The phase 3 EPIC trial, an evaluation of ponatinib (Iclusig) in patients with newly diagnosed chronic myeloid leukemia (CML), is being discontinued due to adverse events.

All trials of ponatinib were placed on partial clinical hold on October 9, after follow-up data from the phase 2 PACE trial revealed an increased incidence of arterial and venous thrombotic events.

That trial involved patients with CML or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who were resistant to or could not tolerate dasatinib or nilotinib.

The partial clinical hold meant that ponatinib’s makers, Ariad Pharmaceuticals, must pause new enrollment in all ponatinib trials, reduce the doses given to existing patients, and reconsider trial eligibility criteria.

Now, Ariad and the US Food and Drug Administration have agreed that the EPIC trial must be terminated.

“Our decision to stop the EPIC trial at this time is based on our current evaluation of the safety data in the trial since it was placed on partial clinical hold last week,” said Timothy P. Clackson, PhD, president of research and development and chief scientific officer at Ariad.

Patients in the EPIC trial are being removed from treatment and will be transferred to the care of their physicians. A total of 307 patients were enrolled.

The EPIC trial was a randomized, 2-arm, multicenter study comparing the efficacy of ponatinib with that of imatinib in adult patients with newly diagnosed CML in the chronic phase. The trial was being conducted at approximately 150 investigational sites in more than 20 countries.

Patients had to be at least 18 years of age and diagnosed with CML within 6 months prior to enrollment. Approximately 500 patients were to be randomized 1:1 to the standard dose of ponatinib (45 mg once daily) or imatinib (400 mg once daily).

Increasing the imatinib dose to 600 mg or 800 mg per day was permitted. The primary endpoint of the trial was major molecular response at 12 months of treatment.

Ponatinib is still commercially available in the US and European Union for patients with resistant or intolerant CML and Ph+ ALL. Ariad said it is working with health authorities to make appropriate changes to the product labeling to reflect the safety findings from the PACE trial.

For more information about the changes in ponatinib trials, visit www.clinicaltrials.gov, email inquiries to [email protected], or call the Ariad US toll-free number (855) 552-7423, the European Union toll-free number 800 00027423, or the international number +1 (617)-503-7423.

The phase 3 EPIC trial, an evaluation of ponatinib (Iclusig) in patients with newly diagnosed chronic myeloid leukemia (CML), is being discontinued due to adverse events.

All trials of ponatinib were placed on partial clinical hold on October 9, after follow-up data from the phase 2 PACE trial revealed an increased incidence of arterial and venous thrombotic events.

That trial involved patients with CML or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who were resistant to or could not tolerate dasatinib or nilotinib.

The partial clinical hold meant that ponatinib’s makers, Ariad Pharmaceuticals, must pause new enrollment in all ponatinib trials, reduce the doses given to existing patients, and reconsider trial eligibility criteria.

Now, Ariad and the US Food and Drug Administration have agreed that the EPIC trial must be terminated.

“Our decision to stop the EPIC trial at this time is based on our current evaluation of the safety data in the trial since it was placed on partial clinical hold last week,” said Timothy P. Clackson, PhD, president of research and development and chief scientific officer at Ariad.

Patients in the EPIC trial are being removed from treatment and will be transferred to the care of their physicians. A total of 307 patients were enrolled.

The EPIC trial was a randomized, 2-arm, multicenter study comparing the efficacy of ponatinib with that of imatinib in adult patients with newly diagnosed CML in the chronic phase. The trial was being conducted at approximately 150 investigational sites in more than 20 countries.

Patients had to be at least 18 years of age and diagnosed with CML within 6 months prior to enrollment. Approximately 500 patients were to be randomized 1:1 to the standard dose of ponatinib (45 mg once daily) or imatinib (400 mg once daily).

Increasing the imatinib dose to 600 mg or 800 mg per day was permitted. The primary endpoint of the trial was major molecular response at 12 months of treatment.

Ponatinib is still commercially available in the US and European Union for patients with resistant or intolerant CML and Ph+ ALL. Ariad said it is working with health authorities to make appropriate changes to the product labeling to reflect the safety findings from the PACE trial.

For more information about the changes in ponatinib trials, visit www.clinicaltrials.gov, email inquiries to [email protected], or call the Ariad US toll-free number (855) 552-7423, the European Union toll-free number 800 00027423, or the international number +1 (617)-503-7423.

The phase 3 EPIC trial, an evaluation of ponatinib (Iclusig) in patients with newly diagnosed chronic myeloid leukemia (CML), is being discontinued due to adverse events.

All trials of ponatinib were placed on partial clinical hold on October 9, after follow-up data from the phase 2 PACE trial revealed an increased incidence of arterial and venous thrombotic events.

That trial involved patients with CML or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who were resistant to or could not tolerate dasatinib or nilotinib.

The partial clinical hold meant that ponatinib’s makers, Ariad Pharmaceuticals, must pause new enrollment in all ponatinib trials, reduce the doses given to existing patients, and reconsider trial eligibility criteria.

Now, Ariad and the US Food and Drug Administration have agreed that the EPIC trial must be terminated.

“Our decision to stop the EPIC trial at this time is based on our current evaluation of the safety data in the trial since it was placed on partial clinical hold last week,” said Timothy P. Clackson, PhD, president of research and development and chief scientific officer at Ariad.

Patients in the EPIC trial are being removed from treatment and will be transferred to the care of their physicians. A total of 307 patients were enrolled.

The EPIC trial was a randomized, 2-arm, multicenter study comparing the efficacy of ponatinib with that of imatinib in adult patients with newly diagnosed CML in the chronic phase. The trial was being conducted at approximately 150 investigational sites in more than 20 countries.

Patients had to be at least 18 years of age and diagnosed with CML within 6 months prior to enrollment. Approximately 500 patients were to be randomized 1:1 to the standard dose of ponatinib (45 mg once daily) or imatinib (400 mg once daily).

Increasing the imatinib dose to 600 mg or 800 mg per day was permitted. The primary endpoint of the trial was major molecular response at 12 months of treatment.

Ponatinib is still commercially available in the US and European Union for patients with resistant or intolerant CML and Ph+ ALL. Ariad said it is working with health authorities to make appropriate changes to the product labeling to reflect the safety findings from the PACE trial.

For more information about the changes in ponatinib trials, visit www.clinicaltrials.gov, email inquiries to [email protected], or call the Ariad US toll-free number (855) 552-7423, the European Union toll-free number 800 00027423, or the international number +1 (617)-503-7423.

Kevin was doing very well in law school, until he showed up at his professor’s house in the middle of the night. Normally a thoughtful, quiet, introverted young man, Kevin was hardly recognizable to his professor, who found him outside yelling loudly and demanding to speak about an underground conspiracy he believed he had uncovered. He had always been a good student, and his family was very proud of his accomplishments up until now. At the age of 24, Kevin’s first manic episode was triggered by late nights studying for his law school exams and marijuana use to cope with stress.

Police responded to noise complaints, and Kevin was hospitalized. The manic episode resolved surprisingly quickly in the absence of marijuana use and with the help of an atypical antipsychotic. The patient’s intelligence and articulate lawyer-in-training charm made his inpatient doctors hard pressed to justify an extended hospital stay, and he was discharged 3 days later with a prescription and instructions for follow-up. He promptly discarded both.

When his next manic episode arose, Kevin disappeared for 2 weeks, and after fearing the worst, Kevin’s family was relieved to receive a call from Kevin’s aunt, who lived across the country and had just found him at her doorstep. This time, without the involvement of law enforcement, there seemed to be no way for Kevin’s mother, father, older sister, and aunt to persuade Kevin to enter the hospital or to take medications. Kevin’s aunt accompanied him on a plane home, and in the face of Kevin’s unwillingness to enter treatment alone, they decided to enter treatment as a family.

Predictors of episodes

The strongest predictors of future episodes and poor outcome in patients with bipolar disorder are a greater number of previous episodes, shorter intervals between episodes, a history of psychosis, a history of anxiety, persistence of affective symptoms and episodes, and stressful life events. Some evidence has suggested that poor job functioning, lack of social support, increased expressed emotion in the family, and introverted or obsessional personality traits all might predict poor outcome in bipolar disorder (J. Psychiatr. Pract. 2006;12:269-82).

