SAN DIEGO – Whether hydroxyurea can avert a first stroke in children with sickle cell disease is a question that may be answered by a soon-to-be-started trial in Nigeria.

An estimated 15,000 children with sickle cell anemia have strokes each year in Nigeria, which is considered to have the largest burden of sickle cell disease in the world. Without treatment, about half of those children will have a second stroke within 2 years.

With completion of its feasibility trial results, SPIN (Primary Stroke Prevention in Children With Sickle Cell Anemia in Nigeria) will begin to examine two doses of hydroxyurea therapy, 20 mg/kg per day and 10 mg/kg per day, to determine whether the drug can prevent a first stroke in high-risk children.

In a video interview, Najibah A. Galadanci, MBBS, MPH, of Aminu Kano (Nigeria) Teaching Hospital, discusses how SPIN is addressing the unresolved clinical issue of hydroxyurea’s risks and benefits in children, and how research in Nigeria may provide adequate patient numbers to address a wide range of clinical questions about sickle cell disease.

[email protected]

On Twitter @maryjodales

SAN DIEGO – Whether hydroxyurea can avert a first stroke in children with sickle cell disease is a question that may be answered by a soon-to-be-started trial in Nigeria.

An estimated 15,000 children with sickle cell anemia have strokes each year in Nigeria, which is considered to have the largest burden of sickle cell disease in the world. Without treatment, about half of those children will have a second stroke within 2 years.

With completion of its feasibility trial results, SPIN (Primary Stroke Prevention in Children With Sickle Cell Anemia in Nigeria) will begin to examine two doses of hydroxyurea therapy, 20 mg/kg per day and 10 mg/kg per day, to determine whether the drug can prevent a first stroke in high-risk children.

In a video interview, Najibah A. Galadanci, MBBS, MPH, of Aminu Kano (Nigeria) Teaching Hospital, discusses how SPIN is addressing the unresolved clinical issue of hydroxyurea’s risks and benefits in children, and how research in Nigeria may provide adequate patient numbers to address a wide range of clinical questions about sickle cell disease.

[email protected]

On Twitter @maryjodales

SAN DIEGO – Whether hydroxyurea can avert a first stroke in children with sickle cell disease is a question that may be answered by a soon-to-be-started trial in Nigeria.

An estimated 15,000 children with sickle cell anemia have strokes each year in Nigeria, which is considered to have the largest burden of sickle cell disease in the world. Without treatment, about half of those children will have a second stroke within 2 years.

With completion of its feasibility trial results, SPIN (Primary Stroke Prevention in Children With Sickle Cell Anemia in Nigeria) will begin to examine two doses of hydroxyurea therapy, 20 mg/kg per day and 10 mg/kg per day, to determine whether the drug can prevent a first stroke in high-risk children.

In a video interview, Najibah A. Galadanci, MBBS, MPH, of Aminu Kano (Nigeria) Teaching Hospital, discusses how SPIN is addressing the unresolved clinical issue of hydroxyurea’s risks and benefits in children, and how research in Nigeria may provide adequate patient numbers to address a wide range of clinical questions about sickle cell disease.

[email protected]

On Twitter @maryjodales

Maintain a high suspicion for cardiac dysfunction and a low threshold for cardiac assessment with any patients who are survivors of adult cancers and may have received cardiotoxic therapy, a new guideline suggests.

The guideline, released by the American Society of Clinical Oncology and endorsed by the American Heart Association, is intended to assist primary care physicians, oncologists, cardiologists, and any members of multidisciplinary cancer care teams in preventing and monitoring systolic cardiac dysfunction, which is “typically detected as low left ventricular ejection fraction,” said Saro H. Armenian, DO, and his associates on the expert panel that drafted the guidelines.

To develop the guidelines, the panel conducted a systematic review of 8 metaanalyses, 12 randomized clinical trials, 49 cohort studies, 32 before-and-after studies, and 3 cross-sectional studies published in 1999-2016. They addressed five key questions: Which cancer survivors are at increased risk for developing cardiac dysfunction? Which preventive strategies minimize that risk before cancer therapy is initiated? Which preventive strategies minimize that risk during administration of potentially cardiotoxic cancer therapies? Which cardiac monitoring approaches are preferred during cancer therapies? And which cardiac monitoring approaches are preferred after cancer therapy is completed?

Regarding the fifth question, the guideline advises clinicians to regularly assess and manage cardiovascular risk factors such as smoking, hypertension, diabetes, dyslipidemia, and obesity in survivors of adult cancers, as well as to complete careful histories and physical examinations regularly. Any signs or symptoms that raise the suspicion of cardiac dysfunction should prompt an ECG (or cardiac MRI or multigated acquisition if an ECG isn’t available or technically feasible), assays of serum cardiac biomarkers, and, depending on the findings of these assessments, referral to a cardiologist.

“Patients also need to be advised that cardiac dysfunction can be a progressive disorder and may initially be asymptomatic; therefore, early and late warning signs and symptoms should be discussed,” said Dr. Armenian, a pediatric hematologist/oncologist and director of outcomes research in the department of population sciences at City of Hope in Duarte, Calif., and his associates.

The guideline also includes a special section concerning health disparities. “Patients with cancer who are members of racial or ethnic minorities suffer disproportionately from comorbidities, experience more obstacles to receiving care, are more likely to be uninsured, and are at greater risk of receiving care of poor quality than other Americans. [They] may have a substantially higher burden of cardiovascular complications during and after cancer treatment, in part because of inequities in the management of cardiovascular risk factors,” the guidelines state (J Clin Oncol. 2016 Dec 5 [doi:10.1200/JCO.2016.70.5400]).

A copy of the guideline and further information, including a data supplement, a methodology supplement, slide sets, and clinical tools and resources, are available at www.asco.org/cardiac-guidelineThis guideline was supported by the American Society of Clinical Oncology. Dr. Armenian reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.

Maintain a high suspicion for cardiac dysfunction and a low threshold for cardiac assessment with any patients who are survivors of adult cancers and may have received cardiotoxic therapy, a new guideline suggests.

The guideline, released by the American Society of Clinical Oncology and endorsed by the American Heart Association, is intended to assist primary care physicians, oncologists, cardiologists, and any members of multidisciplinary cancer care teams in preventing and monitoring systolic cardiac dysfunction, which is “typically detected as low left ventricular ejection fraction,” said Saro H. Armenian, DO, and his associates on the expert panel that drafted the guidelines.

To develop the guidelines, the panel conducted a systematic review of 8 metaanalyses, 12 randomized clinical trials, 49 cohort studies, 32 before-and-after studies, and 3 cross-sectional studies published in 1999-2016. They addressed five key questions: Which cancer survivors are at increased risk for developing cardiac dysfunction? Which preventive strategies minimize that risk before cancer therapy is initiated? Which preventive strategies minimize that risk during administration of potentially cardiotoxic cancer therapies? Which cardiac monitoring approaches are preferred during cancer therapies? And which cardiac monitoring approaches are preferred after cancer therapy is completed?

Regarding the fifth question, the guideline advises clinicians to regularly assess and manage cardiovascular risk factors such as smoking, hypertension, diabetes, dyslipidemia, and obesity in survivors of adult cancers, as well as to complete careful histories and physical examinations regularly. Any signs or symptoms that raise the suspicion of cardiac dysfunction should prompt an ECG (or cardiac MRI or multigated acquisition if an ECG isn’t available or technically feasible), assays of serum cardiac biomarkers, and, depending on the findings of these assessments, referral to a cardiologist.

“Patients also need to be advised that cardiac dysfunction can be a progressive disorder and may initially be asymptomatic; therefore, early and late warning signs and symptoms should be discussed,” said Dr. Armenian, a pediatric hematologist/oncologist and director of outcomes research in the department of population sciences at City of Hope in Duarte, Calif., and his associates.

The guideline also includes a special section concerning health disparities. “Patients with cancer who are members of racial or ethnic minorities suffer disproportionately from comorbidities, experience more obstacles to receiving care, are more likely to be uninsured, and are at greater risk of receiving care of poor quality than other Americans. [They] may have a substantially higher burden of cardiovascular complications during and after cancer treatment, in part because of inequities in the management of cardiovascular risk factors,” the guidelines state (J Clin Oncol. 2016 Dec 5 [doi:10.1200/JCO.2016.70.5400]).

A copy of the guideline and further information, including a data supplement, a methodology supplement, slide sets, and clinical tools and resources, are available at www.asco.org/cardiac-guidelineThis guideline was supported by the American Society of Clinical Oncology. Dr. Armenian reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.

Maintain a high suspicion for cardiac dysfunction and a low threshold for cardiac assessment with any patients who are survivors of adult cancers and may have received cardiotoxic therapy, a new guideline suggests.

