study showed that the rate of repeat endoscopic procedures increased at year 10, largely because of screening colonoscopies which are recommended at 10-year intervals. However in a separate analysis, the authors excluded colonoscopies for a screening indication and still found a similar reduction in the risk of colorectal cancer, compared with the unscreened group.

The data also showed a 22%-87% lower risk of proximal colorectal cancer, a 50%-99% lower risk of distal cancer, a 31%-95% lower risk of early-stage colorectal cancer, and a 56%-96% reduced risk of advanced-stage colorectal cancer among those who had a negative result, compared with those who did not undergo screening.

The authors wrote that this pattern of greater risk reductions in the distal versus proximal cancer had been seen in previous studies and could be the result of incomplete examinations, inadequate bowel cleansing, challenges in identifying right colon polyps and sessile serrated adenomas, or differences in polyp biology in the proximal versus distal colon.

The incidence rates of colorectal cancer among those who had a negative result from colonoscopy ranged from 16.6 per 100,000 person-years at 1 year after screening to 133.2 per 100,000 person-years at the 10-year mark. In comparison, the incidence rates among the unscreened population increased from 62.9 per 100,000 person-years at year 1 to 224.8 after year 12.

Mortality rates from colorectal cancer at year 1 were 6.8 per 100,000 person-years in the negative results group and 10.5 in the unscreened cohort. At year 12, that figure was 92.2 per 100,000 person-years in the negative results cohort, while after year 12 in the unscreened cohort, colorectal cancer mortality rates increased to 192 per 100,000 person years.

While the study made use of a validated cancer registry to ensure they accurately captured cancers and mortality, the authors acknowledged that they weren’t able to adjust for residual confounding factors such as red-meat intake or smoking.

The study was supported by the National Cancer Institute, the American Gastroenterological Association, and the Sylvia Allison Kaplan Foundation. No conflicts of interest were reported.

SOURCE: Lee JK et al. JAMA Intern Med. 2018 Dec 17. doi: 10.1001/jamainternmed.2018.5565.

A negative colonoscopy result is associated with a reduced risk of colorectal cancer for more than 12 years after the examination, compared with an unscreened population, new research has found.

In a retrospective cohort study published in JAMA Internal Medicine, researchers analyzed data from 1,251,318 individuals at average risk of colorectal cancer who were eligible to participate in screening over more than 9 million person-years of follow-up.

They found that screened individuals with a negative result had an adjusted 46%-95% lower risk of colorectal cancer and 29%-96% lower risk of colorectal cancer mortality than unscreened individuals across more than 12 years of follow-up.

At 10 years post colonoscopy, participants who had a negative colonoscopy result still had a significant 46% lower risk of colorectal cancer and 88% lower risk of colorectal cancer mortality. After more than 12 years, there was still a nonsignificant trend towards a lower risk of colorectal cancer incidence and mortality.

Jeffrey K. Lee, MD, of Kaiser Permanente San Francisco, and his coauthors suggested that their findings have implications for the timing of rescreening after a negative colonoscopy result.

“The current guideline-recommended 10-year rescreening interval is not based on a predetermined risk threshold, and while we observed a reduced risk of colorectal cancer and related deaths throughout the more than 12-year follow-up period, an examination of absolute risk [incidence] could provide another justification for the timing for rescreening,” they wrote. “Additional research is needed to evaluate the costs and benefits of earlier versus later rescreening, optimal rescreening tests following a negative colonoscopy result [e.g., another colonoscopy versus annual fecal immunochemical testing], and whether the benefits of rescreening vary between subgroups.”

The study showed that the rate of repeat endoscopic procedures increased at year 10, largely because of screening colonoscopies which are recommended at 10-year intervals. However in a separate analysis, the authors excluded colonoscopies for a screening indication and still found a similar reduction in the risk of colorectal cancer, compared with the unscreened group.

The data also showed a 22%-87% lower risk of proximal colorectal cancer, a 50%-99% lower risk of distal cancer, a 31%-95% lower risk of early-stage colorectal cancer, and a 56%-96% reduced risk of advanced-stage colorectal cancer among those who had a negative result, compared with those who did not undergo screening.

