Importance

The prevention and treatment of traveler’s diarrhea (TD) is a common reason that patients consult their physician prior to foreign travel. TD can result in lost time and opportunity, as well as overseas medical encounters and hospitalization. This guideline by the International Society of Travel Medicine provides clinically relevant, useful, and practical guidance to providers regarding the use of antibiotic and nonantibiotic therapies for the prevention and treatment of TD.

Prophylaxis

The panel recommends that antimicrobial prophylaxis should not be used routinely in travelers, but it should be considered for travelers who are at high risk of health-related complications of TD (both strong recommendations, low/very low level of evidence [LOE]). High-risk individuals include those with a history of clinically significant long-term morbidity following an enteric infection or serious chronic illnesses that predisposes them for TD-related complications. Bismuth subsalicylate (BSS) may be considered for any traveler to prevent TD (3, strong recommendation, high LOE). Studies show that a lower dose of 1.05 g/day is preventive, although it is unclear whether it is as effective as higher doses of 2.1 g/day or 4.2 g/day. When prophylaxis is indicated, travelers should be prescribed rifaximin (strong recommendation, moderate LOE) based on susceptibility of most enteric pathogens and the drug’s extremely favorable safety profile. Fluoroquinolones (FQ) are no longer recommended for prophylaxis (strong recommendation, low/very low LOE) because of neurologic and musculoskeletal side effects that may outweigh benefits, as well as emerging resistance of enteric pathogens (70%-80% in Campylobacter spp. from Nepal and Thailand and 65% in Enterotoxigenic Escherichia coli [ETEC] and Enteroaggregative E. coli [EAEC] in India).

Treatment

The following treatment recommendations are based on the classification of TD using functional effects of severity; therefore, the panel made new definitions for TD severity. This is a change from previous definitions that utilized a traditional frequency-based algorithm in order to tailor therapy for the individual. Individuals can be prescribed antibiotics and antimotility agents to take with them during travel, along with advice regarding how to judge when to use each agent.

Mild: diarrhea that is tolerable, is not distressing, and does not interfere with planned activities.

Encourage supportive measures such as rehydration and nonantibiotic, antimotility drugs, such as loperamide or BSS (both strong recommendations, moderate LOE).

Moderate: diarrhea that is distressing or interferes with planned activities.

Antibiotics may be used (weak recommendation, moderate LOE) as early and effective treatment may mitigate the well-described chronic health consequences including irritable bowel syndrome. Three options exist. FQs may be used outside of Southeast and South Asia (strong recommendation, moderate LOE), but their potential for adverse effects and musculoskeletal consequences must be considered. Azithromycin may be used (strong recommendation, high LOE) because studies show no significant differences in efficacy between it and FQs, limited resistance to common TD pathogens (although concerns exist in Nepal), and good side effect profile. Another choice is rifaximin (weak recommendation, moderate LOE), although one should exercise caution for empirical therapy in regions in which being at high risk of invasive pathogens is anticipated.

Loperamide may be used as adjunctive therapy for moderate to severe TD (strong recommendation, high LOE) to add symptomatic relief with curative treatment or as monotherapy in moderate TD (strong recommendation, high LOE). This is specifically true in children aged 2-11 years, in whom loperamide is beneficial without causing severe side effects.

Severe: diarrhea that is incapacitating or completely prevents planned activities; all dysentery (passage of grossly bloody stools).

Antibiotics should be used (strong recommendation, high LOE). Azithromycin is the preferred choice and is first-line for dysentery or febrile diarrhea (strong recommendation, moderate LOE) because of the likelihood of FQ-resistant bacteria being the cause of dysentery. FQs and rifaximin are also choices that can be used to treat severe, nondysenteric TD (both weak recommendations, moderate LOE).

Furthermore, single-dose antibiotics may be used to treat moderate or severe TD (strong recommendation, high LOE) because studies have shown equivalent efficacy for treatment of watery noninvasive diarrhea among FQs (3 days, single dose), azithromycin (3 days, single dose), and rifaximin (3 days, three times daily).

Persistent: diarrhea lasting longer than 2 weeks.

Functional bowel disease (FBD) may occur after bouts of TD and may meet Rome III or IV criteria for irritable bowel syndrome. Thus, in a traveler without pretravel GI disease, in whom the evaluation for microbial etiologies and underlying GI disease is negative, postinfectious FBD must be considered.

Follow-up and diagnostic testing

The panel recommends microbiological testing in returning travelers with severe or persistent symptoms, bloody/mucousy diarrhea, or in those who fail empiric therapy (strong recommendation, low/very low LOE). Molecular testing, aimed at a broad range of clinically relevant pathogens, is preferred when rapid results are clinically important or nonmolecular tests have failed to establish a diagnosis. Furthermore, molecular testing may, in some cases, detect colonization rather than infection.
 

The bottom line

The expert panel made 20 graded recommendations to help guide the provider with nonantibiotic and antibiotic prophylaxis and treatment of TD. The main take-home points include:

• Prophylaxis should be considered only in high-risk groups; rifaximin is the first choice, and BSS is a second option.
• All travelers should be provided with loperamide and an antibiotic for self-treatment if needed.
• Mild diarrhea should be treated with increased fluid intake and loperamide or BSS.
• Moderate to severe diarrhea should be treated with single-dose antimicrobial therapy of FQ or azithromycin or with rifaximin dosing three times a day.
• Instead of antibiotics, loperamide may be considered as monotherapy for moderate diarrhea; loperamide can be used with antibiotics for both moderate and severe TD.

Dr. Shrestha is a second-year resident in the Family Medicine Residency Program at Abington (Pa.) - Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington - Jefferson Health.

Reference:

J Travel Med. 2017 Apr 1;24(suppl_1):S57-74.

Importance

The prevention and treatment of traveler’s diarrhea (TD) is a common reason that patients consult their physician prior to foreign travel. TD can result in lost time and opportunity, as well as overseas medical encounters and hospitalization. This guideline by the International Society of Travel Medicine provides clinically relevant, useful, and practical guidance to providers regarding the use of antibiotic and nonantibiotic therapies for the prevention and treatment of TD.

Prophylaxis

The panel recommends that antimicrobial prophylaxis should not be used routinely in travelers, but it should be considered for travelers who are at high risk of health-related complications of TD (both strong recommendations, low/very low level of evidence [LOE]). High-risk individuals include those with a history of clinically significant long-term morbidity following an enteric infection or serious chronic illnesses that predisposes them for TD-related complications. Bismuth subsalicylate (BSS) may be considered for any traveler to prevent TD (3, strong recommendation, high LOE). Studies show that a lower dose of 1.05 g/day is preventive, although it is unclear whether it is as effective as higher doses of 2.1 g/day or 4.2 g/day. When prophylaxis is indicated, travelers should be prescribed rifaximin (strong recommendation, moderate LOE) based on susceptibility of most enteric pathogens and the drug’s extremely favorable safety profile. Fluoroquinolones (FQ) are no longer recommended for prophylaxis (strong recommendation, low/very low LOE) because of neurologic and musculoskeletal side effects that may outweigh benefits, as well as emerging resistance of enteric pathogens (70%-80% in Campylobacter spp. from Nepal and Thailand and 65% in Enterotoxigenic Escherichia coli [ETEC] and Enteroaggregative E. coli [EAEC] in India).

Treatment

The following treatment recommendations are based on the classification of TD using functional effects of severity; therefore, the panel made new definitions for TD severity. This is a change from previous definitions that utilized a traditional frequency-based algorithm in order to tailor therapy for the individual. Individuals can be prescribed antibiotics and antimotility agents to take with them during travel, along with advice regarding how to judge when to use each agent.

Mild: diarrhea that is tolerable, is not distressing, and does not interfere with planned activities.

Encourage supportive measures such as rehydration and nonantibiotic, antimotility drugs, such as loperamide or BSS (both strong recommendations, moderate LOE).

Moderate: diarrhea that is distressing or interferes with planned activities.

Antibiotics may be used (weak recommendation, moderate LOE) as early and effective treatment may mitigate the well-described chronic health consequences including irritable bowel syndrome. Three options exist. FQs may be used outside of Southeast and South Asia (strong recommendation, moderate LOE), but their potential for adverse effects and musculoskeletal consequences must be considered. Azithromycin may be used (strong recommendation, high LOE) because studies show no significant differences in efficacy between it and FQs, limited resistance to common TD pathogens (although concerns exist in Nepal), and good side effect profile. Another choice is rifaximin (weak recommendation, moderate LOE), although one should exercise caution for empirical therapy in regions in which being at high risk of invasive pathogens is anticipated.

Loperamide may be used as adjunctive therapy for moderate to severe TD (strong recommendation, high LOE) to add symptomatic relief with curative treatment or as monotherapy in moderate TD (strong recommendation, high LOE). This is specifically true in children aged 2-11 years, in whom loperamide is beneficial without causing severe side effects.

Severe: diarrhea that is incapacitating or completely prevents planned activities; all dysentery (passage of grossly bloody stools).

Antibiotics should be used (strong recommendation, high LOE). Azithromycin is the preferred choice and is first-line for dysentery or febrile diarrhea (strong recommendation, moderate LOE) because of the likelihood of FQ-resistant bacteria being the cause of dysentery. FQs and rifaximin are also choices that can be used to treat severe, nondysenteric TD (both weak recommendations, moderate LOE).

Furthermore, single-dose antibiotics may be used to treat moderate or severe TD (strong recommendation, high LOE) because studies have shown equivalent efficacy for treatment of watery noninvasive diarrhea among FQs (3 days, single dose), azithromycin (3 days, single dose), and rifaximin (3 days, three times daily).

Persistent: diarrhea lasting longer than 2 weeks.

Functional bowel disease (FBD) may occur after bouts of TD and may meet Rome III or IV criteria for irritable bowel syndrome. Thus, in a traveler without pretravel GI disease, in whom the evaluation for microbial etiologies and underlying GI disease is negative, postinfectious FBD must be considered.

Follow-up and diagnostic testing

The panel recommends microbiological testing in returning travelers with severe or persistent symptoms, bloody/mucousy diarrhea, or in those who fail empiric therapy (strong recommendation, low/very low LOE). Molecular testing, aimed at a broad range of clinically relevant pathogens, is preferred when rapid results are clinically important or nonmolecular tests have failed to establish a diagnosis. Furthermore, molecular testing may, in some cases, detect colonization rather than infection.
 

The bottom line

The expert panel made 20 graded recommendations to help guide the provider with nonantibiotic and antibiotic prophylaxis and treatment of TD. The main take-home points include:

• Prophylaxis should be considered only in high-risk groups; rifaximin is the first choice, and BSS is a second option.
• All travelers should be provided with loperamide and an antibiotic for self-treatment if needed.
• Mild diarrhea should be treated with increased fluid intake and loperamide or BSS.
• Moderate to severe diarrhea should be treated with single-dose antimicrobial therapy of FQ or azithromycin or with rifaximin dosing three times a day.
• Instead of antibiotics, loperamide may be considered as monotherapy for moderate diarrhea; loperamide can be used with antibiotics for both moderate and severe TD.

Dr. Shrestha is a second-year resident in the Family Medicine Residency Program at Abington (Pa.) - Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington - Jefferson Health.

Reference:

J Travel Med. 2017 Apr 1;24(suppl_1):S57-74.

Importance

The prevention and treatment of traveler’s diarrhea (TD) is a common reason that patients consult their physician prior to foreign travel. TD can result in lost time and opportunity, as well as overseas medical encounters and hospitalization. This guideline by the International Society of Travel Medicine provides clinically relevant, useful, and practical guidance to providers regarding the use of antibiotic and nonantibiotic therapies for the prevention and treatment of TD.

Prophylaxis

The panel recommends that antimicrobial prophylaxis should not be used routinely in travelers, but it should be considered for travelers who are at high risk of health-related complications of TD (both strong recommendations, low/very low level of evidence [LOE]). High-risk individuals include those with a history of clinically significant long-term morbidity following an enteric infection or serious chronic illnesses that predisposes them for TD-related complications. Bismuth subsalicylate (BSS) may be considered for any traveler to prevent TD (3, strong recommendation, high LOE). Studies show that a lower dose of 1.05 g/day is preventive, although it is unclear whether it is as effective as higher doses of 2.1 g/day or 4.2 g/day. When prophylaxis is indicated, travelers should be prescribed rifaximin (strong recommendation, moderate LOE) based on susceptibility of most enteric pathogens and the drug’s extremely favorable safety profile. Fluoroquinolones (FQ) are no longer recommended for prophylaxis (strong recommendation, low/very low LOE) because of neurologic and musculoskeletal side effects that may outweigh benefits, as well as emerging resistance of enteric pathogens (70%-80% in Campylobacter spp. from Nepal and Thailand and 65% in Enterotoxigenic Escherichia coli [ETEC] and Enteroaggregative E. coli [EAEC] in India).

Treatment

The following treatment recommendations are based on the classification of TD using functional effects of severity; therefore, the panel made new definitions for TD severity. This is a change from previous definitions that utilized a traditional frequency-based algorithm in order to tailor therapy for the individual. Individuals can be prescribed antibiotics and antimotility agents to take with them during travel, along with advice regarding how to judge when to use each agent.

Mild: diarrhea that is tolerable, is not distressing, and does not interfere with planned activities.

Encourage supportive measures such as rehydration and nonantibiotic, antimotility drugs, such as loperamide or BSS (both strong recommendations, moderate LOE).

Moderate: diarrhea that is distressing or interferes with planned activities.

Antibiotics may be used (weak recommendation, moderate LOE) as early and effective treatment may mitigate the well-described chronic health consequences including irritable bowel syndrome. Three options exist. FQs may be used outside of Southeast and South Asia (strong recommendation, moderate LOE), but their potential for adverse effects and musculoskeletal consequences must be considered. Azithromycin may be used (strong recommendation, high LOE) because studies show no significant differences in efficacy between it and FQs, limited resistance to common TD pathogens (although concerns exist in Nepal), and good side effect profile. Another choice is rifaximin (weak recommendation, moderate LOE), although one should exercise caution for empirical therapy in regions in which being at high risk of invasive pathogens is anticipated.