The guideline, released by the American Society of Clinical Oncology and endorsed by the American Heart Association, is intended to assist primary care physicians, oncologists, cardiologists, and any members of multidisciplinary cancer care teams in preventing and monitoring systolic cardiac dysfunction, which is “typically detected as low left ventricular ejection fraction,” said Saro H. Armenian, DO, and his associates on the expert panel that drafted the guidelines.

To develop the guidelines, the panel conducted a systematic review of 8 metaanalyses, 12 randomized clinical trials, 49 cohort studies, 32 before-and-after studies, and 3 cross-sectional studies published in 1999-2016. They addressed five key questions: Which cancer survivors are at increased risk for developing cardiac dysfunction? Which preventive strategies minimize that risk before cancer therapy is initiated? Which preventive strategies minimize that risk during administration of potentially cardiotoxic cancer therapies? Which cardiac monitoring approaches are preferred during cancer therapies? And which cardiac monitoring approaches are preferred after cancer therapy is completed?

Regarding the fifth question, the guideline advises clinicians to regularly assess and manage cardiovascular risk factors such as smoking, hypertension, diabetes, dyslipidemia, and obesity in survivors of adult cancers, as well as to complete careful histories and physical examinations regularly. Any signs or symptoms that raise the suspicion of cardiac dysfunction should prompt an ECG (or cardiac MRI or multigated acquisition if an ECG isn’t available or technically feasible), assays of serum cardiac biomarkers, and, depending on the findings of these assessments, referral to a cardiologist.

“Patients also need to be advised that cardiac dysfunction can be a progressive disorder and may initially be asymptomatic; therefore, early and late warning signs and symptoms should be discussed,” said Dr. Armenian, a pediatric hematologist/oncologist and director of outcomes research in the department of population sciences at City of Hope in Duarte, Calif., and his associates.

The guideline also includes a special section concerning health disparities. “Patients with cancer who are members of racial or ethnic minorities suffer disproportionately from comorbidities, experience more obstacles to receiving care, are more likely to be uninsured, and are at greater risk of receiving care of poor quality than other Americans. [They] may have a substantially higher burden of cardiovascular complications during and after cancer treatment, in part because of inequities in the management of cardiovascular risk factors,” the guidelines state (J Clin Oncol. 2016 Dec 5 [doi:10.1200/JCO.2016.70.5400]).

A copy of the guideline and further information, including a data supplement, a methodology supplement, slide sets, and clinical tools and resources, are available at www.asco.org/cardiac-guidelineThis guideline was supported by the American Society of Clinical Oncology. Dr. Armenian reported having no relevant financial disclosures; his associates reported ties to numerous industry sources.

Researchers in Kenya reported that an active referral program significantly boosted the level of HIV testing in children of HIV-positive adults, according to a study published in JAIDS: The Journal of Acquired Immune Deficiency Syndromes. However, 86% of adults with children younger than 12 years of age did not pursue testing for their kids.

“This case detection approach was efficient, but there are still gaps in uptake that need to urgently be addressed,” said Anjuli Wagner, PhD, MPH, lead author of the study and a postdoctoral research fellow with the department of global health at the University of Washington, Seattle. According to Dr. Wagner, such a strategy is now in place in Kenya and is being adopted by other African countries.

xrender/thinkstockphotos.com

During 2013-2014, at Kenyatta National Hospital, Nairobi, Kenya, hospital staff interviewed 10,426 HIV-infected adults over a 9-month period and referred 611 of them for testing of their children under age 12 years.

Only 74 (14%) of the adults accepted referral and completed testing of their children; 7.4% of those 108 children were HIV positive. Still, after statistical adjustment, the hospital saw a 3.8-fold increase in the number of children tested, compared with the previous 10-month period (13.6 vs. 3.5 per month).

Why did so many parents decline to pursue testing for their children? “The most common reasons cited by parents were that they felt that their children seemed healthy and couldn’t possibly have HIV, and also that they feared a positive diagnosis,” Wagner said. “Parents cited logistical and financial barriers to testing their children as a frequent barrier and were also concerned about disclosure issues brought up by testing their children – disclosure of their own status to their child and partner, as well as disclosure of the child’s status to the child.”

The lesson of the study is that “testing children of HIV-positive adults in care should be integrated as part of comprehensive HIV care in Kenya and elsewhere,” Wagner said. “This approach is currently endorsed in the Kenyan national guidelines, partially as a result of this study, but was not present at the time this study was designed. Other African countries are also in the process of either adopting this approach into guidelines or scaling the already endorsed approach.”

The University of Washington and the National Institutes of Health funded the study. The authors reported no relevant disclosures.

On Twitter @idpractitioner

Researchers in Kenya reported that an active referral program significantly boosted the level of HIV testing in children of HIV-positive adults, according to a study published in JAIDS: The Journal of Acquired Immune Deficiency Syndromes. However, 86% of adults with children younger than 12 years of age did not pursue testing for their kids.

“This case detection approach was efficient, but there are still gaps in uptake that need to urgently be addressed,” said Anjuli Wagner, PhD, MPH, lead author of the study and a postdoctoral research fellow with the department of global health at the University of Washington, Seattle. According to Dr. Wagner, such a strategy is now in place in Kenya and is being adopted by other African countries.

xrender/thinkstockphotos.com

During 2013-2014, at Kenyatta National Hospital, Nairobi, Kenya, hospital staff interviewed 10,426 HIV-infected adults over a 9-month period and referred 611 of them for testing of their children under age 12 years.

Only 74 (14%) of the adults accepted referral and completed testing of their children; 7.4% of those 108 children were HIV positive. Still, after statistical adjustment, the hospital saw a 3.8-fold increase in the number of children tested, compared with the previous 10-month period (13.6 vs. 3.5 per month).

Why did so many parents decline to pursue testing for their children? “The most common reasons cited by parents were that they felt that their children seemed healthy and couldn’t possibly have HIV, and also that they feared a positive diagnosis,” Wagner said. “Parents cited logistical and financial barriers to testing their children as a frequent barrier and were also concerned about disclosure issues brought up by testing their children – disclosure of their own status to their child and partner, as well as disclosure of the child’s status to the child.”

The lesson of the study is that “testing children of HIV-positive adults in care should be integrated as part of comprehensive HIV care in Kenya and elsewhere,” Wagner said. “This approach is currently endorsed in the Kenyan national guidelines, partially as a result of this study, but was not present at the time this study was designed. Other African countries are also in the process of either adopting this approach into guidelines or scaling the already endorsed approach.”

The University of Washington and the National Institutes of Health funded the study. The authors reported no relevant disclosures.

On Twitter @idpractitioner

Researchers in Kenya reported that an active referral program significantly boosted the level of HIV testing in children of HIV-positive adults, according to a study published in JAIDS: The Journal of Acquired Immune Deficiency Syndromes. However, 86% of adults with children younger than 12 years of age did not pursue testing for their kids.

“This case detection approach was efficient, but there are still gaps in uptake that need to urgently be addressed,” said Anjuli Wagner, PhD, MPH, lead author of the study and a postdoctoral research fellow with the department of global health at the University of Washington, Seattle. According to Dr. Wagner, such a strategy is now in place in Kenya and is being adopted by other African countries.

xrender/thinkstockphotos.com

During 2013-2014, at Kenyatta National Hospital, Nairobi, Kenya, hospital staff interviewed 10,426 HIV-infected adults over a 9-month period and referred 611 of them for testing of their children under age 12 years.

Only 74 (14%) of the adults accepted referral and completed testing of their children; 7.4% of those 108 children were HIV positive. Still, after statistical adjustment, the hospital saw a 3.8-fold increase in the number of children tested, compared with the previous 10-month period (13.6 vs. 3.5 per month).

Why did so many parents decline to pursue testing for their children? “The most common reasons cited by parents were that they felt that their children seemed healthy and couldn’t possibly have HIV, and also that they feared a positive diagnosis,” Wagner said. “Parents cited logistical and financial barriers to testing their children as a frequent barrier and were also concerned about disclosure issues brought up by testing their children – disclosure of their own status to their child and partner, as well as disclosure of the child’s status to the child.”

The lesson of the study is that “testing children of HIV-positive adults in care should be integrated as part of comprehensive HIV care in Kenya and elsewhere,” Wagner said. “This approach is currently endorsed in the Kenyan national guidelines, partially as a result of this study, but was not present at the time this study was designed. Other African countries are also in the process of either adopting this approach into guidelines or scaling the already endorsed approach.”

The University of Washington and the National Institutes of Health funded the study. The authors reported no relevant disclosures.

On Twitter @idpractitioner

SAN DIEGO – A new multi-arm clinical trial aims to transform the treatment of de novo acute myeloid leukemia, a deadly blood cancer whose standard of care has remained essentially stagnant for 40 years.