The authors wrote that this pattern of greater risk reductions in the distal versus proximal cancer had been seen in previous studies and could be the result of incomplete examinations, inadequate bowel cleansing, challenges in identifying right colon polyps and sessile serrated adenomas, or differences in polyp biology in the proximal versus distal colon.

The incidence rates of colorectal cancer among those who had a negative result from colonoscopy ranged from 16.6 per 100,000 person-years at 1 year after screening to 133.2 per 100,000 person-years at the 10-year mark. In comparison, the incidence rates among the unscreened population increased from 62.9 per 100,000 person-years at year 1 to 224.8 after year 12.

Mortality rates from colorectal cancer at year 1 were 6.8 per 100,000 person-years in the negative results group and 10.5 in the unscreened cohort. At year 12, that figure was 92.2 per 100,000 person-years in the negative results cohort, while after year 12 in the unscreened cohort, colorectal cancer mortality rates increased to 192 per 100,000 person years.

While the study made use of a validated cancer registry to ensure they accurately captured cancers and mortality, the authors acknowledged that they weren’t able to adjust for residual confounding factors such as red-meat intake or smoking.

The study was supported by the National Cancer Institute, the American Gastroenterological Association, and the Sylvia Allison Kaplan Foundation. No conflicts of interest were reported.

SOURCE: Lee JK et al. JAMA Intern Med. 2018 Dec 17. doi: 10.1001/jamainternmed.2018.5565.

The increased risk of cancer associated with anti-TIF1-Ab-positive dermatomyositis is limited almost exclusively to 3 years on either side of the onset of dermatomyositis, new research suggests.

Idiopathic inflammatory myopathy have been associated with malignancy, in particular dermatomyositis (DM) and the DM-specific antitranscriptional intermediary factor 1 antibody (anti-TIF1-Ab).

Around one-fifth of the 236 patients diagnosed with DM in the current study, published online Dec. 7 in Rheumatology, were anti-TIF1-Ab positive, and these patients had a more than threefold higher risk of developing cancer comapared with patients who were anti-TIF1-Ab negative (hazard ratio = 3.4, 95% confidence interval, 2.2-5.4; P less than .01).

Overall, 38% of patients in the anti-TIF1-Ab-positive group developed cancer during the 10-year follow-up, compared with 15% of patients with anti-TIF1-Ab-negative DM.

However, all the cancers in the anti-TIF1-Ab-positive group occurred within the 3 years before the onset of DM or within 2.5 years after onset. No anti-TIF1-Ab-positive patients developed cancers after this time, but some patients in the anti-TIF1-Ab-negative group did.

“This finding is not likely to be due to a disparity in follow-up time between anti-TIF1-Ab-positive and -negative cases, as the median follow-up times were similar for both groups: 10 years and 12 years, respectively,” wrote Alexander Oldroyd, MBChB, a clinical research fellow in the Centre for Musculoskeletal Research at the University of Manchester (England), and his coauthors. “Further, this finding is unlikely to be due to differences in cancer detection methods, as both cohorts’ cancer diagnoses were identified through HSCIC [U.K. Health and Social Care Information Centre] data, ensuring capture of all incident cancers during the follow-up period.”

Anti-TIF1-Ab-positive patients were more likely to develop cancer if they were older. None of the 15 anti-TIF1-Ab-positive patients who were aged under 39 when they developed DM went on to develop cancer. But cancer developed in around half of the anti-TIF1-Ab-positive patients who were aged 39 years or older when their DM began.


The anti-TIF1 antibody is commonly found in juvenile DM, but previous research has not found an association with an increased risk of cancer in this younger patient population.

“Our findings add strength to the hypothesis that there exists a subset of young adult anti-TIF1-Ab-positive cases who do not have a discernible increased risk of cancer, similar to that observed in TIF1-Ab-positive juvenile DM,” the authors wrote. They suggested that given the increased risk of malignancy in older patients who were anti-TIF1-Ab positive, this group should be subject to more detailed cancer screening.