Loperamide may be used as adjunctive therapy for moderate to severe TD (strong recommendation, high LOE) to add symptomatic relief with curative treatment or as monotherapy in moderate TD (strong recommendation, high LOE). This is specifically true in children aged 2-11 years, in whom loperamide is beneficial without causing severe side effects.

Severe: diarrhea that is incapacitating or completely prevents planned activities; all dysentery (passage of grossly bloody stools).

Antibiotics should be used (strong recommendation, high LOE). Azithromycin is the preferred choice and is first-line for dysentery or febrile diarrhea (strong recommendation, moderate LOE) because of the likelihood of FQ-resistant bacteria being the cause of dysentery. FQs and rifaximin are also choices that can be used to treat severe, nondysenteric TD (both weak recommendations, moderate LOE).

Furthermore, single-dose antibiotics may be used to treat moderate or severe TD (strong recommendation, high LOE) because studies have shown equivalent efficacy for treatment of watery noninvasive diarrhea among FQs (3 days, single dose), azithromycin (3 days, single dose), and rifaximin (3 days, three times daily).

Persistent: diarrhea lasting longer than 2 weeks.

Functional bowel disease (FBD) may occur after bouts of TD and may meet Rome III or IV criteria for irritable bowel syndrome. Thus, in a traveler without pretravel GI disease, in whom the evaluation for microbial etiologies and underlying GI disease is negative, postinfectious FBD must be considered.

Follow-up and diagnostic testing

The panel recommends microbiological testing in returning travelers with severe or persistent symptoms, bloody/mucousy diarrhea, or in those who fail empiric therapy (strong recommendation, low/very low LOE). Molecular testing, aimed at a broad range of clinically relevant pathogens, is preferred when rapid results are clinically important or nonmolecular tests have failed to establish a diagnosis. Furthermore, molecular testing may, in some cases, detect colonization rather than infection.
 

The bottom line

The expert panel made 20 graded recommendations to help guide the provider with nonantibiotic and antibiotic prophylaxis and treatment of TD. The main take-home points include:

• Prophylaxis should be considered only in high-risk groups; rifaximin is the first choice, and BSS is a second option.
• All travelers should be provided with loperamide and an antibiotic for self-treatment if needed.
• Mild diarrhea should be treated with increased fluid intake and loperamide or BSS.
• Moderate to severe diarrhea should be treated with single-dose antimicrobial therapy of FQ or azithromycin or with rifaximin dosing three times a day.
• Instead of antibiotics, loperamide may be considered as monotherapy for moderate diarrhea; loperamide can be used with antibiotics for both moderate and severe TD.

Dr. Shrestha is a second-year resident in the Family Medicine Residency Program at Abington (Pa.) - Jefferson Health. Dr. Skolnik is a professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington - Jefferson Health.

Reference:

J Travel Med. 2017 Apr 1;24(suppl_1):S57-74.

Busulfan plus melphalan could replace melphalan alone as the standard conditioning regimen for multiple myeloma patients undergoing autologous hematopoietic cell transplant, according to researchers.

Courtesy Wikimedia Commons/KGH/Creative Commons License

In a phase 3 trial, patients who received conditioning with busulfan plus melphalan had significantly longer median progression-free survival compared with patients who received melphalan alone – 64.7 months versus 43.5 months (P = .022).

However, there was no overall survival advantage with busulfan plus melphalan, and adverse events were more common with this regimen, reported Qaiser Bashir, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues. The report is in The Lancet Haematology.

To their knowledge, the researchers wrote, this was the first randomized, phase 3 trial showing a significant progression-free survival benefit for busulfan plus melphalan versus the standard of care of melphalan 200 mg/m² pretransplantation conditioning. “These data suggest that busulfan plus melphalan conditioning can serve as a useful platform for further improvement of transplant outcomes in patients with myeloma.”

The current trial (NCT01413178) enrolled 205 multiple myeloma patients who were eligible for transplant. They were randomized to conditioning with melphalan alone or busulfan plus melphalan.

In all, 98 patients received melphalan alone, given at 200 mg/m² on day –2. The 104 patients who received busulfan plus melphalan started with a test dose of busulfan at 32 mg/m², which was followed by pharmacokinetically adjusted doses on days –7, –6, –5, and –4 to achieve a target daily area under the curve of 5,000 mmol/minute. These patients received melphalan at 70 mg/m² per day on days –2 and –1.

The median age at transplant was 57.9 years (range, 31.7-70.9 years) in the busulfan group and 57.6 years (range, 34.3-70.6 years) in the melphalan-alone group.

The most common induction regimen used was bortezomib, lenalidomide, and dexamethasone, which was given to 60% of the busulfan group and 57% of the melphalan-alone group.

Most patients responded to induction – 96% of patients in the busulfan group and 94% of those in the melphalan-alone group.

There was no treatment-related mortality within 100 days of transplant.

At 90 days after transplant, the response rate was 98% in the busulfan group and 97% in the melphalan-alone group. The rate of complete remission/stringent complete remission was 27% and 34%, respectively.

Most patients received posttransplant maintenance. The most common maintenance regimen consisted of lenalidomide monotherapy, which was given to 57% of the busulfan group and 58% of the melphalan-alone group.

Patients continued maintenance until disease progression or unacceptable toxicity. The median duration of maintenance was 16.0 months in the busulfan group and 10.1 months in the melphalan-alone group.

The median follow-up was 22.6 months in the busulfan group and 20.2 months in the melphalan-alone group.

Progression-free survival was superior in the busulfan group. Median progression-free survival was 64.7 months in the busulfan group and 43.5 months in the melphalan-alone group (hazard ratio = 0.53; P = .022). The 3-year progression-free survival rate was 72% and 50%, respectively.

The median overall survival was not reached in either group. The 3-year overall survival rate was 91% in the busulfan group and 89% in the melphalan-alone group.

There were 10 deaths in the busulfan group, 7 due to progression and 3 due to infection. All 7 deaths in the melphalan-alone group were due to progression.

Grade 3-4 nonhematologic toxicity was more common in the busulfan group, occurring in 84% of that group and 33% of the melphalan-alone group (P less than .0001).

Grade 2-3 mucositis occurred in 74% of the busulfan group and 14% of the melphalan-alone group. There were no cases of grade 4 mucositis.

One patient in the busulfan group had grade 4 cardiac toxicity, an acute myocardial infarction, and ventricular fibrillation. However, the patient recovered and was in remission at last follow-up.

Two patients in the busulfan group developed second primary malignancies. One patient developed squamous cell skin cancer and rectal adenocarcinoma, and the other developed melanoma and basal cell skin carcinoma.

Three patients in the melphalan-alone group developed second primary malignancies. Two patients had squamous cell skin cancers and one had myelodysplastic syndrome.

Dr. Bashir and his colleagues noted that this study has limitations, including insufficient data to assess minimal residual disease and its impact on survival. It is a single-center study and induction and maintenance therapies were not prespecified.

“These results should be verified in a cooperative group or a multicenter, randomized study to assess the generalizability of our findings,” the researchers wrote.

Dr. Bashir and his colleagues reported having no competing financial interests. The trial was sponsored by MD Anderson Cancer Center in collaboration with Otsuka Pharmaceutical Development & Commercialization. The work was funded in part by the National Institutes of Health.

jensmith@mdedge.com

SOURCE: Bashir Q et al. Lancet Haematol. 2019 Mar 22. doi: 10.1016/S2352-3026(19)30023-7.

Busulfan plus melphalan could replace melphalan alone as the standard conditioning regimen for multiple myeloma patients undergoing autologous hematopoietic cell transplant, according to researchers.

Courtesy Wikimedia Commons/KGH/Creative Commons License

In a phase 3 trial, patients who received conditioning with busulfan plus melphalan had significantly longer median progression-free survival compared with patients who received melphalan alone – 64.7 months versus 43.5 months (P = .022).

However, there was no overall survival advantage with busulfan plus melphalan, and adverse events were more common with this regimen, reported Qaiser Bashir, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues. The report is in The Lancet Haematology.

To their knowledge, the researchers wrote, this was the first randomized, phase 3 trial showing a significant progression-free survival benefit for busulfan plus melphalan versus the standard of care of melphalan 200 mg/m² pretransplantation conditioning. “These data suggest that busulfan plus melphalan conditioning can serve as a useful platform for further improvement of transplant outcomes in patients with myeloma.”

The current trial (NCT01413178) enrolled 205 multiple myeloma patients who were eligible for transplant. They were randomized to conditioning with melphalan alone or busulfan plus melphalan.

In all, 98 patients received melphalan alone, given at 200 mg/m² on day –2. The 104 patients who received busulfan plus melphalan started with a test dose of busulfan at 32 mg/m², which was followed by pharmacokinetically adjusted doses on days –7, –6, –5, and –4 to achieve a target daily area under the curve of 5,000 mmol/minute. These patients received melphalan at 70 mg/m² per day on days –2 and –1.

The median age at transplant was 57.9 years (range, 31.7-70.9 years) in the busulfan group and 57.6 years (range, 34.3-70.6 years) in the melphalan-alone group.

The most common induction regimen used was bortezomib, lenalidomide, and dexamethasone, which was given to 60% of the busulfan group and 57% of the melphalan-alone group.

Most patients responded to induction – 96% of patients in the busulfan group and 94% of those in the melphalan-alone group.

There was no treatment-related mortality within 100 days of transplant.

At 90 days after transplant, the response rate was 98% in the busulfan group and 97% in the melphalan-alone group. The rate of complete remission/stringent complete remission was 27% and 34%, respectively.

Most patients received posttransplant maintenance. The most common maintenance regimen consisted of lenalidomide monotherapy, which was given to 57% of the busulfan group and 58% of the melphalan-alone group.

Patients continued maintenance until disease progression or unacceptable toxicity. The median duration of maintenance was 16.0 months in the busulfan group and 10.1 months in the melphalan-alone group.

The median follow-up was 22.6 months in the busulfan group and 20.2 months in the melphalan-alone group.

Progression-free survival was superior in the busulfan group. Median progression-free survival was 64.7 months in the busulfan group and 43.5 months in the melphalan-alone group (hazard ratio = 0.53; P = .022). The 3-year progression-free survival rate was 72% and 50%, respectively.

The median overall survival was not reached in either group. The 3-year overall survival rate was 91% in the busulfan group and 89% in the melphalan-alone group.

There were 10 deaths in the busulfan group, 7 due to progression and 3 due to infection. All 7 deaths in the melphalan-alone group were due to progression.

Grade 3-4 nonhematologic toxicity was more common in the busulfan group, occurring in 84% of that group and 33% of the melphalan-alone group (P less than .0001).

Grade 2-3 mucositis occurred in 74% of the busulfan group and 14% of the melphalan-alone group. There were no cases of grade 4 mucositis.

One patient in the busulfan group had grade 4 cardiac toxicity, an acute myocardial infarction, and ventricular fibrillation. However, the patient recovered and was in remission at last follow-up.

Two patients in the busulfan group developed second primary malignancies. One patient developed squamous cell skin cancer and rectal adenocarcinoma, and the other developed melanoma and basal cell skin carcinoma.

Three patients in the melphalan-alone group developed second primary malignancies. Two patients had squamous cell skin cancers and one had myelodysplastic syndrome.

Dr. Bashir and his colleagues noted that this study has limitations, including insufficient data to assess minimal residual disease and its impact on survival. It is a single-center study and induction and maintenance therapies were not prespecified.

“These results should be verified in a cooperative group or a multicenter, randomized study to assess the generalizability of our findings,” the researchers wrote.

Dr. Bashir and his colleagues reported having no competing financial interests. The trial was sponsored by MD Anderson Cancer Center in collaboration with Otsuka Pharmaceutical Development & Commercialization. The work was funded in part by the National Institutes of Health.

jensmith@mdedge.com

SOURCE: Bashir Q et al. Lancet Haematol. 2019 Mar 22. doi: 10.1016/S2352-3026(19)30023-7.

Busulfan plus melphalan could replace melphalan alone as the standard conditioning regimen for multiple myeloma patients undergoing autologous hematopoietic cell transplant, according to researchers.

Courtesy Wikimedia Commons/KGH/Creative Commons License

In a phase 3 trial, patients who received conditioning with busulfan plus melphalan had significantly longer median progression-free survival compared with patients who received melphalan alone – 64.7 months versus 43.5 months (P = .022).

However, there was no overall survival advantage with busulfan plus melphalan, and adverse events were more common with this regimen, reported Qaiser Bashir, MD, of the University of Texas MD Anderson Cancer Center in Houston, and his colleagues. The report is in The Lancet Haematology.

To their knowledge, the researchers wrote, this was the first randomized, phase 3 trial showing a significant progression-free survival benefit for busulfan plus melphalan versus the standard of care of melphalan 200 mg/m² pretransplantation conditioning. “These data suggest that busulfan plus melphalan conditioning can serve as a useful platform for further improvement of transplant outcomes in patients with myeloma.”

The current trial (NCT01413178) enrolled 205 multiple myeloma patients who were eligible for transplant. They were randomized to conditioning with melphalan alone or busulfan plus melphalan.

In all, 98 patients received melphalan alone, given at 200 mg/m² on day –2. The 104 patients who received busulfan plus melphalan started with a test dose of busulfan at 32 mg/m², which was followed by pharmacokinetically adjusted doses on days –7, –6, –5, and –4 to achieve a target daily area under the curve of 5,000 mmol/minute. These patients received melphalan at 70 mg/m² per day on days –2 and –1.

The median age at transplant was 57.9 years (range, 31.7-70.9 years) in the busulfan group and 57.6 years (range, 34.3-70.6 years) in the melphalan-alone group.

The most common induction regimen used was bortezomib, lenalidomide, and dexamethasone, which was given to 60% of the busulfan group and 57% of the melphalan-alone group.

