CHICAGO – Pembrolizumab monotherapy shows promising efficacy and tolerability in treatment-naive patients with advanced clear cell renal cell carcinoma (accRCC), according to findings from the phase 2 KEYNOTE-427 study.

At a median follow-up of 12 months, the overall response rate in 110 study participants with at least one post-baseline assessment was 38%. Three patients (2.7%) achieved a complete response and 39 (35.5%) achieved a partial response, David F. McDermott, MD, reported at the annual meeting of the American Society of Clinical Oncology.

“The disease control rate was 59%,” he said.

Overall, 67% of the patients experienced a reduction in tumor burden, 14% experienced at least an 80% reduction, and 7% experienced a 100% reduction of their target lesion, said Dr. McDermott of Beth Israel Deaconess Medical Center, Boston.

“Most tumor responses occurred early in the course of therapy,” he noted.

The median time to response was 2.8 months, and the median duration of response was not reached at data cutoff, but 74.8% of responders had a response lasting at least 6 months.

An analysis by International Metastatic Renal Cell Carcinoma Database Criteria (IMDC) category showed a confirmed overall response rate (ORR) of 32% among 41 patients with favorable risk, and 42% in 69 patients with intermediate or poor risk.

“Nine of 17 patients in the poor risk group achieved a major response,” Dr. McDermott noted. “Complete and durable responders were seen in all IMDC subgroups.”

In 46 patients with increased PD-L1 expression or a combined positive score of at least 1 the confirmed ORR was 50.0%, and in 53 patients with low PD-L1 expression and a combined positive score less than 1 it was 26%. The ORR was 45% in the remaining patients in whom PD-L1testing could not be performed.

“Of note, all of the complete responses were seen in the PD-L1-high or CPS-greater-than-1 group,” he said.

Median progression-free survival was 8.7 months, and median overall survival has not been reached.

Tolerability of pembrolizumab in this study was acceptable and consistent with that seen with pembrolizumab monotherapy in other tumor types. Although 80% of patients experienced a treatment-related adverse event, the events mainly included fatigue, pruritus, diarrhea, rash, and arthralgia, occurring in 12.7% to 27.3% of patients, he said.

Grade 3/4 events occurred in 21.8% of patients and one patient experienced a fatal grade 5 case of pneumonitis, he added, noting that 11% of patients discontinued treatment because of a treatment-related adverse event.

Overall, 61 patients discontinued therapy, and 33 of those discontinued because of disease progression.

Programmed death-1 (PD-1) inhibitor-based combination therapies have been shown to have clinical benefit when used first-line in accRCC, but data with respect to the clinical impact of first-line PD-1 inhibitor monotherapy are lacking, Dr. McDermott explained.

KEYNOTE-427 was a single-arm, open-label, two-cohort study evaluating the efficacy and safety of pembrolizumab as first-line monotherapy in accRCC and advanced non–clear cell RCC (anccRCC). Patients had accRCC or anccRCC, measurable disease, no prior systemic therapy and Karnofsky Performance Status score of 70% or greater. They were treated with intravenous pembrolizumab at a dose of 200 mg every 3 weeks, and response was assessed at week 12, then every 6 weeks thereafter until week 54, then every 12 weeks.

The current analysis focused on the accRCC cohort and showed that in treatment-naive patients with histologically confirmed accRCC and measurable disease, pembrolizumab shows promising antitumor activity across IMDC risk groups, he said.

“Encouraging activity was also observed in key subgroups, such as the IMDC intermediate/poor risk group ... and patients with [programmed death-ligand 1]-positive tumors,” he said. “The findings ... provide support for the exploration of pembrolizumab in the adjuvant setting and will allow investigators to put the benefit of anti-PD-1-based combination therapies in better context,” he concluded, noting that KEYNOTE-564, a study of pembrolizumab in the adjuvant setting is currently enrolling, and the current study (KEYNOTE-427) cohort B exploring pembrolizumab monotherapy in anccRCC patients is ongoing.

Merck sponsored the study. Dr. McDermott reported consulting or advisory roles with Array BioPharma, Bristol-Myers Squibb, Exelixis, Genentech/Roche, Merck, Novartis, Pfizer, and X4 Pharma. His institution has received research funding from Prometheus Laboratories.

SOURCE: McDermott DF et al., ASCO 2018 Abstract 4500.

CHICAGO – Pembrolizumab monotherapy shows promising efficacy and tolerability in treatment-naive patients with advanced clear cell renal cell carcinoma (accRCC), according to findings from the phase 2 KEYNOTE-427 study.

At a median follow-up of 12 months, the overall response rate in 110 study participants with at least one post-baseline assessment was 38%. Three patients (2.7%) achieved a complete response and 39 (35.5%) achieved a partial response, David F. McDermott, MD, reported at the annual meeting of the American Society of Clinical Oncology.

“The disease control rate was 59%,” he said.

Overall, 67% of the patients experienced a reduction in tumor burden, 14% experienced at least an 80% reduction, and 7% experienced a 100% reduction of their target lesion, said Dr. McDermott of Beth Israel Deaconess Medical Center, Boston.

“Most tumor responses occurred early in the course of therapy,” he noted.

The median time to response was 2.8 months, and the median duration of response was not reached at data cutoff, but 74.8% of responders had a response lasting at least 6 months.

An analysis by International Metastatic Renal Cell Carcinoma Database Criteria (IMDC) category showed a confirmed overall response rate (ORR) of 32% among 41 patients with favorable risk, and 42% in 69 patients with intermediate or poor risk.

“Nine of 17 patients in the poor risk group achieved a major response,” Dr. McDermott noted. “Complete and durable responders were seen in all IMDC subgroups.”

In 46 patients with increased PD-L1 expression or a combined positive score of at least 1 the confirmed ORR was 50.0%, and in 53 patients with low PD-L1 expression and a combined positive score less than 1 it was 26%. The ORR was 45% in the remaining patients in whom PD-L1testing could not be performed.

“Of note, all of the complete responses were seen in the PD-L1-high or CPS-greater-than-1 group,” he said.

Median progression-free survival was 8.7 months, and median overall survival has not been reached.

Tolerability of pembrolizumab in this study was acceptable and consistent with that seen with pembrolizumab monotherapy in other tumor types. Although 80% of patients experienced a treatment-related adverse event, the events mainly included fatigue, pruritus, diarrhea, rash, and arthralgia, occurring in 12.7% to 27.3% of patients, he said.

Grade 3/4 events occurred in 21.8% of patients and one patient experienced a fatal grade 5 case of pneumonitis, he added, noting that 11% of patients discontinued treatment because of a treatment-related adverse event.

Overall, 61 patients discontinued therapy, and 33 of those discontinued because of disease progression.

Programmed death-1 (PD-1) inhibitor-based combination therapies have been shown to have clinical benefit when used first-line in accRCC, but data with respect to the clinical impact of first-line PD-1 inhibitor monotherapy are lacking, Dr. McDermott explained.

KEYNOTE-427 was a single-arm, open-label, two-cohort study evaluating the efficacy and safety of pembrolizumab as first-line monotherapy in accRCC and advanced non–clear cell RCC (anccRCC). Patients had accRCC or anccRCC, measurable disease, no prior systemic therapy and Karnofsky Performance Status score of 70% or greater. They were treated with intravenous pembrolizumab at a dose of 200 mg every 3 weeks, and response was assessed at week 12, then every 6 weeks thereafter until week 54, then every 12 weeks.

The current analysis focused on the accRCC cohort and showed that in treatment-naive patients with histologically confirmed accRCC and measurable disease, pembrolizumab shows promising antitumor activity across IMDC risk groups, he said.

“Encouraging activity was also observed in key subgroups, such as the IMDC intermediate/poor risk group ... and patients with [programmed death-ligand 1]-positive tumors,” he said. “The findings ... provide support for the exploration of pembrolizumab in the adjuvant setting and will allow investigators to put the benefit of anti-PD-1-based combination therapies in better context,” he concluded, noting that KEYNOTE-564, a study of pembrolizumab in the adjuvant setting is currently enrolling, and the current study (KEYNOTE-427) cohort B exploring pembrolizumab monotherapy in anccRCC patients is ongoing.

Merck sponsored the study. Dr. McDermott reported consulting or advisory roles with Array BioPharma, Bristol-Myers Squibb, Exelixis, Genentech/Roche, Merck, Novartis, Pfizer, and X4 Pharma. His institution has received research funding from Prometheus Laboratories.

SOURCE: McDermott DF et al., ASCO 2018 Abstract 4500.

CHICAGO – Pembrolizumab monotherapy shows promising efficacy and tolerability in treatment-naive patients with advanced clear cell renal cell carcinoma (accRCC), according to findings from the phase 2 KEYNOTE-427 study.