Breast cancer was the most common malignancy among both anti-TIF1-Ab-positive and anti-TIF1-Ab-negative patients (33% and 25%, respectively). However, ovarian cancer was significantly more common among the anti-TIF1-Ab-positive patients than among the anti-TIF1-Ab-negative patients (19% vs. 2%; P less than .05); four of the five ovarian cancers in the entire cohort occurred in the anti-TIF1-Ab-positive group.

The authors noted that this confirmed the finding of a number of previous studies suggesting an increased risk of ovarian cancer with DM.

“However, this is the first large study to identify that ovarian cancer is overrepresented in anti-TIF1-Ab-positive individuals, suggesting that the true association between DM and ovarian cancer may be through possession of anti-TIF1-Abs,” they noted.

The authors wrote that they had aimed to inform cancer screening strategies among patients with DM.

“It may be that a focus on screening for cancer within the first 3 years after DM onset and particularly screening for ovarian cancer in anti-TIF1-Ab-positive female patients may be required,” they wrote. “Our findings also strengthen the hypothesis that inflammatory myopathies represent a paraneoplastic reaction initiated by attempted immune-mediated clearance of a cancer.”

The study was supported by Arthritis Research UK, Myositis UK, the European Science Foundation for EuMyoNet, Association Francaise Contre Les Myopathies, the Medical Research Council, and the Manchester Academic Health Science Centre. No conflicts of interest were declared.

SOURCE: Oldroyd A et al. Rheumatology. 2018 Dec 7. doi: 10.1093/rheumatology/key357.

The increased risk of cancer associated with anti-TIF1-Ab-positive dermatomyositis is limited almost exclusively to 3 years on either side of the onset of dermatomyositis, new research suggests.

Idiopathic inflammatory myopathy have been associated with malignancy, in particular dermatomyositis (DM) and the DM-specific antitranscriptional intermediary factor 1 antibody (anti-TIF1-Ab).

Around one-fifth of the 236 patients diagnosed with DM in the current study, published online Dec. 7 in Rheumatology, were anti-TIF1-Ab positive, and these patients had a more than threefold higher risk of developing cancer comapared with patients who were anti-TIF1-Ab negative (hazard ratio = 3.4, 95% confidence interval, 2.2-5.4; P less than .01).

Overall, 38% of patients in the anti-TIF1-Ab-positive group developed cancer during the 10-year follow-up, compared with 15% of patients with anti-TIF1-Ab-negative DM.

However, all the cancers in the anti-TIF1-Ab-positive group occurred within the 3 years before the onset of DM or within 2.5 years after onset. No anti-TIF1-Ab-positive patients developed cancers after this time, but some patients in the anti-TIF1-Ab-negative group did.

“This finding is not likely to be due to a disparity in follow-up time between anti-TIF1-Ab-positive and -negative cases, as the median follow-up times were similar for both groups: 10 years and 12 years, respectively,” wrote Alexander Oldroyd, MBChB, a clinical research fellow in the Centre for Musculoskeletal Research at the University of Manchester (England), and his coauthors. “Further, this finding is unlikely to be due to differences in cancer detection methods, as both cohorts’ cancer diagnoses were identified through HSCIC [U.K. Health and Social Care Information Centre] data, ensuring capture of all incident cancers during the follow-up period.”

Anti-TIF1-Ab-positive patients were more likely to develop cancer if they were older. None of the 15 anti-TIF1-Ab-positive patients who were aged under 39 when they developed DM went on to develop cancer. But cancer developed in around half of the anti-TIF1-Ab-positive patients who were aged 39 years or older when their DM began.


The anti-TIF1 antibody is commonly found in juvenile DM, but previous research has not found an association with an increased risk of cancer in this younger patient population.

“Our findings add strength to the hypothesis that there exists a subset of young adult anti-TIF1-Ab-positive cases who do not have a discernible increased risk of cancer, similar to that observed in TIF1-Ab-positive juvenile DM,” the authors wrote. They suggested that given the increased risk of malignancy in older patients who were anti-TIF1-Ab positive, this group should be subject to more detailed cancer screening.

