More than two-thirds of physicians have personally experienced some level of burnout, according to a new survey by real-time market insights technology firm InCrowd.

The overall prevalence of personal burnout experience was 68% among respondents, and another 28% said that they had not felt burned out but knew other physicians who had, InCrowd reported Aug. 6.

Specialty appeared to play a part given that 79% of primary care physicians reported experiencing burnout versus 57% of specialists. In response to an open-ended question about ability to manage burnout, the most common answer (23%) was that specialty played a large role, with “no role/all specialties affected equally” next at 13%. Equal proportions of respondents, however, said that specialists (24%) and primary care physicians (24%) were the group most affected, InCrowd said.

There was also a disconnect regarding age. When answering another open-ended question about the effects of age, 23% of those surveyed said that older physicians are more affected, compared with 9% who put the greater burden on younger physicians. The self-reporting of burnout, however, showed that younger physicians were much more likely to experience its effects than their older counterparts: 70% of those aged 30-39 years and 74% of those 40-49 versus 22% of those aged 70-80, InCrowd reported.

InCrowd noted that its results fall within the range of other recent surveys involving burnout in physicians that have shown levels that were lower, at 44% (MedScape, 2019) or 43.9% (American Academy of Family Physicians, 2019), and those that were higher, at 77.8% (The Physicians Foundation/Merritt Hawkins, 2018).

“The alarming persistence of physician burnout over the years and across multiple studies unfortunately demonstrates that we have not yet turned the tide on this problematic issue,” Diane Hayes, PhD, president of InCrowd, said in a statement accompanying the survey results. “Since we last looked at this in 2016, there really haven’t been any notable improvements. The healthcare industry would benefit from refining and expanding current initiatives to assure adequate staffing levels needed to deliver the quality care patients deserve.”

The survey was conducted June 6-7, 2019, and involved responses from 612 physicians (51% primary care providers, 49% specialists).

[email protected]

More than two-thirds of physicians have personally experienced some level of burnout, according to a new survey by real-time market insights technology firm InCrowd.

The overall prevalence of personal burnout experience was 68% among respondents, and another 28% said that they had not felt burned out but knew other physicians who had, InCrowd reported Aug. 6.

Specialty appeared to play a part given that 79% of primary care physicians reported experiencing burnout versus 57% of specialists. In response to an open-ended question about ability to manage burnout, the most common answer (23%) was that specialty played a large role, with “no role/all specialties affected equally” next at 13%. Equal proportions of respondents, however, said that specialists (24%) and primary care physicians (24%) were the group most affected, InCrowd said.

There was also a disconnect regarding age. When answering another open-ended question about the effects of age, 23% of those surveyed said that older physicians are more affected, compared with 9% who put the greater burden on younger physicians. The self-reporting of burnout, however, showed that younger physicians were much more likely to experience its effects than their older counterparts: 70% of those aged 30-39 years and 74% of those 40-49 versus 22% of those aged 70-80, InCrowd reported.

InCrowd noted that its results fall within the range of other recent surveys involving burnout in physicians that have shown levels that were lower, at 44% (MedScape, 2019) or 43.9% (American Academy of Family Physicians, 2019), and those that were higher, at 77.8% (The Physicians Foundation/Merritt Hawkins, 2018).

“The alarming persistence of physician burnout over the years and across multiple studies unfortunately demonstrates that we have not yet turned the tide on this problematic issue,” Diane Hayes, PhD, president of InCrowd, said in a statement accompanying the survey results. “Since we last looked at this in 2016, there really haven’t been any notable improvements. The healthcare industry would benefit from refining and expanding current initiatives to assure adequate staffing levels needed to deliver the quality care patients deserve.”

The survey was conducted June 6-7, 2019, and involved responses from 612 physicians (51% primary care providers, 49% specialists).

[email protected]

More than two-thirds of physicians have personally experienced some level of burnout, according to a new survey by real-time market insights technology firm InCrowd.

The overall prevalence of personal burnout experience was 68% among respondents, and another 28% said that they had not felt burned out but knew other physicians who had, InCrowd reported Aug. 6.

Specialty appeared to play a part given that 79% of primary care physicians reported experiencing burnout versus 57% of specialists. In response to an open-ended question about ability to manage burnout, the most common answer (23%) was that specialty played a large role, with “no role/all specialties affected equally” next at 13%. Equal proportions of respondents, however, said that specialists (24%) and primary care physicians (24%) were the group most affected, InCrowd said.

There was also a disconnect regarding age. When answering another open-ended question about the effects of age, 23% of those surveyed said that older physicians are more affected, compared with 9% who put the greater burden on younger physicians. The self-reporting of burnout, however, showed that younger physicians were much more likely to experience its effects than their older counterparts: 70% of those aged 30-39 years and 74% of those 40-49 versus 22% of those aged 70-80, InCrowd reported.

InCrowd noted that its results fall within the range of other recent surveys involving burnout in physicians that have shown levels that were lower, at 44% (MedScape, 2019) or 43.9% (American Academy of Family Physicians, 2019), and those that were higher, at 77.8% (The Physicians Foundation/Merritt Hawkins, 2018).

“The alarming persistence of physician burnout over the years and across multiple studies unfortunately demonstrates that we have not yet turned the tide on this problematic issue,” Diane Hayes, PhD, president of InCrowd, said in a statement accompanying the survey results. “Since we last looked at this in 2016, there really haven’t been any notable improvements. The healthcare industry would benefit from refining and expanding current initiatives to assure adequate staffing levels needed to deliver the quality care patients deserve.”

The survey was conducted June 6-7, 2019, and involved responses from 612 physicians (51% primary care providers, 49% specialists).

[email protected]

Even when a standard HIV RNA test is negative, some patients may still have viral DNA in their cerebrospinal fluid (CSF)—and that could be a predictor of later memory and concentration problems, say researchers who conducted a National Institute of Health (NIH)-funded study of patients on long-term antiretroviral therapy (ART).

The 69 participants, enrolled in the AIDS Clinical Trials Group HIV Reservoirs Cohort Study, had infections controlled with ART for a median of 9 years. Calling it a “striking observation,” the researchers found nearly half of the patients had viral DNA in CSF cells, although the standard viral load tests of the cell-free CSF fluid were positive in only 4% of the patients.

Of the 30 patients with persistent HIV, 9 (30%) experienced neurocognitive difficulties in a 7-domain neuropsychological test battery. Among 35 participants with no detectable HIV DNA in CSF, 4 (11%) were clinically impaired.

The low rates of detectable HIV RNA in the cell-free CSF fraction and within CSF cell pellets suggest low levels of HIV transcription within cells and infrequent release into the extracellular space during systemically suppressive ART, the researchers say.

The brain is one of the first targets of the virus, and CNS manifestations are common. Neurocognitive impairment in HIV-positive patients is probably related to multiple factors, including HIV infection, age, neuroinflammation, and comorbid conditions, including substance abuse, the researchers say. There also may be a “legacy effect,” in which processes associated with long-term exposure to HIV before ART leads to irreversible neurologic injury and more extensive infection of CSF cells. Lack of an association with inflammatory biomarkers in this study suggested that current inflammation does not lead to present neurocognitive dysfunction, the researchers say, but does not rule out prior inflammation as the underlying cause of neuronal injury.

Still, given that brain tissue in living individuals is “inaccessible” (as the researchers put it), CSF offers a window into neuropathogenesis of HIV. Studies have found a range between 15% and 55% of participants develop an HIV-associated neurocognitive disorder (HAND). The new findings may support a role of persistent HIV-infected cells, but the researchers emphasize that the association does not confirm that HIV DNA causes HAND. However, they add, persistent HIV in “sanctuary sites” despite ART presents a barrier to curing the infection. Their study, they say, indicates that examination of CSF cells is important in assessing residual HIV in compartments during ART.

Even when a standard HIV RNA test is negative, some patients may still have viral DNA in their cerebrospinal fluid (CSF)—and that could be a predictor of later memory and concentration problems, say researchers who conducted a National Institute of Health (NIH)-funded study of patients on long-term antiretroviral therapy (ART).

The 69 participants, enrolled in the AIDS Clinical Trials Group HIV Reservoirs Cohort Study, had infections controlled with ART for a median of 9 years. Calling it a “striking observation,” the researchers found nearly half of the patients had viral DNA in CSF cells, although the standard viral load tests of the cell-free CSF fluid were positive in only 4% of the patients.

Of the 30 patients with persistent HIV, 9 (30%) experienced neurocognitive difficulties in a 7-domain neuropsychological test battery. Among 35 participants with no detectable HIV DNA in CSF, 4 (11%) were clinically impaired.

The low rates of detectable HIV RNA in the cell-free CSF fraction and within CSF cell pellets suggest low levels of HIV transcription within cells and infrequent release into the extracellular space during systemically suppressive ART, the researchers say.

The brain is one of the first targets of the virus, and CNS manifestations are common. Neurocognitive impairment in HIV-positive patients is probably related to multiple factors, including HIV infection, age, neuroinflammation, and comorbid conditions, including substance abuse, the researchers say. There also may be a “legacy effect,” in which processes associated with long-term exposure to HIV before ART leads to irreversible neurologic injury and more extensive infection of CSF cells. Lack of an association with inflammatory biomarkers in this study suggested that current inflammation does not lead to present neurocognitive dysfunction, the researchers say, but does not rule out prior inflammation as the underlying cause of neuronal injury.

Still, given that brain tissue in living individuals is “inaccessible” (as the researchers put it), CSF offers a window into neuropathogenesis of HIV. Studies have found a range between 15% and 55% of participants develop an HIV-associated neurocognitive disorder (HAND). The new findings may support a role of persistent HIV-infected cells, but the researchers emphasize that the association does not confirm that HIV DNA causes HAND. However, they add, persistent HIV in “sanctuary sites” despite ART presents a barrier to curing the infection. Their study, they say, indicates that examination of CSF cells is important in assessing residual HIV in compartments during ART.

Even when a standard HIV RNA test is negative, some patients may still have viral DNA in their cerebrospinal fluid (CSF)—and that could be a predictor of later memory and concentration problems, say researchers who conducted a National Institute of Health (NIH)-funded study of patients on long-term antiretroviral therapy (ART).

The 69 participants, enrolled in the AIDS Clinical Trials Group HIV Reservoirs Cohort Study, had infections controlled with ART for a median of 9 years. Calling it a “striking observation,” the researchers found nearly half of the patients had viral DNA in CSF cells, although the standard viral load tests of the cell-free CSF fluid were positive in only 4% of the patients.

Of the 30 patients with persistent HIV, 9 (30%) experienced neurocognitive difficulties in a 7-domain neuropsychological test battery. Among 35 participants with no detectable HIV DNA in CSF, 4 (11%) were clinically impaired.

The low rates of detectable HIV RNA in the cell-free CSF fraction and within CSF cell pellets suggest low levels of HIV transcription within cells and infrequent release into the extracellular space during systemically suppressive ART, the researchers say.

The brain is one of the first targets of the virus, and CNS manifestations are common. Neurocognitive impairment in HIV-positive patients is probably related to multiple factors, including HIV infection, age, neuroinflammation, and comorbid conditions, including substance abuse, the researchers say. There also may be a “legacy effect,” in which processes associated with long-term exposure to HIV before ART leads to irreversible neurologic injury and more extensive infection of CSF cells. Lack of an association with inflammatory biomarkers in this study suggested that current inflammation does not lead to present neurocognitive dysfunction, the researchers say, but does not rule out prior inflammation as the underlying cause of neuronal injury.