An overwhelmingly emotional home environment can make a large contribution to relapse. Multiple studies have shown that a high level of "expressed emotion" (characterized by overinvolvement and excessive criticism) predicts patient relapse independent of medication compliance, baseline symptoms, and demographics (Arch. Gen. Psychiatry 1988;45:225-31)

Because bipolar disorder is an unpredictable, potentially destructive illness, it is important to grab any factors that we and our patients might have control over and do our best to modify them positively. With this in mind, the Family Focused Treatment (FFT) model was developed, with the philosophy that by keeping patients well informed about the facts and realities of the disorder and working on the communication and coping mechanisms operating within the family, relapse prevention and emotional stability will be better maintained. In this way, the predictive factors of stressful life events, poor social support, and family-expressed emotion can be modified. FFT is a time limited (usually 12 sessions), highly effective treatment modality.

The principles of FFT were adapted into an ongoing-treatment model that can be implemented in a community setting, termed Family Inclusive Treatment (FIT) and used by the Family Center for Bipolar in New York City, for example. FIT consists of an engagement period at the initiation of treatment, focused on psychoeducation and relapse prevention planning. FIT is unique in that every patient is required to sign a release of information giving permission for full, open communication at all times between the patient’s clinician and a treatment partner of their choosing.

After the initial engagement period, there are quarterly family visits to supplement regular individual treatment. Other modalities such as individual therapy, pharmacotherapy, and group therapy are used according to the clinician’s judgment.

This form of treatment is innovative in that it treats bipolar illness just like any other chronic illness. It promotes open communication between families of patients with bipolar disorder and the patients themselves with regard to symptoms and medications. In this way patients are not isolated from their families; they can talk openly with one another and their clinician as they would do if somebody in the family had Alzheimer’s disease or diabetes.

It has been reported that up to 46% of the caregivers of patients with bipolar disorder report depression, and up to 32.4% report use of mental health services. These symptoms tend to be dependent on the nature of the caregiving relationship, suggesting that specialized interventions addressing the psychiatric needs of bipolar families might result in improved outcomes for both patients and their family members, in addition to decreases in health care costs (J. Affect. Disord. 2010;121:10-21).

Together with therapy and medication management, clinicians working in the FIT model strive to create an environment that minimizes, as much as possible, the impact of bipolar disorder on the affected individuals and their close loved ones.

Many studies have confirmed the efficacy of various psychosocial treatments for bipolar disorder (J. Consult. Clin. Psychol. 2003;7:482-92; J. Clin. Psychiatry 2006;67 [suppl. 11]:28-33; J. Affect. Disord. 2007;98:11-27), and there has been a push for the integration of psychosocial treatment with pharmacotherapy, as the latter is less often sufficient on its own in preventing relapse.

Patient, family begin journey

Kevin and his family entered into family treatment. They started off with the psychoeducation portion of the treatment, and many of the myths and misinformation that they had held about bipolar disorder were dispelled. Even Kevin was able to engage in the information exchange, which he initially approached from an academic, impersonal vantage point. The communication skills phase proved more problematic as it became more personal, but still, the focus was on the family’s communication and not on Kevin as a psychiatric patient, so he responded well.

It was uncovered that Kevin’s father has always been highly critical, and Kevin’s mother tends to overprotect her children to compensate. They were taught new skills to express their feelings toward one another, and especially toward Kevin, in more productive and positive ways. In addition, they got a chance to practice those skills in subsequent sessions.

The modules continued in this vein until the family portion of treatment had completed. By this time, Kevin had developed a good rapport with his clinician, and he continued treatment despite his persistent reservations about accepting his illness. The family environment improved, and though Kevin was only sporadically compliant with his medication, the reduced stress at home and improved coping skills drove him less often to use marijuana for "self-medication," which decreased his manic episodes.

Kevin’s family periodically rejoined him in treatment sessions at predefined intervals, to check in and assess his and their progress. They were comfortable speaking with Kevin’s doctor and would call when they noticed any of the warning signs that they had collaboratively determined as markers of upcoming mania. In this way, they were all effective at keeping Kevin’s moods stable and keeping him out of the hospital.

The psychiatrist in routine practice might neither follow a manualized algorithm for family treatment nor have the time or resources at her disposal to provide a full "curriculum." Still, she can have the same success in engaging a family in understanding their loved one’s illness and contributing to the family member’s stability.

Objectives for family-focused treatment

The following objectives are adapted from "Bipolar Disorder: A Family-Focused Treatment Approach," 2nd ed. (New York: The Guilford Press, 2010):

• Encourage the patient and the family to admit that there is a vulnerability to future episodes by educating them about the natural course, progression, and chronic nature of bipolar disorder.

• Enable the patient and the family to recognize that medications are important for controlling symptoms. Provide concrete evidence for the importance and efficacy of medications and the risks of discontinuation. Explore reasons for resisting medications, including fears about becoming dependent.

• Help the patient and the family see the differences between the patient’s personality and his/her illness. Make a list of the patient’s positive attributes and a separate list of warning signs of mania. Frequently reinforce the distinction between the two.

• Assist the patient and the family in dealing with stressors that might cause a recurrence and help them rebuild family relationship ruptures after an episode. Suggest methods for positive, constructive communication such as active listening (nodding, making eye contact, paraphrasing, asking relevant questions) and expressing positive feelings toward a family member related to a specific example of a behavior.

Dr. Heru is with the department of psychiatry at the University of Colorado at Denver, Aurora. She is editor of the recently published book, "Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals" (New York: Routledge, 2013). Dr. Mednick is an attending psychiatrist at the Family Center for Bipolar at Beth Israel Medical Center in New York City.

Kevin was doing very well in law school, until he showed up at his professor’s house in the middle of the night. Normally a thoughtful, quiet, introverted young man, Kevin was hardly recognizable to his professor, who found him outside yelling loudly and demanding to speak about an underground conspiracy he believed he had uncovered. He had always been a good student, and his family was very proud of his accomplishments up until now. At the age of 24, Kevin’s first manic episode was triggered by late nights studying for his law school exams and marijuana use to cope with stress.

Police responded to noise complaints, and Kevin was hospitalized. The manic episode resolved surprisingly quickly in the absence of marijuana use and with the help of an atypical antipsychotic. The patient’s intelligence and articulate lawyer-in-training charm made his inpatient doctors hard pressed to justify an extended hospital stay, and he was discharged 3 days later with a prescription and instructions for follow-up. He promptly discarded both.

When his next manic episode arose, Kevin disappeared for 2 weeks, and after fearing the worst, Kevin’s family was relieved to receive a call from Kevin’s aunt, who lived across the country and had just found him at her doorstep. This time, without the involvement of law enforcement, there seemed to be no way for Kevin’s mother, father, older sister, and aunt to persuade Kevin to enter the hospital or to take medications. Kevin’s aunt accompanied him on a plane home, and in the face of Kevin’s unwillingness to enter treatment alone, they decided to enter treatment as a family.

Predictors of episodes

The strongest predictors of future episodes and poor outcome in patients with bipolar disorder are a greater number of previous episodes, shorter intervals between episodes, a history of psychosis, a history of anxiety, persistence of affective symptoms and episodes, and stressful life events. Some evidence has suggested that poor job functioning, lack of social support, increased expressed emotion in the family, and introverted or obsessional personality traits all might predict poor outcome in bipolar disorder (J. Psychiatr. Pract. 2006;12:269-82).

An overwhelmingly emotional home environment can make a large contribution to relapse. Multiple studies have shown that a high level of "expressed emotion" (characterized by overinvolvement and excessive criticism) predicts patient relapse independent of medication compliance, baseline symptoms, and demographics (Arch. Gen. Psychiatry 1988;45:225-31)

Because bipolar disorder is an unpredictable, potentially destructive illness, it is important to grab any factors that we and our patients might have control over and do our best to modify them positively. With this in mind, the Family Focused Treatment (FFT) model was developed, with the philosophy that by keeping patients well informed about the facts and realities of the disorder and working on the communication and coping mechanisms operating within the family, relapse prevention and emotional stability will be better maintained. In this way, the predictive factors of stressful life events, poor social support, and family-expressed emotion can be modified. FFT is a time limited (usually 12 sessions), highly effective treatment modality.

The principles of FFT were adapted into an ongoing-treatment model that can be implemented in a community setting, termed Family Inclusive Treatment (FIT) and used by the Family Center for Bipolar in New York City, for example. FIT consists of an engagement period at the initiation of treatment, focused on psychoeducation and relapse prevention planning. FIT is unique in that every patient is required to sign a release of information giving permission for full, open communication at all times between the patient’s clinician and a treatment partner of their choosing.

After the initial engagement period, there are quarterly family visits to supplement regular individual treatment. Other modalities such as individual therapy, pharmacotherapy, and group therapy are used according to the clinician’s judgment.