At a median follow-up of 12 months, the overall response rate in 110 study participants with at least one post-baseline assessment was 38%. Three patients (2.7%) achieved a complete response and 39 (35.5%) achieved a partial response, David F. McDermott, MD, reported at the annual meeting of the American Society of Clinical Oncology.

“The disease control rate was 59%,” he said.

Overall, 67% of the patients experienced a reduction in tumor burden, 14% experienced at least an 80% reduction, and 7% experienced a 100% reduction of their target lesion, said Dr. McDermott of Beth Israel Deaconess Medical Center, Boston.

“Most tumor responses occurred early in the course of therapy,” he noted.

The median time to response was 2.8 months, and the median duration of response was not reached at data cutoff, but 74.8% of responders had a response lasting at least 6 months.

An analysis by International Metastatic Renal Cell Carcinoma Database Criteria (IMDC) category showed a confirmed overall response rate (ORR) of 32% among 41 patients with favorable risk, and 42% in 69 patients with intermediate or poor risk.

“Nine of 17 patients in the poor risk group achieved a major response,” Dr. McDermott noted. “Complete and durable responders were seen in all IMDC subgroups.”

In 46 patients with increased PD-L1 expression or a combined positive score of at least 1 the confirmed ORR was 50.0%, and in 53 patients with low PD-L1 expression and a combined positive score less than 1 it was 26%. The ORR was 45% in the remaining patients in whom PD-L1testing could not be performed.

“Of note, all of the complete responses were seen in the PD-L1-high or CPS-greater-than-1 group,” he said.

Median progression-free survival was 8.7 months, and median overall survival has not been reached.

Tolerability of pembrolizumab in this study was acceptable and consistent with that seen with pembrolizumab monotherapy in other tumor types. Although 80% of patients experienced a treatment-related adverse event, the events mainly included fatigue, pruritus, diarrhea, rash, and arthralgia, occurring in 12.7% to 27.3% of patients, he said.

Grade 3/4 events occurred in 21.8% of patients and one patient experienced a fatal grade 5 case of pneumonitis, he added, noting that 11% of patients discontinued treatment because of a treatment-related adverse event.

Overall, 61 patients discontinued therapy, and 33 of those discontinued because of disease progression.

Programmed death-1 (PD-1) inhibitor-based combination therapies have been shown to have clinical benefit when used first-line in accRCC, but data with respect to the clinical impact of first-line PD-1 inhibitor monotherapy are lacking, Dr. McDermott explained.

KEYNOTE-427 was a single-arm, open-label, two-cohort study evaluating the efficacy and safety of pembrolizumab as first-line monotherapy in accRCC and advanced non–clear cell RCC (anccRCC). Patients had accRCC or anccRCC, measurable disease, no prior systemic therapy and Karnofsky Performance Status score of 70% or greater. They were treated with intravenous pembrolizumab at a dose of 200 mg every 3 weeks, and response was assessed at week 12, then every 6 weeks thereafter until week 54, then every 12 weeks.

The current analysis focused on the accRCC cohort and showed that in treatment-naive patients with histologically confirmed accRCC and measurable disease, pembrolizumab shows promising antitumor activity across IMDC risk groups, he said.

“Encouraging activity was also observed in key subgroups, such as the IMDC intermediate/poor risk group ... and patients with [programmed death-ligand 1]-positive tumors,” he said. “The findings ... provide support for the exploration of pembrolizumab in the adjuvant setting and will allow investigators to put the benefit of anti-PD-1-based combination therapies in better context,” he concluded, noting that KEYNOTE-564, a study of pembrolizumab in the adjuvant setting is currently enrolling, and the current study (KEYNOTE-427) cohort B exploring pembrolizumab monotherapy in anccRCC patients is ongoing.

Merck sponsored the study. Dr. McDermott reported consulting or advisory roles with Array BioPharma, Bristol-Myers Squibb, Exelixis, Genentech/Roche, Merck, Novartis, Pfizer, and X4 Pharma. His institution has received research funding from Prometheus Laboratories.

SOURCE: McDermott DF et al., ASCO 2018 Abstract 4500.

He’s almost 10 years younger than me.

He’d been in the hospital for 3 weeks. The ICU room had been decorated, as many families do, with pictures of his life. His wedding. His kids. He and his wife dressed as Darth Vader and Princess Leia for a Halloween party. A few religious items.

Stockdevil/Thinkstock

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

He’s almost 10 years younger than me.

He’d been in the hospital for 3 weeks. The ICU room had been decorated, as many families do, with pictures of his life. His wedding. His kids. He and his wife dressed as Darth Vader and Princess Leia for a Halloween party. A few religious items.

Stockdevil/Thinkstock

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

He’s almost 10 years younger than me.

He’d been in the hospital for 3 weeks. The ICU room had been decorated, as many families do, with pictures of his life. His wedding. His kids. He and his wife dressed as Darth Vader and Princess Leia for a Halloween party. A few religious items.

Stockdevil/Thinkstock

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

BARCELONA – The immune checkpoint inhibitor nivolumab (Opdivo) shows activity against biliary tract cancers (BTC) that have progressed on prior systemic therapies, investigators report.

Among 27 patients with intra- and extrahepatic cholangiocarcinoma and cancers of the gallbladder for whom at least one prior line of therapy had failed, the overall response rate with nivolumab monotherapy was 18.5%, reported Richard Kim, MD of Moffitt Cancer Center, in Tampa.

“Nivolumab demonstrated clinical efficacy in BTC patients. It was very well tolerated, with few grade 3 or 4 adverse events,” he said at the European Society of Medical Oncology World Congress on Gastrointestinal Cancer.

The worldwide incidence of biliary tract cancers has grown over the last 4 decades.

“It is a very aggressive disease, with 5-year overall survival rate of advance disease of less than 2%,” he said.

The standard of care for first-line treatment of advanced disease is gemcitabine and cisplatin, but there is no standard treatment available for patients for whom first-line therapy fails.

Median survival of patients with biliary tract cancers who are receiving second- or third-line therapies is approximately 6-7 months, Dr. Kim said.

Neil Osterweil/MDedge News

BARCELONA – The immune checkpoint inhibitor nivolumab (Opdivo) shows activity against biliary tract cancers (BTC) that have progressed on prior systemic therapies, investigators report.

Among 27 patients with intra- and extrahepatic cholangiocarcinoma and cancers of the gallbladder for whom at least one prior line of therapy had failed, the overall response rate with nivolumab monotherapy was 18.5%, reported Richard Kim, MD of Moffitt Cancer Center, in Tampa.

“Nivolumab demonstrated clinical efficacy in BTC patients. It was very well tolerated, with few grade 3 or 4 adverse events,” he said at the European Society of Medical Oncology World Congress on Gastrointestinal Cancer.

The worldwide incidence of biliary tract cancers has grown over the last 4 decades.

“It is a very aggressive disease, with 5-year overall survival rate of advance disease of less than 2%,” he said.

The standard of care for first-line treatment of advanced disease is gemcitabine and cisplatin, but there is no standard treatment available for patients for whom first-line therapy fails.

Median survival of patients with biliary tract cancers who are receiving second- or third-line therapies is approximately 6-7 months, Dr. Kim said.

Neil Osterweil/MDedge News

BARCELONA – The immune checkpoint inhibitor nivolumab (Opdivo) shows activity against biliary tract cancers (BTC) that have progressed on prior systemic therapies, investigators report.

Among 27 patients with intra- and extrahepatic cholangiocarcinoma and cancers of the gallbladder for whom at least one prior line of therapy had failed, the overall response rate with nivolumab monotherapy was 18.5%, reported Richard Kim, MD of Moffitt Cancer Center, in Tampa.

“Nivolumab demonstrated clinical efficacy in BTC patients. It was very well tolerated, with few grade 3 or 4 adverse events,” he said at the European Society of Medical Oncology World Congress on Gastrointestinal Cancer.

The worldwide incidence of biliary tract cancers has grown over the last 4 decades.

“It is a very aggressive disease, with 5-year overall survival rate of advance disease of less than 2%,” he said.

The standard of care for first-line treatment of advanced disease is gemcitabine and cisplatin, but there is no standard treatment available for patients for whom first-line therapy fails.

Median survival of patients with biliary tract cancers who are receiving second- or third-line therapies is approximately 6-7 months, Dr. Kim said.

Neil Osterweil/MDedge News

A 66-year-old man with steroid-dependent asthma, well-controlled diabetes mellitus (DM), and chronic pain on hospice presented to George E. Wahlen Veteran Affairs Medical Center (VAMC) from an extended care facility with a 4-day history of progressive abdominal distention, diffuse pain, and constipation. The patient’s history was remarkable for a 20-year period of managing asthma with 10 to 60 mg prednisone daily. He continued to experience frequent exacerbations despite using maximum medical therapy. Chronic neck, back, and leg pain had been managed with increasing narcotics over the prior year.