Still, given that brain tissue in living individuals is “inaccessible” (as the researchers put it), CSF offers a window into neuropathogenesis of HIV. Studies have found a range between 15% and 55% of participants develop an HIV-associated neurocognitive disorder (HAND). The new findings may support a role of persistent HIV-infected cells, but the researchers emphasize that the association does not confirm that HIV DNA causes HAND. However, they add, persistent HIV in “sanctuary sites” despite ART presents a barrier to curing the infection. Their study, they say, indicates that examination of CSF cells is important in assessing residual HIV in compartments during ART.

About half of papers in a sample of psychiatry and psychology journals have evidence of “spin” in the abstract, according to an analysis published in BMJ Evidence-Based Medicine.

Samuel Jellison, a third-year medical student at Oklahoma State University, Tulsa, and coauthors wrote that the results of randomized, controlled trials should be reported objectively because of their importance for psychiatry clinical practice. However, given that researchers were allowed more latitude in the abstract of a paper to highlight certain results or conclusions, the abstract might not accurately represent the findings of the study.

To evaluate this, the authors investigated the use of spin in abstracts, which they defined as “‘use of specific reporting strategies, from whatever motive, to highlight that the experimental treatment is beneficial, despite a statistically nonsignificant difference for the primary outcome, or to distract the reader from statistically nonsignificant results.”

They analyzed 116 randomized, controlled trials of interventions where there was a nonsignificant primary endpoint and found that 56% of those contained spin in the abstract. Spin was evident in 2% of publication titles, 21% of abstract results sections, and 49.1% of abstract conclusions sections. In 15% of trials, spin was found both in the results and the conclusions.

Spin was more common in trials of pharmacologic treatments, compared with nonpharmacologic treatments. However, the study did not find a higher level of spin in industry-funded studies, and in fact, spin was more common in publicly funded research.

The most common form of spin was focusing on a statistically significant primary or secondary endpoint while omitting one or more nonsignificant primary endpoints. Other spin strategies included claiming noninferiority or equivalence for a statistically nonsignificant endpoint; using phrases such as “trend towards significance”; or focusing on statistically significant subgroup analyses, such as per protocol instead of intention to treat.

The authors observed that most physicians only read article abstracts, and up to one-quarter of editorial decisions are based on the abstract alone.

“Adding spin to the abstract of an article may mislead physicians who are attempting to draw conclusions about a treatment for patients,” they wrote, while calling for efforts to discourage spin in abstracts.

In an interview, Paul S. Nestadt, MD, said the findings were not surprising.

“The proportion [56%] of psychiatry and psychology abstracts which Jellison et al. found to contain spin is similar to that found in broader studies of all biomedical literature in previous reviews,” said Dr. Nestadt, assistant professor in the department of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. “It is disheartening that attempts to mislead have become ‘standard of care’ in medical literature, but it is a predictable outcome of increasing competition for shrinking grant funding, awarded partly on the basis of publication history in leading journals that maintain clear publication biases toward positive results.

“As the authors point out, we all share a responsibility to call out spin when we see it, whether in our role as reviewer, editor, coauthor, or as the writers themselves.”

Neither Mr. Jellison nor his coauthors reported funding or conflicts of interest.

SOURCE: Jellison S et al. BMJ Evid Based Med. 2019 Aug 5. doi: 10.1136/bmjebm-2019-111176.

About half of papers in a sample of psychiatry and psychology journals have evidence of “spin” in the abstract, according to an analysis published in BMJ Evidence-Based Medicine.

Samuel Jellison, a third-year medical student at Oklahoma State University, Tulsa, and coauthors wrote that the results of randomized, controlled trials should be reported objectively because of their importance for psychiatry clinical practice. However, given that researchers were allowed more latitude in the abstract of a paper to highlight certain results or conclusions, the abstract might not accurately represent the findings of the study.

To evaluate this, the authors investigated the use of spin in abstracts, which they defined as “‘use of specific reporting strategies, from whatever motive, to highlight that the experimental treatment is beneficial, despite a statistically nonsignificant difference for the primary outcome, or to distract the reader from statistically nonsignificant results.”

They analyzed 116 randomized, controlled trials of interventions where there was a nonsignificant primary endpoint and found that 56% of those contained spin in the abstract. Spin was evident in 2% of publication titles, 21% of abstract results sections, and 49.1% of abstract conclusions sections. In 15% of trials, spin was found both in the results and the conclusions.

Spin was more common in trials of pharmacologic treatments, compared with nonpharmacologic treatments. However, the study did not find a higher level of spin in industry-funded studies, and in fact, spin was more common in publicly funded research.

The most common form of spin was focusing on a statistically significant primary or secondary endpoint while omitting one or more nonsignificant primary endpoints. Other spin strategies included claiming noninferiority or equivalence for a statistically nonsignificant endpoint; using phrases such as “trend towards significance”; or focusing on statistically significant subgroup analyses, such as per protocol instead of intention to treat.

The authors observed that most physicians only read article abstracts, and up to one-quarter of editorial decisions are based on the abstract alone.

“Adding spin to the abstract of an article may mislead physicians who are attempting to draw conclusions about a treatment for patients,” they wrote, while calling for efforts to discourage spin in abstracts.

In an interview, Paul S. Nestadt, MD, said the findings were not surprising.

“The proportion [56%] of psychiatry and psychology abstracts which Jellison et al. found to contain spin is similar to that found in broader studies of all biomedical literature in previous reviews,” said Dr. Nestadt, assistant professor in the department of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. “It is disheartening that attempts to mislead have become ‘standard of care’ in medical literature, but it is a predictable outcome of increasing competition for shrinking grant funding, awarded partly on the basis of publication history in leading journals that maintain clear publication biases toward positive results.

“As the authors point out, we all share a responsibility to call out spin when we see it, whether in our role as reviewer, editor, coauthor, or as the writers themselves.”

Neither Mr. Jellison nor his coauthors reported funding or conflicts of interest.

SOURCE: Jellison S et al. BMJ Evid Based Med. 2019 Aug 5. doi: 10.1136/bmjebm-2019-111176.

About half of papers in a sample of psychiatry and psychology journals have evidence of “spin” in the abstract, according to an analysis published in BMJ Evidence-Based Medicine.

Samuel Jellison, a third-year medical student at Oklahoma State University, Tulsa, and coauthors wrote that the results of randomized, controlled trials should be reported objectively because of their importance for psychiatry clinical practice. However, given that researchers were allowed more latitude in the abstract of a paper to highlight certain results or conclusions, the abstract might not accurately represent the findings of the study.

To evaluate this, the authors investigated the use of spin in abstracts, which they defined as “‘use of specific reporting strategies, from whatever motive, to highlight that the experimental treatment is beneficial, despite a statistically nonsignificant difference for the primary outcome, or to distract the reader from statistically nonsignificant results.”

They analyzed 116 randomized, controlled trials of interventions where there was a nonsignificant primary endpoint and found that 56% of those contained spin in the abstract. Spin was evident in 2% of publication titles, 21% of abstract results sections, and 49.1% of abstract conclusions sections. In 15% of trials, spin was found both in the results and the conclusions.

Spin was more common in trials of pharmacologic treatments, compared with nonpharmacologic treatments. However, the study did not find a higher level of spin in industry-funded studies, and in fact, spin was more common in publicly funded research.

The most common form of spin was focusing on a statistically significant primary or secondary endpoint while omitting one or more nonsignificant primary endpoints. Other spin strategies included claiming noninferiority or equivalence for a statistically nonsignificant endpoint; using phrases such as “trend towards significance”; or focusing on statistically significant subgroup analyses, such as per protocol instead of intention to treat.

The authors observed that most physicians only read article abstracts, and up to one-quarter of editorial decisions are based on the abstract alone.

“Adding spin to the abstract of an article may mislead physicians who are attempting to draw conclusions about a treatment for patients,” they wrote, while calling for efforts to discourage spin in abstracts.

In an interview, Paul S. Nestadt, MD, said the findings were not surprising.

“The proportion [56%] of psychiatry and psychology abstracts which Jellison et al. found to contain spin is similar to that found in broader studies of all biomedical literature in previous reviews,” said Dr. Nestadt, assistant professor in the department of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore. “It is disheartening that attempts to mislead have become ‘standard of care’ in medical literature, but it is a predictable outcome of increasing competition for shrinking grant funding, awarded partly on the basis of publication history in leading journals that maintain clear publication biases toward positive results.

“As the authors point out, we all share a responsibility to call out spin when we see it, whether in our role as reviewer, editor, coauthor, or as the writers themselves.”

Neither Mr. Jellison nor his coauthors reported funding or conflicts of interest.

SOURCE: Jellison S et al. BMJ Evid Based Med. 2019 Aug 5. doi: 10.1136/bmjebm-2019-111176.

The need for universal screening for Lynch syndrome in elderly patients with newly diagnosed colorectal cancer (CRC) has been questioned, according to results from a retrospective cohort study.

In addition, discontinuing reflex CRC screening for Lynch syndrome in patients over age 80 years could be feasible because of very low efficiency.

“The universal strategy advocates screening all patients with newly diagnosed CRC for Lynch syndrome and has been shown to be the most sensitive method,” wrote Dan Li, MD, of Kaiser Permanente Northern California, Santa Clara, and colleagues. The findings were published in Annals of Internal Medicine.

The researchers studied 3,891 patients with newly diagnosed CRC who were screened for Lynch syndrome from 2011 to 2016. Data were collected from a population-based screening program at Kaiser Permanente Northern California.

“The system provides comprehensive medical care for more than 4 million members across 21 medical centers covering urban, suburban, and semirural areas,” Dr. Li and his colleagues wrote.

To compare universal and age-restricted screening, the team obtained surgical samples of all newly diagnosed CRC tumors and tested them for reflex mismatch repair protein expression using immunohistochemistry.

Subsequently, the age-restricted screening groups were divided into several age categories, ranging from age 50 to 85 years.

The diagnostic yield, defined as the “percentage of patients with pathogenic reflex mismatch repair gene variants among all patients with CRC screened with immunohistochemistry,” was measured and compared with the universal screening technique.

“We calculated the number of patients with CRC who needed to be screened in each age group to identify one case of Lynch syndrome by dividing the number of patients screened in each age group by the number of Lynch syndrome cases diagnosed in that group,” they explained.

After analysis, the researchers detected a total of 63 cases of Lynch syndrome (diagnostic yield, 1.62%) with universal screening, among which 5 (7.9%) were over age 70 years and 1 (1.6%) was over age 80 years.

When patients with CRC who were universally screened were used as the denominator, 58 cases (diagnostic yield, 1.49%) were detected in those with CRC diagnosed at or prior to age 70 years.

In addition, in patients diagnosed at or before age 75 and 80 years, 60 and 62 cases of Lynch syndrome (diagnostic yield, 1.54% and 1.59%) were detected, respectively.

“The incremental diagnostic yield decreased substantially after age 70 to 75 years,” they wrote.

With these findings, Dr. Li and his colleagues suggested that cessation of screening for Lynch syndrome post age 80 years may be acceptable, especially in resource-limited environments.

“Using age as the primary criterion is a simple method of selecting patients for Lynch syndrome screening in clinical practice,” they added.

In accordance with previous studies, a major reduction in Lynch syndrome incidence has been noted among elderly populations.

There remains a need for additional studies exploring the effects of diagnosing Lynch syndrome in elderly patients on family members.