Launched in October 2016, the multicenter BEAT AML Master Trial provides genomic results of bone marrow biopsies in just 7 days, according to Brian J. Druker, MD, director of the Knight Cancer Institute at Oregon Health and Science University, Portland. With results that fast, patients can quickly receive whichever therapy targets the mutation shared by most or all their leukemia cells, Dr. Druker and other researchers said at a press briefing at the annual meeting of the American Society of Hematology.

Patients who lack targetable markers will be offered investigational therapies that have shown broad activity in AML, the researchers said. The goal is for all participants to receive optimized treatment – whether or not that leads to an FDA approval, they emphasized.

Centers now participating in this trial include Memorial Sloan Kettering, Ohio State University, Dana-Farber Cancer Institute, Massachusetts General Hospital, and Oregon Health and Science University. More centers will join soon, according to the Leukemia & Lymphoma Society, which is sponsoring the trial. Researchers designed the trial with input from the FDA and pharmaceutical companies, they said.

In a video interview, Dr. Druker discussed key aspects of the trial and how it could advance treatment options for AML. Dr. Druker, whose work on imatinib helped pioneer precision medicine in cancer, disclosed ties to a number of pharmaceutical companies.

SAN DIEGO – A new multi-arm clinical trial aims to transform the treatment of de novo acute myeloid leukemia, a deadly blood cancer whose standard of care has remained essentially stagnant for 40 years.

Launched in October 2016, the multicenter BEAT AML Master Trial provides genomic results of bone marrow biopsies in just 7 days, according to Brian J. Druker, MD, director of the Knight Cancer Institute at Oregon Health and Science University, Portland. With results that fast, patients can quickly receive whichever therapy targets the mutation shared by most or all their leukemia cells, Dr. Druker and other researchers said at a press briefing at the annual meeting of the American Society of Hematology.

Patients who lack targetable markers will be offered investigational therapies that have shown broad activity in AML, the researchers said. The goal is for all participants to receive optimized treatment – whether or not that leads to an FDA approval, they emphasized.

Centers now participating in this trial include Memorial Sloan Kettering, Ohio State University, Dana-Farber Cancer Institute, Massachusetts General Hospital, and Oregon Health and Science University. More centers will join soon, according to the Leukemia & Lymphoma Society, which is sponsoring the trial. Researchers designed the trial with input from the FDA and pharmaceutical companies, they said.

In a video interview, Dr. Druker discussed key aspects of the trial and how it could advance treatment options for AML. Dr. Druker, whose work on imatinib helped pioneer precision medicine in cancer, disclosed ties to a number of pharmaceutical companies.

SAN DIEGO – A new multi-arm clinical trial aims to transform the treatment of de novo acute myeloid leukemia, a deadly blood cancer whose standard of care has remained essentially stagnant for 40 years.

Launched in October 2016, the multicenter BEAT AML Master Trial provides genomic results of bone marrow biopsies in just 7 days, according to Brian J. Druker, MD, director of the Knight Cancer Institute at Oregon Health and Science University, Portland. With results that fast, patients can quickly receive whichever therapy targets the mutation shared by most or all their leukemia cells, Dr. Druker and other researchers said at a press briefing at the annual meeting of the American Society of Hematology.

Patients who lack targetable markers will be offered investigational therapies that have shown broad activity in AML, the researchers said. The goal is for all participants to receive optimized treatment – whether or not that leads to an FDA approval, they emphasized.

Centers now participating in this trial include Memorial Sloan Kettering, Ohio State University, Dana-Farber Cancer Institute, Massachusetts General Hospital, and Oregon Health and Science University. More centers will join soon, according to the Leukemia & Lymphoma Society, which is sponsoring the trial. Researchers designed the trial with input from the FDA and pharmaceutical companies, they said.

In a video interview, Dr. Druker discussed key aspects of the trial and how it could advance treatment options for AML. Dr. Druker, whose work on imatinib helped pioneer precision medicine in cancer, disclosed ties to a number of pharmaceutical companies.

Baseline and follow-up data from a prospective, multinational cohort of more than 3,000 patients with clinically isolated events allowed researchers to develop an accurate prognostic nomogram to calculate an individual’s risk for conversion to clinically definite multiple sclerosis at 12 months.

“Identification of patient, disease, and examination factors associated with higher probability of second attack in clinical practice may enable clinicians to flag patients that could benefit from more intensive follow-up and consideration of early DMD [disease-modifying drug] treatment intervention, facilitating more favorable patient outcomes,” wrote Tim Spelman, PhD, and his associates.

designer491/Thinkstock

[email protected]

Baseline and follow-up data from a prospective, multinational cohort of more than 3,000 patients with clinically isolated events allowed researchers to develop an accurate prognostic nomogram to calculate an individual’s risk for conversion to clinically definite multiple sclerosis at 12 months.

“Identification of patient, disease, and examination factors associated with higher probability of second attack in clinical practice may enable clinicians to flag patients that could benefit from more intensive follow-up and consideration of early DMD [disease-modifying drug] treatment intervention, facilitating more favorable patient outcomes,” wrote Tim Spelman, PhD, and his associates.

designer491/Thinkstock

[email protected]

Baseline and follow-up data from a prospective, multinational cohort of more than 3,000 patients with clinically isolated events allowed researchers to develop an accurate prognostic nomogram to calculate an individual’s risk for conversion to clinically definite multiple sclerosis at 12 months.

“Identification of patient, disease, and examination factors associated with higher probability of second attack in clinical practice may enable clinicians to flag patients that could benefit from more intensive follow-up and consideration of early DMD [disease-modifying drug] treatment intervention, facilitating more favorable patient outcomes,” wrote Tim Spelman, PhD, and his associates.

designer491/Thinkstock

[email protected]

Postoperative use of both opioid and nonopioid analgesics was lower after robotic surgery than after laparotomy for endometrial cancer, according to a report published in Gynecologic Oncology.

Researchers assessed the use of postoperative pain medication in a single-center retrospective study involving 340 consecutive robotically assisted surgeries for endometrial cancer during a 6-year period. The mean patient age was 65 years, and more than one-third of the women were aged 70 or older. Slightly more than half were obese, and 19% were morbidly obese, said Jeremie Abitbol, PhD, of the division of gynecologic oncology, Jewish General Hospital and McGill University, Montreal, and his associates.

Master Video/Shutterstock

Postoperative use of both opioid and nonopioid analgesics was lower after robotic surgery than after laparotomy for endometrial cancer, according to a report published in Gynecologic Oncology.

Researchers assessed the use of postoperative pain medication in a single-center retrospective study involving 340 consecutive robotically assisted surgeries for endometrial cancer during a 6-year period. The mean patient age was 65 years, and more than one-third of the women were aged 70 or older. Slightly more than half were obese, and 19% were morbidly obese, said Jeremie Abitbol, PhD, of the division of gynecologic oncology, Jewish General Hospital and McGill University, Montreal, and his associates.

Master Video/Shutterstock

Postoperative use of both opioid and nonopioid analgesics was lower after robotic surgery than after laparotomy for endometrial cancer, according to a report published in Gynecologic Oncology.

Researchers assessed the use of postoperative pain medication in a single-center retrospective study involving 340 consecutive robotically assisted surgeries for endometrial cancer during a 6-year period. The mean patient age was 65 years, and more than one-third of the women were aged 70 or older. Slightly more than half were obese, and 19% were morbidly obese, said Jeremie Abitbol, PhD, of the division of gynecologic oncology, Jewish General Hospital and McGill University, Montreal, and his associates.

Master Video/Shutterstock

HOUSTON – Fewer than 8% of adult patients with drug-resistant epilepsy would have been recruitable for recent phase II and III trials of new antiepileptic drugs (AEDs), results from a single-center study showed.

The findings underscore a need to rethink how phase II and III trials of AEDs are conducted, Bernhard J. Steinhoff, MD, said in an interview prior to the annual meeting of the American Epilepsy Society. “In spite of the marketing of numerous new antiepileptic drugs, the percentage of drug-resistant epilepsies has remained almost unchanged,” said Dr. Steinhoff of the Kork (Germany) Epilepsy Center. “I am not aware that anybody involved in the issue of clinical trials with AEDs addressed the problem [of] whether the pivotal trials really cover the patients the new AEDs are developed for: namely, patients with drug-resistant epilepsies. Every time we start with a new drug after licensing, we realize that we have no clue whether this drug will be appropriate for our difficult-to-treat patients. We wondered whether the design of the usual phase II and III randomized controlled trials covers an acceptable percentage of AED-resistant epilepsy patients.”

