Gestational diabetes is a significant health problem worldwide that is associated with immediate and lifelong consequences for the affected woman and her infant. Gestational diabetes increases the risk for pregnancy-related complications, such as induced labor, cesarean delivery, and preeclampsia. There is also an increased risk for neonatal complications, including large-for-gestational-age birth weight, shoulder dystocia, birth injuries, lung disease, jaundice, and hypoglycemia. Regardless of birth weight, neonates born to mothers with gestational diabetes have greater adiposity than do neonates born to mothers without obesity and with normal glucose tolerance, and they have a predilection toward obesity and obesity-related metabolic disorders, including T2D in childhood and adulthood. Similarly, women who develop gestational diabetes have an increased lifetime risk for T2D as well as an increased risk for cardiovascular disease even if they do not progress to T2D.

According to the International Diabetes Federation, 1 in 6 pregnancies is affected by gestational diabetes. Risk factors include higher age and BMI, previous history of gestational diabetes, a family history of T2D, and polycystic ovarian syndrome. Patients may have few, if any, symptoms of gestational diabetes, or they may mistake their symptoms for the normal side effects of pregnancy. Potential symptoms include blurred vision, tingling or numbness in the hands and/or feet, excessive thirst, frequent urination, sores that heal slowly, and excessive fatigue. 

The American Diabetes Association (ADA) states that the treatment of gestational diabetes should include medical nutrition therapy, physical activity, and weight management, depending on pregestational weight. Glucose monitoring is essential: Patients should aim for fasting glucose < 95 mg/dL (5.3 mmol/L) and either 1-hour postprandial glucose < 140 mg/dL (7.8 mmol/L) or 2-hour postprandial glucose < 120 mg/dL (6.7 mmol/L). According to the ADA, insulin should be added to lifestyle modifications if needed to achieve glycemic targets. Metformin and glyburide are not recommended as first-line agents because both cross the placenta to the fetus. Long-term safety data are not available for the use of other oral and noninsulin injectable glucose-lowering medications during pregnancy. 

Courtney Whittle, MD, MSW, Diplomate of ABOM, Pediatric Lead, Obesity Champion, TSPMG, Weight A Minute Clinic, Atlanta, Georgia.

Courtney Whittle, MD, MSW, Diplomate of ABOM, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Gestational diabetes is a significant health problem worldwide that is associated with immediate and lifelong consequences for the affected woman and her infant. Gestational diabetes increases the risk for pregnancy-related complications, such as induced labor, cesarean delivery, and preeclampsia. There is also an increased risk for neonatal complications, including large-for-gestational-age birth weight, shoulder dystocia, birth injuries, lung disease, jaundice, and hypoglycemia. Regardless of birth weight, neonates born to mothers with gestational diabetes have greater adiposity than do neonates born to mothers without obesity and with normal glucose tolerance, and they have a predilection toward obesity and obesity-related metabolic disorders, including T2D in childhood and adulthood. Similarly, women who develop gestational diabetes have an increased lifetime risk for T2D as well as an increased risk for cardiovascular disease even if they do not progress to T2D.

According to the International Diabetes Federation, 1 in 6 pregnancies is affected by gestational diabetes. Risk factors include higher age and BMI, previous history of gestational diabetes, a family history of T2D, and polycystic ovarian syndrome. Patients may have few, if any, symptoms of gestational diabetes, or they may mistake their symptoms for the normal side effects of pregnancy. Potential symptoms include blurred vision, tingling or numbness in the hands and/or feet, excessive thirst, frequent urination, sores that heal slowly, and excessive fatigue. 

The American Diabetes Association (ADA) states that the treatment of gestational diabetes should include medical nutrition therapy, physical activity, and weight management, depending on pregestational weight. Glucose monitoring is essential: Patients should aim for fasting glucose < 95 mg/dL (5.3 mmol/L) and either 1-hour postprandial glucose < 140 mg/dL (7.8 mmol/L) or 2-hour postprandial glucose < 120 mg/dL (6.7 mmol/L). According to the ADA, insulin should be added to lifestyle modifications if needed to achieve glycemic targets. Metformin and glyburide are not recommended as first-line agents because both cross the placenta to the fetus. Long-term safety data are not available for the use of other oral and noninsulin injectable glucose-lowering medications during pregnancy. 

Courtney Whittle, MD, MSW, Diplomate of ABOM, Pediatric Lead, Obesity Champion, TSPMG, Weight A Minute Clinic, Atlanta, Georgia.

Courtney Whittle, MD, MSW, Diplomate of ABOM, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Gestational diabetes is a significant health problem worldwide that is associated with immediate and lifelong consequences for the affected woman and her infant. Gestational diabetes increases the risk for pregnancy-related complications, such as induced labor, cesarean delivery, and preeclampsia. There is also an increased risk for neonatal complications, including large-for-gestational-age birth weight, shoulder dystocia, birth injuries, lung disease, jaundice, and hypoglycemia. Regardless of birth weight, neonates born to mothers with gestational diabetes have greater adiposity than do neonates born to mothers without obesity and with normal glucose tolerance, and they have a predilection toward obesity and obesity-related metabolic disorders, including T2D in childhood and adulthood. Similarly, women who develop gestational diabetes have an increased lifetime risk for T2D as well as an increased risk for cardiovascular disease even if they do not progress to T2D.

According to the International Diabetes Federation, 1 in 6 pregnancies is affected by gestational diabetes. Risk factors include higher age and BMI, previous history of gestational diabetes, a family history of T2D, and polycystic ovarian syndrome. Patients may have few, if any, symptoms of gestational diabetes, or they may mistake their symptoms for the normal side effects of pregnancy. Potential symptoms include blurred vision, tingling or numbness in the hands and/or feet, excessive thirst, frequent urination, sores that heal slowly, and excessive fatigue. 

The American Diabetes Association (ADA) states that the treatment of gestational diabetes should include medical nutrition therapy, physical activity, and weight management, depending on pregestational weight. Glucose monitoring is essential: Patients should aim for fasting glucose < 95 mg/dL (5.3 mmol/L) and either 1-hour postprandial glucose < 140 mg/dL (7.8 mmol/L) or 2-hour postprandial glucose < 120 mg/dL (6.7 mmol/L). According to the ADA, insulin should be added to lifestyle modifications if needed to achieve glycemic targets. Metformin and glyburide are not recommended as first-line agents because both cross the placenta to the fetus. Long-term safety data are not available for the use of other oral and noninsulin injectable glucose-lowering medications during pregnancy. 

Courtney Whittle, MD, MSW, Diplomate of ABOM, Pediatric Lead, Obesity Champion, TSPMG, Weight A Minute Clinic, Atlanta, Georgia.

Courtney Whittle, MD, MSW, Diplomate of ABOM, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

Low levels of serum lactate dehydrogenase were significantly associated with depression and suicide attempts in adults with major depressive disorder, based on data from more than 300 individuals.

The pathogenesis of depression is complex, and recent research has focused on the potential relationship between energy metabolism and depression, wrote Qian Yao, MD, of Wuhan University, Hubei, China, and colleagues.

Previous studies have suggested that serum lactate dehydrogenase (LDH) may be a biomarker for Parkinson’s disease, Huntington’s disease, and post-stroke depression, but the link between lactate metabolism and depression remains unclear, they said.

“We hypothesize that LDH may act as a potential biomarker for MDD, considering it represents a reduced energy metabolic status in depressive patients,” they explained.

In a study published in General Hospital Psychiatry, the researchers examined differences in serum LDH in 232 patients with major depressive disorder (MDD) and 110 healthy controls. They also examined whether LDH was predictive of suicide attempts in the MDD patients. Depression was assessed via the 24-item Hamilton Depression Scale (HAMD-24).

The mean age across both groups was 33 years; other clinical characteristics were similar between the groups.

The serum LDH level of the MDD group was significantly lower than the control group was (177.94 U/L vs. 196.50 U/L; P < .001). Analysis of blood lipid levels showed significantly lower levels of total cholesterol in the MDD group compared with controls, but no significant differences were noted in LDL cholesterol, HDL cholesterol, or triglycerides.

In a further analysis of subgroups of depression, the serum LDH in MDD patients who had attempted suicide was significantly lower compared to those without suicide attempts (169.96 vs. 181.25; P = .002), although the LDH level for the non-suicide MDD patients also was significantly lower than controls (181.25 vs. 196.50; P < .001). No significant correlation was noted between HAMD-24 score and suicide attempts.

Some gender differences also appeared. Both male and female MDD patients had significantly lower LDH levels compared with controls. However, in a regression analysis, a correlation between total cholesterol and LDL cholesterol as potential suicide markers was noted in female MDD patients, but not male MDD patients, which suggests an impact of gender on suicide risk in MDD, the researchers wrote in their discussion.

The findings were limited by several factors including the retrospective design, lack of investigation of changes in LDH isozymes in MDD patients, and lack of assessment of changes in LDH in cerebrospinal fluid, the researchers noted. However, the results “provide clear evidence that the concentration of LDH in serum is associated with early onset and clinical prognosis of depressive symptoms,” in MDD, which may inform diagnosis and guide clinical intervention, including early identification of suicide risk, they concluded.

The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

Low levels of serum lactate dehydrogenase were significantly associated with depression and suicide attempts in adults with major depressive disorder, based on data from more than 300 individuals.

The pathogenesis of depression is complex, and recent research has focused on the potential relationship between energy metabolism and depression, wrote Qian Yao, MD, of Wuhan University, Hubei, China, and colleagues.

Previous studies have suggested that serum lactate dehydrogenase (LDH) may be a biomarker for Parkinson’s disease, Huntington’s disease, and post-stroke depression, but the link between lactate metabolism and depression remains unclear, they said.

“We hypothesize that LDH may act as a potential biomarker for MDD, considering it represents a reduced energy metabolic status in depressive patients,” they explained.

In a study published in General Hospital Psychiatry, the researchers examined differences in serum LDH in 232 patients with major depressive disorder (MDD) and 110 healthy controls. They also examined whether LDH was predictive of suicide attempts in the MDD patients. Depression was assessed via the 24-item Hamilton Depression Scale (HAMD-24).

The mean age across both groups was 33 years; other clinical characteristics were similar between the groups.

The serum LDH level of the MDD group was significantly lower than the control group was (177.94 U/L vs. 196.50 U/L; P < .001). Analysis of blood lipid levels showed significantly lower levels of total cholesterol in the MDD group compared with controls, but no significant differences were noted in LDL cholesterol, HDL cholesterol, or triglycerides.

In a further analysis of subgroups of depression, the serum LDH in MDD patients who had attempted suicide was significantly lower compared to those without suicide attempts (169.96 vs. 181.25; P = .002), although the LDH level for the non-suicide MDD patients also was significantly lower than controls (181.25 vs. 196.50; P < .001). No significant correlation was noted between HAMD-24 score and suicide attempts.

Some gender differences also appeared. Both male and female MDD patients had significantly lower LDH levels compared with controls. However, in a regression analysis, a correlation between total cholesterol and LDL cholesterol as potential suicide markers was noted in female MDD patients, but not male MDD patients, which suggests an impact of gender on suicide risk in MDD, the researchers wrote in their discussion.

The findings were limited by several factors including the retrospective design, lack of investigation of changes in LDH isozymes in MDD patients, and lack of assessment of changes in LDH in cerebrospinal fluid, the researchers noted. However, the results “provide clear evidence that the concentration of LDH in serum is associated with early onset and clinical prognosis of depressive symptoms,” in MDD, which may inform diagnosis and guide clinical intervention, including early identification of suicide risk, they concluded.

The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

Low levels of serum lactate dehydrogenase were significantly associated with depression and suicide attempts in adults with major depressive disorder, based on data from more than 300 individuals.

The pathogenesis of depression is complex, and recent research has focused on the potential relationship between energy metabolism and depression, wrote Qian Yao, MD, of Wuhan University, Hubei, China, and colleagues.

Previous studies have suggested that serum lactate dehydrogenase (LDH) may be a biomarker for Parkinson’s disease, Huntington’s disease, and post-stroke depression, but the link between lactate metabolism and depression remains unclear, they said.

“We hypothesize that LDH may act as a potential biomarker for MDD, considering it represents a reduced energy metabolic status in depressive patients,” they explained.

In a study published in General Hospital Psychiatry, the researchers examined differences in serum LDH in 232 patients with major depressive disorder (MDD) and 110 healthy controls. They also examined whether LDH was predictive of suicide attempts in the MDD patients. Depression was assessed via the 24-item Hamilton Depression Scale (HAMD-24).

The mean age across both groups was 33 years; other clinical characteristics were similar between the groups.

The serum LDH level of the MDD group was significantly lower than the control group was (177.94 U/L vs. 196.50 U/L; P < .001). Analysis of blood lipid levels showed significantly lower levels of total cholesterol in the MDD group compared with controls, but no significant differences were noted in LDL cholesterol, HDL cholesterol, or triglycerides.

In a further analysis of subgroups of depression, the serum LDH in MDD patients who had attempted suicide was significantly lower compared to those without suicide attempts (169.96 vs. 181.25; P = .002), although the LDH level for the non-suicide MDD patients also was significantly lower than controls (181.25 vs. 196.50; P < .001). No significant correlation was noted between HAMD-24 score and suicide attempts.

Some gender differences also appeared. Both male and female MDD patients had significantly lower LDH levels compared with controls. However, in a regression analysis, a correlation between total cholesterol and LDL cholesterol as potential suicide markers was noted in female MDD patients, but not male MDD patients, which suggests an impact of gender on suicide risk in MDD, the researchers wrote in their discussion.

The findings were limited by several factors including the retrospective design, lack of investigation of changes in LDH isozymes in MDD patients, and lack of assessment of changes in LDH in cerebrospinal fluid, the researchers noted. However, the results “provide clear evidence that the concentration of LDH in serum is associated with early onset and clinical prognosis of depressive symptoms,” in MDD, which may inform diagnosis and guide clinical intervention, including early identification of suicide risk, they concluded.

The study was supported by the National Natural Science Foundation of China. The researchers had no financial conflicts to disclose.

Gastroenterology

October 2022

Cryer B et al. Bridging the Racial, Ethnic, and Gender Gap in Gastroenterology. Gastroenterology. 2022 Oct;163(4):800-5. doi: 10.1053/j.gastro.2022.08.037. PMID: 36137708.



Bajaj JS and Nagy LE. Natural History of Alcohol-Associated Liver Disease: Understanding the Changing Landscape of Pathophysiology and Patient Care. Gastroenterology. 2022 Oct;163(4):840-51. doi: 10.1053/j.gastro.2022.05.031. Epub 2022 May 19. PMID: 35598629; PMCID: PMC9509416.



November 2022

Grunvald E et al; AGA Clinical Guidelines Committee. AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity. Gastroenterology. 2022 Nov;163(5):1198-225. doi: 10.1053/j.gastro.2022.08.045. Epub 2022 Oct 20. PMID: 36273831.



December 2022

Blackett JW et al. Comparison of Anorectal Manometry, Rectal Balloon Expulsion Test, and Defecography for Diagnosing Defecatory Disorders. Gastroenterology. 2022 Dec;163(6):1582-92.e2. doi: 10.1053/j.gastro.2022.08.034. Epub 2022 Aug 19. PMID: 35995074; PMCID: PMC9691522.



de Voogd F et al. Intestinal Ultrasound Is Accurate to Determine Endoscopic Response and Remission in Patients With Moderate to Severe Ulcerative Colitis: A Longitudinal Prospective Cohort Study. Gastroenterology. 2022 Dec;163(6):1569-81. doi: 10.1053/j.gastro.2022.08.038. Epub 2022 Aug 24. PMID: 36030056.
 

Clinical Gastroenterology and Hepatology

October 2022

Bhavsar-Burke I et al. How to Promote Professional Identity Development and Support Fellows-In-Training Through Teaching, Coaching, Mentorship, and Sponsorship. Clin Gastroenterol Hepatol. 2022 Oct;20(10):2166-9. doi: 10.1016/j.cgh.2022.05.043. Epub 2022 Aug 7. PMID: 35948073.



van Megen F et al. A Low FODMAP Diet Reduces Symptoms in Treated Celiac Patients With Ongoing Symptoms – A Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2022 Oct;20(10):2258-66.e3. doi: 10.1016/j.cgh.2022.01.011. Epub 2022 Jan 17. PMID: 35051648.