Most patients responded to induction – 96% of patients in the busulfan group and 94% of those in the melphalan-alone group.

There was no treatment-related mortality within 100 days of transplant.

At 90 days after transplant, the response rate was 98% in the busulfan group and 97% in the melphalan-alone group. The rate of complete remission/stringent complete remission was 27% and 34%, respectively.

Most patients received posttransplant maintenance. The most common maintenance regimen consisted of lenalidomide monotherapy, which was given to 57% of the busulfan group and 58% of the melphalan-alone group.

Patients continued maintenance until disease progression or unacceptable toxicity. The median duration of maintenance was 16.0 months in the busulfan group and 10.1 months in the melphalan-alone group.

The median follow-up was 22.6 months in the busulfan group and 20.2 months in the melphalan-alone group.

Progression-free survival was superior in the busulfan group. Median progression-free survival was 64.7 months in the busulfan group and 43.5 months in the melphalan-alone group (hazard ratio = 0.53; P = .022). The 3-year progression-free survival rate was 72% and 50%, respectively.

The median overall survival was not reached in either group. The 3-year overall survival rate was 91% in the busulfan group and 89% in the melphalan-alone group.

There were 10 deaths in the busulfan group, 7 due to progression and 3 due to infection. All 7 deaths in the melphalan-alone group were due to progression.

Grade 3-4 nonhematologic toxicity was more common in the busulfan group, occurring in 84% of that group and 33% of the melphalan-alone group (P less than .0001).

Grade 2-3 mucositis occurred in 74% of the busulfan group and 14% of the melphalan-alone group. There were no cases of grade 4 mucositis.

One patient in the busulfan group had grade 4 cardiac toxicity, an acute myocardial infarction, and ventricular fibrillation. However, the patient recovered and was in remission at last follow-up.

Two patients in the busulfan group developed second primary malignancies. One patient developed squamous cell skin cancer and rectal adenocarcinoma, and the other developed melanoma and basal cell skin carcinoma.

Three patients in the melphalan-alone group developed second primary malignancies. Two patients had squamous cell skin cancers and one had myelodysplastic syndrome.

Dr. Bashir and his colleagues noted that this study has limitations, including insufficient data to assess minimal residual disease and its impact on survival. It is a single-center study and induction and maintenance therapies were not prespecified.

“These results should be verified in a cooperative group or a multicenter, randomized study to assess the generalizability of our findings,” the researchers wrote.

Dr. Bashir and his colleagues reported having no competing financial interests. The trial was sponsored by MD Anderson Cancer Center in collaboration with Otsuka Pharmaceutical Development & Commercialization. The work was funded in part by the National Institutes of Health.

jensmith@mdedge.com

SOURCE: Bashir Q et al. Lancet Haematol. 2019 Mar 22. doi: 10.1016/S2352-3026(19)30023-7.

Perinatal depression is an episode of major or minor depression that occurs during pregnancy or in the 12 months after birth; it affects about 10% of new mothers.¹ Perinatal depression adversely impacts mothers, children, and their families. Pregnant women with depression are at increased risk for preterm birth and low birth weight.² Infants of mothers with postpartum depression have reduced bonding, lower rates of breastfeeding, delayed cognitive and social development, and an increased risk of future mental health issues.³ Timely treatment of perinatal depression can improve health outcomes for the woman, her children, and their family.

Clinicians follow current screening recommendations

The American College of Obstetricians and Gynecologists (ACOG) currently recommends that ObGynsscreen all pregnant women for depression and anxiety symptoms at least once during the perinatal period.¹ Many practices use the Edinburgh Postnatal Depression Scale (EPDS) during pregnancy and postpartum. Women who screen positive are referred to mental health clinicians or have treatment initiated by their primary obstetrician.

Clinicians have been phenomenally successful in screening for perinatal depression. In a recent study from Kaiser Permanente Northern California, 98% of pregnant women were screened for perinatal depression, and a diagnosis of depression was made in 12%.⁴ Of note, only 47% of women who screened positive for depression initiated treatment, although 82% of women with the most severe symptoms initiated treatment. These data demonstrate that ObGyns consistently screen pregnant women for depression but, due to patient and system issues, treatment of all screen-positive women remains a yet unattained goal.^5,6

New USPSTF guideline: Identify women at risk for perinatal depression and refer for counseling

In 2016 the United States Preventive Services Task Force (USPSTF) recommended that pregnant and postpartum women be screened for depression with adequate systems in place to ensure diagnosis, effective treatment, and follow-up.⁷ The 2016 USPSTF recommendation was consistent with prior guidelines from both the American Academy of Pediatrics in 2010⁸ and ACOG in 2015.⁹

Now, the USPSTF is making a bold new recommendation, jumping ahead of professional societies: screen pregnant women to identify those at risk for perinatal depression and refer them for counseling (B recommendation; net benefit is moderate).^10,11 The USPSTF recommendation is based on growing literature that shows counseling women at risk for perinatal depression reduces the risk of having an episode of major depression by 40%.¹¹ Both interpersonal psychotherapy and cognitive behavioral therapy have been reported to be effective for preventing perinatal depression.^12,13

As an example of the relevant literature, in one trial performed in Rhode Island, women who were 20 to 35 weeks pregnant with a high score (≥27) on the Cooper Survey Questionnaire and on public assistance were randomized to counseling or usual care. The counseling intervention involved 4 small group (2 to 5 women) sessions of 90 minutes and one individual session of 50 minutes.¹⁴ The treatment focused on managing the transition to motherhood, developing a support system, improving communication skills to manage conflict, goal setting, and identifying psychosocial supports for new mothers. At 6 months after birth, a depressive episode had occurred in 31% of the control women and 16% of the women who had experienced the intervention (P = .041). At 12 months after birth, a depressive episode had occurred in 40% of control women and 26% of women in the intervention group (P = .052).

Of note, most cases of postpartum depression were diagnosed more than 3 months after birth, a time when new mothers generally no longer are receiving regular postpartum care by an obstetrician. The timing of the diagnosis of perinatal depression indicates that an effective handoff between the obstetrician and primary care and/or mental health clinicians is of great importance. The investigators concluded that pregnant women at very high risk for perinatal depression who receive interpersonal therapy have a lower rate of a postpartum depressive episode than women receiving usual care.¹⁴

Pregnancy, delivery, and the first year following birth are stressful for many women and their families. Women who are young, poor, and with minimal social supports are at especially high risk for developing perinatal depression. However, it will be challenging for obstetric practices to rapidly implement the new USPSTF recommendations because there is no professional consensus on how to screen women to identify those at high risk for perinatal depression, and mental health resources to care for the screen-positive women are not sufficient.

Continue to: Challenges to implementing new USPSTF guideline...

Challenges to implementing new USPSTF guideline

Challenge 1: There is no widely accepted approach for identifying women at risk for perinatal depression. The USPSTF acknowledges “there is no accurate screening tool for identifying who is at risk of perinatal depression and who might benefit from preventive interventions.”¹⁰

Obstetricians have had great success in screening for perinatal depression because validated screening tools are available. Professional societies need to reach a consensus on recommending a specific screening tool for perinatal depression risk that can be used in all obstetric practices.

Challenge 2: The USPSTF guideline identifies many risk factors for perinatal depression. The USPSTF concluded that pregnant women with one (or more) of the following risk factors are at high risk for perinatal depression and recommended that they be offered a counseling intervention:

• personal history of depression
• current depressive symptoms that do not reach a diagnostic threshold
• low income
• all adolescents
• all single mothers
• recent exposure to intimate partner violence
• elevated anxiety symptoms
• a history of significant negative life events.

For many obstetricians, most of their pregnant patients meet the USPSTF criteria for being at high risk for perinatal depression and, per the guideline, these women should have a counseling intervention.

Challenge 3: The counseling intervention recommended by the USPSTF may not be available to all women at risk for perinatal depression. The USPSTF literature review, including a meta-analysis of 49 randomized clinical trials, concluded that for women at risk for perinatal depression, a counseling intervention reduces the risk of depression. In the published literature, many counseling interventions to reduce the risk of perinatal depression involve 6 to 12 hours of contact time over 4 to 8 episodes.

For many health systems, the resources available to provide mental health services are very limited. If most pregnant women need a counseling intervention, the health system must evolve to meet this need. In addition, risk factors for perinatal depression are also risk factors for having difficulty in participating in mental health interventions due to limitations, such as lack of transportation, social support, and money.⁴

Fortunately, clinicians from many backgrounds, including psychologists, social workers, nurse practitioners, and public health workers have the experience and/or training to provide the counseling interventions that have been shown to reduce the risk of perinatal depression. Health systems will need to tap all these resources to accommodate the large numbers of pregnant women who will be referred for counseling interventions. Pilot projects using electronic interventions, including telephone counseling, smartphone apps, and internet programs show promise.^15,16 Electronic interventions have the potential to reach many pregnant women without over-taxing limited mental health resources.

A practical approach

Identify women at the greatest risk for perinatal depression and focus counseling interventions on this group. In my opinion, implementation of the USPSTF recommendation will take time. A practical approach would be to implement them in a staged sequence, focusing first on the women at highest risk, later extending the program to women at lesser risk. The two factors that confer the greatest risk of perinatal depression are a personal history of depression and high depression symptoms that do not meet criteria for depression.¹⁷ Many women with depression who take antidepressants discontinue their medications during pregnancy. These women are at very high risk for perinatal depression and deserve extra attention.¹⁸

Continue to: To identify women with a prior personal history of depression...

To identify women with a prior personal history of depression, it may be helpful to ask open-ended questions about a past diagnosis of depression or a mood disorder or use of antidepressant medications. To identify women with the greatest depression symptoms, utilize a lower cut-off for screening positive in the Edinburgh questionnaire. Practices that use an EPDS screen-positive score of 13 or greater could reduce the cut-off to 10 or 11, which would increase the number of women referred for evaluation and treatment.¹⁹

Clinical judgment and screening

Screening for prevalent depression and screening for women at increased risk for perinatal depression is challenging. ACOG highlights two important clinical issues¹:

“Women with current depression or anxiety, a history of perinatal mood disorders, risk factors for perinatal mood disorders or suicidal thoughts warrant particularly close monitoring, evaluation and assessment.”

When screening for perinatal depression, screening test results should be interpreted within the clinical context. “A normal score for a tearful patient with a flat affect does not exclude depression; an elevated score in the context of an acute stressful event may resolve with close follow-up.”

In addition, women who screen-positive for prevalent depression and are subsequently evaluated by a mental health specialist may be identified as having mental health problems such as an anxiety disorder, substance misuse, or borderline personality disorder.²⁰

Policy changes that support pregnant women and mothers could help to reduce the stress of pregnancy, birth, and childrearing, thereby reducing the risk of perinatal depression. The United States stands alone among rich nations in not providing paid parental leave. Paid maternity and parental leave would help many families respond more effectively to the initial stresses of parenthood.²¹ For women and families living in poverty, improved social support, including secure housing, protection from abusive partners, transportation resources, and access to healthy foods likely will reduce both stress and the risk of depression.

The ultimate goal: A healthy pregnancy

Clinicians have been phenomenally successful in screening for perinatal depression. The new USPSTF recommendation adds the prevention of perinatal depression to the goals of a healthy pregnancy. This recommendation builds upon the foundation of screening for acute illness (depression), pivoting to the public health perspective of disease prevention.

Perinatal depression is an episode of major or minor depression that occurs during pregnancy or in the 12 months after birth; it affects about 10% of new mothers.¹ Perinatal depression adversely impacts mothers, children, and their families. Pregnant women with depression are at increased risk for preterm birth and low birth weight.² Infants of mothers with postpartum depression have reduced bonding, lower rates of breastfeeding, delayed cognitive and social development, and an increased risk of future mental health issues.³ Timely treatment of perinatal depression can improve health outcomes for the woman, her children, and their family.

Clinicians follow current screening recommendations

The American College of Obstetricians and Gynecologists (ACOG) currently recommends that ObGynsscreen all pregnant women for depression and anxiety symptoms at least once during the perinatal period.¹ Many practices use the Edinburgh Postnatal Depression Scale (EPDS) during pregnancy and postpartum. Women who screen positive are referred to mental health clinicians or have treatment initiated by their primary obstetrician.

Clinicians have been phenomenally successful in screening for perinatal depression. In a recent study from Kaiser Permanente Northern California, 98% of pregnant women were screened for perinatal depression, and a diagnosis of depression was made in 12%.⁴ Of note, only 47% of women who screened positive for depression initiated treatment, although 82% of women with the most severe symptoms initiated treatment. These data demonstrate that ObGyns consistently screen pregnant women for depression but, due to patient and system issues, treatment of all screen-positive women remains a yet unattained goal.^5,6

New USPSTF guideline: Identify women at risk for perinatal depression and refer for counseling

In 2016 the United States Preventive Services Task Force (USPSTF) recommended that pregnant and postpartum women be screened for depression with adequate systems in place to ensure diagnosis, effective treatment, and follow-up.⁷ The 2016 USPSTF recommendation was consistent with prior guidelines from both the American Academy of Pediatrics in 2010⁸ and ACOG in 2015.⁹

Now, the USPSTF is making a bold new recommendation, jumping ahead of professional societies: screen pregnant women to identify those at risk for perinatal depression and refer them for counseling (B recommendation; net benefit is moderate).^10,11 The USPSTF recommendation is based on growing literature that shows counseling women at risk for perinatal depression reduces the risk of having an episode of major depression by 40%.¹¹ Both interpersonal psychotherapy and cognitive behavioral therapy have been reported to be effective for preventing perinatal depression.^12,13

As an example of the relevant literature, in one trial performed in Rhode Island, women who were 20 to 35 weeks pregnant with a high score (≥27) on the Cooper Survey Questionnaire and on public assistance were randomized to counseling or usual care. The counseling intervention involved 4 small group (2 to 5 women) sessions of 90 minutes and one individual session of 50 minutes.¹⁴ The treatment focused on managing the transition to motherhood, developing a support system, improving communication skills to manage conflict, goal setting, and identifying psychosocial supports for new mothers. At 6 months after birth, a depressive episode had occurred in 31% of the control women and 16% of the women who had experienced the intervention (P = .041). At 12 months after birth, a depressive episode had occurred in 40% of control women and 26% of women in the intervention group (P = .052).