“The result was frightening because less than 10% [of patients] would have been covered by the trials,” Dr. Steinhoff said. “Therefore, we suggest that a bad trials strategy may be responsible for the fact that the percentage of drug-resistant patients has not been markedly reduced by more than 15 new AEDs that were introduced during the recent years.” He added that pivotal trials with new AEDs “show superiority over placebo as add-on in an extremely limited group of difficult-to-treat patients. After licensing and marketing, we start to learn whether a new AED is appropriate for our drug-resistant patients.”

Medical writing was funded by an unrestricted grant from UCB. Dr. Steinhoff reported having no financial conflicts.

[email protected]

HOUSTON – Fewer than 8% of adult patients with drug-resistant epilepsy would have been recruitable for recent phase II and III trials of new antiepileptic drugs (AEDs), results from a single-center study showed.

The findings underscore a need to rethink how phase II and III trials of AEDs are conducted, Bernhard J. Steinhoff, MD, said in an interview prior to the annual meeting of the American Epilepsy Society. “In spite of the marketing of numerous new antiepileptic drugs, the percentage of drug-resistant epilepsies has remained almost unchanged,” said Dr. Steinhoff of the Kork (Germany) Epilepsy Center. “I am not aware that anybody involved in the issue of clinical trials with AEDs addressed the problem [of] whether the pivotal trials really cover the patients the new AEDs are developed for: namely, patients with drug-resistant epilepsies. Every time we start with a new drug after licensing, we realize that we have no clue whether this drug will be appropriate for our difficult-to-treat patients. We wondered whether the design of the usual phase II and III randomized controlled trials covers an acceptable percentage of AED-resistant epilepsy patients.”

“The result was frightening because less than 10% [of patients] would have been covered by the trials,” Dr. Steinhoff said. “Therefore, we suggest that a bad trials strategy may be responsible for the fact that the percentage of drug-resistant patients has not been markedly reduced by more than 15 new AEDs that were introduced during the recent years.” He added that pivotal trials with new AEDs “show superiority over placebo as add-on in an extremely limited group of difficult-to-treat patients. After licensing and marketing, we start to learn whether a new AED is appropriate for our drug-resistant patients.”

Medical writing was funded by an unrestricted grant from UCB. Dr. Steinhoff reported having no financial conflicts.

[email protected]

HOUSTON – Fewer than 8% of adult patients with drug-resistant epilepsy would have been recruitable for recent phase II and III trials of new antiepileptic drugs (AEDs), results from a single-center study showed.

The findings underscore a need to rethink how phase II and III trials of AEDs are conducted, Bernhard J. Steinhoff, MD, said in an interview prior to the annual meeting of the American Epilepsy Society. “In spite of the marketing of numerous new antiepileptic drugs, the percentage of drug-resistant epilepsies has remained almost unchanged,” said Dr. Steinhoff of the Kork (Germany) Epilepsy Center. “I am not aware that anybody involved in the issue of clinical trials with AEDs addressed the problem [of] whether the pivotal trials really cover the patients the new AEDs are developed for: namely, patients with drug-resistant epilepsies. Every time we start with a new drug after licensing, we realize that we have no clue whether this drug will be appropriate for our difficult-to-treat patients. We wondered whether the design of the usual phase II and III randomized controlled trials covers an acceptable percentage of AED-resistant epilepsy patients.”

“The result was frightening because less than 10% [of patients] would have been covered by the trials,” Dr. Steinhoff said. “Therefore, we suggest that a bad trials strategy may be responsible for the fact that the percentage of drug-resistant patients has not been markedly reduced by more than 15 new AEDs that were introduced during the recent years.” He added that pivotal trials with new AEDs “show superiority over placebo as add-on in an extremely limited group of difficult-to-treat patients. After licensing and marketing, we start to learn whether a new AED is appropriate for our drug-resistant patients.”

Medical writing was funded by an unrestricted grant from UCB. Dr. Steinhoff reported having no financial conflicts.

[email protected]

HOUSTON – The types of diagnostic tests ordered and medication used for treatment of infantile spasms vary considerably, a large study of children’s hospitals showed.

“Children with infantile spasms often require extensive diagnostic work-up to determine etiology, expensive medications for treatment, and hospitalization during the initiation of certain therapies,” researchers led by Sunita N. Misra, MD, PhD, wrote in an abstract presented at the annual meeting of the American Epilepsy Society. “The common diagnostic studies and therapies have evolved over the last several decades.”

Doug Brunk/Frontline Medical News

[email protected]

HOUSTON – The types of diagnostic tests ordered and medication used for treatment of infantile spasms vary considerably, a large study of children’s hospitals showed.

“Children with infantile spasms often require extensive diagnostic work-up to determine etiology, expensive medications for treatment, and hospitalization during the initiation of certain therapies,” researchers led by Sunita N. Misra, MD, PhD, wrote in an abstract presented at the annual meeting of the American Epilepsy Society. “The common diagnostic studies and therapies have evolved over the last several decades.”

Doug Brunk/Frontline Medical News

[email protected]

HOUSTON – The types of diagnostic tests ordered and medication used for treatment of infantile spasms vary considerably, a large study of children’s hospitals showed.

“Children with infantile spasms often require extensive diagnostic work-up to determine etiology, expensive medications for treatment, and hospitalization during the initiation of certain therapies,” researchers led by Sunita N. Misra, MD, PhD, wrote in an abstract presented at the annual meeting of the American Epilepsy Society. “The common diagnostic studies and therapies have evolved over the last several decades.”

Doug Brunk/Frontline Medical News

[email protected]

This month’s column is the second in a series of three articles written by a group from Toronto and Houston. The series imagined that a community of gastroenterologists set out to improve the adenoma detection rates of physicians in their practice. The first article described the design and launch of the project. This month, Dr. Bollegala and her colleagues explain the plan-do-study-act (PDSA) cycle of improvement within a small practice. The PDSA cycle is a fundamental component of successful quality improvement initiatives; it allows a group to systematically analyze what works and what doesn’t. The focus of this article is squarely on small community practices (still the majority of gastrointestinal practices nationally), so its relevance is high. PDSA cycles are small, narrowly focused projects that can be accomplished by all as we strive to improve our care of the patients we serve. Next month, we will learn how to embed a quality initiative within our practices so sustained improvement can be seen.

John I. Allen, MD, MBA, AGAF

Editor in Chief
 

Article 1 of our series focused on the emergence of the adenoma detection rate (ADR) as a quality indicator for colonoscopy-based colorectal cancer screening programs.¹ A target ADR of 25% has been established by several national gastroenterology societies and serves as a focus area for those seeking to develop quality improvement (QI) initiatives aimed at reducing the interval incidence of colorectal cancer.² In this series, you are a community-based urban general gastroenterologist interested in improving your current group ADR of 19% to the established target of 25% for each individual endoscopist within the group over a 12-month period.

This article focuses on a clinician-friendly description of the plan-do-study-act (PDSA) cycle, a key construct within the Model for Improvement framework for QI initiatives. It also describes the importance and key elements of QI data reporting, including the run chart. All core concepts will be framed within the series example of the development of an institutional QI initiative for ADR improvement.
 

Plan-Do-Study-Act cycle

Conventional scientific research in health care generally is based on large-scale projects, performed over long periods of time and producing aggregate data analyzed through summary statistics. QI-related research, as it relates to PDSA, in contrast, is characterized by smaller-scale projects performed over shorter periods of time, with iterative protocols to accommodate local context and therefore optimize intervention success. As such, the framework for their development, implementation, and continual modification requires a conceptual and methodologic shift.

The PDSA cycle is characterized by four key steps. The first step is to plan. This step involves addressing the following questions: 1) what are we trying to accomplish? (aim); 2) how will we know that a change is an improvement? (measure); and 3) what changes can we make that will lead to improvement? (change). Additional considerations include ensuring that the stated goal is attainable, relevant, and that the timeline is feasible. An important aspect of the plan stage is gaining an understanding for the current local context, key participants and their roles, and areas in which performance is excelling or is challenged. This understanding is critical to conceptually linking the identified problem with its proposed solution. Formulating an impact prediction allows subsequent learning and adaptation.

The second step is to do. This step involves execution of the identified plan over a specified period of time. It also involves rigorous qualitative and quantitative data collection, allowing the research team to assess change and document unexpected events. The identification of an implementation leader or champion to ensure protocol adherence, effective communication among team members, and coordinate accurate data collection can be critical for overall success.

The third step is to study. This step requires evaluating whether a change in the outcome measure has occurred, which intervention was successful, and whether an identified change is sustained over time. It also requires interpretation of change within the local context, specifically with respect to unintended consequences, unanticipated events, and the sustainability of any gains. To interpret study findings appropriately, feedback with involved process members, endoscopists, and/or other stakeholder groups may be necessary. This can be important for explaining the results of each cycle, identifying protocol modifications for future cycles, and optimizing the opportunity for success. Studying the data generated by a QI initiative requires clear and accurate data display and rules for interpretation.