This form of treatment is innovative in that it treats bipolar illness just like any other chronic illness. It promotes open communication between families of patients with bipolar disorder and the patients themselves with regard to symptoms and medications. In this way patients are not isolated from their families; they can talk openly with one another and their clinician as they would do if somebody in the family had Alzheimer’s disease or diabetes.

It has been reported that up to 46% of the caregivers of patients with bipolar disorder report depression, and up to 32.4% report use of mental health services. These symptoms tend to be dependent on the nature of the caregiving relationship, suggesting that specialized interventions addressing the psychiatric needs of bipolar families might result in improved outcomes for both patients and their family members, in addition to decreases in health care costs (J. Affect. Disord. 2010;121:10-21).

Together with therapy and medication management, clinicians working in the FIT model strive to create an environment that minimizes, as much as possible, the impact of bipolar disorder on the affected individuals and their close loved ones.

Many studies have confirmed the efficacy of various psychosocial treatments for bipolar disorder (J. Consult. Clin. Psychol. 2003;7:482-92; J. Clin. Psychiatry 2006;67 [suppl. 11]:28-33; J. Affect. Disord. 2007;98:11-27), and there has been a push for the integration of psychosocial treatment with pharmacotherapy, as the latter is less often sufficient on its own in preventing relapse.

Patient, family begin journey

Kevin and his family entered into family treatment. They started off with the psychoeducation portion of the treatment, and many of the myths and misinformation that they had held about bipolar disorder were dispelled. Even Kevin was able to engage in the information exchange, which he initially approached from an academic, impersonal vantage point. The communication skills phase proved more problematic as it became more personal, but still, the focus was on the family’s communication and not on Kevin as a psychiatric patient, so he responded well.

It was uncovered that Kevin’s father has always been highly critical, and Kevin’s mother tends to overprotect her children to compensate. They were taught new skills to express their feelings toward one another, and especially toward Kevin, in more productive and positive ways. In addition, they got a chance to practice those skills in subsequent sessions.

The modules continued in this vein until the family portion of treatment had completed. By this time, Kevin had developed a good rapport with his clinician, and he continued treatment despite his persistent reservations about accepting his illness. The family environment improved, and though Kevin was only sporadically compliant with his medication, the reduced stress at home and improved coping skills drove him less often to use marijuana for "self-medication," which decreased his manic episodes.

Kevin’s family periodically rejoined him in treatment sessions at predefined intervals, to check in and assess his and their progress. They were comfortable speaking with Kevin’s doctor and would call when they noticed any of the warning signs that they had collaboratively determined as markers of upcoming mania. In this way, they were all effective at keeping Kevin’s moods stable and keeping him out of the hospital.

The psychiatrist in routine practice might neither follow a manualized algorithm for family treatment nor have the time or resources at her disposal to provide a full "curriculum." Still, she can have the same success in engaging a family in understanding their loved one’s illness and contributing to the family member’s stability.

Objectives for family-focused treatment

The following objectives are adapted from "Bipolar Disorder: A Family-Focused Treatment Approach," 2nd ed. (New York: The Guilford Press, 2010):

• Encourage the patient and the family to admit that there is a vulnerability to future episodes by educating them about the natural course, progression, and chronic nature of bipolar disorder.

• Enable the patient and the family to recognize that medications are important for controlling symptoms. Provide concrete evidence for the importance and efficacy of medications and the risks of discontinuation. Explore reasons for resisting medications, including fears about becoming dependent.

• Help the patient and the family see the differences between the patient’s personality and his/her illness. Make a list of the patient’s positive attributes and a separate list of warning signs of mania. Frequently reinforce the distinction between the two.

• Assist the patient and the family in dealing with stressors that might cause a recurrence and help them rebuild family relationship ruptures after an episode. Suggest methods for positive, constructive communication such as active listening (nodding, making eye contact, paraphrasing, asking relevant questions) and expressing positive feelings toward a family member related to a specific example of a behavior.

Dr. Heru is with the department of psychiatry at the University of Colorado at Denver, Aurora. She is editor of the recently published book, "Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals" (New York: Routledge, 2013). Dr. Mednick is an attending psychiatrist at the Family Center for Bipolar at Beth Israel Medical Center in New York City.

Kevin was doing very well in law school, until he showed up at his professor’s house in the middle of the night. Normally a thoughtful, quiet, introverted young man, Kevin was hardly recognizable to his professor, who found him outside yelling loudly and demanding to speak about an underground conspiracy he believed he had uncovered. He had always been a good student, and his family was very proud of his accomplishments up until now. At the age of 24, Kevin’s first manic episode was triggered by late nights studying for his law school exams and marijuana use to cope with stress.

Police responded to noise complaints, and Kevin was hospitalized. The manic episode resolved surprisingly quickly in the absence of marijuana use and with the help of an atypical antipsychotic. The patient’s intelligence and articulate lawyer-in-training charm made his inpatient doctors hard pressed to justify an extended hospital stay, and he was discharged 3 days later with a prescription and instructions for follow-up. He promptly discarded both.

When his next manic episode arose, Kevin disappeared for 2 weeks, and after fearing the worst, Kevin’s family was relieved to receive a call from Kevin’s aunt, who lived across the country and had just found him at her doorstep. This time, without the involvement of law enforcement, there seemed to be no way for Kevin’s mother, father, older sister, and aunt to persuade Kevin to enter the hospital or to take medications. Kevin’s aunt accompanied him on a plane home, and in the face of Kevin’s unwillingness to enter treatment alone, they decided to enter treatment as a family.

Predictors of episodes

The strongest predictors of future episodes and poor outcome in patients with bipolar disorder are a greater number of previous episodes, shorter intervals between episodes, a history of psychosis, a history of anxiety, persistence of affective symptoms and episodes, and stressful life events. Some evidence has suggested that poor job functioning, lack of social support, increased expressed emotion in the family, and introverted or obsessional personality traits all might predict poor outcome in bipolar disorder (J. Psychiatr. Pract. 2006;12:269-82).

An overwhelmingly emotional home environment can make a large contribution to relapse. Multiple studies have shown that a high level of "expressed emotion" (characterized by overinvolvement and excessive criticism) predicts patient relapse independent of medication compliance, baseline symptoms, and demographics (Arch. Gen. Psychiatry 1988;45:225-31)

Because bipolar disorder is an unpredictable, potentially destructive illness, it is important to grab any factors that we and our patients might have control over and do our best to modify them positively. With this in mind, the Family Focused Treatment (FFT) model was developed, with the philosophy that by keeping patients well informed about the facts and realities of the disorder and working on the communication and coping mechanisms operating within the family, relapse prevention and emotional stability will be better maintained. In this way, the predictive factors of stressful life events, poor social support, and family-expressed emotion can be modified. FFT is a time limited (usually 12 sessions), highly effective treatment modality.

The principles of FFT were adapted into an ongoing-treatment model that can be implemented in a community setting, termed Family Inclusive Treatment (FIT) and used by the Family Center for Bipolar in New York City, for example. FIT consists of an engagement period at the initiation of treatment, focused on psychoeducation and relapse prevention planning. FIT is unique in that every patient is required to sign a release of information giving permission for full, open communication at all times between the patient’s clinician and a treatment partner of their choosing.

After the initial engagement period, there are quarterly family visits to supplement regular individual treatment. Other modalities such as individual therapy, pharmacotherapy, and group therapy are used according to the clinician’s judgment.

This form of treatment is innovative in that it treats bipolar illness just like any other chronic illness. It promotes open communication between families of patients with bipolar disorder and the patients themselves with regard to symptoms and medications. In this way patients are not isolated from their families; they can talk openly with one another and their clinician as they would do if somebody in the family had Alzheimer’s disease or diabetes.

It has been reported that up to 46% of the caregivers of patients with bipolar disorder report depression, and up to 32.4% report use of mental health services. These symptoms tend to be dependent on the nature of the caregiving relationship, suggesting that specialized interventions addressing the psychiatric needs of bipolar families might result in improved outcomes for both patients and their family members, in addition to decreases in health care costs (J. Affect. Disord. 2010;121:10-21).

Together with therapy and medication management, clinicians working in the FIT model strive to create an environment that minimizes, as much as possible, the impact of bipolar disorder on the affected individuals and their close loved ones.

Many studies have confirmed the efficacy of various psychosocial treatments for bipolar disorder (J. Consult. Clin. Psychol. 2003;7:482-92; J. Clin. Psychiatry 2006;67 [suppl. 11]:28-33; J. Affect. Disord. 2007;98:11-27), and there has been a push for the integration of psychosocial treatment with pharmacotherapy, as the latter is less often sufficient on its own in preventing relapse.