Of note, most cases of postpartum depression were diagnosed more than 3 months after birth, a time when new mothers generally no longer are receiving regular postpartum care by an obstetrician. The timing of the diagnosis of perinatal depression indicates that an effective handoff between the obstetrician and primary care and/or mental health clinicians is of great importance. The investigators concluded that pregnant women at very high risk for perinatal depression who receive interpersonal therapy have a lower rate of a postpartum depressive episode than women receiving usual care.¹⁴

Pregnancy, delivery, and the first year following birth are stressful for many women and their families. Women who are young, poor, and with minimal social supports are at especially high risk for developing perinatal depression. However, it will be challenging for obstetric practices to rapidly implement the new USPSTF recommendations because there is no professional consensus on how to screen women to identify those at high risk for perinatal depression, and mental health resources to care for the screen-positive women are not sufficient.

Continue to: Challenges to implementing new USPSTF guideline...

Challenges to implementing new USPSTF guideline

Challenge 1: There is no widely accepted approach for identifying women at risk for perinatal depression. The USPSTF acknowledges “there is no accurate screening tool for identifying who is at risk of perinatal depression and who might benefit from preventive interventions.”¹⁰

Obstetricians have had great success in screening for perinatal depression because validated screening tools are available. Professional societies need to reach a consensus on recommending a specific screening tool for perinatal depression risk that can be used in all obstetric practices.

Challenge 2: The USPSTF guideline identifies many risk factors for perinatal depression. The USPSTF concluded that pregnant women with one (or more) of the following risk factors are at high risk for perinatal depression and recommended that they be offered a counseling intervention:

• personal history of depression
• current depressive symptoms that do not reach a diagnostic threshold
• low income
• all adolescents
• all single mothers
• recent exposure to intimate partner violence
• elevated anxiety symptoms
• a history of significant negative life events.

For many obstetricians, most of their pregnant patients meet the USPSTF criteria for being at high risk for perinatal depression and, per the guideline, these women should have a counseling intervention.

Challenge 3: The counseling intervention recommended by the USPSTF may not be available to all women at risk for perinatal depression. The USPSTF literature review, including a meta-analysis of 49 randomized clinical trials, concluded that for women at risk for perinatal depression, a counseling intervention reduces the risk of depression. In the published literature, many counseling interventions to reduce the risk of perinatal depression involve 6 to 12 hours of contact time over 4 to 8 episodes.

For many health systems, the resources available to provide mental health services are very limited. If most pregnant women need a counseling intervention, the health system must evolve to meet this need. In addition, risk factors for perinatal depression are also risk factors for having difficulty in participating in mental health interventions due to limitations, such as lack of transportation, social support, and money.⁴

Fortunately, clinicians from many backgrounds, including psychologists, social workers, nurse practitioners, and public health workers have the experience and/or training to provide the counseling interventions that have been shown to reduce the risk of perinatal depression. Health systems will need to tap all these resources to accommodate the large numbers of pregnant women who will be referred for counseling interventions. Pilot projects using electronic interventions, including telephone counseling, smartphone apps, and internet programs show promise.^15,16 Electronic interventions have the potential to reach many pregnant women without over-taxing limited mental health resources.

A practical approach

Identify women at the greatest risk for perinatal depression and focus counseling interventions on this group. In my opinion, implementation of the USPSTF recommendation will take time. A practical approach would be to implement them in a staged sequence, focusing first on the women at highest risk, later extending the program to women at lesser risk. The two factors that confer the greatest risk of perinatal depression are a personal history of depression and high depression symptoms that do not meet criteria for depression.¹⁷ Many women with depression who take antidepressants discontinue their medications during pregnancy. These women are at very high risk for perinatal depression and deserve extra attention.¹⁸

Continue to: To identify women with a prior personal history of depression...

To identify women with a prior personal history of depression, it may be helpful to ask open-ended questions about a past diagnosis of depression or a mood disorder or use of antidepressant medications. To identify women with the greatest depression symptoms, utilize a lower cut-off for screening positive in the Edinburgh questionnaire. Practices that use an EPDS screen-positive score of 13 or greater could reduce the cut-off to 10 or 11, which would increase the number of women referred for evaluation and treatment.¹⁹

Clinical judgment and screening

Screening for prevalent depression and screening for women at increased risk for perinatal depression is challenging. ACOG highlights two important clinical issues¹:

“Women with current depression or anxiety, a history of perinatal mood disorders, risk factors for perinatal mood disorders or suicidal thoughts warrant particularly close monitoring, evaluation and assessment.”

When screening for perinatal depression, screening test results should be interpreted within the clinical context. “A normal score for a tearful patient with a flat affect does not exclude depression; an elevated score in the context of an acute stressful event may resolve with close follow-up.”

In addition, women who screen-positive for prevalent depression and are subsequently evaluated by a mental health specialist may be identified as having mental health problems such as an anxiety disorder, substance misuse, or borderline personality disorder.²⁰

Policy changes that support pregnant women and mothers could help to reduce the stress of pregnancy, birth, and childrearing, thereby reducing the risk of perinatal depression. The United States stands alone among rich nations in not providing paid parental leave. Paid maternity and parental leave would help many families respond more effectively to the initial stresses of parenthood.²¹ For women and families living in poverty, improved social support, including secure housing, protection from abusive partners, transportation resources, and access to healthy foods likely will reduce both stress and the risk of depression.

The ultimate goal: A healthy pregnancy

Clinicians have been phenomenally successful in screening for perinatal depression. The new USPSTF recommendation adds the prevention of perinatal depression to the goals of a healthy pregnancy. This recommendation builds upon the foundation of screening for acute illness (depression), pivoting to the public health perspective of disease prevention.

Perinatal depression is an episode of major or minor depression that occurs during pregnancy or in the 12 months after birth; it affects about 10% of new mothers.¹ Perinatal depression adversely impacts mothers, children, and their families. Pregnant women with depression are at increased risk for preterm birth and low birth weight.² Infants of mothers with postpartum depression have reduced bonding, lower rates of breastfeeding, delayed cognitive and social development, and an increased risk of future mental health issues.³ Timely treatment of perinatal depression can improve health outcomes for the woman, her children, and their family.

Clinicians follow current screening recommendations

The American College of Obstetricians and Gynecologists (ACOG) currently recommends that ObGynsscreen all pregnant women for depression and anxiety symptoms at least once during the perinatal period.¹ Many practices use the Edinburgh Postnatal Depression Scale (EPDS) during pregnancy and postpartum. Women who screen positive are referred to mental health clinicians or have treatment initiated by their primary obstetrician.

Clinicians have been phenomenally successful in screening for perinatal depression. In a recent study from Kaiser Permanente Northern California, 98% of pregnant women were screened for perinatal depression, and a diagnosis of depression was made in 12%.⁴ Of note, only 47% of women who screened positive for depression initiated treatment, although 82% of women with the most severe symptoms initiated treatment. These data demonstrate that ObGyns consistently screen pregnant women for depression but, due to patient and system issues, treatment of all screen-positive women remains a yet unattained goal.^5,6

New USPSTF guideline: Identify women at risk for perinatal depression and refer for counseling

In 2016 the United States Preventive Services Task Force (USPSTF) recommended that pregnant and postpartum women be screened for depression with adequate systems in place to ensure diagnosis, effective treatment, and follow-up.⁷ The 2016 USPSTF recommendation was consistent with prior guidelines from both the American Academy of Pediatrics in 2010⁸ and ACOG in 2015.⁹

Now, the USPSTF is making a bold new recommendation, jumping ahead of professional societies: screen pregnant women to identify those at risk for perinatal depression and refer them for counseling (B recommendation; net benefit is moderate).^10,11 The USPSTF recommendation is based on growing literature that shows counseling women at risk for perinatal depression reduces the risk of having an episode of major depression by 40%.¹¹ Both interpersonal psychotherapy and cognitive behavioral therapy have been reported to be effective for preventing perinatal depression.^12,13

As an example of the relevant literature, in one trial performed in Rhode Island, women who were 20 to 35 weeks pregnant with a high score (≥27) on the Cooper Survey Questionnaire and on public assistance were randomized to counseling or usual care. The counseling intervention involved 4 small group (2 to 5 women) sessions of 90 minutes and one individual session of 50 minutes.¹⁴ The treatment focused on managing the transition to motherhood, developing a support system, improving communication skills to manage conflict, goal setting, and identifying psychosocial supports for new mothers. At 6 months after birth, a depressive episode had occurred in 31% of the control women and 16% of the women who had experienced the intervention (P = .041). At 12 months after birth, a depressive episode had occurred in 40% of control women and 26% of women in the intervention group (P = .052).

Of note, most cases of postpartum depression were diagnosed more than 3 months after birth, a time when new mothers generally no longer are receiving regular postpartum care by an obstetrician. The timing of the diagnosis of perinatal depression indicates that an effective handoff between the obstetrician and primary care and/or mental health clinicians is of great importance. The investigators concluded that pregnant women at very high risk for perinatal depression who receive interpersonal therapy have a lower rate of a postpartum depressive episode than women receiving usual care.¹⁴

Pregnancy, delivery, and the first year following birth are stressful for many women and their families. Women who are young, poor, and with minimal social supports are at especially high risk for developing perinatal depression. However, it will be challenging for obstetric practices to rapidly implement the new USPSTF recommendations because there is no professional consensus on how to screen women to identify those at high risk for perinatal depression, and mental health resources to care for the screen-positive women are not sufficient.

Continue to: Challenges to implementing new USPSTF guideline...

Challenges to implementing new USPSTF guideline

Challenge 1: There is no widely accepted approach for identifying women at risk for perinatal depression. The USPSTF acknowledges “there is no accurate screening tool for identifying who is at risk of perinatal depression and who might benefit from preventive interventions.”¹⁰

Obstetricians have had great success in screening for perinatal depression because validated screening tools are available. Professional societies need to reach a consensus on recommending a specific screening tool for perinatal depression risk that can be used in all obstetric practices.

Challenge 2: The USPSTF guideline identifies many risk factors for perinatal depression. The USPSTF concluded that pregnant women with one (or more) of the following risk factors are at high risk for perinatal depression and recommended that they be offered a counseling intervention:

• personal history of depression
• current depressive symptoms that do not reach a diagnostic threshold
• low income
• all adolescents
• all single mothers
• recent exposure to intimate partner violence
• elevated anxiety symptoms
• a history of significant negative life events.

For many obstetricians, most of their pregnant patients meet the USPSTF criteria for being at high risk for perinatal depression and, per the guideline, these women should have a counseling intervention.

Challenge 3: The counseling intervention recommended by the USPSTF may not be available to all women at risk for perinatal depression. The USPSTF literature review, including a meta-analysis of 49 randomized clinical trials, concluded that for women at risk for perinatal depression, a counseling intervention reduces the risk of depression. In the published literature, many counseling interventions to reduce the risk of perinatal depression involve 6 to 12 hours of contact time over 4 to 8 episodes.

For many health systems, the resources available to provide mental health services are very limited. If most pregnant women need a counseling intervention, the health system must evolve to meet this need. In addition, risk factors for perinatal depression are also risk factors for having difficulty in participating in mental health interventions due to limitations, such as lack of transportation, social support, and money.⁴

Fortunately, clinicians from many backgrounds, including psychologists, social workers, nurse practitioners, and public health workers have the experience and/or training to provide the counseling interventions that have been shown to reduce the risk of perinatal depression. Health systems will need to tap all these resources to accommodate the large numbers of pregnant women who will be referred for counseling interventions. Pilot projects using electronic interventions, including telephone counseling, smartphone apps, and internet programs show promise.^15,16 Electronic interventions have the potential to reach many pregnant women without over-taxing limited mental health resources.

A practical approach

Identify women at the greatest risk for perinatal depression and focus counseling interventions on this group. In my opinion, implementation of the USPSTF recommendation will take time. A practical approach would be to implement them in a staged sequence, focusing first on the women at highest risk, later extending the program to women at lesser risk. The two factors that confer the greatest risk of perinatal depression are a personal history of depression and high depression symptoms that do not meet criteria for depression.¹⁷ Many women with depression who take antidepressants discontinue their medications during pregnancy. These women are at very high risk for perinatal depression and deserve extra attention.¹⁸

Continue to: To identify women with a prior personal history of depression...

To identify women with a prior personal history of depression, it may be helpful to ask open-ended questions about a past diagnosis of depression or a mood disorder or use of antidepressant medications. To identify women with the greatest depression symptoms, utilize a lower cut-off for screening positive in the Edinburgh questionnaire. Practices that use an EPDS screen-positive score of 13 or greater could reduce the cut-off to 10 or 11, which would increase the number of women referred for evaluation and treatment.¹⁹

Clinical judgment and screening

Screening for prevalent depression and screening for women at increased risk for perinatal depression is challenging. ACOG highlights two important clinical issues¹:

“Women with current depression or anxiety, a history of perinatal mood disorders, risk factors for perinatal mood disorders or suicidal thoughts warrant particularly close monitoring, evaluation and assessment.”

When screening for perinatal depression, screening test results should be interpreted within the clinical context. “A normal score for a tearful patient with a flat affect does not exclude depression; an elevated score in the context of an acute stressful event may resolve with close follow-up.”

In addition, women who screen-positive for prevalent depression and are subsequently evaluated by a mental health specialist may be identified as having mental health problems such as an anxiety disorder, substance misuse, or borderline personality disorder.²⁰

Policy changes that support pregnant women and mothers could help to reduce the stress of pregnancy, birth, and childrearing, thereby reducing the risk of perinatal depression. The United States stands alone among rich nations in not providing paid parental leave. Paid maternity and parental leave would help many families respond more effectively to the initial stresses of parenthood.²¹ For women and families living in poverty, improved social support, including secure housing, protection from abusive partners, transportation resources, and access to healthy foods likely will reduce both stress and the risk of depression.

