ORLANDO – Use of romosozumab (Evenity) by patients with osteoporosis in various stages of renal insufficiency did not appear to affect increases in bone mineral density, the rate of new vertebral fractures, or the number of adverse events when compared with placebo, Paul D. Miller, MD, said at the annual meeting of the American Society for Bone and Mineral Research.

“Romosozumab could be considered a treatment option for osteoporotic patients with mild to moderate reductions in renal function,” said Dr. Miller, distinguished clinical professor of medicine at the University of Colorado at Denver, Aurora.

Since bisphosphonates are not recommended for use in patients with an estimated glomerular filtration rate (eGFR) of less than 30 or 35 mL/min/1.73 m², other osteoporosis treatments such as romosozumab should also be examined. “It is important to evaluate other osteoporosis treatments in this setting, particularly in the context of monoclonal antibodies, which are not cleared in the kidneys and are metabolized in the reticular endothelial system, and have no FDA ... cut-off for their use,” Dr. Miller said.

Dr. Miller and colleagues performed a post hoc analysis of patients in the FRAME study, which enrolled 3,589 patients who received a monthly dose of subcutaneous romosozumab (215 mg) and 3,591 patients who received placebo in a double-blinded study for 12 months before moving to a 12-month, open-label portion of the study where all patients received 60 mg of subcutaneous denosumab every 6 months. After 12 months, the researchers analyzed the least squares mean (LSM) percentage change in bone mineral density (BMD) at the total hip, lumbar spine, and femoral neck as well as whether patients had any new vertebral fractures or experienced adverse events from treatment.

Patients were postmenopausal women between ages 55 and 90 years with a BMD T-score between –2.5 and –3.5 at the total hip or femoral neck. Researchers divided patients into four eGFR groups based chronic kidney disease (CKD) stage: normal (90 mL/min/1.73 m² or higher; 848 patients), mild CKD (60-89 mL/min/1.73 m²; 4,939 patients), moderate CKD (30-59 mL/min/1.73 m²; 1,360 patients), and severe (15-29 mL/min/1.73 m²; 18 patients).

The LSM percentage change was 13.1% in the lumbar spine (95% confidence interval, 12.8%-13.3%) for the romosozumab group, compared with 0.4% in the placebo group (95% CI, 0.2%-0.5%). The LSM percentage change for total hip was 6.0% in the romosozumab group (95% CI, 5.9%-6.2%), compared with 0.3% in the placebo group (95% CI, 0.1%-0.4%), while the LSM percentage change for the femoral neck was 5.5% in the romosozumab group (95% CI, 5.2%-5.7%) and 0.3% in the placebo group (0.1%-0.5%).

“[The] risk of new vertebral fractures was decreased in all eGFR subgroups and did not appear to be affected by eGFR level,” he said.

Specifically, vertebral fracture incidence was 0.5% in the romosozumab group, compared with 3.0% in the placebo group, for patients with normal renal function, 0.4% in the romosozumab group, compared with 1.5% in the placebo group, for patients with mild chronic kidney disease, and 0.6% in the romosozumab group vs. 2.1% in the placebo group for patients with moderate chronic kidney disease. The incidence of adverse events, serious adverse events, and positively adjudicated cardiovascular events were similar between patients in the romosozumab group regardless of renal function status. The researchers reported 1 patient in the romosozumab group who experienced grade 2 hypocalcemia, and 14 patients in the romosozumab group who experienced mild to moderate decreases in calcium, compared with 4 patients in the placebo group.

Dr. Miller noted the study was limited by having few patients with an eGFR of less than 30 mL/min/1.73 m² and no patients with an eGFR of less than 15 mL/min/1.73 m², but said the study strengths were its large randomized nature and well-balanced baseline characteristics between each group.

This study was sponsored in part by Amgen, Astellas, and UCB Pharma. Dr. Miller reported receiving grants from Alexion, Amgen, Radius, Regeneron, UCB, and Ultragenyx. Amgen and UCB assisted in and provided financial assistance for the preparation of Dr. Miller’s presentation.

SOURCE: Miller P et al. ASBMR 2019. Abstract 1085.

ORLANDO – Use of romosozumab (Evenity) by patients with osteoporosis in various stages of renal insufficiency did not appear to affect increases in bone mineral density, the rate of new vertebral fractures, or the number of adverse events when compared with placebo, Paul D. Miller, MD, said at the annual meeting of the American Society for Bone and Mineral Research.

“Romosozumab could be considered a treatment option for osteoporotic patients with mild to moderate reductions in renal function,” said Dr. Miller, distinguished clinical professor of medicine at the University of Colorado at Denver, Aurora.

Since bisphosphonates are not recommended for use in patients with an estimated glomerular filtration rate (eGFR) of less than 30 or 35 mL/min/1.73 m², other osteoporosis treatments such as romosozumab should also be examined. “It is important to evaluate other osteoporosis treatments in this setting, particularly in the context of monoclonal antibodies, which are not cleared in the kidneys and are metabolized in the reticular endothelial system, and have no FDA ... cut-off for their use,” Dr. Miller said.

Dr. Miller and colleagues performed a post hoc analysis of patients in the FRAME study, which enrolled 3,589 patients who received a monthly dose of subcutaneous romosozumab (215 mg) and 3,591 patients who received placebo in a double-blinded study for 12 months before moving to a 12-month, open-label portion of the study where all patients received 60 mg of subcutaneous denosumab every 6 months. After 12 months, the researchers analyzed the least squares mean (LSM) percentage change in bone mineral density (BMD) at the total hip, lumbar spine, and femoral neck as well as whether patients had any new vertebral fractures or experienced adverse events from treatment.

Patients were postmenopausal women between ages 55 and 90 years with a BMD T-score between –2.5 and –3.5 at the total hip or femoral neck. Researchers divided patients into four eGFR groups based chronic kidney disease (CKD) stage: normal (90 mL/min/1.73 m² or higher; 848 patients), mild CKD (60-89 mL/min/1.73 m²; 4,939 patients), moderate CKD (30-59 mL/min/1.73 m²; 1,360 patients), and severe (15-29 mL/min/1.73 m²; 18 patients).

The LSM percentage change was 13.1% in the lumbar spine (95% confidence interval, 12.8%-13.3%) for the romosozumab group, compared with 0.4% in the placebo group (95% CI, 0.2%-0.5%). The LSM percentage change for total hip was 6.0% in the romosozumab group (95% CI, 5.9%-6.2%), compared with 0.3% in the placebo group (95% CI, 0.1%-0.4%), while the LSM percentage change for the femoral neck was 5.5% in the romosozumab group (95% CI, 5.2%-5.7%) and 0.3% in the placebo group (0.1%-0.5%).

“[The] risk of new vertebral fractures was decreased in all eGFR subgroups and did not appear to be affected by eGFR level,” he said.

Specifically, vertebral fracture incidence was 0.5% in the romosozumab group, compared with 3.0% in the placebo group, for patients with normal renal function, 0.4% in the romosozumab group, compared with 1.5% in the placebo group, for patients with mild chronic kidney disease, and 0.6% in the romosozumab group vs. 2.1% in the placebo group for patients with moderate chronic kidney disease. The incidence of adverse events, serious adverse events, and positively adjudicated cardiovascular events were similar between patients in the romosozumab group regardless of renal function status. The researchers reported 1 patient in the romosozumab group who experienced grade 2 hypocalcemia, and 14 patients in the romosozumab group who experienced mild to moderate decreases in calcium, compared with 4 patients in the placebo group.

Dr. Miller noted the study was limited by having few patients with an eGFR of less than 30 mL/min/1.73 m² and no patients with an eGFR of less than 15 mL/min/1.73 m², but said the study strengths were its large randomized nature and well-balanced baseline characteristics between each group.

This study was sponsored in part by Amgen, Astellas, and UCB Pharma. Dr. Miller reported receiving grants from Alexion, Amgen, Radius, Regeneron, UCB, and Ultragenyx. Amgen and UCB assisted in and provided financial assistance for the preparation of Dr. Miller’s presentation.

SOURCE: Miller P et al. ASBMR 2019. Abstract 1085.

ORLANDO – Use of romosozumab (Evenity) by patients with osteoporosis in various stages of renal insufficiency did not appear to affect increases in bone mineral density, the rate of new vertebral fractures, or the number of adverse events when compared with placebo, Paul D. Miller, MD, said at the annual meeting of the American Society for Bone and Mineral Research.

“Romosozumab could be considered a treatment option for osteoporotic patients with mild to moderate reductions in renal function,” said Dr. Miller, distinguished clinical professor of medicine at the University of Colorado at Denver, Aurora.

Since bisphosphonates are not recommended for use in patients with an estimated glomerular filtration rate (eGFR) of less than 30 or 35 mL/min/1.73 m², other osteoporosis treatments such as romosozumab should also be examined. “It is important to evaluate other osteoporosis treatments in this setting, particularly in the context of monoclonal antibodies, which are not cleared in the kidneys and are metabolized in the reticular endothelial system, and have no FDA ... cut-off for their use,” Dr. Miller said.

Dr. Miller and colleagues performed a post hoc analysis of patients in the FRAME study, which enrolled 3,589 patients who received a monthly dose of subcutaneous romosozumab (215 mg) and 3,591 patients who received placebo in a double-blinded study for 12 months before moving to a 12-month, open-label portion of the study where all patients received 60 mg of subcutaneous denosumab every 6 months. After 12 months, the researchers analyzed the least squares mean (LSM) percentage change in bone mineral density (BMD) at the total hip, lumbar spine, and femoral neck as well as whether patients had any new vertebral fractures or experienced adverse events from treatment.

Patients were postmenopausal women between ages 55 and 90 years with a BMD T-score between –2.5 and –3.5 at the total hip or femoral neck. Researchers divided patients into four eGFR groups based chronic kidney disease (CKD) stage: normal (90 mL/min/1.73 m² or higher; 848 patients), mild CKD (60-89 mL/min/1.73 m²; 4,939 patients), moderate CKD (30-59 mL/min/1.73 m²; 1,360 patients), and severe (15-29 mL/min/1.73 m²; 18 patients).

The LSM percentage change was 13.1% in the lumbar spine (95% confidence interval, 12.8%-13.3%) for the romosozumab group, compared with 0.4% in the placebo group (95% CI, 0.2%-0.5%). The LSM percentage change for total hip was 6.0% in the romosozumab group (95% CI, 5.9%-6.2%), compared with 0.3% in the placebo group (95% CI, 0.1%-0.4%), while the LSM percentage change for the femoral neck was 5.5% in the romosozumab group (95% CI, 5.2%-5.7%) and 0.3% in the placebo group (0.1%-0.5%).

“[The] risk of new vertebral fractures was decreased in all eGFR subgroups and did not appear to be affected by eGFR level,” he said.

Specifically, vertebral fracture incidence was 0.5% in the romosozumab group, compared with 3.0% in the placebo group, for patients with normal renal function, 0.4% in the romosozumab group, compared with 1.5% in the placebo group, for patients with mild chronic kidney disease, and 0.6% in the romosozumab group vs. 2.1% in the placebo group for patients with moderate chronic kidney disease. The incidence of adverse events, serious adverse events, and positively adjudicated cardiovascular events were similar between patients in the romosozumab group regardless of renal function status. The researchers reported 1 patient in the romosozumab group who experienced grade 2 hypocalcemia, and 14 patients in the romosozumab group who experienced mild to moderate decreases in calcium, compared with 4 patients in the placebo group.

Dr. Miller noted the study was limited by having few patients with an eGFR of less than 30 mL/min/1.73 m² and no patients with an eGFR of less than 15 mL/min/1.73 m², but said the study strengths were its large randomized nature and well-balanced baseline characteristics between each group.

This study was sponsored in part by Amgen, Astellas, and UCB Pharma. Dr. Miller reported receiving grants from Alexion, Amgen, Radius, Regeneron, UCB, and Ultragenyx. Amgen and UCB assisted in and provided financial assistance for the preparation of Dr. Miller’s presentation.

SOURCE: Miller P et al. ASBMR 2019. Abstract 1085.