The fourth step is to act. This final step allows team members to reflect on the results generated and decide whether the same intervention should be continued, modified, or changed, thereby incorporating lessons learned from previous PDSA cycles (Figure 1).³

AGA Institute

Displaying data

The documentation, analysis, and interpretation of data generated by multiple PDSA cycles must be displayed accurately and succinctly. The run chart has been developed as a simple technique for identifying nonrandom patterns (that is, signals), which allows QI researchers to determine the impact of each cycle of change and the stability of that change over a given time period.⁹ This often is contrasted with conventional statistical approaches that aggregate data and perform summary statistical comparisons at static time points. Instead, the run chart allows for an appreciation of the dynamic nature of PDSA-driven process manipulation and resulting outcome changes.

Correct interpretation of the presented data requires an understanding of common cause variation (CCV) and special cause variation (SCV). CCV occurs randomly and is present in all health care processes. It can never be eliminated completely. SCV, in contrast, is the result of external factors that are imposed on normal processes. For example, the introduction of audible timers within endoscopy rooms to ensure adequate withdrawal time may result in an increase in the ADR. The relatively stable ADR measured in both the pre-intervention and postintervention periods are subject to CCV. However, the postintervention increase in ADR is the result of SCV.¹⁰

As shown in Figure 2, the horizontal axis shows the time scale and spans the entire duration of the intervention period. The y-axis shows the outcome measure of interest. A horizontal line representing the median is shown.⁹ A goal line also may be depicted. Annotations to indicate the implementation of change or other important events (such as unintended consequences or unexpected events) also may be added to facilitate data interpretation.

AGA Institute

Summary and next steps

This article selectively reviews the process of change framed by the PDSA cycle. We also discuss the role of data display and interpretation using a run chart. The final article in this series will cover how to sustain change and support a culture of continuous improvement.

References

1. Corley, D.A., Jensen, C.D., Marks, A.R., et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med. 2014;370:1298-306.

2. Cohen, J., Schoenfeld, P., Park, W., et al. Quality indicators for colonoscopy. Gastrointest Endosc. 2015;81:31-53.

3. Module 5: Improvement Cycle. (2013). Available at: http://implementation.fpg.unc.edu/book/export/html/326. Accessed Feb. 1, 2016.

4. Taylor, M.J., McNicholas, C., Nicolay, C., et al. Systematic review of the application of the plan-do-study-act method to improve quality in healthcare. BMJ Qual Saf. 2014;23(4):290-8.

5. Davidoff, F., Batalden, P., Stevens, D. et al. Publication guidelines for quality improvement in health care: evolution of the SQUIRE project. Qual Saf Health Care. 2008;17:i3-9.

6. Ogrinc, G., Mooney, S., Estrada, C., et al. The SQUIRE (standards for Quality Improvement Reporting Excellence) guidelines for quality improvement reporting: explanation and elaboration. Qual Saf Health Care. 2008;17:i13-32.

7. Nelson, E.C., Batalden, B.P., Godfrey, M.M. Quality by design: a clinical microsystems approach. Jossey-Bass, San Francisco; 2007.

8. Coe, S.G.C.J., Diehl, N.N., Wallace, M.B. An endoscopic quality improvement program improves detection of colorectal adenomas. Am J Gastroenterol. 2013;108(2):219-26.

9. Perla, R.J., Provost, L.P., Murray, S.K. The run chart: a simple analytical tool for learning from variation in healthcare processes. BMJ Qual Saf. 2011;20:46-51.

10. Neuhauser, D., Provost, L., Bergman, B. The meaning of variation to healthcare managers, clinical and health-services researchers, and individual patients. BMJ Qual Saf. 2011;20:i36-40.

11. Swed, F.S. Eisenhart, C. Tables for testing randomness of grouping in a sequence of alternatives. Ann Math Statist. 1943;14:66-87

Dr. Bollegala is in the division of gastroenterology, department of medicine, Women’s College Hospital; Dr. Mosko is in the division of gastroenterology, department of medicine, St. Michael’s Hospital, and the Institute of Health Policy, Management, and Evaluation; Dr. Bernstein is in the division of gastroenterology, department of medicine, Sunnybrook Health Sciences Centre; Dr. Brahmania is in the Toronto Center for Liver Diseases, division of gastroenterology, department of medicine, University Health Network; Dr. Liu is in the division of gastroenterology, department of medicine, University Health Network; Dr. Steinhart is at Mount Sinai Hospital Centre for Inflammatory Bowel Disease, department of medicine and Institute of Health Policy, Management, and Evaluation; Dr. Silver is in the division of nephrology, St. Michael’s Hospital; Dr. Bell is in the division of internal medicine, department of medicine, Mount Sinai Hospital; Dr. Nguyen is at Mount Sinai Hospital Centre for Inflammatory Bowel Disease, department of medicine; Dr. Weizman is at the Mount Sinai Hospital Centre for Inflammatory Bowel Disease, department of medicine, and Institute of Health Policy, Management and Evaluation. All are at the University of Toronto. Dr. Patel is in the division of gastroenterology and hepatology, department of medicine, Baylor College of Medicine, Houston. The authors disclose no conflicts.

This month’s column is the second in a series of three articles written by a group from Toronto and Houston. The series imagined that a community of gastroenterologists set out to improve the adenoma detection rates of physicians in their practice. The first article described the design and launch of the project. This month, Dr. Bollegala and her colleagues explain the plan-do-study-act (PDSA) cycle of improvement within a small practice. The PDSA cycle is a fundamental component of successful quality improvement initiatives; it allows a group to systematically analyze what works and what doesn’t. The focus of this article is squarely on small community practices (still the majority of gastrointestinal practices nationally), so its relevance is high. PDSA cycles are small, narrowly focused projects that can be accomplished by all as we strive to improve our care of the patients we serve. Next month, we will learn how to embed a quality initiative within our practices so sustained improvement can be seen.

John I. Allen, MD, MBA, AGAF

Editor in Chief
 

Article 1 of our series focused on the emergence of the adenoma detection rate (ADR) as a quality indicator for colonoscopy-based colorectal cancer screening programs.¹ A target ADR of 25% has been established by several national gastroenterology societies and serves as a focus area for those seeking to develop quality improvement (QI) initiatives aimed at reducing the interval incidence of colorectal cancer.² In this series, you are a community-based urban general gastroenterologist interested in improving your current group ADR of 19% to the established target of 25% for each individual endoscopist within the group over a 12-month period.

This article focuses on a clinician-friendly description of the plan-do-study-act (PDSA) cycle, a key construct within the Model for Improvement framework for QI initiatives. It also describes the importance and key elements of QI data reporting, including the run chart. All core concepts will be framed within the series example of the development of an institutional QI initiative for ADR improvement.
 

Plan-Do-Study-Act cycle

Conventional scientific research in health care generally is based on large-scale projects, performed over long periods of time and producing aggregate data analyzed through summary statistics. QI-related research, as it relates to PDSA, in contrast, is characterized by smaller-scale projects performed over shorter periods of time, with iterative protocols to accommodate local context and therefore optimize intervention success. As such, the framework for their development, implementation, and continual modification requires a conceptual and methodologic shift.

The PDSA cycle is characterized by four key steps. The first step is to plan. This step involves addressing the following questions: 1) what are we trying to accomplish? (aim); 2) how will we know that a change is an improvement? (measure); and 3) what changes can we make that will lead to improvement? (change). Additional considerations include ensuring that the stated goal is attainable, relevant, and that the timeline is feasible. An important aspect of the plan stage is gaining an understanding for the current local context, key participants and their roles, and areas in which performance is excelling or is challenged. This understanding is critical to conceptually linking the identified problem with its proposed solution. Formulating an impact prediction allows subsequent learning and adaptation.

The second step is to do. This step involves execution of the identified plan over a specified period of time. It also involves rigorous qualitative and quantitative data collection, allowing the research team to assess change and document unexpected events. The identification of an implementation leader or champion to ensure protocol adherence, effective communication among team members, and coordinate accurate data collection can be critical for overall success.

The third step is to study. This step requires evaluating whether a change in the outcome measure has occurred, which intervention was successful, and whether an identified change is sustained over time. It also requires interpretation of change within the local context, specifically with respect to unintended consequences, unanticipated events, and the sustainability of any gains. To interpret study findings appropriately, feedback with involved process members, endoscopists, and/or other stakeholder groups may be necessary. This can be important for explaining the results of each cycle, identifying protocol modifications for future cycles, and optimizing the opportunity for success. Studying the data generated by a QI initiative requires clear and accurate data display and rules for interpretation.