The ultimate goal: A healthy pregnancy

Clinicians have been phenomenally successful in screening for perinatal depression. The new USPSTF recommendation adds the prevention of perinatal depression to the goals of a healthy pregnancy. This recommendation builds upon the foundation of screening for acute illness (depression), pivoting to the public health perspective of disease prevention.

Hospitalists can have a role in helping patients choose and receive high-value care from the vast array of health care choices they face. Helping them use quality and cost reports is one way to do that, according to a recent editorial by Jeffrey T. Kullgren, MD, MS, MPH.

We know that if consumers used public reporting of quality and costs to choose facilities that generate the best health outcomes for the resources utilized, it might improve the overall value of health care spending. But most people choose health care services based on personal recommendations or the requirements of their insurance network. Even if they wanted to use reports of quality or cost, the information in these reports is meant for providers and would likely be unhelpful for consumers.

Research suggests that different presentation of the information could make a difference. “Simpler presentations of information in public reports may be more likely to help consumers choose higher-value providers and facilities,” Dr. Kullgren said.

He concluded that consumers may also need additional incentives, “such as financial incentives to encourage high-value choices or programs that educate consumers about how to use cost and quality information when seeking care,” he said.

There’s an opportunity for hospitalists to help consumers learn to use that information. “This strategy would approach consumerism as a teachable health behavior and could be particularly helpful for consumers with ongoing medical needs who face high cost sharing,” he wrote.

“Some hospitalists may be involved in the implementation of programs to publicly report quality and costs for their institutions,” he said. “Others may treat patients who have chosen hospitals based on publicly reported information, or patients who might be interested in using such information to choose sites of postdischarge outpatient care. In each of these cases, it is important for hospitalists to understand the opportunities and limits of such public reports so as to best help patients receive high-value care.” 

Reference

Kullgren JT. Helping consumers make high value health care choices: The devil is in the details. Health Serv Res. 2018;53(4). http://www.hsr.org/hsr/abstract.jsp?aid=53301961729.

Hospitalists can have a role in helping patients choose and receive high-value care from the vast array of health care choices they face. Helping them use quality and cost reports is one way to do that, according to a recent editorial by Jeffrey T. Kullgren, MD, MS, MPH.

We know that if consumers used public reporting of quality and costs to choose facilities that generate the best health outcomes for the resources utilized, it might improve the overall value of health care spending. But most people choose health care services based on personal recommendations or the requirements of their insurance network. Even if they wanted to use reports of quality or cost, the information in these reports is meant for providers and would likely be unhelpful for consumers.

Research suggests that different presentation of the information could make a difference. “Simpler presentations of information in public reports may be more likely to help consumers choose higher-value providers and facilities,” Dr. Kullgren said.

He concluded that consumers may also need additional incentives, “such as financial incentives to encourage high-value choices or programs that educate consumers about how to use cost and quality information when seeking care,” he said.

There’s an opportunity for hospitalists to help consumers learn to use that information. “This strategy would approach consumerism as a teachable health behavior and could be particularly helpful for consumers with ongoing medical needs who face high cost sharing,” he wrote.

“Some hospitalists may be involved in the implementation of programs to publicly report quality and costs for their institutions,” he said. “Others may treat patients who have chosen hospitals based on publicly reported information, or patients who might be interested in using such information to choose sites of postdischarge outpatient care. In each of these cases, it is important for hospitalists to understand the opportunities and limits of such public reports so as to best help patients receive high-value care.” 

Reference

Kullgren JT. Helping consumers make high value health care choices: The devil is in the details. Health Serv Res. 2018;53(4). http://www.hsr.org/hsr/abstract.jsp?aid=53301961729.

Hospitalists can have a role in helping patients choose and receive high-value care from the vast array of health care choices they face. Helping them use quality and cost reports is one way to do that, according to a recent editorial by Jeffrey T. Kullgren, MD, MS, MPH.

We know that if consumers used public reporting of quality and costs to choose facilities that generate the best health outcomes for the resources utilized, it might improve the overall value of health care spending. But most people choose health care services based on personal recommendations or the requirements of their insurance network. Even if they wanted to use reports of quality or cost, the information in these reports is meant for providers and would likely be unhelpful for consumers.

Research suggests that different presentation of the information could make a difference. “Simpler presentations of information in public reports may be more likely to help consumers choose higher-value providers and facilities,” Dr. Kullgren said.

He concluded that consumers may also need additional incentives, “such as financial incentives to encourage high-value choices or programs that educate consumers about how to use cost and quality information when seeking care,” he said.

There’s an opportunity for hospitalists to help consumers learn to use that information. “This strategy would approach consumerism as a teachable health behavior and could be particularly helpful for consumers with ongoing medical needs who face high cost sharing,” he wrote.

“Some hospitalists may be involved in the implementation of programs to publicly report quality and costs for their institutions,” he said. “Others may treat patients who have chosen hospitals based on publicly reported information, or patients who might be interested in using such information to choose sites of postdischarge outpatient care. In each of these cases, it is important for hospitalists to understand the opportunities and limits of such public reports so as to best help patients receive high-value care.” 

Reference

Kullgren JT. Helping consumers make high value health care choices: The devil is in the details. Health Serv Res. 2018;53(4). http://www.hsr.org/hsr/abstract.jsp?aid=53301961729.

TUCSON, ARIZ. – Following pelvic floor surgery, patients regard failure to achieve functional goals as severe adverse events, according to results of a new study. Such negative reactions occur more frequently as time passes and may be related to incongruent patient expectations, which may in turn affect physician-patient communication.

Alexander Raths/Fotolia

“We must bridge the gap between expectations and the occurrence of an unanticipated problem. What this study highlights is a need for counseling beyond the traditional complications, and more discussion about the possibility of failure in terms of the things that the patients identify as important,” Brenna McGuire, MD, a resident at the University of New Mexico, Albuquerque, said while presenting the results at the annual scientific meeting of the Society of Gynecologic Surgeons.

The work highlights the need to look at outcomes in a different way, said Vivian Sung, MD, who was not involved in the research and was a discussant following the presentation. “Most of our studies are designed with methodology to emphasize efficacy and often secondary outcomes to capture complications and adverse events. But there is a gray area. It’s something that’s evolving, and we’re getting better at,” Dr. Sung, professor of obstetrics and gynecology at Brown University and a urogynecologist at Women and Infants Hospital, both in Providence, R.I., said in an interview.

The success of a procedure is typically evaluated by determining incontinence during an office visit, but the problem may not be occurring at that particular moment, and the patient may not be happy with the overall outcome. “Sometimes you can fix one problem, and the other problems become more prominent, or new problems develop. [Incontinence alone is] not a perfect picture or what the patient was envisioning her outcome to be,” Dr. Sung said.

Expectations can potentially be better managed through better patient counseling, but that’s not a simple fix either, she noted. Most surgeons counsel patients on negative outcomes, but adverse events with a 5%-10% probability may fail to make an impression. “Really, the rate is zero or 100%. It’s not that it doesn’t seem like a meaningful complication, it’s just that it doesn’t seem like it will happen to you. And then when it does, it can be very devastating depending on what it is and what your expectation was.”

Dr. McGuire and her associates followed 20 women (mean age, 55 years; 50% non-Hispanic white, 25% Hispanic, 25% Native American) at a single institution in New Mexico who underwent surgeries for pelvic floor disorders. They interviewed each participant before and after surgery, at 4-6 weeks, and 6 months after surgery, asking them to rank adverse events at each time point.

Before surgery, patients expressed concerns about postoperative pain, injury, and catheter issues. At 6-8 weeks, the chief concerns were daily activities, sexual activity, and symptom reduction. At 6 months, incontinence, sexual dysfunction, and mental health issues predominated. In other words, concerns migrated from traditional complications to functional outcomes over time.

At the 6-8 week interview, a representative quote was: “It’s the fact that it didn’t work. It’s the fact that I’m still suffering from all the same symptoms.” At 6 months, another quote was: “I hate this so much. It really does impact my life negatively. It affects my work, it affects everything, and makes me very angry.”

Traditional adverse events such as pain and infection dropped in frequency between the preoperative interview and the 6-month interview from 7.5%-10.0% to 2.5%-5.0% by 6 months. However, functional outcomes were a different matter: Concerns about a failed surgery increased from 10% to 25%, sexual dysfunction from 4% to 8%, and effect on daily function from 4% to 11%.

The study was funded by the University of New Mexico. Dr. McGuire and Dr. Sung reported no relevant financial disclosures.

SOURCE: McGuire B et al. SGS 2019, Abstract 01.

TUCSON, ARIZ. – Following pelvic floor surgery, patients regard failure to achieve functional goals as severe adverse events, according to results of a new study. Such negative reactions occur more frequently as time passes and may be related to incongruent patient expectations, which may in turn affect physician-patient communication.

Alexander Raths/Fotolia

“We must bridge the gap between expectations and the occurrence of an unanticipated problem. What this study highlights is a need for counseling beyond the traditional complications, and more discussion about the possibility of failure in terms of the things that the patients identify as important,” Brenna McGuire, MD, a resident at the University of New Mexico, Albuquerque, said while presenting the results at the annual scientific meeting of the Society of Gynecologic Surgeons.

The work highlights the need to look at outcomes in a different way, said Vivian Sung, MD, who was not involved in the research and was a discussant following the presentation. “Most of our studies are designed with methodology to emphasize efficacy and often secondary outcomes to capture complications and adverse events. But there is a gray area. It’s something that’s evolving, and we’re getting better at,” Dr. Sung, professor of obstetrics and gynecology at Brown University and a urogynecologist at Women and Infants Hospital, both in Providence, R.I., said in an interview.

The success of a procedure is typically evaluated by determining incontinence during an office visit, but the problem may not be occurring at that particular moment, and the patient may not be happy with the overall outcome. “Sometimes you can fix one problem, and the other problems become more prominent, or new problems develop. [Incontinence alone is] not a perfect picture or what the patient was envisioning her outcome to be,” Dr. Sung said.

Expectations can potentially be better managed through better patient counseling, but that’s not a simple fix either, she noted. Most surgeons counsel patients on negative outcomes, but adverse events with a 5%-10% probability may fail to make an impression. “Really, the rate is zero or 100%. It’s not that it doesn’t seem like a meaningful complication, it’s just that it doesn’t seem like it will happen to you. And then when it does, it can be very devastating depending on what it is and what your expectation was.”

Dr. McGuire and her associates followed 20 women (mean age, 55 years; 50% non-Hispanic white, 25% Hispanic, 25% Native American) at a single institution in New Mexico who underwent surgeries for pelvic floor disorders. They interviewed each participant before and after surgery, at 4-6 weeks, and 6 months after surgery, asking them to rank adverse events at each time point.

Before surgery, patients expressed concerns about postoperative pain, injury, and catheter issues. At 6-8 weeks, the chief concerns were daily activities, sexual activity, and symptom reduction. At 6 months, incontinence, sexual dysfunction, and mental health issues predominated. In other words, concerns migrated from traditional complications to functional outcomes over time.

At the 6-8 week interview, a representative quote was: “It’s the fact that it didn’t work. It’s the fact that I’m still suffering from all the same symptoms.” At 6 months, another quote was: “I hate this so much. It really does impact my life negatively. It affects my work, it affects everything, and makes me very angry.”

Traditional adverse events such as pain and infection dropped in frequency between the preoperative interview and the 6-month interview from 7.5%-10.0% to 2.5%-5.0% by 6 months. However, functional outcomes were a different matter: Concerns about a failed surgery increased from 10% to 25%, sexual dysfunction from 4% to 8%, and effect on daily function from 4% to 11%.

The study was funded by the University of New Mexico. Dr. McGuire and Dr. Sung reported no relevant financial disclosures.

SOURCE: McGuire B et al. SGS 2019, Abstract 01.

TUCSON, ARIZ. – Following pelvic floor surgery, patients regard failure to achieve functional goals as severe adverse events, according to results of a new study. Such negative reactions occur more frequently as time passes and may be related to incongruent patient expectations, which may in turn affect physician-patient communication.

Alexander Raths/Fotolia

“We must bridge the gap between expectations and the occurrence of an unanticipated problem. What this study highlights is a need for counseling beyond the traditional complications, and more discussion about the possibility of failure in terms of the things that the patients identify as important,” Brenna McGuire, MD, a resident at the University of New Mexico, Albuquerque, said while presenting the results at the annual scientific meeting of the Society of Gynecologic Surgeons.

The work highlights the need to look at outcomes in a different way, said Vivian Sung, MD, who was not involved in the research and was a discussant following the presentation. “Most of our studies are designed with methodology to emphasize efficacy and often secondary outcomes to capture complications and adverse events. But there is a gray area. It’s something that’s evolving, and we’re getting better at,” Dr. Sung, professor of obstetrics and gynecology at Brown University and a urogynecologist at Women and Infants Hospital, both in Providence, R.I., said in an interview.

The success of a procedure is typically evaluated by determining incontinence during an office visit, but the problem may not be occurring at that particular moment, and the patient may not be happy with the overall outcome. “Sometimes you can fix one problem, and the other problems become more prominent, or new problems develop. [Incontinence alone is] not a perfect picture or what the patient was envisioning her outcome to be,” Dr. Sung said.

Expectations can potentially be better managed through better patient counseling, but that’s not a simple fix either, she noted. Most surgeons counsel patients on negative outcomes, but adverse events with a 5%-10% probability may fail to make an impression. “Really, the rate is zero or 100%. It’s not that it doesn’t seem like a meaningful complication, it’s just that it doesn’t seem like it will happen to you. And then when it does, it can be very devastating depending on what it is and what your expectation was.”