CHICAGO – The need for additional intervention after repair of the ascending aorta in extended type A aortic dissection has been thought to follow the practice for type B dissection and favor preemptive thoracic endovascular aortic repair. However, preemptive TEVAR may, at least in the midterm, provide no benefit in patients with extended type A dissections, according to results reported at the annual meeting of the Midwestern Vascular Surgery Society.

DAJ/Thinkstock

“TEVAR does not appear to be indicated in patients with extended type A dissections after acute aortic repair,” said Amy B. Reed, MD, of the University of Minnesota.

The study’s hypothesis was that growth rates of dissection and the need for additional intervention in the descending thoracic aorta are similar between extended type A (ExTA) and type B aortic dissection after initial repair of the ascending aorta. Dr. Reed noted that investigators from the INSTEAD-XL trial reported that preemptive TEVAR improved outcomes in patients with type B dissections (Circ Cardiovasc Interv. 2013;6:407-16). “The thinking has been that patients with uncomplicated ExTA would also benefit from early TEVAR,” Dr. Reed said.

The study evaluated 87 consecutive patients from 2011 to 2018, 43 with ExTA and 44 with type B dissections. Characteristics of both groups were similar, except the type B group had a significantly higher rate of coronary artery disease, 16% vs. 0% (P = .01). The distal extent of the dissection was beyond the aortic bifurcation in 75% of the ExTA patients and 52% of the type B group, “so we felt that these groups were really well matched,” Dr. Reed said.

Of the 43 ExTA patients, five had repair and 38 had no intervention. At an average follow-up of 33 months, 23 of the no-intervention patients showed no growth of their dissection, Dr. Reed said. In the type B group, 15 had no repair, and of those nine showed no growth (one patient died early and five did show growth).

“When we look at intervention-free survival, there’s a significant difference between our ExTA patients vs. our type B patients over time, with significantly more type B patients requiring intervention,” she said. At 28 months, 88% of ExTA were intervention free, whereas at 9 months 35% of type B patients were.

“We feel that, following the repair of ascending acute aortic dissection, in those patients with ExTA dissections, there does appear to be a slow progression of distal aortic disease,” Dr. Reed said. “Rarely do these patients develop complications such as dissection needing intervention either in the acute hospital period or delayed.”

Because the findings are based on medium-term follow-up, she said, “We certainly need further follow-up to confirm these midterm findings.”

Dr. Reed had no relevant financial relationships to disclose.

CHICAGO – The need for additional intervention after repair of the ascending aorta in extended type A aortic dissection has been thought to follow the practice for type B dissection and favor preemptive thoracic endovascular aortic repair. However, preemptive TEVAR may, at least in the midterm, provide no benefit in patients with extended type A dissections, according to results reported at the annual meeting of the Midwestern Vascular Surgery Society.

DAJ/Thinkstock

“TEVAR does not appear to be indicated in patients with extended type A dissections after acute aortic repair,” said Amy B. Reed, MD, of the University of Minnesota.

The study’s hypothesis was that growth rates of dissection and the need for additional intervention in the descending thoracic aorta are similar between extended type A (ExTA) and type B aortic dissection after initial repair of the ascending aorta. Dr. Reed noted that investigators from the INSTEAD-XL trial reported that preemptive TEVAR improved outcomes in patients with type B dissections (Circ Cardiovasc Interv. 2013;6:407-16). “The thinking has been that patients with uncomplicated ExTA would also benefit from early TEVAR,” Dr. Reed said.

The study evaluated 87 consecutive patients from 2011 to 2018, 43 with ExTA and 44 with type B dissections. Characteristics of both groups were similar, except the type B group had a significantly higher rate of coronary artery disease, 16% vs. 0% (P = .01). The distal extent of the dissection was beyond the aortic bifurcation in 75% of the ExTA patients and 52% of the type B group, “so we felt that these groups were really well matched,” Dr. Reed said.

Of the 43 ExTA patients, five had repair and 38 had no intervention. At an average follow-up of 33 months, 23 of the no-intervention patients showed no growth of their dissection, Dr. Reed said. In the type B group, 15 had no repair, and of those nine showed no growth (one patient died early and five did show growth).

“When we look at intervention-free survival, there’s a significant difference between our ExTA patients vs. our type B patients over time, with significantly more type B patients requiring intervention,” she said. At 28 months, 88% of ExTA were intervention free, whereas at 9 months 35% of type B patients were.

“We feel that, following the repair of ascending acute aortic dissection, in those patients with ExTA dissections, there does appear to be a slow progression of distal aortic disease,” Dr. Reed said. “Rarely do these patients develop complications such as dissection needing intervention either in the acute hospital period or delayed.”

Because the findings are based on medium-term follow-up, she said, “We certainly need further follow-up to confirm these midterm findings.”

Dr. Reed had no relevant financial relationships to disclose.

CHICAGO – The need for additional intervention after repair of the ascending aorta in extended type A aortic dissection has been thought to follow the practice for type B dissection and favor preemptive thoracic endovascular aortic repair. However, preemptive TEVAR may, at least in the midterm, provide no benefit in patients with extended type A dissections, according to results reported at the annual meeting of the Midwestern Vascular Surgery Society.

DAJ/Thinkstock

“TEVAR does not appear to be indicated in patients with extended type A dissections after acute aortic repair,” said Amy B. Reed, MD, of the University of Minnesota.

The study’s hypothesis was that growth rates of dissection and the need for additional intervention in the descending thoracic aorta are similar between extended type A (ExTA) and type B aortic dissection after initial repair of the ascending aorta. Dr. Reed noted that investigators from the INSTEAD-XL trial reported that preemptive TEVAR improved outcomes in patients with type B dissections (Circ Cardiovasc Interv. 2013;6:407-16). “The thinking has been that patients with uncomplicated ExTA would also benefit from early TEVAR,” Dr. Reed said.

The study evaluated 87 consecutive patients from 2011 to 2018, 43 with ExTA and 44 with type B dissections. Characteristics of both groups were similar, except the type B group had a significantly higher rate of coronary artery disease, 16% vs. 0% (P = .01). The distal extent of the dissection was beyond the aortic bifurcation in 75% of the ExTA patients and 52% of the type B group, “so we felt that these groups were really well matched,” Dr. Reed said.

Of the 43 ExTA patients, five had repair and 38 had no intervention. At an average follow-up of 33 months, 23 of the no-intervention patients showed no growth of their dissection, Dr. Reed said. In the type B group, 15 had no repair, and of those nine showed no growth (one patient died early and five did show growth).

“When we look at intervention-free survival, there’s a significant difference between our ExTA patients vs. our type B patients over time, with significantly more type B patients requiring intervention,” she said. At 28 months, 88% of ExTA were intervention free, whereas at 9 months 35% of type B patients were.

“We feel that, following the repair of ascending acute aortic dissection, in those patients with ExTA dissections, there does appear to be a slow progression of distal aortic disease,” Dr. Reed said. “Rarely do these patients develop complications such as dissection needing intervention either in the acute hospital period or delayed.”

Because the findings are based on medium-term follow-up, she said, “We certainly need further follow-up to confirm these midterm findings.”

Dr. Reed had no relevant financial relationships to disclose.

Hospitalization can be a challenging and vulnerable time for patients and their families. While challenges associated with the quality and safety of hospital care are well documented, perspectives of patients, families, caregivers, and other stakeholders are not as easily understood and are important targets of improvement research.

This led to the initiation of the i-HOPE Patient Engagement Study, a collaboration including the Society for Hospital Medicine’s Center for Quality Improvement. The team completed a systematic and broad engagement process with patients, families, and caregivers, followed by an in-person prioritization meeting to generate a priority list of research topics that describe the most important gaps in the care of hospitalized patients.

The Hospitalist recently spoke with Luci Leykum, MD, MSc, MBA, SFHM, principal investigator for the i-HOPE Study, professor of medicine and investigator in the South Texas Veterans Health Care System and incoming associate chair for clinical innovation at the University of Texas at Austin.

Why is it so important to include the perspective of the patient during a hospital stay?

We cannot optimally improve outcomes of hospitalized patients if we don’t have patients’ perspectives on what needs to be improved. Hearing these perspectives also provides insights into how we can address gaps in hospital care.

How were patients and other stakeholders engaged during the i-HOPE program?

Patients, caregivers, and stakeholders were engaged throughout the entire project, from conceptualization to dissemination of results.

We worked with seven patient partners to develop the proposal that we submitted to the Patient-Centered Outcomes Research Institute. They were involved in all phases of the project, from developing the informational webinars and surveys to analyzing our results.

We engaged additional patients, caregivers, and stakeholders to submit their highest priority unanswered research questions for improving hospital care. A total of 117 patients and 127 caregivers submitted questions. Our patient partners and more than 30 stakeholders were involved in prioritizing those research questions to develop our final agenda.

What is unique about the approach in the i-HOPE project, compared with other projects that may have had similar intended objectives?

Our project is unique in several respects. First, it was completely patient partnered. Having patients as equal members of the team changed our approach at every level – from how we communicated with patients and stakeholders to how we analyzed and presented our data. Second, we worked with a larger number of stakeholders representing a broad range of constituencies, from professional societies to health care delivery systems to payers.

How has SHM’s Center for Quality Improvement helped the i-HOPE program to realize its goals?

The Center for Quality Improvement helped considerably with the execution of the project. The researchers involved in i-HOPE were all members of the SHM Research Committee and were familiar with SHM’s capability as a partner in these larger-scale projects. The SHM Meetings team was instrumental in making our in-person patient and stakeholder prioritization meeting happen as well.

How can the findings of the i-HOPE program be applied?

We hope everyone can utilize our findings. Patients, families, and caregivers can use our results to improve their own care. Providers and delivery systems can target their improvement efforts using our findings to ensure that their work has the greatest impact on patients. Policy makers and funders can use our findings to direct work to the priority areas we identified. And finally, we hope the hospital research community uses our results to develop novel interventions to improve care.

For more information on the i-HOPE Patient Engagement Study, visit hospitalmedicine.org/ihope.

Hospitalization can be a challenging and vulnerable time for patients and their families. While challenges associated with the quality and safety of hospital care are well documented, perspectives of patients, families, caregivers, and other stakeholders are not as easily understood and are important targets of improvement research.

This led to the initiation of the i-HOPE Patient Engagement Study, a collaboration including the Society for Hospital Medicine’s Center for Quality Improvement. The team completed a systematic and broad engagement process with patients, families, and caregivers, followed by an in-person prioritization meeting to generate a priority list of research topics that describe the most important gaps in the care of hospitalized patients.

The Hospitalist recently spoke with Luci Leykum, MD, MSc, MBA, SFHM, principal investigator for the i-HOPE Study, professor of medicine and investigator in the South Texas Veterans Health Care System and incoming associate chair for clinical innovation at the University of Texas at Austin.

Why is it so important to include the perspective of the patient during a hospital stay?

We cannot optimally improve outcomes of hospitalized patients if we don’t have patients’ perspectives on what needs to be improved. Hearing these perspectives also provides insights into how we can address gaps in hospital care.

How were patients and other stakeholders engaged during the i-HOPE program?

Patients, caregivers, and stakeholders were engaged throughout the entire project, from conceptualization to dissemination of results.

We worked with seven patient partners to develop the proposal that we submitted to the Patient-Centered Outcomes Research Institute. They were involved in all phases of the project, from developing the informational webinars and surveys to analyzing our results.

We engaged additional patients, caregivers, and stakeholders to submit their highest priority unanswered research questions for improving hospital care. A total of 117 patients and 127 caregivers submitted questions. Our patient partners and more than 30 stakeholders were involved in prioritizing those research questions to develop our final agenda.

What is unique about the approach in the i-HOPE project, compared with other projects that may have had similar intended objectives?

Our project is unique in several respects. First, it was completely patient partnered. Having patients as equal members of the team changed our approach at every level – from how we communicated with patients and stakeholders to how we analyzed and presented our data. Second, we worked with a larger number of stakeholders representing a broad range of constituencies, from professional societies to health care delivery systems to payers.

How has SHM’s Center for Quality Improvement helped the i-HOPE program to realize its goals?

The Center for Quality Improvement helped considerably with the execution of the project. The researchers involved in i-HOPE were all members of the SHM Research Committee and were familiar with SHM’s capability as a partner in these larger-scale projects. The SHM Meetings team was instrumental in making our in-person patient and stakeholder prioritization meeting happen as well.