On presentation, the patient reported taking the following medications: daily oxycodone 20 to 30 mg, tramadol 200 mg, gabapentin 1,200 mg, and frequent doses of morphine concentrate. Due to episodes of constipation and diarrhea, the veteran had recently self-discontinued taking stool softener (Senna plus). One month prior to this admission, the patient was enrolled in hospice service by his primary physician for severe COPD due to chronic hypoxic respiratory failure and worsening frailty. His baseline oxygen requirement was 4 to 5 L of supplemental oxygen with continued dyspnea upon any ambulation. The patient reported frequent falls prior to admission. Despite chronic steroid use, the patient’s DM was well controlled with metformin His hemoglobin A_1c ranged from 6.0 to 7.8.

The patient was supine and appeared to be uncomfortable but not in acute distress on exam. His body habitus was Cushingoid, and he appeared much older than his stated age. His vitals were as follows: temperature 100.2°F, heart rate of 104 beats per minute, blood pressure of 98/56 mm Hg, and 95% oxygen on 4L nasal cannula (baseline 4-5L). A respiratory exam revealed distant breath sounds without wheeze, rhonchi, or rales, and a cardiac exam revealed no murmurs. He was in sinus rhythm with tachycardia. The abdomen was obese with purple straie and markedly distended. On percussion, his abdomen was tympanic with tinkling bowel sounds. He had no rebound tenderness, peritoneal signs, or fluid wave.

Laboratory results revealed a white blood cell (WBC) count of 13,790 cells/μL with a neutrophilic shift of 82.0, and an elevated creatinine of 2.16 mg/dL up from a baseline of 1.12 mg/dL. The chemistry panel was abnormal with a 125 mmol/L sodium (reference range 137-145 mmol/L). 

Diagnosis

On admission, the authors’ differential diagnosis included fecal impaction with large bowel obstruction, colitis, narcotic induced ileus, dehydration leading to severe constipation, and delayed gastric emptying secondary to long-standing DM. Ciprofloxacin and metronidazole antibiotics were initiated out of concern for possible colitis and potential bacterial translocation. Intravenous fluids were initiated, and the patient was instructed to have nothing by mouth (NPO) aside from the antibiotics. All opioids, including tramadol, were held. Out of concern for narcotic-induced constipation, a dose of methylnaltrexone to induce stooling was administered but had no effect on the constipation.

The gastroenterology department was consulted for a possible endoscopy to aid in decompression of the sigmoid. However, given the amount of distention and concern for perforation with endoscopy, the patient did not undergo endoscopy on admission. The patient remained afebrile on hospital day 3, and all antibiotics were discontinued. His WBC count normalized with complete resolution of the kidney injury. Antibiotic stewardship and infectious disease consults at George E. Wahlen VAMC reviewed the case and supported the decision to stop all antibiotics since it was not clear whether or not the patient was infected. Despite aggressive bowel care that included a nasogastric tube for large-volume polyethylene glycol and lactulose, various enemas and suppositories, the patient remained constipated.

On hospital day 5, still NPO, the patient had several bilious liquid stools that appeared to have a sediment quality to them. His abdomen remained distended, tympanic, and uncomfortable to palpation., He was examined frequently due to concern for possible perforation. On hospital day 8, gastroenterology reevaluated the need for endoscopy and proceeded with a flexible sigmoidoscopy. 

Polymerase chain reaction analysis of the colonoscopy stool samples were positive for Clostridium difficile (C difficile). The patient was started on IV metronidazole and oral vancomycin. His diet advanced and over the next few days he began stooling. He was subsequently discharged back to an extended care facility for rehabilitation. During this hospitalization, he made it clear he wished to be discharged from hospice services. He wanted to regain his strength through aggressive physical and occupational therapies.

Conclusion

Typical clinical manifestations of fulminant colitis include fever, diarrhea, abdominal pain, distention, and frequently WBC counts > 20,000 cells/μL. However, C difficile colitis, also known as pseudomembranous colitis, occasionally can present as an acute ileus, with little or no diarrhea.¹ This veteran had several risk factors for C difficile infection, which included long-term residence in an extended care facility, frequent asthma exacerbations that required antibiotics, severe chronic disease, aged > 65 years,and ciprofloxacin given the first 3 days of this hospitalization.² Until the endoscopy results were presented, no one on the patient’s care team, including gastroenterology and infectious disease, had included an infectious etiology in the differential diagnosis. This case reinforces the need to broaden differential diagnoses and look beyond assumptions that opioids without an adequate bowel regime were the cause. Avoiding anchoring heuristics can be a challenge as this case demonstrates.

A 66-year-old man with steroid-dependent asthma, well-controlled diabetes mellitus (DM), and chronic pain on hospice presented to George E. Wahlen Veteran Affairs Medical Center (VAMC) from an extended care facility with a 4-day history of progressive abdominal distention, diffuse pain, and constipation. The patient’s history was remarkable for a 20-year period of managing asthma with 10 to 60 mg prednisone daily. He continued to experience frequent exacerbations despite using maximum medical therapy. Chronic neck, back, and leg pain had been managed with increasing narcotics over the prior year.

On presentation, the patient reported taking the following medications: daily oxycodone 20 to 30 mg, tramadol 200 mg, gabapentin 1,200 mg, and frequent doses of morphine concentrate. Due to episodes of constipation and diarrhea, the veteran had recently self-discontinued taking stool softener (Senna plus). One month prior to this admission, the patient was enrolled in hospice service by his primary physician for severe COPD due to chronic hypoxic respiratory failure and worsening frailty. His baseline oxygen requirement was 4 to 5 L of supplemental oxygen with continued dyspnea upon any ambulation. The patient reported frequent falls prior to admission. Despite chronic steroid use, the patient’s DM was well controlled with metformin His hemoglobin A_1c ranged from 6.0 to 7.8.

The patient was supine and appeared to be uncomfortable but not in acute distress on exam. His body habitus was Cushingoid, and he appeared much older than his stated age. His vitals were as follows: temperature 100.2°F, heart rate of 104 beats per minute, blood pressure of 98/56 mm Hg, and 95% oxygen on 4L nasal cannula (baseline 4-5L). A respiratory exam revealed distant breath sounds without wheeze, rhonchi, or rales, and a cardiac exam revealed no murmurs. He was in sinus rhythm with tachycardia. The abdomen was obese with purple straie and markedly distended. On percussion, his abdomen was tympanic with tinkling bowel sounds. He had no rebound tenderness, peritoneal signs, or fluid wave.

Laboratory results revealed a white blood cell (WBC) count of 13,790 cells/μL with a neutrophilic shift of 82.0, and an elevated creatinine of 2.16 mg/dL up from a baseline of 1.12 mg/dL. The chemistry panel was abnormal with a 125 mmol/L sodium (reference range 137-145 mmol/L). 

Diagnosis

On admission, the authors’ differential diagnosis included fecal impaction with large bowel obstruction, colitis, narcotic induced ileus, dehydration leading to severe constipation, and delayed gastric emptying secondary to long-standing DM. Ciprofloxacin and metronidazole antibiotics were initiated out of concern for possible colitis and potential bacterial translocation. Intravenous fluids were initiated, and the patient was instructed to have nothing by mouth (NPO) aside from the antibiotics. All opioids, including tramadol, were held. Out of concern for narcotic-induced constipation, a dose of methylnaltrexone to induce stooling was administered but had no effect on the constipation.

The gastroenterology department was consulted for a possible endoscopy to aid in decompression of the sigmoid. However, given the amount of distention and concern for perforation with endoscopy, the patient did not undergo endoscopy on admission. The patient remained afebrile on hospital day 3, and all antibiotics were discontinued. His WBC count normalized with complete resolution of the kidney injury. Antibiotic stewardship and infectious disease consults at George E. Wahlen VAMC reviewed the case and supported the decision to stop all antibiotics since it was not clear whether or not the patient was infected. Despite aggressive bowel care that included a nasogastric tube for large-volume polyethylene glycol and lactulose, various enemas and suppositories, the patient remained constipated.

On hospital day 5, still NPO, the patient had several bilious liquid stools that appeared to have a sediment quality to them. His abdomen remained distended, tympanic, and uncomfortable to palpation., He was examined frequently due to concern for possible perforation. On hospital day 8, gastroenterology reevaluated the need for endoscopy and proceeded with a flexible sigmoidoscopy. 

Polymerase chain reaction analysis of the colonoscopy stool samples were positive for Clostridium difficile (C difficile). The patient was started on IV metronidazole and oral vancomycin. His diet advanced and over the next few days he began stooling. He was subsequently discharged back to an extended care facility for rehabilitation. During this hospitalization, he made it clear he wished to be discharged from hospice services. He wanted to regain his strength through aggressive physical and occupational therapies.