November 2022

Sharzehi K et al. AGA Clinical Practice Update on Management of Subepithelial Lesions Encountered During Routine Endoscopy: Expert Review. Clin Gastroenterol Hepatol. 2022 Nov;20(11):2435-43.e4. doi: 10.1016/j.cgh.2022.05.054. Epub 2022 Jul 13. PMID: 35842117.



December 2022

Kardashian A et al. Food Insecurity is Associated With Mortality Among U.S. Adults With Nonalcoholic Fatty Liver Disease and Advanced Fibrosis. Clin Gastroenterol Hepatol. 2022 Dec;20(12):2790-9.e4. doi: 10.1016/j.cgh.2021.11.029. Epub 2021 Dec 16. PMID: 34958747.



Schuitenmaker JM et al. Sleep Positional Therapy for Nocturnal Gastroesophageal Reflux: A Double-Blind, Randomized, Sham-Controlled Trial. Clin Gastroenterol Hepatol. 2022 Dec;20(12):2753-62.e2. doi: 10.1016/j.cgh.2022.02.058. Epub 2022 Mar 14. PMID: 35301135.
 

Techniques and Innovations in Gastrointestinal Endoscopy

Azizian JM et al. Yield of Post-Acute Diverticulitis Colonoscopy for Ruling Out Colorectal Cancer. Tech Innov Gastrointest Endosc. 2022;24(3):254-61. doi: 10.1016/j.tige.2022.04.001. Epub 2022 Apr 18. PMID: 36540108; PMCID: PMC9762736.
 

Gastro Hep Advances

Kim RW et al. Timely Albumin Improves Survival in Patients With Cirrhosis on Diuretic Therapy Who Develop Acute Kidney Injury: Real-World Evidence in the United States. Gastro Hep Advances. 2023;2(2):252-60. doi: 10.1016/j.gastha.2022.10.008.

Gastroenterology

October 2022

Cryer B et al. Bridging the Racial, Ethnic, and Gender Gap in Gastroenterology. Gastroenterology. 2022 Oct;163(4):800-5. doi: 10.1053/j.gastro.2022.08.037. PMID: 36137708.



Bajaj JS and Nagy LE. Natural History of Alcohol-Associated Liver Disease: Understanding the Changing Landscape of Pathophysiology and Patient Care. Gastroenterology. 2022 Oct;163(4):840-51. doi: 10.1053/j.gastro.2022.05.031. Epub 2022 May 19. PMID: 35598629; PMCID: PMC9509416.



November 2022

Grunvald E et al; AGA Clinical Guidelines Committee. AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity. Gastroenterology. 2022 Nov;163(5):1198-225. doi: 10.1053/j.gastro.2022.08.045. Epub 2022 Oct 20. PMID: 36273831.



December 2022

Blackett JW et al. Comparison of Anorectal Manometry, Rectal Balloon Expulsion Test, and Defecography for Diagnosing Defecatory Disorders. Gastroenterology. 2022 Dec;163(6):1582-92.e2. doi: 10.1053/j.gastro.2022.08.034. Epub 2022 Aug 19. PMID: 35995074; PMCID: PMC9691522.



de Voogd F et al. Intestinal Ultrasound Is Accurate to Determine Endoscopic Response and Remission in Patients With Moderate to Severe Ulcerative Colitis: A Longitudinal Prospective Cohort Study. Gastroenterology. 2022 Dec;163(6):1569-81. doi: 10.1053/j.gastro.2022.08.038. Epub 2022 Aug 24. PMID: 36030056.
 

Clinical Gastroenterology and Hepatology

October 2022

Bhavsar-Burke I et al. How to Promote Professional Identity Development and Support Fellows-In-Training Through Teaching, Coaching, Mentorship, and Sponsorship. Clin Gastroenterol Hepatol. 2022 Oct;20(10):2166-9. doi: 10.1016/j.cgh.2022.05.043. Epub 2022 Aug 7. PMID: 35948073.



van Megen F et al. A Low FODMAP Diet Reduces Symptoms in Treated Celiac Patients With Ongoing Symptoms – A Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2022 Oct;20(10):2258-66.e3. doi: 10.1016/j.cgh.2022.01.011. Epub 2022 Jan 17. PMID: 35051648.



November 2022

Sharzehi K et al. AGA Clinical Practice Update on Management of Subepithelial Lesions Encountered During Routine Endoscopy: Expert Review. Clin Gastroenterol Hepatol. 2022 Nov;20(11):2435-43.e4. doi: 10.1016/j.cgh.2022.05.054. Epub 2022 Jul 13. PMID: 35842117.



December 2022

Kardashian A et al. Food Insecurity is Associated With Mortality Among U.S. Adults With Nonalcoholic Fatty Liver Disease and Advanced Fibrosis. Clin Gastroenterol Hepatol. 2022 Dec;20(12):2790-9.e4. doi: 10.1016/j.cgh.2021.11.029. Epub 2021 Dec 16. PMID: 34958747.



Schuitenmaker JM et al. Sleep Positional Therapy for Nocturnal Gastroesophageal Reflux: A Double-Blind, Randomized, Sham-Controlled Trial. Clin Gastroenterol Hepatol. 2022 Dec;20(12):2753-62.e2. doi: 10.1016/j.cgh.2022.02.058. Epub 2022 Mar 14. PMID: 35301135.
 

Techniques and Innovations in Gastrointestinal Endoscopy

Azizian JM et al. Yield of Post-Acute Diverticulitis Colonoscopy for Ruling Out Colorectal Cancer. Tech Innov Gastrointest Endosc. 2022;24(3):254-61. doi: 10.1016/j.tige.2022.04.001. Epub 2022 Apr 18. PMID: 36540108; PMCID: PMC9762736.
 

Gastro Hep Advances

Kim RW et al. Timely Albumin Improves Survival in Patients With Cirrhosis on Diuretic Therapy Who Develop Acute Kidney Injury: Real-World Evidence in the United States. Gastro Hep Advances. 2023;2(2):252-60. doi: 10.1016/j.gastha.2022.10.008.

Gastroenterology

October 2022

Cryer B et al. Bridging the Racial, Ethnic, and Gender Gap in Gastroenterology. Gastroenterology. 2022 Oct;163(4):800-5. doi: 10.1053/j.gastro.2022.08.037. PMID: 36137708.



Bajaj JS and Nagy LE. Natural History of Alcohol-Associated Liver Disease: Understanding the Changing Landscape of Pathophysiology and Patient Care. Gastroenterology. 2022 Oct;163(4):840-51. doi: 10.1053/j.gastro.2022.05.031. Epub 2022 May 19. PMID: 35598629; PMCID: PMC9509416.



November 2022

Grunvald E et al; AGA Clinical Guidelines Committee. AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity. Gastroenterology. 2022 Nov;163(5):1198-225. doi: 10.1053/j.gastro.2022.08.045. Epub 2022 Oct 20. PMID: 36273831.



December 2022

Blackett JW et al. Comparison of Anorectal Manometry, Rectal Balloon Expulsion Test, and Defecography for Diagnosing Defecatory Disorders. Gastroenterology. 2022 Dec;163(6):1582-92.e2. doi: 10.1053/j.gastro.2022.08.034. Epub 2022 Aug 19. PMID: 35995074; PMCID: PMC9691522.



de Voogd F et al. Intestinal Ultrasound Is Accurate to Determine Endoscopic Response and Remission in Patients With Moderate to Severe Ulcerative Colitis: A Longitudinal Prospective Cohort Study. Gastroenterology. 2022 Dec;163(6):1569-81. doi: 10.1053/j.gastro.2022.08.038. Epub 2022 Aug 24. PMID: 36030056.
 

Clinical Gastroenterology and Hepatology

October 2022

Bhavsar-Burke I et al. How to Promote Professional Identity Development and Support Fellows-In-Training Through Teaching, Coaching, Mentorship, and Sponsorship. Clin Gastroenterol Hepatol. 2022 Oct;20(10):2166-9. doi: 10.1016/j.cgh.2022.05.043. Epub 2022 Aug 7. PMID: 35948073.



van Megen F et al. A Low FODMAP Diet Reduces Symptoms in Treated Celiac Patients With Ongoing Symptoms – A Randomized Controlled Trial. Clin Gastroenterol Hepatol. 2022 Oct;20(10):2258-66.e3. doi: 10.1016/j.cgh.2022.01.011. Epub 2022 Jan 17. PMID: 35051648.



November 2022

Sharzehi K et al. AGA Clinical Practice Update on Management of Subepithelial Lesions Encountered During Routine Endoscopy: Expert Review. Clin Gastroenterol Hepatol. 2022 Nov;20(11):2435-43.e4. doi: 10.1016/j.cgh.2022.05.054. Epub 2022 Jul 13. PMID: 35842117.



December 2022

Kardashian A et al. Food Insecurity is Associated With Mortality Among U.S. Adults With Nonalcoholic Fatty Liver Disease and Advanced Fibrosis. Clin Gastroenterol Hepatol. 2022 Dec;20(12):2790-9.e4. doi: 10.1016/j.cgh.2021.11.029. Epub 2021 Dec 16. PMID: 34958747.



Schuitenmaker JM et al. Sleep Positional Therapy for Nocturnal Gastroesophageal Reflux: A Double-Blind, Randomized, Sham-Controlled Trial. Clin Gastroenterol Hepatol. 2022 Dec;20(12):2753-62.e2. doi: 10.1016/j.cgh.2022.02.058. Epub 2022 Mar 14. PMID: 35301135.
 

Techniques and Innovations in Gastrointestinal Endoscopy

Azizian JM et al. Yield of Post-Acute Diverticulitis Colonoscopy for Ruling Out Colorectal Cancer. Tech Innov Gastrointest Endosc. 2022;24(3):254-61. doi: 10.1016/j.tige.2022.04.001. Epub 2022 Apr 18. PMID: 36540108; PMCID: PMC9762736.
 

Gastro Hep Advances

Kim RW et al. Timely Albumin Improves Survival in Patients With Cirrhosis on Diuretic Therapy Who Develop Acute Kidney Injury: Real-World Evidence in the United States. Gastro Hep Advances. 2023;2(2):252-60. doi: 10.1016/j.gastha.2022.10.008.

A statewide quality initiative can improve severe maternal morbidity (SMM) and reduce the incidence of maternal morbidity and mortality from postpartum hemorrhage (PPH), a modeling analysis found. Such measures could potentially provide savings to birthing hospitals, according to the California cost-effectiveness study, published in Obstetrics & Gynecology.

A team led by Eric C. Wiesehan, MHA, MBA, a PhD candidate in health policy at Stanford (Calif.) University, examined the effects of the safety initiative of the California Maternal Quality Care Collaborative (CMQCC) in a theoretical cohort of 480,000 births across a mix of hospital settings and sizes. The CMQCC developed a PPH toolkit and quality-improvement protocol to increase recognition, measurement, and timely response to PPH.

Drawing retrospectively on a large 2017 California implementation study, the simulation estimated that collaborative implementation of the CMQCC added 182 quality-adjusted life-years (0.000379 per birth) by averting 913 cases of SMM, 28 emergency hysterectomies, and one maternal mortality. Additionally, it saved $9 million ($17.78 per birth) owing to avoided SMM costs.

According to the Centers for Disease Control and Prevention, pregnancy-related maternal deaths in the United States have increased from 7.2 per 100,000 live births to 16.9 per 100,000 live births over the past 20 years, making it the only country in the Organization for Economic Cooperation and Development with rising rates of maternal mortality. PPH accounts for 11% of maternal deaths.

As to the study’s broader applicability, Dr. Wiesehan said in an interview, “findings of effectiveness in terms of reducing PPH-related SMM are well known outside of California. In terms of costs, however, it is more of an unknown how much is generalizable. It would go a long way if another state quality care collaborative implementing such a project recorded costs prospectively. Prospective costing, particularly microcosting, would be optimal to precisely place where the most, or least, value of this quality improvement project is achieved.”

Studies of PPH safety programs in other U.S. jurisdictions showing reductions in blood transfusions and maternal morbidities suggest the current findings are relevant to a range of hospital settings and regions. “With state perinatal collaboratives already in 47 states, examination of implementation of the PPH-SMM reduction initiative within additional collaboratives would add further robustness to our findings,” the authors wrote.

In 2022, a New York City hospital study reported that learning collaboratives that optimize practice and raise staff awareness could be important tools for improving maternal outcomes.

Still to be answered, said Dr. Wiesehan, are questions about the long-term effectiveness and sustainability of the quality initiative project beyond the early pre/post periods. 

The authors indicated no specific funding for the study and had no conflicts of interest to disclose.

A statewide quality initiative can improve severe maternal morbidity (SMM) and reduce the incidence of maternal morbidity and mortality from postpartum hemorrhage (PPH), a modeling analysis found. Such measures could potentially provide savings to birthing hospitals, according to the California cost-effectiveness study, published in Obstetrics & Gynecology.

A team led by Eric C. Wiesehan, MHA, MBA, a PhD candidate in health policy at Stanford (Calif.) University, examined the effects of the safety initiative of the California Maternal Quality Care Collaborative (CMQCC) in a theoretical cohort of 480,000 births across a mix of hospital settings and sizes. The CMQCC developed a PPH toolkit and quality-improvement protocol to increase recognition, measurement, and timely response to PPH.

Drawing retrospectively on a large 2017 California implementation study, the simulation estimated that collaborative implementation of the CMQCC added 182 quality-adjusted life-years (0.000379 per birth) by averting 913 cases of SMM, 28 emergency hysterectomies, and one maternal mortality. Additionally, it saved $9 million ($17.78 per birth) owing to avoided SMM costs.

According to the Centers for Disease Control and Prevention, pregnancy-related maternal deaths in the United States have increased from 7.2 per 100,000 live births to 16.9 per 100,000 live births over the past 20 years, making it the only country in the Organization for Economic Cooperation and Development with rising rates of maternal mortality. PPH accounts for 11% of maternal deaths.

As to the study’s broader applicability, Dr. Wiesehan said in an interview, “findings of effectiveness in terms of reducing PPH-related SMM are well known outside of California. In terms of costs, however, it is more of an unknown how much is generalizable. It would go a long way if another state quality care collaborative implementing such a project recorded costs prospectively. Prospective costing, particularly microcosting, would be optimal to precisely place where the most, or least, value of this quality improvement project is achieved.”

Studies of PPH safety programs in other U.S. jurisdictions showing reductions in blood transfusions and maternal morbidities suggest the current findings are relevant to a range of hospital settings and regions. “With state perinatal collaboratives already in 47 states, examination of implementation of the PPH-SMM reduction initiative within additional collaboratives would add further robustness to our findings,” the authors wrote.

In 2022, a New York City hospital study reported that learning collaboratives that optimize practice and raise staff awareness could be important tools for improving maternal outcomes.

Still to be answered, said Dr. Wiesehan, are questions about the long-term effectiveness and sustainability of the quality initiative project beyond the early pre/post periods. 

The authors indicated no specific funding for the study and had no conflicts of interest to disclose.

A statewide quality initiative can improve severe maternal morbidity (SMM) and reduce the incidence of maternal morbidity and mortality from postpartum hemorrhage (PPH), a modeling analysis found. Such measures could potentially provide savings to birthing hospitals, according to the California cost-effectiveness study, published in Obstetrics & Gynecology.

A team led by Eric C. Wiesehan, MHA, MBA, a PhD candidate in health policy at Stanford (Calif.) University, examined the effects of the safety initiative of the California Maternal Quality Care Collaborative (CMQCC) in a theoretical cohort of 480,000 births across a mix of hospital settings and sizes. The CMQCC developed a PPH toolkit and quality-improvement protocol to increase recognition, measurement, and timely response to PPH.

Drawing retrospectively on a large 2017 California implementation study, the simulation estimated that collaborative implementation of the CMQCC added 182 quality-adjusted life-years (0.000379 per birth) by averting 913 cases of SMM, 28 emergency hysterectomies, and one maternal mortality. Additionally, it saved $9 million ($17.78 per birth) owing to avoided SMM costs.