How can the findings of the i-HOPE program be applied?

We hope everyone can utilize our findings. Patients, families, and caregivers can use our results to improve their own care. Providers and delivery systems can target their improvement efforts using our findings to ensure that their work has the greatest impact on patients. Policy makers and funders can use our findings to direct work to the priority areas we identified. And finally, we hope the hospital research community uses our results to develop novel interventions to improve care.

For more information on the i-HOPE Patient Engagement Study, visit hospitalmedicine.org/ihope.

Hospitalization can be a challenging and vulnerable time for patients and their families. While challenges associated with the quality and safety of hospital care are well documented, perspectives of patients, families, caregivers, and other stakeholders are not as easily understood and are important targets of improvement research.

This led to the initiation of the i-HOPE Patient Engagement Study, a collaboration including the Society for Hospital Medicine’s Center for Quality Improvement. The team completed a systematic and broad engagement process with patients, families, and caregivers, followed by an in-person prioritization meeting to generate a priority list of research topics that describe the most important gaps in the care of hospitalized patients.

The Hospitalist recently spoke with Luci Leykum, MD, MSc, MBA, SFHM, principal investigator for the i-HOPE Study, professor of medicine and investigator in the South Texas Veterans Health Care System and incoming associate chair for clinical innovation at the University of Texas at Austin.

Why is it so important to include the perspective of the patient during a hospital stay?

We cannot optimally improve outcomes of hospitalized patients if we don’t have patients’ perspectives on what needs to be improved. Hearing these perspectives also provides insights into how we can address gaps in hospital care.

How were patients and other stakeholders engaged during the i-HOPE program?

Patients, caregivers, and stakeholders were engaged throughout the entire project, from conceptualization to dissemination of results.

We worked with seven patient partners to develop the proposal that we submitted to the Patient-Centered Outcomes Research Institute. They were involved in all phases of the project, from developing the informational webinars and surveys to analyzing our results.

We engaged additional patients, caregivers, and stakeholders to submit their highest priority unanswered research questions for improving hospital care. A total of 117 patients and 127 caregivers submitted questions. Our patient partners and more than 30 stakeholders were involved in prioritizing those research questions to develop our final agenda.

What is unique about the approach in the i-HOPE project, compared with other projects that may have had similar intended objectives?

Our project is unique in several respects. First, it was completely patient partnered. Having patients as equal members of the team changed our approach at every level – from how we communicated with patients and stakeholders to how we analyzed and presented our data. Second, we worked with a larger number of stakeholders representing a broad range of constituencies, from professional societies to health care delivery systems to payers.

How has SHM’s Center for Quality Improvement helped the i-HOPE program to realize its goals?

The Center for Quality Improvement helped considerably with the execution of the project. The researchers involved in i-HOPE were all members of the SHM Research Committee and were familiar with SHM’s capability as a partner in these larger-scale projects. The SHM Meetings team was instrumental in making our in-person patient and stakeholder prioritization meeting happen as well.

How can the findings of the i-HOPE program be applied?

We hope everyone can utilize our findings. Patients, families, and caregivers can use our results to improve their own care. Providers and delivery systems can target their improvement efforts using our findings to ensure that their work has the greatest impact on patients. Policy makers and funders can use our findings to direct work to the priority areas we identified. And finally, we hope the hospital research community uses our results to develop novel interventions to improve care.

For more information on the i-HOPE Patient Engagement Study, visit hospitalmedicine.org/ihope.

Eltrombopag showed good safety and promising clinical activity in patients with immune thrombocytopenia (ITP) secondary to chronic lymphoproliferative disorders, according to results from a phase 2 trial.

Carlo Visco, MD, of the University of Verona (Italy), and colleagues investigated the efficacy and safety of eltrombopag in increasing platelet counts in patients with ITP that was secondary to chronic lymphoproliferative disorders. The findings were published in Blood.

The single-arm, open-label study included 18 patients with ITP secondary to chronic lymphocytic leukemia (14), Waldenstrom macroglobulinemia (2), and classical Hodgkin lymphoma (2). The median age at baseline was 70 years (range, 43-83 years), and all patients were previously treated with ITP.

Study participants were recruited from seven Italian centers from September 2012 to November 2015. Eligible participants were enrolled into an extension phase if a response was observed.

Study patients received oral eltrombopag at 50 mg daily, up to a maximum of 150 mg daily. At weeks 4 and 24, the median dose was 50 mg (ranges, 25-100 mg and 25-150 mg, respectively), with a median total exposure time of 16 months.

At 4 weeks, the researchers found that the platelet response rate was 78%, with a complete response rate of 50%.

After 24 weeks of therapy, the platelet response rate was 59%, with a complete response rate of 30%.

With respect to safety, the therapy was well tolerated, with no adverse events higher than grade 2 reported.

Fifteen patients discontinued therapy: eight due to loss of response, six for disease progression or death, and one for inefficacy and protocol violation, they reported.

The researchers acknowledged two key limitations of the study: the small sample size and lack of a comparison group. “Further prospective studies comparing eltrombopag to standard of care are needed to confirm our findings on the efficacy of this treatment and also to expand our knowledge on its safety, including the potential increased risk of thrombosis,” they wrote.

The study was funded by the Hematology Project Foundation, Vicenza. The authors reported financial affiliations with Amgen, Argenx, and Novartis.

SOURCE: Visco C et al. Blood. 2019 Sep 30. doi: 10.1182/blood.2019001617.

Eltrombopag showed good safety and promising clinical activity in patients with immune thrombocytopenia (ITP) secondary to chronic lymphoproliferative disorders, according to results from a phase 2 trial.

Carlo Visco, MD, of the University of Verona (Italy), and colleagues investigated the efficacy and safety of eltrombopag in increasing platelet counts in patients with ITP that was secondary to chronic lymphoproliferative disorders. The findings were published in Blood.

The single-arm, open-label study included 18 patients with ITP secondary to chronic lymphocytic leukemia (14), Waldenstrom macroglobulinemia (2), and classical Hodgkin lymphoma (2). The median age at baseline was 70 years (range, 43-83 years), and all patients were previously treated with ITP.

Study participants were recruited from seven Italian centers from September 2012 to November 2015. Eligible participants were enrolled into an extension phase if a response was observed.

Study patients received oral eltrombopag at 50 mg daily, up to a maximum of 150 mg daily. At weeks 4 and 24, the median dose was 50 mg (ranges, 25-100 mg and 25-150 mg, respectively), with a median total exposure time of 16 months.

At 4 weeks, the researchers found that the platelet response rate was 78%, with a complete response rate of 50%.

After 24 weeks of therapy, the platelet response rate was 59%, with a complete response rate of 30%.

With respect to safety, the therapy was well tolerated, with no adverse events higher than grade 2 reported.

Fifteen patients discontinued therapy: eight due to loss of response, six for disease progression or death, and one for inefficacy and protocol violation, they reported.

The researchers acknowledged two key limitations of the study: the small sample size and lack of a comparison group. “Further prospective studies comparing eltrombopag to standard of care are needed to confirm our findings on the efficacy of this treatment and also to expand our knowledge on its safety, including the potential increased risk of thrombosis,” they wrote.

The study was funded by the Hematology Project Foundation, Vicenza. The authors reported financial affiliations with Amgen, Argenx, and Novartis.

SOURCE: Visco C et al. Blood. 2019 Sep 30. doi: 10.1182/blood.2019001617.

Eltrombopag showed good safety and promising clinical activity in patients with immune thrombocytopenia (ITP) secondary to chronic lymphoproliferative disorders, according to results from a phase 2 trial.

Carlo Visco, MD, of the University of Verona (Italy), and colleagues investigated the efficacy and safety of eltrombopag in increasing platelet counts in patients with ITP that was secondary to chronic lymphoproliferative disorders. The findings were published in Blood.

The single-arm, open-label study included 18 patients with ITP secondary to chronic lymphocytic leukemia (14), Waldenstrom macroglobulinemia (2), and classical Hodgkin lymphoma (2). The median age at baseline was 70 years (range, 43-83 years), and all patients were previously treated with ITP.

Study participants were recruited from seven Italian centers from September 2012 to November 2015. Eligible participants were enrolled into an extension phase if a response was observed.

Study patients received oral eltrombopag at 50 mg daily, up to a maximum of 150 mg daily. At weeks 4 and 24, the median dose was 50 mg (ranges, 25-100 mg and 25-150 mg, respectively), with a median total exposure time of 16 months.

At 4 weeks, the researchers found that the platelet response rate was 78%, with a complete response rate of 50%.

After 24 weeks of therapy, the platelet response rate was 59%, with a complete response rate of 30%.

With respect to safety, the therapy was well tolerated, with no adverse events higher than grade 2 reported.

Fifteen patients discontinued therapy: eight due to loss of response, six for disease progression or death, and one for inefficacy and protocol violation, they reported.

The researchers acknowledged two key limitations of the study: the small sample size and lack of a comparison group. “Further prospective studies comparing eltrombopag to standard of care are needed to confirm our findings on the efficacy of this treatment and also to expand our knowledge on its safety, including the potential increased risk of thrombosis,” they wrote.

The study was funded by the Hematology Project Foundation, Vicenza. The authors reported financial affiliations with Amgen, Argenx, and Novartis.

SOURCE: Visco C et al. Blood. 2019 Sep 30. doi: 10.1182/blood.2019001617.

The Diagnosis: Lichenoid and Granulomatous Dermatitis in the Setting of Secondary Syphilis  

Syphilis, an infectious disease that has risen in incidence and is most commonly reported in men who have sex with men, involves a vast array of clinical and histologic presentations.¹ Clinically, secondary syphilis involves an erythematous maculopapular eruption on the face, trunk, palms, soles, or genital area.² The characteristic histologic features for secondary syphilis include endothelial swelling, interstitial inflammatory array, irregular acanthosis, elongated rete ridges, and vacuolar interface dermatitis with lymphocytes and plasma cells.¹ Syphilitic infection has been associated with lichenoid and granulomatous dermatitis, which is an inflammatory skin disease described by Magro and Crowson.³ Lichenoid and granulomatous dermatitis has been linked to various systemic disorders, including chronic hepatitis C, Crohn disease, rheumatoid arthritis, endocrinopathy, subacute cutaneous lupus erythematosus, secondary syphilis, prior herpes infection, tuberculoid leprosy, mycobacterial infection, and human immunodeficiency virus infection.^3-7 For this patient, given histopathology findings, clinical presentation, and positive rapid plasma reagin serologies, a diagnosis of lichenoid and granulomatous dermatitis in the setting of a secondary syphilis infection was established. A comprehensive investigation should be conducted to consider secondary syphilis or other systemic diseases in patients with a histologic finding of lichenoid and granulomatous dermatitis. 

Histologically, lichenoid and granulomatous dermatitis cases show a bandlike infiltrate of lymphocytes with neighboring histiocytes along the dermoepidermal junction, accompanied by epithelial changes of dyskeratosis, vasculopathy, and colloid body formation, in addition to a dermal histiocytic component.³ Our patient's biopsy showed a lichenoid reaction pattern with vacuolar interface changes, dyskeratosis, plump endothelial cells, and small collections of plasma cells. Additionally, there was a granulomatous component in the dermis with histiocytes admixed with lymphocytes and plasma cells. The presence of spirochetes was confirmed with antitreponemal immunohistochemical stain (Figure 1). Quantitative rapid plasma reagin was 1:64 (reference range, <1:1) and Treponema pallidum antibody was reactive. 

Interstitial granulomatous dermatitis has a variable clinical presentation, often with red-purple annular plaques, hyperpigmented papules, and nodules frequently in a linear arrangement and predominantly on the trunk, thighs, groin, or buttocks.^8,9 On histopathology, there are histiocytes in the reticular dermis and/or a macrophage infiltrate in the mid to deep dermis with collections of degenerated collagen (Figure 2).^8,10 An interstitial infiltrate of eosinophils and neutrophils also may be appreciated, but mucin generally is absent.^8,11 This condition often coexists with rheumatic and systemic autoimmune diseases.^8-10  

Interstitial granuloma annulare is a noninfectious granulomatous skin condition that often presents clinically as asymptomatic annular red-brown patches, usually on the extremities.^11-13 On histopathology, an interstitial or palisaded inflammatory infiltrate with histiocytes and multinucleated giant cells may be seen along with collagen degeneration or collagen bundles without necrosis (Figure 3).⁹ Mucin often is associated with the histiocytes.¹¹ Of note, our patient's skin biopsy shows interface dermatitis, differentiating it from both interstitial granuloma annulare and interstitial granulomatous dermatitis. 