Patient, family begin journey

Kevin and his family entered into family treatment. They started off with the psychoeducation portion of the treatment, and many of the myths and misinformation that they had held about bipolar disorder were dispelled. Even Kevin was able to engage in the information exchange, which he initially approached from an academic, impersonal vantage point. The communication skills phase proved more problematic as it became more personal, but still, the focus was on the family’s communication and not on Kevin as a psychiatric patient, so he responded well.

It was uncovered that Kevin’s father has always been highly critical, and Kevin’s mother tends to overprotect her children to compensate. They were taught new skills to express their feelings toward one another, and especially toward Kevin, in more productive and positive ways. In addition, they got a chance to practice those skills in subsequent sessions.

The modules continued in this vein until the family portion of treatment had completed. By this time, Kevin had developed a good rapport with his clinician, and he continued treatment despite his persistent reservations about accepting his illness. The family environment improved, and though Kevin was only sporadically compliant with his medication, the reduced stress at home and improved coping skills drove him less often to use marijuana for "self-medication," which decreased his manic episodes.

Kevin’s family periodically rejoined him in treatment sessions at predefined intervals, to check in and assess his and their progress. They were comfortable speaking with Kevin’s doctor and would call when they noticed any of the warning signs that they had collaboratively determined as markers of upcoming mania. In this way, they were all effective at keeping Kevin’s moods stable and keeping him out of the hospital.

The psychiatrist in routine practice might neither follow a manualized algorithm for family treatment nor have the time or resources at her disposal to provide a full "curriculum." Still, she can have the same success in engaging a family in understanding their loved one’s illness and contributing to the family member’s stability.

Objectives for family-focused treatment

The following objectives are adapted from "Bipolar Disorder: A Family-Focused Treatment Approach," 2nd ed. (New York: The Guilford Press, 2010):

• Encourage the patient and the family to admit that there is a vulnerability to future episodes by educating them about the natural course, progression, and chronic nature of bipolar disorder.

• Enable the patient and the family to recognize that medications are important for controlling symptoms. Provide concrete evidence for the importance and efficacy of medications and the risks of discontinuation. Explore reasons for resisting medications, including fears about becoming dependent.

• Help the patient and the family see the differences between the patient’s personality and his/her illness. Make a list of the patient’s positive attributes and a separate list of warning signs of mania. Frequently reinforce the distinction between the two.

• Assist the patient and the family in dealing with stressors that might cause a recurrence and help them rebuild family relationship ruptures after an episode. Suggest methods for positive, constructive communication such as active listening (nodding, making eye contact, paraphrasing, asking relevant questions) and expressing positive feelings toward a family member related to a specific example of a behavior.

Dr. Heru is with the department of psychiatry at the University of Colorado at Denver, Aurora. She is editor of the recently published book, "Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals" (New York: Routledge, 2013). Dr. Mednick is an attending psychiatrist at the Family Center for Bipolar at Beth Israel Medical Center in New York City.

The investigational agent ridaforolimus reduced the risk for progression and death by 28% in previously treated patients with advanced sarcoma in a large phase III study.

Results of the SUCCEED (Sarcoma Multicenter Clinical Evaluation of the Efficacy of Ridaforolimus) study showed that there was a small, but significant median progression-free survival (PFS) gain of 3.3 weeks vs. placebo (17.7 vs. 14.6 weeks, hazard ratio, 0.72; P less than .001) by independent review.

"The absolute magnitude of this statistically significant improvement in disease control was small because of the more rapid than expected progression in all patients in this study," said Dr. George D. Demetri of the Dana-Farber Cancer Institute and Harvard Medical School in Boston, and his associates (J. Clin. Oncol. 2013;31:2485-92).

"This finding confirms the aggressive nature of advanced sarcomas and underscores the medical need of these patients to improve with available therapy."

"To our knowledge, this is the first study demonstrating a statistically significant, although clinically small, impact on maintenance treatment on tumor progression in patients with sarcomas," the researchers said. "Future studies will build on these results in an effort to improve the outcomes of this rapidly progressive life-threatening disease."

The study was designed with the premise that the median time to progression would be around 6-9 months in the control arm. In fact, it was less than 4 months, and there was a 6-month PFS rate of 23% and average tumor growth of 10% in target lesions.

"This finding confirms the aggressive nature of advanced sarcomas and underscores the medical need of these patients to improve with available therapy," the researchers said.

The SUCCEED trial was an international, randomized, double blind, placebo-controlled trial of 711 patients with advanced soft tissue or bone sarcomas who had achieved stable disease or a continued partial or complete response to immediately preceding cytotoxic chemotherapy Patients were randomized to receive either the mammalian target of rapamycin inhibitor ridaforolimus (n = 347), given at a dose of four 10 mg tablets/day for 5 days every week, or matching placebo tablets (n = 364).

Baseline patient characteristics were similar between the two study groups. The mean age of patients was 52 years in the ridaforolimus arm and 50 years in the placebo arm. The majority (89.3%) of patients had soft tissue sarcomas, with the remainder having bone sarcomas. Almost 75% of tumors were high grade, 66.6% of patients had metastatic disease involving the lung, 14.4% involving the liver, and 11.5% involving the bone. Around 40% of patients had received two or more prior cytotoxic chemotherapy regimens, and the best response to treatment had been stable disease in 74.4%, a partial response in 18.4%, and a complete response in 5.5%.

Investigator-assessed PFS showed slightly better median survival rates of 22.4 vs. 14.7 weeks (HR, 0.69; P less than .001). There was mean decrease in target lesion size of 1.3% in the ridaforolimus arm vs. a 10.3% increase in size in the placebo arm (P less than .001).

No overall survival benefit was observed in the trial. Based on 478 death events and a minimum of 2 years’ follow-up, median overall survival was 90.6 weeks vs. 85.3 weeks (HR, 0.93; P = .46). Dr. Demetri and his coworkers point out, however, that the study was not powered to determine an overall survival benefit.

Adverse effects of any grade occurred in 100% of ridaforolimus-treated and 93.6% of placebo-treated patients. Adverse effects of note that occurred to a greater extent in the active treatment arm included stomatitis, thrombocytopenia, infections, rash, hypertriglyceridemia, and anemia. Grade 3 or higher adverse events occurred in 64.1% of patients treated with ridaforolimus and 25.6% of those in the placebo arm.

This was an unselected patient population but no potential biomarkers or predictors for response have been identified. As ridaforolimus improved, the best target lesion response and the clinical benefit rate, it might contribute to tumor growth control, the researchers speculated. They therefore suggested that it might be better suited as an element of combination treatment with other tumor-signaling inhibitors.

The SUCCEED study was funded by Merck, Sharp, and Dohme. Dr. Demetri has received consultancy fees and research funding from Merck and ARIAD Pharmaceuticals. Several of his coauthors had also received honoraria from Merck or were employees of the company.

The investigational agent ridaforolimus reduced the risk for progression and death by 28% in previously treated patients with advanced sarcoma in a large phase III study.

Results of the SUCCEED (Sarcoma Multicenter Clinical Evaluation of the Efficacy of Ridaforolimus) study showed that there was a small, but significant median progression-free survival (PFS) gain of 3.3 weeks vs. placebo (17.7 vs. 14.6 weeks, hazard ratio, 0.72; P less than .001) by independent review.

"The absolute magnitude of this statistically significant improvement in disease control was small because of the more rapid than expected progression in all patients in this study," said Dr. George D. Demetri of the Dana-Farber Cancer Institute and Harvard Medical School in Boston, and his associates (J. Clin. Oncol. 2013;31:2485-92).

"This finding confirms the aggressive nature of advanced sarcomas and underscores the medical need of these patients to improve with available therapy."

"To our knowledge, this is the first study demonstrating a statistically significant, although clinically small, impact on maintenance treatment on tumor progression in patients with sarcomas," the researchers said. "Future studies will build on these results in an effort to improve the outcomes of this rapidly progressive life-threatening disease."

The study was designed with the premise that the median time to progression would be around 6-9 months in the control arm. In fact, it was less than 4 months, and there was a 6-month PFS rate of 23% and average tumor growth of 10% in target lesions.

"This finding confirms the aggressive nature of advanced sarcomas and underscores the medical need of these patients to improve with available therapy," the researchers said.