The researchers acknowledged a key limitation of the study was that patients who did not finish germline analysis but were eligible for it were excluded from certain measurements. To reduce potential bias, the team conducted a sensitivity analysis, and the findings were negligible with respect to main results.

“Given the geographic variation in the reported prevalence of Lynch syndrome, the diagnostic efficiency of Lynch syndrome screening among elderly populations should be further investigated in other populations,” they concluded.

The study was funded by Kaiser Permanente Northern California. The authors reported financial affiliations with Bayer, Clinical Genomics, Covidien, Exact Sciences, Motus GI, Quorum, Universal DX, and the National Cancer Institute.

SOURCE: Li D et al. Ann Intern Med. 2019 Jun 11. doi: 10.7326/M18-3316.

The need for universal screening for Lynch syndrome in elderly patients with newly diagnosed colorectal cancer (CRC) has been questioned, according to results from a retrospective cohort study.

In addition, discontinuing reflex CRC screening for Lynch syndrome in patients over age 80 years could be feasible because of very low efficiency.

“The universal strategy advocates screening all patients with newly diagnosed CRC for Lynch syndrome and has been shown to be the most sensitive method,” wrote Dan Li, MD, of Kaiser Permanente Northern California, Santa Clara, and colleagues. The findings were published in Annals of Internal Medicine.

The researchers studied 3,891 patients with newly diagnosed CRC who were screened for Lynch syndrome from 2011 to 2016. Data were collected from a population-based screening program at Kaiser Permanente Northern California.

“The system provides comprehensive medical care for more than 4 million members across 21 medical centers covering urban, suburban, and semirural areas,” Dr. Li and his colleagues wrote.

To compare universal and age-restricted screening, the team obtained surgical samples of all newly diagnosed CRC tumors and tested them for reflex mismatch repair protein expression using immunohistochemistry.

Subsequently, the age-restricted screening groups were divided into several age categories, ranging from age 50 to 85 years.

The diagnostic yield, defined as the “percentage of patients with pathogenic reflex mismatch repair gene variants among all patients with CRC screened with immunohistochemistry,” was measured and compared with the universal screening technique.

“We calculated the number of patients with CRC who needed to be screened in each age group to identify one case of Lynch syndrome by dividing the number of patients screened in each age group by the number of Lynch syndrome cases diagnosed in that group,” they explained.

After analysis, the researchers detected a total of 63 cases of Lynch syndrome (diagnostic yield, 1.62%) with universal screening, among which 5 (7.9%) were over age 70 years and 1 (1.6%) was over age 80 years.

When patients with CRC who were universally screened were used as the denominator, 58 cases (diagnostic yield, 1.49%) were detected in those with CRC diagnosed at or prior to age 70 years.

In addition, in patients diagnosed at or before age 75 and 80 years, 60 and 62 cases of Lynch syndrome (diagnostic yield, 1.54% and 1.59%) were detected, respectively.

“The incremental diagnostic yield decreased substantially after age 70 to 75 years,” they wrote.

With these findings, Dr. Li and his colleagues suggested that cessation of screening for Lynch syndrome post age 80 years may be acceptable, especially in resource-limited environments.

“Using age as the primary criterion is a simple method of selecting patients for Lynch syndrome screening in clinical practice,” they added.

In accordance with previous studies, a major reduction in Lynch syndrome incidence has been noted among elderly populations.

There remains a need for additional studies exploring the effects of diagnosing Lynch syndrome in elderly patients on family members.

The researchers acknowledged a key limitation of the study was that patients who did not finish germline analysis but were eligible for it were excluded from certain measurements. To reduce potential bias, the team conducted a sensitivity analysis, and the findings were negligible with respect to main results.

“Given the geographic variation in the reported prevalence of Lynch syndrome, the diagnostic efficiency of Lynch syndrome screening among elderly populations should be further investigated in other populations,” they concluded.

The study was funded by Kaiser Permanente Northern California. The authors reported financial affiliations with Bayer, Clinical Genomics, Covidien, Exact Sciences, Motus GI, Quorum, Universal DX, and the National Cancer Institute.

SOURCE: Li D et al. Ann Intern Med. 2019 Jun 11. doi: 10.7326/M18-3316.

The need for universal screening for Lynch syndrome in elderly patients with newly diagnosed colorectal cancer (CRC) has been questioned, according to results from a retrospective cohort study.

In addition, discontinuing reflex CRC screening for Lynch syndrome in patients over age 80 years could be feasible because of very low efficiency.

“The universal strategy advocates screening all patients with newly diagnosed CRC for Lynch syndrome and has been shown to be the most sensitive method,” wrote Dan Li, MD, of Kaiser Permanente Northern California, Santa Clara, and colleagues. The findings were published in Annals of Internal Medicine.

The researchers studied 3,891 patients with newly diagnosed CRC who were screened for Lynch syndrome from 2011 to 2016. Data were collected from a population-based screening program at Kaiser Permanente Northern California.

“The system provides comprehensive medical care for more than 4 million members across 21 medical centers covering urban, suburban, and semirural areas,” Dr. Li and his colleagues wrote.

To compare universal and age-restricted screening, the team obtained surgical samples of all newly diagnosed CRC tumors and tested them for reflex mismatch repair protein expression using immunohistochemistry.

Subsequently, the age-restricted screening groups were divided into several age categories, ranging from age 50 to 85 years.

The diagnostic yield, defined as the “percentage of patients with pathogenic reflex mismatch repair gene variants among all patients with CRC screened with immunohistochemistry,” was measured and compared with the universal screening technique.

“We calculated the number of patients with CRC who needed to be screened in each age group to identify one case of Lynch syndrome by dividing the number of patients screened in each age group by the number of Lynch syndrome cases diagnosed in that group,” they explained.

After analysis, the researchers detected a total of 63 cases of Lynch syndrome (diagnostic yield, 1.62%) with universal screening, among which 5 (7.9%) were over age 70 years and 1 (1.6%) was over age 80 years.

When patients with CRC who were universally screened were used as the denominator, 58 cases (diagnostic yield, 1.49%) were detected in those with CRC diagnosed at or prior to age 70 years.

In addition, in patients diagnosed at or before age 75 and 80 years, 60 and 62 cases of Lynch syndrome (diagnostic yield, 1.54% and 1.59%) were detected, respectively.

“The incremental diagnostic yield decreased substantially after age 70 to 75 years,” they wrote.

With these findings, Dr. Li and his colleagues suggested that cessation of screening for Lynch syndrome post age 80 years may be acceptable, especially in resource-limited environments.

“Using age as the primary criterion is a simple method of selecting patients for Lynch syndrome screening in clinical practice,” they added.

In accordance with previous studies, a major reduction in Lynch syndrome incidence has been noted among elderly populations.

There remains a need for additional studies exploring the effects of diagnosing Lynch syndrome in elderly patients on family members.

The researchers acknowledged a key limitation of the study was that patients who did not finish germline analysis but were eligible for it were excluded from certain measurements. To reduce potential bias, the team conducted a sensitivity analysis, and the findings were negligible with respect to main results.

“Given the geographic variation in the reported prevalence of Lynch syndrome, the diagnostic efficiency of Lynch syndrome screening among elderly populations should be further investigated in other populations,” they concluded.

The study was funded by Kaiser Permanente Northern California. The authors reported financial affiliations with Bayer, Clinical Genomics, Covidien, Exact Sciences, Motus GI, Quorum, Universal DX, and the National Cancer Institute.

SOURCE: Li D et al. Ann Intern Med. 2019 Jun 11. doi: 10.7326/M18-3316.

When it comes to cardiovascular disease (CVD) risk after a breast cancer diagnosis, it’s not so much a matter of the amount of body fat carried but rather where it is located, results of a retrospective cohort study of nearly 3,000 survivors suggest.

“It is well known that higher body mass index (BMI) is associated with CVD mortality in the general population. However, BMI is not always an accurate proxy for individual-level adiposity and does not describe adipose tissue distribution,” note lead investigator Elizabeth M. Cespedes Feliciano, ScD, of Kaiser Permanente Northern California, Oakland, Calif., and coinvestigators.

The investigators studied 2,943 survivors of nonmetastatic breast cancer having a mean age of 56 years who were initially CVD free, using clinically acquired CT scans obtained near diagnosis to measure adiposity in three compartments: visceral, subcutaneous, and intramuscular.

The cohort experienced 328 CVD events (nonfatal stroke, myocardial infarction, heart failure, or CVD death) during a median follow-up of 6 years, the investigators reported in Journal of Clinical Oncology. The 10-year cumulative incidence was 15%.

In analyses that were adjusted for potential confounders and took into account competing risks, survivors’ CVD risk increased significantly with each standard deviation (SD) increase in visceral adiposity (hazard ratio, 1.15; 95% confidence interval, 1.03-1.29) and each SD increase in intramuscular adiposity (HR, 1.21; 95% CI, 1.06-1.37). The association for subcutaneous adiposity was not significant.

Findings were similar across all BMI categories. Of particular note, among survivors having a normal BMI, risk of CVD events increased by 70% with each SD greater visceral adiposity (HR, 1.70; 95% CI, 1.10-2.62).

Risk also rose with BMI exceeding the normal range, but the association became significant only in survivors with a BMI placing them in obesity class II (35 kg/m² or greater) (HR, 1.70; 95% CI, 1.20-2.42).

“Although it has been assumed that excess adiposity increases the risk of CVD after breast cancer, this first-of-its-kind study demonstrates that adipose tissue distribution best identifies patients with breast cancer with higher CVD risk after diagnosis, including those with normal BMI,” Dr. Cespedes Feliciano and coinvestigators note.

“Software is now available that automatically measures body composition from clinically acquired CT scans, facilitating clinical integration,” they note. “Measures of adipose tissue distribution from CT or anthropometry (e.g., waist circumference) may help identify individuals with high CVD risk and tailor prevention efforts to patients’ body composition.”

Dr. Cespedes Feliciano disclosed no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Cespedes Feliciano EM et al. J Clin Oncol. 2019 Aug 1. doi: 10.1200/JCO.19.00286.

When it comes to cardiovascular disease (CVD) risk after a breast cancer diagnosis, it’s not so much a matter of the amount of body fat carried but rather where it is located, results of a retrospective cohort study of nearly 3,000 survivors suggest.

“It is well known that higher body mass index (BMI) is associated with CVD mortality in the general population. However, BMI is not always an accurate proxy for individual-level adiposity and does not describe adipose tissue distribution,” note lead investigator Elizabeth M. Cespedes Feliciano, ScD, of Kaiser Permanente Northern California, Oakland, Calif., and coinvestigators.

The investigators studied 2,943 survivors of nonmetastatic breast cancer having a mean age of 56 years who were initially CVD free, using clinically acquired CT scans obtained near diagnosis to measure adiposity in three compartments: visceral, subcutaneous, and intramuscular.

The cohort experienced 328 CVD events (nonfatal stroke, myocardial infarction, heart failure, or CVD death) during a median follow-up of 6 years, the investigators reported in Journal of Clinical Oncology. The 10-year cumulative incidence was 15%.

In analyses that were adjusted for potential confounders and took into account competing risks, survivors’ CVD risk increased significantly with each standard deviation (SD) increase in visceral adiposity (hazard ratio, 1.15; 95% confidence interval, 1.03-1.29) and each SD increase in intramuscular adiposity (HR, 1.21; 95% CI, 1.06-1.37). The association for subcutaneous adiposity was not significant.