Conclusion

Typical clinical manifestations of fulminant colitis include fever, diarrhea, abdominal pain, distention, and frequently WBC counts > 20,000 cells/μL. However, C difficile colitis, also known as pseudomembranous colitis, occasionally can present as an acute ileus, with little or no diarrhea.¹ This veteran had several risk factors for C difficile infection, which included long-term residence in an extended care facility, frequent asthma exacerbations that required antibiotics, severe chronic disease, aged > 65 years,and ciprofloxacin given the first 3 days of this hospitalization.² Until the endoscopy results were presented, no one on the patient’s care team, including gastroenterology and infectious disease, had included an infectious etiology in the differential diagnosis. This case reinforces the need to broaden differential diagnoses and look beyond assumptions that opioids without an adequate bowel regime were the cause. Avoiding anchoring heuristics can be a challenge as this case demonstrates.

A 66-year-old man with steroid-dependent asthma, well-controlled diabetes mellitus (DM), and chronic pain on hospice presented to George E. Wahlen Veteran Affairs Medical Center (VAMC) from an extended care facility with a 4-day history of progressive abdominal distention, diffuse pain, and constipation. The patient’s history was remarkable for a 20-year period of managing asthma with 10 to 60 mg prednisone daily. He continued to experience frequent exacerbations despite using maximum medical therapy. Chronic neck, back, and leg pain had been managed with increasing narcotics over the prior year.

On presentation, the patient reported taking the following medications: daily oxycodone 20 to 30 mg, tramadol 200 mg, gabapentin 1,200 mg, and frequent doses of morphine concentrate. Due to episodes of constipation and diarrhea, the veteran had recently self-discontinued taking stool softener (Senna plus). One month prior to this admission, the patient was enrolled in hospice service by his primary physician for severe COPD due to chronic hypoxic respiratory failure and worsening frailty. His baseline oxygen requirement was 4 to 5 L of supplemental oxygen with continued dyspnea upon any ambulation. The patient reported frequent falls prior to admission. Despite chronic steroid use, the patient’s DM was well controlled with metformin His hemoglobin A_1c ranged from 6.0 to 7.8.

The patient was supine and appeared to be uncomfortable but not in acute distress on exam. His body habitus was Cushingoid, and he appeared much older than his stated age. His vitals were as follows: temperature 100.2°F, heart rate of 104 beats per minute, blood pressure of 98/56 mm Hg, and 95% oxygen on 4L nasal cannula (baseline 4-5L). A respiratory exam revealed distant breath sounds without wheeze, rhonchi, or rales, and a cardiac exam revealed no murmurs. He was in sinus rhythm with tachycardia. The abdomen was obese with purple straie and markedly distended. On percussion, his abdomen was tympanic with tinkling bowel sounds. He had no rebound tenderness, peritoneal signs, or fluid wave.

Laboratory results revealed a white blood cell (WBC) count of 13,790 cells/μL with a neutrophilic shift of 82.0, and an elevated creatinine of 2.16 mg/dL up from a baseline of 1.12 mg/dL. The chemistry panel was abnormal with a 125 mmol/L sodium (reference range 137-145 mmol/L). 

Diagnosis

On admission, the authors’ differential diagnosis included fecal impaction with large bowel obstruction, colitis, narcotic induced ileus, dehydration leading to severe constipation, and delayed gastric emptying secondary to long-standing DM. Ciprofloxacin and metronidazole antibiotics were initiated out of concern for possible colitis and potential bacterial translocation. Intravenous fluids were initiated, and the patient was instructed to have nothing by mouth (NPO) aside from the antibiotics. All opioids, including tramadol, were held. Out of concern for narcotic-induced constipation, a dose of methylnaltrexone to induce stooling was administered but had no effect on the constipation.

The gastroenterology department was consulted for a possible endoscopy to aid in decompression of the sigmoid. However, given the amount of distention and concern for perforation with endoscopy, the patient did not undergo endoscopy on admission. The patient remained afebrile on hospital day 3, and all antibiotics were discontinued. His WBC count normalized with complete resolution of the kidney injury. Antibiotic stewardship and infectious disease consults at George E. Wahlen VAMC reviewed the case and supported the decision to stop all antibiotics since it was not clear whether or not the patient was infected. Despite aggressive bowel care that included a nasogastric tube for large-volume polyethylene glycol and lactulose, various enemas and suppositories, the patient remained constipated.

On hospital day 5, still NPO, the patient had several bilious liquid stools that appeared to have a sediment quality to them. His abdomen remained distended, tympanic, and uncomfortable to palpation., He was examined frequently due to concern for possible perforation. On hospital day 8, gastroenterology reevaluated the need for endoscopy and proceeded with a flexible sigmoidoscopy. 

Polymerase chain reaction analysis of the colonoscopy stool samples were positive for Clostridium difficile (C difficile). The patient was started on IV metronidazole and oral vancomycin. His diet advanced and over the next few days he began stooling. He was subsequently discharged back to an extended care facility for rehabilitation. During this hospitalization, he made it clear he wished to be discharged from hospice services. He wanted to regain his strength through aggressive physical and occupational therapies.

Conclusion

Typical clinical manifestations of fulminant colitis include fever, diarrhea, abdominal pain, distention, and frequently WBC counts > 20,000 cells/μL. However, C difficile colitis, also known as pseudomembranous colitis, occasionally can present as an acute ileus, with little or no diarrhea.¹ This veteran had several risk factors for C difficile infection, which included long-term residence in an extended care facility, frequent asthma exacerbations that required antibiotics, severe chronic disease, aged > 65 years,and ciprofloxacin given the first 3 days of this hospitalization.² Until the endoscopy results were presented, no one on the patient’s care team, including gastroenterology and infectious disease, had included an infectious etiology in the differential diagnosis. This case reinforces the need to broaden differential diagnoses and look beyond assumptions that opioids without an adequate bowel regime were the cause. Avoiding anchoring heuristics can be a challenge as this case demonstrates.

Photo from EHA

STOCKHOLM—The KIT/PDGFRA inhibitor avapritinib has produced durable responses in patients with systemic mastocytosis (SM).

In the phase 1 EXPLORER trial, avapritinib produced an overall response rate of 83%.

Responses have lasted up to 22 months, and 79% of responders remained on avapritinib as of the data cutoff.

The most common treatment-related adverse events (AEs) were periorbital edema, anemia, nausea, and fatigue.

These data were presented in a poster (abstract PF612) at the 23rd Congress of the European Hematology Association (EHA).

The trial was sponsored by Blueprint Medicines Corporation.

As of the data cutoff (April 30, 2018), 52 patients had been treated with avapritinib in the dose-escalation and expansion portions of the EXPLORER trial.

This included 25 patients with aggressive SM (ASM), 15 with advanced SM and an associated hematologic neoplasm (SM-AHN), 5 with mast cell leukemia (MCL), 5 pending central pathology diagnosis, and 2 with smoldering SM.

Thirty-five patients (67%) were previously treated, including 10 (19%) who previously received midostaurin. The patients’ median age was 63 (range, 34-83), and 52% were male.

Treatment

Thirty-two patients were treated in the dose-escalation portion of the study and received avapritinib at doses ranging from 30 mg to 400 mg daily. The 35 patients in the expansion portion received avapritinib at 300 mg daily.

Among all 52 enrolled patients, 42 remained on treatment as of the data cutoff date. Four patients discontinued treatment with avapritinib due to AEs. Three of these were treatment-related, and 1 was unrelated.

Three patients discontinued treatment due to clinical progression as determined by the investigator. None of the patients had documented disease progression by IWG-MRT-ECNM criteria.

Two patients discontinued due to investigator decision, and 1 withdrew consent.

Safety

All 52 patients were evaluable for safety.

Treatment-related AEs included periorbital edema (62%), anemia (33%), nausea (33%), fatigue (31%), peripheral edema (27%), diarrhea (25%), hair color changes (23%), thrombocytopenia (19%), cognitive effects (19%), vomiting (19%), and dizziness (12%).

Grade 3 or higher AEs, regardless of drug relationship, included thrombocytopenia (17%), anemia (15%), fatigue (6%), vomiting (6%), periorbital edema (4%), nausea (4%), diarrhea (2%), hair color changes (2%), and cognitive effects (2%).

Efficacy

As of the data cutoff, 23 patients were evaluable for response by IWG-MRT-ECNM criteria. This included 8 patients with ASM, 10 with SM-AHN, and 5 with MCL.

The overall response rate was 83% (n=19). All responses observed in the dose-escalation portion of the trial have been confirmed, and all responses in the dose-expansion portion of the trial are pending confirmation.

Four patients (17%) had a confirmed complete response with a full (n=1) or partial (n=3) recovery of peripheral blood counts. All of these responses occurred in patients with ASM.

Twelve patients (52%) had a partial response (7 confirmed, 5 pending confirmation). This included 6 patients with SM-AHN, 4 with MCL, and 2 with ASM.