The SUCCEED trial was an international, randomized, double blind, placebo-controlled trial of 711 patients with advanced soft tissue or bone sarcomas who had achieved stable disease or a continued partial or complete response to immediately preceding cytotoxic chemotherapy Patients were randomized to receive either the mammalian target of rapamycin inhibitor ridaforolimus (n = 347), given at a dose of four 10 mg tablets/day for 5 days every week, or matching placebo tablets (n = 364).

Baseline patient characteristics were similar between the two study groups. The mean age of patients was 52 years in the ridaforolimus arm and 50 years in the placebo arm. The majority (89.3%) of patients had soft tissue sarcomas, with the remainder having bone sarcomas. Almost 75% of tumors were high grade, 66.6% of patients had metastatic disease involving the lung, 14.4% involving the liver, and 11.5% involving the bone. Around 40% of patients had received two or more prior cytotoxic chemotherapy regimens, and the best response to treatment had been stable disease in 74.4%, a partial response in 18.4%, and a complete response in 5.5%.

Investigator-assessed PFS showed slightly better median survival rates of 22.4 vs. 14.7 weeks (HR, 0.69; P less than .001). There was mean decrease in target lesion size of 1.3% in the ridaforolimus arm vs. a 10.3% increase in size in the placebo arm (P less than .001).

No overall survival benefit was observed in the trial. Based on 478 death events and a minimum of 2 years’ follow-up, median overall survival was 90.6 weeks vs. 85.3 weeks (HR, 0.93; P = .46). Dr. Demetri and his coworkers point out, however, that the study was not powered to determine an overall survival benefit.

Adverse effects of any grade occurred in 100% of ridaforolimus-treated and 93.6% of placebo-treated patients. Adverse effects of note that occurred to a greater extent in the active treatment arm included stomatitis, thrombocytopenia, infections, rash, hypertriglyceridemia, and anemia. Grade 3 or higher adverse events occurred in 64.1% of patients treated with ridaforolimus and 25.6% of those in the placebo arm.

This was an unselected patient population but no potential biomarkers or predictors for response have been identified. As ridaforolimus improved, the best target lesion response and the clinical benefit rate, it might contribute to tumor growth control, the researchers speculated. They therefore suggested that it might be better suited as an element of combination treatment with other tumor-signaling inhibitors.

The SUCCEED study was funded by Merck, Sharp, and Dohme. Dr. Demetri has received consultancy fees and research funding from Merck and ARIAD Pharmaceuticals. Several of his coauthors had also received honoraria from Merck or were employees of the company.

The investigational agent ridaforolimus reduced the risk for progression and death by 28% in previously treated patients with advanced sarcoma in a large phase III study.

Results of the SUCCEED (Sarcoma Multicenter Clinical Evaluation of the Efficacy of Ridaforolimus) study showed that there was a small, but significant median progression-free survival (PFS) gain of 3.3 weeks vs. placebo (17.7 vs. 14.6 weeks, hazard ratio, 0.72; P less than .001) by independent review.

"The absolute magnitude of this statistically significant improvement in disease control was small because of the more rapid than expected progression in all patients in this study," said Dr. George D. Demetri of the Dana-Farber Cancer Institute and Harvard Medical School in Boston, and his associates (J. Clin. Oncol. 2013;31:2485-92).

"This finding confirms the aggressive nature of advanced sarcomas and underscores the medical need of these patients to improve with available therapy."

"To our knowledge, this is the first study demonstrating a statistically significant, although clinically small, impact on maintenance treatment on tumor progression in patients with sarcomas," the researchers said. "Future studies will build on these results in an effort to improve the outcomes of this rapidly progressive life-threatening disease."

The study was designed with the premise that the median time to progression would be around 6-9 months in the control arm. In fact, it was less than 4 months, and there was a 6-month PFS rate of 23% and average tumor growth of 10% in target lesions.

"This finding confirms the aggressive nature of advanced sarcomas and underscores the medical need of these patients to improve with available therapy," the researchers said.

The SUCCEED trial was an international, randomized, double blind, placebo-controlled trial of 711 patients with advanced soft tissue or bone sarcomas who had achieved stable disease or a continued partial or complete response to immediately preceding cytotoxic chemotherapy Patients were randomized to receive either the mammalian target of rapamycin inhibitor ridaforolimus (n = 347), given at a dose of four 10 mg tablets/day for 5 days every week, or matching placebo tablets (n = 364).

Baseline patient characteristics were similar between the two study groups. The mean age of patients was 52 years in the ridaforolimus arm and 50 years in the placebo arm. The majority (89.3%) of patients had soft tissue sarcomas, with the remainder having bone sarcomas. Almost 75% of tumors were high grade, 66.6% of patients had metastatic disease involving the lung, 14.4% involving the liver, and 11.5% involving the bone. Around 40% of patients had received two or more prior cytotoxic chemotherapy regimens, and the best response to treatment had been stable disease in 74.4%, a partial response in 18.4%, and a complete response in 5.5%.

Investigator-assessed PFS showed slightly better median survival rates of 22.4 vs. 14.7 weeks (HR, 0.69; P less than .001). There was mean decrease in target lesion size of 1.3% in the ridaforolimus arm vs. a 10.3% increase in size in the placebo arm (P less than .001).

No overall survival benefit was observed in the trial. Based on 478 death events and a minimum of 2 years’ follow-up, median overall survival was 90.6 weeks vs. 85.3 weeks (HR, 0.93; P = .46). Dr. Demetri and his coworkers point out, however, that the study was not powered to determine an overall survival benefit.

Adverse effects of any grade occurred in 100% of ridaforolimus-treated and 93.6% of placebo-treated patients. Adverse effects of note that occurred to a greater extent in the active treatment arm included stomatitis, thrombocytopenia, infections, rash, hypertriglyceridemia, and anemia. Grade 3 or higher adverse events occurred in 64.1% of patients treated with ridaforolimus and 25.6% of those in the placebo arm.

This was an unselected patient population but no potential biomarkers or predictors for response have been identified. As ridaforolimus improved, the best target lesion response and the clinical benefit rate, it might contribute to tumor growth control, the researchers speculated. They therefore suggested that it might be better suited as an element of combination treatment with other tumor-signaling inhibitors.

The SUCCEED study was funded by Merck, Sharp, and Dohme. Dr. Demetri has received consultancy fees and research funding from Merck and ARIAD Pharmaceuticals. Several of his coauthors had also received honoraria from Merck or were employees of the company.

B-cell lymphoma

The UK’s National Institute for Health and Care Excellence (NICE) has re-examined its draft guidance for pixantrone (Pixuvri) but come to the same conclusion as before.

The organization is still not recommending pixantrone monotherapy to treat multiply relapsed or refractory B-cell non-Hodgkin lymphoma (NHL).

Of course, this recommendation may change, as this is not NICE’s final guidance on pixantrone.

For this second consultation on the draft guidance, an independent appraisal committee re-examined the clinical and cost-effectiveness of pixantrone.

This time, the committee took into consideration a patient access scheme submitted by pixantrone’s manufacturer, Cell Therapeutics. The scheme was designed to make the drug more cost-effective for the National Health Service (NHS).

“Unfortunately, the committee concluded that this scheme . . . does not overcome the uncertainties in the evidence for the drug’s clinical effectiveness over and above current treatments for this disease,” said NICE Chief Executive Sir Andrew Dillon.

In fact, the committee found the scheme did not make pixantrone cost-effective according to the accepted definition—costing £20,000 to £30,000 per quality-adjusted life year (QALY) gained.

Evaluating trial data

When considering the clinical effectiveness of pixantrone, the appraisal committee analyzed data from the EXTEND PIX301 trial, which was submitted by the manufacturer.

The trial enrolled adults with aggressive, de novo, or transformed NHL that had relapsed after 2 or more chemotherapy regimens, including at least 1 standard anthracycline-containing regimen with a response that lasted at least 24 weeks. Seventy patients were randomized to pixantrone, and 70 were randomized to a physician’s choice of single-agent comparators.

The committee pointed out a number of uncertainties associated with the trial. One was that it did not include the planned number of patients (which was 320), so it may not have been sufficiently powered to detect differences between the treatment arms.

Another concern was that the trial’s primary endpoint was complete or unconfirmed complete response, rather than overall survival or progression-free survival. In fact, there was a lack of statistically significant difference in overall survival between treatment arms. And other differences between the treatment arms were not always statistically significant.

These factors led the committee to conclude that there is insufficient evidence to suggest pixantrone is more clinically effective than treatments currently used in clinical practice.

Suitability for the UK

The appraisal committee also heard evidence from clinical experts and patient representatives. This information revealed differences in previous treatment between the PIX301 trial population and UK clinical practice.

Therefore, the committee said it could not determine the clinical effectiveness of pixantrone for a UK population.