Findings were similar across all BMI categories. Of particular note, among survivors having a normal BMI, risk of CVD events increased by 70% with each SD greater visceral adiposity (HR, 1.70; 95% CI, 1.10-2.62).

Risk also rose with BMI exceeding the normal range, but the association became significant only in survivors with a BMI placing them in obesity class II (35 kg/m² or greater) (HR, 1.70; 95% CI, 1.20-2.42).

“Although it has been assumed that excess adiposity increases the risk of CVD after breast cancer, this first-of-its-kind study demonstrates that adipose tissue distribution best identifies patients with breast cancer with higher CVD risk after diagnosis, including those with normal BMI,” Dr. Cespedes Feliciano and coinvestigators note.

“Software is now available that automatically measures body composition from clinically acquired CT scans, facilitating clinical integration,” they note. “Measures of adipose tissue distribution from CT or anthropometry (e.g., waist circumference) may help identify individuals with high CVD risk and tailor prevention efforts to patients’ body composition.”

Dr. Cespedes Feliciano disclosed no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Cespedes Feliciano EM et al. J Clin Oncol. 2019 Aug 1. doi: 10.1200/JCO.19.00286.

When it comes to cardiovascular disease (CVD) risk after a breast cancer diagnosis, it’s not so much a matter of the amount of body fat carried but rather where it is located, results of a retrospective cohort study of nearly 3,000 survivors suggest.

“It is well known that higher body mass index (BMI) is associated with CVD mortality in the general population. However, BMI is not always an accurate proxy for individual-level adiposity and does not describe adipose tissue distribution,” note lead investigator Elizabeth M. Cespedes Feliciano, ScD, of Kaiser Permanente Northern California, Oakland, Calif., and coinvestigators.

The investigators studied 2,943 survivors of nonmetastatic breast cancer having a mean age of 56 years who were initially CVD free, using clinically acquired CT scans obtained near diagnosis to measure adiposity in three compartments: visceral, subcutaneous, and intramuscular.

The cohort experienced 328 CVD events (nonfatal stroke, myocardial infarction, heart failure, or CVD death) during a median follow-up of 6 years, the investigators reported in Journal of Clinical Oncology. The 10-year cumulative incidence was 15%.

In analyses that were adjusted for potential confounders and took into account competing risks, survivors’ CVD risk increased significantly with each standard deviation (SD) increase in visceral adiposity (hazard ratio, 1.15; 95% confidence interval, 1.03-1.29) and each SD increase in intramuscular adiposity (HR, 1.21; 95% CI, 1.06-1.37). The association for subcutaneous adiposity was not significant.

Findings were similar across all BMI categories. Of particular note, among survivors having a normal BMI, risk of CVD events increased by 70% with each SD greater visceral adiposity (HR, 1.70; 95% CI, 1.10-2.62).

Risk also rose with BMI exceeding the normal range, but the association became significant only in survivors with a BMI placing them in obesity class II (35 kg/m² or greater) (HR, 1.70; 95% CI, 1.20-2.42).

“Although it has been assumed that excess adiposity increases the risk of CVD after breast cancer, this first-of-its-kind study demonstrates that adipose tissue distribution best identifies patients with breast cancer with higher CVD risk after diagnosis, including those with normal BMI,” Dr. Cespedes Feliciano and coinvestigators note.

“Software is now available that automatically measures body composition from clinically acquired CT scans, facilitating clinical integration,” they note. “Measures of adipose tissue distribution from CT or anthropometry (e.g., waist circumference) may help identify individuals with high CVD risk and tailor prevention efforts to patients’ body composition.”

Dr. Cespedes Feliciano disclosed no relevant conflicts of interest. The study did not receive any specific funding.

SOURCE: Cespedes Feliciano EM et al. J Clin Oncol. 2019 Aug 1. doi: 10.1200/JCO.19.00286.

The heterogeneity of lupus and the subsequent lack of a clear disease definition have been identified by an international group of experts as the primary barriers hindering timely diagnosis, improved treatment options, and appropriate access to care.

A report published in Lupus Science & Medicine titled “Global Consensus Building and Prioritization of Fundamental Lupus Challenges: The ALPHA Project” describes the results of a first-ever global consensus on key barriers to advances in lupus care, including a lack of validated biomarkers and flawed clinical trial design.

A lack of access to medical professionals familiar with lupus, challenges in managing lupus because of social determinants, and lack of treatment adherence were also considered to be barriers to improving the outcomes of people living with lupus.

First author Susan Manzi, MD, codirector of the Lupus Center of Excellence at Allegheny Health Network, Pittsburgh, and her colleagues said that, in contrast to other autoimmune diseases such as rheumatoid arthritis and psoriasis, the field of lupus has struggled with establishing a clear pathway for lupus drug development because of “persistent challenges in understanding the biology of the disease, defining clinical trial entry criteria and end points, developing instruments to measure changes in clinical activity, and controlling background medications.”

The authors noted that the intention of the Addressing Lupus Pillars for Health Advancement (ALPHA) Project was to build on the work of other initiatives, including some that were international in scope or were still ongoing.

“The ALPHA project was founded as the first step in an ongoing commitment to identify, prioritize, and implement strategies to address the most pressing challenges that limit progress in lupus across the continuum,” they wrote. In a joint initiative, the Lupus Foundation of America (LFA) and the Tufts Center for the Study of Drug Development (Tufts CSDD) set up a Global Advisory Committee (GAC) that included 13 lupus experts from the United States, Australia, United Kingdom, Germany, and South Korea to guide and oversee the study. Members had extensive knowledge of the disease, with specific expertise in rheumatology, dermatology, immunology, nephrology, and pediatrics.

Next, in-depth interviews were conducted with 17 experts who were well respected in the lupus scientific and care communities and represented all stakeholders. Using information garnered from these interviews, the LFA, Tufts CSDD, and GAC collaborated to develop a survey that included 23 questions addressing attitudes and perceptions about lupus as well as the prioritization of the most pressing challenges to improving diagnosis, care, treatment, and research.

The online survey was sent to 366 candidates, from whom the researchers received 127 completed responses. Of these, 82 (65%) were clinician-researcher-scientists and 14 (11%) worked in industry/biotechnology, 13 (10%) were researcher-scientists, and 12 (9%) were clinicians; 5% marked “other.”

The research team used a weighting system to prioritize barriers ranked by respondents, whereby higher ratings represented the challenges of highest impact (a score of 9 was highest rating, with 1 the lowest).

Survey respondents ranked the following as the top barriers to improving outcomes in lupus:
 

• A lack of diagnostic, predictive, and prognostic biomarkers for lupus (weighted prioritization score of 7.294) and lack of biomarkers to predict drug response in clinical trials (weighted prioritization score of 6.614).
• Flawed clinical trial design (weighted prioritization score of 6.370).
• Lack of access to clinicians familiar with lupus (weighted prioritization score of 6.873), and limited awareness of lupus among nonexpert medical professionals (weighted prioritization score of 5.800).
• Barriers to effective management of lupus because of social determinants of care in predominantly lower socioeconomic status areas (weighted prioritization score of 6.937).
• A lack of treatment adherence (weighted prioritization score of 6.717).

“A strong consensus built throughout the study, as themes and insights gathered from the in-depth interviews were highly consistent with those collected in the survey,” the researchers noted.

They said it was not surprising that the development of biomarkers had received a high ranking, as advances in this area would help accelerate drug development and precision medicine as well as more practical aspects of clinical care.

The research team acknowledged that substantial funds would be needed to address the top priorities identified in the study, and some of the issues may be more easily addressed than others.

“In the past decade, the overall funding landscape for lupus has been on a decline, particularly through the National Institutes of Health – the largest public funder of lupus research in the world – during a time in which arguably, lupus research has been prolific,” they wrote.

They concluded that comprehensive measures were needed to transform the lupus research and health care landscape.

“Lupus experts must convene to determine feasible and coordinated approaches for addressing long-standing barriers across the global lupus community,” they stressed.

The next part of the project will involve an international stakeholder meeting to develop a global road map of specific recommendations to address identified barriers, which “may include multipronged strategies using regulatory and advocacy approaches, scientific consensus building, communication efforts, among other possible tactics,” they added.

The ALPHA Project was launched in partnership with founding partner EMD Serono Research & Development (a business of Merck KGaA) and through additional support by GlaxoSmithKline. Many authors of the report had financial connections to the pharmaceutical industry.

SOURCE: Manzi S et al. Lupus Sci Med. 2019;6:e000342. doi: 10.1136/lupus-2019-000342.

The heterogeneity of lupus and the subsequent lack of a clear disease definition have been identified by an international group of experts as the primary barriers hindering timely diagnosis, improved treatment options, and appropriate access to care.

A report published in Lupus Science & Medicine titled “Global Consensus Building and Prioritization of Fundamental Lupus Challenges: The ALPHA Project” describes the results of a first-ever global consensus on key barriers to advances in lupus care, including a lack of validated biomarkers and flawed clinical trial design.

A lack of access to medical professionals familiar with lupus, challenges in managing lupus because of social determinants, and lack of treatment adherence were also considered to be barriers to improving the outcomes of people living with lupus.

First author Susan Manzi, MD, codirector of the Lupus Center of Excellence at Allegheny Health Network, Pittsburgh, and her colleagues said that, in contrast to other autoimmune diseases such as rheumatoid arthritis and psoriasis, the field of lupus has struggled with establishing a clear pathway for lupus drug development because of “persistent challenges in understanding the biology of the disease, defining clinical trial entry criteria and end points, developing instruments to measure changes in clinical activity, and controlling background medications.”

The authors noted that the intention of the Addressing Lupus Pillars for Health Advancement (ALPHA) Project was to build on the work of other initiatives, including some that were international in scope or were still ongoing.

“The ALPHA project was founded as the first step in an ongoing commitment to identify, prioritize, and implement strategies to address the most pressing challenges that limit progress in lupus across the continuum,” they wrote. In a joint initiative, the Lupus Foundation of America (LFA) and the Tufts Center for the Study of Drug Development (Tufts CSDD) set up a Global Advisory Committee (GAC) that included 13 lupus experts from the United States, Australia, United Kingdom, Germany, and South Korea to guide and oversee the study. Members had extensive knowledge of the disease, with specific expertise in rheumatology, dermatology, immunology, nephrology, and pediatrics.

Next, in-depth interviews were conducted with 17 experts who were well respected in the lupus scientific and care communities and represented all stakeholders. Using information garnered from these interviews, the LFA, Tufts CSDD, and GAC collaborated to develop a survey that included 23 questions addressing attitudes and perceptions about lupus as well as the prioritization of the most pressing challenges to improving diagnosis, care, treatment, and research.

The online survey was sent to 366 candidates, from whom the researchers received 127 completed responses. Of these, 82 (65%) were clinician-researcher-scientists and 14 (11%) worked in industry/biotechnology, 13 (10%) were researcher-scientists, and 12 (9%) were clinicians; 5% marked “other.”

The research team used a weighting system to prioritize barriers ranked by respondents, whereby higher ratings represented the challenges of highest impact (a score of 9 was highest rating, with 1 the lowest).