Postviral granulomatous reactions are the most frequently reported types of reactions to occur at the location of herpes zoster infection up to years after the initial disease. Wolf isotopic reaction encompasses skin reactions in the body region of formerly resolved skin disease, commonly herpesvirus infection.^14,15 This manifestation may occur due to a hypersensitivity reaction from enduring viral proteins, resident memory T cells, or local neuroimmune imbalance from herpesvirus-induced injury to dermal sensory nerve fibers.^14-17 Clinically, patients present with red-purple pruritic papules and plaques in a bandlike unilateral pattern, usually in the same region as the prior herpes infection and often accompanied by postherpetic neuralgia.^16-19 Of note, our patient's clinical findings were more diffuse than the frequently localized and often linear distribution seen in postherpetic granulomatous reaction. On histopathology, granulomatous or lichenoid tissue reaction most commonly is appreciated.¹⁵ Specifically, interstitial granulomatous dermatitis with histiocytes, lymphocytes, and multinucleated giant cells showing elastophagocytosis and an inflammatory infiltrate with lymphocytes and plasma cells around vasculature, eccrine glands, and nerves can be noted (Figure 4).¹⁹  

Lupus erythematosus is an autoimmune condition with a wide array of clinical features, including skin manifestations and systemic symptoms. Specifically, discoid lupus erythematosus presents with clearly outlined, red-pink macules or papules with scaling. Histologic features include keratotic follicular plugging, acanthosis, dermal mucin, thickening of the basement membrane zone, and dense lymphocytic infiltrate (Figure 5).²⁰  

The Diagnosis: Lichenoid and Granulomatous Dermatitis in the Setting of Secondary Syphilis  

Syphilis, an infectious disease that has risen in incidence and is most commonly reported in men who have sex with men, involves a vast array of clinical and histologic presentations.¹ Clinically, secondary syphilis involves an erythematous maculopapular eruption on the face, trunk, palms, soles, or genital area.² The characteristic histologic features for secondary syphilis include endothelial swelling, interstitial inflammatory array, irregular acanthosis, elongated rete ridges, and vacuolar interface dermatitis with lymphocytes and plasma cells.¹ Syphilitic infection has been associated with lichenoid and granulomatous dermatitis, which is an inflammatory skin disease described by Magro and Crowson.³ Lichenoid and granulomatous dermatitis has been linked to various systemic disorders, including chronic hepatitis C, Crohn disease, rheumatoid arthritis, endocrinopathy, subacute cutaneous lupus erythematosus, secondary syphilis, prior herpes infection, tuberculoid leprosy, mycobacterial infection, and human immunodeficiency virus infection.^3-7 For this patient, given histopathology findings, clinical presentation, and positive rapid plasma reagin serologies, a diagnosis of lichenoid and granulomatous dermatitis in the setting of a secondary syphilis infection was established. A comprehensive investigation should be conducted to consider secondary syphilis or other systemic diseases in patients with a histologic finding of lichenoid and granulomatous dermatitis. 

Histologically, lichenoid and granulomatous dermatitis cases show a bandlike infiltrate of lymphocytes with neighboring histiocytes along the dermoepidermal junction, accompanied by epithelial changes of dyskeratosis, vasculopathy, and colloid body formation, in addition to a dermal histiocytic component.³ Our patient's biopsy showed a lichenoid reaction pattern with vacuolar interface changes, dyskeratosis, plump endothelial cells, and small collections of plasma cells. Additionally, there was a granulomatous component in the dermis with histiocytes admixed with lymphocytes and plasma cells. The presence of spirochetes was confirmed with antitreponemal immunohistochemical stain (Figure 1). Quantitative rapid plasma reagin was 1:64 (reference range, <1:1) and Treponema pallidum antibody was reactive. 

Interstitial granulomatous dermatitis has a variable clinical presentation, often with red-purple annular plaques, hyperpigmented papules, and nodules frequently in a linear arrangement and predominantly on the trunk, thighs, groin, or buttocks.^8,9 On histopathology, there are histiocytes in the reticular dermis and/or a macrophage infiltrate in the mid to deep dermis with collections of degenerated collagen (Figure 2).^8,10 An interstitial infiltrate of eosinophils and neutrophils also may be appreciated, but mucin generally is absent.^8,11 This condition often coexists with rheumatic and systemic autoimmune diseases.^8-10  

Interstitial granuloma annulare is a noninfectious granulomatous skin condition that often presents clinically as asymptomatic annular red-brown patches, usually on the extremities.^11-13 On histopathology, an interstitial or palisaded inflammatory infiltrate with histiocytes and multinucleated giant cells may be seen along with collagen degeneration or collagen bundles without necrosis (Figure 3).⁹ Mucin often is associated with the histiocytes.¹¹ Of note, our patient's skin biopsy shows interface dermatitis, differentiating it from both interstitial granuloma annulare and interstitial granulomatous dermatitis. 

Postviral granulomatous reactions are the most frequently reported types of reactions to occur at the location of herpes zoster infection up to years after the initial disease. Wolf isotopic reaction encompasses skin reactions in the body region of formerly resolved skin disease, commonly herpesvirus infection.^14,15 This manifestation may occur due to a hypersensitivity reaction from enduring viral proteins, resident memory T cells, or local neuroimmune imbalance from herpesvirus-induced injury to dermal sensory nerve fibers.^14-17 Clinically, patients present with red-purple pruritic papules and plaques in a bandlike unilateral pattern, usually in the same region as the prior herpes infection and often accompanied by postherpetic neuralgia.^16-19 Of note, our patient's clinical findings were more diffuse than the frequently localized and often linear distribution seen in postherpetic granulomatous reaction. On histopathology, granulomatous or lichenoid tissue reaction most commonly is appreciated.¹⁵ Specifically, interstitial granulomatous dermatitis with histiocytes, lymphocytes, and multinucleated giant cells showing elastophagocytosis and an inflammatory infiltrate with lymphocytes and plasma cells around vasculature, eccrine glands, and nerves can be noted (Figure 4).¹⁹  

Lupus erythematosus is an autoimmune condition with a wide array of clinical features, including skin manifestations and systemic symptoms. Specifically, discoid lupus erythematosus presents with clearly outlined, red-pink macules or papules with scaling. Histologic features include keratotic follicular plugging, acanthosis, dermal mucin, thickening of the basement membrane zone, and dense lymphocytic infiltrate (Figure 5).²⁰  

The Diagnosis: Lichenoid and Granulomatous Dermatitis in the Setting of Secondary Syphilis  

Syphilis, an infectious disease that has risen in incidence and is most commonly reported in men who have sex with men, involves a vast array of clinical and histologic presentations.¹ Clinically, secondary syphilis involves an erythematous maculopapular eruption on the face, trunk, palms, soles, or genital area.² The characteristic histologic features for secondary syphilis include endothelial swelling, interstitial inflammatory array, irregular acanthosis, elongated rete ridges, and vacuolar interface dermatitis with lymphocytes and plasma cells.¹ Syphilitic infection has been associated with lichenoid and granulomatous dermatitis, which is an inflammatory skin disease described by Magro and Crowson.³ Lichenoid and granulomatous dermatitis has been linked to various systemic disorders, including chronic hepatitis C, Crohn disease, rheumatoid arthritis, endocrinopathy, subacute cutaneous lupus erythematosus, secondary syphilis, prior herpes infection, tuberculoid leprosy, mycobacterial infection, and human immunodeficiency virus infection.^3-7 For this patient, given histopathology findings, clinical presentation, and positive rapid plasma reagin serologies, a diagnosis of lichenoid and granulomatous dermatitis in the setting of a secondary syphilis infection was established. A comprehensive investigation should be conducted to consider secondary syphilis or other systemic diseases in patients with a histologic finding of lichenoid and granulomatous dermatitis. 

Histologically, lichenoid and granulomatous dermatitis cases show a bandlike infiltrate of lymphocytes with neighboring histiocytes along the dermoepidermal junction, accompanied by epithelial changes of dyskeratosis, vasculopathy, and colloid body formation, in addition to a dermal histiocytic component.³ Our patient's biopsy showed a lichenoid reaction pattern with vacuolar interface changes, dyskeratosis, plump endothelial cells, and small collections of plasma cells. Additionally, there was a granulomatous component in the dermis with histiocytes admixed with lymphocytes and plasma cells. The presence of spirochetes was confirmed with antitreponemal immunohistochemical stain (Figure 1). Quantitative rapid plasma reagin was 1:64 (reference range, <1:1) and Treponema pallidum antibody was reactive. 

Interstitial granulomatous dermatitis has a variable clinical presentation, often with red-purple annular plaques, hyperpigmented papules, and nodules frequently in a linear arrangement and predominantly on the trunk, thighs, groin, or buttocks.^8,9 On histopathology, there are histiocytes in the reticular dermis and/or a macrophage infiltrate in the mid to deep dermis with collections of degenerated collagen (Figure 2).^8,10 An interstitial infiltrate of eosinophils and neutrophils also may be appreciated, but mucin generally is absent.^8,11 This condition often coexists with rheumatic and systemic autoimmune diseases.^8-10  

Interstitial granuloma annulare is a noninfectious granulomatous skin condition that often presents clinically as asymptomatic annular red-brown patches, usually on the extremities.^11-13 On histopathology, an interstitial or palisaded inflammatory infiltrate with histiocytes and multinucleated giant cells may be seen along with collagen degeneration or collagen bundles without necrosis (Figure 3).⁹ Mucin often is associated with the histiocytes.¹¹ Of note, our patient's skin biopsy shows interface dermatitis, differentiating it from both interstitial granuloma annulare and interstitial granulomatous dermatitis. 

Postviral granulomatous reactions are the most frequently reported types of reactions to occur at the location of herpes zoster infection up to years after the initial disease. Wolf isotopic reaction encompasses skin reactions in the body region of formerly resolved skin disease, commonly herpesvirus infection.^14,15 This manifestation may occur due to a hypersensitivity reaction from enduring viral proteins, resident memory T cells, or local neuroimmune imbalance from herpesvirus-induced injury to dermal sensory nerve fibers.^14-17 Clinically, patients present with red-purple pruritic papules and plaques in a bandlike unilateral pattern, usually in the same region as the prior herpes infection and often accompanied by postherpetic neuralgia.^16-19 Of note, our patient's clinical findings were more diffuse than the frequently localized and often linear distribution seen in postherpetic granulomatous reaction. On histopathology, granulomatous or lichenoid tissue reaction most commonly is appreciated.¹⁵ Specifically, interstitial granulomatous dermatitis with histiocytes, lymphocytes, and multinucleated giant cells showing elastophagocytosis and an inflammatory infiltrate with lymphocytes and plasma cells around vasculature, eccrine glands, and nerves can be noted (Figure 4).¹⁹  

Lupus erythematosus is an autoimmune condition with a wide array of clinical features, including skin manifestations and systemic symptoms. Specifically, discoid lupus erythematosus presents with clearly outlined, red-pink macules or papules with scaling. Histologic features include keratotic follicular plugging, acanthosis, dermal mucin, thickening of the basement membrane zone, and dense lymphocytic infiltrate (Figure 5).²⁰  

The recent drop in U.S. twin birthrates after more than three decades of increases was not distributed evenly among demographic groups, according to the National Center for Health Statistics.

The twin birthrate, which had increased by 79% during 1980-2014, fell by 4% during 2014-2018, but that decline was “not universal across maternal age and race and Hispanic-origin groups,” the NCHS investigators said.

Twin birthrates fell by at least 10% for mothers aged 30 years and older from 2014 to 2018 but held steady for women in their twenties. Over that same period, the twin birthrate fell by a significant 7% among non-Hispanic white women (36.7 to 34.3 per 1,000 total births) but increased just slightly for non-Hispanic black women (40.0 to 40.5 per 1,000) and Hispanic women (24.1 to 24.4), the investigators reported.