Dr. McGuire and her associates followed 20 women (mean age, 55 years; 50% non-Hispanic white, 25% Hispanic, 25% Native American) at a single institution in New Mexico who underwent surgeries for pelvic floor disorders. They interviewed each participant before and after surgery, at 4-6 weeks, and 6 months after surgery, asking them to rank adverse events at each time point.

Before surgery, patients expressed concerns about postoperative pain, injury, and catheter issues. At 6-8 weeks, the chief concerns were daily activities, sexual activity, and symptom reduction. At 6 months, incontinence, sexual dysfunction, and mental health issues predominated. In other words, concerns migrated from traditional complications to functional outcomes over time.

At the 6-8 week interview, a representative quote was: “It’s the fact that it didn’t work. It’s the fact that I’m still suffering from all the same symptoms.” At 6 months, another quote was: “I hate this so much. It really does impact my life negatively. It affects my work, it affects everything, and makes me very angry.”

Traditional adverse events such as pain and infection dropped in frequency between the preoperative interview and the 6-month interview from 7.5%-10.0% to 2.5%-5.0% by 6 months. However, functional outcomes were a different matter: Concerns about a failed surgery increased from 10% to 25%, sexual dysfunction from 4% to 8%, and effect on daily function from 4% to 11%.

The study was funded by the University of New Mexico. Dr. McGuire and Dr. Sung reported no relevant financial disclosures.

SOURCE: McGuire B et al. SGS 2019, Abstract 01.

Children with proliferative lupus nephritis appear to do similarly well after using induction treatment with mycophenolate mofetil or IV cyclophosphamide, according to findings in the real-world U.K. Juvenile Systemic Lupus Erythematosus Cohort Study.

HYWARDS/Getty Images

The study involved 34 patients who received mycophenolate mofetil and 17 who received IV cyclophosphamide as induction therapy for proliferative lupus nephritis in juvenile-onset systemic lupus erythematosus (JSLE). Along with her coinvestigators, first author Eve M.D. Smith, MD, PhD, of the University of Liverpool (England) and Alder Hey Children’s NHS Foundation Trust, described it as the largest study to date investigating induction treatments for proliferative lupus nephritis in JSLE.

The patients were aged 16 years or younger at diagnosis and monitored during 2006-2018 as part of the U.K. JSLE Cohort Study. They met four or more American College of Rheumatology SLE classification criteria and had a renal biopsy result demonstrating proliferative lupus nephritis, defined as class III or IV lupus nephritis by the International Society of Nephrology/Renal Pathology Society. Within the mycophenolate group, half received oral prednisolone only and half received both IV methylprednisolone and oral prednisolone, whereas 2 in the cyclophosphamide group received oral prednisolone only and 15 received both IV methylprednisolone and oral prednisolone.

All the patient demographic factors at baseline – including gender, ethnicity, age at diagnosis, and age at lupus nephritis onset – were similar in both treatment groups.

The investigators detected no significant differences between the two treatment groups at 4-8 and 10-14 months post renal biopsy and last follow-up in renal pediatric British Isles Lupus Assessment Grade scores, urine albumin/creatinine ratio, serum creatinine, erythrocyte sedimentation rate, anti-double stranded DNA antibody, Complement 3 levels, and patient/physician global scores. JSLE-related damage on the Systemic Lupus International Collaborating Clinics Standardized Damage Index also was no different between the groups after a median 13 months following renal biopsy. Lupus nephritis became inactive in 82%-85% of each group, taking a median of 262 days with mycophenolate and 151 days with IV cyclophosphamide, while flares occurred in 69% treated with mycophenolate at a median of 451 days and in 50% with cyclophosphamide at a median of 343 days.

“Results from the presented study highlight the need for prospective comparison of mycophenolate mofetil versus IV cyclophosphamide induction treatment to better inform lupus nephritis treatment protocols for children, especially given IV cyclophosphamide’s poor safety profile,” the investigators wrote.

jevans@mdedge.com

SOURCE: Smith EMD et al. Lupus. 2019 Mar 14. doi: 10.1177/0961203319836712.

Children with proliferative lupus nephritis appear to do similarly well after using induction treatment with mycophenolate mofetil or IV cyclophosphamide, according to findings in the real-world U.K. Juvenile Systemic Lupus Erythematosus Cohort Study.

HYWARDS/Getty Images

The study involved 34 patients who received mycophenolate mofetil and 17 who received IV cyclophosphamide as induction therapy for proliferative lupus nephritis in juvenile-onset systemic lupus erythematosus (JSLE). Along with her coinvestigators, first author Eve M.D. Smith, MD, PhD, of the University of Liverpool (England) and Alder Hey Children’s NHS Foundation Trust, described it as the largest study to date investigating induction treatments for proliferative lupus nephritis in JSLE.

The patients were aged 16 years or younger at diagnosis and monitored during 2006-2018 as part of the U.K. JSLE Cohort Study. They met four or more American College of Rheumatology SLE classification criteria and had a renal biopsy result demonstrating proliferative lupus nephritis, defined as class III or IV lupus nephritis by the International Society of Nephrology/Renal Pathology Society. Within the mycophenolate group, half received oral prednisolone only and half received both IV methylprednisolone and oral prednisolone, whereas 2 in the cyclophosphamide group received oral prednisolone only and 15 received both IV methylprednisolone and oral prednisolone.

All the patient demographic factors at baseline – including gender, ethnicity, age at diagnosis, and age at lupus nephritis onset – were similar in both treatment groups.

The investigators detected no significant differences between the two treatment groups at 4-8 and 10-14 months post renal biopsy and last follow-up in renal pediatric British Isles Lupus Assessment Grade scores, urine albumin/creatinine ratio, serum creatinine, erythrocyte sedimentation rate, anti-double stranded DNA antibody, Complement 3 levels, and patient/physician global scores. JSLE-related damage on the Systemic Lupus International Collaborating Clinics Standardized Damage Index also was no different between the groups after a median 13 months following renal biopsy. Lupus nephritis became inactive in 82%-85% of each group, taking a median of 262 days with mycophenolate and 151 days with IV cyclophosphamide, while flares occurred in 69% treated with mycophenolate at a median of 451 days and in 50% with cyclophosphamide at a median of 343 days.

“Results from the presented study highlight the need for prospective comparison of mycophenolate mofetil versus IV cyclophosphamide induction treatment to better inform lupus nephritis treatment protocols for children, especially given IV cyclophosphamide’s poor safety profile,” the investigators wrote.

jevans@mdedge.com

SOURCE: Smith EMD et al. Lupus. 2019 Mar 14. doi: 10.1177/0961203319836712.

Children with proliferative lupus nephritis appear to do similarly well after using induction treatment with mycophenolate mofetil or IV cyclophosphamide, according to findings in the real-world U.K. Juvenile Systemic Lupus Erythematosus Cohort Study.

HYWARDS/Getty Images

The study involved 34 patients who received mycophenolate mofetil and 17 who received IV cyclophosphamide as induction therapy for proliferative lupus nephritis in juvenile-onset systemic lupus erythematosus (JSLE). Along with her coinvestigators, first author Eve M.D. Smith, MD, PhD, of the University of Liverpool (England) and Alder Hey Children’s NHS Foundation Trust, described it as the largest study to date investigating induction treatments for proliferative lupus nephritis in JSLE.

The patients were aged 16 years or younger at diagnosis and monitored during 2006-2018 as part of the U.K. JSLE Cohort Study. They met four or more American College of Rheumatology SLE classification criteria and had a renal biopsy result demonstrating proliferative lupus nephritis, defined as class III or IV lupus nephritis by the International Society of Nephrology/Renal Pathology Society. Within the mycophenolate group, half received oral prednisolone only and half received both IV methylprednisolone and oral prednisolone, whereas 2 in the cyclophosphamide group received oral prednisolone only and 15 received both IV methylprednisolone and oral prednisolone.

All the patient demographic factors at baseline – including gender, ethnicity, age at diagnosis, and age at lupus nephritis onset – were similar in both treatment groups.

The investigators detected no significant differences between the two treatment groups at 4-8 and 10-14 months post renal biopsy and last follow-up in renal pediatric British Isles Lupus Assessment Grade scores, urine albumin/creatinine ratio, serum creatinine, erythrocyte sedimentation rate, anti-double stranded DNA antibody, Complement 3 levels, and patient/physician global scores. JSLE-related damage on the Systemic Lupus International Collaborating Clinics Standardized Damage Index also was no different between the groups after a median 13 months following renal biopsy. Lupus nephritis became inactive in 82%-85% of each group, taking a median of 262 days with mycophenolate and 151 days with IV cyclophosphamide, while flares occurred in 69% treated with mycophenolate at a median of 451 days and in 50% with cyclophosphamide at a median of 343 days.

“Results from the presented study highlight the need for prospective comparison of mycophenolate mofetil versus IV cyclophosphamide induction treatment to better inform lupus nephritis treatment protocols for children, especially given IV cyclophosphamide’s poor safety profile,” the investigators wrote.

jevans@mdedge.com

SOURCE: Smith EMD et al. Lupus. 2019 Mar 14. doi: 10.1177/0961203319836712.

The Diagnosis:  Primary Cutaneous Perivascular Epithelioid Cell Tumor  

Perivascular epithelioid cell tumors (PEComas) were first described in 1996.¹ They comprise a family of rare mesenchymal neoplasms that have a unique characteristic of staining positive for melanocytic and smooth muscle markers on immunohistochemistry.² These neoplasms have been described in many areas of the body including the uterus, bladder, heart, pancreas, and prostate. The majority of PEComas are extracutaneous, with only 8% of reported cases originating on the skin.³ A case of primary cutaneous PEComa (pcPEComa) was described in 2003.⁴ The primary cutaneous form is extremely rare.^3,5-7  

A broad deep shave biopsy was performed in our patient in an attempt to sample the entire lesion. Histopathologic examination of the nodule demonstrated a dermal neoplasm comprised of a diffuse proliferation of large polygonal cells with abundant clear cytoplasm, fine chromatin, and prominent nucleoli (Figure 1A). Higher-power magnification showed moderate nuclear pleomorphism and only rare mitotic figures (Figure 1B).

Immunohistochemical staining revealed positivity for myomelanocytic markers with positivity for human melanoma black 45 (HMB-45)(Figure 2) and desmin (not shown). Additionally, the tumor was positive for CD163 and negative for smooth muscle actin, cytokeratin, and S-100 protein.  

Perivascular epithelioid cell tumors are characterized histologically as mesenchymal neoplasms containing large epithelioid to spindled cells with a slightly granular, vacuolated cytoplasm. These cells often are found in close proximity to vascular structures.^3,5,8 The hallmark of PEComas is the expression of both melanocytic and muscle markers.^3,8 A review of staining patterns of pcPEComas emphasized that immunophenotypes between visceral and primary cutaneous forms may vary considerably.^3,5,8 The most consistent and sensitive melanocytic marker is HMB-45 (88%-92% positive).^3,8 Positive Melan-A staining varies in the literature from 0% to 50% of cases.³ Our patient's neoplasm expressed the characteristic myomelanocytic immunophenotype with both HMB-45 and desmin positivity. 

Given the histologic characteristics, these lesions can be mistaken for melanocytic and other nonmelanocytic tumors with a clear cell morphology such as balloon cell nevus, hypomelanotic blue nevus, and melanoma.^2,3 A pigmented case of pcPEComa was reported in 2015 and was originally diagnosed as metastatic melanoma.⁶ Unlike pcPEComa, melanoma usually stains positive with S-100 protein in up to 99% of cases⁸ and is negative for muscle markers; however, a case series reported S-100 protein positivity in 38% of pcPEComas.³ Nonmelanocytic neoplasms in the histologic differential diagnosis include clear cell sarcoma and clear cell renal cell carcinoma, both of which show immunoreactivity for cytokeratin.⁹  

Histologic criteria exist for establishing malignancy potential for visceral PEComas but not for pcPEComas, though it has been suggested that the same malignancy criteria should be applied to pcPEComas.^3,9 Features associated with malignancy include size greater than 8 cm, mitotic activity greater than 1 mitosis per 50 high-power fields, infiltrative growth pattern, high nuclear grade, necrosis, and vascular invasion. Based on these criteria, fulfilling 2 or more features technically classifies the lesion as malignant, 1 feature classifies it as uncertain malignant potential, and a lack of these features renders the lesion benign.⁹  

The overwhelming majority of pcPEComas are considered benign. One case of pcPEComa was considered malignant with a high mitotic rate (5 mitoses per 10 high-power fields) and nuclear atypia.¹⁰ Further workup with thoracic computed tomography and positron emission tomography-computed tomography was negative for metastasis. Treatment with wide excision and radiotherapy was performed with no sign of recurrence at 24-month follow-up.¹⁰  

Although pcPEComas arising from the dermis seem to be benign overall, PEComas originating from the subcutaneous tissue may have greater malignancy potential. Two cases of subcutaneous PEComas presenting as nodules resulted in metastasis; one case had local nodal metastasis and another developed metastasis to the lungs months later.^10,11 

The Diagnosis:  Primary Cutaneous Perivascular Epithelioid Cell Tumor  

Perivascular epithelioid cell tumors (PEComas) were first described in 1996.¹ They comprise a family of rare mesenchymal neoplasms that have a unique characteristic of staining positive for melanocytic and smooth muscle markers on immunohistochemistry.² These neoplasms have been described in many areas of the body including the uterus, bladder, heart, pancreas, and prostate. The majority of PEComas are extracutaneous, with only 8% of reported cases originating on the skin.³ A case of primary cutaneous PEComa (pcPEComa) was described in 2003.⁴ The primary cutaneous form is extremely rare.^3,5-7  

A broad deep shave biopsy was performed in our patient in an attempt to sample the entire lesion. Histopathologic examination of the nodule demonstrated a dermal neoplasm comprised of a diffuse proliferation of large polygonal cells with abundant clear cytoplasm, fine chromatin, and prominent nucleoli (Figure 1A). Higher-power magnification showed moderate nuclear pleomorphism and only rare mitotic figures (Figure 1B).