Survey respondents ranked the following as the top barriers to improving outcomes in lupus:
 

• A lack of diagnostic, predictive, and prognostic biomarkers for lupus (weighted prioritization score of 7.294) and lack of biomarkers to predict drug response in clinical trials (weighted prioritization score of 6.614).
• Flawed clinical trial design (weighted prioritization score of 6.370).
• Lack of access to clinicians familiar with lupus (weighted prioritization score of 6.873), and limited awareness of lupus among nonexpert medical professionals (weighted prioritization score of 5.800).
• Barriers to effective management of lupus because of social determinants of care in predominantly lower socioeconomic status areas (weighted prioritization score of 6.937).
• A lack of treatment adherence (weighted prioritization score of 6.717).

“A strong consensus built throughout the study, as themes and insights gathered from the in-depth interviews were highly consistent with those collected in the survey,” the researchers noted.

They said it was not surprising that the development of biomarkers had received a high ranking, as advances in this area would help accelerate drug development and precision medicine as well as more practical aspects of clinical care.

The research team acknowledged that substantial funds would be needed to address the top priorities identified in the study, and some of the issues may be more easily addressed than others.

“In the past decade, the overall funding landscape for lupus has been on a decline, particularly through the National Institutes of Health – the largest public funder of lupus research in the world – during a time in which arguably, lupus research has been prolific,” they wrote.

They concluded that comprehensive measures were needed to transform the lupus research and health care landscape.

“Lupus experts must convene to determine feasible and coordinated approaches for addressing long-standing barriers across the global lupus community,” they stressed.

The next part of the project will involve an international stakeholder meeting to develop a global road map of specific recommendations to address identified barriers, which “may include multipronged strategies using regulatory and advocacy approaches, scientific consensus building, communication efforts, among other possible tactics,” they added.

The ALPHA Project was launched in partnership with founding partner EMD Serono Research & Development (a business of Merck KGaA) and through additional support by GlaxoSmithKline. Many authors of the report had financial connections to the pharmaceutical industry.

SOURCE: Manzi S et al. Lupus Sci Med. 2019;6:e000342. doi: 10.1136/lupus-2019-000342.

The heterogeneity of lupus and the subsequent lack of a clear disease definition have been identified by an international group of experts as the primary barriers hindering timely diagnosis, improved treatment options, and appropriate access to care.

A report published in Lupus Science & Medicine titled “Global Consensus Building and Prioritization of Fundamental Lupus Challenges: The ALPHA Project” describes the results of a first-ever global consensus on key barriers to advances in lupus care, including a lack of validated biomarkers and flawed clinical trial design.

A lack of access to medical professionals familiar with lupus, challenges in managing lupus because of social determinants, and lack of treatment adherence were also considered to be barriers to improving the outcomes of people living with lupus.

First author Susan Manzi, MD, codirector of the Lupus Center of Excellence at Allegheny Health Network, Pittsburgh, and her colleagues said that, in contrast to other autoimmune diseases such as rheumatoid arthritis and psoriasis, the field of lupus has struggled with establishing a clear pathway for lupus drug development because of “persistent challenges in understanding the biology of the disease, defining clinical trial entry criteria and end points, developing instruments to measure changes in clinical activity, and controlling background medications.”

The authors noted that the intention of the Addressing Lupus Pillars for Health Advancement (ALPHA) Project was to build on the work of other initiatives, including some that were international in scope or were still ongoing.

“The ALPHA project was founded as the first step in an ongoing commitment to identify, prioritize, and implement strategies to address the most pressing challenges that limit progress in lupus across the continuum,” they wrote. In a joint initiative, the Lupus Foundation of America (LFA) and the Tufts Center for the Study of Drug Development (Tufts CSDD) set up a Global Advisory Committee (GAC) that included 13 lupus experts from the United States, Australia, United Kingdom, Germany, and South Korea to guide and oversee the study. Members had extensive knowledge of the disease, with specific expertise in rheumatology, dermatology, immunology, nephrology, and pediatrics.

Next, in-depth interviews were conducted with 17 experts who were well respected in the lupus scientific and care communities and represented all stakeholders. Using information garnered from these interviews, the LFA, Tufts CSDD, and GAC collaborated to develop a survey that included 23 questions addressing attitudes and perceptions about lupus as well as the prioritization of the most pressing challenges to improving diagnosis, care, treatment, and research.

The online survey was sent to 366 candidates, from whom the researchers received 127 completed responses. Of these, 82 (65%) were clinician-researcher-scientists and 14 (11%) worked in industry/biotechnology, 13 (10%) were researcher-scientists, and 12 (9%) were clinicians; 5% marked “other.”

The research team used a weighting system to prioritize barriers ranked by respondents, whereby higher ratings represented the challenges of highest impact (a score of 9 was highest rating, with 1 the lowest).

Survey respondents ranked the following as the top barriers to improving outcomes in lupus:
 

• A lack of diagnostic, predictive, and prognostic biomarkers for lupus (weighted prioritization score of 7.294) and lack of biomarkers to predict drug response in clinical trials (weighted prioritization score of 6.614).
• Flawed clinical trial design (weighted prioritization score of 6.370).
• Lack of access to clinicians familiar with lupus (weighted prioritization score of 6.873), and limited awareness of lupus among nonexpert medical professionals (weighted prioritization score of 5.800).
• Barriers to effective management of lupus because of social determinants of care in predominantly lower socioeconomic status areas (weighted prioritization score of 6.937).
• A lack of treatment adherence (weighted prioritization score of 6.717).

“A strong consensus built throughout the study, as themes and insights gathered from the in-depth interviews were highly consistent with those collected in the survey,” the researchers noted.

They said it was not surprising that the development of biomarkers had received a high ranking, as advances in this area would help accelerate drug development and precision medicine as well as more practical aspects of clinical care.

The research team acknowledged that substantial funds would be needed to address the top priorities identified in the study, and some of the issues may be more easily addressed than others.

“In the past decade, the overall funding landscape for lupus has been on a decline, particularly through the National Institutes of Health – the largest public funder of lupus research in the world – during a time in which arguably, lupus research has been prolific,” they wrote.

They concluded that comprehensive measures were needed to transform the lupus research and health care landscape.

“Lupus experts must convene to determine feasible and coordinated approaches for addressing long-standing barriers across the global lupus community,” they stressed.

The next part of the project will involve an international stakeholder meeting to develop a global road map of specific recommendations to address identified barriers, which “may include multipronged strategies using regulatory and advocacy approaches, scientific consensus building, communication efforts, among other possible tactics,” they added.

The ALPHA Project was launched in partnership with founding partner EMD Serono Research & Development (a business of Merck KGaA) and through additional support by GlaxoSmithKline. Many authors of the report had financial connections to the pharmaceutical industry.

SOURCE: Manzi S et al. Lupus Sci Med. 2019;6:e000342. doi: 10.1136/lupus-2019-000342.

Surprisingly, the cervical cancer death rate is greater among women aged >65 years than among younger women^1,2 (FIGURE). Paradoxically, most of our screening programs focus on women <65 years of age. A nationwide study from Denmark estimated that the cervical cancer death rate per 100,000 women at ages 40 to 44 and 65 to 69 was 3.8 and 9.0, respectively.¹ In other words, the cervical cancer death rate at age 65 to 69 years was 2.36 times higher than at age 40 to 44 years.¹

A study from the United States estimated that the cervical cancer death rate per 100,000 white women at ages 40 to 44 and 65 to 69 was 3.3 and 8.6, respectively,² very similar to the findings from Denmark. The same US study estimated that the cervical cancer death rate per 100,000 black women at ages 40 to 44 and 65 to 69 was 5.3 and 23.8, highlighting the fact that, in the United States, cervical cancer disease burden is disproportionately greater among black than among white women.² In addition, the cervical cancer death rate among black women at age 65 to 69 was 4.49 times higher than at age 40 to 44 years.²

Given the high death rate from cervical cancer in women >65 years of age, it is paradoxical that most professional society guidelines recommend discontinuing cervical cancer screening at 65 years of age, if previous cervical cancer screening is normal.^3,4 Is the problem due to an inability to implement the current guidelines? Or is the problem that the guidelines are not optimally designed to reduce cervical cancer risk in women >65 years of age?

The American College of Obstetricians and Gynecologists (ACOG) and the US Preventive Services Task Force (USPSTF) recommend against cervical cancer screening in women >65 years of age who have had adequate prior screening and are not otherwise at high risk for cervical cancer. However, ACOG and the USPSTF caution that there are many groups of women that may benefit from continued screening after 65 years of age, including women with HIV infection, a compromised immune system, or previous high-grade precancerous lesion or cervicalcancer; women with limited access to care; women from racial/ethnic minority groups; and migrant women.⁴ Many clinicians remember the guidance, “discontinue cervical cancer screening at 65 years” but do not recall all the clinical factors that might warrant continued screening past age 65. Of special concern is that black,² Hispanic,⁵ and migrant women⁶ are at much higher risk for invasive cervical cancer than white or US-born women.

The optimal implementation of the ACOG and USPSTF guidelines are undermined by a fractured health care system, where key pieces of information may be unavailable to the clinician tasked with making a decision about discontinuing cervical cancer screening. Imagine the case in which a 65-year-old woman pre‑sents to her primary care physician for cervical cancer screening. The clinician performs a cervical cytology test and obtains a report of “no intraepithelial lesion or malignancy.” The clinician then recommends that the patient discontinue cervical cancer screening. Unbeknownst to the clinician, the patient had a positive HPV 16/18/45 test within the past 10 years in another health system. In this case, it would be inappropriate to terminate the patient from cervical cancer screening.

Continue to: Testing for hrHPV is superior to cervical cytology in women >65 years...

Testing for hrHPV is superior to cervical cytology in women >65 years

In Sweden, about 30% of cervical cancer cases occur in women aged >60 years.⁷ To assess the prevalence of oncogenic high-risk HPV (hrHPV), women at ages 60, 65, 70, and 75 years were invited to send sequential self-collected vaginal samples for nucleic acid testing for hrHPV. The prevalence of hrHPV was found to be 4.4%. Women with a second positive, self-collected, hrHPV test were invited for colposcopy, cervical biopsy, and cytology testing. Among the women with two positive hrHPV tests, cervical biopsy revealed 7 cases of cervical intraepithelial neoplasia grade 2 (CIN2), 6 cases of CIN1, and 4 biopsies without CIN. In these women 94% of the cervical cytology samples returned, “no intraepithelial lesion or malignancy” and 6% revealed atypical squamous cells of undetermined significance. This study suggests that, in women aged >65 years, cervical cytology may have a high rate of false-negative results, possibly due to epithelial atrophy. An evolving clinical pearl is that, when using the current cervical cancer screening guidelines, the final screen for cervical cancer must include a nucleic acid test for hrHPV.

In women 65 to 90 years, the prevalence of hrHPV is approximately 5%

In a study of 40,382 women aged 14 to 95 years, the prevalence of hrHPV was 46% in 20- to 23-year-old women and 5.7% in women older than 65 years of age.⁸ In a study of more than 108,000 women aged 69 to >89 years the prevalence of hrHPV was 4.3%, and similar prevalence rates were seen across all ages from 69 to >89 years.⁹ The carcinogenic role of persistent hrHPV infection in women >65 years is an important area for future research.

Latent HPV virus infection

Following a primary varicella-zoster infection (chickenpox), the virus may remain in a latent state in sensory ganglia, reactivating later in life to cause shingles. Thirty percent of people who have a primary chickenpox infection eventually will develop a case of shingles. Immunocompromised populations are at an increased risk of developing shingles because of reduced T-cell mediated immunity.