Three patients (13%) had clinical improvement (2 confirmed, 1 pending confirmation), and 4 had stable disease. None of the patients progressed.

The duration of response ranged from 8 months to 22 months, and 79% of responders (15/19) remained on treatment at the data cutoff.

“As a clinician treating patients with this devastating and sometimes fatal rare disease, I’m excited to see that most patients with advanced systemic mastocytosis respond to treatment with avapritinib, and these responses deepen over time and are durable,” said study investigator Michael W. Deininger, MD, PhD, of Huntsman Cancer Institute at the University of Utah in Salt Lake City.

“These data further support avapritinib’s unique approach of selectively targeting D816V mutant KIT, the disease driver in most patients with systemic mastocytosis. If these results are confirmed in the planned phase 2 trial, avapritinib has the potential to become a new standard of care for patients with advanced forms of the disease.”

Photo from EHA

STOCKHOLM—The KIT/PDGFRA inhibitor avapritinib has produced durable responses in patients with systemic mastocytosis (SM).

In the phase 1 EXPLORER trial, avapritinib produced an overall response rate of 83%.

Responses have lasted up to 22 months, and 79% of responders remained on avapritinib as of the data cutoff.

The most common treatment-related adverse events (AEs) were periorbital edema, anemia, nausea, and fatigue.

These data were presented in a poster (abstract PF612) at the 23rd Congress of the European Hematology Association (EHA).

The trial was sponsored by Blueprint Medicines Corporation.

As of the data cutoff (April 30, 2018), 52 patients had been treated with avapritinib in the dose-escalation and expansion portions of the EXPLORER trial.

This included 25 patients with aggressive SM (ASM), 15 with advanced SM and an associated hematologic neoplasm (SM-AHN), 5 with mast cell leukemia (MCL), 5 pending central pathology diagnosis, and 2 with smoldering SM.

Thirty-five patients (67%) were previously treated, including 10 (19%) who previously received midostaurin. The patients’ median age was 63 (range, 34-83), and 52% were male.

Treatment

Thirty-two patients were treated in the dose-escalation portion of the study and received avapritinib at doses ranging from 30 mg to 400 mg daily. The 35 patients in the expansion portion received avapritinib at 300 mg daily.

Among all 52 enrolled patients, 42 remained on treatment as of the data cutoff date. Four patients discontinued treatment with avapritinib due to AEs. Three of these were treatment-related, and 1 was unrelated.

Three patients discontinued treatment due to clinical progression as determined by the investigator. None of the patients had documented disease progression by IWG-MRT-ECNM criteria.

Two patients discontinued due to investigator decision, and 1 withdrew consent.

Safety

All 52 patients were evaluable for safety.

Treatment-related AEs included periorbital edema (62%), anemia (33%), nausea (33%), fatigue (31%), peripheral edema (27%), diarrhea (25%), hair color changes (23%), thrombocytopenia (19%), cognitive effects (19%), vomiting (19%), and dizziness (12%).

Grade 3 or higher AEs, regardless of drug relationship, included thrombocytopenia (17%), anemia (15%), fatigue (6%), vomiting (6%), periorbital edema (4%), nausea (4%), diarrhea (2%), hair color changes (2%), and cognitive effects (2%).

Efficacy

As of the data cutoff, 23 patients were evaluable for response by IWG-MRT-ECNM criteria. This included 8 patients with ASM, 10 with SM-AHN, and 5 with MCL.

The overall response rate was 83% (n=19). All responses observed in the dose-escalation portion of the trial have been confirmed, and all responses in the dose-expansion portion of the trial are pending confirmation.

Four patients (17%) had a confirmed complete response with a full (n=1) or partial (n=3) recovery of peripheral blood counts. All of these responses occurred in patients with ASM.

Twelve patients (52%) had a partial response (7 confirmed, 5 pending confirmation). This included 6 patients with SM-AHN, 4 with MCL, and 2 with ASM.

Three patients (13%) had clinical improvement (2 confirmed, 1 pending confirmation), and 4 had stable disease. None of the patients progressed.

The duration of response ranged from 8 months to 22 months, and 79% of responders (15/19) remained on treatment at the data cutoff.

“As a clinician treating patients with this devastating and sometimes fatal rare disease, I’m excited to see that most patients with advanced systemic mastocytosis respond to treatment with avapritinib, and these responses deepen over time and are durable,” said study investigator Michael W. Deininger, MD, PhD, of Huntsman Cancer Institute at the University of Utah in Salt Lake City.

“These data further support avapritinib’s unique approach of selectively targeting D816V mutant KIT, the disease driver in most patients with systemic mastocytosis. If these results are confirmed in the planned phase 2 trial, avapritinib has the potential to become a new standard of care for patients with advanced forms of the disease.”

Photo from EHA

STOCKHOLM—The KIT/PDGFRA inhibitor avapritinib has produced durable responses in patients with systemic mastocytosis (SM).

In the phase 1 EXPLORER trial, avapritinib produced an overall response rate of 83%.

Responses have lasted up to 22 months, and 79% of responders remained on avapritinib as of the data cutoff.

The most common treatment-related adverse events (AEs) were periorbital edema, anemia, nausea, and fatigue.

These data were presented in a poster (abstract PF612) at the 23rd Congress of the European Hematology Association (EHA).

The trial was sponsored by Blueprint Medicines Corporation.

As of the data cutoff (April 30, 2018), 52 patients had been treated with avapritinib in the dose-escalation and expansion portions of the EXPLORER trial.

This included 25 patients with aggressive SM (ASM), 15 with advanced SM and an associated hematologic neoplasm (SM-AHN), 5 with mast cell leukemia (MCL), 5 pending central pathology diagnosis, and 2 with smoldering SM.

Thirty-five patients (67%) were previously treated, including 10 (19%) who previously received midostaurin. The patients’ median age was 63 (range, 34-83), and 52% were male.

Treatment

Thirty-two patients were treated in the dose-escalation portion of the study and received avapritinib at doses ranging from 30 mg to 400 mg daily. The 35 patients in the expansion portion received avapritinib at 300 mg daily.

Among all 52 enrolled patients, 42 remained on treatment as of the data cutoff date. Four patients discontinued treatment with avapritinib due to AEs. Three of these were treatment-related, and 1 was unrelated.

Three patients discontinued treatment due to clinical progression as determined by the investigator. None of the patients had documented disease progression by IWG-MRT-ECNM criteria.

Two patients discontinued due to investigator decision, and 1 withdrew consent.

Safety

All 52 patients were evaluable for safety.

Treatment-related AEs included periorbital edema (62%), anemia (33%), nausea (33%), fatigue (31%), peripheral edema (27%), diarrhea (25%), hair color changes (23%), thrombocytopenia (19%), cognitive effects (19%), vomiting (19%), and dizziness (12%).

Grade 3 or higher AEs, regardless of drug relationship, included thrombocytopenia (17%), anemia (15%), fatigue (6%), vomiting (6%), periorbital edema (4%), nausea (4%), diarrhea (2%), hair color changes (2%), and cognitive effects (2%).

Efficacy

As of the data cutoff, 23 patients were evaluable for response by IWG-MRT-ECNM criteria. This included 8 patients with ASM, 10 with SM-AHN, and 5 with MCL.

The overall response rate was 83% (n=19). All responses observed in the dose-escalation portion of the trial have been confirmed, and all responses in the dose-expansion portion of the trial are pending confirmation.

Four patients (17%) had a confirmed complete response with a full (n=1) or partial (n=3) recovery of peripheral blood counts. All of these responses occurred in patients with ASM.

Twelve patients (52%) had a partial response (7 confirmed, 5 pending confirmation). This included 6 patients with SM-AHN, 4 with MCL, and 2 with ASM.

Three patients (13%) had clinical improvement (2 confirmed, 1 pending confirmation), and 4 had stable disease. None of the patients progressed.

The duration of response ranged from 8 months to 22 months, and 79% of responders (15/19) remained on treatment at the data cutoff.

“As a clinician treating patients with this devastating and sometimes fatal rare disease, I’m excited to see that most patients with advanced systemic mastocytosis respond to treatment with avapritinib, and these responses deepen over time and are durable,” said study investigator Michael W. Deininger, MD, PhD, of Huntsman Cancer Institute at the University of Utah in Salt Lake City.

“These data further support avapritinib’s unique approach of selectively targeting D816V mutant KIT, the disease driver in most patients with systemic mastocytosis. If these results are confirmed in the planned phase 2 trial, avapritinib has the potential to become a new standard of care for patients with advanced forms of the disease.”

All parents-to-be, especially first-time parents, should visit a pediatrician during the third trimester of pregnancy to establish a relationship, according to an updated clinical report on the prenatal visit issued by the American Academy of Pediatrics. The report was published online June 25 and in the July issue of Pediatrics.