According to the Centers for Disease Control and Prevention, pregnancy-related maternal deaths in the United States have increased from 7.2 per 100,000 live births to 16.9 per 100,000 live births over the past 20 years, making it the only country in the Organization for Economic Cooperation and Development with rising rates of maternal mortality. PPH accounts for 11% of maternal deaths.

As to the study’s broader applicability, Dr. Wiesehan said in an interview, “findings of effectiveness in terms of reducing PPH-related SMM are well known outside of California. In terms of costs, however, it is more of an unknown how much is generalizable. It would go a long way if another state quality care collaborative implementing such a project recorded costs prospectively. Prospective costing, particularly microcosting, would be optimal to precisely place where the most, or least, value of this quality improvement project is achieved.”

Studies of PPH safety programs in other U.S. jurisdictions showing reductions in blood transfusions and maternal morbidities suggest the current findings are relevant to a range of hospital settings and regions. “With state perinatal collaboratives already in 47 states, examination of implementation of the PPH-SMM reduction initiative within additional collaboratives would add further robustness to our findings,” the authors wrote.

In 2022, a New York City hospital study reported that learning collaboratives that optimize practice and raise staff awareness could be important tools for improving maternal outcomes.

Still to be answered, said Dr. Wiesehan, are questions about the long-term effectiveness and sustainability of the quality initiative project beyond the early pre/post periods. 

The authors indicated no specific funding for the study and had no conflicts of interest to disclose.

Bariatric surgery for severe obesity does not appear to raise the risk of esophageal and gastric cancer, a new study shows.

In fact, an analysis of close to 1 million French adults suggests that the weight-loss surgery may offer some protection against these cancers.

The study results present a “clinical paradox,” according to authors of a commentary published this week along with the study in JAMA Surgery. A procedure known to increase the risk of gastroesophageal reflux disease (GERD), and potentially adenocarcinoma of the distal esophagus and gastroesophageal junction, may help shield patients from esophagogastric cancer.

The study marks “an important step toward improving the understanding of potential lifetime risks of bariatric surgery and overall major health benefits of surgically induced weight loss,” commentary authors Piotr Gorecki, MD, and Michael Zenilman, MD, with Weill Cornell Medicine in New York, write.

Recent data indicate that excess body weight is associated with nearly 8% of cancer cases and 6.5% of cancer deaths. Studies also show that bariatric surgery can reduce the risk of some cancers, but whether this extends to esophageal and gastric cancer remains unclear.

To investigate, the researchers used French national data to compare the incidence of esophageal and gastric cancer in 303,709 mostly female patients with obesity who underwent bariatric surgery and a matched group of 605,140 patients with obesity who did not undergo the surgery.

The mean age of the cohort was about 40 years. The mean period of follow-up was 6 years for the surgery group and 5.6 years for the control arm. A total of 337 patients underwent esophagogastric cancer – 83 in the surgical group and 254 in the control group. Gastric cancer was about two times more common than esophageal cancer (225 vs. 112 patients).

The incidence rate of esophagogastric cancer was higher in the control group than in the surgery group – 6.9 vs. 4.9 cases per 100,000 population per year, for an incidence rate ratio of 1.42 (P = .005).

Bariatric surgery was associated with a significant 24% lower risk of esophagogastric cancer (hazard ratio, 0.76; P = .03) and a 40% lower risk of overall in-hospital mortality, defined as “any death occurring during a hospital stay regardless of the cause” (HR, 0.60; P < .001).

The authors also found no significant difference in cancer outcomes and type of bariatric procedure, which included sleeve gastrectomy, gastric bypass, and adjustable gastric banding.

They note that key study limitations include the retrospective design, limited follow-up period, and lack of histologic data on the specific cancers. In addition, the study population was relatively young, whereas esophageal cancer is more common in older people.

But overall, the findings suggest that bariatric surgery can be performed to treat severe obesity without increasing the risk of esophageal and gastric cancer, the authors conclude.

“It seems that the balance between protective factors (weight loss, metabolic effects, and eradication of H. pylori infection) and risk factors (GERD and bile reflux) for cancer after bariatric surgery is in favor of protective factors,” the authors, led by Andrea Lazzati, MD, PhD, of Centre Hospitalier Intercommunal de Créteil, France, explain.

Although the potential protective mechanisms remain unclear, in their commentary, Dr. Gorecki and Dr. Zenilman suggest that a reduction in chronic inflammation and immunosuppression following bariatric surgery could help explain the results.

Although the study provides “reassurance of the protective clinical benefits of weight loss surgery,” more large-scale studies are needed to “better identify, elucidate, and address the pathophysiological processes of bariatric procedure,” Dr. Gorecki and Dr. Zenilman conclude.

No specific funding for the study was reported. Dr. Lazzati has received personal fees from Johnson & Johnson, Medtronic, and Gore. Dr. Zenilman has received personal fees from Academic Medical Professionals Insurance and Mohamed & Obaid Almulla Group.

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

Bariatric surgery for severe obesity does not appear to raise the risk of esophageal and gastric cancer, a new study shows.

In fact, an analysis of close to 1 million French adults suggests that the weight-loss surgery may offer some protection against these cancers.

The study results present a “clinical paradox,” according to authors of a commentary published this week along with the study in JAMA Surgery. A procedure known to increase the risk of gastroesophageal reflux disease (GERD), and potentially adenocarcinoma of the distal esophagus and gastroesophageal junction, may help shield patients from esophagogastric cancer.

The study marks “an important step toward improving the understanding of potential lifetime risks of bariatric surgery and overall major health benefits of surgically induced weight loss,” commentary authors Piotr Gorecki, MD, and Michael Zenilman, MD, with Weill Cornell Medicine in New York, write.

Recent data indicate that excess body weight is associated with nearly 8% of cancer cases and 6.5% of cancer deaths. Studies also show that bariatric surgery can reduce the risk of some cancers, but whether this extends to esophageal and gastric cancer remains unclear.

To investigate, the researchers used French national data to compare the incidence of esophageal and gastric cancer in 303,709 mostly female patients with obesity who underwent bariatric surgery and a matched group of 605,140 patients with obesity who did not undergo the surgery.

The mean age of the cohort was about 40 years. The mean period of follow-up was 6 years for the surgery group and 5.6 years for the control arm. A total of 337 patients underwent esophagogastric cancer – 83 in the surgical group and 254 in the control group. Gastric cancer was about two times more common than esophageal cancer (225 vs. 112 patients).

The incidence rate of esophagogastric cancer was higher in the control group than in the surgery group – 6.9 vs. 4.9 cases per 100,000 population per year, for an incidence rate ratio of 1.42 (P = .005).

Bariatric surgery was associated with a significant 24% lower risk of esophagogastric cancer (hazard ratio, 0.76; P = .03) and a 40% lower risk of overall in-hospital mortality, defined as “any death occurring during a hospital stay regardless of the cause” (HR, 0.60; P < .001).

The authors also found no significant difference in cancer outcomes and type of bariatric procedure, which included sleeve gastrectomy, gastric bypass, and adjustable gastric banding.

They note that key study limitations include the retrospective design, limited follow-up period, and lack of histologic data on the specific cancers. In addition, the study population was relatively young, whereas esophageal cancer is more common in older people.

But overall, the findings suggest that bariatric surgery can be performed to treat severe obesity without increasing the risk of esophageal and gastric cancer, the authors conclude.

“It seems that the balance between protective factors (weight loss, metabolic effects, and eradication of H. pylori infection) and risk factors (GERD and bile reflux) for cancer after bariatric surgery is in favor of protective factors,” the authors, led by Andrea Lazzati, MD, PhD, of Centre Hospitalier Intercommunal de Créteil, France, explain.

Although the potential protective mechanisms remain unclear, in their commentary, Dr. Gorecki and Dr. Zenilman suggest that a reduction in chronic inflammation and immunosuppression following bariatric surgery could help explain the results.

Although the study provides “reassurance of the protective clinical benefits of weight loss surgery,” more large-scale studies are needed to “better identify, elucidate, and address the pathophysiological processes of bariatric procedure,” Dr. Gorecki and Dr. Zenilman conclude.

No specific funding for the study was reported. Dr. Lazzati has received personal fees from Johnson & Johnson, Medtronic, and Gore. Dr. Zenilman has received personal fees from Academic Medical Professionals Insurance and Mohamed & Obaid Almulla Group.

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

Bariatric surgery for severe obesity does not appear to raise the risk of esophageal and gastric cancer, a new study shows.

In fact, an analysis of close to 1 million French adults suggests that the weight-loss surgery may offer some protection against these cancers.

The study results present a “clinical paradox,” according to authors of a commentary published this week along with the study in JAMA Surgery. A procedure known to increase the risk of gastroesophageal reflux disease (GERD), and potentially adenocarcinoma of the distal esophagus and gastroesophageal junction, may help shield patients from esophagogastric cancer.

The study marks “an important step toward improving the understanding of potential lifetime risks of bariatric surgery and overall major health benefits of surgically induced weight loss,” commentary authors Piotr Gorecki, MD, and Michael Zenilman, MD, with Weill Cornell Medicine in New York, write.

Recent data indicate that excess body weight is associated with nearly 8% of cancer cases and 6.5% of cancer deaths. Studies also show that bariatric surgery can reduce the risk of some cancers, but whether this extends to esophageal and gastric cancer remains unclear.

To investigate, the researchers used French national data to compare the incidence of esophageal and gastric cancer in 303,709 mostly female patients with obesity who underwent bariatric surgery and a matched group of 605,140 patients with obesity who did not undergo the surgery.

The mean age of the cohort was about 40 years. The mean period of follow-up was 6 years for the surgery group and 5.6 years for the control arm. A total of 337 patients underwent esophagogastric cancer – 83 in the surgical group and 254 in the control group. Gastric cancer was about two times more common than esophageal cancer (225 vs. 112 patients).

The incidence rate of esophagogastric cancer was higher in the control group than in the surgery group – 6.9 vs. 4.9 cases per 100,000 population per year, for an incidence rate ratio of 1.42 (P = .005).

Bariatric surgery was associated with a significant 24% lower risk of esophagogastric cancer (hazard ratio, 0.76; P = .03) and a 40% lower risk of overall in-hospital mortality, defined as “any death occurring during a hospital stay regardless of the cause” (HR, 0.60; P < .001).

The authors also found no significant difference in cancer outcomes and type of bariatric procedure, which included sleeve gastrectomy, gastric bypass, and adjustable gastric banding.

They note that key study limitations include the retrospective design, limited follow-up period, and lack of histologic data on the specific cancers. In addition, the study population was relatively young, whereas esophageal cancer is more common in older people.

But overall, the findings suggest that bariatric surgery can be performed to treat severe obesity without increasing the risk of esophageal and gastric cancer, the authors conclude.

“It seems that the balance between protective factors (weight loss, metabolic effects, and eradication of H. pylori infection) and risk factors (GERD and bile reflux) for cancer after bariatric surgery is in favor of protective factors,” the authors, led by Andrea Lazzati, MD, PhD, of Centre Hospitalier Intercommunal de Créteil, France, explain.

Although the potential protective mechanisms remain unclear, in their commentary, Dr. Gorecki and Dr. Zenilman suggest that a reduction in chronic inflammation and immunosuppression following bariatric surgery could help explain the results.

Although the study provides “reassurance of the protective clinical benefits of weight loss surgery,” more large-scale studies are needed to “better identify, elucidate, and address the pathophysiological processes of bariatric procedure,” Dr. Gorecki and Dr. Zenilman conclude.

No specific funding for the study was reported. Dr. Lazzati has received personal fees from Johnson & Johnson, Medtronic, and Gore. Dr. Zenilman has received personal fees from Academic Medical Professionals Insurance and Mohamed & Obaid Almulla Group.

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

Patients with moderate to severe active ulcerative colitis (UC) who received induction therapy with either ritlecitinib or brepocitinib showed significant improvement across multiple outcome metrics in a phase 2b “umbrella” study of the two investigational agents.

The study by William J. Sandborn, MD, division of gastroenterology, University of California, San Diego, and colleagues was published online in Clinical Gastroenterology and Hepatology.

Ritlecitinib is a dual inhibitor that selectively inhibits Janus kinase 3 (JAK3) and the TEC family of tyrosine kinases, while brepocitinib is a dual tyrosine kinase 2 (TYK2) and JAK1 inhibitor.

Both agents have demonstrated efficacy and acceptable safety in the treatment of alopecia areata and rheumatoid arthritis and are being evaluated for treating vitiligo, Crohn’s disease, and UC.

The different JAK selectivity profiles of ritlecitinib (JAK3/TEC) and brepocitinib (TYK2/JAK1), compared with other JAK inhibitors, could further the understanding of the role these pathways play in UC, the investigators note.
 

The VIBRATO study

As part of the phase 2b VIBRATO study, 317 patients with moderate to severe active UC (total Mayo Score ≥ 6) were randomly assigned to an 8-week induction course of once-daily oral ritlecitinib (20, 70, or 200 mg), brepocitinib (10, 30, or 60 mg), or matching placebo.

At week 8, compared with placebo, treatment with ritlecitinib or brepocitinib was associated with significantly lower mean total Mayo Scores (the primary endpoint) and higher rates of clinical remission, endoscopic and histologic improvement, and mucosal healing.

For both drugs, improvement on most metrics was dose dependent, with greater benefit at the highest dose.

For example, the placebo-adjusted mean total Mayo Score at week 8 was −4.6 for ritlecitinib 200 mg (P < .001) and −3.2 for brepocitinib 60 mg (P < .001). Both agents showed a “rapid” onset of action, with significant effects on the partial Mayo Score seen after just 2 weeks of treatment, the authors report.

Modified clinical remission at week 8 (a key secondary endpoint) was achieved in 36% of patients taking ritlecitinib 200 mg and 25.5% of those taking brepocitinib 60 mg (vs. 0% for patients taking placebo).

Endoscopic and histologic improvement, clinical response, mucosal healing, and the patient-reported outcome on the Inflammatory Bowel Disease Questionnaire followed a similar pattern, with a dose-dependent increase in treatment effect observed in most parameters at week 8, compared with placebo.
 

Longer-term data needed

Both agents were well tolerated with “acceptable short-term safety profiles,” the authors say.

There were no clinically significant findings for any laboratory parameters evaluated. Adverse events were mostly mild.

Infections were observed in 8.7% of patients taking ritlecitinib and 16.9% of those taking brepocitinib, compared with 4% of patients taking placebo. No serious cases of herpes zoster occurred.

One patient taking ritlecitinib suffered myocardial infarction and died, and one patient taking brepocitinib had peripheral artery thrombosis (left tibial artery). Both cases were considered unrelated to the study drug.

“As JAK inhibitors are associated with increased risk of major cardiovascular events and venous thromboembolisms, larger studies are needed for ritlecitinib and brepocitinib to fully understand their safety profiles,” the investigators say.

Limitations of the study include the small sample size and short 8-week treatment period. Longer-term safety and efficacy of both agents are being investigated.

The study was sponsored by Pfizer, which is developing both drugs. Dr. Sandborn and several coauthors have disclosed financial relationships with the company.

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

Patients with moderate to severe active ulcerative colitis (UC) who received induction therapy with either ritlecitinib or brepocitinib showed significant improvement across multiple outcome metrics in a phase 2b “umbrella” study of the two investigational agents.

The study by William J. Sandborn, MD, division of gastroenterology, University of California, San Diego, and colleagues was published online in Clinical Gastroenterology and Hepatology.

Ritlecitinib is a dual inhibitor that selectively inhibits Janus kinase 3 (JAK3) and the TEC family of tyrosine kinases, while brepocitinib is a dual tyrosine kinase 2 (TYK2) and JAK1 inhibitor.

Both agents have demonstrated efficacy and acceptable safety in the treatment of alopecia areata and rheumatoid arthritis and are being evaluated for treating vitiligo, Crohn’s disease, and UC.

The different JAK selectivity profiles of ritlecitinib (JAK3/TEC) and brepocitinib (TYK2/JAK1), compared with other JAK inhibitors, could further the understanding of the role these pathways play in UC, the investigators note.
 