For women 30 years and older, the drops in twin births got larger as age increased and were significant for each age group. The rate for women aged 30-34 years fell 10% as it went from 40.3 per 1,000 total births in 2014 to 36.2 per 1,000. The decrease was 12% (from 48.6 per 1,000 to 42.8) for women aged 35-39 and 23% (from 66.0 to 51.1) for those aged 40 years and older, they said based on data from the National Vital Statistics System.

The rates were basically unchanged for women in their 20s, from 23.0 to 23.2 in 20- to 24-year-olds and 30.5 to 30.4 in 25- to 29-year-olds – but there was a significant increase for the youngest group with rates among those younger than 20 years going from 16.0 to 17.1 per 1,000, the report showed.

rfranki@mdedge.com

The recent drop in U.S. twin birthrates after more than three decades of increases was not distributed evenly among demographic groups, according to the National Center for Health Statistics.

The twin birthrate, which had increased by 79% during 1980-2014, fell by 4% during 2014-2018, but that decline was “not universal across maternal age and race and Hispanic-origin groups,” the NCHS investigators said.

Twin birthrates fell by at least 10% for mothers aged 30 years and older from 2014 to 2018 but held steady for women in their twenties. Over that same period, the twin birthrate fell by a significant 7% among non-Hispanic white women (36.7 to 34.3 per 1,000 total births) but increased just slightly for non-Hispanic black women (40.0 to 40.5 per 1,000) and Hispanic women (24.1 to 24.4), the investigators reported.

For women 30 years and older, the drops in twin births got larger as age increased and were significant for each age group. The rate for women aged 30-34 years fell 10% as it went from 40.3 per 1,000 total births in 2014 to 36.2 per 1,000. The decrease was 12% (from 48.6 per 1,000 to 42.8) for women aged 35-39 and 23% (from 66.0 to 51.1) for those aged 40 years and older, they said based on data from the National Vital Statistics System.

The rates were basically unchanged for women in their 20s, from 23.0 to 23.2 in 20- to 24-year-olds and 30.5 to 30.4 in 25- to 29-year-olds – but there was a significant increase for the youngest group with rates among those younger than 20 years going from 16.0 to 17.1 per 1,000, the report showed.

rfranki@mdedge.com

The recent drop in U.S. twin birthrates after more than three decades of increases was not distributed evenly among demographic groups, according to the National Center for Health Statistics.

The twin birthrate, which had increased by 79% during 1980-2014, fell by 4% during 2014-2018, but that decline was “not universal across maternal age and race and Hispanic-origin groups,” the NCHS investigators said.

Twin birthrates fell by at least 10% for mothers aged 30 years and older from 2014 to 2018 but held steady for women in their twenties. Over that same period, the twin birthrate fell by a significant 7% among non-Hispanic white women (36.7 to 34.3 per 1,000 total births) but increased just slightly for non-Hispanic black women (40.0 to 40.5 per 1,000) and Hispanic women (24.1 to 24.4), the investigators reported.

For women 30 years and older, the drops in twin births got larger as age increased and were significant for each age group. The rate for women aged 30-34 years fell 10% as it went from 40.3 per 1,000 total births in 2014 to 36.2 per 1,000. The decrease was 12% (from 48.6 per 1,000 to 42.8) for women aged 35-39 and 23% (from 66.0 to 51.1) for those aged 40 years and older, they said based on data from the National Vital Statistics System.

The rates were basically unchanged for women in their 20s, from 23.0 to 23.2 in 20- to 24-year-olds and 30.5 to 30.4 in 25- to 29-year-olds – but there was a significant increase for the youngest group with rates among those younger than 20 years going from 16.0 to 17.1 per 1,000, the report showed.

rfranki@mdedge.com

Dr. John Hickner’s editorial, “Doing our part to dismantle the opioid crisis” (J Fam Pract 2019;68:308) had important inaccuracies.

The Joint Commission, for which I serve as an executive vice president, did not “dub pain assessment the ‘fifth vital sign’. ” The concept of the fifth vital sign was developed by the American Pain Society in the 1990s.¹ It gained national attention through a Veterans Health Administration initiative in 1999.² And in 2001, the Joint Commission (then the Joint Commission on Accreditation of Healthcare Organizations or JCAHO) issued its Pain Standards.

Dr. Hickner wrote that the push to assess for pain as the fifth vital sign was a central cause of the opioid epidemic; however, this is contrary to published data on the epidemic. Total opioid prescriptions had been steadily increasing in the United States for at least a decade before the Pain Standards went into effect in 2001 (FIGURE).³ Between 1991 and 1997, the number of prescriptions increased from 76 million to 97 million. The rate of increase from 1997 to 2011 appears to have been more rapid, which is likely due to the 1995 approval of the new sustained-release opioid OxyContin and the associated aggressive marketing campaigns to physicians.

Your readers should know that we, at the Joint Commission, are also “doing our part to dismantle the opioid crisis.” In 2016, we completely revised our Pain Standards, adding new criteria to help address the epidemic. Some adjustments include: requiring improved availability of nonpharmacologic therapy, encouraging engagement of patients in pain management plans, enhancing accessibility of Physician Drug Monitoring Program tools, and monitoring opioid prescribing.

David W. Baker, MD, FACP, executive vice president
The Joint Commission, Oakbrook Terrace, IL

Dr. John Hickner’s editorial, “Doing our part to dismantle the opioid crisis” (J Fam Pract 2019;68:308) had important inaccuracies.

The Joint Commission, for which I serve as an executive vice president, did not “dub pain assessment the ‘fifth vital sign’. ” The concept of the fifth vital sign was developed by the American Pain Society in the 1990s.¹ It gained national attention through a Veterans Health Administration initiative in 1999.² And in 2001, the Joint Commission (then the Joint Commission on Accreditation of Healthcare Organizations or JCAHO) issued its Pain Standards.

Dr. Hickner wrote that the push to assess for pain as the fifth vital sign was a central cause of the opioid epidemic; however, this is contrary to published data on the epidemic. Total opioid prescriptions had been steadily increasing in the United States for at least a decade before the Pain Standards went into effect in 2001 (FIGURE).³ Between 1991 and 1997, the number of prescriptions increased from 76 million to 97 million. The rate of increase from 1997 to 2011 appears to have been more rapid, which is likely due to the 1995 approval of the new sustained-release opioid OxyContin and the associated aggressive marketing campaigns to physicians.

Your readers should know that we, at the Joint Commission, are also “doing our part to dismantle the opioid crisis.” In 2016, we completely revised our Pain Standards, adding new criteria to help address the epidemic. Some adjustments include: requiring improved availability of nonpharmacologic therapy, encouraging engagement of patients in pain management plans, enhancing accessibility of Physician Drug Monitoring Program tools, and monitoring opioid prescribing.

David W. Baker, MD, FACP, executive vice president
The Joint Commission, Oakbrook Terrace, IL

Dr. John Hickner’s editorial, “Doing our part to dismantle the opioid crisis” (J Fam Pract 2019;68:308) had important inaccuracies.

The Joint Commission, for which I serve as an executive vice president, did not “dub pain assessment the ‘fifth vital sign’. ” The concept of the fifth vital sign was developed by the American Pain Society in the 1990s.¹ It gained national attention through a Veterans Health Administration initiative in 1999.² And in 2001, the Joint Commission (then the Joint Commission on Accreditation of Healthcare Organizations or JCAHO) issued its Pain Standards.

Dr. Hickner wrote that the push to assess for pain as the fifth vital sign was a central cause of the opioid epidemic; however, this is contrary to published data on the epidemic. Total opioid prescriptions had been steadily increasing in the United States for at least a decade before the Pain Standards went into effect in 2001 (FIGURE).³ Between 1991 and 1997, the number of prescriptions increased from 76 million to 97 million. The rate of increase from 1997 to 2011 appears to have been more rapid, which is likely due to the 1995 approval of the new sustained-release opioid OxyContin and the associated aggressive marketing campaigns to physicians.

Your readers should know that we, at the Joint Commission, are also “doing our part to dismantle the opioid crisis.” In 2016, we completely revised our Pain Standards, adding new criteria to help address the epidemic. Some adjustments include: requiring improved availability of nonpharmacologic therapy, encouraging engagement of patients in pain management plans, enhancing accessibility of Physician Drug Monitoring Program tools, and monitoring opioid prescribing.

David W. Baker, MD, FACP, executive vice president
The Joint Commission, Oakbrook Terrace, IL

This month’s cover story addresses a phenomenon familiar to all of us: burnout. Mohanty and colleagues provide an excellent, concise summary of what burnout is, the probable causes of it, and possible solutions.

What has puzzled me about burnout is why there was no discussion of it 30 years ago when physicians worked easily as many hours but did not complain of being “burned out.” We just described ourselves as being tired. One could argue that the disconnect is due to a change in physicians’ expectations, but that theory does not hold up because burnout is common in both older and younger physicians.

No amount of yoga, mindfulness, meditation, or exercise will be sufficient to combat physician burnout.

I think that Dr. Wendy Dean, a psychiatrist at the Henry M. Jackson Foundation for the Advancement of Military Medicine, and her colleagues are correct in identifying a different culprit. They contend that the real issue is that we are “increasingly forced to consider the demands of other stakeholders—the electronic medical record (EMR), the insurers, the hospital, the health care system, even our own financial security—before the needs of our patients.”¹ To redefine the problem of burnout, Dr. Dean uses a different term to label this phenomenon of exhaustion, demoralization, and depersonalization. She calls it “moral injury.”

“Moral injury . . . describes the challenge of simultaneously knowing what care patients need but being unable to provide it due to constraints that are beyond our control.”¹

So what needs to change? No amount of yoga, mindfulness, meditation, or exercise will be sufficient, although these are great therapeutic activities. Office redesign, however, has already been shown to be highly effective in reducing physician burnout. For example, in an intensive practice redesign project in Colorado that included hiring more medical assistants, physician burnout declined from 56% to 25% in the first practice and from 40% to 0% in the second practice!²

One of the oldest examples of using team care to reduce physician burnout was implemented by Dr. Peter Anderson in 2003.³ Dr. Anderson was on the brink of throwing in the towel when he hired a second nurse and redistributed many tasks to the nurses. In a few years he had a thriving and satisfying practice for himself, his staff, and his patients.

These are only 2 examples of many successful redesign projects around the country. If you are getting burned out, change your practice, not yourself.

This month’s cover story addresses a phenomenon familiar to all of us: burnout. Mohanty and colleagues provide an excellent, concise summary of what burnout is, the probable causes of it, and possible solutions.

What has puzzled me about burnout is why there was no discussion of it 30 years ago when physicians worked easily as many hours but did not complain of being “burned out.” We just described ourselves as being tired. One could argue that the disconnect is due to a change in physicians’ expectations, but that theory does not hold up because burnout is common in both older and younger physicians.

No amount of yoga, mindfulness, meditation, or exercise will be sufficient to combat physician burnout.

I think that Dr. Wendy Dean, a psychiatrist at the Henry M. Jackson Foundation for the Advancement of Military Medicine, and her colleagues are correct in identifying a different culprit. They contend that the real issue is that we are “increasingly forced to consider the demands of other stakeholders—the electronic medical record (EMR), the insurers, the hospital, the health care system, even our own financial security—before the needs of our patients.”¹ To redefine the problem of burnout, Dr. Dean uses a different term to label this phenomenon of exhaustion, demoralization, and depersonalization. She calls it “moral injury.”

“Moral injury . . . describes the challenge of simultaneously knowing what care patients need but being unable to provide it due to constraints that are beyond our control.”¹

So what needs to change? No amount of yoga, mindfulness, meditation, or exercise will be sufficient, although these are great therapeutic activities. Office redesign, however, has already been shown to be highly effective in reducing physician burnout. For example, in an intensive practice redesign project in Colorado that included hiring more medical assistants, physician burnout declined from 56% to 25% in the first practice and from 40% to 0% in the second practice!²

One of the oldest examples of using team care to reduce physician burnout was implemented by Dr. Peter Anderson in 2003.³ Dr. Anderson was on the brink of throwing in the towel when he hired a second nurse and redistributed many tasks to the nurses. In a few years he had a thriving and satisfying practice for himself, his staff, and his patients.