“It’s a chance to talk about how to keep a baby safe and thriving physically, but also ways to build strong parent-child bonds that promote resilience and help a child stay emotionally healthy,” Michael Yogman, MD, of Harvard Medical School, Boston, said in a statement. Dr. Yogman was the lead author of the report and chair of the AAP Committee on Psychosocial Aspects of Child and Family Health.

Vesnaandjic/E+/Getty Images

A comprehensive prenatal visit gives pediatricians the opportunity to meet four objectives: build a trusting relationship with parents, gather information about family history, provide advice and guidance on infant care and safety, and identify risk factors for psychosocial issues such as perinatal depression, according to the report in Pediatrics.

The prenatal visit allows families and clinicians to learn whether their philosophies align to start a relationship that may last for many years and this visit can include extended family members such as grandparents. In addition, pediatricians can use the prenatal visit as an opportunity to learn more about family history including past pregnancies, failed and successful, as well as pregnancy complications, chronic medical conditions in family members that may affect the home environment, and plans for child care if parents will be working outside the home.

The report also emphasizes “positive parenting” and the role of pediatricians at a prenatal visit in offering support and guidance to help prepare parents for infant care. This guidance may include advice on feeding, sleeping, diapering, and bathing, as well as acknowledging cultural practices.

The authors noted that a prime opporunity to schedule the prenatal visit is when an expectant parent seeking information about insurance, practice hours, and whether the practice is taking new patients.

The AAP advises clinicians to encourage same sex parents, parents expecting via surrogate, and parents who are adopting to schedule a prenatal visit to identify particular concerns they may have.

“This is the only routine child wellness visit recommended by the American Academy of Pediatrics that doesn’t actually require a child in the room,” coauthor Arthur Lavin, MD, also of Harvard Medical School, said in a statement.

The prenatal visit “gives parents an opportunity to really focus on any questions and concerns they may have. They can talk with a pediatrician before the fatigue of new parenthood sets in and there’s an adorably distracting little human in their arms who may be crying, spitting up, or in immediate need of feeding or a diaper change,” Dr. Lavin said.

“At its heart and soul,” Dr. Lavin noted, “this visit is about laying a foundation for a trusting, supportive relationship between the family and their pediatrician, who will work together to keep the child healthy for the next 18 or 20 years.”

The report recommends the Bright Futures: Guidelines for Health Supervision of Infants, Children, and Adolescents, Fourth Edition, as a resource for clinicians. The researchers had no financial conflicts to disclose.

SOURCE: Yogman M et al. Pediatrics. 2018; doi: 10.1542/peds. 2018-1218

All parents-to-be, especially first-time parents, should visit a pediatrician during the third trimester of pregnancy to establish a relationship, according to an updated clinical report on the prenatal visit issued by the American Academy of Pediatrics. The report was published online June 25 and in the July issue of Pediatrics.

“It’s a chance to talk about how to keep a baby safe and thriving physically, but also ways to build strong parent-child bonds that promote resilience and help a child stay emotionally healthy,” Michael Yogman, MD, of Harvard Medical School, Boston, said in a statement. Dr. Yogman was the lead author of the report and chair of the AAP Committee on Psychosocial Aspects of Child and Family Health.

Vesnaandjic/E+/Getty Images

A comprehensive prenatal visit gives pediatricians the opportunity to meet four objectives: build a trusting relationship with parents, gather information about family history, provide advice and guidance on infant care and safety, and identify risk factors for psychosocial issues such as perinatal depression, according to the report in Pediatrics.

The prenatal visit allows families and clinicians to learn whether their philosophies align to start a relationship that may last for many years and this visit can include extended family members such as grandparents. In addition, pediatricians can use the prenatal visit as an opportunity to learn more about family history including past pregnancies, failed and successful, as well as pregnancy complications, chronic medical conditions in family members that may affect the home environment, and plans for child care if parents will be working outside the home.

The report also emphasizes “positive parenting” and the role of pediatricians at a prenatal visit in offering support and guidance to help prepare parents for infant care. This guidance may include advice on feeding, sleeping, diapering, and bathing, as well as acknowledging cultural practices.

The authors noted that a prime opporunity to schedule the prenatal visit is when an expectant parent seeking information about insurance, practice hours, and whether the practice is taking new patients.

The AAP advises clinicians to encourage same sex parents, parents expecting via surrogate, and parents who are adopting to schedule a prenatal visit to identify particular concerns they may have.

“This is the only routine child wellness visit recommended by the American Academy of Pediatrics that doesn’t actually require a child in the room,” coauthor Arthur Lavin, MD, also of Harvard Medical School, said in a statement.

The prenatal visit “gives parents an opportunity to really focus on any questions and concerns they may have. They can talk with a pediatrician before the fatigue of new parenthood sets in and there’s an adorably distracting little human in their arms who may be crying, spitting up, or in immediate need of feeding or a diaper change,” Dr. Lavin said.

“At its heart and soul,” Dr. Lavin noted, “this visit is about laying a foundation for a trusting, supportive relationship between the family and their pediatrician, who will work together to keep the child healthy for the next 18 or 20 years.”

The report recommends the Bright Futures: Guidelines for Health Supervision of Infants, Children, and Adolescents, Fourth Edition, as a resource for clinicians. The researchers had no financial conflicts to disclose.

SOURCE: Yogman M et al. Pediatrics. 2018; doi: 10.1542/peds. 2018-1218

All parents-to-be, especially first-time parents, should visit a pediatrician during the third trimester of pregnancy to establish a relationship, according to an updated clinical report on the prenatal visit issued by the American Academy of Pediatrics. The report was published online June 25 and in the July issue of Pediatrics.

“It’s a chance to talk about how to keep a baby safe and thriving physically, but also ways to build strong parent-child bonds that promote resilience and help a child stay emotionally healthy,” Michael Yogman, MD, of Harvard Medical School, Boston, said in a statement. Dr. Yogman was the lead author of the report and chair of the AAP Committee on Psychosocial Aspects of Child and Family Health.

Vesnaandjic/E+/Getty Images

A comprehensive prenatal visit gives pediatricians the opportunity to meet four objectives: build a trusting relationship with parents, gather information about family history, provide advice and guidance on infant care and safety, and identify risk factors for psychosocial issues such as perinatal depression, according to the report in Pediatrics.

The prenatal visit allows families and clinicians to learn whether their philosophies align to start a relationship that may last for many years and this visit can include extended family members such as grandparents. In addition, pediatricians can use the prenatal visit as an opportunity to learn more about family history including past pregnancies, failed and successful, as well as pregnancy complications, chronic medical conditions in family members that may affect the home environment, and plans for child care if parents will be working outside the home.

The report also emphasizes “positive parenting” and the role of pediatricians at a prenatal visit in offering support and guidance to help prepare parents for infant care. This guidance may include advice on feeding, sleeping, diapering, and bathing, as well as acknowledging cultural practices.

The authors noted that a prime opporunity to schedule the prenatal visit is when an expectant parent seeking information about insurance, practice hours, and whether the practice is taking new patients.

The AAP advises clinicians to encourage same sex parents, parents expecting via surrogate, and parents who are adopting to schedule a prenatal visit to identify particular concerns they may have.

“This is the only routine child wellness visit recommended by the American Academy of Pediatrics that doesn’t actually require a child in the room,” coauthor Arthur Lavin, MD, also of Harvard Medical School, said in a statement.

The prenatal visit “gives parents an opportunity to really focus on any questions and concerns they may have. They can talk with a pediatrician before the fatigue of new parenthood sets in and there’s an adorably distracting little human in their arms who may be crying, spitting up, or in immediate need of feeding or a diaper change,” Dr. Lavin said.

“At its heart and soul,” Dr. Lavin noted, “this visit is about laying a foundation for a trusting, supportive relationship between the family and their pediatrician, who will work together to keep the child healthy for the next 18 or 20 years.”

The report recommends the Bright Futures: Guidelines for Health Supervision of Infants, Children, and Adolescents, Fourth Edition, as a resource for clinicians. The researchers had no financial conflicts to disclose.

SOURCE: Yogman M et al. Pediatrics. 2018; doi: 10.1542/peds. 2018-1218

Eleven children died from exposure to buprenorphine – a drug used to treat opioid exposure – from 2007 to 2016, mostly very young children who accidentally ingested the drug.

Four deaths, however, were teens who took buprenorphine recreationally or used it in a suicide attempt, according to a new database review by Sara Post, MS, of the Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, and her associates.

Fuse/thinkstockphotos.com

[email protected]

SOURCE: Post et al. Pediatrics. 2018;142:e20173652.

Eleven children died from exposure to buprenorphine – a drug used to treat opioid exposure – from 2007 to 2016, mostly very young children who accidentally ingested the drug.

Four deaths, however, were teens who took buprenorphine recreationally or used it in a suicide attempt, according to a new database review by Sara Post, MS, of the Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, and her associates.

Fuse/thinkstockphotos.com

[email protected]

SOURCE: Post et al. Pediatrics. 2018;142:e20173652.

Eleven children died from exposure to buprenorphine – a drug used to treat opioid exposure – from 2007 to 2016, mostly very young children who accidentally ingested the drug.

Four deaths, however, were teens who took buprenorphine recreationally or used it in a suicide attempt, according to a new database review by Sara Post, MS, of the Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, and her associates.

Fuse/thinkstockphotos.com

[email protected]

SOURCE: Post et al. Pediatrics. 2018;142:e20173652.

Is it possible to get more exercise and still gain weight? In America it is.

The steady increase in obesity prevalence among adults in the United States has been exceeded over the last decade by the percentage of adults who are getting the recommended amount of exercise, according to the National Center for Health Statistics.

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Is it possible to get more exercise and still gain weight? In America it is.

The steady increase in obesity prevalence among adults in the United States has been exceeded over the last decade by the percentage of adults who are getting the recommended amount of exercise, according to the National Center for Health Statistics.

[email protected]

Is it possible to get more exercise and still gain weight? In America it is.

The steady increase in obesity prevalence among adults in the United States has been exceeded over the last decade by the percentage of adults who are getting the recommended amount of exercise, according to the National Center for Health Statistics.

[email protected]

The Trump administration seeks to reorganize several federal agencies as part of a sweeping reform proposal, issued June 21.

“Government in the 21st century is fundamentally a services business, and modern information technology should be at the heart of the U.S. government service delivery model,” according to the administration’s reform proposal. “And yet, today’s Executive branch is still aligned to the stove-piped organizational constructs of the 20th century, which in many cases have grown inefficient and out of date. Consequently, the public and our workforce are frustrated with government’s ability to deliver its mission in an effective, efficient, and secure way.”

tupungato/Thinkstock

Under the proposal, nutrition assistance programs currently run out of the U.S. Department of Agriculture (USDA) including the Supplemental Nutrition Assistance Program (SNAP) and the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) would move to the Department of Health and Human Services, which would be rebranded the Department of Health and Public Welfare.

Moving these programs “would allow for better and easier coordination across programs that serve similar populations, ensuring consistent policies and a single point of administration for the major public assistance programs,” according to the proposal. “This single point of administration would lead to reduced duplication in state reporting requirements and other administrative burdens, and a more streamlined process for issuing guidance, writing regulations, and approving waivers.”

Food oversight functions would move from the Food and Drug Administration to the USDA; FDA would be rebranded the Federal Drug Administration and focus on drugs, devices, biologics, tobacco, dietary supplements, and cosmetics.

The administration also proposed to created a Council on Public Assistance comprised of “all federal agencies that administer public benefits, with a statutory authority to set cross-cutting program policies, including uniform work requirements.”

Other functions of the council would include approving service plans and waivers by states under Welfare-to-Work projects; resolving disputes when multiple agencies disagree on a particular policy; and recommending policy changes to eliminate barriers at the federal, state, and local level to getting welfare beneficiaries to work.

The proposal also calls for a restructuring of the National Institutes of Health “to ensure operations are effective and efficient,” with no detail provided. It would also place the Agency for Healthcare Research and Quality under the auspices of NIH.

The Strategic National Stockpile would be managed by the Assistant Secretary for Preparedness and Response “to consolidate strategic decision making around the development and procurement of medical countermeasures, and streamline operational decisions during responses to public health and other emergencies to improve responsiveness.”

[email protected]

The Trump administration seeks to reorganize several federal agencies as part of a sweeping reform proposal, issued June 21.

“Government in the 21st century is fundamentally a services business, and modern information technology should be at the heart of the U.S. government service delivery model,” according to the administration’s reform proposal. “And yet, today’s Executive branch is still aligned to the stove-piped organizational constructs of the 20th century, which in many cases have grown inefficient and out of date. Consequently, the public and our workforce are frustrated with government’s ability to deliver its mission in an effective, efficient, and secure way.”

tupungato/Thinkstock

Under the proposal, nutrition assistance programs currently run out of the U.S. Department of Agriculture (USDA) including the Supplemental Nutrition Assistance Program (SNAP) and the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) would move to the Department of Health and Human Services, which would be rebranded the Department of Health and Public Welfare.

Moving these programs “would allow for better and easier coordination across programs that serve similar populations, ensuring consistent policies and a single point of administration for the major public assistance programs,” according to the proposal. “This single point of administration would lead to reduced duplication in state reporting requirements and other administrative burdens, and a more streamlined process for issuing guidance, writing regulations, and approving waivers.”

Food oversight functions would move from the Food and Drug Administration to the USDA; FDA would be rebranded the Federal Drug Administration and focus on drugs, devices, biologics, tobacco, dietary supplements, and cosmetics.

The administration also proposed to created a Council on Public Assistance comprised of “all federal agencies that administer public benefits, with a statutory authority to set cross-cutting program policies, including uniform work requirements.”

Other functions of the council would include approving service plans and waivers by states under Welfare-to-Work projects; resolving disputes when multiple agencies disagree on a particular policy; and recommending policy changes to eliminate barriers at the federal, state, and local level to getting welfare beneficiaries to work.

The proposal also calls for a restructuring of the National Institutes of Health “to ensure operations are effective and efficient,” with no detail provided. It would also place the Agency for Healthcare Research and Quality under the auspices of NIH.

The Strategic National Stockpile would be managed by the Assistant Secretary for Preparedness and Response “to consolidate strategic decision making around the development and procurement of medical countermeasures, and streamline operational decisions during responses to public health and other emergencies to improve responsiveness.”

[email protected]

The Trump administration seeks to reorganize several federal agencies as part of a sweeping reform proposal, issued June 21.

“Government in the 21st century is fundamentally a services business, and modern information technology should be at the heart of the U.S. government service delivery model,” according to the administration’s reform proposal. “And yet, today’s Executive branch is still aligned to the stove-piped organizational constructs of the 20th century, which in many cases have grown inefficient and out of date. Consequently, the public and our workforce are frustrated with government’s ability to deliver its mission in an effective, efficient, and secure way.”

tupungato/Thinkstock

Under the proposal, nutrition assistance programs currently run out of the U.S. Department of Agriculture (USDA) including the Supplemental Nutrition Assistance Program (SNAP) and the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) would move to the Department of Health and Human Services, which would be rebranded the Department of Health and Public Welfare.

Moving these programs “would allow for better and easier coordination across programs that serve similar populations, ensuring consistent policies and a single point of administration for the major public assistance programs,” according to the proposal. “This single point of administration would lead to reduced duplication in state reporting requirements and other administrative burdens, and a more streamlined process for issuing guidance, writing regulations, and approving waivers.”

Food oversight functions would move from the Food and Drug Administration to the USDA; FDA would be rebranded the Federal Drug Administration and focus on drugs, devices, biologics, tobacco, dietary supplements, and cosmetics.

The administration also proposed to created a Council on Public Assistance comprised of “all federal agencies that administer public benefits, with a statutory authority to set cross-cutting program policies, including uniform work requirements.”

Other functions of the council would include approving service plans and waivers by states under Welfare-to-Work projects; resolving disputes when multiple agencies disagree on a particular policy; and recommending policy changes to eliminate barriers at the federal, state, and local level to getting welfare beneficiaries to work.

The proposal also calls for a restructuring of the National Institutes of Health “to ensure operations are effective and efficient,” with no detail provided. It would also place the Agency for Healthcare Research and Quality under the auspices of NIH.

The Strategic National Stockpile would be managed by the Assistant Secretary for Preparedness and Response “to consolidate strategic decision making around the development and procurement of medical countermeasures, and streamline operational decisions during responses to public health and other emergencies to improve responsiveness.”

[email protected]

ORLANDO – Longer-term data are providing more evidence of a possible link between maternal diabetes and autism spectrum disorder in their children.

Anny Xiang, PhD, and coathors with Kaiser Permanente of Southern California sought to further understand the possible effect of maternal T1D on offspring’s development of autism spectrum disorder (ASD) by expanding the cohort and timeline of their earlier work (JAMA. 2015;313(14):1425-1434).

The current study includes data on to 419,425 children (51% boys) born at Kaiser Permanente Southern California hospitals from 1995-2012. The children were followed for a median of 6.9 years, through 2017.

A total of 621 children were exposed in utero to T1D , 9,453 to T2D, 11,922 to gestational diabetes diagnosed by 26 weeks, and 24,505 to gestational diabetes diagnosed after 26 weeks.

Across the cohort, 1.3% of children were diagnosed with autism spectrum disorder (ASD). The rate was barely different, at 1.5%, for those whose mothers developed gestational diabetes after 26 weeks. But rates of ASD were higher – 3.1%, 2.5%, 2.1% – among those whose mothers had T1D, T2D, and gestational diabetes that developed at 26 weeks or earlier, respectively. The findings were adjusted for co-founders such as birth year, age at delivery, eduction level and income, Dr. Xiang said at the annual scientific sessions of the American Diabetes Association.

Compared to offspring of mothers without diabetes, ASD was more common in the children of mothers with T1D (adjusted HR=2.36, 95% CI, 1.36-4.12) mothers with type 2 diabetes (AHR= 1.45, 95% CI, 1.24-1.70) and gestational diabetes mellitus that developed by 26 weeks gestation (1.30, 95% CI, 1.12-1.51).

The numbers remained similar after they were adjusted for smoking during pregnancy and prepregnancy BMI, statistics which were available for about 36% of the subjects, according to the findings which were published simultaneously in JAMA (June 23, 2018. doi:10.1001/jama.2018.7614).

Possible explanations for the link between ASD and maternal diabetes include maternal glycemic control, prematurity, and levels of neonatal hypoglycemia, Dr. Xiang said.

The results do not take into account any paternal risks for offspring developing ASD, which also includes diabetes, Dr. Xiang said, noting that two previous studies linked diabetes in fathers to ASD, although to a lesser extent than diabetes in mothers. (Epidemiology. 2010 Nov;21(6):805-8; Pediatrics. 2009 Aug;124(2):687-94)

The study also doesn’t take breastfeeding into account, Dr. Xiang noted. A 2016 study found that women with T2D were less likely to breastfeed (J Matern Fetal Neonatal Med. 2016;29(15):2513-8), and some research has suggested that breastfeeding may be protective against the development of ASD in children (Nutrition 2012;28(7-8):e27-32).

In addition, the study doesn’t track maternal glucose levels over time.

Session co-chair Peter Damm, MD, professor of obstetrics at the University of Copenhagen, said in an interview that he is impressed by the study. He cautioned, however, that it does not prove a connection.“This not a proof, but it seems likely, or like a possibility,” he said.

One possible explanation for a diabetes/ASD connection is the fact that the fetal brain is evolving throughout pregnancy unlike other body organs, which simply grow after developing in the first trimester, he said. As a result, glucose levels may affect the brain’s development in a unique way compared to other organs.

SOURCE: Xiang A, et al. ADA 2018 Abstract OR-117.

ORLANDO – Longer-term data are providing more evidence of a possible link between maternal diabetes and autism spectrum disorder in their children.

Anny Xiang, PhD, and coathors with Kaiser Permanente of Southern California sought to further understand the possible effect of maternal T1D on offspring’s development of autism spectrum disorder (ASD) by expanding the cohort and timeline of their earlier work (JAMA. 2015;313(14):1425-1434).

The current study includes data on to 419,425 children (51% boys) born at Kaiser Permanente Southern California hospitals from 1995-2012. The children were followed for a median of 6.9 years, through 2017.

A total of 621 children were exposed in utero to T1D , 9,453 to T2D, 11,922 to gestational diabetes diagnosed by 26 weeks, and 24,505 to gestational diabetes diagnosed after 26 weeks.

Across the cohort, 1.3% of children were diagnosed with autism spectrum disorder (ASD). The rate was barely different, at 1.5%, for those whose mothers developed gestational diabetes after 26 weeks. But rates of ASD were higher – 3.1%, 2.5%, 2.1% – among those whose mothers had T1D, T2D, and gestational diabetes that developed at 26 weeks or earlier, respectively. The findings were adjusted for co-founders such as birth year, age at delivery, eduction level and income, Dr. Xiang said at the annual scientific sessions of the American Diabetes Association.

Compared to offspring of mothers without diabetes, ASD was more common in the children of mothers with T1D (adjusted HR=2.36, 95% CI, 1.36-4.12) mothers with type 2 diabetes (AHR= 1.45, 95% CI, 1.24-1.70) and gestational diabetes mellitus that developed by 26 weeks gestation (1.30, 95% CI, 1.12-1.51).

The numbers remained similar after they were adjusted for smoking during pregnancy and prepregnancy BMI, statistics which were available for about 36% of the subjects, according to the findings which were published simultaneously in JAMA (June 23, 2018. doi:10.1001/jama.2018.7614).

Possible explanations for the link between ASD and maternal diabetes include maternal glycemic control, prematurity, and levels of neonatal hypoglycemia, Dr. Xiang said.

The results do not take into account any paternal risks for offspring developing ASD, which also includes diabetes, Dr. Xiang said, noting that two previous studies linked diabetes in fathers to ASD, although to a lesser extent than diabetes in mothers. (Epidemiology. 2010 Nov;21(6):805-8; Pediatrics. 2009 Aug;124(2):687-94)

The study also doesn’t take breastfeeding into account, Dr. Xiang noted. A 2016 study found that women with T2D were less likely to breastfeed (J Matern Fetal Neonatal Med. 2016;29(15):2513-8), and some research has suggested that breastfeeding may be protective against the development of ASD in children (Nutrition 2012;28(7-8):e27-32).

In addition, the study doesn’t track maternal glucose levels over time.

Session co-chair Peter Damm, MD, professor of obstetrics at the University of Copenhagen, said in an interview that he is impressed by the study. He cautioned, however, that it does not prove a connection.“This not a proof, but it seems likely, or like a possibility,” he said.

One possible explanation for a diabetes/ASD connection is the fact that the fetal brain is evolving throughout pregnancy unlike other body organs, which simply grow after developing in the first trimester, he said. As a result, glucose levels may affect the brain’s development in a unique way compared to other organs.

SOURCE: Xiang A, et al. ADA 2018 Abstract OR-117.

ORLANDO – Longer-term data are providing more evidence of a possible link between maternal diabetes and autism spectrum disorder in their children.

Anny Xiang, PhD, and coathors with Kaiser Permanente of Southern California sought to further understand the possible effect of maternal T1D on offspring’s development of autism spectrum disorder (ASD) by expanding the cohort and timeline of their earlier work (JAMA. 2015;313(14):1425-1434).

The current study includes data on to 419,425 children (51% boys) born at Kaiser Permanente Southern California hospitals from 1995-2012. The children were followed for a median of 6.9 years, through 2017.

A total of 621 children were exposed in utero to T1D , 9,453 to T2D, 11,922 to gestational diabetes diagnosed by 26 weeks, and 24,505 to gestational diabetes diagnosed after 26 weeks.

Across the cohort, 1.3% of children were diagnosed with autism spectrum disorder (ASD). The rate was barely different, at 1.5%, for those whose mothers developed gestational diabetes after 26 weeks. But rates of ASD were higher – 3.1%, 2.5%, 2.1% – among those whose mothers had T1D, T2D, and gestational diabetes that developed at 26 weeks or earlier, respectively. The findings were adjusted for co-founders such as birth year, age at delivery, eduction level and income, Dr. Xiang said at the annual scientific sessions of the American Diabetes Association.

Compared to offspring of mothers without diabetes, ASD was more common in the children of mothers with T1D (adjusted HR=2.36, 95% CI, 1.36-4.12) mothers with type 2 diabetes (AHR= 1.45, 95% CI, 1.24-1.70) and gestational diabetes mellitus that developed by 26 weeks gestation (1.30, 95% CI, 1.12-1.51).

The numbers remained similar after they were adjusted for smoking during pregnancy and prepregnancy BMI, statistics which were available for about 36% of the subjects, according to the findings which were published simultaneously in JAMA (June 23, 2018. doi:10.1001/jama.2018.7614).

Possible explanations for the link between ASD and maternal diabetes include maternal glycemic control, prematurity, and levels of neonatal hypoglycemia, Dr. Xiang said.

The results do not take into account any paternal risks for offspring developing ASD, which also includes diabetes, Dr. Xiang said, noting that two previous studies linked diabetes in fathers to ASD, although to a lesser extent than diabetes in mothers. (Epidemiology. 2010 Nov;21(6):805-8; Pediatrics. 2009 Aug;124(2):687-94)

The study also doesn’t take breastfeeding into account, Dr. Xiang noted. A 2016 study found that women with T2D were less likely to breastfeed (J Matern Fetal Neonatal Med. 2016;29(15):2513-8), and some research has suggested that breastfeeding may be protective against the development of ASD in children (Nutrition 2012;28(7-8):e27-32).

In addition, the study doesn’t track maternal glucose levels over time.

Session co-chair Peter Damm, MD, professor of obstetrics at the University of Copenhagen, said in an interview that he is impressed by the study. He cautioned, however, that it does not prove a connection.“This not a proof, but it seems likely, or like a possibility,” he said.

One possible explanation for a diabetes/ASD connection is the fact that the fetal brain is evolving throughout pregnancy unlike other body organs, which simply grow after developing in the first trimester, he said. As a result, glucose levels may affect the brain’s development in a unique way compared to other organs.

SOURCE: Xiang A, et al. ADA 2018 Abstract OR-117.