The VIBRATO study

As part of the phase 2b VIBRATO study, 317 patients with moderate to severe active UC (total Mayo Score ≥ 6) were randomly assigned to an 8-week induction course of once-daily oral ritlecitinib (20, 70, or 200 mg), brepocitinib (10, 30, or 60 mg), or matching placebo.

At week 8, compared with placebo, treatment with ritlecitinib or brepocitinib was associated with significantly lower mean total Mayo Scores (the primary endpoint) and higher rates of clinical remission, endoscopic and histologic improvement, and mucosal healing.

For both drugs, improvement on most metrics was dose dependent, with greater benefit at the highest dose.

For example, the placebo-adjusted mean total Mayo Score at week 8 was −4.6 for ritlecitinib 200 mg (P < .001) and −3.2 for brepocitinib 60 mg (P < .001). Both agents showed a “rapid” onset of action, with significant effects on the partial Mayo Score seen after just 2 weeks of treatment, the authors report.

Modified clinical remission at week 8 (a key secondary endpoint) was achieved in 36% of patients taking ritlecitinib 200 mg and 25.5% of those taking brepocitinib 60 mg (vs. 0% for patients taking placebo).

Endoscopic and histologic improvement, clinical response, mucosal healing, and the patient-reported outcome on the Inflammatory Bowel Disease Questionnaire followed a similar pattern, with a dose-dependent increase in treatment effect observed in most parameters at week 8, compared with placebo.
 

Longer-term data needed

Both agents were well tolerated with “acceptable short-term safety profiles,” the authors say.

There were no clinically significant findings for any laboratory parameters evaluated. Adverse events were mostly mild.

Infections were observed in 8.7% of patients taking ritlecitinib and 16.9% of those taking brepocitinib, compared with 4% of patients taking placebo. No serious cases of herpes zoster occurred.

One patient taking ritlecitinib suffered myocardial infarction and died, and one patient taking brepocitinib had peripheral artery thrombosis (left tibial artery). Both cases were considered unrelated to the study drug.

“As JAK inhibitors are associated with increased risk of major cardiovascular events and venous thromboembolisms, larger studies are needed for ritlecitinib and brepocitinib to fully understand their safety profiles,” the investigators say.

Limitations of the study include the small sample size and short 8-week treatment period. Longer-term safety and efficacy of both agents are being investigated.

The study was sponsored by Pfizer, which is developing both drugs. Dr. Sandborn and several coauthors have disclosed financial relationships with the company.

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

Patients with moderate to severe active ulcerative colitis (UC) who received induction therapy with either ritlecitinib or brepocitinib showed significant improvement across multiple outcome metrics in a phase 2b “umbrella” study of the two investigational agents.

The study by William J. Sandborn, MD, division of gastroenterology, University of California, San Diego, and colleagues was published online in Clinical Gastroenterology and Hepatology.

Ritlecitinib is a dual inhibitor that selectively inhibits Janus kinase 3 (JAK3) and the TEC family of tyrosine kinases, while brepocitinib is a dual tyrosine kinase 2 (TYK2) and JAK1 inhibitor.

Both agents have demonstrated efficacy and acceptable safety in the treatment of alopecia areata and rheumatoid arthritis and are being evaluated for treating vitiligo, Crohn’s disease, and UC.

The different JAK selectivity profiles of ritlecitinib (JAK3/TEC) and brepocitinib (TYK2/JAK1), compared with other JAK inhibitors, could further the understanding of the role these pathways play in UC, the investigators note.
 

The VIBRATO study

As part of the phase 2b VIBRATO study, 317 patients with moderate to severe active UC (total Mayo Score ≥ 6) were randomly assigned to an 8-week induction course of once-daily oral ritlecitinib (20, 70, or 200 mg), brepocitinib (10, 30, or 60 mg), or matching placebo.

At week 8, compared with placebo, treatment with ritlecitinib or brepocitinib was associated with significantly lower mean total Mayo Scores (the primary endpoint) and higher rates of clinical remission, endoscopic and histologic improvement, and mucosal healing.

For both drugs, improvement on most metrics was dose dependent, with greater benefit at the highest dose.

For example, the placebo-adjusted mean total Mayo Score at week 8 was −4.6 for ritlecitinib 200 mg (P < .001) and −3.2 for brepocitinib 60 mg (P < .001). Both agents showed a “rapid” onset of action, with significant effects on the partial Mayo Score seen after just 2 weeks of treatment, the authors report.

Modified clinical remission at week 8 (a key secondary endpoint) was achieved in 36% of patients taking ritlecitinib 200 mg and 25.5% of those taking brepocitinib 60 mg (vs. 0% for patients taking placebo).

Endoscopic and histologic improvement, clinical response, mucosal healing, and the patient-reported outcome on the Inflammatory Bowel Disease Questionnaire followed a similar pattern, with a dose-dependent increase in treatment effect observed in most parameters at week 8, compared with placebo.
 

Longer-term data needed

Both agents were well tolerated with “acceptable short-term safety profiles,” the authors say.

There were no clinically significant findings for any laboratory parameters evaluated. Adverse events were mostly mild.

Infections were observed in 8.7% of patients taking ritlecitinib and 16.9% of those taking brepocitinib, compared with 4% of patients taking placebo. No serious cases of herpes zoster occurred.

One patient taking ritlecitinib suffered myocardial infarction and died, and one patient taking brepocitinib had peripheral artery thrombosis (left tibial artery). Both cases were considered unrelated to the study drug.

“As JAK inhibitors are associated with increased risk of major cardiovascular events and venous thromboembolisms, larger studies are needed for ritlecitinib and brepocitinib to fully understand their safety profiles,” the investigators say.

Limitations of the study include the small sample size and short 8-week treatment period. Longer-term safety and efficacy of both agents are being investigated.

The study was sponsored by Pfizer, which is developing both drugs. Dr. Sandborn and several coauthors have disclosed financial relationships with the company.

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

Treatment with interleukin-6 receptor antagonists or antiplatelet agents improves survival and outcomes at 6 months for critically ill patients with COVID-19, according to new data.

However, survival wasn’t improved with therapeutic anticoagulation, convalescent plasma, or lopinavir-ritonavir, and survival was worsened with hydroxychloroquine.

“After critically ill patients leave the hospital, there’s a high risk of readmission, death after discharge, or exacerbations of chronic illness,” study author Patrick Lawler, MD, a clinician-scientist at the Peter Munk Cardiac Centre at University Health Network and an assistant professor of medicine at the University of Toronto, said in an interview.

“When looking at the impact of treatment, we don’t want to improve short-term outcomes yet worsen long-term disability,” he said. “That long-term, 6-month horizon is what matters most to patients.”

The study was published online in JAMA.
 

Investigating treatments

The investigators analyzed data from an ongoing platform trial called Randomized Embedded Multifactorial Adaptive Platform for Community Acquired Pneumonia (REMAP-CAP). The trial is evaluating treatments for patients with severe pneumonia in pandemic and nonpandemic settings.

In the trial, patients are randomly assigned to receive one or more interventions within the following six treatment domains: immune modulators, convalescent plasma, antiplatelet therapy, anticoagulation, antivirals, and corticosteroids. The trial’s primary outcome for patients with COVID-19 is hospital survival and organ support–free days up to 21 days. Researchers previously observed improvement after treatment with IL-6 receptor antagonists (which are immune modulators).

For this study, the research team analyzed data for 4,869 critically ill adult patients with COVID-19 who were enrolled between March 2020 and June 2021 at 197 sites in 14 countries. A 180-day follow-up was completed in March 2022. The critically ill patients had been admitted to an intensive care unit and had received respiratory or cardiovascular organ support.

The researchers examined survival through day 180. A hazard ratio of less than 1 represented improved survival, and an HR greater than 1 represented harm. Futility was represented by a relative improvement in outcome of less than 20%, which was shown by an HR greater than 0.83.

Among the 4,869 patients, 4,107 patients had a known mortality status, and 2,590 were alive at day 180. Among the 1,517 patients who died by day 180, 91 deaths (6%) occurred between hospital discharge and day 180.

Overall, use of IL-6 receptor antagonists (either tocilizumab or sarilumab) had a greater than 99.9% probability of improving 6-month survival, and use of antiplatelet agents (aspirin or a P2Y12 inhibitor such as clopidogrel, prasugrel, or ticagrelor) had a 95% probability of improving 6-month survival, compared with control therapies.

In contrast, long-term survival wasn’t improved with therapeutic anticoagulation (11.5%), convalescent plasma (54.7%), or lopinavir-ritonavir (31.9%). The probability of trial-defined statistical futility was high for anticoagulation (99.9%), convalescent plasma (99.2%), and lopinavir-ritonavir (96.6%).

Long-term survival was worsened with hydroxychloroquine, with a posterior probability of harm of 96.9%. In addition, the combination of lopinavir-ritonavir and hydroxychloroquine had a 96.8% probability of harm.

Corticosteroids didn’t improve long-term outcomes, although enrollment in the treatment domain was terminated early in response to external evidence. The probability of improving 6-month survival ranged from 57.1% to 61.6% for various hydrocortisone dosing strategies.
 

Consistent treatment effects

When considered along with previously reported short-term results from the REMAP-CAP trial, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.

“We were very relieved to see that treatments with a favorable benefit for patients in the short term also appeared to be beneficial through 180 days,” said Dr. Lawler. “This supports the current clinical practice strategy in providing treatment to critically ill patients with COVID-19.”

In a subgroup analysis of 989 patients, health-related quality of life at day 180 was higher among those treated with IL-6 receptor antagonists and antiplatelet agents. The average quality-of-life score for the lopinavir-ritonavir group was lower than for control patients.

Among 720 survivors, 273 patients (37.9%) had moderate, severe, or complete disability at day 180. IL-6 receptor antagonists had a 92.6% probability of reducing disability, and anakinra (an IL-1 receptor antagonist) had a 90.8% probability of reducing disability. However, lopinavir-ritonavir had a 91.7% probability of worsening disability.

The REMAP-CAP trial investigators will continue to assess treatment domains and long-term outcomes among COVID-19 patients. They will evaluate additional data regarding disability, quality of life, and long-COVID outcomes.
 

“Reassuring” results

Commenting on the study, Angela Cheung, MD, PhD, a professor of medicine at the University of Toronto and senior scientist at the Toronto General Research Institute, said, “It is important to look at the longer-term effects of these therapies, as sometimes we may improve things in the short term, but that may not translate to longer-term gains. Historically, most trials conducted in this patient population assess only short outcomes, such as organ failure or 28-day mortality.”

Dr. Cheung, who wasn’t involved with this study, serves as the co-lead for the Canadian COVID-19 Prospective Cohort Study (CANCOV) and the Recovering From COVID-19 Lingering Symptoms Adaptive Integrative Medicine Trial (RECLAIM). These studies are also analyzing long-term outcomes among COVID-19 patients.

“It is reassuring to see that the 6-month outcomes are consistent with the short-term outcomes,” she said. “This study will help guide critical care medicine physicians in their treatment of critically ill patients with COVID-19.”

The study was supported by numerous grants and funds, including the Canadian Institute of Health Research COVID-19 Rapid Research Funding. Amgen and Eisai also provided funding. Dr. Lawler received grants from Canadian Institutes for Health Research and the Heart and Stroke Foundation of Canada during the conduct of the study and personal fees from Novartis, CorEvitas, Partners Healthcare, and the American College of Cardiology outside the submitted work. Dr. Cheung has disclosed no relevant financial relationships.

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

Treatment with interleukin-6 receptor antagonists or antiplatelet agents improves survival and outcomes at 6 months for critically ill patients with COVID-19, according to new data.

However, survival wasn’t improved with therapeutic anticoagulation, convalescent plasma, or lopinavir-ritonavir, and survival was worsened with hydroxychloroquine.

“After critically ill patients leave the hospital, there’s a high risk of readmission, death after discharge, or exacerbations of chronic illness,” study author Patrick Lawler, MD, a clinician-scientist at the Peter Munk Cardiac Centre at University Health Network and an assistant professor of medicine at the University of Toronto, said in an interview.

“When looking at the impact of treatment, we don’t want to improve short-term outcomes yet worsen long-term disability,” he said. “That long-term, 6-month horizon is what matters most to patients.”

The study was published online in JAMA.
 

Investigating treatments

The investigators analyzed data from an ongoing platform trial called Randomized Embedded Multifactorial Adaptive Platform for Community Acquired Pneumonia (REMAP-CAP). The trial is evaluating treatments for patients with severe pneumonia in pandemic and nonpandemic settings.

In the trial, patients are randomly assigned to receive one or more interventions within the following six treatment domains: immune modulators, convalescent plasma, antiplatelet therapy, anticoagulation, antivirals, and corticosteroids. The trial’s primary outcome for patients with COVID-19 is hospital survival and organ support–free days up to 21 days. Researchers previously observed improvement after treatment with IL-6 receptor antagonists (which are immune modulators).

For this study, the research team analyzed data for 4,869 critically ill adult patients with COVID-19 who were enrolled between March 2020 and June 2021 at 197 sites in 14 countries. A 180-day follow-up was completed in March 2022. The critically ill patients had been admitted to an intensive care unit and had received respiratory or cardiovascular organ support.

The researchers examined survival through day 180. A hazard ratio of less than 1 represented improved survival, and an HR greater than 1 represented harm. Futility was represented by a relative improvement in outcome of less than 20%, which was shown by an HR greater than 0.83.

Among the 4,869 patients, 4,107 patients had a known mortality status, and 2,590 were alive at day 180. Among the 1,517 patients who died by day 180, 91 deaths (6%) occurred between hospital discharge and day 180.

Overall, use of IL-6 receptor antagonists (either tocilizumab or sarilumab) had a greater than 99.9% probability of improving 6-month survival, and use of antiplatelet agents (aspirin or a P2Y12 inhibitor such as clopidogrel, prasugrel, or ticagrelor) had a 95% probability of improving 6-month survival, compared with control therapies.

In contrast, long-term survival wasn’t improved with therapeutic anticoagulation (11.5%), convalescent plasma (54.7%), or lopinavir-ritonavir (31.9%). The probability of trial-defined statistical futility was high for anticoagulation (99.9%), convalescent plasma (99.2%), and lopinavir-ritonavir (96.6%).

Long-term survival was worsened with hydroxychloroquine, with a posterior probability of harm of 96.9%. In addition, the combination of lopinavir-ritonavir and hydroxychloroquine had a 96.8% probability of harm.

Corticosteroids didn’t improve long-term outcomes, although enrollment in the treatment domain was terminated early in response to external evidence. The probability of improving 6-month survival ranged from 57.1% to 61.6% for various hydrocortisone dosing strategies.
 

Consistent treatment effects

When considered along with previously reported short-term results from the REMAP-CAP trial, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.

“We were very relieved to see that treatments with a favorable benefit for patients in the short term also appeared to be beneficial through 180 days,” said Dr. Lawler. “This supports the current clinical practice strategy in providing treatment to critically ill patients with COVID-19.”

In a subgroup analysis of 989 patients, health-related quality of life at day 180 was higher among those treated with IL-6 receptor antagonists and antiplatelet agents. The average quality-of-life score for the lopinavir-ritonavir group was lower than for control patients.

Among 720 survivors, 273 patients (37.9%) had moderate, severe, or complete disability at day 180. IL-6 receptor antagonists had a 92.6% probability of reducing disability, and anakinra (an IL-1 receptor antagonist) had a 90.8% probability of reducing disability. However, lopinavir-ritonavir had a 91.7% probability of worsening disability.

The REMAP-CAP trial investigators will continue to assess treatment domains and long-term outcomes among COVID-19 patients. They will evaluate additional data regarding disability, quality of life, and long-COVID outcomes.
 

“Reassuring” results

Commenting on the study, Angela Cheung, MD, PhD, a professor of medicine at the University of Toronto and senior scientist at the Toronto General Research Institute, said, “It is important to look at the longer-term effects of these therapies, as sometimes we may improve things in the short term, but that may not translate to longer-term gains. Historically, most trials conducted in this patient population assess only short outcomes, such as organ failure or 28-day mortality.”