Immunohistochemical staining revealed positivity for myomelanocytic markers with positivity for human melanoma black 45 (HMB-45)(Figure 2) and desmin (not shown). Additionally, the tumor was positive for CD163 and negative for smooth muscle actin, cytokeratin, and S-100 protein.  

Perivascular epithelioid cell tumors are characterized histologically as mesenchymal neoplasms containing large epithelioid to spindled cells with a slightly granular, vacuolated cytoplasm. These cells often are found in close proximity to vascular structures.^3,5,8 The hallmark of PEComas is the expression of both melanocytic and muscle markers.^3,8 A review of staining patterns of pcPEComas emphasized that immunophenotypes between visceral and primary cutaneous forms may vary considerably.^3,5,8 The most consistent and sensitive melanocytic marker is HMB-45 (88%-92% positive).^3,8 Positive Melan-A staining varies in the literature from 0% to 50% of cases.³ Our patient's neoplasm expressed the characteristic myomelanocytic immunophenotype with both HMB-45 and desmin positivity. 

Given the histologic characteristics, these lesions can be mistaken for melanocytic and other nonmelanocytic tumors with a clear cell morphology such as balloon cell nevus, hypomelanotic blue nevus, and melanoma.^2,3 A pigmented case of pcPEComa was reported in 2015 and was originally diagnosed as metastatic melanoma.⁶ Unlike pcPEComa, melanoma usually stains positive with S-100 protein in up to 99% of cases⁸ and is negative for muscle markers; however, a case series reported S-100 protein positivity in 38% of pcPEComas.³ Nonmelanocytic neoplasms in the histologic differential diagnosis include clear cell sarcoma and clear cell renal cell carcinoma, both of which show immunoreactivity for cytokeratin.⁹  

Histologic criteria exist for establishing malignancy potential for visceral PEComas but not for pcPEComas, though it has been suggested that the same malignancy criteria should be applied to pcPEComas.^3,9 Features associated with malignancy include size greater than 8 cm, mitotic activity greater than 1 mitosis per 50 high-power fields, infiltrative growth pattern, high nuclear grade, necrosis, and vascular invasion. Based on these criteria, fulfilling 2 or more features technically classifies the lesion as malignant, 1 feature classifies it as uncertain malignant potential, and a lack of these features renders the lesion benign.⁹  

The overwhelming majority of pcPEComas are considered benign. One case of pcPEComa was considered malignant with a high mitotic rate (5 mitoses per 10 high-power fields) and nuclear atypia.¹⁰ Further workup with thoracic computed tomography and positron emission tomography-computed tomography was negative for metastasis. Treatment with wide excision and radiotherapy was performed with no sign of recurrence at 24-month follow-up.¹⁰  

Although pcPEComas arising from the dermis seem to be benign overall, PEComas originating from the subcutaneous tissue may have greater malignancy potential. Two cases of subcutaneous PEComas presenting as nodules resulted in metastasis; one case had local nodal metastasis and another developed metastasis to the lungs months later.^10,11 

The Diagnosis:  Primary Cutaneous Perivascular Epithelioid Cell Tumor  

Perivascular epithelioid cell tumors (PEComas) were first described in 1996.¹ They comprise a family of rare mesenchymal neoplasms that have a unique characteristic of staining positive for melanocytic and smooth muscle markers on immunohistochemistry.² These neoplasms have been described in many areas of the body including the uterus, bladder, heart, pancreas, and prostate. The majority of PEComas are extracutaneous, with only 8% of reported cases originating on the skin.³ A case of primary cutaneous PEComa (pcPEComa) was described in 2003.⁴ The primary cutaneous form is extremely rare.^3,5-7  

A broad deep shave biopsy was performed in our patient in an attempt to sample the entire lesion. Histopathologic examination of the nodule demonstrated a dermal neoplasm comprised of a diffuse proliferation of large polygonal cells with abundant clear cytoplasm, fine chromatin, and prominent nucleoli (Figure 1A). Higher-power magnification showed moderate nuclear pleomorphism and only rare mitotic figures (Figure 1B).

Immunohistochemical staining revealed positivity for myomelanocytic markers with positivity for human melanoma black 45 (HMB-45)(Figure 2) and desmin (not shown). Additionally, the tumor was positive for CD163 and negative for smooth muscle actin, cytokeratin, and S-100 protein.  

Perivascular epithelioid cell tumors are characterized histologically as mesenchymal neoplasms containing large epithelioid to spindled cells with a slightly granular, vacuolated cytoplasm. These cells often are found in close proximity to vascular structures.^3,5,8 The hallmark of PEComas is the expression of both melanocytic and muscle markers.^3,8 A review of staining patterns of pcPEComas emphasized that immunophenotypes between visceral and primary cutaneous forms may vary considerably.^3,5,8 The most consistent and sensitive melanocytic marker is HMB-45 (88%-92% positive).^3,8 Positive Melan-A staining varies in the literature from 0% to 50% of cases.³ Our patient's neoplasm expressed the characteristic myomelanocytic immunophenotype with both HMB-45 and desmin positivity. 

Given the histologic characteristics, these lesions can be mistaken for melanocytic and other nonmelanocytic tumors with a clear cell morphology such as balloon cell nevus, hypomelanotic blue nevus, and melanoma.^2,3 A pigmented case of pcPEComa was reported in 2015 and was originally diagnosed as metastatic melanoma.⁶ Unlike pcPEComa, melanoma usually stains positive with S-100 protein in up to 99% of cases⁸ and is negative for muscle markers; however, a case series reported S-100 protein positivity in 38% of pcPEComas.³ Nonmelanocytic neoplasms in the histologic differential diagnosis include clear cell sarcoma and clear cell renal cell carcinoma, both of which show immunoreactivity for cytokeratin.⁹  

Histologic criteria exist for establishing malignancy potential for visceral PEComas but not for pcPEComas, though it has been suggested that the same malignancy criteria should be applied to pcPEComas.^3,9 Features associated with malignancy include size greater than 8 cm, mitotic activity greater than 1 mitosis per 50 high-power fields, infiltrative growth pattern, high nuclear grade, necrosis, and vascular invasion. Based on these criteria, fulfilling 2 or more features technically classifies the lesion as malignant, 1 feature classifies it as uncertain malignant potential, and a lack of these features renders the lesion benign.⁹  

The overwhelming majority of pcPEComas are considered benign. One case of pcPEComa was considered malignant with a high mitotic rate (5 mitoses per 10 high-power fields) and nuclear atypia.¹⁰ Further workup with thoracic computed tomography and positron emission tomography-computed tomography was negative for metastasis. Treatment with wide excision and radiotherapy was performed with no sign of recurrence at 24-month follow-up.¹⁰  

Although pcPEComas arising from the dermis seem to be benign overall, PEComas originating from the subcutaneous tissue may have greater malignancy potential. Two cases of subcutaneous PEComas presenting as nodules resulted in metastasis; one case had local nodal metastasis and another developed metastasis to the lungs months later.^10,11 

Improvements to the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) food package guidelines in 2009 appear responsible for reversing the upward trend in obesity prevalence among WIC toddler participants, Madeleine I.G. Daepp, of the Massachusetts Institute of Technology, Cambridge, and her associates reported in Pediatrics.

Courtesy National Cancer Institute

Using data.gov files from 2008, 2010, 2012, and 2014, Ms. Daepp and her colleagues conducted a quasi-experimental interrupted time series analysis to compare state-level population trends in obesity prevalence among children aged 2-4 years before and after 2009. The goal of the study was to determine whether the WIC package changes had any influence on obesity trends among program participants. Altogether, data from 2,253,471 children in 2000 and 3,152,137 children in 2012 was included in the analysis.

Among the guidelines updated to encourage healthier eating habits were the addition of cash allowances for the purchase of more fruits and vegetables, reduction by half in the allowable portions of juice, reduction in cheese, transition of toddlers aged 2-4 years to low-fat or skim milk, and replacement of refined-grain products with healthier whole grain products.

Across all states included in the study, the authors reported average obesity prevalence of 13% in 2000 and 15% in 2008. Although no change was observed in 2010, by 2014 the obesity prevalence decreased to 14%. Hawaii was excluded because of concerns about data quality.

Ms. Daepp and her associates “estimated a pre-2009 annual trend of a 0.23% increase in childhood obesity prevalence.” After the 2009 package revision, they estimated “a decline in childhood obesity of 0.34% per year [P less than .001].”

This change could not be explained by racial-ethnic makeup or child poverty, changes in maternal prepregnancy body mass indices, or prevalence of macrosomia. Speculating that “unmeasured heterogeneity in WIC populations across states” might explain the difference, the authors also suggested that variance in how effectively the package changes were implemented from state to state could be a factor.

Ms. Daepp and her associates recommended that future studies should focus on evaluating differences in how closely vendors follow the package changes, as well as considering whether any other implementation factors could have an influence on state-by-state trends in childhood obesity.

Study limitations noted included an absence of individual body mass index data and information on changes in energy intake and expenditure.

This study was funded by the National Institutes of Health. Ms. Daepp was supported by a National Science Foundation Graduate Research Fellowship grant. Three coauthors were supported by the JPB Foundation; a fourth was supported by an NIH grant.

SOURCE: Daepp MIG et al. Pediatrics. 2019 Apr 1. doi: 10.1542/peds.2018-2841.

Improvements to the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) food package guidelines in 2009 appear responsible for reversing the upward trend in obesity prevalence among WIC toddler participants, Madeleine I.G. Daepp, of the Massachusetts Institute of Technology, Cambridge, and her associates reported in Pediatrics.

Courtesy National Cancer Institute

Using data.gov files from 2008, 2010, 2012, and 2014, Ms. Daepp and her colleagues conducted a quasi-experimental interrupted time series analysis to compare state-level population trends in obesity prevalence among children aged 2-4 years before and after 2009. The goal of the study was to determine whether the WIC package changes had any influence on obesity trends among program participants. Altogether, data from 2,253,471 children in 2000 and 3,152,137 children in 2012 was included in the analysis.

Among the guidelines updated to encourage healthier eating habits were the addition of cash allowances for the purchase of more fruits and vegetables, reduction by half in the allowable portions of juice, reduction in cheese, transition of toddlers aged 2-4 years to low-fat or skim milk, and replacement of refined-grain products with healthier whole grain products.

Across all states included in the study, the authors reported average obesity prevalence of 13% in 2000 and 15% in 2008. Although no change was observed in 2010, by 2014 the obesity prevalence decreased to 14%. Hawaii was excluded because of concerns about data quality.

Ms. Daepp and her associates “estimated a pre-2009 annual trend of a 0.23% increase in childhood obesity prevalence.” After the 2009 package revision, they estimated “a decline in childhood obesity of 0.34% per year [P less than .001].”

This change could not be explained by racial-ethnic makeup or child poverty, changes in maternal prepregnancy body mass indices, or prevalence of macrosomia. Speculating that “unmeasured heterogeneity in WIC populations across states” might explain the difference, the authors also suggested that variance in how effectively the package changes were implemented from state to state could be a factor.

Ms. Daepp and her associates recommended that future studies should focus on evaluating differences in how closely vendors follow the package changes, as well as considering whether any other implementation factors could have an influence on state-by-state trends in childhood obesity.

Study limitations noted included an absence of individual body mass index data and information on changes in energy intake and expenditure.

This study was funded by the National Institutes of Health. Ms. Daepp was supported by a National Science Foundation Graduate Research Fellowship grant. Three coauthors were supported by the JPB Foundation; a fourth was supported by an NIH grant.

SOURCE: Daepp MIG et al. Pediatrics. 2019 Apr 1. doi: 10.1542/peds.2018-2841.

Improvements to the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) food package guidelines in 2009 appear responsible for reversing the upward trend in obesity prevalence among WIC toddler participants, Madeleine I.G. Daepp, of the Massachusetts Institute of Technology, Cambridge, and her associates reported in Pediatrics.

Courtesy National Cancer Institute

Using data.gov files from 2008, 2010, 2012, and 2014, Ms. Daepp and her colleagues conducted a quasi-experimental interrupted time series analysis to compare state-level population trends in obesity prevalence among children aged 2-4 years before and after 2009. The goal of the study was to determine whether the WIC package changes had any influence on obesity trends among program participants. Altogether, data from 2,253,471 children in 2000 and 3,152,137 children in 2012 was included in the analysis.

Among the guidelines updated to encourage healthier eating habits were the addition of cash allowances for the purchase of more fruits and vegetables, reduction by half in the allowable portions of juice, reduction in cheese, transition of toddlers aged 2-4 years to low-fat or skim milk, and replacement of refined-grain products with healthier whole grain products.

Across all states included in the study, the authors reported average obesity prevalence of 13% in 2000 and 15% in 2008. Although no change was observed in 2010, by 2014 the obesity prevalence decreased to 14%. Hawaii was excluded because of concerns about data quality.

Ms. Daepp and her associates “estimated a pre-2009 annual trend of a 0.23% increase in childhood obesity prevalence.” After the 2009 package revision, they estimated “a decline in childhood obesity of 0.34% per year [P less than .001].”

This change could not be explained by racial-ethnic makeup or child poverty, changes in maternal prepregnancy body mass indices, or prevalence of macrosomia. Speculating that “unmeasured heterogeneity in WIC populations across states” might explain the difference, the authors also suggested that variance in how effectively the package changes were implemented from state to state could be a factor.

Ms. Daepp and her associates recommended that future studies should focus on evaluating differences in how closely vendors follow the package changes, as well as considering whether any other implementation factors could have an influence on state-by-state trends in childhood obesity.

Study limitations noted included an absence of individual body mass index data and information on changes in energy intake and expenditure.

This study was funded by the National Institutes of Health. Ms. Daepp was supported by a National Science Foundation Graduate Research Fellowship grant. Three coauthors were supported by the JPB Foundation; a fourth was supported by an NIH grant.