Breast cancer was the most common malignancy among both anti-TIF1-Ab-positive and anti-TIF1-Ab-negative patients (33% and 25%, respectively). However, ovarian cancer was significantly more common among the anti-TIF1-Ab-positive patients than among the anti-TIF1-Ab-negative patients (19% vs. 2%; P less than .05); four of the five ovarian cancers in the entire cohort occurred in the anti-TIF1-Ab-positive group.

The authors noted that this confirmed the finding of a number of previous studies suggesting an increased risk of ovarian cancer with DM.

“However, this is the first large study to identify that ovarian cancer is overrepresented in anti-TIF1-Ab-positive individuals, suggesting that the true association between DM and ovarian cancer may be through possession of anti-TIF1-Abs,” they noted.

The authors wrote that they had aimed to inform cancer screening strategies among patients with DM.

“It may be that a focus on screening for cancer within the first 3 years after DM onset and particularly screening for ovarian cancer in anti-TIF1-Ab-positive female patients may be required,” they wrote. “Our findings also strengthen the hypothesis that inflammatory myopathies represent a paraneoplastic reaction initiated by attempted immune-mediated clearance of a cancer.”

The study was supported by Arthritis Research UK, Myositis UK, the European Science Foundation for EuMyoNet, Association Francaise Contre Les Myopathies, the Medical Research Council, and the Manchester Academic Health Science Centre. No conflicts of interest were declared.

SOURCE: Oldroyd A et al. Rheumatology. 2018 Dec 7. doi: 10.1093/rheumatology/key357.

The increased risk of cancer associated with anti-TIF1-Ab-positive dermatomyositis is limited almost exclusively to 3 years on either side of the onset of dermatomyositis, new research suggests.

Idiopathic inflammatory myopathy have been associated with malignancy, in particular dermatomyositis (DM) and the DM-specific antitranscriptional intermediary factor 1 antibody (anti-TIF1-Ab).

Around one-fifth of the 236 patients diagnosed with DM in the current study, published online Dec. 7 in Rheumatology, were anti-TIF1-Ab positive, and these patients had a more than threefold higher risk of developing cancer comapared with patients who were anti-TIF1-Ab negative (hazard ratio = 3.4, 95% confidence interval, 2.2-5.4; P less than .01).

Overall, 38% of patients in the anti-TIF1-Ab-positive group developed cancer during the 10-year follow-up, compared with 15% of patients with anti-TIF1-Ab-negative DM.

However, all the cancers in the anti-TIF1-Ab-positive group occurred within the 3 years before the onset of DM or within 2.5 years after onset. No anti-TIF1-Ab-positive patients developed cancers after this time, but some patients in the anti-TIF1-Ab-negative group did.

“This finding is not likely to be due to a disparity in follow-up time between anti-TIF1-Ab-positive and -negative cases, as the median follow-up times were similar for both groups: 10 years and 12 years, respectively,” wrote Alexander Oldroyd, MBChB, a clinical research fellow in the Centre for Musculoskeletal Research at the University of Manchester (England), and his coauthors. “Further, this finding is unlikely to be due to differences in cancer detection methods, as both cohorts’ cancer diagnoses were identified through HSCIC [U.K. Health and Social Care Information Centre] data, ensuring capture of all incident cancers during the follow-up period.”

Anti-TIF1-Ab-positive patients were more likely to develop cancer if they were older. None of the 15 anti-TIF1-Ab-positive patients who were aged under 39 when they developed DM went on to develop cancer. But cancer developed in around half of the anti-TIF1-Ab-positive patients who were aged 39 years or older when their DM began.


The anti-TIF1 antibody is commonly found in juvenile DM, but previous research has not found an association with an increased risk of cancer in this younger patient population.

“Our findings add strength to the hypothesis that there exists a subset of young adult anti-TIF1-Ab-positive cases who do not have a discernible increased risk of cancer, similar to that observed in TIF1-Ab-positive juvenile DM,” the authors wrote. They suggested that given the increased risk of malignancy in older patients who were anti-TIF1-Ab positive, this group should be subject to more detailed cancer screening.

Breast cancer was the most common malignancy among both anti-TIF1-Ab-positive and anti-TIF1-Ab-negative patients (33% and 25%, respectively). However, ovarian cancer was significantly more common among the anti-TIF1-Ab-positive patients than among the anti-TIF1-Ab-negative patients (19% vs. 2%; P less than .05); four of the five ovarian cancers in the entire cohort occurred in the anti-TIF1-Ab-positive group.

The authors noted that this confirmed the finding of a number of previous studies suggesting an increased risk of ovarian cancer with DM.

“However, this is the first large study to identify that ovarian cancer is overrepresented in anti-TIF1-Ab-positive individuals, suggesting that the true association between DM and ovarian cancer may be through possession of anti-TIF1-Abs,” they noted.

The authors wrote that they had aimed to inform cancer screening strategies among patients with DM.

“It may be that a focus on screening for cancer within the first 3 years after DM onset and particularly screening for ovarian cancer in anti-TIF1-Ab-positive female patients may be required,” they wrote. “Our findings also strengthen the hypothesis that inflammatory myopathies represent a paraneoplastic reaction initiated by attempted immune-mediated clearance of a cancer.”

The study was supported by Arthritis Research UK, Myositis UK, the European Science Foundation for EuMyoNet, Association Francaise Contre Les Myopathies, the Medical Research Council, and the Manchester Academic Health Science Centre. No conflicts of interest were declared.

SOURCE: Oldroyd A et al. Rheumatology. 2018 Dec 7. doi: 10.1093/rheumatology/key357.

A significant number of patients who receive only a placebo in a clinical trial of cancer immunotherapy still experience grade three or grade four adverse events, research suggests.

Writing in JAMA Network Open, researchers reported the outcomes of a systematic review and meta-analysis of 10 randomized, double-blind, placebo-controlled, phase 3 trials of targeted therapy or immunotherapy drugs for cancer, in which patients in the placebo group were treated only with placebo and no other anticancer drugs.

Among the 4,873 patients who were randomized to placebo, a mean of 85.1% experienced some sort of placebo adverse event. The overall incidence of grade 3-4 placebo adverse events was 18% but was as high as 25% in two trials – one in renal cell carcinoma and one in melanoma – and as low as 11% in one trial.

Hypertension was the most frequent grade 3-4 adverse event among patients on placebo, experienced by a mean of 2.8% of patients, followed by fatigue (1%) and diarrhea (0.8%).

Neither route of administration nor cancer type made a significant difference in terms of the rate of placebo adverse events. No deaths attributed to the placebo were reported, but the mean rate of discontinuation due to placebo adverse events was 3.9%, and was higher than 5% for four trials.

The median duration of placebo administration ranged from 10 to 15 months for all but one study, and the authors noted that the longer the placebo exposure, the higher the proportion of grade 3-4 adverse events.

The investigators – Matías Rodrigo Chacón, MD, and his colleagues in the research department at the Argentine Association of Clinical Oncology – said that studies with a lower incidence of grade 3-4 adverse events in the treatment arm also had a lower incidence of grade 3-4 placebo adverse events, while the higher incidences of placebo adverse events were seen in studies that also had a higher incidence of treatment-related adverse events.

They suggested that “contextual factors,” such as the information given during the informed consent process, could contribute to negative expectations of adverse events.

“To illustrate this point, in an RCT [randomized controlled trial] of aspirin as a treatment for unstable angina, a higher incidence of gastrointestinal irritation was reported in centers that specified its potential occurrence in the informed consent compared with research units that did not include that risk,” they wrote.

They also suggested that patients may experience anxiety associated with the uncertainty about whether they had received active treatment or placebo, and this could also affect their distress levels.

No conflicts of interest were declared.

SOURCE: Chacón M et al. JAMA Network Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5617.

A significant number of patients who receive only a placebo in a clinical trial of cancer immunotherapy still experience grade three or grade four adverse events, research suggests.

Writing in JAMA Network Open, researchers reported the outcomes of a systematic review and meta-analysis of 10 randomized, double-blind, placebo-controlled, phase 3 trials of targeted therapy or immunotherapy drugs for cancer, in which patients in the placebo group were treated only with placebo and no other anticancer drugs.

Among the 4,873 patients who were randomized to placebo, a mean of 85.1% experienced some sort of placebo adverse event. The overall incidence of grade 3-4 placebo adverse events was 18% but was as high as 25% in two trials – one in renal cell carcinoma and one in melanoma – and as low as 11% in one trial.

Hypertension was the most frequent grade 3-4 adverse event among patients on placebo, experienced by a mean of 2.8% of patients, followed by fatigue (1%) and diarrhea (0.8%).

Neither route of administration nor cancer type made a significant difference in terms of the rate of placebo adverse events. No deaths attributed to the placebo were reported, but the mean rate of discontinuation due to placebo adverse events was 3.9%, and was higher than 5% for four trials.

The median duration of placebo administration ranged from 10 to 15 months for all but one study, and the authors noted that the longer the placebo exposure, the higher the proportion of grade 3-4 adverse events.

The investigators – Matías Rodrigo Chacón, MD, and his colleagues in the research department at the Argentine Association of Clinical Oncology – said that studies with a lower incidence of grade 3-4 adverse events in the treatment arm also had a lower incidence of grade 3-4 placebo adverse events, while the higher incidences of placebo adverse events were seen in studies that also had a higher incidence of treatment-related adverse events.

They suggested that “contextual factors,” such as the information given during the informed consent process, could contribute to negative expectations of adverse events.

“To illustrate this point, in an RCT [randomized controlled trial] of aspirin as a treatment for unstable angina, a higher incidence of gastrointestinal irritation was reported in centers that specified its potential occurrence in the informed consent compared with research units that did not include that risk,” they wrote.

They also suggested that patients may experience anxiety associated with the uncertainty about whether they had received active treatment or placebo, and this could also affect their distress levels.

No conflicts of interest were declared.

SOURCE: Chacón M et al. JAMA Network Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5617.

A significant number of patients who receive only a placebo in a clinical trial of cancer immunotherapy still experience grade three or grade four adverse events, research suggests.

Writing in JAMA Network Open, researchers reported the outcomes of a systematic review and meta-analysis of 10 randomized, double-blind, placebo-controlled, phase 3 trials of targeted therapy or immunotherapy drugs for cancer, in which patients in the placebo group were treated only with placebo and no other anticancer drugs.

Among the 4,873 patients who were randomized to placebo, a mean of 85.1% experienced some sort of placebo adverse event. The overall incidence of grade 3-4 placebo adverse events was 18% but was as high as 25% in two trials – one in renal cell carcinoma and one in melanoma – and as low as 11% in one trial.

Hypertension was the most frequent grade 3-4 adverse event among patients on placebo, experienced by a mean of 2.8% of patients, followed by fatigue (1%) and diarrhea (0.8%).

Neither route of administration nor cancer type made a significant difference in terms of the rate of placebo adverse events. No deaths attributed to the placebo were reported, but the mean rate of discontinuation due to placebo adverse events was 3.9%, and was higher than 5% for four trials.

The median duration of placebo administration ranged from 10 to 15 months for all but one study, and the authors noted that the longer the placebo exposure, the higher the proportion of grade 3-4 adverse events.

The investigators – Matías Rodrigo Chacón, MD, and his colleagues in the research department at the Argentine Association of Clinical Oncology – said that studies with a lower incidence of grade 3-4 adverse events in the treatment arm also had a lower incidence of grade 3-4 placebo adverse events, while the higher incidences of placebo adverse events were seen in studies that also had a higher incidence of treatment-related adverse events.

They suggested that “contextual factors,” such as the information given during the informed consent process, could contribute to negative expectations of adverse events.

“To illustrate this point, in an RCT [randomized controlled trial] of aspirin as a treatment for unstable angina, a higher incidence of gastrointestinal irritation was reported in centers that specified its potential occurrence in the informed consent compared with research units that did not include that risk,” they wrote.

They also suggested that patients may experience anxiety associated with the uncertainty about whether they had received active treatment or placebo, and this could also affect their distress levels.

No conflicts of interest were declared.

SOURCE: Chacón M et al. JAMA Network Open. 2018 Dec 7. doi: 10.1001/jamanetworkopen.2018.5617.