These are only 2 examples of many successful redesign projects around the country. If you are getting burned out, change your practice, not yourself.

This month’s cover story addresses a phenomenon familiar to all of us: burnout. Mohanty and colleagues provide an excellent, concise summary of what burnout is, the probable causes of it, and possible solutions.

What has puzzled me about burnout is why there was no discussion of it 30 years ago when physicians worked easily as many hours but did not complain of being “burned out.” We just described ourselves as being tired. One could argue that the disconnect is due to a change in physicians’ expectations, but that theory does not hold up because burnout is common in both older and younger physicians.

No amount of yoga, mindfulness, meditation, or exercise will be sufficient to combat physician burnout.

I think that Dr. Wendy Dean, a psychiatrist at the Henry M. Jackson Foundation for the Advancement of Military Medicine, and her colleagues are correct in identifying a different culprit. They contend that the real issue is that we are “increasingly forced to consider the demands of other stakeholders—the electronic medical record (EMR), the insurers, the hospital, the health care system, even our own financial security—before the needs of our patients.”¹ To redefine the problem of burnout, Dr. Dean uses a different term to label this phenomenon of exhaustion, demoralization, and depersonalization. She calls it “moral injury.”

“Moral injury . . . describes the challenge of simultaneously knowing what care patients need but being unable to provide it due to constraints that are beyond our control.”¹

So what needs to change? No amount of yoga, mindfulness, meditation, or exercise will be sufficient, although these are great therapeutic activities. Office redesign, however, has already been shown to be highly effective in reducing physician burnout. For example, in an intensive practice redesign project in Colorado that included hiring more medical assistants, physician burnout declined from 56% to 25% in the first practice and from 40% to 0% in the second practice!²

One of the oldest examples of using team care to reduce physician burnout was implemented by Dr. Peter Anderson in 2003.³ Dr. Anderson was on the brink of throwing in the towel when he hired a second nurse and redistributed many tasks to the nurses. In a few years he had a thriving and satisfying practice for himself, his staff, and his patients.

These are only 2 examples of many successful redesign projects around the country. If you are getting burned out, change your practice, not yourself.

EVIDENCE SUMMARY

To evaluate the longstanding belief that a short IPI after miscarriage is associated with adverse outcomes in subsequent pregnancies, a 2017 systematic review and meta-­analysis of 16 studies (3 randomized controlled trials [RCTs] and 13 retrospective cohort studies) with a total of more than 1 million patients compared IPIs shorter and longer than 6 months (miscarriage was defined as any pregnancy loss ­before 24 weeks).¹ The meta-analysis included 10 of the studies (2 RCTs and 8 cohort studies), with a total of 977,972 women and excluded 6 studies because of insufficient data. The outcomes investigated were recurrent miscarriage, preterm birth, stillbirth, pre-eclampsia, and low birthweight in the pregnancy following miscarriage.

Only 1 study reported the specific gestational age of the index miscarriage at 8.6 ± 2.8 weeks.² All studies adjusted data for age, and some considered other confounders, such as race, smoking status, and body mass index (BMI).

Women included in the meta-analysis were from Asia, Europe, South America, and the United States and had a history of at least 1 miscarriage.¹ A study of 257,908 subjects (Conde-Agudelo) also included women with a history of induced abortion from Latin American countries, where abortion is illegal, and made no distinction between spontaneous and induced abortions in those data sets.³ Women with a history of illegal abortion could be at greater risk of subsequent miscarriage than women who underwent a legally performed abortion.

IPI shorter than 6 months carries fewer risks

Excluding the Conde-Agudelo study, women with an IPI < 6 months, compared with > 6 months, had lower risks of subsequent miscarriage (7 studies, 46,313 women; risk ratio [RR] = 0.82; 95% confidence interval [CI], 0.78-0.86) and preterm delivery (7 studies, 60,772 women; RR = 0.79; 95% CI, 0.75-0.83); a higher rate of live births (4 studies, 44,586 women; RR = 1.06; 95% CI, 1.01-1.11); and no increase in stillbirths (4 studies, 44,586 women; RR = 0.88; 95% CI, 0.76-1.02), low birthweight (4 studies, 284,222 women; RR = 1.05; 95% CI, 0.48-2.29) or pre-eclampsia (5 studies, 284,899 women; RR = 0.95; 95% CI, 0.88-1.02) in the subsequent pregnancy.

Including the Conde-Agudelo study, the risk of preterm delivery was the same in women with an IPI < 6 months and > 6 months (8 studies, 318,880 women; RR = 0.93; 95% CI, 0.58-1.48).¹ Four of the 10 studies evaluated the risk of miscarriage with an IPI < 3 months compared with > 3 months and found either no difference or a lower risk of subsequent miscarriage.^2,4-6

IPI shorter than 3 months has lowest risk of all

A 2017 prospective cohort study examined the association between IPI length and risk of recurrent miscarriage in 514 women who had experienced recent miscarriage (defined as spontaneous pregnancy loss before 20 weeks of gestation).⁷ Average gestational age at the time of initial miscarriage wasn’t reported. Study participants were 30 years of age on average and predominantly white (76.8%); 12.3% were black.

The authors compared IPIs of < 3 months, 3 to 6 months, and > 18 months with IPIs of 6 to 18 months, which correlates with the IPIs recommended by the World Health Organization (WHO).⁸ They adjusted for maternal age, race, parity, BMI, and education. An IPI < 3 months was associated with the lowest risk of subsequent miscarriage (7.3% compared with 22.1%; adjusted hazard ratio = 0.33; 95% CI, 0.16-0.71). Women with IPIs of 3 to 6 months and > 18 months didn’t experience statistically significant differences in subsequent miscarriage rates compared with IPIs of 6 to 18 months.⁷

Continue to: But a short IPI after second-trimester loss increases risk of miscarriage

 

 

But a short IPI after second-trimester loss increases risk of miscarriage

By including all miscarriages, the meta-analysis effectively examined IPI after first-trimester loss because first-trimester loss occurs far more frequently than does second-trimester loss.¹ A retrospective cohort study of Australian women, not included in the meta-analysis, assessed 4290 patients with a second-trimester pregnancy loss to specifically examine the association between IPI and risk of recurrent pregnancy loss.⁹

After a pregnancy loss at 14 to 19 weeks, women with an IPI < 3 months, compared with an IPI of 9 to 12 months, had an increased risk of recurrent pregnancy loss (21.9 vs 11.3%; P < .001). Women with an IPI > 9 to 12 months had rates of pregnancy loss similar to an IPI of 3 to 6 months (RR = 1.24; 95% CI, 0.89-1.7) and 6 to 9 months (RR = 1.02; 95% CI, 0.7-1.5). Women who experienced an initial loss at 20 to 23 weeks, for unclear reasons, showed no evidence that the IPI affected the risk of subsequent loss.

Short IPI may be linked to anxiety in first trimester of next pregnancy

A large cohort study of 20,308 pregnant Chinese women, including 1495 with a previous miscarriage, explored the mental health impact of IPI after miscarriage compared with no miscarriage.¹⁰ Investigators used the Self-Rating Anxiety Scale to evaluate anxiety and the Center for Epidemiologic Studies Depression Scale to evaluate depression.

An interpregnancy interval of < 6 months after miscarriage is associated with a higher live birth rate in the subsequent pregnancy than a longer IPI.

Women with an IPI of < 7 months after miscarriage were more likely to experience anxiety symptoms in the subsequent pregnancy than were women with no previous miscarriage (adjusted odds ratio [AOR] = 2.76; 95% CI, 1.4-5.5), whereas women with a history of miscarriage and IPI > 6 months weren’t. Women with IPIs < 7 months and 7 to 12 months, compared with women who had no miscarriage, had an increased risk of depression (AOR = 2.5; 95% CI, 1.4-4.5, and AOR = 2.6; 95% CI, 1.3-5.2, respectively). Women with an IPI > 12 months had no increased risk of depression compared with women with no history of miscarriage.

The odds ratios were adjusted for age, education, BMI, income, and place of residence. The higher rates of depression and anxiety didn’t persist beyond the first trimester of the subsequent pregnancy.

Continue to: RECOMMENDATIONS

RECOMMENDATIONS

The American College of Obstetricians and Gynecologists’ Practice Bulletin on Early Pregnancy Loss states that no quality data exist to support delaying conception after early pregnancy loss (defined as loss of an intrauterine pregnancy in the first trimester) to prevent subsequent pregnancy loss or other pregnancy complications.¹¹

WHO recommends a minimum IPI of at least 6 months after a spontaneous or elective abortion. This recommendation is based on a single multi-center cohort study in Latin America that included women with both spontaneous and induced abortions.⁸

Editor’s takeaway

High-quality evidence now shows that shorter IPIs after first-trimester miscarriages result in safe subsequent pregnancies. However, some concern remains about second-trimester miscarriages and maternal mental health following a shorter IPI, based on lower-quality evidence.

EVIDENCE SUMMARY

To evaluate the longstanding belief that a short IPI after miscarriage is associated with adverse outcomes in subsequent pregnancies, a 2017 systematic review and meta-­analysis of 16 studies (3 randomized controlled trials [RCTs] and 13 retrospective cohort studies) with a total of more than 1 million patients compared IPIs shorter and longer than 6 months (miscarriage was defined as any pregnancy loss ­before 24 weeks).¹ The meta-analysis included 10 of the studies (2 RCTs and 8 cohort studies), with a total of 977,972 women and excluded 6 studies because of insufficient data. The outcomes investigated were recurrent miscarriage, preterm birth, stillbirth, pre-eclampsia, and low birthweight in the pregnancy following miscarriage.

Only 1 study reported the specific gestational age of the index miscarriage at 8.6 ± 2.8 weeks.² All studies adjusted data for age, and some considered other confounders, such as race, smoking status, and body mass index (BMI).

Women included in the meta-analysis were from Asia, Europe, South America, and the United States and had a history of at least 1 miscarriage.¹ A study of 257,908 subjects (Conde-Agudelo) also included women with a history of induced abortion from Latin American countries, where abortion is illegal, and made no distinction between spontaneous and induced abortions in those data sets.³ Women with a history of illegal abortion could be at greater risk of subsequent miscarriage than women who underwent a legally performed abortion.

IPI shorter than 6 months carries fewer risks

Excluding the Conde-Agudelo study, women with an IPI < 6 months, compared with > 6 months, had lower risks of subsequent miscarriage (7 studies, 46,313 women; risk ratio [RR] = 0.82; 95% confidence interval [CI], 0.78-0.86) and preterm delivery (7 studies, 60,772 women; RR = 0.79; 95% CI, 0.75-0.83); a higher rate of live births (4 studies, 44,586 women; RR = 1.06; 95% CI, 1.01-1.11); and no increase in stillbirths (4 studies, 44,586 women; RR = 0.88; 95% CI, 0.76-1.02), low birthweight (4 studies, 284,222 women; RR = 1.05; 95% CI, 0.48-2.29) or pre-eclampsia (5 studies, 284,899 women; RR = 0.95; 95% CI, 0.88-1.02) in the subsequent pregnancy.

Including the Conde-Agudelo study, the risk of preterm delivery was the same in women with an IPI < 6 months and > 6 months (8 studies, 318,880 women; RR = 0.93; 95% CI, 0.58-1.48).¹ Four of the 10 studies evaluated the risk of miscarriage with an IPI < 3 months compared with > 3 months and found either no difference or a lower risk of subsequent miscarriage.^2,4-6

IPI shorter than 3 months has lowest risk of all

A 2017 prospective cohort study examined the association between IPI length and risk of recurrent miscarriage in 514 women who had experienced recent miscarriage (defined as spontaneous pregnancy loss before 20 weeks of gestation).⁷ Average gestational age at the time of initial miscarriage wasn’t reported. Study participants were 30 years of age on average and predominantly white (76.8%); 12.3% were black.