In addition, there is doubt regarding the clinical benefit of pixantrone in patients who previously received rituximab. And this applies to virtually all patients with relapsed or refractory aggressive B-cell lymphoma in England and Wales, the committee noted.

(The European Medicines Agency’s conditional approval of pixantrone stipulated that an additional trial must confirm the clinical benefit of the drug in patients who have previously received rituximab.)

Calculating costs

The committee estimated the patient access scheme for pixantrone would most likely result in an incremental cost-effectiveness ratio of £30,700 per QALY gained. This is above the range normally considered to be cost-effective—usually £20,000 to £30,000 per QALY gained.

This factor, along with the lack of clinical effectiveness, prompted the committee to conclude that pixantrone would not be a cost-effective use of NHS resources.

According to Cell Therapeutics, pixantrone costs £553.50 per 20 mL vial. The recommended dosage of pixantrone is 50 mg/m² on days 1, 8, and 15 of each 28-day cycle, for up to 6 cycles.

The estimated cost of a course of treatment is £19,926. This is based on the median length of treatment in the PIX301 trial—4 cycles, using an average of 3 vials per dose.

About the guidance

Individuals can comment on the pixantrone draft guidance via the NICE website. It is open until November 4, 2013. 

This is the third version of the draft guidance published and the second consultation launched. The draft guidance was initially published for consultation in April 2013, followed by a final draft guidance in June 2013. But this document was withdrawn during the appeal stage because the manufacturer submitted the patient access scheme.

Until the final guidance is issued to the NHS, organizations should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations.

B-cell lymphoma

The UK’s National Institute for Health and Care Excellence (NICE) has re-examined its draft guidance for pixantrone (Pixuvri) but come to the same conclusion as before.

The organization is still not recommending pixantrone monotherapy to treat multiply relapsed or refractory B-cell non-Hodgkin lymphoma (NHL).

Of course, this recommendation may change, as this is not NICE’s final guidance on pixantrone.

For this second consultation on the draft guidance, an independent appraisal committee re-examined the clinical and cost-effectiveness of pixantrone.

This time, the committee took into consideration a patient access scheme submitted by pixantrone’s manufacturer, Cell Therapeutics. The scheme was designed to make the drug more cost-effective for the National Health Service (NHS).

“Unfortunately, the committee concluded that this scheme . . . does not overcome the uncertainties in the evidence for the drug’s clinical effectiveness over and above current treatments for this disease,” said NICE Chief Executive Sir Andrew Dillon.

In fact, the committee found the scheme did not make pixantrone cost-effective according to the accepted definition—costing £20,000 to £30,000 per quality-adjusted life year (QALY) gained.

Evaluating trial data

When considering the clinical effectiveness of pixantrone, the appraisal committee analyzed data from the EXTEND PIX301 trial, which was submitted by the manufacturer.

The trial enrolled adults with aggressive, de novo, or transformed NHL that had relapsed after 2 or more chemotherapy regimens, including at least 1 standard anthracycline-containing regimen with a response that lasted at least 24 weeks. Seventy patients were randomized to pixantrone, and 70 were randomized to a physician’s choice of single-agent comparators.

The committee pointed out a number of uncertainties associated with the trial. One was that it did not include the planned number of patients (which was 320), so it may not have been sufficiently powered to detect differences between the treatment arms.

Another concern was that the trial’s primary endpoint was complete or unconfirmed complete response, rather than overall survival or progression-free survival. In fact, there was a lack of statistically significant difference in overall survival between treatment arms. And other differences between the treatment arms were not always statistically significant.

These factors led the committee to conclude that there is insufficient evidence to suggest pixantrone is more clinically effective than treatments currently used in clinical practice.

Suitability for the UK

The appraisal committee also heard evidence from clinical experts and patient representatives. This information revealed differences in previous treatment between the PIX301 trial population and UK clinical practice.

Therefore, the committee said it could not determine the clinical effectiveness of pixantrone for a UK population.

In addition, there is doubt regarding the clinical benefit of pixantrone in patients who previously received rituximab. And this applies to virtually all patients with relapsed or refractory aggressive B-cell lymphoma in England and Wales, the committee noted.

(The European Medicines Agency’s conditional approval of pixantrone stipulated that an additional trial must confirm the clinical benefit of the drug in patients who have previously received rituximab.)

Calculating costs

The committee estimated the patient access scheme for pixantrone would most likely result in an incremental cost-effectiveness ratio of £30,700 per QALY gained. This is above the range normally considered to be cost-effective—usually £20,000 to £30,000 per QALY gained.

This factor, along with the lack of clinical effectiveness, prompted the committee to conclude that pixantrone would not be a cost-effective use of NHS resources.

According to Cell Therapeutics, pixantrone costs £553.50 per 20 mL vial. The recommended dosage of pixantrone is 50 mg/m² on days 1, 8, and 15 of each 28-day cycle, for up to 6 cycles.

The estimated cost of a course of treatment is £19,926. This is based on the median length of treatment in the PIX301 trial—4 cycles, using an average of 3 vials per dose.

About the guidance

Individuals can comment on the pixantrone draft guidance via the NICE website. It is open until November 4, 2013. 

This is the third version of the draft guidance published and the second consultation launched. The draft guidance was initially published for consultation in April 2013, followed by a final draft guidance in June 2013. But this document was withdrawn during the appeal stage because the manufacturer submitted the patient access scheme.

Until the final guidance is issued to the NHS, organizations should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations.

B-cell lymphoma

The UK’s National Institute for Health and Care Excellence (NICE) has re-examined its draft guidance for pixantrone (Pixuvri) but come to the same conclusion as before.

The organization is still not recommending pixantrone monotherapy to treat multiply relapsed or refractory B-cell non-Hodgkin lymphoma (NHL).

Of course, this recommendation may change, as this is not NICE’s final guidance on pixantrone.

For this second consultation on the draft guidance, an independent appraisal committee re-examined the clinical and cost-effectiveness of pixantrone.

This time, the committee took into consideration a patient access scheme submitted by pixantrone’s manufacturer, Cell Therapeutics. The scheme was designed to make the drug more cost-effective for the National Health Service (NHS).

“Unfortunately, the committee concluded that this scheme . . . does not overcome the uncertainties in the evidence for the drug’s clinical effectiveness over and above current treatments for this disease,” said NICE Chief Executive Sir Andrew Dillon.

In fact, the committee found the scheme did not make pixantrone cost-effective according to the accepted definition—costing £20,000 to £30,000 per quality-adjusted life year (QALY) gained.

Evaluating trial data

When considering the clinical effectiveness of pixantrone, the appraisal committee analyzed data from the EXTEND PIX301 trial, which was submitted by the manufacturer.

The trial enrolled adults with aggressive, de novo, or transformed NHL that had relapsed after 2 or more chemotherapy regimens, including at least 1 standard anthracycline-containing regimen with a response that lasted at least 24 weeks. Seventy patients were randomized to pixantrone, and 70 were randomized to a physician’s choice of single-agent comparators.

The committee pointed out a number of uncertainties associated with the trial. One was that it did not include the planned number of patients (which was 320), so it may not have been sufficiently powered to detect differences between the treatment arms.

Another concern was that the trial’s primary endpoint was complete or unconfirmed complete response, rather than overall survival or progression-free survival. In fact, there was a lack of statistically significant difference in overall survival between treatment arms. And other differences between the treatment arms were not always statistically significant.

These factors led the committee to conclude that there is insufficient evidence to suggest pixantrone is more clinically effective than treatments currently used in clinical practice.

Suitability for the UK

The appraisal committee also heard evidence from clinical experts and patient representatives. This information revealed differences in previous treatment between the PIX301 trial population and UK clinical practice.

Therefore, the committee said it could not determine the clinical effectiveness of pixantrone for a UK population.

In addition, there is doubt regarding the clinical benefit of pixantrone in patients who previously received rituximab. And this applies to virtually all patients with relapsed or refractory aggressive B-cell lymphoma in England and Wales, the committee noted.

(The European Medicines Agency’s conditional approval of pixantrone stipulated that an additional trial must confirm the clinical benefit of the drug in patients who have previously received rituximab.)

Calculating costs

The committee estimated the patient access scheme for pixantrone would most likely result in an incremental cost-effectiveness ratio of £30,700 per QALY gained. This is above the range normally considered to be cost-effective—usually £20,000 to £30,000 per QALY gained.

This factor, along with the lack of clinical effectiveness, prompted the committee to conclude that pixantrone would not be a cost-effective use of NHS resources.