The fourth step is to act. This final step allows team members to reflect on the results generated and decide whether the same intervention should be continued, modified, or changed, thereby incorporating lessons learned from previous PDSA cycles (Figure 1).³

AGA Institute

Displaying data

The documentation, analysis, and interpretation of data generated by multiple PDSA cycles must be displayed accurately and succinctly. The run chart has been developed as a simple technique for identifying nonrandom patterns (that is, signals), which allows QI researchers to determine the impact of each cycle of change and the stability of that change over a given time period.⁹ This often is contrasted with conventional statistical approaches that aggregate data and perform summary statistical comparisons at static time points. Instead, the run chart allows for an appreciation of the dynamic nature of PDSA-driven process manipulation and resulting outcome changes.

Correct interpretation of the presented data requires an understanding of common cause variation (CCV) and special cause variation (SCV). CCV occurs randomly and is present in all health care processes. It can never be eliminated completely. SCV, in contrast, is the result of external factors that are imposed on normal processes. For example, the introduction of audible timers within endoscopy rooms to ensure adequate withdrawal time may result in an increase in the ADR. The relatively stable ADR measured in both the pre-intervention and postintervention periods are subject to CCV. However, the postintervention increase in ADR is the result of SCV.¹⁰

As shown in Figure 2, the horizontal axis shows the time scale and spans the entire duration of the intervention period. The y-axis shows the outcome measure of interest. A horizontal line representing the median is shown.⁹ A goal line also may be depicted. Annotations to indicate the implementation of change or other important events (such as unintended consequences or unexpected events) also may be added to facilitate data interpretation.

AGA Institute

Summary and next steps

This article selectively reviews the process of change framed by the PDSA cycle. We also discuss the role of data display and interpretation using a run chart. The final article in this series will cover how to sustain change and support a culture of continuous improvement.

References

1. Corley, D.A., Jensen, C.D., Marks, A.R., et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med. 2014;370:1298-306.

2. Cohen, J., Schoenfeld, P., Park, W., et al. Quality indicators for colonoscopy. Gastrointest Endosc. 2015;81:31-53.

3. Module 5: Improvement Cycle. (2013). Available at: http://implementation.fpg.unc.edu/book/export/html/326. Accessed Feb. 1, 2016.

4. Taylor, M.J., McNicholas, C., Nicolay, C., et al. Systematic review of the application of the plan-do-study-act method to improve quality in healthcare. BMJ Qual Saf. 2014;23(4):290-8.

5. Davidoff, F., Batalden, P., Stevens, D. et al. Publication guidelines for quality improvement in health care: evolution of the SQUIRE project. Qual Saf Health Care. 2008;17:i3-9.

6. Ogrinc, G., Mooney, S., Estrada, C., et al. The SQUIRE (standards for Quality Improvement Reporting Excellence) guidelines for quality improvement reporting: explanation and elaboration. Qual Saf Health Care. 2008;17:i13-32.

7. Nelson, E.C., Batalden, B.P., Godfrey, M.M. Quality by design: a clinical microsystems approach. Jossey-Bass, San Francisco; 2007.

8. Coe, S.G.C.J., Diehl, N.N., Wallace, M.B. An endoscopic quality improvement program improves detection of colorectal adenomas. Am J Gastroenterol. 2013;108(2):219-26.

9. Perla, R.J., Provost, L.P., Murray, S.K. The run chart: a simple analytical tool for learning from variation in healthcare processes. BMJ Qual Saf. 2011;20:46-51.

10. Neuhauser, D., Provost, L., Bergman, B. The meaning of variation to healthcare managers, clinical and health-services researchers, and individual patients. BMJ Qual Saf. 2011;20:i36-40.

11. Swed, F.S. Eisenhart, C. Tables for testing randomness of grouping in a sequence of alternatives. Ann Math Statist. 1943;14:66-87

Dr. Bollegala is in the division of gastroenterology, department of medicine, Women’s College Hospital; Dr. Mosko is in the division of gastroenterology, department of medicine, St. Michael’s Hospital, and the Institute of Health Policy, Management, and Evaluation; Dr. Bernstein is in the division of gastroenterology, department of medicine, Sunnybrook Health Sciences Centre; Dr. Brahmania is in the Toronto Center for Liver Diseases, division of gastroenterology, department of medicine, University Health Network; Dr. Liu is in the division of gastroenterology, department of medicine, University Health Network; Dr. Steinhart is at Mount Sinai Hospital Centre for Inflammatory Bowel Disease, department of medicine and Institute of Health Policy, Management, and Evaluation; Dr. Silver is in the division of nephrology, St. Michael’s Hospital; Dr. Bell is in the division of internal medicine, department of medicine, Mount Sinai Hospital; Dr. Nguyen is at Mount Sinai Hospital Centre for Inflammatory Bowel Disease, department of medicine; Dr. Weizman is at the Mount Sinai Hospital Centre for Inflammatory Bowel Disease, department of medicine, and Institute of Health Policy, Management and Evaluation. All are at the University of Toronto. Dr. Patel is in the division of gastroenterology and hepatology, department of medicine, Baylor College of Medicine, Houston. The authors disclose no conflicts.

This month’s column is the second in a series of three articles written by a group from Toronto and Houston. The series imagined that a community of gastroenterologists set out to improve the adenoma detection rates of physicians in their practice. The first article described the design and launch of the project. This month, Dr. Bollegala and her colleagues explain the plan-do-study-act (PDSA) cycle of improvement within a small practice. The PDSA cycle is a fundamental component of successful quality improvement initiatives; it allows a group to systematically analyze what works and what doesn’t. The focus of this article is squarely on small community practices (still the majority of gastrointestinal practices nationally), so its relevance is high. PDSA cycles are small, narrowly focused projects that can be accomplished by all as we strive to improve our care of the patients we serve. Next month, we will learn how to embed a quality initiative within our practices so sustained improvement can be seen.

John I. Allen, MD, MBA, AGAF

Editor in Chief
 

Article 1 of our series focused on the emergence of the adenoma detection rate (ADR) as a quality indicator for colonoscopy-based colorectal cancer screening programs.¹ A target ADR of 25% has been established by several national gastroenterology societies and serves as a focus area for those seeking to develop quality improvement (QI) initiatives aimed at reducing the interval incidence of colorectal cancer.² In this series, you are a community-based urban general gastroenterologist interested in improving your current group ADR of 19% to the established target of 25% for each individual endoscopist within the group over a 12-month period.

This article focuses on a clinician-friendly description of the plan-do-study-act (PDSA) cycle, a key construct within the Model for Improvement framework for QI initiatives. It also describes the importance and key elements of QI data reporting, including the run chart. All core concepts will be framed within the series example of the development of an institutional QI initiative for ADR improvement.
 

Plan-Do-Study-Act cycle

Conventional scientific research in health care generally is based on large-scale projects, performed over long periods of time and producing aggregate data analyzed through summary statistics. QI-related research, as it relates to PDSA, in contrast, is characterized by smaller-scale projects performed over shorter periods of time, with iterative protocols to accommodate local context and therefore optimize intervention success. As such, the framework for their development, implementation, and continual modification requires a conceptual and methodologic shift.

The PDSA cycle is characterized by four key steps. The first step is to plan. This step involves addressing the following questions: 1) what are we trying to accomplish? (aim); 2) how will we know that a change is an improvement? (measure); and 3) what changes can we make that will lead to improvement? (change). Additional considerations include ensuring that the stated goal is attainable, relevant, and that the timeline is feasible. An important aspect of the plan stage is gaining an understanding for the current local context, key participants and their roles, and areas in which performance is excelling or is challenged. This understanding is critical to conceptually linking the identified problem with its proposed solution. Formulating an impact prediction allows subsequent learning and adaptation.

The second step is to do. This step involves execution of the identified plan over a specified period of time. It also involves rigorous qualitative and quantitative data collection, allowing the research team to assess change and document unexpected events. The identification of an implementation leader or champion to ensure protocol adherence, effective communication among team members, and coordinate accurate data collection can be critical for overall success.

The third step is to study. This step requires evaluating whether a change in the outcome measure has occurred, which intervention was successful, and whether an identified change is sustained over time. It also requires interpretation of change within the local context, specifically with respect to unintended consequences, unanticipated events, and the sustainability of any gains. To interpret study findings appropriately, feedback with involved process members, endoscopists, and/or other stakeholder groups may be necessary. This can be important for explaining the results of each cycle, identifying protocol modifications for future cycles, and optimizing the opportunity for success. Studying the data generated by a QI initiative requires clear and accurate data display and rules for interpretation.