A recent hypothesis is that in immunocompromised and older women, latent HPV can reactivate and cause clinically significant infection.¹⁰ Following renal transplantation investigators have reported a significant increase in the prevalence of genital HPV, without a change in sexual behavior.¹¹ In cervical tissue from women with no evidence of active HPV infection, highly sensitive PCR-based assays detected HPV16 virus in a latent state in some women, possibly due to disruption of the viral E2 gene.¹² If latent HPV infection is a valid biological concept, it suggests that there is no “safe age” at which to discontinue screening for HPV infection because the virus cannot be detected in screening samples while it is latent.

Options for cervical cancer screening in women >65 years

Three options might reduce the morbidity and mortality associated with cervical cancer in women >65 years.

Option 1: Double-down on trying to effectively implement current guidelines. The high rate of cervical cancer mortality in women >65 years of age indicates that the current guidelines, as implemented in real clinical practice, are not working. A problem with the current screening guidelines is that clinicians are expected to be capable of finding all relevant cervical cancer test results and properly interpreting the results. Clinicians are over-taxed and fallible, and the current approach is not likely to be successful unless additional information technology solutions are implemented.

Continue to: Health systems could use information...

Health systems could use information technology to mitigate these problems. For example, health systems could deploy software to assemble every cervical screening result on each woman and pre‑sent those results to clinicians in a single integrated view in the electronic record. Additionally, once all lifetime screening results are consolidated in one view, artificial intelligence systems could be used to analyze the totality of results and identify women who would benefit by continued screening past age 65 and women who could safely discontinue screening.

Option 2: Adopt the Australian approach to cervical cancer screening. The current Australian approach to cervical cancer screening is built on 3 pillars: 1) school-based vaccination of all children against hrHPV, 2) screening all women from 25 to 74 years of age every 5 years using nucleic acid testing for hrHPV, and 3) providing a system for the testing of samples self-collected by women who are reluctant to visit a clinician for screening.¹³ Australia has one of the lowest cervical cancer death rates in the world.

Option 3: Continue screening most women past age 65. Women >65 years of age are known to be infected with hrHPV genotypes. hrHPV infection causes cervical cancer. Cervical cancer causes many deaths in women aged >65 years. There is no strong rationale for ignoring these three facts. hrHPV screening every 5 years as long as the woman is healthy and has a reasonable life expectancy is an option that could be evaluated in randomized studies.

Given the high rate of cervical cancer death in women >65 years of age, I plan to be very cautious about discontinuing cervical cancer screening until I can personally ensure that my patient has no evidence of hrHPV infection.

Surprisingly, the cervical cancer death rate is greater among women aged >65 years than among younger women^1,2 (FIGURE). Paradoxically, most of our screening programs focus on women <65 years of age. A nationwide study from Denmark estimated that the cervical cancer death rate per 100,000 women at ages 40 to 44 and 65 to 69 was 3.8 and 9.0, respectively.¹ In other words, the cervical cancer death rate at age 65 to 69 years was 2.36 times higher than at age 40 to 44 years.¹

A study from the United States estimated that the cervical cancer death rate per 100,000 white women at ages 40 to 44 and 65 to 69 was 3.3 and 8.6, respectively,² very similar to the findings from Denmark. The same US study estimated that the cervical cancer death rate per 100,000 black women at ages 40 to 44 and 65 to 69 was 5.3 and 23.8, highlighting the fact that, in the United States, cervical cancer disease burden is disproportionately greater among black than among white women.² In addition, the cervical cancer death rate among black women at age 65 to 69 was 4.49 times higher than at age 40 to 44 years.²

Given the high death rate from cervical cancer in women >65 years of age, it is paradoxical that most professional society guidelines recommend discontinuing cervical cancer screening at 65 years of age, if previous cervical cancer screening is normal.^3,4 Is the problem due to an inability to implement the current guidelines? Or is the problem that the guidelines are not optimally designed to reduce cervical cancer risk in women >65 years of age?

The American College of Obstetricians and Gynecologists (ACOG) and the US Preventive Services Task Force (USPSTF) recommend against cervical cancer screening in women >65 years of age who have had adequate prior screening and are not otherwise at high risk for cervical cancer. However, ACOG and the USPSTF caution that there are many groups of women that may benefit from continued screening after 65 years of age, including women with HIV infection, a compromised immune system, or previous high-grade precancerous lesion or cervicalcancer; women with limited access to care; women from racial/ethnic minority groups; and migrant women.⁴ Many clinicians remember the guidance, “discontinue cervical cancer screening at 65 years” but do not recall all the clinical factors that might warrant continued screening past age 65. Of special concern is that black,² Hispanic,⁵ and migrant women⁶ are at much higher risk for invasive cervical cancer than white or US-born women.

The optimal implementation of the ACOG and USPSTF guidelines are undermined by a fractured health care system, where key pieces of information may be unavailable to the clinician tasked with making a decision about discontinuing cervical cancer screening. Imagine the case in which a 65-year-old woman pre‑sents to her primary care physician for cervical cancer screening. The clinician performs a cervical cytology test and obtains a report of “no intraepithelial lesion or malignancy.” The clinician then recommends that the patient discontinue cervical cancer screening. Unbeknownst to the clinician, the patient had a positive HPV 16/18/45 test within the past 10 years in another health system. In this case, it would be inappropriate to terminate the patient from cervical cancer screening.

Continue to: Testing for hrHPV is superior to cervical cytology in women >65 years...

Testing for hrHPV is superior to cervical cytology in women >65 years

In Sweden, about 30% of cervical cancer cases occur in women aged >60 years.⁷ To assess the prevalence of oncogenic high-risk HPV (hrHPV), women at ages 60, 65, 70, and 75 years were invited to send sequential self-collected vaginal samples for nucleic acid testing for hrHPV. The prevalence of hrHPV was found to be 4.4%. Women with a second positive, self-collected, hrHPV test were invited for colposcopy, cervical biopsy, and cytology testing. Among the women with two positive hrHPV tests, cervical biopsy revealed 7 cases of cervical intraepithelial neoplasia grade 2 (CIN2), 6 cases of CIN1, and 4 biopsies without CIN. In these women 94% of the cervical cytology samples returned, “no intraepithelial lesion or malignancy” and 6% revealed atypical squamous cells of undetermined significance. This study suggests that, in women aged >65 years, cervical cytology may have a high rate of false-negative results, possibly due to epithelial atrophy. An evolving clinical pearl is that, when using the current cervical cancer screening guidelines, the final screen for cervical cancer must include a nucleic acid test for hrHPV.

In women 65 to 90 years, the prevalence of hrHPV is approximately 5%

In a study of 40,382 women aged 14 to 95 years, the prevalence of hrHPV was 46% in 20- to 23-year-old women and 5.7% in women older than 65 years of age.⁸ In a study of more than 108,000 women aged 69 to >89 years the prevalence of hrHPV was 4.3%, and similar prevalence rates were seen across all ages from 69 to >89 years.⁹ The carcinogenic role of persistent hrHPV infection in women >65 years is an important area for future research.

Latent HPV virus infection

Following a primary varicella-zoster infection (chickenpox), the virus may remain in a latent state in sensory ganglia, reactivating later in life to cause shingles. Thirty percent of people who have a primary chickenpox infection eventually will develop a case of shingles. Immunocompromised populations are at an increased risk of developing shingles because of reduced T-cell mediated immunity.

A recent hypothesis is that in immunocompromised and older women, latent HPV can reactivate and cause clinically significant infection.¹⁰ Following renal transplantation investigators have reported a significant increase in the prevalence of genital HPV, without a change in sexual behavior.¹¹ In cervical tissue from women with no evidence of active HPV infection, highly sensitive PCR-based assays detected HPV16 virus in a latent state in some women, possibly due to disruption of the viral E2 gene.¹² If latent HPV infection is a valid biological concept, it suggests that there is no “safe age” at which to discontinue screening for HPV infection because the virus cannot be detected in screening samples while it is latent.

Options for cervical cancer screening in women >65 years

Three options might reduce the morbidity and mortality associated with cervical cancer in women >65 years.

Option 1: Double-down on trying to effectively implement current guidelines. The high rate of cervical cancer mortality in women >65 years of age indicates that the current guidelines, as implemented in real clinical practice, are not working. A problem with the current screening guidelines is that clinicians are expected to be capable of finding all relevant cervical cancer test results and properly interpreting the results. Clinicians are over-taxed and fallible, and the current approach is not likely to be successful unless additional information technology solutions are implemented.

Continue to: Health systems could use information...

Health systems could use information technology to mitigate these problems. For example, health systems could deploy software to assemble every cervical screening result on each woman and pre‑sent those results to clinicians in a single integrated view in the electronic record. Additionally, once all lifetime screening results are consolidated in one view, artificial intelligence systems could be used to analyze the totality of results and identify women who would benefit by continued screening past age 65 and women who could safely discontinue screening.

Option 2: Adopt the Australian approach to cervical cancer screening. The current Australian approach to cervical cancer screening is built on 3 pillars: 1) school-based vaccination of all children against hrHPV, 2) screening all women from 25 to 74 years of age every 5 years using nucleic acid testing for hrHPV, and 3) providing a system for the testing of samples self-collected by women who are reluctant to visit a clinician for screening.¹³ Australia has one of the lowest cervical cancer death rates in the world.

Option 3: Continue screening most women past age 65. Women >65 years of age are known to be infected with hrHPV genotypes. hrHPV infection causes cervical cancer. Cervical cancer causes many deaths in women aged >65 years. There is no strong rationale for ignoring these three facts. hrHPV screening every 5 years as long as the woman is healthy and has a reasonable life expectancy is an option that could be evaluated in randomized studies.

Given the high rate of cervical cancer death in women >65 years of age, I plan to be very cautious about discontinuing cervical cancer screening until I can personally ensure that my patient has no evidence of hrHPV infection.

Surprisingly, the cervical cancer death rate is greater among women aged >65 years than among younger women^1,2 (FIGURE). Paradoxically, most of our screening programs focus on women <65 years of age. A nationwide study from Denmark estimated that the cervical cancer death rate per 100,000 women at ages 40 to 44 and 65 to 69 was 3.8 and 9.0, respectively.¹ In other words, the cervical cancer death rate at age 65 to 69 years was 2.36 times higher than at age 40 to 44 years.¹

A study from the United States estimated that the cervical cancer death rate per 100,000 white women at ages 40 to 44 and 65 to 69 was 3.3 and 8.6, respectively,² very similar to the findings from Denmark. The same US study estimated that the cervical cancer death rate per 100,000 black women at ages 40 to 44 and 65 to 69 was 5.3 and 23.8, highlighting the fact that, in the United States, cervical cancer disease burden is disproportionately greater among black than among white women.² In addition, the cervical cancer death rate among black women at age 65 to 69 was 4.49 times higher than at age 40 to 44 years.²

Given the high death rate from cervical cancer in women >65 years of age, it is paradoxical that most professional society guidelines recommend discontinuing cervical cancer screening at 65 years of age, if previous cervical cancer screening is normal.^3,4 Is the problem due to an inability to implement the current guidelines? Or is the problem that the guidelines are not optimally designed to reduce cervical cancer risk in women >65 years of age?

The American College of Obstetricians and Gynecologists (ACOG) and the US Preventive Services Task Force (USPSTF) recommend against cervical cancer screening in women >65 years of age who have had adequate prior screening and are not otherwise at high risk for cervical cancer. However, ACOG and the USPSTF caution that there are many groups of women that may benefit from continued screening after 65 years of age, including women with HIV infection, a compromised immune system, or previous high-grade precancerous lesion or cervicalcancer; women with limited access to care; women from racial/ethnic minority groups; and migrant women.⁴ Many clinicians remember the guidance, “discontinue cervical cancer screening at 65 years” but do not recall all the clinical factors that might warrant continued screening past age 65. Of special concern is that black,² Hispanic,⁵ and migrant women⁶ are at much higher risk for invasive cervical cancer than white or US-born women.