Dr. Cheung, who wasn’t involved with this study, serves as the co-lead for the Canadian COVID-19 Prospective Cohort Study (CANCOV) and the Recovering From COVID-19 Lingering Symptoms Adaptive Integrative Medicine Trial (RECLAIM). These studies are also analyzing long-term outcomes among COVID-19 patients.

“It is reassuring to see that the 6-month outcomes are consistent with the short-term outcomes,” she said. “This study will help guide critical care medicine physicians in their treatment of critically ill patients with COVID-19.”

The study was supported by numerous grants and funds, including the Canadian Institute of Health Research COVID-19 Rapid Research Funding. Amgen and Eisai also provided funding. Dr. Lawler received grants from Canadian Institutes for Health Research and the Heart and Stroke Foundation of Canada during the conduct of the study and personal fees from Novartis, CorEvitas, Partners Healthcare, and the American College of Cardiology outside the submitted work. Dr. Cheung has disclosed no relevant financial relationships.

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

Treatment with interleukin-6 receptor antagonists or antiplatelet agents improves survival and outcomes at 6 months for critically ill patients with COVID-19, according to new data.

However, survival wasn’t improved with therapeutic anticoagulation, convalescent plasma, or lopinavir-ritonavir, and survival was worsened with hydroxychloroquine.

“After critically ill patients leave the hospital, there’s a high risk of readmission, death after discharge, or exacerbations of chronic illness,” study author Patrick Lawler, MD, a clinician-scientist at the Peter Munk Cardiac Centre at University Health Network and an assistant professor of medicine at the University of Toronto, said in an interview.

“When looking at the impact of treatment, we don’t want to improve short-term outcomes yet worsen long-term disability,” he said. “That long-term, 6-month horizon is what matters most to patients.”

The study was published online in JAMA.
 

Investigating treatments

The investigators analyzed data from an ongoing platform trial called Randomized Embedded Multifactorial Adaptive Platform for Community Acquired Pneumonia (REMAP-CAP). The trial is evaluating treatments for patients with severe pneumonia in pandemic and nonpandemic settings.

In the trial, patients are randomly assigned to receive one or more interventions within the following six treatment domains: immune modulators, convalescent plasma, antiplatelet therapy, anticoagulation, antivirals, and corticosteroids. The trial’s primary outcome for patients with COVID-19 is hospital survival and organ support–free days up to 21 days. Researchers previously observed improvement after treatment with IL-6 receptor antagonists (which are immune modulators).

For this study, the research team analyzed data for 4,869 critically ill adult patients with COVID-19 who were enrolled between March 2020 and June 2021 at 197 sites in 14 countries. A 180-day follow-up was completed in March 2022. The critically ill patients had been admitted to an intensive care unit and had received respiratory or cardiovascular organ support.

The researchers examined survival through day 180. A hazard ratio of less than 1 represented improved survival, and an HR greater than 1 represented harm. Futility was represented by a relative improvement in outcome of less than 20%, which was shown by an HR greater than 0.83.

Among the 4,869 patients, 4,107 patients had a known mortality status, and 2,590 were alive at day 180. Among the 1,517 patients who died by day 180, 91 deaths (6%) occurred between hospital discharge and day 180.

Overall, use of IL-6 receptor antagonists (either tocilizumab or sarilumab) had a greater than 99.9% probability of improving 6-month survival, and use of antiplatelet agents (aspirin or a P2Y12 inhibitor such as clopidogrel, prasugrel, or ticagrelor) had a 95% probability of improving 6-month survival, compared with control therapies.

In contrast, long-term survival wasn’t improved with therapeutic anticoagulation (11.5%), convalescent plasma (54.7%), or lopinavir-ritonavir (31.9%). The probability of trial-defined statistical futility was high for anticoagulation (99.9%), convalescent plasma (99.2%), and lopinavir-ritonavir (96.6%).

Long-term survival was worsened with hydroxychloroquine, with a posterior probability of harm of 96.9%. In addition, the combination of lopinavir-ritonavir and hydroxychloroquine had a 96.8% probability of harm.

Corticosteroids didn’t improve long-term outcomes, although enrollment in the treatment domain was terminated early in response to external evidence. The probability of improving 6-month survival ranged from 57.1% to 61.6% for various hydrocortisone dosing strategies.
 

Consistent treatment effects

When considered along with previously reported short-term results from the REMAP-CAP trial, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months.

“We were very relieved to see that treatments with a favorable benefit for patients in the short term also appeared to be beneficial through 180 days,” said Dr. Lawler. “This supports the current clinical practice strategy in providing treatment to critically ill patients with COVID-19.”

In a subgroup analysis of 989 patients, health-related quality of life at day 180 was higher among those treated with IL-6 receptor antagonists and antiplatelet agents. The average quality-of-life score for the lopinavir-ritonavir group was lower than for control patients.

Among 720 survivors, 273 patients (37.9%) had moderate, severe, or complete disability at day 180. IL-6 receptor antagonists had a 92.6% probability of reducing disability, and anakinra (an IL-1 receptor antagonist) had a 90.8% probability of reducing disability. However, lopinavir-ritonavir had a 91.7% probability of worsening disability.

The REMAP-CAP trial investigators will continue to assess treatment domains and long-term outcomes among COVID-19 patients. They will evaluate additional data regarding disability, quality of life, and long-COVID outcomes.
 

“Reassuring” results

Commenting on the study, Angela Cheung, MD, PhD, a professor of medicine at the University of Toronto and senior scientist at the Toronto General Research Institute, said, “It is important to look at the longer-term effects of these therapies, as sometimes we may improve things in the short term, but that may not translate to longer-term gains. Historically, most trials conducted in this patient population assess only short outcomes, such as organ failure or 28-day mortality.”

Dr. Cheung, who wasn’t involved with this study, serves as the co-lead for the Canadian COVID-19 Prospective Cohort Study (CANCOV) and the Recovering From COVID-19 Lingering Symptoms Adaptive Integrative Medicine Trial (RECLAIM). These studies are also analyzing long-term outcomes among COVID-19 patients.

“It is reassuring to see that the 6-month outcomes are consistent with the short-term outcomes,” she said. “This study will help guide critical care medicine physicians in their treatment of critically ill patients with COVID-19.”

The study was supported by numerous grants and funds, including the Canadian Institute of Health Research COVID-19 Rapid Research Funding. Amgen and Eisai also provided funding. Dr. Lawler received grants from Canadian Institutes for Health Research and the Heart and Stroke Foundation of Canada during the conduct of the study and personal fees from Novartis, CorEvitas, Partners Healthcare, and the American College of Cardiology outside the submitted work. Dr. Cheung has disclosed no relevant financial relationships.

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

Two classes of drugs may be more effective than others for the treatment of gastroparesis, though the overall quality of evidence remains low to moderate and additional data are needed, according to a new report.

Oral dopamine antagonists and tachykinin-1 antagonists appear superior to placebo, finds the study. In addition, some drugs rank higher for addressing individual symptoms.

“Gastroparesis has a substantial impact on quality of life and societal functioning for patients, and the costs to the health service are high,” Alexander Ford, MBChB, MD, a professor of gastroenterology and honorary consultant gastroenterologist at the Leeds (England) Institute of Medical Research at St. James’s, University of Leeds, said in an interview.

“There are very few licensed therapies, but some novel drugs are in the pipeline, some existing drugs that are licensed for other conditions could be repurposed if efficacious, and some older drugs that have safety concerns may be beneficial,” he said. “Given the impact on patients and their symptoms, they may be willing to accept these safety risks in return for symptom improvement.”

Only one drug, the dopamine antagonist metoclopramide, has Food and Drug Administration approval for the treatment of gastroparesis, noted Dr. Ford and colleagues. The lack of other recommended drugs or new medications has resulted in off-label use of drugs in other classes.

The study was published online in Gastroenterology.
 

Investigating treatments

To address the lack of evidence supporting the efficacy and safety of licensed and unlicensed drugs for the condition, the researchers conducted a systematic review and network meta-analysis of randomized controlled trials of drugs for gastroparesis dating from 1947 to September 2022. The trials involved more than dozen drugs in several classes.

They determined drug efficacy on the basis of global symptoms of gastroparesis and individual symptoms such as nausea, vomiting, abdominal pain, bloating, or fullness. They judged safety on the basis of total adverse events and adverse events leading to withdrawal.

The research team extracted data as intention-to-treat analyses, assuming dropouts to be treatment failures. They reported efficacy as a pooled relative risk of symptoms not improving and ranked the drugs according to P-score.

The analysis included 29 randomized controlled trials with 3,772 patients. Only four trials were at low risk of bias.

Overall, only two drug classes were considered efficacious: oral dopamine antagonists (RR, 0.58; P-score, 0.96) and tachykinin-1 antagonists (RR, 0.69; P-score, 0.83).

On the basis of 25 trials that reported on global symptoms, clebopride ranked first for efficacy (RR, 0.30; P-score, 0.99), followed by domperidone (RR, 0.69; P-score, 0.76). None of the other drugs were superior to the placebo. After direct and indirect comparisons, clebopride was superior to all other drugs except aprepitant.

After excluding three trials with a placebo run-in and a trial where only responders to single-blind domperidone were randomized, the researchers analyzed 21 trials with 2,233 patients. In this analysis, domperidone ranked first (RR, 0.48; P-score, 0.93), followed by oral metoclopramide (RR, 0.54; P-score, 0.87). None of the other drugs were superior to placebo.

Among 16 trials, including 1,381 patients, that confirmed delayed gastric emptying among all participants, only clebopride and metoclopramide were more efficacious than placebo. Clebopride ranked first (RR, 0.30; P-score, 0.95) and metoclopramide ranked third (RR, 0.48).

Among 13 trials with 785 patients with diabetic gastroparesis, none of the active drugs were superior to placebo. Among 12 trials recruiting patients with idiopathic or mixed etiology gastroparesis, clebopride ranked first (RR, 0.30; P-score, 0.93).

On the basis of trials that assessed individual symptoms, oral metoclopramide ranked first for nausea (RR, 0.46; P-score, 0.95), fullness (RR, 0.67; P-score, 0.86), and bloating (RR, 0.53; P-score, 0.97). However, the data came from one small trial. Tradipitant and TZP-102, a ghrelin agonist, were efficacious for nausea, and TZP-102 ranked second for fullness. No drugs were more efficacious than the placebo for abdominal pain or vomiting.

Among 20 trials that reported on the total number of adverse events, camicinal was the least likely to be associated with adverse events (RR, 0.77; P-score, 0.93) and prucalopride was the most likely to be associated with adverse events (RR, 2.96; P-score, 0.10). Prucalopride, oral metoclopramide, and aprepitant also were more likely than placebo to be associated with adverse events.

In 23 trials that reported on withdrawals caused by adverse events, camicinal was the least likely to be associated with withdrawals (RR, 0.20; P-score, 0.87). Nortriptyline was the most likely to be associated with withdrawals (RR, 3.33; P-score, 0.16). However, there were no significant differences between any individual drug and placebo.
 

Urgent need remains

More trials of drugs to treat gastroparesis are needed, Ford said.

“We need to consider the reintroduction of dopamine antagonists, if patients are willing to accept the safety concerns,” he added. “The other important point is most drugs were not of benefit. There is an urgent need to find efficacious therapies, and these should be fast-tracked for licensing approval if efficacy is proven.”

The study is “helpful for practicing clinicians since it provides a comprehensive review of clinical trials in gastroparesis,” Anthony Lembo, MD, a gastroenterologist at the Cleveland Clinic, said in an interview.

Dr. Lembo, who wasn’t involved with this study, has researched several drugs for gastroparesis, including relamorelin and TZP-102. He agreed that additional research is needed.

“There is a paucity of novel treatments currently in development,” he said. “However, there is interest in developing a product similar to domperidone without cardiac side effects, as well as performing larger studies with botulinum toxin injection.”

The authors did not disclose a funding source for the study. One author disclosed research funding from the National Institutes of Health and consulting roles with various pharmaceutical companies. Ford and the other authors reported no disclosures. Dr. Lembo reported no relevant disclosures.

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

Two classes of drugs may be more effective than others for the treatment of gastroparesis, though the overall quality of evidence remains low to moderate and additional data are needed, according to a new report.

Oral dopamine antagonists and tachykinin-1 antagonists appear superior to placebo, finds the study. In addition, some drugs rank higher for addressing individual symptoms.

“Gastroparesis has a substantial impact on quality of life and societal functioning for patients, and the costs to the health service are high,” Alexander Ford, MBChB, MD, a professor of gastroenterology and honorary consultant gastroenterologist at the Leeds (England) Institute of Medical Research at St. James’s, University of Leeds, said in an interview.

“There are very few licensed therapies, but some novel drugs are in the pipeline, some existing drugs that are licensed for other conditions could be repurposed if efficacious, and some older drugs that have safety concerns may be beneficial,” he said. “Given the impact on patients and their symptoms, they may be willing to accept these safety risks in return for symptom improvement.”

Only one drug, the dopamine antagonist metoclopramide, has Food and Drug Administration approval for the treatment of gastroparesis, noted Dr. Ford and colleagues. The lack of other recommended drugs or new medications has resulted in off-label use of drugs in other classes.

The study was published online in Gastroenterology.
 

Investigating treatments

To address the lack of evidence supporting the efficacy and safety of licensed and unlicensed drugs for the condition, the researchers conducted a systematic review and network meta-analysis of randomized controlled trials of drugs for gastroparesis dating from 1947 to September 2022. The trials involved more than dozen drugs in several classes.

They determined drug efficacy on the basis of global symptoms of gastroparesis and individual symptoms such as nausea, vomiting, abdominal pain, bloating, or fullness. They judged safety on the basis of total adverse events and adverse events leading to withdrawal.

The research team extracted data as intention-to-treat analyses, assuming dropouts to be treatment failures. They reported efficacy as a pooled relative risk of symptoms not improving and ranked the drugs according to P-score.

The analysis included 29 randomized controlled trials with 3,772 patients. Only four trials were at low risk of bias.

Overall, only two drug classes were considered efficacious: oral dopamine antagonists (RR, 0.58; P-score, 0.96) and tachykinin-1 antagonists (RR, 0.69; P-score, 0.83).

On the basis of 25 trials that reported on global symptoms, clebopride ranked first for efficacy (RR, 0.30; P-score, 0.99), followed by domperidone (RR, 0.69; P-score, 0.76). None of the other drugs were superior to the placebo. After direct and indirect comparisons, clebopride was superior to all other drugs except aprepitant.

After excluding three trials with a placebo run-in and a trial where only responders to single-blind domperidone were randomized, the researchers analyzed 21 trials with 2,233 patients. In this analysis, domperidone ranked first (RR, 0.48; P-score, 0.93), followed by oral metoclopramide (RR, 0.54; P-score, 0.87). None of the other drugs were superior to placebo.

Among 16 trials, including 1,381 patients, that confirmed delayed gastric emptying among all participants, only clebopride and metoclopramide were more efficacious than placebo. Clebopride ranked first (RR, 0.30; P-score, 0.95) and metoclopramide ranked third (RR, 0.48).

Among 13 trials with 785 patients with diabetic gastroparesis, none of the active drugs were superior to placebo. Among 12 trials recruiting patients with idiopathic or mixed etiology gastroparesis, clebopride ranked first (RR, 0.30; P-score, 0.93).

On the basis of trials that assessed individual symptoms, oral metoclopramide ranked first for nausea (RR, 0.46; P-score, 0.95), fullness (RR, 0.67; P-score, 0.86), and bloating (RR, 0.53; P-score, 0.97). However, the data came from one small trial. Tradipitant and TZP-102, a ghrelin agonist, were efficacious for nausea, and TZP-102 ranked second for fullness. No drugs were more efficacious than the placebo for abdominal pain or vomiting.

Among 20 trials that reported on the total number of adverse events, camicinal was the least likely to be associated with adverse events (RR, 0.77; P-score, 0.93) and prucalopride was the most likely to be associated with adverse events (RR, 2.96; P-score, 0.10). Prucalopride, oral metoclopramide, and aprepitant also were more likely than placebo to be associated with adverse events.

In 23 trials that reported on withdrawals caused by adverse events, camicinal was the least likely to be associated with withdrawals (RR, 0.20; P-score, 0.87). Nortriptyline was the most likely to be associated with withdrawals (RR, 3.33; P-score, 0.16). However, there were no significant differences between any individual drug and placebo.
 

Urgent need remains

More trials of drugs to treat gastroparesis are needed, Ford said.

“We need to consider the reintroduction of dopamine antagonists, if patients are willing to accept the safety concerns,” he added. “The other important point is most drugs were not of benefit. There is an urgent need to find efficacious therapies, and these should be fast-tracked for licensing approval if efficacy is proven.”

The study is “helpful for practicing clinicians since it provides a comprehensive review of clinical trials in gastroparesis,” Anthony Lembo, MD, a gastroenterologist at the Cleveland Clinic, said in an interview.

Dr. Lembo, who wasn’t involved with this study, has researched several drugs for gastroparesis, including relamorelin and TZP-102. He agreed that additional research is needed.

“There is a paucity of novel treatments currently in development,” he said. “However, there is interest in developing a product similar to domperidone without cardiac side effects, as well as performing larger studies with botulinum toxin injection.”

The authors did not disclose a funding source for the study. One author disclosed research funding from the National Institutes of Health and consulting roles with various pharmaceutical companies. Ford and the other authors reported no disclosures. Dr. Lembo reported no relevant disclosures.

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

Two classes of drugs may be more effective than others for the treatment of gastroparesis, though the overall quality of evidence remains low to moderate and additional data are needed, according to a new report.

Oral dopamine antagonists and tachykinin-1 antagonists appear superior to placebo, finds the study. In addition, some drugs rank higher for addressing individual symptoms.

“Gastroparesis has a substantial impact on quality of life and societal functioning for patients, and the costs to the health service are high,” Alexander Ford, MBChB, MD, a professor of gastroenterology and honorary consultant gastroenterologist at the Leeds (England) Institute of Medical Research at St. James’s, University of Leeds, said in an interview.

“There are very few licensed therapies, but some novel drugs are in the pipeline, some existing drugs that are licensed for other conditions could be repurposed if efficacious, and some older drugs that have safety concerns may be beneficial,” he said. “Given the impact on patients and their symptoms, they may be willing to accept these safety risks in return for symptom improvement.”

Only one drug, the dopamine antagonist metoclopramide, has Food and Drug Administration approval for the treatment of gastroparesis, noted Dr. Ford and colleagues. The lack of other recommended drugs or new medications has resulted in off-label use of drugs in other classes.

The study was published online in Gastroenterology.
 

Investigating treatments

To address the lack of evidence supporting the efficacy and safety of licensed and unlicensed drugs for the condition, the researchers conducted a systematic review and network meta-analysis of randomized controlled trials of drugs for gastroparesis dating from 1947 to September 2022. The trials involved more than dozen drugs in several classes.

They determined drug efficacy on the basis of global symptoms of gastroparesis and individual symptoms such as nausea, vomiting, abdominal pain, bloating, or fullness. They judged safety on the basis of total adverse events and adverse events leading to withdrawal.

The research team extracted data as intention-to-treat analyses, assuming dropouts to be treatment failures. They reported efficacy as a pooled relative risk of symptoms not improving and ranked the drugs according to P-score.

The analysis included 29 randomized controlled trials with 3,772 patients. Only four trials were at low risk of bias.

Overall, only two drug classes were considered efficacious: oral dopamine antagonists (RR, 0.58; P-score, 0.96) and tachykinin-1 antagonists (RR, 0.69; P-score, 0.83).

On the basis of 25 trials that reported on global symptoms, clebopride ranked first for efficacy (RR, 0.30; P-score, 0.99), followed by domperidone (RR, 0.69; P-score, 0.76). None of the other drugs were superior to the placebo. After direct and indirect comparisons, clebopride was superior to all other drugs except aprepitant.

After excluding three trials with a placebo run-in and a trial where only responders to single-blind domperidone were randomized, the researchers analyzed 21 trials with 2,233 patients. In this analysis, domperidone ranked first (RR, 0.48; P-score, 0.93), followed by oral metoclopramide (RR, 0.54; P-score, 0.87). None of the other drugs were superior to placebo.

Among 16 trials, including 1,381 patients, that confirmed delayed gastric emptying among all participants, only clebopride and metoclopramide were more efficacious than placebo. Clebopride ranked first (RR, 0.30; P-score, 0.95) and metoclopramide ranked third (RR, 0.48).

Among 13 trials with 785 patients with diabetic gastroparesis, none of the active drugs were superior to placebo. Among 12 trials recruiting patients with idiopathic or mixed etiology gastroparesis, clebopride ranked first (RR, 0.30; P-score, 0.93).

On the basis of trials that assessed individual symptoms, oral metoclopramide ranked first for nausea (RR, 0.46; P-score, 0.95), fullness (RR, 0.67; P-score, 0.86), and bloating (RR, 0.53; P-score, 0.97). However, the data came from one small trial. Tradipitant and TZP-102, a ghrelin agonist, were efficacious for nausea, and TZP-102 ranked second for fullness. No drugs were more efficacious than the placebo for abdominal pain or vomiting.

Among 20 trials that reported on the total number of adverse events, camicinal was the least likely to be associated with adverse events (RR, 0.77; P-score, 0.93) and prucalopride was the most likely to be associated with adverse events (RR, 2.96; P-score, 0.10). Prucalopride, oral metoclopramide, and aprepitant also were more likely than placebo to be associated with adverse events.

In 23 trials that reported on withdrawals caused by adverse events, camicinal was the least likely to be associated with withdrawals (RR, 0.20; P-score, 0.87). Nortriptyline was the most likely to be associated with withdrawals (RR, 3.33; P-score, 0.16). However, there were no significant differences between any individual drug and placebo.
 

Urgent need remains

More trials of drugs to treat gastroparesis are needed, Ford said.

“We need to consider the reintroduction of dopamine antagonists, if patients are willing to accept the safety concerns,” he added. “The other important point is most drugs were not of benefit. There is an urgent need to find efficacious therapies, and these should be fast-tracked for licensing approval if efficacy is proven.”

The study is “helpful for practicing clinicians since it provides a comprehensive review of clinical trials in gastroparesis,” Anthony Lembo, MD, a gastroenterologist at the Cleveland Clinic, said in an interview.

Dr. Lembo, who wasn’t involved with this study, has researched several drugs for gastroparesis, including relamorelin and TZP-102. He agreed that additional research is needed.

“There is a paucity of novel treatments currently in development,” he said. “However, there is interest in developing a product similar to domperidone without cardiac side effects, as well as performing larger studies with botulinum toxin injection.”

The authors did not disclose a funding source for the study. One author disclosed research funding from the National Institutes of Health and consulting roles with various pharmaceutical companies. Ford and the other authors reported no disclosures. Dr. Lembo reported no relevant disclosures.

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

The assessment and diagnosis of bipolar disorder in youth has a complicated and controversial history. I recall from my child and adolescent fellowship training that there was a thinly veiled faculty argument about the diagnosis itself with strong opinions on each side. To revisit this quandary, I reviewed the most up-to-date literature and outlined a case-based approach to the initial screening assessment. Certainly, the assessment by a child and adolescent psychiatrist would be the standard for diagnosis, but we do know that the pediatrician’s office may be the first setting for a child and parent to present with mood symptoms and concerns about bipolar disorder. What can you do to address this adolescent, Carrie, and her mother’s concerns?

Case

Carrie is a 17-year-old girl who has struggled through her childhood and adolescence with anxious and depressive symptoms which have ebbed and flowed with major life stressors, including her parent’s divorce. She has tried cognitive-behavioral therapy and selective serotonin reuptake inhibitors, but the SSRI seemed to cause feelings of anxiousness and agitation, so she stopped it within weeks.

Her mother presents to you concerned that Carrie has had a more persistently irritable mood toward her, often just wanting to be with her friends or otherwise isolate in her room when home to study.

Most concerning to her mother is that Carrie, as a straight A student, has also developed a pattern of staying up all night to study for tests and then “crashes” and sleeps through the weekend, avoiding her mother and only brightening with her friends.

To complicate matters, Carrie’s biological father had type 1 bipolar disorder and an addiction. Her mother comes to you with an initially nonparticipatory Carrie in tow and says: “My former husband began his manic episodes with a lack of sleep and Carrie is so irritable towards me. I feel like I am walking on eggshells all the time. Could this be bipolar disorder?”
 

Case discussion

First, it’s always useful to frame a visit stating that you will spend some time with the patient and some time with both the patient and parent. Emphasizing confidentiality about issues such as drug use, which can be comorbid with mood symptoms and go undetected in high-achieving students such as Carrie, is also important. Further emphasizing that information will not be reflexively shared with the parent unless the child presents a danger to herself or others is also paramount to receive an honest report of symptoms.

Second, there are many signs and symptoms of bipolar disorder that naturally overlap with other conditions such as distractibility with attention-deficit/hyperactivity disorder, or irritability in either a unipolar depression or disruptive mood dysregulation disorder.1 You are looking for an episodic (not chronic) course of symptoms with episodes that last over 5 days for hypomania and over the course of weeks for mania all while meeting all the classic criteria for bipolar disorder.

Note that the broadening of diagnostic criteria has been thought to contribute to an inflated sense of prevalence. The actual expert estimate of prevalence is around 0.8%-1.8% in pediatric populations, although there is a large published range depending on whether the criteria are modified or not.2 Use of the unmodified criteria from the DSM-5 is the recommended approach. Bipolar disorder is exceedingly rare in prepubertal children, and it would be more common for prodromal symptoms such as Carrie’s to emerge and escalate over the teenage years, culminating in a clearer diagnosis in the later teens or 20s.3

In my screening questions, I find the idea of an “infatiguable state” is the most pathognomonic one in considering mania in bipolar disorder.4 Carrie’s “crashing” after nights of studying shows that she clearly fatigues. Patients with bipolar disorder within episodes of hypomania or mania have a seismic shift in perceived energy and a matching lack of ability to sleep that can affect their thought processes, speech, and decision-making. At first blush, Carrie’s history does not indicate current symptoms of bipolar disorder.3
 

Case, continued

When you meet with Carrie alone she shares that she has been experimenting with prescribed stimulants from her older college-aged brother in order to study and ace her tests. She is also experimenting with alcohol and marijuana with her friends. You provide her the CRAFFT tool to deepen your screening of this issue.5

With her mother, you administer the Parent General Behavior Inventory6 and the and the Child Mania Rating Scale7. From these scales, you note that the irritability is more specific to Carrie’s family than pan-present in school and with friends. Her lack of sleep occurs at high-pressure and discreet times.

At this point, you reassure Carrie and her mother that Carrie does not present with symptoms of bipolar disorder but that certainly you will continue screening assessments over time, as they are a good means to track symptoms. You also recommend that Carrie consider mood tracking so she can develop insights into her mood and its relationship to sleep and other events as she prepares for college.8
 

Case discussion, continued

The strongest risk factor for bipolar disorder in youth is family history (specifically a parent) with bipolar disorder).9 If there is the chance to explore the parent’s illness with open-ended questions, you will want to hear about the parent’s age of symptom onset, course of treatment, any hospitalizations, and stabilizing medications because this has prognostic power for your patient. It is important to ensure that the parent indeed has a diagnosis of bipolar disorder and that it is not just being used colloquially to characterize an adult who has labile moods from hour to hour or day to day. This would give undue anticipatory anxiety to a youth about their risk, which is up to 8- to 10-fold greater with a parent with bipolar disorder.9

Even with a strong family history, we do not often see bipolar disorder emerge in prepubertal children.10,11 There may be still concerning prodromal symptoms in which a diagnosis of unipolar depression with more irritable features and mood lability seems more commonly complicated by substance use, as with Carrie.

Activation with an SSRI, as in Carrie’s case, even if not resulting in full mania or hypomania, can also be a soft sign of the serotonergic sensitivity present in bipolar disorder. However, if there are not additional symptoms of bipolar disorder and you are concerned based on family history alone, you do not want to withhold antidepressant treatment because fear of risk. You would want to consider a “dose low and go slow” titration process with more frequent monitoring.

A diagnostic interview with a child and adolescent psychiatrist and administration of scales such as the Young Mania Rating Scale and the Modified Child Depression Rating Scale are the standard means to assess for bipolar symptoms.12 Considering the dearth of child psychiatrists nationally, it would be useful to improve one’s screening in primary care so as to not inadvertently “refer out” all patients for whom mood dysregulation is a concern.

There is also a more expanded tool that includes several scales integrated with clinical information (parent’s age of mood disorder onset, child’s age) which can culminate in a risk score.13

Lastly, I provide my patients with a handout of the Young Mania Rating Scale to take home as a reference and to complete before our next visit.14

You can repeat scales to monitor for more striking bipolar disorder signs and symptoms that emerge over the course of one’s longitudinal treatment of a pediatric patient. This can be an ongoing, episodic assessment since the emergence of bipolar disorder has been shown to range from the teenage years and beyond into the 20s and sometimes 30s.
 

Case, continued

Carrie presents to you again while in her first semester of college at the age of 19. She is taking a leave of absence after she began experimenting with cocaine at college and had a manic episode characterized by a lack of sleep without fatigue, persistent unabating energy, rapid and pressured speech, and ultimately, concern from her college friends. She was admitted to a psychiatric unit and stabilized on a second-generation antipsychotic, risperidone, which has solid evidence for mania, but she and you are now concerned about longer-term metabolic effects.15,16

You discuss monitoring her lipid profile and hemoglobin A1c, in addition to weight gain and waist circumference. She has connected with a therapist and psychiatrist through the college counseling center and hopes to return next semester with a fresh start and commitment to sobriety and social rhythms therapy known to be helpful for patients with bipolar disorder.17

While it is challenging to manage a chronic illness at her age, she feels hopeful that she can make better choices for her overall health with your support and the support of her family and mental health team.

Dr. Pawlowski is a child and adolescent consulting psychiatrist. She is a division chief at the University of Vermont Medical Center, Burlington, where she focuses on primary care mental health integration within primary care pediatrics, internal medicine, and family medicine.
 

References

1. Bipolar Disord. 2016 Jan 9 doi: 10.1111/bdi.12358.

2. Int J Bipolar Disord. 2021 Jun 25. doi: 10.1186/s40345-021-00225-5.

3. Am J Psychiatry. 2018 Dec 11. doi: 10.1176/appi.ajp.2018.18040461.

4. DSM-5 Changes: Implications for Child Serious Emotional Disturbance. Rockville, Md.: Substance Abuse and Mental Health Services Administration, 2016.

5. The CRAFFT tool.

6. General Behavior Inventory. Parent Version (P-GBI) Short Form – H/B (Revised Version, 2008).

7. Child Mania Rating Scale, Parent Version (CMRS-P).

8. https://www.moodtracker.com.

9. J Clin Psychiatry. 2000 Sep. doi: 10.4088/jcp.v61n0906.

10. Int J Bipolar Disord. 2020 Apr 20. doi: 10.1186/s40345-020-00185-2.

11. Int J Bipolar Disord. 2021 Jun 25. doi: 10.1186/s40345-021-00225-5.

12. Bipolar Disord. 2017 Sep 25. doi: 10.1111/bdi.12556.

13. www.cabsresearch.pitt.edu/bpriskcalculator/.

14. Parent Version of the Young Mania Rating Scale (PYMRS).

15. Arch Gen Psychiatry. 2012 Jan 2. doi: 10.1001/archgenpsychiatry.2011.1508.

16. The Carlat Child Psychiatry Report. “Bipolar Disorder” Newburyport, Mass.: Carlat Publishing, 2012.

17. https://www.ipsrt.org/.

The assessment and diagnosis of bipolar disorder in youth has a complicated and controversial history. I recall from my child and adolescent fellowship training that there was a thinly veiled faculty argument about the diagnosis itself with strong opinions on each side. To revisit this quandary, I reviewed the most up-to-date literature and outlined a case-based approach to the initial screening assessment. Certainly, the assessment by a child and adolescent psychiatrist would be the standard for diagnosis, but we do know that the pediatrician’s office may be the first setting for a child and parent to present with mood symptoms and concerns about bipolar disorder. What can you do to address this adolescent, Carrie, and her mother’s concerns?

Case

Carrie is a 17-year-old girl who has struggled through her childhood and adolescence with anxious and depressive symptoms which have ebbed and flowed with major life stressors, including her parent’s divorce. She has tried cognitive-behavioral therapy and selective serotonin reuptake inhibitors, but the SSRI seemed to cause feelings of anxiousness and agitation, so she stopped it within weeks.

Her mother presents to you concerned that Carrie has had a more persistently irritable mood toward her, often just wanting to be with her friends or otherwise isolate in her room when home to study.

Most concerning to her mother is that Carrie, as a straight A student, has also developed a pattern of staying up all night to study for tests and then “crashes” and sleeps through the weekend, avoiding her mother and only brightening with her friends.

To complicate matters, Carrie’s biological father had type 1 bipolar disorder and an addiction. Her mother comes to you with an initially nonparticipatory Carrie in tow and says: “My former husband began his manic episodes with a lack of sleep and Carrie is so irritable towards me. I feel like I am walking on eggshells all the time. Could this be bipolar disorder?”
 

Case discussion

First, it’s always useful to frame a visit stating that you will spend some time with the patient and some time with both the patient and parent. Emphasizing confidentiality about issues such as drug use, which can be comorbid with mood symptoms and go undetected in high-achieving students such as Carrie, is also important. Further emphasizing that information will not be reflexively shared with the parent unless the child presents a danger to herself or others is also paramount to receive an honest report of symptoms.

Second, there are many signs and symptoms of bipolar disorder that naturally overlap with other conditions such as distractibility with attention-deficit/hyperactivity disorder, or irritability in either a unipolar depression or disruptive mood dysregulation disorder.1 You are looking for an episodic (not chronic) course of symptoms with episodes that last over 5 days for hypomania and over the course of weeks for mania all while meeting all the classic criteria for bipolar disorder.

Note that the broadening of diagnostic criteria has been thought to contribute to an inflated sense of prevalence. The actual expert estimate of prevalence is around 0.8%-1.8% in pediatric populations, although there is a large published range depending on whether the criteria are modified or not.2 Use of the unmodified criteria from the DSM-5 is the recommended approach. Bipolar disorder is exceedingly rare in prepubertal children, and it would be more common for prodromal symptoms such as Carrie’s to emerge and escalate over the teenage years, culminating in a clearer diagnosis in the later teens or 20s.3

In my screening questions, I find the idea of an “infatiguable state” is the most pathognomonic one in considering mania in bipolar disorder.4 Carrie’s “crashing” after nights of studying shows that she clearly fatigues. Patients with bipolar disorder within episodes of hypomania or mania have a seismic shift in perceived energy and a matching lack of ability to sleep that can affect their thought processes, speech, and decision-making. At first blush, Carrie’s history does not indicate current symptoms of bipolar disorder.3
 

Case, continued

When you meet with Carrie alone she shares that she has been experimenting with prescribed stimulants from her older college-aged brother in order to study and ace her tests. She is also experimenting with alcohol and marijuana with her friends. You provide her the CRAFFT tool to deepen your screening of this issue.5

With her mother, you administer the Parent General Behavior Inventory6 and the and the Child Mania Rating Scale7. From these scales, you note that the irritability is more specific to Carrie’s family than pan-present in school and with friends. Her lack of sleep occurs at high-pressure and discreet times.

At this point, you reassure Carrie and her mother that Carrie does not present with symptoms of bipolar disorder but that certainly you will continue screening assessments over time, as they are a good means to track symptoms. You also recommend that Carrie consider mood tracking so she can develop insights into her mood and its relationship to sleep and other events as she prepares for college.8
 

Case discussion, continued

The strongest risk factor for bipolar disorder in youth is family history (specifically a parent) with bipolar disorder).9 If there is the chance to explore the parent’s illness with open-ended questions, you will want to hear about the parent’s age of symptom onset, course of treatment, any hospitalizations, and stabilizing medications because this has prognostic power for your patient. It is important to ensure that the parent indeed has a diagnosis of bipolar disorder and that it is not just being used colloquially to characterize an adult who has labile moods from hour to hour or day to day. This would give undue anticipatory anxiety to a youth about their risk, which is up to 8- to 10-fold greater with a parent with bipolar disorder.9

Even with a strong family history, we do not often see bipolar disorder emerge in prepubertal children.10,11 There may be still concerning prodromal symptoms in which a diagnosis of unipolar depression with more irritable features and mood lability seems more commonly complicated by substance use, as with Carrie.

Activation with an SSRI, as in Carrie’s case, even if not resulting in full mania or hypomania, can also be a soft sign of the serotonergic sensitivity present in bipolar disorder. However, if there are not additional symptoms of bipolar disorder and you are concerned based on family history alone, you do not want to withhold antidepressant treatment because fear of risk. You would want to consider a “dose low and go slow” titration process with more frequent monitoring.

A diagnostic interview with a child and adolescent psychiatrist and administration of scales such as the Young Mania Rating Scale and the Modified Child Depression Rating Scale are the standard means to assess for bipolar symptoms.12 Considering the dearth of child psychiatrists nationally, it would be useful to improve one’s screening in primary care so as to not inadvertently “refer out” all patients for whom mood dysregulation is a concern.

There is also a more expanded tool that includes several scales integrated with clinical information (parent’s age of mood disorder onset, child’s age) which can culminate in a risk score.13

Lastly, I provide my patients with a handout of the Young Mania Rating Scale to take home as a reference and to complete before our next visit.14

You can repeat scales to monitor for more striking bipolar disorder signs and symptoms that emerge over the course of one’s longitudinal treatment of a pediatric patient. This can be an ongoing, episodic assessment since the emergence of bipolar disorder has been shown to range from the teenage years and beyond into the 20s and sometimes 30s.
 

Case, continued

Carrie presents to you again while in her first semester of college at the age of 19. She is taking a leave of absence after she began experimenting with cocaine at college and had a manic episode characterized by a lack of sleep without fatigue, persistent unabating energy, rapid and pressured speech, and ultimately, concern from her college friends. She was admitted to a psychiatric unit and stabilized on a second-generation antipsychotic, risperidone, which has solid evidence for mania, but she and you are now concerned about longer-term metabolic effects.15,16

You discuss monitoring her lipid profile and hemoglobin A1c, in addition to weight gain and waist circumference. She has connected with a therapist and psychiatrist through the college counseling center and hopes to return next semester with a fresh start and commitment to sobriety and social rhythms therapy known to be helpful for patients with bipolar disorder.17

While it is challenging to manage a chronic illness at her age, she feels hopeful that she can make better choices for her overall health with your support and the support of her family and mental health team.

Dr. Pawlowski is a child and adolescent consulting psychiatrist. She is a division chief at the University of Vermont Medical Center, Burlington, where she focuses on primary care mental health integration within primary care pediatrics, internal medicine, and family medicine.
 

References

1. Bipolar Disord. 2016 Jan 9 doi: 10.1111/bdi.12358.

2. Int J Bipolar Disord. 2021 Jun 25. doi: 10.1186/s40345-021-00225-5.

3. Am J Psychiatry. 2018 Dec 11. doi: 10.1176/appi.ajp.2018.18040461.

4. DSM-5 Changes: Implications for Child Serious Emotional Disturbance. Rockville, Md.: Substance Abuse and Mental Health Services Administration, 2016.

5. The CRAFFT tool.

6. General Behavior Inventory. Parent Version (P-GBI) Short Form – H/B (Revised Version, 2008).

7. Child Mania Rating Scale, Parent Version (CMRS-P).

8. https://www.moodtracker.com.

9. J Clin Psychiatry. 2000 Sep. doi: 10.4088/jcp.v61n0906.

10. Int J Bipolar Disord. 2020 Apr 20. doi: 10.1186/s40345-020-00185-2.

11. Int J Bipolar Disord. 2021 Jun 25. doi: 10.1186/s40345-021-00225-5.

12. Bipolar Disord. 2017 Sep 25. doi: 10.1111/bdi.12556.

13. www.cabsresearch.pitt.edu/bpriskcalculator/.

14. Parent Version of the Young Mania Rating Scale (PYMRS).

15. Arch Gen Psychiatry. 2012 Jan 2. doi: 10.1001/archgenpsychiatry.2011.1508.

16. The Carlat Child Psychiatry Report. “Bipolar Disorder” Newburyport, Mass.: Carlat Publishing, 2012.

17. https://www.ipsrt.org/.

The assessment and diagnosis of bipolar disorder in youth has a complicated and controversial history. I recall from my child and adolescent fellowship training that there was a thinly veiled faculty argument about the diagnosis itself with strong opinions on each side. To revisit this quandary, I reviewed the most up-to-date literature and outlined a case-based approach to the initial screening assessment. Certainly, the assessment by a child and adolescent psychiatrist would be the standard for diagnosis, but we do know that the pediatrician’s office may be the first setting for a child and parent to present with mood symptoms and concerns about bipolar disorder. What can you do to address this adolescent, Carrie, and her mother’s concerns?

Case

Carrie is a 17-year-old girl who has struggled through her childhood and adolescence with anxious and depressive symptoms which have ebbed and flowed with major life stressors, including her parent’s divorce. She has tried cognitive-behavioral therapy and selective serotonin reuptake inhibitors, but the SSRI seemed to cause feelings of anxiousness and agitation, so she stopped it within weeks.

Her mother presents to you concerned that Carrie has had a more persistently irritable mood toward her, often just wanting to be with her friends or otherwise isolate in her room when home to study.

Most concerning to her mother is that Carrie, as a straight A student, has also developed a pattern of staying up all night to study for tests and then “crashes” and sleeps through the weekend, avoiding her mother and only brightening with her friends.

To complicate matters, Carrie’s biological father had type 1 bipolar disorder and an addiction. Her mother comes to you with an initially nonparticipatory Carrie in tow and says: “My former husband began his manic episodes with a lack of sleep and Carrie is so irritable towards me. I feel like I am walking on eggshells all the time. Could this be bipolar disorder?”
 

Case discussion

First, it’s always useful to frame a visit stating that you will spend some time with the patient and some time with both the patient and parent. Emphasizing confidentiality about issues such as drug use, which can be comorbid with mood symptoms and go undetected in high-achieving students such as Carrie, is also important. Further emphasizing that information will not be reflexively shared with the parent unless the child presents a danger to herself or others is also paramount to receive an honest report of symptoms.

Second, there are many signs and symptoms of bipolar disorder that naturally overlap with other conditions such as distractibility with attention-deficit/hyperactivity disorder, or irritability in either a unipolar depression or disruptive mood dysregulation disorder.1 You are looking for an episodic (not chronic) course of symptoms with episodes that last over 5 days for hypomania and over the course of weeks for mania all while meeting all the classic criteria for bipolar disorder.

Note that the broadening of diagnostic criteria has been thought to contribute to an inflated sense of prevalence. The actual expert estimate of prevalence is around 0.8%-1.8% in pediatric populations, although there is a large published range depending on whether the criteria are modified or not.2 Use of the unmodified criteria from the DSM-5 is the recommended approach. Bipolar disorder is exceedingly rare in prepubertal children, and it would be more common for prodromal symptoms such as Carrie’s to emerge and escalate over the teenage years, culminating in a clearer diagnosis in the later teens or 20s.3

In my screening questions, I find the idea of an “infatiguable state” is the most pathognomonic one in considering mania in bipolar disorder.4 Carrie’s “crashing” after nights of studying shows that she clearly fatigues. Patients with bipolar disorder within episodes of hypomania or mania have a seismic shift in perceived energy and a matching lack of ability to sleep that can affect their thought processes, speech, and decision-making. At first blush, Carrie’s history does not indicate current symptoms of bipolar disorder.3
 

Case, continued

When you meet with Carrie alone she shares that she has been experimenting with prescribed stimulants from her older college-aged brother in order to study and ace her tests. She is also experimenting with alcohol and marijuana with her friends. You provide her the CRAFFT tool to deepen your screening of this issue.5

With her mother, you administer the Parent General Behavior Inventory6 and the and the Child Mania Rating Scale7. From these scales, you note that the irritability is more specific to Carrie’s family than pan-present in school and with friends. Her lack of sleep occurs at high-pressure and discreet times.

At this point, you reassure Carrie and her mother that Carrie does not present with symptoms of bipolar disorder but that certainly you will continue screening assessments over time, as they are a good means to track symptoms. You also recommend that Carrie consider mood tracking so she can develop insights into her mood and its relationship to sleep and other events as she prepares for college.8
 

Case discussion, continued

The strongest risk factor for bipolar disorder in youth is family history (specifically a parent) with bipolar disorder).9 If there is the chance to explore the parent’s illness with open-ended questions, you will want to hear about the parent’s age of symptom onset, course of treatment, any hospitalizations, and stabilizing medications because this has prognostic power for your patient. It is important to ensure that the parent indeed has a diagnosis of bipolar disorder and that it is not just being used colloquially to characterize an adult who has labile moods from hour to hour or day to day. This would give undue anticipatory anxiety to a youth about their risk, which is up to 8- to 10-fold greater with a parent with bipolar disorder.9

Even with a strong family history, we do not often see bipolar disorder emerge in prepubertal children.10,11 There may be still concerning prodromal symptoms in which a diagnosis of unipolar depression with more irritable features and mood lability seems more commonly complicated by substance use, as with Carrie.

Activation with an SSRI, as in Carrie’s case, even if not resulting in full mania or hypomania, can also be a soft sign of the serotonergic sensitivity present in bipolar disorder. However, if there are not additional symptoms of bipolar disorder and you are concerned based on family history alone, you do not want to withhold antidepressant treatment because fear of risk. You would want to consider a “dose low and go slow” titration process with more frequent monitoring.

A diagnostic interview with a child and adolescent psychiatrist and administration of scales such as the Young Mania Rating Scale and the Modified Child Depression Rating Scale are the standard means to assess for bipolar symptoms.12 Considering the dearth of child psychiatrists nationally, it would be useful to improve one’s screening in primary care so as to not inadvertently “refer out” all patients for whom mood dysregulation is a concern.

There is also a more expanded tool that includes several scales integrated with clinical information (parent’s age of mood disorder onset, child’s age) which can culminate in a risk score.13

Lastly, I provide my patients with a handout of the Young Mania Rating Scale to take home as a reference and to complete before our next visit.14

You can repeat scales to monitor for more striking bipolar disorder signs and symptoms that emerge over the course of one’s longitudinal treatment of a pediatric patient. This can be an ongoing, episodic assessment since the emergence of bipolar disorder has been shown to range from the teenage years and beyond into the 20s and sometimes 30s.
 

Case, continued

Carrie presents to you again while in her first semester of college at the age of 19. She is taking a leave of absence after she began experimenting with cocaine at college and had a manic episode characterized by a lack of sleep without fatigue, persistent unabating energy, rapid and pressured speech, and ultimately, concern from her college friends. She was admitted to a psychiatric unit and stabilized on a second-generation antipsychotic, risperidone, which has solid evidence for mania, but she and you are now concerned about longer-term metabolic effects.15,16

You discuss monitoring her lipid profile and hemoglobin A1c, in addition to weight gain and waist circumference. She has connected with a therapist and psychiatrist through the college counseling center and hopes to return next semester with a fresh start and commitment to sobriety and social rhythms therapy known to be helpful for patients with bipolar disorder.17

While it is challenging to manage a chronic illness at her age, she feels hopeful that she can make better choices for her overall health with your support and the support of her family and mental health team.

Dr. Pawlowski is a child and adolescent consulting psychiatrist. She is a division chief at the University of Vermont Medical Center, Burlington, where she focuses on primary care mental health integration within primary care pediatrics, internal medicine, and family medicine.
 

References

1. Bipolar Disord. 2016 Jan 9 doi: 10.1111/bdi.12358.

2. Int J Bipolar Disord. 2021 Jun 25. doi: 10.1186/s40345-021-00225-5.

3. Am J Psychiatry. 2018 Dec 11. doi: 10.1176/appi.ajp.2018.18040461.

4. DSM-5 Changes: Implications for Child Serious Emotional Disturbance. Rockville, Md.: Substance Abuse and Mental Health Services Administration, 2016.

5. The CRAFFT tool.

6. General Behavior Inventory. Parent Version (P-GBI) Short Form – H/B (Revised Version, 2008).

7. Child Mania Rating Scale, Parent Version (CMRS-P).

8. https://www.moodtracker.com.

9. J Clin Psychiatry. 2000 Sep. doi: 10.4088/jcp.v61n0906.

10. Int J Bipolar Disord. 2020 Apr 20. doi: 10.1186/s40345-020-00185-2.

11. Int J Bipolar Disord. 2021 Jun 25. doi: 10.1186/s40345-021-00225-5.

12. Bipolar Disord. 2017 Sep 25. doi: 10.1111/bdi.12556.

13. www.cabsresearch.pitt.edu/bpriskcalculator/.

14. Parent Version of the Young Mania Rating Scale (PYMRS).

15. Arch Gen Psychiatry. 2012 Jan 2. doi: 10.1001/archgenpsychiatry.2011.1508.

16. The Carlat Child Psychiatry Report. “Bipolar Disorder” Newburyport, Mass.: Carlat Publishing, 2012.

17. https://www.ipsrt.org/.

A program to increase the use of magnesium sulfate to reduce the risk of cerebral palsy is effective, say researchers. Giving magnesium sulfate to women at risk of premature birth can reduce the risk of a child having cerebral palsy by a third, and costs just £1 per dose.

However, the authors of the new observational study, published in Archives of Disease in Childhood – Fetal and Neonatal Edition, pointed out that in 2017 only around two-thirds (64%) of eligible women were being given magnesium sulfate in England, Scotland, and Wales, with “wide regional variations.”

To address this, in 2014 the PReCePT (Preventing Cerebral Palsy in Pre Term labor) quality improvement toolkit was developed by both parents and staff with the aim of supporting all maternity units in England to improve maternity staff awareness and increase the use of magnesium sulfate in mothers at risk of giving birth at 30 weeks’ gestation or under. PReCePT provided practical tools and training to support hospital staff to give magnesium sulfate to eligible mothers.

The pilot study in 2015, which involved five maternity units, found an increase in uptake from 21% to 88% associated with the PReCePT approach. Subsequently, in 2018, NHS England funded the National PReCePT Programme, which scaled up the intervention for national roll-out and provided the PReCePT quality toolkit – which includes preterm labor proforma, staff training presentations, parent information leaflet, posters for the unit, and a learning log – to each maternity unit.
 

Improvement ‘over and above’ expectation

For the first evaluation of a U.K. universally implemented national perinatal quality improvement program to increase administration of an evidence-based drug, researchers, led by University of Bristol, England, set out to evaluate the effectiveness and cost-effectiveness of the National PReCePT Programme in increasing use of magnesium sulfate in preterm births.

Using data from the U.K. National Neonatal Research Database for the year before and the year after PReCePT was implemented in maternity units in England, the researchers performed a before-and-after study that involved 137 maternity units within NHS England. Participants were babies born at 30 weeks’ gestation or under admitted to neonatal units in England, and the main outcome measure was magnesium sulfate uptake before and after the implementation of the National PReCePT Programme. In addition, implementation and lifetime costs were estimated.

During the first year, post implementation of the program, uptake increased by an average of 6.3 percentage points (to 83.1%) across all maternity units in England, which the authors explained was “over and above” the increase that would be expected over time as the practice spread organically. The researchers also found that after adjusting for variations in when maternity units started the program, the increase in use of magnesium sulfate was 9.5 percentage points. “By May 2020, on average 86.4% of eligible mothers were receiving magnesium sulfate,” they said.

Professor John Macleod, NIHR ARC West Director, professor in clinical epidemiology and primary care, University of Bristol, and principal investigator of the evaluation, said: “Our in-depth analysis has been able to demonstrate that the PReCePT program is both effective and cost-effective. The program has increased uptake of magnesium sulfate, which we know is a cost-effective medicine to prevent cerebral palsy, much more quickly than we could have otherwise expected.”

From a societal and lifetime perspective, the health gains and cost savings associated with the National PReCePT Programme generated a “net monetary benefit of £866 per preterm baby,” with the probability of the program being cost-effective being “greater than 95%,” the authors highlighted.

The researchers also estimated that the program’s first year could be associated with a lifetime saving to society of £3 million – which accounts for the costs of the program, of administering the treatment, of cerebral palsy to society over a lifetime, and the associated health gains of avoiding cases. “This is across all the extra babies the program helped get access to the treatment during the first year,” they said.

The authors highlighted that in the five pilot sites, the improved use of magnesium sulfate has been “sustained over the years” since PReCePT was implemented. As the program costs were mostly in the first year of implementation, longer-term national analysis may show that PReCePT is “even more cost-effective over a longer period,” they postulated.
 

Accelerate uptake

Uptake of new evidence or guidelines is often “slow” due to practical barriers, lack of knowledge, and need for behavior change, and can “take decades to become embedded” in perinatal clinical practice, expressed the authors, which in turn comes at a “high clinical and economic cost.”

Karen Luyt, professor in neonatal medicine, University of Bristol, said: “The PReCePT national quality improvement program demonstrates that a collaborative and coordinated perinatal implementation program supporting every hospital in England can accelerate the uptake of new evidence-based treatments into routine practice, enabling equitable health benefits to babies and ultimately reductions in lifetime societal costs.”

The authors said the PReCePT model “may serve as a blueprint for future interventions to improve perinatal care.”

Professor Lucy Chappell, chief executive officer of the National Institute for Health and Care Research, said: “This important study shows the impact of taking a promising intervention that had been shown to work in a research setting and scaling it up across the country. Giving magnesium sulfate to prevent cerebral palsy in premature babies is a simple, inexpensive intervention that can make such a difference to families and the health service.”

Prof. Macleod added: “We are pleased to have played a part in helping get this cheap yet effective treatment to more babies.”

This work was jointly funded by the National Institute for Health and Care Research Applied Research Collaboration West and the AHSN Network funded by NHS England. The Health Foundation funded the health economics evaluation. The authors declare that the study management group has no competing financial, professional, or personal interests that might have influenced the study design or conduct.

A version of this article first appeared on Medscape UK.

A program to increase the use of magnesium sulfate to reduce the risk of cerebral palsy is effective, say researchers. Giving magnesium sulfate to women at risk of premature birth can reduce the risk of a child having cerebral palsy by a third, and costs just £1 per dose.

However, the authors of the new observational study, published in Archives of Disease in Childhood – Fetal and Neonatal Edition, pointed out that in 2017 only around two-thirds (64%) of eligible women were being given magnesium sulfate in England, Scotland, and Wales, with “wide regional variations.”

To address this, in 2014 the PReCePT (Preventing Cerebral Palsy in Pre Term labor) quality improvement toolkit was developed by both parents and staff with the aim of supporting all maternity units in England to improve maternity staff awareness and increase the use of magnesium sulfate in mothers at risk of giving birth at 30 weeks’ gestation or under. PReCePT provided practical tools and training to support hospital staff to give magnesium sulfate to eligible mothers.

The pilot study in 2015, which involved five maternity units, found an increase in uptake from 21% to 88% associated with the PReCePT approach. Subsequently, in 2018, NHS England funded the National PReCePT Programme, which scaled up the intervention for national roll-out and provided the PReCePT quality toolkit – which includes preterm labor proforma, staff training presentations, parent information leaflet, posters for the unit, and a learning log – to each maternity unit.
 

Improvement ‘over and above’ expectation

For the first evaluation of a U.K. universally implemented national perinatal quality improvement program to increase administration of an evidence-based drug, researchers, led by University of Bristol, England, set out to evaluate the effectiveness and cost-effectiveness of the National PReCePT Programme in increasing use of magnesium sulfate in preterm births.

Using data from the U.K. National Neonatal Research Database for the year before and the year after PReCePT was implemented in maternity units in England, the researchers performed a before-and-after study that involved 137 maternity units within NHS England. Participants were babies born at 30 weeks’ gestation or under admitted to neonatal units in England, and the main outcome measure was magnesium sulfate uptake before and after the implementation of the National PReCePT Programme. In addition, implementation and lifetime costs were estimated.

During the first year, post implementation of the program, uptake increased by an average of 6.3 percentage points (to 83.1%) across all maternity units in England, which the authors explained was “over and above” the increase that would be expected over time as the practice spread organically. The researchers also found that after adjusting for variations in when maternity units started the program, the increase in use of magnesium sulfate was 9.5 percentage points. “By May 2020, on average 86.4% of eligible mothers were receiving magnesium sulfate,” they said.

Professor John Macleod, NIHR ARC West Director, professor in clinical epidemiology and primary care, University of Bristol, and principal investigator of the evaluation, said: “Our in-depth analysis has been able to demonstrate that the PReCePT program is both effective and cost-effective. The program has increased uptake of magnesium sulfate, which we know is a cost-effective medicine to prevent cerebral palsy, much more quickly than we could have otherwise expected.”

From a societal and lifetime perspective, the health gains and cost savings associated with the National PReCePT Programme generated a “net monetary benefit of £866 per preterm baby,” with the probability of the program being cost-effective being “greater than 95%,” the authors highlighted.

The researchers also estimated that the program’s first year could be associated with a lifetime saving to society of £3 million – which accounts for the costs of the program, of administering the treatment, of cerebral palsy to society over a lifetime, and the associated health gains of avoiding cases. “This is across all the extra babies the program helped get access to the treatment during the first year,” they said.

The authors highlighted that in the five pilot sites, the improved use of magnesium sulfate has been “sustained over the years” since PReCePT was implemented. As the program costs were mostly in the first year of implementation, longer-term national analysis may show that PReCePT is “even more cost-effective over a longer period,” they postulated.
 

Accelerate uptake

Uptake of new evidence or guidelines is often “slow” due to practical barriers, lack of knowledge, and need for behavior change, and can “take decades to become embedded” in perinatal clinical practice, expressed the authors, which in turn comes at a “high clinical and economic cost.”

Karen Luyt, professor in neonatal medicine, University of Bristol, said: “The PReCePT national quality improvement program demonstrates that a collaborative and coordinated perinatal implementation program supporting every hospital in England can accelerate the uptake of new evidence-based treatments into routine practice, enabling equitable health benefits to babies and ultimately reductions in lifetime societal costs.”

The authors said the PReCePT model “may serve as a blueprint for future interventions to improve perinatal care.”

Professor Lucy Chappell, chief executive officer of the National Institute for Health and Care Research, said: “This important study shows the impact of taking a promising intervention that had been shown to work in a research setting and scaling it up across the country. Giving magnesium sulfate to prevent cerebral palsy in premature babies is a simple, inexpensive intervention that can make such a difference to families and the health service.”

Prof. Macleod added: “We are pleased to have played a part in helping get this cheap yet effective treatment to more babies.”

This work was jointly funded by the National Institute for Health and Care Research Applied Research Collaboration West and the AHSN Network funded by NHS England. The Health Foundation funded the health economics evaluation. The authors declare that the study management group has no competing financial, professional, or personal interests that might have influenced the study design or conduct.

A version of this article first appeared on Medscape UK.

A program to increase the use of magnesium sulfate to reduce the risk of cerebral palsy is effective, say researchers. Giving magnesium sulfate to women at risk of premature birth can reduce the risk of a child having cerebral palsy by a third, and costs just £1 per dose.

However, the authors of the new observational study, published in Archives of Disease in Childhood – Fetal and Neonatal Edition, pointed out that in 2017 only around two-thirds (64%) of eligible women were being given magnesium sulfate in England, Scotland, and Wales, with “wide regional variations.”

To address this, in 2014 the PReCePT (Preventing Cerebral Palsy in Pre Term labor) quality improvement toolkit was developed by both parents and staff with the aim of supporting all maternity units in England to improve maternity staff awareness and increase the use of magnesium sulfate in mothers at risk of giving birth at 30 weeks’ gestation or under. PReCePT provided practical tools and training to support hospital staff to give magnesium sulfate to eligible mothers.

The pilot study in 2015, which involved five maternity units, found an increase in uptake from 21% to 88% associated with the PReCePT approach. Subsequently, in 2018, NHS England funded the National PReCePT Programme, which scaled up the intervention for national roll-out and provided the PReCePT quality toolkit – which includes preterm labor proforma, staff training presentations, parent information leaflet, posters for the unit, and a learning log – to each maternity unit.
 

Improvement ‘over and above’ expectation

For the first evaluation of a U.K. universally implemented national perinatal quality improvement program to increase administration of an evidence-based drug, researchers, led by University of Bristol, England, set out to evaluate the effectiveness and cost-effectiveness of the National PReCePT Programme in increasing use of magnesium sulfate in preterm births.

Using data from the U.K. National Neonatal Research Database for the year before and the year after PReCePT was implemented in maternity units in England, the researchers performed a before-and-after study that involved 137 maternity units within NHS England. Participants were babies born at 30 weeks’ gestation or under admitted to neonatal units in England, and the main outcome measure was magnesium sulfate uptake before and after the implementation of the National PReCePT Programme. In addition, implementation and lifetime costs were estimated.

During the first year, post implementation of the program, uptake increased by an average of 6.3 percentage points (to 83.1%) across all maternity units in England, which the authors explained was “over and above” the increase that would be expected over time as the practice spread organically. The researchers also found that after adjusting for variations in when maternity units started the program, the increase in use of magnesium sulfate was 9.5 percentage points. “By May 2020, on average 86.4% of eligible mothers were receiving magnesium sulfate,” they said.

Professor John Macleod, NIHR ARC West Director, professor in clinical epidemiology and primary care, University of Bristol, and principal investigator of the evaluation, said: “Our in-depth analysis has been able to demonstrate that the PReCePT program is both effective and cost-effective. The program has increased uptake of magnesium sulfate, which we know is a cost-effective medicine to prevent cerebral palsy, much more quickly than we could have otherwise expected.”

From a societal and lifetime perspective, the health gains and cost savings associated with the National PReCePT Programme generated a “net monetary benefit of £866 per preterm baby,” with the probability of the program being cost-effective being “greater than 95%,” the authors highlighted.

The researchers also estimated that the program’s first year could be associated with a lifetime saving to society of £3 million – which accounts for the costs of the program, of administering the treatment, of cerebral palsy to society over a lifetime, and the associated health gains of avoiding cases. “This is across all the extra babies the program helped get access to the treatment during the first year,” they said.

The authors highlighted that in the five pilot sites, the improved use of magnesium sulfate has been “sustained over the years” since PReCePT was implemented. As the program costs were mostly in the first year of implementation, longer-term national analysis may show that PReCePT is “even more cost-effective over a longer period,” they postulated.
 

Accelerate uptake

Uptake of new evidence or guidelines is often “slow” due to practical barriers, lack of knowledge, and need for behavior change, and can “take decades to become embedded” in perinatal clinical practice, expressed the authors, which in turn comes at a “high clinical and economic cost.”

Karen Luyt, professor in neonatal medicine, University of Bristol, said: “The PReCePT national quality improvement program demonstrates that a collaborative and coordinated perinatal implementation program supporting every hospital in England can accelerate the uptake of new evidence-based treatments into routine practice, enabling equitable health benefits to babies and ultimately reductions in lifetime societal costs.”

The authors said the PReCePT model “may serve as a blueprint for future interventions to improve perinatal care.”

Professor Lucy Chappell, chief executive officer of the National Institute for Health and Care Research, said: “This important study shows the impact of taking a promising intervention that had been shown to work in a research setting and scaling it up across the country. Giving magnesium sulfate to prevent cerebral palsy in premature babies is a simple, inexpensive intervention that can make such a difference to families and the health service.”

Prof. Macleod added: “We are pleased to have played a part in helping get this cheap yet effective treatment to more babies.”

This work was jointly funded by the National Institute for Health and Care Research Applied Research Collaboration West and the AHSN Network funded by NHS England. The Health Foundation funded the health economics evaluation. The authors declare that the study management group has no competing financial, professional, or personal interests that might have influenced the study design or conduct.

A version of this article first appeared on Medscape UK.