The fourth step is to act. This final step allows team members to reflect on the results generated and decide whether the same intervention should be continued, modified, or changed, thereby incorporating lessons learned from previous PDSA cycles (Figure 1).³

AGA Institute

Displaying data

The documentation, analysis, and interpretation of data generated by multiple PDSA cycles must be displayed accurately and succinctly. The run chart has been developed as a simple technique for identifying nonrandom patterns (that is, signals), which allows QI researchers to determine the impact of each cycle of change and the stability of that change over a given time period.⁹ This often is contrasted with conventional statistical approaches that aggregate data and perform summary statistical comparisons at static time points. Instead, the run chart allows for an appreciation of the dynamic nature of PDSA-driven process manipulation and resulting outcome changes.

Correct interpretation of the presented data requires an understanding of common cause variation (CCV) and special cause variation (SCV). CCV occurs randomly and is present in all health care processes. It can never be eliminated completely. SCV, in contrast, is the result of external factors that are imposed on normal processes. For example, the introduction of audible timers within endoscopy rooms to ensure adequate withdrawal time may result in an increase in the ADR. The relatively stable ADR measured in both the pre-intervention and postintervention periods are subject to CCV. However, the postintervention increase in ADR is the result of SCV.¹⁰

As shown in Figure 2, the horizontal axis shows the time scale and spans the entire duration of the intervention period. The y-axis shows the outcome measure of interest. A horizontal line representing the median is shown.⁹ A goal line also may be depicted. Annotations to indicate the implementation of change or other important events (such as unintended consequences or unexpected events) also may be added to facilitate data interpretation.

AGA Institute

Summary and next steps

This article selectively reviews the process of change framed by the PDSA cycle. We also discuss the role of data display and interpretation using a run chart. The final article in this series will cover how to sustain change and support a culture of continuous improvement.

References

1. Corley, D.A., Jensen, C.D., Marks, A.R., et al. Adenoma detection rate and risk of colorectal cancer and death. N Engl J Med. 2014;370:1298-306.

2. Cohen, J., Schoenfeld, P., Park, W., et al. Quality indicators for colonoscopy. Gastrointest Endosc. 2015;81:31-53.

3. Module 5: Improvement Cycle. (2013). Available at: http://implementation.fpg.unc.edu/book/export/html/326. Accessed Feb. 1, 2016.

4. Taylor, M.J., McNicholas, C., Nicolay, C., et al. Systematic review of the application of the plan-do-study-act method to improve quality in healthcare. BMJ Qual Saf. 2014;23(4):290-8.

5. Davidoff, F., Batalden, P., Stevens, D. et al. Publication guidelines for quality improvement in health care: evolution of the SQUIRE project. Qual Saf Health Care. 2008;17:i3-9.

6. Ogrinc, G., Mooney, S., Estrada, C., et al. The SQUIRE (standards for Quality Improvement Reporting Excellence) guidelines for quality improvement reporting: explanation and elaboration. Qual Saf Health Care. 2008;17:i13-32.

7. Nelson, E.C., Batalden, B.P., Godfrey, M.M. Quality by design: a clinical microsystems approach. Jossey-Bass, San Francisco; 2007.

8. Coe, S.G.C.J., Diehl, N.N., Wallace, M.B. An endoscopic quality improvement program improves detection of colorectal adenomas. Am J Gastroenterol. 2013;108(2):219-26.

9. Perla, R.J., Provost, L.P., Murray, S.K. The run chart: a simple analytical tool for learning from variation in healthcare processes. BMJ Qual Saf. 2011;20:46-51.

10. Neuhauser, D., Provost, L., Bergman, B. The meaning of variation to healthcare managers, clinical and health-services researchers, and individual patients. BMJ Qual Saf. 2011;20:i36-40.

11. Swed, F.S. Eisenhart, C. Tables for testing randomness of grouping in a sequence of alternatives. Ann Math Statist. 1943;14:66-87

Dr. Bollegala is in the division of gastroenterology, department of medicine, Women’s College Hospital; Dr. Mosko is in the division of gastroenterology, department of medicine, St. Michael’s Hospital, and the Institute of Health Policy, Management, and Evaluation; Dr. Bernstein is in the division of gastroenterology, department of medicine, Sunnybrook Health Sciences Centre; Dr. Brahmania is in the Toronto Center for Liver Diseases, division of gastroenterology, department of medicine, University Health Network; Dr. Liu is in the division of gastroenterology, department of medicine, University Health Network; Dr. Steinhart is at Mount Sinai Hospital Centre for Inflammatory Bowel Disease, department of medicine and Institute of Health Policy, Management, and Evaluation; Dr. Silver is in the division of nephrology, St. Michael’s Hospital; Dr. Bell is in the division of internal medicine, department of medicine, Mount Sinai Hospital; Dr. Nguyen is at Mount Sinai Hospital Centre for Inflammatory Bowel Disease, department of medicine; Dr. Weizman is at the Mount Sinai Hospital Centre for Inflammatory Bowel Disease, department of medicine, and Institute of Health Policy, Management and Evaluation. All are at the University of Toronto. Dr. Patel is in the division of gastroenterology and hepatology, department of medicine, Baylor College of Medicine, Houston. The authors disclose no conflicts.

Interior view of San Diego

Convention Center, site of

the 2016 ASH Annual Meeting

SAN DIEGO—Results of a phase 1 study suggest that SCD-101, a botanical extract based on an herbal medicine used in Nigeria to treat sickle cell disease (SCD), can reduce pain and fatigue in people with SCD.

The anti-sickling drug also improves the shape of red blood cells but doesn’t produce a change in hemoglobin, according to researchers.

Peter Gillette, MD, of SUNY Downstate in Brooklyn, New York, reported these results at the 2016 ASH Annual Meeting (abstract 121*).

A 6-month phase 2b study conducted previously in Nigeria showed that the herbal medicine Niprisan reduced pain crises and school absenteeism and raised hemoglobin levels compared to placebo.

Based on this study and positive preclinical activity, Dr Gillette and his colleagues undertook a phase 1 study to determine the safety of escalating doses of SCD-101.

Dr Gillette pointed out that Niprisan had been produced commercially in Nigeria but was later removed by the government from the commercial market because of production problems.

The researchers evaluated 23 patients with homozygous SCD or S/beta0 thalassemia.

Patients were aged 18 to 55 years with hemoglobin F of 15% or less and hemoglobin levels between 6.0 and 9.5 g/dL.

Patients could not have had hydroxyurea treatment within 6 months of enrollment, red blood cell transfusion within 3 months, or hospitalization within 4 weeks.

Patients received SCD-101 orally for 28 days administered 2 times daily (BID) or 3 times daily (TID). Doses were 550 mg BID, 1100 mg BID, 2200 mg BID, 4400 mg BID, and 2750 mg TID.

Dr Gillette explained that by distributing the highest dose 3 times over the course of a day, the researchers were able to decrease the side effects of bloating and flatulence on the highest dose.

“Interestingly, with the dose-distributed TID, we found that the hemoglobin had increased by 10%,” he said. “In other words, it appears that the effects are very short-acting, and that by going from a Q12 to a Q8 dosage, the hemoglobin suddenly looks like it might be significant, although this is not a significant change.”

Laboratory outcomes included hemoglobin and hemolysis (LDH, bilirubin, and reticulocyte measurements). Patient-reported outcomes included pain and fatigue.

The most common adverse events (AEs) were pain, flatulence, bloating, diarrhea, constipation, nausea, and headache.

Seven patients in the 2200 mg BID and 4400 mg BID cohorts had dose-related bloating, gas, flatulence or diarrhea, which subsided in a few days.

Patients in the 2750 mg TID cohort did not experience gas side effects.

The gastrointestinal symptoms were most likely dose-related from an excipient of SCD-101, Dr Gillette said.

He and his colleagues found no significant side effects after 28 days of dosing, and there were no dose reductions or interruptions due to drug-related AEs.

There were also no laboratory or electrocardiogram abnormalities.

“Almost all pain AEs stopped by day 13 in 22 of 23 patients,” Dr Gillette said.

“And unexpectedly, patients began to report that they slept better and had improved energy and cognition,” he noted.

Six patients in the 2200 and 4400 mg BID cohorts reported reduced fatigue as measured by the PROMIS fatigue questionnaire.

And 2 patients with ankle ulcers in the 2 highest dose cohorts reported improved healing.

Two weeks after treatment stopped, patients were almost back to baseline in terms of their chronic pain and fatigue levels, Dr Gillette said.

A parallel design, double-blind, placebo-controlled pilot study of the 2750 mg TID dose is ongoing.

Future studies include a crossover-design, exploratory study of the 2750 mg TID dose and a phase 2 parallel design study of the 2200 mg BID and 2750 mg TID doses.

While the researchers are uncertain about the mechanism of action of SCD-101, they hypothesize that its effects could be due to increased vascular flow, increased oxygen delivery, or a reduction in inflammation.

“This is a promising drug potentially for low-income countries or middle-income countries elsewhere in the world where gene therapy and transplant are really not that feasible,” Dr Gillette said.

Research for this study was supported in part by the National Heart, Lung, and Blood Institute and National Center for Complementary and Integrative Health of the National Institutes of Health.

*Information presented at the meeting differs from the abstract.

Interior view of San Diego

Convention Center, site of

the 2016 ASH Annual Meeting

SAN DIEGO—Results of a phase 1 study suggest that SCD-101, a botanical extract based on an herbal medicine used in Nigeria to treat sickle cell disease (SCD), can reduce pain and fatigue in people with SCD.

The anti-sickling drug also improves the shape of red blood cells but doesn’t produce a change in hemoglobin, according to researchers.

Peter Gillette, MD, of SUNY Downstate in Brooklyn, New York, reported these results at the 2016 ASH Annual Meeting (abstract 121*).

A 6-month phase 2b study conducted previously in Nigeria showed that the herbal medicine Niprisan reduced pain crises and school absenteeism and raised hemoglobin levels compared to placebo.

Based on this study and positive preclinical activity, Dr Gillette and his colleagues undertook a phase 1 study to determine the safety of escalating doses of SCD-101.

Dr Gillette pointed out that Niprisan had been produced commercially in Nigeria but was later removed by the government from the commercial market because of production problems.

The researchers evaluated 23 patients with homozygous SCD or S/beta0 thalassemia.

Patients were aged 18 to 55 years with hemoglobin F of 15% or less and hemoglobin levels between 6.0 and 9.5 g/dL.

Patients could not have had hydroxyurea treatment within 6 months of enrollment, red blood cell transfusion within 3 months, or hospitalization within 4 weeks.

Patients received SCD-101 orally for 28 days administered 2 times daily (BID) or 3 times daily (TID). Doses were 550 mg BID, 1100 mg BID, 2200 mg BID, 4400 mg BID, and 2750 mg TID.

Dr Gillette explained that by distributing the highest dose 3 times over the course of a day, the researchers were able to decrease the side effects of bloating and flatulence on the highest dose.

“Interestingly, with the dose-distributed TID, we found that the hemoglobin had increased by 10%,” he said. “In other words, it appears that the effects are very short-acting, and that by going from a Q12 to a Q8 dosage, the hemoglobin suddenly looks like it might be significant, although this is not a significant change.”

Laboratory outcomes included hemoglobin and hemolysis (LDH, bilirubin, and reticulocyte measurements). Patient-reported outcomes included pain and fatigue.

The most common adverse events (AEs) were pain, flatulence, bloating, diarrhea, constipation, nausea, and headache.

Seven patients in the 2200 mg BID and 4400 mg BID cohorts had dose-related bloating, gas, flatulence or diarrhea, which subsided in a few days.

Patients in the 2750 mg TID cohort did not experience gas side effects.

The gastrointestinal symptoms were most likely dose-related from an excipient of SCD-101, Dr Gillette said.

He and his colleagues found no significant side effects after 28 days of dosing, and there were no dose reductions or interruptions due to drug-related AEs.

There were also no laboratory or electrocardiogram abnormalities.

“Almost all pain AEs stopped by day 13 in 22 of 23 patients,” Dr Gillette said.

“And unexpectedly, patients began to report that they slept better and had improved energy and cognition,” he noted.

Six patients in the 2200 and 4400 mg BID cohorts reported reduced fatigue as measured by the PROMIS fatigue questionnaire.

And 2 patients with ankle ulcers in the 2 highest dose cohorts reported improved healing.

Two weeks after treatment stopped, patients were almost back to baseline in terms of their chronic pain and fatigue levels, Dr Gillette said.

A parallel design, double-blind, placebo-controlled pilot study of the 2750 mg TID dose is ongoing.

Future studies include a crossover-design, exploratory study of the 2750 mg TID dose and a phase 2 parallel design study of the 2200 mg BID and 2750 mg TID doses.

While the researchers are uncertain about the mechanism of action of SCD-101, they hypothesize that its effects could be due to increased vascular flow, increased oxygen delivery, or a reduction in inflammation.

“This is a promising drug potentially for low-income countries or middle-income countries elsewhere in the world where gene therapy and transplant are really not that feasible,” Dr Gillette said.

Research for this study was supported in part by the National Heart, Lung, and Blood Institute and National Center for Complementary and Integrative Health of the National Institutes of Health.

*Information presented at the meeting differs from the abstract.

Interior view of San Diego

Convention Center, site of

the 2016 ASH Annual Meeting

SAN DIEGO—Results of a phase 1 study suggest that SCD-101, a botanical extract based on an herbal medicine used in Nigeria to treat sickle cell disease (SCD), can reduce pain and fatigue in people with SCD.

The anti-sickling drug also improves the shape of red blood cells but doesn’t produce a change in hemoglobin, according to researchers.

Peter Gillette, MD, of SUNY Downstate in Brooklyn, New York, reported these results at the 2016 ASH Annual Meeting (abstract 121*).

A 6-month phase 2b study conducted previously in Nigeria showed that the herbal medicine Niprisan reduced pain crises and school absenteeism and raised hemoglobin levels compared to placebo.

Based on this study and positive preclinical activity, Dr Gillette and his colleagues undertook a phase 1 study to determine the safety of escalating doses of SCD-101.

Dr Gillette pointed out that Niprisan had been produced commercially in Nigeria but was later removed by the government from the commercial market because of production problems.

The researchers evaluated 23 patients with homozygous SCD or S/beta0 thalassemia.

Patients were aged 18 to 55 years with hemoglobin F of 15% or less and hemoglobin levels between 6.0 and 9.5 g/dL.

Patients could not have had hydroxyurea treatment within 6 months of enrollment, red blood cell transfusion within 3 months, or hospitalization within 4 weeks.

Patients received SCD-101 orally for 28 days administered 2 times daily (BID) or 3 times daily (TID). Doses were 550 mg BID, 1100 mg BID, 2200 mg BID, 4400 mg BID, and 2750 mg TID.

Dr Gillette explained that by distributing the highest dose 3 times over the course of a day, the researchers were able to decrease the side effects of bloating and flatulence on the highest dose.

“Interestingly, with the dose-distributed TID, we found that the hemoglobin had increased by 10%,” he said. “In other words, it appears that the effects are very short-acting, and that by going from a Q12 to a Q8 dosage, the hemoglobin suddenly looks like it might be significant, although this is not a significant change.”

Laboratory outcomes included hemoglobin and hemolysis (LDH, bilirubin, and reticulocyte measurements). Patient-reported outcomes included pain and fatigue.

The most common adverse events (AEs) were pain, flatulence, bloating, diarrhea, constipation, nausea, and headache.

Seven patients in the 2200 mg BID and 4400 mg BID cohorts had dose-related bloating, gas, flatulence or diarrhea, which subsided in a few days.

Patients in the 2750 mg TID cohort did not experience gas side effects.

The gastrointestinal symptoms were most likely dose-related from an excipient of SCD-101, Dr Gillette said.

He and his colleagues found no significant side effects after 28 days of dosing, and there were no dose reductions or interruptions due to drug-related AEs.

There were also no laboratory or electrocardiogram abnormalities.

“Almost all pain AEs stopped by day 13 in 22 of 23 patients,” Dr Gillette said.

“And unexpectedly, patients began to report that they slept better and had improved energy and cognition,” he noted.

Six patients in the 2200 and 4400 mg BID cohorts reported reduced fatigue as measured by the PROMIS fatigue questionnaire.

And 2 patients with ankle ulcers in the 2 highest dose cohorts reported improved healing.

Two weeks after treatment stopped, patients were almost back to baseline in terms of their chronic pain and fatigue levels, Dr Gillette said.

A parallel design, double-blind, placebo-controlled pilot study of the 2750 mg TID dose is ongoing.

Future studies include a crossover-design, exploratory study of the 2750 mg TID dose and a phase 2 parallel design study of the 2200 mg BID and 2750 mg TID doses.

While the researchers are uncertain about the mechanism of action of SCD-101, they hypothesize that its effects could be due to increased vascular flow, increased oxygen delivery, or a reduction in inflammation.

“This is a promising drug potentially for low-income countries or middle-income countries elsewhere in the world where gene therapy and transplant are really not that feasible,” Dr Gillette said.

Research for this study was supported in part by the National Heart, Lung, and Blood Institute and National Center for Complementary and Integrative Health of the National Institutes of Health.

*Information presented at the meeting differs from the abstract.