SOURCE: Daepp MIG et al. Pediatrics. 2019 Apr 1. doi: 10.1542/peds.2018-2841.

NEW ORLEANS – When HIV-negative children born to mothers infected with HIV are evaluated in adolescence, they are found to have far higher rates of obesity and reactive airway disease than are those with no such exposure, according to research that provides a compelling link between inflammatory activity in utero and subsequent risk of metabolic disorders.

Most supportive of that link was a near-linear inverse relationship between CD4 counts during the time of pregnancy and risk of both obesity and reactive respiratory disease more than a decade later, according to research presented by Lindsay Fourman, MD, an instructor in medicine at Massachusetts General Hospital, Boston, during the annual meeting of the Endocrine Society.

In this video interview, Dr. Fourman discusses the effort to understand the long-term health consequences of being exposed to HIV and antiretroviral therapies while in utero, a group known by the acronym HIV-exposed uninfected (HEU). With effective therapies now routinely preventing mother-to-child transmission, this population of children is growing quickly.

For this study, 50 HEU individuals were identified from a patient database. They were matched in a 3:1 ratio to a control group for a variety of demographic and socioeconomic variables. At a median age of 18 years, the HEU population was found to have a “strikingly” higher rate of obesity, compared with controls (42% vs. 25%, respectively; P = .04). The rate of reactive airway disease was similarly increased in the HEU group (40% vs. 24%; P = .04).

These data are important for considering health risks in an HEU population, but Dr. Fourman explained that it provides support for looking at metabolic risks from other in utero exposures linked to upregulated inflammation, such as gestational diabetes or obesity.

Dr Fourman and her colleagues reported no disclosures or financial conflicts of interest.

SOURCE: Fourman L et al. ENDO 2019, Session P10 (SAT-256).

NEW ORLEANS – When HIV-negative children born to mothers infected with HIV are evaluated in adolescence, they are found to have far higher rates of obesity and reactive airway disease than are those with no such exposure, according to research that provides a compelling link between inflammatory activity in utero and subsequent risk of metabolic disorders.

Most supportive of that link was a near-linear inverse relationship between CD4 counts during the time of pregnancy and risk of both obesity and reactive respiratory disease more than a decade later, according to research presented by Lindsay Fourman, MD, an instructor in medicine at Massachusetts General Hospital, Boston, during the annual meeting of the Endocrine Society.

In this video interview, Dr. Fourman discusses the effort to understand the long-term health consequences of being exposed to HIV and antiretroviral therapies while in utero, a group known by the acronym HIV-exposed uninfected (HEU). With effective therapies now routinely preventing mother-to-child transmission, this population of children is growing quickly.

For this study, 50 HEU individuals were identified from a patient database. They were matched in a 3:1 ratio to a control group for a variety of demographic and socioeconomic variables. At a median age of 18 years, the HEU population was found to have a “strikingly” higher rate of obesity, compared with controls (42% vs. 25%, respectively; P = .04). The rate of reactive airway disease was similarly increased in the HEU group (40% vs. 24%; P = .04).

These data are important for considering health risks in an HEU population, but Dr. Fourman explained that it provides support for looking at metabolic risks from other in utero exposures linked to upregulated inflammation, such as gestational diabetes or obesity.

Dr Fourman and her colleagues reported no disclosures or financial conflicts of interest.

SOURCE: Fourman L et al. ENDO 2019, Session P10 (SAT-256).

NEW ORLEANS – When HIV-negative children born to mothers infected with HIV are evaluated in adolescence, they are found to have far higher rates of obesity and reactive airway disease than are those with no such exposure, according to research that provides a compelling link between inflammatory activity in utero and subsequent risk of metabolic disorders.

Most supportive of that link was a near-linear inverse relationship between CD4 counts during the time of pregnancy and risk of both obesity and reactive respiratory disease more than a decade later, according to research presented by Lindsay Fourman, MD, an instructor in medicine at Massachusetts General Hospital, Boston, during the annual meeting of the Endocrine Society.

In this video interview, Dr. Fourman discusses the effort to understand the long-term health consequences of being exposed to HIV and antiretroviral therapies while in utero, a group known by the acronym HIV-exposed uninfected (HEU). With effective therapies now routinely preventing mother-to-child transmission, this population of children is growing quickly.

For this study, 50 HEU individuals were identified from a patient database. They were matched in a 3:1 ratio to a control group for a variety of demographic and socioeconomic variables. At a median age of 18 years, the HEU population was found to have a “strikingly” higher rate of obesity, compared with controls (42% vs. 25%, respectively; P = .04). The rate of reactive airway disease was similarly increased in the HEU group (40% vs. 24%; P = .04).

These data are important for considering health risks in an HEU population, but Dr. Fourman explained that it provides support for looking at metabolic risks from other in utero exposures linked to upregulated inflammation, such as gestational diabetes or obesity.

Dr Fourman and her colleagues reported no disclosures or financial conflicts of interest.

SOURCE: Fourman L et al. ENDO 2019, Session P10 (SAT-256).

“Doctor, I have a question for you.”

“Yes?”

“Have you ever had a patient – I mean, someone like me, someone in my ... state ... get cured without any treatment?”

Mr. B thought he felt too well to have an aggressive cancer infiltrating his liver, abdominal wall, and lungs. He lived an active life, going to church, volunteering, and playing with his grandchildren. But the biopsy results were back. It wasn’t an infection. It wasn’t inflammation. It was stage 4 cancer.

And just like that, his life changed.

His prognosis was likely months, with a best case scenario of several years. But gone were the days of thinking 10, 20, and 30 years ahead.

It’s not a bad thing. It’s an adaptive mechanism and positive outlooks can even be associated with better medical outcomes. There’s almost always a “but” if you look hard enough. And in the face of life-changing news, we are incentivized to look really, really hard.

Yet Mr. B caught me off guard because he wasn’t asking me to maintain hope. He was pushing me one step further.

At one point in our conversation, he revealed this clearly. “Doctor, I don’t even care if it’s false hope – just tell me the cancer will disappear.”

Mr. B was asking me to lie to him.

The last thing I wanted was to take away hope, closing the door on a future that truly was clouded in uncertainty. But I also couldn’t look him in the eye and tell him his incurable disease was, in fact, curable.

That doesn’t mean there aren’t ways to phrase things kindly. Patients respond differently to “there’s a 90% chance of survival” and “there’s a 10% chance of death” even though the facts are identical.

When I sense a person like Mr. B is looking to me for hope, I try to frame that initial conversation in the style of the first statement. It’s not dishonest. With an already overwhelming piece of information, it’s choosing to share the most positive version of a narrative that can be told in many different ways and will evolve over time.

Moreover, being hopeful and realistic are not mutually exclusive. Just because someone is seeking the rare chance of a good outcome doesn’t mean he or she doesn’t understand the seriousness of the situation. It is possible to seek out experimental drugs while also considering hospice. It is possible to hope for a plan A while preparing for a plan B. Those are two compatible beliefs, and it’s OK – preferred, even – to hold them at once.

The challenge is avoiding getting pulled into an outlook that is not just positive, not just unlikely – but one with no basis in reality. There’s hope – and then there’s false hope. There’s a positive take – and then there’s lying. It can be a fine line, and with the intention of being kind it can be all too easy to “yes, but” our way into untruths.

The best we can do is set limits with compassion, and understand that telling the truth doesn’t always mean that someone hears it.

“Have you ever had a patient – I mean, someone like me, someone in my ... state ... get cured without any treatment?”

The chances of Mr. B’s cancer responding to chemotherapy were not good but hardly impossible. But without any therapy at all?

“I have not.”

“What about at other places ... in other states or countries. Have you ever heard of a person like me who was cured without treatment?”

“I have not.”

“I guess what I’m asking, Doctor, is ... have you ever seen where the cancer was there and then one day was not ... have you ever seen a miracle?”

Reaching. Grasping.

“I have not.”

“Well,” he said, “Maybe I will be the first.”

We look at each other, pondering this. In my silence is the answer.

Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz.

“Doctor, I have a question for you.”

“Yes?”

“Have you ever had a patient – I mean, someone like me, someone in my ... state ... get cured without any treatment?”

Mr. B thought he felt too well to have an aggressive cancer infiltrating his liver, abdominal wall, and lungs. He lived an active life, going to church, volunteering, and playing with his grandchildren. But the biopsy results were back. It wasn’t an infection. It wasn’t inflammation. It was stage 4 cancer.

And just like that, his life changed.

His prognosis was likely months, with a best case scenario of several years. But gone were the days of thinking 10, 20, and 30 years ahead.

It’s not a bad thing. It’s an adaptive mechanism and positive outlooks can even be associated with better medical outcomes. There’s almost always a “but” if you look hard enough. And in the face of life-changing news, we are incentivized to look really, really hard.

Yet Mr. B caught me off guard because he wasn’t asking me to maintain hope. He was pushing me one step further.

At one point in our conversation, he revealed this clearly. “Doctor, I don’t even care if it’s false hope – just tell me the cancer will disappear.”

Mr. B was asking me to lie to him.

The last thing I wanted was to take away hope, closing the door on a future that truly was clouded in uncertainty. But I also couldn’t look him in the eye and tell him his incurable disease was, in fact, curable.

That doesn’t mean there aren’t ways to phrase things kindly. Patients respond differently to “there’s a 90% chance of survival” and “there’s a 10% chance of death” even though the facts are identical.

When I sense a person like Mr. B is looking to me for hope, I try to frame that initial conversation in the style of the first statement. It’s not dishonest. With an already overwhelming piece of information, it’s choosing to share the most positive version of a narrative that can be told in many different ways and will evolve over time.

Moreover, being hopeful and realistic are not mutually exclusive. Just because someone is seeking the rare chance of a good outcome doesn’t mean he or she doesn’t understand the seriousness of the situation. It is possible to seek out experimental drugs while also considering hospice. It is possible to hope for a plan A while preparing for a plan B. Those are two compatible beliefs, and it’s OK – preferred, even – to hold them at once.

The challenge is avoiding getting pulled into an outlook that is not just positive, not just unlikely – but one with no basis in reality. There’s hope – and then there’s false hope. There’s a positive take – and then there’s lying. It can be a fine line, and with the intention of being kind it can be all too easy to “yes, but” our way into untruths.

The best we can do is set limits with compassion, and understand that telling the truth doesn’t always mean that someone hears it.

“Have you ever had a patient – I mean, someone like me, someone in my ... state ... get cured without any treatment?”

The chances of Mr. B’s cancer responding to chemotherapy were not good but hardly impossible. But without any therapy at all?

“I have not.”

“What about at other places ... in other states or countries. Have you ever heard of a person like me who was cured without treatment?”

“I have not.”

“I guess what I’m asking, Doctor, is ... have you ever seen where the cancer was there and then one day was not ... have you ever seen a miracle?”

Reaching. Grasping.

“I have not.”

“Well,” he said, “Maybe I will be the first.”

We look at each other, pondering this. In my silence is the answer.

Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz.

“Doctor, I have a question for you.”

“Yes?”

“Have you ever had a patient – I mean, someone like me, someone in my ... state ... get cured without any treatment?”

Mr. B thought he felt too well to have an aggressive cancer infiltrating his liver, abdominal wall, and lungs. He lived an active life, going to church, volunteering, and playing with his grandchildren. But the biopsy results were back. It wasn’t an infection. It wasn’t inflammation. It was stage 4 cancer.

And just like that, his life changed.

His prognosis was likely months, with a best case scenario of several years. But gone were the days of thinking 10, 20, and 30 years ahead.

It’s not a bad thing. It’s an adaptive mechanism and positive outlooks can even be associated with better medical outcomes. There’s almost always a “but” if you look hard enough. And in the face of life-changing news, we are incentivized to look really, really hard.

Yet Mr. B caught me off guard because he wasn’t asking me to maintain hope. He was pushing me one step further.

At one point in our conversation, he revealed this clearly. “Doctor, I don’t even care if it’s false hope – just tell me the cancer will disappear.”

Mr. B was asking me to lie to him.

The last thing I wanted was to take away hope, closing the door on a future that truly was clouded in uncertainty. But I also couldn’t look him in the eye and tell him his incurable disease was, in fact, curable.

That doesn’t mean there aren’t ways to phrase things kindly. Patients respond differently to “there’s a 90% chance of survival” and “there’s a 10% chance of death” even though the facts are identical.

When I sense a person like Mr. B is looking to me for hope, I try to frame that initial conversation in the style of the first statement. It’s not dishonest. With an already overwhelming piece of information, it’s choosing to share the most positive version of a narrative that can be told in many different ways and will evolve over time.

Moreover, being hopeful and realistic are not mutually exclusive. Just because someone is seeking the rare chance of a good outcome doesn’t mean he or she doesn’t understand the seriousness of the situation. It is possible to seek out experimental drugs while also considering hospice. It is possible to hope for a plan A while preparing for a plan B. Those are two compatible beliefs, and it’s OK – preferred, even – to hold them at once.

The challenge is avoiding getting pulled into an outlook that is not just positive, not just unlikely – but one with no basis in reality. There’s hope – and then there’s false hope. There’s a positive take – and then there’s lying. It can be a fine line, and with the intention of being kind it can be all too easy to “yes, but” our way into untruths.

The best we can do is set limits with compassion, and understand that telling the truth doesn’t always mean that someone hears it.

“Have you ever had a patient – I mean, someone like me, someone in my ... state ... get cured without any treatment?”

The chances of Mr. B’s cancer responding to chemotherapy were not good but hardly impossible. But without any therapy at all?

“I have not.”

“What about at other places ... in other states or countries. Have you ever heard of a person like me who was cured without treatment?”

“I have not.”

“I guess what I’m asking, Doctor, is ... have you ever seen where the cancer was there and then one day was not ... have you ever seen a miracle?”

Reaching. Grasping.

“I have not.”

“Well,” he said, “Maybe I will be the first.”

We look at each other, pondering this. In my silence is the answer.

Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz.