Key clinical point: Palbociclib+endocrine therapy (ET) did not yield superior progression-free survival (PFS) vs. capecitabine in patients with aromatase inhibitor-resistant metastatic breast cancer (AIR-MBC) but was well tolerated and improved quality of life (QoL).

Major finding: Median PFS with palbociclib+fulvestrant vs. capecitabine was 7.5 vs. 10.0 months (adjusted hazard ratio [aHR], 1.13; P = .398). Palbociclib+ET did not show PFS superiority vs. capecitabine in patients with wild-type estrogen receptor-1 AIR-MBC (8.0 vs. 10.6 months; aHR, 1.11; P = .404). Palbociclib+ET was better tolerated and improved QoL (aHR, 0.67; P = .001).

Study details: Phase 3 PEARL trial randomly allocated postmenopausal women with AIR-MBC to receive either palbociclib+exemestane or capecitabine (n=296) or palbociclib+fulvestrant or capecitabine (n=305).

Disclosures: This study was supported by Pfizer and AstraZeneca and sponsored by GEICAM Spanish Breast Cancer Group. The lead author reported ties with AstraZeneca, Pfizer, Amgen, Taiho Oncology, Roche/Genentech, Novartis, PharmaMar, Eli Lilly, PUMA, and Daiichi-Sankyo. Other investigators reported owning stocks, being an employee, receiving support, and/or consulting for various pharmaceutical companies including Pfizer and AstraZeneca.

Source: Martin M et al. Ann Oncol. 2020 Dec 29. doi: 10.1016/j.annonc.2020.12.013.

Key clinical point: Palbociclib+endocrine therapy (ET) did not yield superior progression-free survival (PFS) vs. capecitabine in patients with aromatase inhibitor-resistant metastatic breast cancer (AIR-MBC) but was well tolerated and improved quality of life (QoL).

Major finding: Median PFS with palbociclib+fulvestrant vs. capecitabine was 7.5 vs. 10.0 months (adjusted hazard ratio [aHR], 1.13; P = .398). Palbociclib+ET did not show PFS superiority vs. capecitabine in patients with wild-type estrogen receptor-1 AIR-MBC (8.0 vs. 10.6 months; aHR, 1.11; P = .404). Palbociclib+ET was better tolerated and improved QoL (aHR, 0.67; P = .001).

Study details: Phase 3 PEARL trial randomly allocated postmenopausal women with AIR-MBC to receive either palbociclib+exemestane or capecitabine (n=296) or palbociclib+fulvestrant or capecitabine (n=305).

Disclosures: This study was supported by Pfizer and AstraZeneca and sponsored by GEICAM Spanish Breast Cancer Group. The lead author reported ties with AstraZeneca, Pfizer, Amgen, Taiho Oncology, Roche/Genentech, Novartis, PharmaMar, Eli Lilly, PUMA, and Daiichi-Sankyo. Other investigators reported owning stocks, being an employee, receiving support, and/or consulting for various pharmaceutical companies including Pfizer and AstraZeneca.

Source: Martin M et al. Ann Oncol. 2020 Dec 29. doi: 10.1016/j.annonc.2020.12.013.

Key clinical point: Palbociclib+endocrine therapy (ET) did not yield superior progression-free survival (PFS) vs. capecitabine in patients with aromatase inhibitor-resistant metastatic breast cancer (AIR-MBC) but was well tolerated and improved quality of life (QoL).

Major finding: Median PFS with palbociclib+fulvestrant vs. capecitabine was 7.5 vs. 10.0 months (adjusted hazard ratio [aHR], 1.13; P = .398). Palbociclib+ET did not show PFS superiority vs. capecitabine in patients with wild-type estrogen receptor-1 AIR-MBC (8.0 vs. 10.6 months; aHR, 1.11; P = .404). Palbociclib+ET was better tolerated and improved QoL (aHR, 0.67; P = .001).

Study details: Phase 3 PEARL trial randomly allocated postmenopausal women with AIR-MBC to receive either palbociclib+exemestane or capecitabine (n=296) or palbociclib+fulvestrant or capecitabine (n=305).

Disclosures: This study was supported by Pfizer and AstraZeneca and sponsored by GEICAM Spanish Breast Cancer Group. The lead author reported ties with AstraZeneca, Pfizer, Amgen, Taiho Oncology, Roche/Genentech, Novartis, PharmaMar, Eli Lilly, PUMA, and Daiichi-Sankyo. Other investigators reported owning stocks, being an employee, receiving support, and/or consulting for various pharmaceutical companies including Pfizer and AstraZeneca.

Source: Martin M et al. Ann Oncol. 2020 Dec 29. doi: 10.1016/j.annonc.2020.12.013.

Key clinical point: Incidence of brain metastases is high in patients with human epidermal growth factor receptor 2-positive (HER2+) and triple-negative metastatic breast cancer (MBC), highlighting the need for relevant screening in these high-risk populations.

Major finding: The pooled cumulative incidence of brain metastases in patients with HER2+ and triple-negative MBC was 31% (interquartile range [IQR], 24.0-34.0) and 32% (IQR,18.5-40.6) during a median follow-up of 30.7 and 32.8 months, respectively. The incidence of brain metastases per patient-year was 13% for HER2+ and triple negative MBC.

Study details: Meta-analysis of 25 studies including patients with HER2+ MBC (n=5,971), triple-negative (n=4,102), and hormone receptor+/HER2− MBC (n=14,656).

Disclosures: This study did not receive any funding. The lead author reported no disclosures. Some of his coinvestigators reported ties with various pharmaceutical companies.

Source: Kuksis M et al. Neuro Oncol. 2020 Dec 23. doi: 10.1093/neuonc/noaa285.

Key clinical point: Incidence of brain metastases is high in patients with human epidermal growth factor receptor 2-positive (HER2+) and triple-negative metastatic breast cancer (MBC), highlighting the need for relevant screening in these high-risk populations.

Major finding: The pooled cumulative incidence of brain metastases in patients with HER2+ and triple-negative MBC was 31% (interquartile range [IQR], 24.0-34.0) and 32% (IQR,18.5-40.6) during a median follow-up of 30.7 and 32.8 months, respectively. The incidence of brain metastases per patient-year was 13% for HER2+ and triple negative MBC.

Study details: Meta-analysis of 25 studies including patients with HER2+ MBC (n=5,971), triple-negative (n=4,102), and hormone receptor+/HER2− MBC (n=14,656).

Disclosures: This study did not receive any funding. The lead author reported no disclosures. Some of his coinvestigators reported ties with various pharmaceutical companies.

Source: Kuksis M et al. Neuro Oncol. 2020 Dec 23. doi: 10.1093/neuonc/noaa285.

Key clinical point: Incidence of brain metastases is high in patients with human epidermal growth factor receptor 2-positive (HER2+) and triple-negative metastatic breast cancer (MBC), highlighting the need for relevant screening in these high-risk populations.

Major finding: The pooled cumulative incidence of brain metastases in patients with HER2+ and triple-negative MBC was 31% (interquartile range [IQR], 24.0-34.0) and 32% (IQR,18.5-40.6) during a median follow-up of 30.7 and 32.8 months, respectively. The incidence of brain metastases per patient-year was 13% for HER2+ and triple negative MBC.

Study details: Meta-analysis of 25 studies including patients with HER2+ MBC (n=5,971), triple-negative (n=4,102), and hormone receptor+/HER2− MBC (n=14,656).

Disclosures: This study did not receive any funding. The lead author reported no disclosures. Some of his coinvestigators reported ties with various pharmaceutical companies.

Source: Kuksis M et al. Neuro Oncol. 2020 Dec 23. doi: 10.1093/neuonc/noaa285.

Key clinical point: Rates of ipsilateral breast tumor recurrence (IBTR) were similar between partial breast irradiation (PBI) and whole breast irradiation (WBI). Acute skin toxicities were lower with PBI.

Major finding: The rate of IBTR at 5 years was not different between PBI (1.8%; 95% highest posterior density [HPD], 0.68%-3.2%) and WBI (1.7%; 95% HPD, 0.92%-2.4%). Rates of grade 2 or greater acute skin toxicity were lower with PBI (7.1%; 95% HPD, 0%-63.4%) vs. WBI (47.5%; 95% HPD, 0%-93.4%).

Study details: Meta-analysis of 7 randomized trials including 9,758 patients receiving either WBI (n=4,840) or PBI (n=4,918).

Disclosures: No funding source was identified. The lead author reported ties with Impedimed, PreludeDX, Varian Medical Systems, and Vision RT. Some other coinvestigators reported receiving grants or consultation fees from various pharmaceutical companies.

Source: Shah C et al. Ann Surg Oncol. 2021 Jan 3. doi: 10.1245/s10434-020-09447-w.

Key clinical point: Rates of ipsilateral breast tumor recurrence (IBTR) were similar between partial breast irradiation (PBI) and whole breast irradiation (WBI). Acute skin toxicities were lower with PBI.

Major finding: The rate of IBTR at 5 years was not different between PBI (1.8%; 95% highest posterior density [HPD], 0.68%-3.2%) and WBI (1.7%; 95% HPD, 0.92%-2.4%). Rates of grade 2 or greater acute skin toxicity were lower with PBI (7.1%; 95% HPD, 0%-63.4%) vs. WBI (47.5%; 95% HPD, 0%-93.4%).

Study details: Meta-analysis of 7 randomized trials including 9,758 patients receiving either WBI (n=4,840) or PBI (n=4,918).

Disclosures: No funding source was identified. The lead author reported ties with Impedimed, PreludeDX, Varian Medical Systems, and Vision RT. Some other coinvestigators reported receiving grants or consultation fees from various pharmaceutical companies.

Source: Shah C et al. Ann Surg Oncol. 2021 Jan 3. doi: 10.1245/s10434-020-09447-w.

Key clinical point: Rates of ipsilateral breast tumor recurrence (IBTR) were similar between partial breast irradiation (PBI) and whole breast irradiation (WBI). Acute skin toxicities were lower with PBI.

Major finding: The rate of IBTR at 5 years was not different between PBI (1.8%; 95% highest posterior density [HPD], 0.68%-3.2%) and WBI (1.7%; 95% HPD, 0.92%-2.4%). Rates of grade 2 or greater acute skin toxicity were lower with PBI (7.1%; 95% HPD, 0%-63.4%) vs. WBI (47.5%; 95% HPD, 0%-93.4%).

Study details: Meta-analysis of 7 randomized trials including 9,758 patients receiving either WBI (n=4,840) or PBI (n=4,918).

Disclosures: No funding source was identified. The lead author reported ties with Impedimed, PreludeDX, Varian Medical Systems, and Vision RT. Some other coinvestigators reported receiving grants or consultation fees from various pharmaceutical companies.

Source: Shah C et al. Ann Surg Oncol. 2021 Jan 3. doi: 10.1245/s10434-020-09447-w.

Significant racial and ethnic differences in diagnostic imaging rates exist among children receiving care in pediatric EDs across the United States, Jennifer R. Marin, MD, of the University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, and associates reported.

Specifically, visits with non-Hispanic Black and Hispanic patients less frequently included radiography, CT, ultrasonography, and MRI than those of non-Hispanic White patients. The findings persisted across most diagnostic groups, even when stratified according to insurance type, Dr. Marin and colleagues reported in a multicenter cross-sectional study in JAMA Network Open.

The authors collected administrative data from the Pediatric Health Information System on 44 tertiary care children’s hospitals in 17 major metropolitan areas across the United States. They evaluated a total of 13,087,522 ED visits by 6,230,911 patients that occurred between Jan. 1, 2016, and Dec. 31, 2019. Of these, 28.2% included at least one imaging study. Altogether, 33.5% were performed on non-Hispanic White children, compared with just 24.1% of non-Hispanic Black children (adjusted odds ratio, 0.82) and 26.1% of Hispanic children (aOR, 0.87). After adjusting for relevant confounding factors, non-Hispanic Black and Hispanic children were less likely to have any imaging at all during their visits.

“Our findings suggest that a child’s race and ethnicity may be independently associated with the decision to perform imaging during ED visits,” Dr. Marin and associates said, adding that “the differential use of diagnostic imaging by race/ethnicity may reflect underuse of imaging in non-Hispanic Black and Hispanic children, or alternatively, overuse in non-Hispanic White children.”
 

Overuse vs. underuse: Racial bias or parental anxiety?

Overuse of imaging carries its own risks, but underuse can lead to misdiagnosis, the need for additional care, and possibly worse outcomes in the long run, Dr. Marin and colleagues explained. “Although we were unable to discern underuse from overuse using an administrative database, it is likely that much of the imaging in White children is unnecessary.”

Higher parental anxiety was just one of the explanations the authors offered for excessive imaging in White children. Especially in cases of diagnostic imaging for head trauma, one survey of adult ED patients showed that the peace of mind CT offers with its more definitive diagnosis was worth the additional possible risk of radiation.

Language barriers in non–English-speaking patients may also affect likelihood of testing as part of an ED visit.

Implicit physician racial bias, which can be amplified under the stress of working in an ED, can affect patient interactions, treatment decisions and adherence, and ultimately overall health outcomes, the authors noted. The goal in ensuring parity is to routinely follow clinical guidelines and use objective scoring tools that minimize subjectivity. At the institutional level, internal quality assurance evaluations go a long way toward understanding and limiting bias.

Historically, White patients are more likely than minority patients to have a medical home, which can influence whether ED physicians order imaging studies and whether imaging of White patients may have been triggered by a primary care physician referral, Dr. Marin and associates said.

In an accompanying editorial, Anupam B. Kharbanda, MD, said these findings are “consistent with decades of previous research documenting inequalities in health care delivery ... [and] must be examined in the context of inequities within the social framework of a community.”
 

Going back to the drawing board

“Physicians, researchers, and health care leaders must partner with the communities they serve to develop and implement interventions to address these substantial inequities in care,” said Dr. Kharbanda, pediatric emergency medicine physician at Children’s Minnesota Hospital, Minneapolis. As previous studies have demonstrated, implicit bias and antiracism training are needed to help physicians develop empathy so they are better equipped to help patients and families in a multicultural environment. Partnering with community-based organizations to ensure that care is more community centered, as has been done successfully within the Kaiser Permanente health system, for example, and employing a more diverse workforce that mirrors the populations cared for will go a long way.

Citing a 1966 speech of the late Dr. Martin Luther King, Jr., in which he said: “Of all the forms of inequality, injustice in health care is the most shocking and inhumane,” Dr. Kharbanda urged clinicians to not only hear but believe these words and act on them by working in partnerships with the communities they serve.

In a separate interview, Walter Palmer, MD, pediatric emergency medicine fellow at Children’s National Medical Center, Washington, noted: “This study’s findings are disappointing and yet not at all unexpected, as the authors convincingly identify yet another step at which patients of color are treated unequally in the U.S. health care system. It highlights a frightening truth: That we are all at risk of letting invisible implicit biases impact our clinical decision-making process. This is especially true in the busy emergency department environment, where pressure to make swift decisions regarding diagnostic workup and management invites the influence of imperceptible biases. It is now incumbent upon us as health care providers to monitor our personal and departmental patterns of practice for areas in which we can improve racial health equity and become advocates for the children and families who entrust us with their care.”

The authors reported multiple financial disclosures. Dr. Kharbanda and Dr. Palmer had no conflicts of interest and reported no disclosures.

Significant racial and ethnic differences in diagnostic imaging rates exist among children receiving care in pediatric EDs across the United States, Jennifer R. Marin, MD, of the University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, and associates reported.

Specifically, visits with non-Hispanic Black and Hispanic patients less frequently included radiography, CT, ultrasonography, and MRI than those of non-Hispanic White patients. The findings persisted across most diagnostic groups, even when stratified according to insurance type, Dr. Marin and colleagues reported in a multicenter cross-sectional study in JAMA Network Open.

The authors collected administrative data from the Pediatric Health Information System on 44 tertiary care children’s hospitals in 17 major metropolitan areas across the United States. They evaluated a total of 13,087,522 ED visits by 6,230,911 patients that occurred between Jan. 1, 2016, and Dec. 31, 2019. Of these, 28.2% included at least one imaging study. Altogether, 33.5% were performed on non-Hispanic White children, compared with just 24.1% of non-Hispanic Black children (adjusted odds ratio, 0.82) and 26.1% of Hispanic children (aOR, 0.87). After adjusting for relevant confounding factors, non-Hispanic Black and Hispanic children were less likely to have any imaging at all during their visits.

“Our findings suggest that a child’s race and ethnicity may be independently associated with the decision to perform imaging during ED visits,” Dr. Marin and associates said, adding that “the differential use of diagnostic imaging by race/ethnicity may reflect underuse of imaging in non-Hispanic Black and Hispanic children, or alternatively, overuse in non-Hispanic White children.”
 

Overuse vs. underuse: Racial bias or parental anxiety?

Overuse of imaging carries its own risks, but underuse can lead to misdiagnosis, the need for additional care, and possibly worse outcomes in the long run, Dr. Marin and colleagues explained. “Although we were unable to discern underuse from overuse using an administrative database, it is likely that much of the imaging in White children is unnecessary.”

Higher parental anxiety was just one of the explanations the authors offered for excessive imaging in White children. Especially in cases of diagnostic imaging for head trauma, one survey of adult ED patients showed that the peace of mind CT offers with its more definitive diagnosis was worth the additional possible risk of radiation.

Language barriers in non–English-speaking patients may also affect likelihood of testing as part of an ED visit.

Implicit physician racial bias, which can be amplified under the stress of working in an ED, can affect patient interactions, treatment decisions and adherence, and ultimately overall health outcomes, the authors noted. The goal in ensuring parity is to routinely follow clinical guidelines and use objective scoring tools that minimize subjectivity. At the institutional level, internal quality assurance evaluations go a long way toward understanding and limiting bias.

Historically, White patients are more likely than minority patients to have a medical home, which can influence whether ED physicians order imaging studies and whether imaging of White patients may have been triggered by a primary care physician referral, Dr. Marin and associates said.

In an accompanying editorial, Anupam B. Kharbanda, MD, said these findings are “consistent with decades of previous research documenting inequalities in health care delivery ... [and] must be examined in the context of inequities within the social framework of a community.”
 

Going back to the drawing board

“Physicians, researchers, and health care leaders must partner with the communities they serve to develop and implement interventions to address these substantial inequities in care,” said Dr. Kharbanda, pediatric emergency medicine physician at Children’s Minnesota Hospital, Minneapolis. As previous studies have demonstrated, implicit bias and antiracism training are needed to help physicians develop empathy so they are better equipped to help patients and families in a multicultural environment. Partnering with community-based organizations to ensure that care is more community centered, as has been done successfully within the Kaiser Permanente health system, for example, and employing a more diverse workforce that mirrors the populations cared for will go a long way.

Citing a 1966 speech of the late Dr. Martin Luther King, Jr., in which he said: “Of all the forms of inequality, injustice in health care is the most shocking and inhumane,” Dr. Kharbanda urged clinicians to not only hear but believe these words and act on them by working in partnerships with the communities they serve.

In a separate interview, Walter Palmer, MD, pediatric emergency medicine fellow at Children’s National Medical Center, Washington, noted: “This study’s findings are disappointing and yet not at all unexpected, as the authors convincingly identify yet another step at which patients of color are treated unequally in the U.S. health care system. It highlights a frightening truth: That we are all at risk of letting invisible implicit biases impact our clinical decision-making process. This is especially true in the busy emergency department environment, where pressure to make swift decisions regarding diagnostic workup and management invites the influence of imperceptible biases. It is now incumbent upon us as health care providers to monitor our personal and departmental patterns of practice for areas in which we can improve racial health equity and become advocates for the children and families who entrust us with their care.”

The authors reported multiple financial disclosures. Dr. Kharbanda and Dr. Palmer had no conflicts of interest and reported no disclosures.

Significant racial and ethnic differences in diagnostic imaging rates exist among children receiving care in pediatric EDs across the United States, Jennifer R. Marin, MD, of the University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh, and associates reported.

Specifically, visits with non-Hispanic Black and Hispanic patients less frequently included radiography, CT, ultrasonography, and MRI than those of non-Hispanic White patients. The findings persisted across most diagnostic groups, even when stratified according to insurance type, Dr. Marin and colleagues reported in a multicenter cross-sectional study in JAMA Network Open.

The authors collected administrative data from the Pediatric Health Information System on 44 tertiary care children’s hospitals in 17 major metropolitan areas across the United States. They evaluated a total of 13,087,522 ED visits by 6,230,911 patients that occurred between Jan. 1, 2016, and Dec. 31, 2019. Of these, 28.2% included at least one imaging study. Altogether, 33.5% were performed on non-Hispanic White children, compared with just 24.1% of non-Hispanic Black children (adjusted odds ratio, 0.82) and 26.1% of Hispanic children (aOR, 0.87). After adjusting for relevant confounding factors, non-Hispanic Black and Hispanic children were less likely to have any imaging at all during their visits.

“Our findings suggest that a child’s race and ethnicity may be independently associated with the decision to perform imaging during ED visits,” Dr. Marin and associates said, adding that “the differential use of diagnostic imaging by race/ethnicity may reflect underuse of imaging in non-Hispanic Black and Hispanic children, or alternatively, overuse in non-Hispanic White children.”
 

Overuse vs. underuse: Racial bias or parental anxiety?

Overuse of imaging carries its own risks, but underuse can lead to misdiagnosis, the need for additional care, and possibly worse outcomes in the long run, Dr. Marin and colleagues explained. “Although we were unable to discern underuse from overuse using an administrative database, it is likely that much of the imaging in White children is unnecessary.”

Higher parental anxiety was just one of the explanations the authors offered for excessive imaging in White children. Especially in cases of diagnostic imaging for head trauma, one survey of adult ED patients showed that the peace of mind CT offers with its more definitive diagnosis was worth the additional possible risk of radiation.

Language barriers in non–English-speaking patients may also affect likelihood of testing as part of an ED visit.

Implicit physician racial bias, which can be amplified under the stress of working in an ED, can affect patient interactions, treatment decisions and adherence, and ultimately overall health outcomes, the authors noted. The goal in ensuring parity is to routinely follow clinical guidelines and use objective scoring tools that minimize subjectivity. At the institutional level, internal quality assurance evaluations go a long way toward understanding and limiting bias.

Historically, White patients are more likely than minority patients to have a medical home, which can influence whether ED physicians order imaging studies and whether imaging of White patients may have been triggered by a primary care physician referral, Dr. Marin and associates said.

In an accompanying editorial, Anupam B. Kharbanda, MD, said these findings are “consistent with decades of previous research documenting inequalities in health care delivery ... [and] must be examined in the context of inequities within the social framework of a community.”
 

Going back to the drawing board

“Physicians, researchers, and health care leaders must partner with the communities they serve to develop and implement interventions to address these substantial inequities in care,” said Dr. Kharbanda, pediatric emergency medicine physician at Children’s Minnesota Hospital, Minneapolis. As previous studies have demonstrated, implicit bias and antiracism training are needed to help physicians develop empathy so they are better equipped to help patients and families in a multicultural environment. Partnering with community-based organizations to ensure that care is more community centered, as has been done successfully within the Kaiser Permanente health system, for example, and employing a more diverse workforce that mirrors the populations cared for will go a long way.

Citing a 1966 speech of the late Dr. Martin Luther King, Jr., in which he said: “Of all the forms of inequality, injustice in health care is the most shocking and inhumane,” Dr. Kharbanda urged clinicians to not only hear but believe these words and act on them by working in partnerships with the communities they serve.

In a separate interview, Walter Palmer, MD, pediatric emergency medicine fellow at Children’s National Medical Center, Washington, noted: “This study’s findings are disappointing and yet not at all unexpected, as the authors convincingly identify yet another step at which patients of color are treated unequally in the U.S. health care system. It highlights a frightening truth: That we are all at risk of letting invisible implicit biases impact our clinical decision-making process. This is especially true in the busy emergency department environment, where pressure to make swift decisions regarding diagnostic workup and management invites the influence of imperceptible biases. It is now incumbent upon us as health care providers to monitor our personal and departmental patterns of practice for areas in which we can improve racial health equity and become advocates for the children and families who entrust us with their care.”

The authors reported multiple financial disclosures. Dr. Kharbanda and Dr. Palmer had no conflicts of interest and reported no disclosures.

Multiple sclerosis (MS) may not pose a higher risk for complications in pregnant women, according to a new study published online Feb. 3 in Neurology Clinical Practice. While pregnancy and childbirth are not regarded as conditions that engender high-risk pregnancy in the MS population, previous studies evaluating the effects of MS on pregnancy and parturition have yet to fully elucidate some outcomes for pregnant women and their babies in multiple sclerosis.

“Women with multiple sclerosis may be understandably concerned about the risk of pregnancy,” said Melinda Magyari, MD, PhD, a consultant at the University of Copenhagen. “While previous research has shown there is no higher risk of birth defect for babies born to women with MS, we wanted to find out if women with MS are at risk for a variety of pregnancy complications.”

MS is regarded as a progressive, neurological disease mediated by the immune system that demands careful consideration of numerous situations and life changes including family planning. The MS population is overwhelmingly female, as women account for three out of every four cases of MS. The majority of these women range from 20 to 40 years of age at the time of being diagnosed with MS. Despite the unknown risks of pregnancy-related complications and various perinatal complications in this patient population, women who have MS are not discouraged from conceiving.
 

Assessing pregnancy outcomes

This nationwide, population-based, cross-sectional study evaluated the pregnancies of 2,930 women with MS between Jan. 1, 1997, and Dec. 31, 2016, registered in the Danish Multiple Sclerosis Registry. The researchers compared pregnancy-related and prenatal outcomes to a 5% random sample of 56,958 randomly-selected pregnant women from Denmark’s general population who did not have MS. They found no differences in the risks associated with several pregnancy-related complications (e.g., preeclampsia, gestational diabetes, or placental complications), emergency Cesarean section (C-section), instrumental delivery, stillbirth, preterm birth, or congenital malformation. Apgar scores were low in both groups. A composite of various biometrics in newborns such as reflexes, muscle tone, and heart rate immediately following birth, the Apgar score is used to help assess the neonatal health, with a value of less than 7 considered low. Here, preterm birth is defined as delivery occurring before 37 weeks of gestation, and stillbirth describes a fetus born dead after 22 weeks of gestation.

Women in the MS cohort were more likely to have elective C-sections (odds ratio, 2.89 [95% confidence interval, 1.65-2.16]), induced labor (OR, 1.15 [95%CI, 1.01-1.31]) and have babies with low birth weight based on their gestational age (OR, 1.29 [95% CI, 1.04-1.60]). Nearly 30% of babies born in the cohort (n = 851) were born to mothers who had received disease-modifying therapy (DMT). Neonates exposed to DMT weighed an average of 116 g less than babies born to mothers who had not received DMT (3,378 g vs. 3,494 g) with a slightly lower gestational age (39 weeks as opposed to 40 weeks). However, babies born to mothers with MS were less likely to show signs of asphyxia (OR, 0.87 [95% CI, 0.78-0.97]) than the comparison cohort.

“We found overall, their pregnancies were just as healthy as those of the moms without MS,” Dr. Magyari said.
 

Comprehensive data

Denmark’s health care system has two key features that make it an attractive setting in which to conduct such a study – the first being its universal health care. The second advantage is that the country enacted several health registries in the 1970s and 1980s that enable the collection of more comprehensive data. For example, the Danish National Patient Register is a population-based registry that spans the entire nation, facilitating epidemiological research with what the study’s authors describe as “high generalizability.” Providing additional insights regarding the patient story helps add context to pregnancy and outcomes. Among the data collected on the women studied were demographics, contact information, and abortions, both spontaneous and medically induced. The country uses other databases and registries to capture additional data. For example, the Register of Legally Induced Abortions provides data regarding the context of medically induced abortions. In contrast, the Danish Medical Birth Registry provides context regarding specified variables regarding women’s pregnancies, delivery, and perinatal outcomes. Finally, the population’s education register offers information regarding patients’ educational history.

A key strength of this study is that the long duration of follow-up data from the Danish Medical Birth Registry, along with its comprehensive data collection, eliminates recall bias. Universal access to health care also improves the generalizability of data. A limitation of the study is its lack of data on maternal smoking and its effects on low gestational weights. The study also has some data gaps, including body mass index information missing from a large portion of the cohort. Finally, the sample size of newborns born to mothers who had received DMT therapy within the last 6 months of gestation was too underpowered to stratify based on first on first-line or second-line treatment.

Dr. Magyari served on scientific advisory boards for Biogen, Sanofi, Teva, Roche, Novartis, and Merck. She has also received honoraria for lecturing from Biogen, Merck, Novartis, Sanofi, Genzyme, and has received research support and support for congress participation from Biogen, Genzyme, Teva, Roche, Merck, and Novartis. Coauthors disclosed various fees received from Merck, Novartis, Biogen, Roche, Sanofi Genzyme, and Teva.

Multiple sclerosis (MS) may not pose a higher risk for complications in pregnant women, according to a new study published online Feb. 3 in Neurology Clinical Practice. While pregnancy and childbirth are not regarded as conditions that engender high-risk pregnancy in the MS population, previous studies evaluating the effects of MS on pregnancy and parturition have yet to fully elucidate some outcomes for pregnant women and their babies in multiple sclerosis.

“Women with multiple sclerosis may be understandably concerned about the risk of pregnancy,” said Melinda Magyari, MD, PhD, a consultant at the University of Copenhagen. “While previous research has shown there is no higher risk of birth defect for babies born to women with MS, we wanted to find out if women with MS are at risk for a variety of pregnancy complications.”

MS is regarded as a progressive, neurological disease mediated by the immune system that demands careful consideration of numerous situations and life changes including family planning. The MS population is overwhelmingly female, as women account for three out of every four cases of MS. The majority of these women range from 20 to 40 years of age at the time of being diagnosed with MS. Despite the unknown risks of pregnancy-related complications and various perinatal complications in this patient population, women who have MS are not discouraged from conceiving.
 

Assessing pregnancy outcomes

This nationwide, population-based, cross-sectional study evaluated the pregnancies of 2,930 women with MS between Jan. 1, 1997, and Dec. 31, 2016, registered in the Danish Multiple Sclerosis Registry. The researchers compared pregnancy-related and prenatal outcomes to a 5% random sample of 56,958 randomly-selected pregnant women from Denmark’s general population who did not have MS. They found no differences in the risks associated with several pregnancy-related complications (e.g., preeclampsia, gestational diabetes, or placental complications), emergency Cesarean section (C-section), instrumental delivery, stillbirth, preterm birth, or congenital malformation. Apgar scores were low in both groups. A composite of various biometrics in newborns such as reflexes, muscle tone, and heart rate immediately following birth, the Apgar score is used to help assess the neonatal health, with a value of less than 7 considered low. Here, preterm birth is defined as delivery occurring before 37 weeks of gestation, and stillbirth describes a fetus born dead after 22 weeks of gestation.

Women in the MS cohort were more likely to have elective C-sections (odds ratio, 2.89 [95% confidence interval, 1.65-2.16]), induced labor (OR, 1.15 [95%CI, 1.01-1.31]) and have babies with low birth weight based on their gestational age (OR, 1.29 [95% CI, 1.04-1.60]). Nearly 30% of babies born in the cohort (n = 851) were born to mothers who had received disease-modifying therapy (DMT). Neonates exposed to DMT weighed an average of 116 g less than babies born to mothers who had not received DMT (3,378 g vs. 3,494 g) with a slightly lower gestational age (39 weeks as opposed to 40 weeks). However, babies born to mothers with MS were less likely to show signs of asphyxia (OR, 0.87 [95% CI, 0.78-0.97]) than the comparison cohort.

“We found overall, their pregnancies were just as healthy as those of the moms without MS,” Dr. Magyari said.
 

Comprehensive data

Denmark’s health care system has two key features that make it an attractive setting in which to conduct such a study – the first being its universal health care. The second advantage is that the country enacted several health registries in the 1970s and 1980s that enable the collection of more comprehensive data. For example, the Danish National Patient Register is a population-based registry that spans the entire nation, facilitating epidemiological research with what the study’s authors describe as “high generalizability.” Providing additional insights regarding the patient story helps add context to pregnancy and outcomes. Among the data collected on the women studied were demographics, contact information, and abortions, both spontaneous and medically induced. The country uses other databases and registries to capture additional data. For example, the Register of Legally Induced Abortions provides data regarding the context of medically induced abortions. In contrast, the Danish Medical Birth Registry provides context regarding specified variables regarding women’s pregnancies, delivery, and perinatal outcomes. Finally, the population’s education register offers information regarding patients’ educational history.

A key strength of this study is that the long duration of follow-up data from the Danish Medical Birth Registry, along with its comprehensive data collection, eliminates recall bias. Universal access to health care also improves the generalizability of data. A limitation of the study is its lack of data on maternal smoking and its effects on low gestational weights. The study also has some data gaps, including body mass index information missing from a large portion of the cohort. Finally, the sample size of newborns born to mothers who had received DMT therapy within the last 6 months of gestation was too underpowered to stratify based on first on first-line or second-line treatment.

Dr. Magyari served on scientific advisory boards for Biogen, Sanofi, Teva, Roche, Novartis, and Merck. She has also received honoraria for lecturing from Biogen, Merck, Novartis, Sanofi, Genzyme, and has received research support and support for congress participation from Biogen, Genzyme, Teva, Roche, Merck, and Novartis. Coauthors disclosed various fees received from Merck, Novartis, Biogen, Roche, Sanofi Genzyme, and Teva.

Multiple sclerosis (MS) may not pose a higher risk for complications in pregnant women, according to a new study published online Feb. 3 in Neurology Clinical Practice. While pregnancy and childbirth are not regarded as conditions that engender high-risk pregnancy in the MS population, previous studies evaluating the effects of MS on pregnancy and parturition have yet to fully elucidate some outcomes for pregnant women and their babies in multiple sclerosis.

“Women with multiple sclerosis may be understandably concerned about the risk of pregnancy,” said Melinda Magyari, MD, PhD, a consultant at the University of Copenhagen. “While previous research has shown there is no higher risk of birth defect for babies born to women with MS, we wanted to find out if women with MS are at risk for a variety of pregnancy complications.”

MS is regarded as a progressive, neurological disease mediated by the immune system that demands careful consideration of numerous situations and life changes including family planning. The MS population is overwhelmingly female, as women account for three out of every four cases of MS. The majority of these women range from 20 to 40 years of age at the time of being diagnosed with MS. Despite the unknown risks of pregnancy-related complications and various perinatal complications in this patient population, women who have MS are not discouraged from conceiving.
 

Assessing pregnancy outcomes

This nationwide, population-based, cross-sectional study evaluated the pregnancies of 2,930 women with MS between Jan. 1, 1997, and Dec. 31, 2016, registered in the Danish Multiple Sclerosis Registry. The researchers compared pregnancy-related and prenatal outcomes to a 5% random sample of 56,958 randomly-selected pregnant women from Denmark’s general population who did not have MS. They found no differences in the risks associated with several pregnancy-related complications (e.g., preeclampsia, gestational diabetes, or placental complications), emergency Cesarean section (C-section), instrumental delivery, stillbirth, preterm birth, or congenital malformation. Apgar scores were low in both groups. A composite of various biometrics in newborns such as reflexes, muscle tone, and heart rate immediately following birth, the Apgar score is used to help assess the neonatal health, with a value of less than 7 considered low. Here, preterm birth is defined as delivery occurring before 37 weeks of gestation, and stillbirth describes a fetus born dead after 22 weeks of gestation.

Women in the MS cohort were more likely to have elective C-sections (odds ratio, 2.89 [95% confidence interval, 1.65-2.16]), induced labor (OR, 1.15 [95%CI, 1.01-1.31]) and have babies with low birth weight based on their gestational age (OR, 1.29 [95% CI, 1.04-1.60]). Nearly 30% of babies born in the cohort (n = 851) were born to mothers who had received disease-modifying therapy (DMT). Neonates exposed to DMT weighed an average of 116 g less than babies born to mothers who had not received DMT (3,378 g vs. 3,494 g) with a slightly lower gestational age (39 weeks as opposed to 40 weeks). However, babies born to mothers with MS were less likely to show signs of asphyxia (OR, 0.87 [95% CI, 0.78-0.97]) than the comparison cohort.

“We found overall, their pregnancies were just as healthy as those of the moms without MS,” Dr. Magyari said.
 

Comprehensive data

Denmark’s health care system has two key features that make it an attractive setting in which to conduct such a study – the first being its universal health care. The second advantage is that the country enacted several health registries in the 1970s and 1980s that enable the collection of more comprehensive data. For example, the Danish National Patient Register is a population-based registry that spans the entire nation, facilitating epidemiological research with what the study’s authors describe as “high generalizability.” Providing additional insights regarding the patient story helps add context to pregnancy and outcomes. Among the data collected on the women studied were demographics, contact information, and abortions, both spontaneous and medically induced. The country uses other databases and registries to capture additional data. For example, the Register of Legally Induced Abortions provides data regarding the context of medically induced abortions. In contrast, the Danish Medical Birth Registry provides context regarding specified variables regarding women’s pregnancies, delivery, and perinatal outcomes. Finally, the population’s education register offers information regarding patients’ educational history.

A key strength of this study is that the long duration of follow-up data from the Danish Medical Birth Registry, along with its comprehensive data collection, eliminates recall bias. Universal access to health care also improves the generalizability of data. A limitation of the study is its lack of data on maternal smoking and its effects on low gestational weights. The study also has some data gaps, including body mass index information missing from a large portion of the cohort. Finally, the sample size of newborns born to mothers who had received DMT therapy within the last 6 months of gestation was too underpowered to stratify based on first on first-line or second-line treatment.

Dr. Magyari served on scientific advisory boards for Biogen, Sanofi, Teva, Roche, Novartis, and Merck. She has also received honoraria for lecturing from Biogen, Merck, Novartis, Sanofi, Genzyme, and has received research support and support for congress participation from Biogen, Genzyme, Teva, Roche, Merck, and Novartis. Coauthors disclosed various fees received from Merck, Novartis, Biogen, Roche, Sanofi Genzyme, and Teva.

When many people across the country, not to mention in public office, believe that the world is run by a group of Satanic pedophiles that includes top Democrats and Hollywood elites, and that former President Trump is leading a secret mission to bring these evildoers to justice, one can’t help but ask if they’re at least to some degree mentally impaired.

Conspiracy theories are often received with psychiatric connotations; associated with paranoid plan-hatchers, and nonbelieving outsiders. But whereas theories such as QAnon strain credibility for many people, we would argue that they are likely not the product of psychosis or mental illness; nor do conspiracy theories in general represent delusions.

For one thing, surveys have consistently revealed that about 50% of the population believes in at least one conspiracy theory. Furthermore, there are several substantive differences between conspiracy theory beliefs and delusions.

Some researchers consider conspiracy theories to be “a subset of false beliefs,” but  most scholars, ourselves included, do not prejudge their validity or veracity. Real-life conspiracies, such as the CIA’s MK-Ultra program, have clearly occurred throughout history.

Our central contention is that belief in conspiracy theories is distinct from psychosis, and more closely resembles extreme but subculturally sanctioned religious or political beliefs. However, the line between believing in conspiracies and being delusional becomes blurred when the believer becomes part of the conspiracy theory and feels compelled to act on the belief as part of a personal mission.

Take Edgar Maddison Welch, a 28-year-old man who firmly believed the so-called “Pizzagate” conspiracy theory – the baseless claim that Hillary Clinton and Democratic elites were running a child sex-trafficking ring out of a Washington, DC, pizzeria. Seeing himself a potential savior of children, Mr. Welch drove 350 miles to the pizza shop from his home in North Carolina in December 2016 and fired three shots from an AR-15 style rifle into a locked closet door, ultimately surrendering to police. However, on questioning he quickly conceded, “The intel on this wasn’t 100%.”

Who believes in conspiracy theories?

Given that half the population believes in at least one conspiracy theory, it should come as little surprise that there is no reliable “profile” for believers. Although some studies have suggested associations with low education, right-wing political orientation, and certain personality traits like subclinical paranoia and schizotypy, such findings have been inconsistent and may vary across specific conspiracy theory. Associations between conspiracy belief and paranoia suggest overlap within a “conspiratorial mindset,” with recent evidence that “distrust of officialdom” is a key mediator between believing in conspiracies and political ideology.

Other quantitative “cognitive quirks” reported in those who believe in conspiracies are a need for certainty and control, a need for uniqueness, illusory pattern perception, and lack of analytical thinking. It’s unclear which of these factors may represent universal cognitive explanations for conspiratorial beliefs, vs. those that might be related to specific beliefs, such as the need for certainty during times of crisis and societal upheaval, when conspiracy theories tend to flourish.

Much of the research on conspiracy theory belief is based on the questionable premise that it’s best understood at the level of the individual’s psychopathology, or the “deficit model,” as it’s called. One of us (JMP) has instead proposed a two-component model that includes social and informational contexts. The first component – epistemic mistrust – involves mistrusting conventional, “authoritative” knowledge. The second involves biased information processing and exposure to misinformation, often transmitted by word of mouth, or through social networks. With this model, believing in conspiracy theories could be conceived as involving “delusion-like beliefs,” but not frank psychosis or full-blown delusions, as one might see, for example, in schizophrenia.

Indeed, many of the cognitive characteristics associated with conspiracy theory belief are universal, continuously distributed traits, varying in quantity, rather than all-or-none variables or distinct symptoms of mental illness.

Essentially, delusions are fixed, false, usually unshared beliefs, often based on subjective “inner” experience. (One rare exception is the so-called folie à deux, in which two people appear to “share” the same delusion; however, psychiatrists have long debated whether both individuals should be considered truly delusional). The delusion’s content is often “self-referential”; i.e., focused primarily on the believer.

In contrast, conspiracy theories are usually, but not necessarily, false. They are typically shared beliefs that don’t explicitly or directly involve the believer, and are based on evidence that one finds “out there,” such as on the Internet. This speaks to the highly communal nature of so many conspiracy theories – networks of like-minded individuals reinforcing one another’s beliefs in a particular socio-cultural context.
 

Conspiracy theory belief, COVID-19, and medical intervention

As for medical conspiracy theories, none have flourished recently more so than those involving the COVID-19 pandemic. As a recent editorial by Stein and colleagues noted, “Some conspiratorial claims include assertions that COVID‐19 is a hoax; arguments that the virus was created artificially and spread on purpose as a bioweapon; or allegations that governments are using the emergency situation to pursue their antidemocratic goals. … Other conspiracies argued that people in power are taking advantage of the pandemic as a plan to inject microchip quantum-dot spy software and monitor people.”

Stein and colleagues make the important point that a “key difference between COVID‐19 and the 1918 flu pandemic ... is that [now] a highly interconnected world, to a great extent on social media, is setting the stage for distributing information and misinformation about COVID‐19.”

Consider the following composite vignette: Mr. A is a 70-year-old retiree with a history of COPD who has been advised by his PCP to get vaccinated against COVID-19. He is extremely reluctant to do so, fearing that “the vaccine is going to change my DNA” and “might even give me COVID.” He has heard from friends on social media that vaccine developers “faked the results” and are “in cahoots with the federal government.” Mr. A has heard “experts” declare the vaccines safe, but does not trust them. Mr. A has no psychiatric or substance abuse history, and there are no cognitive, perceptual, or other abnormalities in Mr. A’s mental status exam.

Mr. A’s beliefs qualify as a “conspiracy theory,” but probably represent widely held misconceptions about COVID-19 vaccines, as well as widespread mistrust of pharmaceutical companies and the federal government. Based on the information provided, there is no basis for concluding that Mr. A is psychotic or delusional. His beliefs appear to be the result of “epistemic mistrust” of authoritative informational accounts, biased information processing, and exposure to misinformation.

How should the physician manage and care for patients like Mr. A? Absent frank delusions, there is no role for antipsychotic medication, though for extremely anxious patients, a time-limited course of an antianxiety agent may sometimes be warranted. In addition to providing accurate medical information to the patient, the physician should avoid arguing, or trying to “talk the patient out of” his or her belief. Instead, the focus should be on sustaining and strengthening the physician-patient alliance, establishing an atmosphere of respect and safety, clarifying differences in trusted sources of medical information, and allowing the patient time to process the physician’s recommendations.

One-to-one engagement with health care providers has proved effective in reducing vaccine hesitancy and correcting misinformation. For patients with less fixed conspiracy theory beliefs, it may sometimes be helpful to gently offer alternative hypotheses to the patient’s conspiracy theory, using elements of cognitive-behavioral therapy (CBT). For example, a physician might ask, “Is it possible that the online source you read was mistaken about the vaccine changing your DNA?” while reminding patients that – contrary to popular belief – mRNA vaccines have been in development against cancer for several decades.

Challenging beliefs collaboratively and acknowledging areas of uncertainty, rather than confronting or arguing about false beliefs, can foster trust between physician and patient and, at the very least, open a dialogue regarding potential exposure to medical misinformation. “Inoculation” strategies that present and then dispel misinformation before patients become aware of it are among the best supported strategies for mitigating conspiracy theory belief. Ideally, physicians and health care systems should maintain an ongoing “inventory” of medical misinformation circulating online and “beat it to the punch” with reliable information.

Finally, because believing in conspiracy theories is often associated with a sense of uncertainty, and feeling that one’s life is “out of control,” medical interventions can be framed as ways of regaining control and appealing to patients’ values; for example, saying, “By getting the vaccine, you’ll be more likely to stay in good health, protect your family, and do all the things you want to do.”
 

Dr. Pies is professor of psychiatry and a lecturer on bioethics and humanities at State University of New York, Syracuse. Dr. Pierre is a health sciences clinical professor in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles. A version of this article first appeared on Medscape.com.

When many people across the country, not to mention in public office, believe that the world is run by a group of Satanic pedophiles that includes top Democrats and Hollywood elites, and that former President Trump is leading a secret mission to bring these evildoers to justice, one can’t help but ask if they’re at least to some degree mentally impaired.

Conspiracy theories are often received with psychiatric connotations; associated with paranoid plan-hatchers, and nonbelieving outsiders. But whereas theories such as QAnon strain credibility for many people, we would argue that they are likely not the product of psychosis or mental illness; nor do conspiracy theories in general represent delusions.

For one thing, surveys have consistently revealed that about 50% of the population believes in at least one conspiracy theory. Furthermore, there are several substantive differences between conspiracy theory beliefs and delusions.

Some researchers consider conspiracy theories to be “a subset of false beliefs,” but  most scholars, ourselves included, do not prejudge their validity or veracity. Real-life conspiracies, such as the CIA’s MK-Ultra program, have clearly occurred throughout history.

Our central contention is that belief in conspiracy theories is distinct from psychosis, and more closely resembles extreme but subculturally sanctioned religious or political beliefs. However, the line between believing in conspiracies and being delusional becomes blurred when the believer becomes part of the conspiracy theory and feels compelled to act on the belief as part of a personal mission.

Take Edgar Maddison Welch, a 28-year-old man who firmly believed the so-called “Pizzagate” conspiracy theory – the baseless claim that Hillary Clinton and Democratic elites were running a child sex-trafficking ring out of a Washington, DC, pizzeria. Seeing himself a potential savior of children, Mr. Welch drove 350 miles to the pizza shop from his home in North Carolina in December 2016 and fired three shots from an AR-15 style rifle into a locked closet door, ultimately surrendering to police. However, on questioning he quickly conceded, “The intel on this wasn’t 100%.”

Who believes in conspiracy theories?

Given that half the population believes in at least one conspiracy theory, it should come as little surprise that there is no reliable “profile” for believers. Although some studies have suggested associations with low education, right-wing political orientation, and certain personality traits like subclinical paranoia and schizotypy, such findings have been inconsistent and may vary across specific conspiracy theory. Associations between conspiracy belief and paranoia suggest overlap within a “conspiratorial mindset,” with recent evidence that “distrust of officialdom” is a key mediator between believing in conspiracies and political ideology.

Other quantitative “cognitive quirks” reported in those who believe in conspiracies are a need for certainty and control, a need for uniqueness, illusory pattern perception, and lack of analytical thinking. It’s unclear which of these factors may represent universal cognitive explanations for conspiratorial beliefs, vs. those that might be related to specific beliefs, such as the need for certainty during times of crisis and societal upheaval, when conspiracy theories tend to flourish.

Much of the research on conspiracy theory belief is based on the questionable premise that it’s best understood at the level of the individual’s psychopathology, or the “deficit model,” as it’s called. One of us (JMP) has instead proposed a two-component model that includes social and informational contexts. The first component – epistemic mistrust – involves mistrusting conventional, “authoritative” knowledge. The second involves biased information processing and exposure to misinformation, often transmitted by word of mouth, or through social networks. With this model, believing in conspiracy theories could be conceived as involving “delusion-like beliefs,” but not frank psychosis or full-blown delusions, as one might see, for example, in schizophrenia.

Indeed, many of the cognitive characteristics associated with conspiracy theory belief are universal, continuously distributed traits, varying in quantity, rather than all-or-none variables or distinct symptoms of mental illness.

Essentially, delusions are fixed, false, usually unshared beliefs, often based on subjective “inner” experience. (One rare exception is the so-called folie à deux, in which two people appear to “share” the same delusion; however, psychiatrists have long debated whether both individuals should be considered truly delusional). The delusion’s content is often “self-referential”; i.e., focused primarily on the believer.

In contrast, conspiracy theories are usually, but not necessarily, false. They are typically shared beliefs that don’t explicitly or directly involve the believer, and are based on evidence that one finds “out there,” such as on the Internet. This speaks to the highly communal nature of so many conspiracy theories – networks of like-minded individuals reinforcing one another’s beliefs in a particular socio-cultural context.
 

Conspiracy theory belief, COVID-19, and medical intervention

As for medical conspiracy theories, none have flourished recently more so than those involving the COVID-19 pandemic. As a recent editorial by Stein and colleagues noted, “Some conspiratorial claims include assertions that COVID‐19 is a hoax; arguments that the virus was created artificially and spread on purpose as a bioweapon; or allegations that governments are using the emergency situation to pursue their antidemocratic goals. … Other conspiracies argued that people in power are taking advantage of the pandemic as a plan to inject microchip quantum-dot spy software and monitor people.”

Stein and colleagues make the important point that a “key difference between COVID‐19 and the 1918 flu pandemic ... is that [now] a highly interconnected world, to a great extent on social media, is setting the stage for distributing information and misinformation about COVID‐19.”

Consider the following composite vignette: Mr. A is a 70-year-old retiree with a history of COPD who has been advised by his PCP to get vaccinated against COVID-19. He is extremely reluctant to do so, fearing that “the vaccine is going to change my DNA” and “might even give me COVID.” He has heard from friends on social media that vaccine developers “faked the results” and are “in cahoots with the federal government.” Mr. A has heard “experts” declare the vaccines safe, but does not trust them. Mr. A has no psychiatric or substance abuse history, and there are no cognitive, perceptual, or other abnormalities in Mr. A’s mental status exam.

Mr. A’s beliefs qualify as a “conspiracy theory,” but probably represent widely held misconceptions about COVID-19 vaccines, as well as widespread mistrust of pharmaceutical companies and the federal government. Based on the information provided, there is no basis for concluding that Mr. A is psychotic or delusional. His beliefs appear to be the result of “epistemic mistrust” of authoritative informational accounts, biased information processing, and exposure to misinformation.

How should the physician manage and care for patients like Mr. A? Absent frank delusions, there is no role for antipsychotic medication, though for extremely anxious patients, a time-limited course of an antianxiety agent may sometimes be warranted. In addition to providing accurate medical information to the patient, the physician should avoid arguing, or trying to “talk the patient out of” his or her belief. Instead, the focus should be on sustaining and strengthening the physician-patient alliance, establishing an atmosphere of respect and safety, clarifying differences in trusted sources of medical information, and allowing the patient time to process the physician’s recommendations.

One-to-one engagement with health care providers has proved effective in reducing vaccine hesitancy and correcting misinformation. For patients with less fixed conspiracy theory beliefs, it may sometimes be helpful to gently offer alternative hypotheses to the patient’s conspiracy theory, using elements of cognitive-behavioral therapy (CBT). For example, a physician might ask, “Is it possible that the online source you read was mistaken about the vaccine changing your DNA?” while reminding patients that – contrary to popular belief – mRNA vaccines have been in development against cancer for several decades.

Challenging beliefs collaboratively and acknowledging areas of uncertainty, rather than confronting or arguing about false beliefs, can foster trust between physician and patient and, at the very least, open a dialogue regarding potential exposure to medical misinformation. “Inoculation” strategies that present and then dispel misinformation before patients become aware of it are among the best supported strategies for mitigating conspiracy theory belief. Ideally, physicians and health care systems should maintain an ongoing “inventory” of medical misinformation circulating online and “beat it to the punch” with reliable information.

Finally, because believing in conspiracy theories is often associated with a sense of uncertainty, and feeling that one’s life is “out of control,” medical interventions can be framed as ways of regaining control and appealing to patients’ values; for example, saying, “By getting the vaccine, you’ll be more likely to stay in good health, protect your family, and do all the things you want to do.”
 

Dr. Pies is professor of psychiatry and a lecturer on bioethics and humanities at State University of New York, Syracuse. Dr. Pierre is a health sciences clinical professor in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles. A version of this article first appeared on Medscape.com.

When many people across the country, not to mention in public office, believe that the world is run by a group of Satanic pedophiles that includes top Democrats and Hollywood elites, and that former President Trump is leading a secret mission to bring these evildoers to justice, one can’t help but ask if they’re at least to some degree mentally impaired.

Conspiracy theories are often received with psychiatric connotations; associated with paranoid plan-hatchers, and nonbelieving outsiders. But whereas theories such as QAnon strain credibility for many people, we would argue that they are likely not the product of psychosis or mental illness; nor do conspiracy theories in general represent delusions.

For one thing, surveys have consistently revealed that about 50% of the population believes in at least one conspiracy theory. Furthermore, there are several substantive differences between conspiracy theory beliefs and delusions.

Some researchers consider conspiracy theories to be “a subset of false beliefs,” but  most scholars, ourselves included, do not prejudge their validity or veracity. Real-life conspiracies, such as the CIA’s MK-Ultra program, have clearly occurred throughout history.

Our central contention is that belief in conspiracy theories is distinct from psychosis, and more closely resembles extreme but subculturally sanctioned religious or political beliefs. However, the line between believing in conspiracies and being delusional becomes blurred when the believer becomes part of the conspiracy theory and feels compelled to act on the belief as part of a personal mission.

Take Edgar Maddison Welch, a 28-year-old man who firmly believed the so-called “Pizzagate” conspiracy theory – the baseless claim that Hillary Clinton and Democratic elites were running a child sex-trafficking ring out of a Washington, DC, pizzeria. Seeing himself a potential savior of children, Mr. Welch drove 350 miles to the pizza shop from his home in North Carolina in December 2016 and fired three shots from an AR-15 style rifle into a locked closet door, ultimately surrendering to police. However, on questioning he quickly conceded, “The intel on this wasn’t 100%.”

Who believes in conspiracy theories?

Given that half the population believes in at least one conspiracy theory, it should come as little surprise that there is no reliable “profile” for believers. Although some studies have suggested associations with low education, right-wing political orientation, and certain personality traits like subclinical paranoia and schizotypy, such findings have been inconsistent and may vary across specific conspiracy theory. Associations between conspiracy belief and paranoia suggest overlap within a “conspiratorial mindset,” with recent evidence that “distrust of officialdom” is a key mediator between believing in conspiracies and political ideology.

Other quantitative “cognitive quirks” reported in those who believe in conspiracies are a need for certainty and control, a need for uniqueness, illusory pattern perception, and lack of analytical thinking. It’s unclear which of these factors may represent universal cognitive explanations for conspiratorial beliefs, vs. those that might be related to specific beliefs, such as the need for certainty during times of crisis and societal upheaval, when conspiracy theories tend to flourish.

Much of the research on conspiracy theory belief is based on the questionable premise that it’s best understood at the level of the individual’s psychopathology, or the “deficit model,” as it’s called. One of us (JMP) has instead proposed a two-component model that includes social and informational contexts. The first component – epistemic mistrust – involves mistrusting conventional, “authoritative” knowledge. The second involves biased information processing and exposure to misinformation, often transmitted by word of mouth, or through social networks. With this model, believing in conspiracy theories could be conceived as involving “delusion-like beliefs,” but not frank psychosis or full-blown delusions, as one might see, for example, in schizophrenia.

Indeed, many of the cognitive characteristics associated with conspiracy theory belief are universal, continuously distributed traits, varying in quantity, rather than all-or-none variables or distinct symptoms of mental illness.

Essentially, delusions are fixed, false, usually unshared beliefs, often based on subjective “inner” experience. (One rare exception is the so-called folie à deux, in which two people appear to “share” the same delusion; however, psychiatrists have long debated whether both individuals should be considered truly delusional). The delusion’s content is often “self-referential”; i.e., focused primarily on the believer.

In contrast, conspiracy theories are usually, but not necessarily, false. They are typically shared beliefs that don’t explicitly or directly involve the believer, and are based on evidence that one finds “out there,” such as on the Internet. This speaks to the highly communal nature of so many conspiracy theories – networks of like-minded individuals reinforcing one another’s beliefs in a particular socio-cultural context.
 

Conspiracy theory belief, COVID-19, and medical intervention

As for medical conspiracy theories, none have flourished recently more so than those involving the COVID-19 pandemic. As a recent editorial by Stein and colleagues noted, “Some conspiratorial claims include assertions that COVID‐19 is a hoax; arguments that the virus was created artificially and spread on purpose as a bioweapon; or allegations that governments are using the emergency situation to pursue their antidemocratic goals. … Other conspiracies argued that people in power are taking advantage of the pandemic as a plan to inject microchip quantum-dot spy software and monitor people.”

Stein and colleagues make the important point that a “key difference between COVID‐19 and the 1918 flu pandemic ... is that [now] a highly interconnected world, to a great extent on social media, is setting the stage for distributing information and misinformation about COVID‐19.”

Consider the following composite vignette: Mr. A is a 70-year-old retiree with a history of COPD who has been advised by his PCP to get vaccinated against COVID-19. He is extremely reluctant to do so, fearing that “the vaccine is going to change my DNA” and “might even give me COVID.” He has heard from friends on social media that vaccine developers “faked the results” and are “in cahoots with the federal government.” Mr. A has heard “experts” declare the vaccines safe, but does not trust them. Mr. A has no psychiatric or substance abuse history, and there are no cognitive, perceptual, or other abnormalities in Mr. A’s mental status exam.

Mr. A’s beliefs qualify as a “conspiracy theory,” but probably represent widely held misconceptions about COVID-19 vaccines, as well as widespread mistrust of pharmaceutical companies and the federal government. Based on the information provided, there is no basis for concluding that Mr. A is psychotic or delusional. His beliefs appear to be the result of “epistemic mistrust” of authoritative informational accounts, biased information processing, and exposure to misinformation.

How should the physician manage and care for patients like Mr. A? Absent frank delusions, there is no role for antipsychotic medication, though for extremely anxious patients, a time-limited course of an antianxiety agent may sometimes be warranted. In addition to providing accurate medical information to the patient, the physician should avoid arguing, or trying to “talk the patient out of” his or her belief. Instead, the focus should be on sustaining and strengthening the physician-patient alliance, establishing an atmosphere of respect and safety, clarifying differences in trusted sources of medical information, and allowing the patient time to process the physician’s recommendations.

One-to-one engagement with health care providers has proved effective in reducing vaccine hesitancy and correcting misinformation. For patients with less fixed conspiracy theory beliefs, it may sometimes be helpful to gently offer alternative hypotheses to the patient’s conspiracy theory, using elements of cognitive-behavioral therapy (CBT). For example, a physician might ask, “Is it possible that the online source you read was mistaken about the vaccine changing your DNA?” while reminding patients that – contrary to popular belief – mRNA vaccines have been in development against cancer for several decades.

Challenging beliefs collaboratively and acknowledging areas of uncertainty, rather than confronting or arguing about false beliefs, can foster trust between physician and patient and, at the very least, open a dialogue regarding potential exposure to medical misinformation. “Inoculation” strategies that present and then dispel misinformation before patients become aware of it are among the best supported strategies for mitigating conspiracy theory belief. Ideally, physicians and health care systems should maintain an ongoing “inventory” of medical misinformation circulating online and “beat it to the punch” with reliable information.

Finally, because believing in conspiracy theories is often associated with a sense of uncertainty, and feeling that one’s life is “out of control,” medical interventions can be framed as ways of regaining control and appealing to patients’ values; for example, saying, “By getting the vaccine, you’ll be more likely to stay in good health, protect your family, and do all the things you want to do.”
 

Dr. Pies is professor of psychiatry and a lecturer on bioethics and humanities at State University of New York, Syracuse. Dr. Pierre is a health sciences clinical professor in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles. A version of this article first appeared on Medscape.com.

Systemic therapy advances for metastatic breast cancer (MBC) have led to improved overall survival; however, the CNS sanctuary site can be challenging to treat and cause significant neurologic symptoms. Kuksis and colleagues reported that HER2-positive and triple-negative breast MBC subtypes have high incidence of brain metastases, with pooled cumulative incidences of 31% and 32%, respectively. The incidence per patient-year was 13% for both subtypes. The treatment landscape for HER2-positive MBC is rapidly evolving. The combination of tucatinib/capecitabine/trastuzumab demonstrated reduced risk of intracranial progression or death (HR 0.32), improvement in intracranial objective response rate (47.3% versus 20.0%) and reduced risk of death (0.58) in the HER2CLIMB study. An MRI screening program may enhance early detection and study prevention of brain metastases.

Trastuzumab and pertuzumab have significantly improved outcomes in early-stage and advanced HER2-positive breast cancer. These monoclonal antibodies are given with chemotherapy initially, followed by dual antibody therapy to complete one year for curative treatment and until disease progression in the metastatic setting. The FeDeriCa randomized phase 3 study demonstrated that fixed-dose subcutaneous combination of pertuzumab and trastuzumab was non-inferior to intravenous formulations with a geometric mean ratio of cycle 7 pertuzumab serum trough concentration of 1.22 (90% CI 1.14-1.31). Furthermore, efficacy appeared similar with pathologic complete response rates of 60% for both groups. Trastuzumab and pertuzumab administration in an infusion center requires hospital resources, cost, and patient’s time. The MetasphHER study showed that patients preferred subcutaneous trastuzumab compared to IV, and further investigation into long-term outcomes and impact on quality of life and resource allocation is desired.

The phase 3 CLEOPATRA study demonstrated improvement in overall survival with the addition of pertuzumab to docetaxel and trastuzumab in patients with HER2-positive MBC. Rash and diarrhea are well-recognized potential side effects related to pertuzumab. Ferreira et al demonstrated that rash was prognostic for PFS and OS both during and after docetaxel discontinuation, while diarrhea was only prognostic after docetaxel. Neither rash nor diarrhea were predictive of pertuzumab benefit. Studies have shown that patients who developed immune-related adverse events during anti-PD-1 treatment had PFS and OS benefit compared to those who did not. These results may help inform and encourage patients and providers regarding benefit of various treatments in the setting of toxicities. Future research exploring biomarker prognostic and predictive capability is certainly warranted. 

Endocrine therapy plus a CDK 4/6 inhibitor is standard first-line treatment for hormone receptor-positive MBC. Progression that occurs rapidly or through multiple lines of endocrine therapy combinations, may indicate endocrine resistance. The phase 3 PEARL trial did not demonstrate superior PFS among patients with wild type ESR1 AI-resistant MBC with palbociclib/endocrine therapy compared to capecitabine (mPFS 8.0 vs 10.6 months, adjusted HR 1.11; p=0.404); similar PFS and aHR were seen in palbociclib/fulvestrant versus capecitabine cohort. Therapy sequencing in HR+/HER2-negative MBC is indeed relevant, and a previous meta-analysis demonstrated chemotherapy was not better than endocrine therapy plus CDK 4/6 inhibitor in first- or second-line setting. Importantly, palbociclib plus endocrine therapy was associated with better tolerability and quality of life, which should be considered when selecting treatment with similar PFS outcomes.

References:

Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, Hurvitz S, Loi S, Okines A, Abramson V, Bedard PL, Oliveira M, Mueller V, Zelnak A, DiGiovanna MP, Bachelot T, Chien AJ, O'Regan R, Wardley A, Conlin A, Cameron D, Carey L, Curigliano G, Gelmon K, Loibl S, Mayor J, McGoldrick S, An X, Winer EP. Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial. J Clin Oncol. 2020;38:2610-2619.

Pivot X, Spano JP, Espie M, Cottu P, Jouannaud C, Pottier V, Moreau L, Extra JM, Lortholary A, Rivera P, Spaeth D, Attar-Rabia H, Benkanoun C, Dima-Martinez L, Esposito N, Gligorov J. Patients' preference of trastuzumab administration (subcutaneous versus intravenous) in HER2-positive metastatic breast cancer: Results of the randomised MetaspHer study. Eur J Cancer. 2017;82:230-236.

Das S, Ciombor KK, Haraldsdottir S, Pumpalova Y, Sahin IH, Pineda G, Shyr Y, Lin EP, Hsu CY, Chu SK, Goff LW, Cardin DB, Bilen MA, Fisher GA, Wu C, Berlin J. Immune-related adverse events and immune checkpoint inhibitor efficacy in patients with gastrointestinal cancer with Food and Drug Administration-approved indications for immunotherapy. Oncologist. 2020;25:669-679.

Giuliano M, Schettini F, Rognoni C, Milani M, Jerusalem G, Bachelot T, De Laurentiis M, Thomas G, De Placido P, Arpino G, De Placido S, Cristofanilli M, Giordano A, Puglisi F, Pistilli B, Prat A, Del Mastro L, Venturini S, Generali D. Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis. Lancet Oncol. 2019;20:1360-1369.

Systemic therapy advances for metastatic breast cancer (MBC) have led to improved overall survival; however, the CNS sanctuary site can be challenging to treat and cause significant neurologic symptoms. Kuksis and colleagues reported that HER2-positive and triple-negative breast MBC subtypes have high incidence of brain metastases, with pooled cumulative incidences of 31% and 32%, respectively. The incidence per patient-year was 13% for both subtypes. The treatment landscape for HER2-positive MBC is rapidly evolving. The combination of tucatinib/capecitabine/trastuzumab demonstrated reduced risk of intracranial progression or death (HR 0.32), improvement in intracranial objective response rate (47.3% versus 20.0%) and reduced risk of death (0.58) in the HER2CLIMB study. An MRI screening program may enhance early detection and study prevention of brain metastases.

Trastuzumab and pertuzumab have significantly improved outcomes in early-stage and advanced HER2-positive breast cancer. These monoclonal antibodies are given with chemotherapy initially, followed by dual antibody therapy to complete one year for curative treatment and until disease progression in the metastatic setting. The FeDeriCa randomized phase 3 study demonstrated that fixed-dose subcutaneous combination of pertuzumab and trastuzumab was non-inferior to intravenous formulations with a geometric mean ratio of cycle 7 pertuzumab serum trough concentration of 1.22 (90% CI 1.14-1.31). Furthermore, efficacy appeared similar with pathologic complete response rates of 60% for both groups. Trastuzumab and pertuzumab administration in an infusion center requires hospital resources, cost, and patient’s time. The MetasphHER study showed that patients preferred subcutaneous trastuzumab compared to IV, and further investigation into long-term outcomes and impact on quality of life and resource allocation is desired.

The phase 3 CLEOPATRA study demonstrated improvement in overall survival with the addition of pertuzumab to docetaxel and trastuzumab in patients with HER2-positive MBC. Rash and diarrhea are well-recognized potential side effects related to pertuzumab. Ferreira et al demonstrated that rash was prognostic for PFS and OS both during and after docetaxel discontinuation, while diarrhea was only prognostic after docetaxel. Neither rash nor diarrhea were predictive of pertuzumab benefit. Studies have shown that patients who developed immune-related adverse events during anti-PD-1 treatment had PFS and OS benefit compared to those who did not. These results may help inform and encourage patients and providers regarding benefit of various treatments in the setting of toxicities. Future research exploring biomarker prognostic and predictive capability is certainly warranted. 

Endocrine therapy plus a CDK 4/6 inhibitor is standard first-line treatment for hormone receptor-positive MBC. Progression that occurs rapidly or through multiple lines of endocrine therapy combinations, may indicate endocrine resistance. The phase 3 PEARL trial did not demonstrate superior PFS among patients with wild type ESR1 AI-resistant MBC with palbociclib/endocrine therapy compared to capecitabine (mPFS 8.0 vs 10.6 months, adjusted HR 1.11; p=0.404); similar PFS and aHR were seen in palbociclib/fulvestrant versus capecitabine cohort. Therapy sequencing in HR+/HER2-negative MBC is indeed relevant, and a previous meta-analysis demonstrated chemotherapy was not better than endocrine therapy plus CDK 4/6 inhibitor in first- or second-line setting. Importantly, palbociclib plus endocrine therapy was associated with better tolerability and quality of life, which should be considered when selecting treatment with similar PFS outcomes.

References:

Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, Hurvitz S, Loi S, Okines A, Abramson V, Bedard PL, Oliveira M, Mueller V, Zelnak A, DiGiovanna MP, Bachelot T, Chien AJ, O'Regan R, Wardley A, Conlin A, Cameron D, Carey L, Curigliano G, Gelmon K, Loibl S, Mayor J, McGoldrick S, An X, Winer EP. Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial. J Clin Oncol. 2020;38:2610-2619.

Pivot X, Spano JP, Espie M, Cottu P, Jouannaud C, Pottier V, Moreau L, Extra JM, Lortholary A, Rivera P, Spaeth D, Attar-Rabia H, Benkanoun C, Dima-Martinez L, Esposito N, Gligorov J. Patients' preference of trastuzumab administration (subcutaneous versus intravenous) in HER2-positive metastatic breast cancer: Results of the randomised MetaspHer study. Eur J Cancer. 2017;82:230-236.

Das S, Ciombor KK, Haraldsdottir S, Pumpalova Y, Sahin IH, Pineda G, Shyr Y, Lin EP, Hsu CY, Chu SK, Goff LW, Cardin DB, Bilen MA, Fisher GA, Wu C, Berlin J. Immune-related adverse events and immune checkpoint inhibitor efficacy in patients with gastrointestinal cancer with Food and Drug Administration-approved indications for immunotherapy. Oncologist. 2020;25:669-679.

Giuliano M, Schettini F, Rognoni C, Milani M, Jerusalem G, Bachelot T, De Laurentiis M, Thomas G, De Placido P, Arpino G, De Placido S, Cristofanilli M, Giordano A, Puglisi F, Pistilli B, Prat A, Del Mastro L, Venturini S, Generali D. Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis. Lancet Oncol. 2019;20:1360-1369.

Systemic therapy advances for metastatic breast cancer (MBC) have led to improved overall survival; however, the CNS sanctuary site can be challenging to treat and cause significant neurologic symptoms. Kuksis and colleagues reported that HER2-positive and triple-negative breast MBC subtypes have high incidence of brain metastases, with pooled cumulative incidences of 31% and 32%, respectively. The incidence per patient-year was 13% for both subtypes. The treatment landscape for HER2-positive MBC is rapidly evolving. The combination of tucatinib/capecitabine/trastuzumab demonstrated reduced risk of intracranial progression or death (HR 0.32), improvement in intracranial objective response rate (47.3% versus 20.0%) and reduced risk of death (0.58) in the HER2CLIMB study. An MRI screening program may enhance early detection and study prevention of brain metastases.

Trastuzumab and pertuzumab have significantly improved outcomes in early-stage and advanced HER2-positive breast cancer. These monoclonal antibodies are given with chemotherapy initially, followed by dual antibody therapy to complete one year for curative treatment and until disease progression in the metastatic setting. The FeDeriCa randomized phase 3 study demonstrated that fixed-dose subcutaneous combination of pertuzumab and trastuzumab was non-inferior to intravenous formulations with a geometric mean ratio of cycle 7 pertuzumab serum trough concentration of 1.22 (90% CI 1.14-1.31). Furthermore, efficacy appeared similar with pathologic complete response rates of 60% for both groups. Trastuzumab and pertuzumab administration in an infusion center requires hospital resources, cost, and patient’s time. The MetasphHER study showed that patients preferred subcutaneous trastuzumab compared to IV, and further investigation into long-term outcomes and impact on quality of life and resource allocation is desired.

The phase 3 CLEOPATRA study demonstrated improvement in overall survival with the addition of pertuzumab to docetaxel and trastuzumab in patients with HER2-positive MBC. Rash and diarrhea are well-recognized potential side effects related to pertuzumab. Ferreira et al demonstrated that rash was prognostic for PFS and OS both during and after docetaxel discontinuation, while diarrhea was only prognostic after docetaxel. Neither rash nor diarrhea were predictive of pertuzumab benefit. Studies have shown that patients who developed immune-related adverse events during anti-PD-1 treatment had PFS and OS benefit compared to those who did not. These results may help inform and encourage patients and providers regarding benefit of various treatments in the setting of toxicities. Future research exploring biomarker prognostic and predictive capability is certainly warranted. 

Endocrine therapy plus a CDK 4/6 inhibitor is standard first-line treatment for hormone receptor-positive MBC. Progression that occurs rapidly or through multiple lines of endocrine therapy combinations, may indicate endocrine resistance. The phase 3 PEARL trial did not demonstrate superior PFS among patients with wild type ESR1 AI-resistant MBC with palbociclib/endocrine therapy compared to capecitabine (mPFS 8.0 vs 10.6 months, adjusted HR 1.11; p=0.404); similar PFS and aHR were seen in palbociclib/fulvestrant versus capecitabine cohort. Therapy sequencing in HR+/HER2-negative MBC is indeed relevant, and a previous meta-analysis demonstrated chemotherapy was not better than endocrine therapy plus CDK 4/6 inhibitor in first- or second-line setting. Importantly, palbociclib plus endocrine therapy was associated with better tolerability and quality of life, which should be considered when selecting treatment with similar PFS outcomes.

References:

Lin NU, Borges V, Anders C, Murthy RK, Paplomata E, Hamilton E, Hurvitz S, Loi S, Okines A, Abramson V, Bedard PL, Oliveira M, Mueller V, Zelnak A, DiGiovanna MP, Bachelot T, Chien AJ, O'Regan R, Wardley A, Conlin A, Cameron D, Carey L, Curigliano G, Gelmon K, Loibl S, Mayor J, McGoldrick S, An X, Winer EP. Intracranial efficacy and survival with tucatinib plus trastuzumab and capecitabine for previously treated HER2-positive breast cancer with brain metastases in the HER2CLIMB trial. J Clin Oncol. 2020;38:2610-2619.

Pivot X, Spano JP, Espie M, Cottu P, Jouannaud C, Pottier V, Moreau L, Extra JM, Lortholary A, Rivera P, Spaeth D, Attar-Rabia H, Benkanoun C, Dima-Martinez L, Esposito N, Gligorov J. Patients' preference of trastuzumab administration (subcutaneous versus intravenous) in HER2-positive metastatic breast cancer: Results of the randomised MetaspHer study. Eur J Cancer. 2017;82:230-236.

Das S, Ciombor KK, Haraldsdottir S, Pumpalova Y, Sahin IH, Pineda G, Shyr Y, Lin EP, Hsu CY, Chu SK, Goff LW, Cardin DB, Bilen MA, Fisher GA, Wu C, Berlin J. Immune-related adverse events and immune checkpoint inhibitor efficacy in patients with gastrointestinal cancer with Food and Drug Administration-approved indications for immunotherapy. Oncologist. 2020;25:669-679.

Giuliano M, Schettini F, Rognoni C, Milani M, Jerusalem G, Bachelot T, De Laurentiis M, Thomas G, De Placido P, Arpino G, De Placido S, Cristofanilli M, Giordano A, Puglisi F, Pistilli B, Prat A, Del Mastro L, Venturini S, Generali D. Endocrine treatment versus chemotherapy in postmenopausal women with hormone receptor-positive, HER2-negative, metastatic breast cancer: a systematic review and network meta-analysis. Lancet Oncol. 2019;20:1360-1369.

COVID-19 cases are continuing to fall in the United States, according to the New York Times tracker, though the number of deaths from the disease again neared 4,000 on Feb. 3.

janiecbros/iStock/Getty Images Plus

The United States has averaged 141,146 cases a day in the past week, down 30% from the average 2 weeks ago. For the first time since November 2020, the country is averaging fewer than 150,000 cases a day, according to the tracker.

However, Rochelle Walensky, MD, MPH, director of the Centers for Disease Control and Prevention, warned that new COVID-19 variants popping up widely could threaten that progress.

“Although we have seen declines in cases and admissions and a recent slowing of deaths, cases remain extraordinarily high, still twice as high as the peak number of cases over the summer. And the continued proliferation of variants, variants that likely have increased transmissibility, that spread more easily, threatens to reverse these recent trends.

“Based on contact tracing of recent variant cases, not wearing masks and participating in in-person social gatherings have contributed to the variants’ spread,” she said at a White House COVID-19 briefing on Feb. 3, 2021.

The number of cases worldwide neared 104 million on Feb. 3 and the U.S. numbers made up 26.4 million of that total.

As of Feb. 4, COVID-19 had killed at least 454,000 people and infected about 26.6 million in the United States since January 2020, according to the Johns Hopkins University tracker.

The Johns Hopkins tracker found that, per capita, North Dakota, South Dakota, and Rhode Island have reported the most cases while New Jersey and New York have recorded the most deaths.

According to the COVID tracking project, hospitalizations for COVID-19 nationwide were down to 91,440 on Feb. 3.

The tracking report noted, “compared to last week, the number of people currently hospitalized with COVID-19 is down by 10% or more in 38 states.”

Even in hard-hit Los Angeles County, infections and case numbers are on the decline, according to the Los Angeles Times. However, officials, warn the numbers remain well above presurge levels. Over the past week, 201 city residents have died every day.

Reuters also reports that Anthony S. Fauci, MD, the government’s top infectious disease expert, said despite some good news in the numbers, Americans should continue to follow social distancing guidelines. He added that double-masking may add protection.

A version of this article first appeared on Medscape.com.

COVID-19 cases are continuing to fall in the United States, according to the New York Times tracker, though the number of deaths from the disease again neared 4,000 on Feb. 3.

janiecbros/iStock/Getty Images Plus

The United States has averaged 141,146 cases a day in the past week, down 30% from the average 2 weeks ago. For the first time since November 2020, the country is averaging fewer than 150,000 cases a day, according to the tracker.

However, Rochelle Walensky, MD, MPH, director of the Centers for Disease Control and Prevention, warned that new COVID-19 variants popping up widely could threaten that progress.

“Although we have seen declines in cases and admissions and a recent slowing of deaths, cases remain extraordinarily high, still twice as high as the peak number of cases over the summer. And the continued proliferation of variants, variants that likely have increased transmissibility, that spread more easily, threatens to reverse these recent trends.

“Based on contact tracing of recent variant cases, not wearing masks and participating in in-person social gatherings have contributed to the variants’ spread,” she said at a White House COVID-19 briefing on Feb. 3, 2021.

The number of cases worldwide neared 104 million on Feb. 3 and the U.S. numbers made up 26.4 million of that total.

As of Feb. 4, COVID-19 had killed at least 454,000 people and infected about 26.6 million in the United States since January 2020, according to the Johns Hopkins University tracker.

The Johns Hopkins tracker found that, per capita, North Dakota, South Dakota, and Rhode Island have reported the most cases while New Jersey and New York have recorded the most deaths.

According to the COVID tracking project, hospitalizations for COVID-19 nationwide were down to 91,440 on Feb. 3.

The tracking report noted, “compared to last week, the number of people currently hospitalized with COVID-19 is down by 10% or more in 38 states.”

Even in hard-hit Los Angeles County, infections and case numbers are on the decline, according to the Los Angeles Times. However, officials, warn the numbers remain well above presurge levels. Over the past week, 201 city residents have died every day.

Reuters also reports that Anthony S. Fauci, MD, the government’s top infectious disease expert, said despite some good news in the numbers, Americans should continue to follow social distancing guidelines. He added that double-masking may add protection.

A version of this article first appeared on Medscape.com.

COVID-19 cases are continuing to fall in the United States, according to the New York Times tracker, though the number of deaths from the disease again neared 4,000 on Feb. 3.

janiecbros/iStock/Getty Images Plus

The United States has averaged 141,146 cases a day in the past week, down 30% from the average 2 weeks ago. For the first time since November 2020, the country is averaging fewer than 150,000 cases a day, according to the tracker.

However, Rochelle Walensky, MD, MPH, director of the Centers for Disease Control and Prevention, warned that new COVID-19 variants popping up widely could threaten that progress.

“Although we have seen declines in cases and admissions and a recent slowing of deaths, cases remain extraordinarily high, still twice as high as the peak number of cases over the summer. And the continued proliferation of variants, variants that likely have increased transmissibility, that spread more easily, threatens to reverse these recent trends.

“Based on contact tracing of recent variant cases, not wearing masks and participating in in-person social gatherings have contributed to the variants’ spread,” she said at a White House COVID-19 briefing on Feb. 3, 2021.

The number of cases worldwide neared 104 million on Feb. 3 and the U.S. numbers made up 26.4 million of that total.

As of Feb. 4, COVID-19 had killed at least 454,000 people and infected about 26.6 million in the United States since January 2020, according to the Johns Hopkins University tracker.

The Johns Hopkins tracker found that, per capita, North Dakota, South Dakota, and Rhode Island have reported the most cases while New Jersey and New York have recorded the most deaths.

According to the COVID tracking project, hospitalizations for COVID-19 nationwide were down to 91,440 on Feb. 3.

The tracking report noted, “compared to last week, the number of people currently hospitalized with COVID-19 is down by 10% or more in 38 states.”

Even in hard-hit Los Angeles County, infections and case numbers are on the decline, according to the Los Angeles Times. However, officials, warn the numbers remain well above presurge levels. Over the past week, 201 city residents have died every day.

Reuters also reports that Anthony S. Fauci, MD, the government’s top infectious disease expert, said despite some good news in the numbers, Americans should continue to follow social distancing guidelines. He added that double-masking may add protection.

A version of this article first appeared on Medscape.com.

Internal medicine physicians’ and family physicians’ attitudes have changed in recent years on several ethical issues, according to the Medscape Internal Medicine Ethics Report 2020 and the corresponding report for Family Medicine.

An example comes in an apparent loosening of attitudes about romantic/sexual relationships with former patients. Now, 31% of internists believe such a relationship is acceptable at least 6 months after the medical relationship has ended. That’s up from 22% in 2018. The number of family physicians this year who said 6 months later was acceptable also increased, but by a smaller margin – from 28% in 2018 to 33% in 2020.

“It’s acceptable as long as there is no undue influence,” David Fleming, MD, a member of the American Medical Association Council on Ethical and Judicial Affairs, said in an interview. “The important thing is that you don’t mix the two.”
 

Thoughts on upcoding

Views on billing are also shifting. Ten years ago, 17% of physicians overall thought upcoding was acceptable when submitting claims or getting prior authorization. Today just 8% of physicians overall said it was, as did 8% of family medicine (FM) physicians, according to responses.

The number of internal medicine (IM) physicians clearly opposed to upcoding declined a bit from 79% in 2018 to 75% this year, while the number saying “it depends” increased from 11% to 15%.

Many responders in both specialties said they would upgrade a code in the interest of patient advocacy.

An internist put it this way: “If the system is set up so that the only thing that would work for the patient’s condition can be obtained by an upcode, then I would consider this.”
 

More than a third say random drug checks needed

More than one-third of physicians in both specialties (34% in IM and 38% in FM) said physicians should be subjected to random alcohol and drug testing.

However, many say testing should only happen if abuse is suspected.

Some said specialty matters when it comes to random checks. An internist responded: “I think this is more important for procedure-based physicians.”

Some family physicians said that, if other health care workers were subjected to the same checks in the same circumstances, they would not object, but said doctors shouldn’t be singled out.
 

Vast majority would report an impaired peer

Nine out of 10 internists and family physicians say they would report a physician who occasionally seemed impaired but most (60% of IM respondents and 62% of FM respondents) said they would do so only after talking with the physician first.

Some noted their decision would depend on the setting.

“Big difference if they are on vacation and drink too much so they need a ride home versus being impaired at work or when on call,” one FM physician said.

About one-third of family physicians (34%) and internists (33%) now favor physician-assisted dying/suicide for incurable suffering. A substantial number (26%-28%) hesitated to make a clear decision in both specialties, responding “it depends.”

“Patient control over quality of life can be even more important than control over its quantity/duration,” one internist wrote.

The proportion of physicians who agreed physician-assisted dying/suicide should be legalized for the terminally ill was much larger, with 49% of family physicians and 52% of IM physicians saying it should.
 

Talking politics

Data in this survey were collected in summer months of 2020, before the U.S. presidential election, in a highly polarized climate. Some numbers reflect increasing distaste for such conversations with patients.

For example, the number of family physicians who said talking about politics with patients was ethical dropped from 31% in 2018 to 23% in the latest survey. The numbers remained nearly flat among IM physicians in the past 2 years – at 21% in 2018 and 23% this year.
 

Should a flu shot be mandatory?

Almost three-fourths of physicians overall – and 76% of IM physicians – say annual flu shots should be required for physicians who have patient contact. Agreement was somewhat lower among family physicians at 68%.

Some family physicians cited “freedom of choice” and that they would want to see a higher effectiveness rate before they were mandatory.

Data for this survey, with 5,130 respondents, were collected before COVID-19 vaccines became available.

A version of this article first appeared on Medscape.com.

Internal medicine physicians’ and family physicians’ attitudes have changed in recent years on several ethical issues, according to the Medscape Internal Medicine Ethics Report 2020 and the corresponding report for Family Medicine.

An example comes in an apparent loosening of attitudes about romantic/sexual relationships with former patients. Now, 31% of internists believe such a relationship is acceptable at least 6 months after the medical relationship has ended. That’s up from 22% in 2018. The number of family physicians this year who said 6 months later was acceptable also increased, but by a smaller margin – from 28% in 2018 to 33% in 2020.

“It’s acceptable as long as there is no undue influence,” David Fleming, MD, a member of the American Medical Association Council on Ethical and Judicial Affairs, said in an interview. “The important thing is that you don’t mix the two.”
 

Thoughts on upcoding

Views on billing are also shifting. Ten years ago, 17% of physicians overall thought upcoding was acceptable when submitting claims or getting prior authorization. Today just 8% of physicians overall said it was, as did 8% of family medicine (FM) physicians, according to responses.

The number of internal medicine (IM) physicians clearly opposed to upcoding declined a bit from 79% in 2018 to 75% this year, while the number saying “it depends” increased from 11% to 15%.

Many responders in both specialties said they would upgrade a code in the interest of patient advocacy.

An internist put it this way: “If the system is set up so that the only thing that would work for the patient’s condition can be obtained by an upcode, then I would consider this.”
 

More than a third say random drug checks needed

More than one-third of physicians in both specialties (34% in IM and 38% in FM) said physicians should be subjected to random alcohol and drug testing.

However, many say testing should only happen if abuse is suspected.

Some said specialty matters when it comes to random checks. An internist responded: “I think this is more important for procedure-based physicians.”

Some family physicians said that, if other health care workers were subjected to the same checks in the same circumstances, they would not object, but said doctors shouldn’t be singled out.
 

Vast majority would report an impaired peer

Nine out of 10 internists and family physicians say they would report a physician who occasionally seemed impaired but most (60% of IM respondents and 62% of FM respondents) said they would do so only after talking with the physician first.

Some noted their decision would depend on the setting.

“Big difference if they are on vacation and drink too much so they need a ride home versus being impaired at work or when on call,” one FM physician said.

About one-third of family physicians (34%) and internists (33%) now favor physician-assisted dying/suicide for incurable suffering. A substantial number (26%-28%) hesitated to make a clear decision in both specialties, responding “it depends.”

“Patient control over quality of life can be even more important than control over its quantity/duration,” one internist wrote.

The proportion of physicians who agreed physician-assisted dying/suicide should be legalized for the terminally ill was much larger, with 49% of family physicians and 52% of IM physicians saying it should.
 

Talking politics

Data in this survey were collected in summer months of 2020, before the U.S. presidential election, in a highly polarized climate. Some numbers reflect increasing distaste for such conversations with patients.

For example, the number of family physicians who said talking about politics with patients was ethical dropped from 31% in 2018 to 23% in the latest survey. The numbers remained nearly flat among IM physicians in the past 2 years – at 21% in 2018 and 23% this year.
 

Should a flu shot be mandatory?

Almost three-fourths of physicians overall – and 76% of IM physicians – say annual flu shots should be required for physicians who have patient contact. Agreement was somewhat lower among family physicians at 68%.

Some family physicians cited “freedom of choice” and that they would want to see a higher effectiveness rate before they were mandatory.

Data for this survey, with 5,130 respondents, were collected before COVID-19 vaccines became available.

A version of this article first appeared on Medscape.com.

Internal medicine physicians’ and family physicians’ attitudes have changed in recent years on several ethical issues, according to the Medscape Internal Medicine Ethics Report 2020 and the corresponding report for Family Medicine.

An example comes in an apparent loosening of attitudes about romantic/sexual relationships with former patients. Now, 31% of internists believe such a relationship is acceptable at least 6 months after the medical relationship has ended. That’s up from 22% in 2018. The number of family physicians this year who said 6 months later was acceptable also increased, but by a smaller margin – from 28% in 2018 to 33% in 2020.

“It’s acceptable as long as there is no undue influence,” David Fleming, MD, a member of the American Medical Association Council on Ethical and Judicial Affairs, said in an interview. “The important thing is that you don’t mix the two.”
 

Thoughts on upcoding

Views on billing are also shifting. Ten years ago, 17% of physicians overall thought upcoding was acceptable when submitting claims or getting prior authorization. Today just 8% of physicians overall said it was, as did 8% of family medicine (FM) physicians, according to responses.

The number of internal medicine (IM) physicians clearly opposed to upcoding declined a bit from 79% in 2018 to 75% this year, while the number saying “it depends” increased from 11% to 15%.

Many responders in both specialties said they would upgrade a code in the interest of patient advocacy.

An internist put it this way: “If the system is set up so that the only thing that would work for the patient’s condition can be obtained by an upcode, then I would consider this.”
 

More than a third say random drug checks needed

More than one-third of physicians in both specialties (34% in IM and 38% in FM) said physicians should be subjected to random alcohol and drug testing.

However, many say testing should only happen if abuse is suspected.

Some said specialty matters when it comes to random checks. An internist responded: “I think this is more important for procedure-based physicians.”

Some family physicians said that, if other health care workers were subjected to the same checks in the same circumstances, they would not object, but said doctors shouldn’t be singled out.
 

Vast majority would report an impaired peer

Nine out of 10 internists and family physicians say they would report a physician who occasionally seemed impaired but most (60% of IM respondents and 62% of FM respondents) said they would do so only after talking with the physician first.

Some noted their decision would depend on the setting.

“Big difference if they are on vacation and drink too much so they need a ride home versus being impaired at work or when on call,” one FM physician said.

About one-third of family physicians (34%) and internists (33%) now favor physician-assisted dying/suicide for incurable suffering. A substantial number (26%-28%) hesitated to make a clear decision in both specialties, responding “it depends.”

“Patient control over quality of life can be even more important than control over its quantity/duration,” one internist wrote.

The proportion of physicians who agreed physician-assisted dying/suicide should be legalized for the terminally ill was much larger, with 49% of family physicians and 52% of IM physicians saying it should.
 

Talking politics

Data in this survey were collected in summer months of 2020, before the U.S. presidential election, in a highly polarized climate. Some numbers reflect increasing distaste for such conversations with patients.

For example, the number of family physicians who said talking about politics with patients was ethical dropped from 31% in 2018 to 23% in the latest survey. The numbers remained nearly flat among IM physicians in the past 2 years – at 21% in 2018 and 23% this year.
 

Should a flu shot be mandatory?

Almost three-fourths of physicians overall – and 76% of IM physicians – say annual flu shots should be required for physicians who have patient contact. Agreement was somewhat lower among family physicians at 68%.

Some family physicians cited “freedom of choice” and that they would want to see a higher effectiveness rate before they were mandatory.

Data for this survey, with 5,130 respondents, were collected before COVID-19 vaccines became available.

A version of this article first appeared on Medscape.com.

Obesity, a risk factor for nonalcoholic fatty liver disease (NAFLD) and a prevalent comorbidity among people with cirrhosis of all etiologies, is associated with a number of untoward health outcomes, and weight loss is an important goal, according to a clinical practice update from the American Gastroenterological Association. According to one study cited in the update, approximately 30% of patients with cirrhosis have comorbid obesity, and this figure may increase even further as the epidemic of NAFLD progresses.

For obese patients with cirrhosis, weight loss “is an important therapeutic goal” because obesity heightens risks of portal vein thrombosis, portal hypertension, hepatocellular carcinoma, liver failure in acute on chronic liver disease, and other concerns. Despite no longer being an absolute contraindication, obesity can also complicate liver transplantation considerations, Heather Patton, MD, of the Veterans Affairs San Diego Healthcare System and associates wrote in Clinical Gastroenterology and Hepatology. Consideration of individuals with cirrhosis, however, requires careful scrutiny of surgical candidacy, appropriate resources for care of patients with advanced liver disease, and a high-volume bariatric surgical center given the inherent risks of surgical procedures in this patient population.

For patients with cirrhosis and obesity, laparoscopic sleeve gastrectomy is probably the best option for bariatric surgery because it preserves endoscopic access to the biliary tree, facilitates gradual weight loss, and does not cause malabsorption, according to the update.

Clinicians and patients should time bariatric surgery based on liver disease stage – for patients with decompensated disease, surgery should be performed only at the same time as or after liver transplantation, the experts wrote. Clinicians should also evaluate candidacy for liver transplantation before bariatric surgery “so that patients who are ineligible for transplant (and their families) have a clear understanding of this, avoiding the need for the medical team to address this issue urgently if the patient’s condition deteriorates postoperatively.”

One review suggested that bariatric surgery is “the most effective and durable” means of weight loss, according to the authors of the update; however, another review suggested increased surgical risk for bariatric surgery among patients with cirrhosis, so the update’s authors advised individualized risk-benefit assessments. These assessments are made even more complicated by scarcity of relevant randomized trial data, so the experts identified PubMed-indexed, peer-reviewed articles published between 2000 and 2020 and used these to make 10 best practice advice statements for bariatric surgery in obese patients with cirrhosis.

The surgical, anesthesia, and medical teams must be well versed in assessing and operating on patients with portal hypertension and cirrhosis and in managing these patients postoperatively, the experts wrote. The preoperative assessment should include cirrhosis status (compensated versus decompensated), the presence and severity of sarcopenia, ascites, and portal hypertension, and candidacy for liver transplantation. It is vital to check for clinically significant portal hypertension (CSPH) because endoscopic devices should not be used in patients with gastric and/or esophageal varices. To do so, upper endoscopy and cross-sectional imaging are advised, pending better data on noninvasive assessment methods. For patients without CSPH, endoscopic bariatric treatment can be somewhat less effective for weight loss but also might be less likely to lead to postoperative complications. However, head-to-head and long-term safety data are not yet available.

The experts also noted that bariatric surgery increases the effects (blood levels) of alcohol and can increase patients’ risk for developing an alcohol use disorder. Therefore, clinicians should carefully the history of alcohol use and repeatedly educate patients about the risks of consuming alcohol after bariatric surgery. According to a study from 2012 and a review from 2015, male sex, younger age, less social support, and regular or “problematic” alcohol use before bariatric surgery heighten the risk for developing an alcohol use disorder afterward, the experts noted.

Funding sources included the Robert H. Yauk Charitable Trust Gift for Liver Transplant Research 2017-2020 and Regenerative Medicine for Prevention of Post-Transplant Biliary Complications. The authors reported having no conflicts of interest.

This article was updated Feb. 23, 2021.

Obesity, a risk factor for nonalcoholic fatty liver disease (NAFLD) and a prevalent comorbidity among people with cirrhosis of all etiologies, is associated with a number of untoward health outcomes, and weight loss is an important goal, according to a clinical practice update from the American Gastroenterological Association. According to one study cited in the update, approximately 30% of patients with cirrhosis have comorbid obesity, and this figure may increase even further as the epidemic of NAFLD progresses.

For obese patients with cirrhosis, weight loss “is an important therapeutic goal” because obesity heightens risks of portal vein thrombosis, portal hypertension, hepatocellular carcinoma, liver failure in acute on chronic liver disease, and other concerns. Despite no longer being an absolute contraindication, obesity can also complicate liver transplantation considerations, Heather Patton, MD, of the Veterans Affairs San Diego Healthcare System and associates wrote in Clinical Gastroenterology and Hepatology. Consideration of individuals with cirrhosis, however, requires careful scrutiny of surgical candidacy, appropriate resources for care of patients with advanced liver disease, and a high-volume bariatric surgical center given the inherent risks of surgical procedures in this patient population.

For patients with cirrhosis and obesity, laparoscopic sleeve gastrectomy is probably the best option for bariatric surgery because it preserves endoscopic access to the biliary tree, facilitates gradual weight loss, and does not cause malabsorption, according to the update.

Clinicians and patients should time bariatric surgery based on liver disease stage – for patients with decompensated disease, surgery should be performed only at the same time as or after liver transplantation, the experts wrote. Clinicians should also evaluate candidacy for liver transplantation before bariatric surgery “so that patients who are ineligible for transplant (and their families) have a clear understanding of this, avoiding the need for the medical team to address this issue urgently if the patient’s condition deteriorates postoperatively.”

One review suggested that bariatric surgery is “the most effective and durable” means of weight loss, according to the authors of the update; however, another review suggested increased surgical risk for bariatric surgery among patients with cirrhosis, so the update’s authors advised individualized risk-benefit assessments. These assessments are made even more complicated by scarcity of relevant randomized trial data, so the experts identified PubMed-indexed, peer-reviewed articles published between 2000 and 2020 and used these to make 10 best practice advice statements for bariatric surgery in obese patients with cirrhosis.

The surgical, anesthesia, and medical teams must be well versed in assessing and operating on patients with portal hypertension and cirrhosis and in managing these patients postoperatively, the experts wrote. The preoperative assessment should include cirrhosis status (compensated versus decompensated), the presence and severity of sarcopenia, ascites, and portal hypertension, and candidacy for liver transplantation. It is vital to check for clinically significant portal hypertension (CSPH) because endoscopic devices should not be used in patients with gastric and/or esophageal varices. To do so, upper endoscopy and cross-sectional imaging are advised, pending better data on noninvasive assessment methods. For patients without CSPH, endoscopic bariatric treatment can be somewhat less effective for weight loss but also might be less likely to lead to postoperative complications. However, head-to-head and long-term safety data are not yet available.

The experts also noted that bariatric surgery increases the effects (blood levels) of alcohol and can increase patients’ risk for developing an alcohol use disorder. Therefore, clinicians should carefully the history of alcohol use and repeatedly educate patients about the risks of consuming alcohol after bariatric surgery. According to a study from 2012 and a review from 2015, male sex, younger age, less social support, and regular or “problematic” alcohol use before bariatric surgery heighten the risk for developing an alcohol use disorder afterward, the experts noted.

Funding sources included the Robert H. Yauk Charitable Trust Gift for Liver Transplant Research 2017-2020 and Regenerative Medicine for Prevention of Post-Transplant Biliary Complications. The authors reported having no conflicts of interest.

This article was updated Feb. 23, 2021.

Obesity, a risk factor for nonalcoholic fatty liver disease (NAFLD) and a prevalent comorbidity among people with cirrhosis of all etiologies, is associated with a number of untoward health outcomes, and weight loss is an important goal, according to a clinical practice update from the American Gastroenterological Association. According to one study cited in the update, approximately 30% of patients with cirrhosis have comorbid obesity, and this figure may increase even further as the epidemic of NAFLD progresses.

For obese patients with cirrhosis, weight loss “is an important therapeutic goal” because obesity heightens risks of portal vein thrombosis, portal hypertension, hepatocellular carcinoma, liver failure in acute on chronic liver disease, and other concerns. Despite no longer being an absolute contraindication, obesity can also complicate liver transplantation considerations, Heather Patton, MD, of the Veterans Affairs San Diego Healthcare System and associates wrote in Clinical Gastroenterology and Hepatology. Consideration of individuals with cirrhosis, however, requires careful scrutiny of surgical candidacy, appropriate resources for care of patients with advanced liver disease, and a high-volume bariatric surgical center given the inherent risks of surgical procedures in this patient population.

For patients with cirrhosis and obesity, laparoscopic sleeve gastrectomy is probably the best option for bariatric surgery because it preserves endoscopic access to the biliary tree, facilitates gradual weight loss, and does not cause malabsorption, according to the update.

Clinicians and patients should time bariatric surgery based on liver disease stage – for patients with decompensated disease, surgery should be performed only at the same time as or after liver transplantation, the experts wrote. Clinicians should also evaluate candidacy for liver transplantation before bariatric surgery “so that patients who are ineligible for transplant (and their families) have a clear understanding of this, avoiding the need for the medical team to address this issue urgently if the patient’s condition deteriorates postoperatively.”

One review suggested that bariatric surgery is “the most effective and durable” means of weight loss, according to the authors of the update; however, another review suggested increased surgical risk for bariatric surgery among patients with cirrhosis, so the update’s authors advised individualized risk-benefit assessments. These assessments are made even more complicated by scarcity of relevant randomized trial data, so the experts identified PubMed-indexed, peer-reviewed articles published between 2000 and 2020 and used these to make 10 best practice advice statements for bariatric surgery in obese patients with cirrhosis.

The surgical, anesthesia, and medical teams must be well versed in assessing and operating on patients with portal hypertension and cirrhosis and in managing these patients postoperatively, the experts wrote. The preoperative assessment should include cirrhosis status (compensated versus decompensated), the presence and severity of sarcopenia, ascites, and portal hypertension, and candidacy for liver transplantation. It is vital to check for clinically significant portal hypertension (CSPH) because endoscopic devices should not be used in patients with gastric and/or esophageal varices. To do so, upper endoscopy and cross-sectional imaging are advised, pending better data on noninvasive assessment methods. For patients without CSPH, endoscopic bariatric treatment can be somewhat less effective for weight loss but also might be less likely to lead to postoperative complications. However, head-to-head and long-term safety data are not yet available.

The experts also noted that bariatric surgery increases the effects (blood levels) of alcohol and can increase patients’ risk for developing an alcohol use disorder. Therefore, clinicians should carefully the history of alcohol use and repeatedly educate patients about the risks of consuming alcohol after bariatric surgery. According to a study from 2012 and a review from 2015, male sex, younger age, less social support, and regular or “problematic” alcohol use before bariatric surgery heighten the risk for developing an alcohol use disorder afterward, the experts noted.

Funding sources included the Robert H. Yauk Charitable Trust Gift for Liver Transplant Research 2017-2020 and Regenerative Medicine for Prevention of Post-Transplant Biliary Complications. The authors reported having no conflicts of interest.

This article was updated Feb. 23, 2021.