The authors compared IPIs of < 3 months, 3 to 6 months, and > 18 months with IPIs of 6 to 18 months, which correlates with the IPIs recommended by the World Health Organization (WHO).⁸ They adjusted for maternal age, race, parity, BMI, and education. An IPI < 3 months was associated with the lowest risk of subsequent miscarriage (7.3% compared with 22.1%; adjusted hazard ratio = 0.33; 95% CI, 0.16-0.71). Women with IPIs of 3 to 6 months and > 18 months didn’t experience statistically significant differences in subsequent miscarriage rates compared with IPIs of 6 to 18 months.⁷

Continue to: But a short IPI after second-trimester loss increases risk of miscarriage

 

 

But a short IPI after second-trimester loss increases risk of miscarriage

By including all miscarriages, the meta-analysis effectively examined IPI after first-trimester loss because first-trimester loss occurs far more frequently than does second-trimester loss.¹ A retrospective cohort study of Australian women, not included in the meta-analysis, assessed 4290 patients with a second-trimester pregnancy loss to specifically examine the association between IPI and risk of recurrent pregnancy loss.⁹

After a pregnancy loss at 14 to 19 weeks, women with an IPI < 3 months, compared with an IPI of 9 to 12 months, had an increased risk of recurrent pregnancy loss (21.9 vs 11.3%; P < .001). Women with an IPI > 9 to 12 months had rates of pregnancy loss similar to an IPI of 3 to 6 months (RR = 1.24; 95% CI, 0.89-1.7) and 6 to 9 months (RR = 1.02; 95% CI, 0.7-1.5). Women who experienced an initial loss at 20 to 23 weeks, for unclear reasons, showed no evidence that the IPI affected the risk of subsequent loss.

Short IPI may be linked to anxiety in first trimester of next pregnancy

A large cohort study of 20,308 pregnant Chinese women, including 1495 with a previous miscarriage, explored the mental health impact of IPI after miscarriage compared with no miscarriage.¹⁰ Investigators used the Self-Rating Anxiety Scale to evaluate anxiety and the Center for Epidemiologic Studies Depression Scale to evaluate depression.

An interpregnancy interval of < 6 months after miscarriage is associated with a higher live birth rate in the subsequent pregnancy than a longer IPI.

Women with an IPI of < 7 months after miscarriage were more likely to experience anxiety symptoms in the subsequent pregnancy than were women with no previous miscarriage (adjusted odds ratio [AOR] = 2.76; 95% CI, 1.4-5.5), whereas women with a history of miscarriage and IPI > 6 months weren’t. Women with IPIs < 7 months and 7 to 12 months, compared with women who had no miscarriage, had an increased risk of depression (AOR = 2.5; 95% CI, 1.4-4.5, and AOR = 2.6; 95% CI, 1.3-5.2, respectively). Women with an IPI > 12 months had no increased risk of depression compared with women with no history of miscarriage.

The odds ratios were adjusted for age, education, BMI, income, and place of residence. The higher rates of depression and anxiety didn’t persist beyond the first trimester of the subsequent pregnancy.

Continue to: RECOMMENDATIONS

RECOMMENDATIONS

The American College of Obstetricians and Gynecologists’ Practice Bulletin on Early Pregnancy Loss states that no quality data exist to support delaying conception after early pregnancy loss (defined as loss of an intrauterine pregnancy in the first trimester) to prevent subsequent pregnancy loss or other pregnancy complications.¹¹

WHO recommends a minimum IPI of at least 6 months after a spontaneous or elective abortion. This recommendation is based on a single multi-center cohort study in Latin America that included women with both spontaneous and induced abortions.⁸

Editor’s takeaway

High-quality evidence now shows that shorter IPIs after first-trimester miscarriages result in safe subsequent pregnancies. However, some concern remains about second-trimester miscarriages and maternal mental health following a shorter IPI, based on lower-quality evidence.

EVIDENCE SUMMARY

To evaluate the longstanding belief that a short IPI after miscarriage is associated with adverse outcomes in subsequent pregnancies, a 2017 systematic review and meta-­analysis of 16 studies (3 randomized controlled trials [RCTs] and 13 retrospective cohort studies) with a total of more than 1 million patients compared IPIs shorter and longer than 6 months (miscarriage was defined as any pregnancy loss ­before 24 weeks).¹ The meta-analysis included 10 of the studies (2 RCTs and 8 cohort studies), with a total of 977,972 women and excluded 6 studies because of insufficient data. The outcomes investigated were recurrent miscarriage, preterm birth, stillbirth, pre-eclampsia, and low birthweight in the pregnancy following miscarriage.

Only 1 study reported the specific gestational age of the index miscarriage at 8.6 ± 2.8 weeks.² All studies adjusted data for age, and some considered other confounders, such as race, smoking status, and body mass index (BMI).

Women included in the meta-analysis were from Asia, Europe, South America, and the United States and had a history of at least 1 miscarriage.¹ A study of 257,908 subjects (Conde-Agudelo) also included women with a history of induced abortion from Latin American countries, where abortion is illegal, and made no distinction between spontaneous and induced abortions in those data sets.³ Women with a history of illegal abortion could be at greater risk of subsequent miscarriage than women who underwent a legally performed abortion.

IPI shorter than 6 months carries fewer risks

Excluding the Conde-Agudelo study, women with an IPI < 6 months, compared with > 6 months, had lower risks of subsequent miscarriage (7 studies, 46,313 women; risk ratio [RR] = 0.82; 95% confidence interval [CI], 0.78-0.86) and preterm delivery (7 studies, 60,772 women; RR = 0.79; 95% CI, 0.75-0.83); a higher rate of live births (4 studies, 44,586 women; RR = 1.06; 95% CI, 1.01-1.11); and no increase in stillbirths (4 studies, 44,586 women; RR = 0.88; 95% CI, 0.76-1.02), low birthweight (4 studies, 284,222 women; RR = 1.05; 95% CI, 0.48-2.29) or pre-eclampsia (5 studies, 284,899 women; RR = 0.95; 95% CI, 0.88-1.02) in the subsequent pregnancy.

Including the Conde-Agudelo study, the risk of preterm delivery was the same in women with an IPI < 6 months and > 6 months (8 studies, 318,880 women; RR = 0.93; 95% CI, 0.58-1.48).¹ Four of the 10 studies evaluated the risk of miscarriage with an IPI < 3 months compared with > 3 months and found either no difference or a lower risk of subsequent miscarriage.^2,4-6

IPI shorter than 3 months has lowest risk of all

A 2017 prospective cohort study examined the association between IPI length and risk of recurrent miscarriage in 514 women who had experienced recent miscarriage (defined as spontaneous pregnancy loss before 20 weeks of gestation).⁷ Average gestational age at the time of initial miscarriage wasn’t reported. Study participants were 30 years of age on average and predominantly white (76.8%); 12.3% were black.

The authors compared IPIs of < 3 months, 3 to 6 months, and > 18 months with IPIs of 6 to 18 months, which correlates with the IPIs recommended by the World Health Organization (WHO).⁸ They adjusted for maternal age, race, parity, BMI, and education. An IPI < 3 months was associated with the lowest risk of subsequent miscarriage (7.3% compared with 22.1%; adjusted hazard ratio = 0.33; 95% CI, 0.16-0.71). Women with IPIs of 3 to 6 months and > 18 months didn’t experience statistically significant differences in subsequent miscarriage rates compared with IPIs of 6 to 18 months.⁷

Continue to: But a short IPI after second-trimester loss increases risk of miscarriage

 

 

But a short IPI after second-trimester loss increases risk of miscarriage

By including all miscarriages, the meta-analysis effectively examined IPI after first-trimester loss because first-trimester loss occurs far more frequently than does second-trimester loss.¹ A retrospective cohort study of Australian women, not included in the meta-analysis, assessed 4290 patients with a second-trimester pregnancy loss to specifically examine the association between IPI and risk of recurrent pregnancy loss.⁹

After a pregnancy loss at 14 to 19 weeks, women with an IPI < 3 months, compared with an IPI of 9 to 12 months, had an increased risk of recurrent pregnancy loss (21.9 vs 11.3%; P < .001). Women with an IPI > 9 to 12 months had rates of pregnancy loss similar to an IPI of 3 to 6 months (RR = 1.24; 95% CI, 0.89-1.7) and 6 to 9 months (RR = 1.02; 95% CI, 0.7-1.5). Women who experienced an initial loss at 20 to 23 weeks, for unclear reasons, showed no evidence that the IPI affected the risk of subsequent loss.

Short IPI may be linked to anxiety in first trimester of next pregnancy

A large cohort study of 20,308 pregnant Chinese women, including 1495 with a previous miscarriage, explored the mental health impact of IPI after miscarriage compared with no miscarriage.¹⁰ Investigators used the Self-Rating Anxiety Scale to evaluate anxiety and the Center for Epidemiologic Studies Depression Scale to evaluate depression.

An interpregnancy interval of < 6 months after miscarriage is associated with a higher live birth rate in the subsequent pregnancy than a longer IPI.

Women with an IPI of < 7 months after miscarriage were more likely to experience anxiety symptoms in the subsequent pregnancy than were women with no previous miscarriage (adjusted odds ratio [AOR] = 2.76; 95% CI, 1.4-5.5), whereas women with a history of miscarriage and IPI > 6 months weren’t. Women with IPIs < 7 months and 7 to 12 months, compared with women who had no miscarriage, had an increased risk of depression (AOR = 2.5; 95% CI, 1.4-4.5, and AOR = 2.6; 95% CI, 1.3-5.2, respectively). Women with an IPI > 12 months had no increased risk of depression compared with women with no history of miscarriage.

The odds ratios were adjusted for age, education, BMI, income, and place of residence. The higher rates of depression and anxiety didn’t persist beyond the first trimester of the subsequent pregnancy.

Continue to: RECOMMENDATIONS

RECOMMENDATIONS

The American College of Obstetricians and Gynecologists’ Practice Bulletin on Early Pregnancy Loss states that no quality data exist to support delaying conception after early pregnancy loss (defined as loss of an intrauterine pregnancy in the first trimester) to prevent subsequent pregnancy loss or other pregnancy complications.¹¹

WHO recommends a minimum IPI of at least 6 months after a spontaneous or elective abortion. This recommendation is based on a single multi-center cohort study in Latin America that included women with both spontaneous and induced abortions.⁸

Editor’s takeaway

High-quality evidence now shows that shorter IPIs after first-trimester miscarriages result in safe subsequent pregnancies. However, some concern remains about second-trimester miscarriages and maternal mental health following a shorter IPI, based on lower-quality evidence.

A 52-year-old Chinese woman presented to a tertiary hospital in Singapore with a 3-month history of persistent and intermittently painful rashes over her right calf and foot (FIGURE). The patient had pancytopenia due to ongoing chemotherapy for metastatic nasopharyngeal carcinoma. She was systemically well and denied other dermatoses. Examination demonstrated scattered crops of tense hemorrhagic vesicles, each surrounded by a livid purpuric base, over the right plantar aspect of the foot, with areas of eschar over the right medial hallux. No allodynia, hyperaesthesia, or lymphadenopathy was noted.

A punch biopsy of an intact vesicle was performed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis:

Herpes zoster

Histopathologic examination showed full-thickness epidermal necrosis with ballooning degeneration resulting in an intra-epidermal blister. Multinucleated keratinocytes with nuclear moulding were seen within the blister cavity. Grocott-Gomori methenamine-silver (GMS), acid-fast, and Gram stains were negative. Granular immunoglobulin (Ig) G, IgM, and C3 were seen intramurally. DNA analysis of vesicular fluid was positive for varicella zoster virus (VZV). A diagnosis of herpes zoster (HZ) of the right S1 dermatome with primary obliterative vasculitis was established.

Immunocompromised people—those who have impaired T-cell immunity (eg, recipients of organ or hematopoietic stem-cell transplants), take immunosuppressive therapy, or have lymphoma, leukemia, or human immunodeficiency virus (HIV) infection—have an increased risk for HZ. For example, in patients with acquired immunodeficiency syndrome (AIDS), HZ uniquely manifests as recurrent shingles. An estimated 20% to 30% of HIV-infected patients will have more than 1 episode of HZ, which may involve the same or different dermatomes.^1,2 Furthermore, HZ in this population is more commonly associated with atypical presentations.³

What an atypical presentation may look like

In immunocompromised patients, HZ may present with atypical cutaneous manifestations or with atypical generalized symptoms.