According to Cell Therapeutics, pixantrone costs £553.50 per 20 mL vial. The recommended dosage of pixantrone is 50 mg/m² on days 1, 8, and 15 of each 28-day cycle, for up to 6 cycles.

The estimated cost of a course of treatment is £19,926. This is based on the median length of treatment in the PIX301 trial—4 cycles, using an average of 3 vials per dose.

About the guidance

Individuals can comment on the pixantrone draft guidance via the NICE website. It is open until November 4, 2013. 

This is the third version of the draft guidance published and the second consultation launched. The draft guidance was initially published for consultation in April 2013, followed by a final draft guidance in June 2013. But this document was withdrawn during the appeal stage because the manufacturer submitted the patient access scheme.

Until the final guidance is issued to the NHS, organizations should make decisions locally on the funding of specific treatments. Once NICE issues its final guidance on a technology, it replaces local recommendations.

Clinical question

Does implementation of the I COUGH strategy improve pulmonary outcomes in postoperative patients?

Bottom line

Although not statistically significant, data from this before-and-after trial shows that the I COUGH strategy (emphasizing lung expansion, early mobilization, oral hygiene, and patient and provider education) may decrease postoperative pulmonary complications in hospitalized patients. (LOE = 2c)

Reference

Cassidy MR, Rosenkranz P, McCabe K, Rosen JE, McAneny D. I COUGH: Reducing postoperative pulmonary complications with a multidisciplinary patient care program. JAMA Surg 2013;148(8):740-745.

Study design

Other

Funding source

Unknown/not stated

Allocation

Uncertain

Setting

Inpatient (any location)

Synopsis

Data from the National Surgical Quality Improvement Program (NQSIP) showed that the Boston Medical Center was a high outlier for postoperative pulmonary complications. To address this, a pulmonary care working group including surgeons, internists, nurses, and respiratory therapists was formed. The group reviewed the literature on preventing postoperative pulmonary complications and devised the I COUGH strategy: (1) Incentive spirometry, (2) Coughing and deep breathing, (3) Oral care, (4) Understanding (patient and family education), (5) Getting out of bed, and (6) Head-of-bed elevation. Postoperative pain control was also emphasized. Educational materials including videos and brochures were developed for patients and families and distributed in surgery and perioperative clinics. Incentive spirometry technique was taught and reinforced in the preoperative setting. Frontline nurses and physicians also received education regarding the baseline outcomes data and the reasons for developing the program. Finally, standardized order sets outlining the components of I COUGH were created. The I COUGH strategy was implemented for all hospitalized general and vascular surgery patients in the institution. More patients were out of bed postintervention than preintervention (70% vs 20%; P < .001). Similarly, more patients had incentive spirometry available and within reach postintervention (77% vs 53%; P < .001). Note, however, that the preintervention audits were unannounced observations of nursing practices whereas postintervention audits were by review of nursing documentation only. Although not statistically significant, the NSQIP data revealed trends toward decreased incidences of postoperative pneumonia (2.6% vs 1.6%; P = .09) and unplanned intubations (2.0% vs 1.2%; P = .09) after I COUGH implementation. National averages for postoperative pneumonias and unplanned intubations for comparable hospitals during this period were 1.4% to 1.7% and 1.4% to 1.6%, respectively.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does implementation of the I COUGH strategy improve pulmonary outcomes in postoperative patients?

Bottom line

Although not statistically significant, data from this before-and-after trial shows that the I COUGH strategy (emphasizing lung expansion, early mobilization, oral hygiene, and patient and provider education) may decrease postoperative pulmonary complications in hospitalized patients. (LOE = 2c)

Reference

Cassidy MR, Rosenkranz P, McCabe K, Rosen JE, McAneny D. I COUGH: Reducing postoperative pulmonary complications with a multidisciplinary patient care program. JAMA Surg 2013;148(8):740-745.

Study design

Other

Funding source

Unknown/not stated

Allocation

Uncertain

Setting

Inpatient (any location)

Synopsis

Data from the National Surgical Quality Improvement Program (NQSIP) showed that the Boston Medical Center was a high outlier for postoperative pulmonary complications. To address this, a pulmonary care working group including surgeons, internists, nurses, and respiratory therapists was formed. The group reviewed the literature on preventing postoperative pulmonary complications and devised the I COUGH strategy: (1) Incentive spirometry, (2) Coughing and deep breathing, (3) Oral care, (4) Understanding (patient and family education), (5) Getting out of bed, and (6) Head-of-bed elevation. Postoperative pain control was also emphasized. Educational materials including videos and brochures were developed for patients and families and distributed in surgery and perioperative clinics. Incentive spirometry technique was taught and reinforced in the preoperative setting. Frontline nurses and physicians also received education regarding the baseline outcomes data and the reasons for developing the program. Finally, standardized order sets outlining the components of I COUGH were created. The I COUGH strategy was implemented for all hospitalized general and vascular surgery patients in the institution. More patients were out of bed postintervention than preintervention (70% vs 20%; P < .001). Similarly, more patients had incentive spirometry available and within reach postintervention (77% vs 53%; P < .001). Note, however, that the preintervention audits were unannounced observations of nursing practices whereas postintervention audits were by review of nursing documentation only. Although not statistically significant, the NSQIP data revealed trends toward decreased incidences of postoperative pneumonia (2.6% vs 1.6%; P = .09) and unplanned intubations (2.0% vs 1.2%; P = .09) after I COUGH implementation. National averages for postoperative pneumonias and unplanned intubations for comparable hospitals during this period were 1.4% to 1.7% and 1.4% to 1.6%, respectively.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

Does implementation of the I COUGH strategy improve pulmonary outcomes in postoperative patients?

Bottom line

Although not statistically significant, data from this before-and-after trial shows that the I COUGH strategy (emphasizing lung expansion, early mobilization, oral hygiene, and patient and provider education) may decrease postoperative pulmonary complications in hospitalized patients. (LOE = 2c)

Reference

Cassidy MR, Rosenkranz P, McCabe K, Rosen JE, McAneny D. I COUGH: Reducing postoperative pulmonary complications with a multidisciplinary patient care program. JAMA Surg 2013;148(8):740-745.

Study design

Other

Funding source

Unknown/not stated

Allocation

Uncertain

Setting

Inpatient (any location)

Synopsis

Data from the National Surgical Quality Improvement Program (NQSIP) showed that the Boston Medical Center was a high outlier for postoperative pulmonary complications. To address this, a pulmonary care working group including surgeons, internists, nurses, and respiratory therapists was formed. The group reviewed the literature on preventing postoperative pulmonary complications and devised the I COUGH strategy: (1) Incentive spirometry, (2) Coughing and deep breathing, (3) Oral care, (4) Understanding (patient and family education), (5) Getting out of bed, and (6) Head-of-bed elevation. Postoperative pain control was also emphasized. Educational materials including videos and brochures were developed for patients and families and distributed in surgery and perioperative clinics. Incentive spirometry technique was taught and reinforced in the preoperative setting. Frontline nurses and physicians also received education regarding the baseline outcomes data and the reasons for developing the program. Finally, standardized order sets outlining the components of I COUGH were created. The I COUGH strategy was implemented for all hospitalized general and vascular surgery patients in the institution. More patients were out of bed postintervention than preintervention (70% vs 20%; P < .001). Similarly, more patients had incentive spirometry available and within reach postintervention (77% vs 53%; P < .001). Note, however, that the preintervention audits were unannounced observations of nursing practices whereas postintervention audits were by review of nursing documentation only. Although not statistically significant, the NSQIP data revealed trends toward decreased incidences of postoperative pneumonia (2.6% vs 1.6%; P = .09) and unplanned intubations (2.0% vs 1.2%; P = .09) after I COUGH implementation. National averages for postoperative pneumonias and unplanned intubations for comparable hospitals during this period were 1.4% to 1.7% and 1.4% to 1.6%, respectively.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

How effective is intensive smoking cessation support for hospitalized patients?

Bottom line

Therapy provided by highly trained smoking cessation practitioners, combined with pharmacotherapy and community support referrals upon discharge, may increase short-term quit rates among hospitalized smokers. However, this effect did not persist at 6 months. Moreover, this study did not address the cost-effectiveness of such an intensive strategy. (LOE = 1b-)

Reference

Murray RL, Leonardi-Bee J, Marsh J, et al. Systematic identification and treatment of smokers by hospital based cessation practitioners in a secondary care setting: cluster randomised controlled trial. BMJ 2013;347:f4004.