The optimal implementation of the ACOG and USPSTF guidelines are undermined by a fractured health care system, where key pieces of information may be unavailable to the clinician tasked with making a decision about discontinuing cervical cancer screening. Imagine the case in which a 65-year-old woman pre‑sents to her primary care physician for cervical cancer screening. The clinician performs a cervical cytology test and obtains a report of “no intraepithelial lesion or malignancy.” The clinician then recommends that the patient discontinue cervical cancer screening. Unbeknownst to the clinician, the patient had a positive HPV 16/18/45 test within the past 10 years in another health system. In this case, it would be inappropriate to terminate the patient from cervical cancer screening.

Continue to: Testing for hrHPV is superior to cervical cytology in women >65 years...

Testing for hrHPV is superior to cervical cytology in women >65 years

In Sweden, about 30% of cervical cancer cases occur in women aged >60 years.⁷ To assess the prevalence of oncogenic high-risk HPV (hrHPV), women at ages 60, 65, 70, and 75 years were invited to send sequential self-collected vaginal samples for nucleic acid testing for hrHPV. The prevalence of hrHPV was found to be 4.4%. Women with a second positive, self-collected, hrHPV test were invited for colposcopy, cervical biopsy, and cytology testing. Among the women with two positive hrHPV tests, cervical biopsy revealed 7 cases of cervical intraepithelial neoplasia grade 2 (CIN2), 6 cases of CIN1, and 4 biopsies without CIN. In these women 94% of the cervical cytology samples returned, “no intraepithelial lesion or malignancy” and 6% revealed atypical squamous cells of undetermined significance. This study suggests that, in women aged >65 years, cervical cytology may have a high rate of false-negative results, possibly due to epithelial atrophy. An evolving clinical pearl is that, when using the current cervical cancer screening guidelines, the final screen for cervical cancer must include a nucleic acid test for hrHPV.

In women 65 to 90 years, the prevalence of hrHPV is approximately 5%

In a study of 40,382 women aged 14 to 95 years, the prevalence of hrHPV was 46% in 20- to 23-year-old women and 5.7% in women older than 65 years of age.⁸ In a study of more than 108,000 women aged 69 to >89 years the prevalence of hrHPV was 4.3%, and similar prevalence rates were seen across all ages from 69 to >89 years.⁹ The carcinogenic role of persistent hrHPV infection in women >65 years is an important area for future research.

Latent HPV virus infection

Following a primary varicella-zoster infection (chickenpox), the virus may remain in a latent state in sensory ganglia, reactivating later in life to cause shingles. Thirty percent of people who have a primary chickenpox infection eventually will develop a case of shingles. Immunocompromised populations are at an increased risk of developing shingles because of reduced T-cell mediated immunity.

A recent hypothesis is that in immunocompromised and older women, latent HPV can reactivate and cause clinically significant infection.¹⁰ Following renal transplantation investigators have reported a significant increase in the prevalence of genital HPV, without a change in sexual behavior.¹¹ In cervical tissue from women with no evidence of active HPV infection, highly sensitive PCR-based assays detected HPV16 virus in a latent state in some women, possibly due to disruption of the viral E2 gene.¹² If latent HPV infection is a valid biological concept, it suggests that there is no “safe age” at which to discontinue screening for HPV infection because the virus cannot be detected in screening samples while it is latent.

Options for cervical cancer screening in women >65 years

Three options might reduce the morbidity and mortality associated with cervical cancer in women >65 years.

Option 1: Double-down on trying to effectively implement current guidelines. The high rate of cervical cancer mortality in women >65 years of age indicates that the current guidelines, as implemented in real clinical practice, are not working. A problem with the current screening guidelines is that clinicians are expected to be capable of finding all relevant cervical cancer test results and properly interpreting the results. Clinicians are over-taxed and fallible, and the current approach is not likely to be successful unless additional information technology solutions are implemented.

Continue to: Health systems could use information...

Health systems could use information technology to mitigate these problems. For example, health systems could deploy software to assemble every cervical screening result on each woman and pre‑sent those results to clinicians in a single integrated view in the electronic record. Additionally, once all lifetime screening results are consolidated in one view, artificial intelligence systems could be used to analyze the totality of results and identify women who would benefit by continued screening past age 65 and women who could safely discontinue screening.

Option 2: Adopt the Australian approach to cervical cancer screening. The current Australian approach to cervical cancer screening is built on 3 pillars: 1) school-based vaccination of all children against hrHPV, 2) screening all women from 25 to 74 years of age every 5 years using nucleic acid testing for hrHPV, and 3) providing a system for the testing of samples self-collected by women who are reluctant to visit a clinician for screening.¹³ Australia has one of the lowest cervical cancer death rates in the world.

Option 3: Continue screening most women past age 65. Women >65 years of age are known to be infected with hrHPV genotypes. hrHPV infection causes cervical cancer. Cervical cancer causes many deaths in women aged >65 years. There is no strong rationale for ignoring these three facts. hrHPV screening every 5 years as long as the woman is healthy and has a reasonable life expectancy is an option that could be evaluated in randomized studies.

Given the high rate of cervical cancer death in women >65 years of age, I plan to be very cautious about discontinuing cervical cancer screening until I can personally ensure that my patient has no evidence of hrHPV infection.

Q2. Correct answer: E  
 
Rationale:  
Radiographic evaluation is commonly employed in the diagnosis and management of patients with lower GI bleeding. CT scans, tagged red blood cell scintigraphy, and angiography all have roles in the care of these patients. Though tagged red blood cell scintigraphy is the most sensitive modality at detecting active bleeding, requiring rates from 0.05-0.1 cc/min, it is relatively poor at localizing the bleeding, accurately predicting the location in only 60%-70% of cases. CT scans have the advantage of being quickly performed and are widely available. If extravasation is seen, its location is also accurately determined. It is not as sensitive as red blood cell scintigraphy, however, and requires bleeding rates of 0.3-0.5 cc/min to be positive. Angiography has the advantage of being both diagnostic and potentially therapeutic. It is best performed in sicker patients with hypotension and high transfusion demands as it is higher yield in these situations. Angiography is the least sensitive of these modalities, requiring bleeding rates between 0.5 and 1 cc/min to be positive.  

Reference:  
1. Strate LL, Naumann CR. The role of colonoscopy and radiological procedures in the management of acute lower intestinal bleeding. Clin Gastroenterol Hepatol. 2010 Apr;8(4):333-43. 

[email protected]

Q2. Correct answer: E  
 
Rationale:  
Radiographic evaluation is commonly employed in the diagnosis and management of patients with lower GI bleeding. CT scans, tagged red blood cell scintigraphy, and angiography all have roles in the care of these patients. Though tagged red blood cell scintigraphy is the most sensitive modality at detecting active bleeding, requiring rates from 0.05-0.1 cc/min, it is relatively poor at localizing the bleeding, accurately predicting the location in only 60%-70% of cases. CT scans have the advantage of being quickly performed and are widely available. If extravasation is seen, its location is also accurately determined. It is not as sensitive as red blood cell scintigraphy, however, and requires bleeding rates of 0.3-0.5 cc/min to be positive. Angiography has the advantage of being both diagnostic and potentially therapeutic. It is best performed in sicker patients with hypotension and high transfusion demands as it is higher yield in these situations. Angiography is the least sensitive of these modalities, requiring bleeding rates between 0.5 and 1 cc/min to be positive.  

Reference:  
1. Strate LL, Naumann CR. The role of colonoscopy and radiological procedures in the management of acute lower intestinal bleeding. Clin Gastroenterol Hepatol. 2010 Apr;8(4):333-43. 

[email protected]

Q2. Correct answer: E  
 
Rationale:  
Radiographic evaluation is commonly employed in the diagnosis and management of patients with lower GI bleeding. CT scans, tagged red blood cell scintigraphy, and angiography all have roles in the care of these patients. Though tagged red blood cell scintigraphy is the most sensitive modality at detecting active bleeding, requiring rates from 0.05-0.1 cc/min, it is relatively poor at localizing the bleeding, accurately predicting the location in only 60%-70% of cases. CT scans have the advantage of being quickly performed and are widely available. If extravasation is seen, its location is also accurately determined. It is not as sensitive as red blood cell scintigraphy, however, and requires bleeding rates of 0.3-0.5 cc/min to be positive. Angiography has the advantage of being both diagnostic and potentially therapeutic. It is best performed in sicker patients with hypotension and high transfusion demands as it is higher yield in these situations. Angiography is the least sensitive of these modalities, requiring bleeding rates between 0.5 and 1 cc/min to be positive.  

Reference:  
1. Strate LL, Naumann CR. The role of colonoscopy and radiological procedures in the management of acute lower intestinal bleeding. Clin Gastroenterol Hepatol. 2010 Apr;8(4):333-43. 

[email protected]

Q1. Correct answer: C 
 
Rationale: 
The two standard treatment regimens for AIH include corticosteroids (prednisone or prednisolone) alone, or corticosteroids combined with azathioprine. The combination regimen allows for a lower dose of steroids and fewer side effects with the same therapeutic efficacy. This patient appears to have developed azathioprine-induced pancreatitis, which is a rare complication more often seen in patients with Crohn's disease treated with azathioprine. In patients who are intolerant of azathioprine, mycophenolate mofetil and calcineurin inhibitors have been used with success.  
There are data supporting the use of budesonide in place of prednisone, but this regimen is not as effective in patients with cirrhosis or advanced fibrosis, so it is reserved for patients with lesser degrees of liver fibrosis. The TNF-alpha inhibitors are not used to treat AIH, nor is the IL-1 inhibitor anakinra. 
 
References: 
1. Czaja AJ. Diagnosis and management of autoimmune hepatitis: Current status and future directions. Gut Liver. 2016;10:177-203. 
2. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Autoimmune Hepatitis. J Hepatol. 2015:63:971-1004. 
3. Manns MP, et al. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010;51:1-31.

Q1. Correct answer: C 
 
Rationale: 
The two standard treatment regimens for AIH include corticosteroids (prednisone or prednisolone) alone, or corticosteroids combined with azathioprine. The combination regimen allows for a lower dose of steroids and fewer side effects with the same therapeutic efficacy. This patient appears to have developed azathioprine-induced pancreatitis, which is a rare complication more often seen in patients with Crohn's disease treated with azathioprine. In patients who are intolerant of azathioprine, mycophenolate mofetil and calcineurin inhibitors have been used with success.  
There are data supporting the use of budesonide in place of prednisone, but this regimen is not as effective in patients with cirrhosis or advanced fibrosis, so it is reserved for patients with lesser degrees of liver fibrosis. The TNF-alpha inhibitors are not used to treat AIH, nor is the IL-1 inhibitor anakinra. 
 
References: 
1. Czaja AJ. Diagnosis and management of autoimmune hepatitis: Current status and future directions. Gut Liver. 2016;10:177-203. 
2. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Autoimmune Hepatitis. J Hepatol. 2015:63:971-1004. 
3. Manns MP, et al. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010;51:1-31.

Q1. Correct answer: C 
 
Rationale: 
The two standard treatment regimens for AIH include corticosteroids (prednisone or prednisolone) alone, or corticosteroids combined with azathioprine. The combination regimen allows for a lower dose of steroids and fewer side effects with the same therapeutic efficacy. This patient appears to have developed azathioprine-induced pancreatitis, which is a rare complication more often seen in patients with Crohn's disease treated with azathioprine. In patients who are intolerant of azathioprine, mycophenolate mofetil and calcineurin inhibitors have been used with success.  
There are data supporting the use of budesonide in place of prednisone, but this regimen is not as effective in patients with cirrhosis or advanced fibrosis, so it is reserved for patients with lesser degrees of liver fibrosis. The TNF-alpha inhibitors are not used to treat AIH, nor is the IL-1 inhibitor anakinra. 
 
References: 
1. Czaja AJ. Diagnosis and management of autoimmune hepatitis: Current status and future directions. Gut Liver. 2016;10:177-203. 
2. European Association for the Study of the Liver. EASL Clinical Practice Guidelines: Autoimmune Hepatitis. J Hepatol. 2015:63:971-1004. 
3. Manns MP, et al. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010;51:1-31.

Hauspurg A, Parry S, Mercer BM, et al. Blood pressure trajectory and category and risk of hypertensive disorders of pregnancy in nulliparous women. Am J Obstet Gynecol. 2019. pii: S0002-9378(19)30807-5. doi: 10.1016/j.ajog.2019.06.031.

EXPERT COMMENTARY

Hauspurg and colleagues set out to determine whether redefined BP category (normal, < 120/80 mm Hg) and trajectory (a difference of ≥ 5 mm Hg systolic, diastolic, or mean arterial pressure between the first and second prenatal visit) helps to identify women at increased risk for developing hypertensive disorders of pregnancy or preeclampsia.

With respect to the former variable, such an association was demonstrated in the first National Institutes of Health–funded preeclampsia prevention trial published in 1993, which used low-dose aspirin.¹ In that trial, low-dose aspirin was not found to be effective in preventing preeclampsia in young, healthy nulliparous women. Interestingly, the 2 factors most associated with developing preeclampsia were an initial systolic BP of 120 to 134 mm Hg and an initial weight of >60 kg. For most clinicians, these findings would not be helpful in trying to better identify a high-risk group.

Details of the study

The idea of BP “trajectory” is interesting in the Hauspurg and colleagues’ study. The authors analyzed data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b), a prospective cohort study, and included a very large population of almost 9,000 women in the analysis. Participants were classified according to their BP measurement at the first study visit, with BP categories based on updated American College of Cardiology/American Heart Association guidelines. The primary outcome was the risk of hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia.

The data analysis found that elevated BP was associated with an adjusted risk ratio (aRR) of 1.54 (95% confidence interval [CI], 1.18–2.02). Stage 1 hypertension was associated with an aRR of 2.16 (95% CI, 1.31–3.57). Compared with women whose BP had a downward systolic trajectory, women with normal BP and an upward systolic trajectory had a 41% increased risk of any hypertensive disorder of pregnancy (aRR, 1.41; 95% CI, 1.20–1.65).

Study strengths and limitations

While the large study population is a strength of this study, there are a number of limitations, such as the use of BP measurements during pregnancy only, without having pre-pregnancy measurements available. Further, a single BP measurement during each visit is also a drawback, although the standardized measurement by study staff is a strength.

Anticlimactic conclusions. The conclusions of the study, however, are either not surprising, not clinically meaningful, or of little value to clinicians at present, at least with respect to patient management.

Continue to: Conclusions that were not surprising included...

Conclusions that were not surprising included a statistically lower chance of indicated preterm delivery in the normal BP group than in the elevated BP or stage 1 hypertension groups. Conclusions that were not meaningful included a statistically significant lower birthweight in the elevated BP group (3,269 g) and in the stage 1 hypertension group (3,258 g) compared with the normal BP group (3,279 g), but the clinical significance of these differences is arguable.

Lastly is the issue of what these data mean for clinical practice. The idea of identifying high-risk groups is attractive, provided that there are effective intervention strategies available. If one follows the United States Preventive Services Task Force (USPSTF) recommendations for preeclampsia prevention,² then virtually every nulliparous woman is a candidate for low-dose aspirin for preeclampsia prophylaxis. Beyond that, the current data do not support any change in the standard clinical practice of managing these “now identified” high-risk women. Increasing prenatal visits, using biomarkers to further delineate risk, and using uterine artery Doppler studies are all strategies that have been or are being investigated, but as yet they are not supported by conclusive data documenting improved outcomes—a sentiment supported by both the USPSTF³ and the authors of the study.

Hauspurg A, Parry S, Mercer BM, et al. Blood pressure trajectory and category and risk of hypertensive disorders of pregnancy in nulliparous women. Am J Obstet Gynecol. 2019. pii: S0002-9378(19)30807-5. doi: 10.1016/j.ajog.2019.06.031.

EXPERT COMMENTARY

Hauspurg and colleagues set out to determine whether redefined BP category (normal, < 120/80 mm Hg) and trajectory (a difference of ≥ 5 mm Hg systolic, diastolic, or mean arterial pressure between the first and second prenatal visit) helps to identify women at increased risk for developing hypertensive disorders of pregnancy or preeclampsia.

With respect to the former variable, such an association was demonstrated in the first National Institutes of Health–funded preeclampsia prevention trial published in 1993, which used low-dose aspirin.¹ In that trial, low-dose aspirin was not found to be effective in preventing preeclampsia in young, healthy nulliparous women. Interestingly, the 2 factors most associated with developing preeclampsia were an initial systolic BP of 120 to 134 mm Hg and an initial weight of >60 kg. For most clinicians, these findings would not be helpful in trying to better identify a high-risk group.

Details of the study

The idea of BP “trajectory” is interesting in the Hauspurg and colleagues’ study. The authors analyzed data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b), a prospective cohort study, and included a very large population of almost 9,000 women in the analysis. Participants were classified according to their BP measurement at the first study visit, with BP categories based on updated American College of Cardiology/American Heart Association guidelines. The primary outcome was the risk of hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia.

The data analysis found that elevated BP was associated with an adjusted risk ratio (aRR) of 1.54 (95% confidence interval [CI], 1.18–2.02). Stage 1 hypertension was associated with an aRR of 2.16 (95% CI, 1.31–3.57). Compared with women whose BP had a downward systolic trajectory, women with normal BP and an upward systolic trajectory had a 41% increased risk of any hypertensive disorder of pregnancy (aRR, 1.41; 95% CI, 1.20–1.65).

Study strengths and limitations

While the large study population is a strength of this study, there are a number of limitations, such as the use of BP measurements during pregnancy only, without having pre-pregnancy measurements available. Further, a single BP measurement during each visit is also a drawback, although the standardized measurement by study staff is a strength.

Anticlimactic conclusions. The conclusions of the study, however, are either not surprising, not clinically meaningful, or of little value to clinicians at present, at least with respect to patient management.

Continue to: Conclusions that were not surprising included...

Conclusions that were not surprising included a statistically lower chance of indicated preterm delivery in the normal BP group than in the elevated BP or stage 1 hypertension groups. Conclusions that were not meaningful included a statistically significant lower birthweight in the elevated BP group (3,269 g) and in the stage 1 hypertension group (3,258 g) compared with the normal BP group (3,279 g), but the clinical significance of these differences is arguable.

Lastly is the issue of what these data mean for clinical practice. The idea of identifying high-risk groups is attractive, provided that there are effective intervention strategies available. If one follows the United States Preventive Services Task Force (USPSTF) recommendations for preeclampsia prevention,² then virtually every nulliparous woman is a candidate for low-dose aspirin for preeclampsia prophylaxis. Beyond that, the current data do not support any change in the standard clinical practice of managing these “now identified” high-risk women. Increasing prenatal visits, using biomarkers to further delineate risk, and using uterine artery Doppler studies are all strategies that have been or are being investigated, but as yet they are not supported by conclusive data documenting improved outcomes—a sentiment supported by both the USPSTF³ and the authors of the study.

Hauspurg A, Parry S, Mercer BM, et al. Blood pressure trajectory and category and risk of hypertensive disorders of pregnancy in nulliparous women. Am J Obstet Gynecol. 2019. pii: S0002-9378(19)30807-5. doi: 10.1016/j.ajog.2019.06.031.

EXPERT COMMENTARY

Hauspurg and colleagues set out to determine whether redefined BP category (normal, < 120/80 mm Hg) and trajectory (a difference of ≥ 5 mm Hg systolic, diastolic, or mean arterial pressure between the first and second prenatal visit) helps to identify women at increased risk for developing hypertensive disorders of pregnancy or preeclampsia.

With respect to the former variable, such an association was demonstrated in the first National Institutes of Health–funded preeclampsia prevention trial published in 1993, which used low-dose aspirin.¹ In that trial, low-dose aspirin was not found to be effective in preventing preeclampsia in young, healthy nulliparous women. Interestingly, the 2 factors most associated with developing preeclampsia were an initial systolic BP of 120 to 134 mm Hg and an initial weight of >60 kg. For most clinicians, these findings would not be helpful in trying to better identify a high-risk group.

Details of the study

The idea of BP “trajectory” is interesting in the Hauspurg and colleagues’ study. The authors analyzed data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b), a prospective cohort study, and included a very large population of almost 9,000 women in the analysis. Participants were classified according to their BP measurement at the first study visit, with BP categories based on updated American College of Cardiology/American Heart Association guidelines. The primary outcome was the risk of hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia.

The data analysis found that elevated BP was associated with an adjusted risk ratio (aRR) of 1.54 (95% confidence interval [CI], 1.18–2.02). Stage 1 hypertension was associated with an aRR of 2.16 (95% CI, 1.31–3.57). Compared with women whose BP had a downward systolic trajectory, women with normal BP and an upward systolic trajectory had a 41% increased risk of any hypertensive disorder of pregnancy (aRR, 1.41; 95% CI, 1.20–1.65).

Study strengths and limitations

While the large study population is a strength of this study, there are a number of limitations, such as the use of BP measurements during pregnancy only, without having pre-pregnancy measurements available. Further, a single BP measurement during each visit is also a drawback, although the standardized measurement by study staff is a strength.

Anticlimactic conclusions. The conclusions of the study, however, are either not surprising, not clinically meaningful, or of little value to clinicians at present, at least with respect to patient management.

Continue to: Conclusions that were not surprising included...

Conclusions that were not surprising included a statistically lower chance of indicated preterm delivery in the normal BP group than in the elevated BP or stage 1 hypertension groups. Conclusions that were not meaningful included a statistically significant lower birthweight in the elevated BP group (3,269 g) and in the stage 1 hypertension group (3,258 g) compared with the normal BP group (3,279 g), but the clinical significance of these differences is arguable.

Lastly is the issue of what these data mean for clinical practice. The idea of identifying high-risk groups is attractive, provided that there are effective intervention strategies available. If one follows the United States Preventive Services Task Force (USPSTF) recommendations for preeclampsia prevention,² then virtually every nulliparous woman is a candidate for low-dose aspirin for preeclampsia prophylaxis. Beyond that, the current data do not support any change in the standard clinical practice of managing these “now identified” high-risk women. Increasing prenatal visits, using biomarkers to further delineate risk, and using uterine artery Doppler studies are all strategies that have been or are being investigated, but as yet they are not supported by conclusive data documenting improved outcomes—a sentiment supported by both the USPSTF³ and the authors of the study.