Atypical cutaneous manifestations, as in disseminated zoster, manifest with multiple hyperkeratotic papules (3-20 mm in diameter) that follow no dermatomal pattern. These lesions may be chronic, persisting for months or years, and may be associated with acyclovir-resistant strains of VZV.^2,3 Another dermatologic variant is ecthymatous VZV, which manifests with multiple large (10-30 mm) punched-out ulcerations with a central black eschar and a peripheral rim of vesicles.⁴ Viral folliculitis—in which infection is limited to the hair follicle, with no associated blisters—has also been reported in atypical HZ.⁵

It’s been proposed that in atypical presentations, the reactivated VZV spreads from adjacent nerves to the outermost layer of the arterial wall, giving lesions a vasculitic appearance.

Our patient presented with hemorrhagic vesicles mimicking vasculitic lesions, which had persisted over a 3-month period with intermittent localized pain. It has been proposed that in atypical presentations, the reactivated VZV spreads transaxonally from adjacent nerves to the outermost adventitial layer of the arterial wall, leading to a vasculitic appearance of the vesicles.⁶ Viral-induced vasculitis may also result either directly from infection of the blood vessels or secondary to vascular damage from an inflammatory immune ­complex–mediated reaction, cell-­mediated hypersensitivity, or inflammation due to immune dysregulation.^7,8

Continue to: Differential includes vesiculobullous conditions

 

 

Differential includes vesiculobullous conditions

There are several important items to consider in the differential.

Cutaneous vasculitis, in severe cases, may manifest with vesicles or bullae that resemble the lesions seen in HZ. However, its unilateral nature and distribution distinguish it.

Angioinvasive fungal infections in immunocompromised patients may manifest with scattered ulceronecrotic lesions to purpuric vesiculobullous dermatoses.⁹ However, no fungal organisms were seen on GMS staining of the biopsied tissue.

Atypical hand-foot-and-mouth disease tends to affect adults and is associated with Coxsackievirus A6 infection.¹⁰ It may manifest as generalized vesiculobullous exanthem resembling varicella. The chronic nature and restricted extent of the patient’s rash made this diagnosis unlikely.

Successful management depends on timely identification

Although most cases of HZ can be diagnosed clinically, atypical rashes may require a biopsy and direct immunofluorescence assay for VZV antigen or a polymerase-chain-reaction (PCR) assay for VZV DNA in cells from the base of blisters. Therefore, it is important to consider the diagnosis of HZ in immunocompromised patients presenting with an atypical rash to avoid misdiagnosis and costly testing.

Continue to: Our patient was treated...

Our patient was treated with oral acyclovir 800 mg 5 times/day for 10 days, with prompt resolution of her rash.

CORRESPONDENCE
Joel Hua-Liang Lim, MBBS, MRCP, MMed, 1 Mandalay Road, Singapore 308205; joellimhl@nsc.com.sg

A 52-year-old Chinese woman presented to a tertiary hospital in Singapore with a 3-month history of persistent and intermittently painful rashes over her right calf and foot (FIGURE). The patient had pancytopenia due to ongoing chemotherapy for metastatic nasopharyngeal carcinoma. She was systemically well and denied other dermatoses. Examination demonstrated scattered crops of tense hemorrhagic vesicles, each surrounded by a livid purpuric base, over the right plantar aspect of the foot, with areas of eschar over the right medial hallux. No allodynia, hyperaesthesia, or lymphadenopathy was noted.

A punch biopsy of an intact vesicle was performed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis:

Herpes zoster

Histopathologic examination showed full-thickness epidermal necrosis with ballooning degeneration resulting in an intra-epidermal blister. Multinucleated keratinocytes with nuclear moulding were seen within the blister cavity. Grocott-Gomori methenamine-silver (GMS), acid-fast, and Gram stains were negative. Granular immunoglobulin (Ig) G, IgM, and C3 were seen intramurally. DNA analysis of vesicular fluid was positive for varicella zoster virus (VZV). A diagnosis of herpes zoster (HZ) of the right S1 dermatome with primary obliterative vasculitis was established.

Immunocompromised people—those who have impaired T-cell immunity (eg, recipients of organ or hematopoietic stem-cell transplants), take immunosuppressive therapy, or have lymphoma, leukemia, or human immunodeficiency virus (HIV) infection—have an increased risk for HZ. For example, in patients with acquired immunodeficiency syndrome (AIDS), HZ uniquely manifests as recurrent shingles. An estimated 20% to 30% of HIV-infected patients will have more than 1 episode of HZ, which may involve the same or different dermatomes.^1,2 Furthermore, HZ in this population is more commonly associated with atypical presentations.³

What an atypical presentation may look like

In immunocompromised patients, HZ may present with atypical cutaneous manifestations or with atypical generalized symptoms.

Atypical cutaneous manifestations, as in disseminated zoster, manifest with multiple hyperkeratotic papules (3-20 mm in diameter) that follow no dermatomal pattern. These lesions may be chronic, persisting for months or years, and may be associated with acyclovir-resistant strains of VZV.^2,3 Another dermatologic variant is ecthymatous VZV, which manifests with multiple large (10-30 mm) punched-out ulcerations with a central black eschar and a peripheral rim of vesicles.⁴ Viral folliculitis—in which infection is limited to the hair follicle, with no associated blisters—has also been reported in atypical HZ.⁵

It’s been proposed that in atypical presentations, the reactivated VZV spreads from adjacent nerves to the outermost layer of the arterial wall, giving lesions a vasculitic appearance.

Our patient presented with hemorrhagic vesicles mimicking vasculitic lesions, which had persisted over a 3-month period with intermittent localized pain. It has been proposed that in atypical presentations, the reactivated VZV spreads transaxonally from adjacent nerves to the outermost adventitial layer of the arterial wall, leading to a vasculitic appearance of the vesicles.⁶ Viral-induced vasculitis may also result either directly from infection of the blood vessels or secondary to vascular damage from an inflammatory immune ­complex–mediated reaction, cell-­mediated hypersensitivity, or inflammation due to immune dysregulation.^7,8

Continue to: Differential includes vesiculobullous conditions

 

 

Differential includes vesiculobullous conditions

There are several important items to consider in the differential.

Cutaneous vasculitis, in severe cases, may manifest with vesicles or bullae that resemble the lesions seen in HZ. However, its unilateral nature and distribution distinguish it.

Angioinvasive fungal infections in immunocompromised patients may manifest with scattered ulceronecrotic lesions to purpuric vesiculobullous dermatoses.⁹ However, no fungal organisms were seen on GMS staining of the biopsied tissue.

Atypical hand-foot-and-mouth disease tends to affect adults and is associated with Coxsackievirus A6 infection.¹⁰ It may manifest as generalized vesiculobullous exanthem resembling varicella. The chronic nature and restricted extent of the patient’s rash made this diagnosis unlikely.

Successful management depends on timely identification

Although most cases of HZ can be diagnosed clinically, atypical rashes may require a biopsy and direct immunofluorescence assay for VZV antigen or a polymerase-chain-reaction (PCR) assay for VZV DNA in cells from the base of blisters. Therefore, it is important to consider the diagnosis of HZ in immunocompromised patients presenting with an atypical rash to avoid misdiagnosis and costly testing.

Continue to: Our patient was treated...

Our patient was treated with oral acyclovir 800 mg 5 times/day for 10 days, with prompt resolution of her rash.

CORRESPONDENCE
Joel Hua-Liang Lim, MBBS, MRCP, MMed, 1 Mandalay Road, Singapore 308205; joellimhl@nsc.com.sg

A 52-year-old Chinese woman presented to a tertiary hospital in Singapore with a 3-month history of persistent and intermittently painful rashes over her right calf and foot (FIGURE). The patient had pancytopenia due to ongoing chemotherapy for metastatic nasopharyngeal carcinoma. She was systemically well and denied other dermatoses. Examination demonstrated scattered crops of tense hemorrhagic vesicles, each surrounded by a livid purpuric base, over the right plantar aspect of the foot, with areas of eschar over the right medial hallux. No allodynia, hyperaesthesia, or lymphadenopathy was noted.

A punch biopsy of an intact vesicle was performed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis:

Herpes zoster

Histopathologic examination showed full-thickness epidermal necrosis with ballooning degeneration resulting in an intra-epidermal blister. Multinucleated keratinocytes with nuclear moulding were seen within the blister cavity. Grocott-Gomori methenamine-silver (GMS), acid-fast, and Gram stains were negative. Granular immunoglobulin (Ig) G, IgM, and C3 were seen intramurally. DNA analysis of vesicular fluid was positive for varicella zoster virus (VZV). A diagnosis of herpes zoster (HZ) of the right S1 dermatome with primary obliterative vasculitis was established.

Immunocompromised people—those who have impaired T-cell immunity (eg, recipients of organ or hematopoietic stem-cell transplants), take immunosuppressive therapy, or have lymphoma, leukemia, or human immunodeficiency virus (HIV) infection—have an increased risk for HZ. For example, in patients with acquired immunodeficiency syndrome (AIDS), HZ uniquely manifests as recurrent shingles. An estimated 20% to 30% of HIV-infected patients will have more than 1 episode of HZ, which may involve the same or different dermatomes.^1,2 Furthermore, HZ in this population is more commonly associated with atypical presentations.³

What an atypical presentation may look like

In immunocompromised patients, HZ may present with atypical cutaneous manifestations or with atypical generalized symptoms.

Atypical cutaneous manifestations, as in disseminated zoster, manifest with multiple hyperkeratotic papules (3-20 mm in diameter) that follow no dermatomal pattern. These lesions may be chronic, persisting for months or years, and may be associated with acyclovir-resistant strains of VZV.^2,3 Another dermatologic variant is ecthymatous VZV, which manifests with multiple large (10-30 mm) punched-out ulcerations with a central black eschar and a peripheral rim of vesicles.⁴ Viral folliculitis—in which infection is limited to the hair follicle, with no associated blisters—has also been reported in atypical HZ.⁵

It’s been proposed that in atypical presentations, the reactivated VZV spreads from adjacent nerves to the outermost layer of the arterial wall, giving lesions a vasculitic appearance.

Our patient presented with hemorrhagic vesicles mimicking vasculitic lesions, which had persisted over a 3-month period with intermittent localized pain. It has been proposed that in atypical presentations, the reactivated VZV spreads transaxonally from adjacent nerves to the outermost adventitial layer of the arterial wall, leading to a vasculitic appearance of the vesicles.⁶ Viral-induced vasculitis may also result either directly from infection of the blood vessels or secondary to vascular damage from an inflammatory immune ­complex–mediated reaction, cell-­mediated hypersensitivity, or inflammation due to immune dysregulation.^7,8

Continue to: Differential includes vesiculobullous conditions

 

 

Differential includes vesiculobullous conditions

There are several important items to consider in the differential.

Cutaneous vasculitis, in severe cases, may manifest with vesicles or bullae that resemble the lesions seen in HZ. However, its unilateral nature and distribution distinguish it.

Angioinvasive fungal infections in immunocompromised patients may manifest with scattered ulceronecrotic lesions to purpuric vesiculobullous dermatoses.⁹ However, no fungal organisms were seen on GMS staining of the biopsied tissue.

Atypical hand-foot-and-mouth disease tends to affect adults and is associated with Coxsackievirus A6 infection.¹⁰ It may manifest as generalized vesiculobullous exanthem resembling varicella. The chronic nature and restricted extent of the patient’s rash made this diagnosis unlikely.

Successful management depends on timely identification

Although most cases of HZ can be diagnosed clinically, atypical rashes may require a biopsy and direct immunofluorescence assay for VZV antigen or a polymerase-chain-reaction (PCR) assay for VZV DNA in cells from the base of blisters. Therefore, it is important to consider the diagnosis of HZ in immunocompromised patients presenting with an atypical rash to avoid misdiagnosis and costly testing.

Continue to: Our patient was treated...

Our patient was treated with oral acyclovir 800 mg 5 times/day for 10 days, with prompt resolution of her rash.

CORRESPONDENCE
Joel Hua-Liang Lim, MBBS, MRCP, MMed, 1 Mandalay Road, Singapore 308205; joellimhl@nsc.com.sg