Study design

Randomized controlled trial (nonblinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Investigators at a large teaching hospital in the United Kingdom randomized 18 medical wards, using concealed allocation, to deliver either usual care for smoking cessation or the intervention strategy. Almost 500 patients were enrolled in the study and received smoking cessation treatment based on the allocation of their admission ward. The intervention consisted of identification of smokers upon admission, followed by delivery of smoking advice and offer of cessation support. Patients who accepted the support received daily in-hospital counseling by a trained smoking cessation practitioner. Initial sessions lasted 20 minutes to 30 minutes; subsequent sessions were 10 minutes long. Patients were also prescribed dual nicotine replacement therapy (transdermal patch plus either gum, lozenge, or nasal spray) or varenicline therapy, if preferred. Additionally, intervention patients received referrals to community cessation support services upon discharge. Patients on the usual care ward received cessation advice and support according to the usual practices of the providers involved in their care. The intervention group patients were younger and more likely to be male. Additionally, because of randomization by admission ward, the majority of intervention patients came from cardiac wards, whereas the majority of usual care patients came from respiratory wards. Finally, many eligible oncology patients were not included in the trial because of their doctors’ reluctance to have the study team approach these terminally ill patients. All patients in the intervention group received advice to quit compared with less than half of the patients in the usual care group. The use of pharmacotherapy and cessation support therapy, both in the hospital and upon discharge, was greater in the intervention group. The quit rate at 4 weeks, defined as self-reported smoking cessation validated by exhaled carbon monoxide measurement, favored the intervention group (38% vs 17%; P = .06), but did not quite reach statistical significance. When oncology patients (n = 45) were excluded from the analysis retrospectively, however, the result was significant (42% quit rate in the intervention group vs 17% in the usual care group; P = .006). Six-month cessation rates, though also higher in the intervention group, were not statistically different (19% vs 9%; P = .37).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

How effective is intensive smoking cessation support for hospitalized patients?

Bottom line

Therapy provided by highly trained smoking cessation practitioners, combined with pharmacotherapy and community support referrals upon discharge, may increase short-term quit rates among hospitalized smokers. However, this effect did not persist at 6 months. Moreover, this study did not address the cost-effectiveness of such an intensive strategy. (LOE = 1b-)

Reference

Murray RL, Leonardi-Bee J, Marsh J, et al. Systematic identification and treatment of smokers by hospital based cessation practitioners in a secondary care setting: cluster randomised controlled trial. BMJ 2013;347:f4004.

Study design

Randomized controlled trial (nonblinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Investigators at a large teaching hospital in the United Kingdom randomized 18 medical wards, using concealed allocation, to deliver either usual care for smoking cessation or the intervention strategy. Almost 500 patients were enrolled in the study and received smoking cessation treatment based on the allocation of their admission ward. The intervention consisted of identification of smokers upon admission, followed by delivery of smoking advice and offer of cessation support. Patients who accepted the support received daily in-hospital counseling by a trained smoking cessation practitioner. Initial sessions lasted 20 minutes to 30 minutes; subsequent sessions were 10 minutes long. Patients were also prescribed dual nicotine replacement therapy (transdermal patch plus either gum, lozenge, or nasal spray) or varenicline therapy, if preferred. Additionally, intervention patients received referrals to community cessation support services upon discharge. Patients on the usual care ward received cessation advice and support according to the usual practices of the providers involved in their care. The intervention group patients were younger and more likely to be male. Additionally, because of randomization by admission ward, the majority of intervention patients came from cardiac wards, whereas the majority of usual care patients came from respiratory wards. Finally, many eligible oncology patients were not included in the trial because of their doctors’ reluctance to have the study team approach these terminally ill patients. All patients in the intervention group received advice to quit compared with less than half of the patients in the usual care group. The use of pharmacotherapy and cessation support therapy, both in the hospital and upon discharge, was greater in the intervention group. The quit rate at 4 weeks, defined as self-reported smoking cessation validated by exhaled carbon monoxide measurement, favored the intervention group (38% vs 17%; P = .06), but did not quite reach statistical significance. When oncology patients (n = 45) were excluded from the analysis retrospectively, however, the result was significant (42% quit rate in the intervention group vs 17% in the usual care group; P = .006). Six-month cessation rates, though also higher in the intervention group, were not statistically different (19% vs 9%; P = .37).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question

How effective is intensive smoking cessation support for hospitalized patients?

Bottom line

Therapy provided by highly trained smoking cessation practitioners, combined with pharmacotherapy and community support referrals upon discharge, may increase short-term quit rates among hospitalized smokers. However, this effect did not persist at 6 months. Moreover, this study did not address the cost-effectiveness of such an intensive strategy. (LOE = 1b-)

Reference

Murray RL, Leonardi-Bee J, Marsh J, et al. Systematic identification and treatment of smokers by hospital based cessation practitioners in a secondary care setting: cluster randomised controlled trial. BMJ 2013;347:f4004.

Study design

Randomized controlled trial (nonblinded)

Funding source

Government

Allocation

Concealed

Setting

Inpatient (any location) with outpatient follow-up

Synopsis

Investigators at a large teaching hospital in the United Kingdom randomized 18 medical wards, using concealed allocation, to deliver either usual care for smoking cessation or the intervention strategy. Almost 500 patients were enrolled in the study and received smoking cessation treatment based on the allocation of their admission ward. The intervention consisted of identification of smokers upon admission, followed by delivery of smoking advice and offer of cessation support. Patients who accepted the support received daily in-hospital counseling by a trained smoking cessation practitioner. Initial sessions lasted 20 minutes to 30 minutes; subsequent sessions were 10 minutes long. Patients were also prescribed dual nicotine replacement therapy (transdermal patch plus either gum, lozenge, or nasal spray) or varenicline therapy, if preferred. Additionally, intervention patients received referrals to community cessation support services upon discharge. Patients on the usual care ward received cessation advice and support according to the usual practices of the providers involved in their care. The intervention group patients were younger and more likely to be male. Additionally, because of randomization by admission ward, the majority of intervention patients came from cardiac wards, whereas the majority of usual care patients came from respiratory wards. Finally, many eligible oncology patients were not included in the trial because of their doctors’ reluctance to have the study team approach these terminally ill patients. All patients in the intervention group received advice to quit compared with less than half of the patients in the usual care group. The use of pharmacotherapy and cessation support therapy, both in the hospital and upon discharge, was greater in the intervention group. The quit rate at 4 weeks, defined as self-reported smoking cessation validated by exhaled carbon monoxide measurement, favored the intervention group (38% vs 17%; P = .06), but did not quite reach statistical significance. When oncology patients (n = 45) were excluded from the analysis retrospectively, however, the result was significant (42% quit rate in the intervention group vs 17% in the usual care group; P = .006). Six-month cessation rates, though also higher in the intervention group, were not statistically different (19% vs 9%; P = .37).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

The diagnosis of otitis media absolutely requires visualization of the tympanic membrane. So it may be time to upgrade your tools to do a better job in diagnosing. Think about how often you use your otoscope. Are you using the best available technology, or are you using the otoscope you got in medical school, perhaps quite a few years ago? It may be time for an upgrade. Considering how often you might use an otoscope, you can afford it. You deserve it.

The improved features of new otoscopes include remarkably better illumination. The quality of the light not only has to do with the lumens, but also the color of the light. Also there is a version of an otoscope called a Macro View (Welch Allyn, Skaneateles Falls, N.Y.). It allows you to increase the magnification on the tympanic membrane (TM) as needed. There is an option to purchase a lighter and smaller handle for the scope, and that can improve ease of use for persons with small hands.

For all otoscopes, the bulb should be replaced when illumination begins to fade and you cannot get back the intensity of light with a battery recharge. For most primary care practitioners, bulbs usually require replacement annually.

Speculum size is key to getting the most light onto the TM; the bigger the speculum, the better. Advancing the speculum as far into the external ear canal as you can without causing discomfort helps improve the intensity of the light shone on the TM. While it is convenient to use disposable specula, they are not as good as reusable ones because the finish on the inside of disposable specula is duller than on reusable specula, thus decreasing the amount of light shone on the TM. Also, disposable specula often are too short, and that too reduces the light shone on the TM.

Many clinicians have not been trained on using pneumatic otoscopy, or even if trained, they find it inconvenient and/or problematic to use because it requires a seal of the speculum against the external auditory canal; this makes children cry. The problem is that you really need to use pneumatic otoscopy in some cases to determine if the TM is retracted (no acute infection) or bulging (acute infection, or AOM). I use pneumatic otoscopy in about one-third of cases, and to this day I am surprised sometimes when the negative pressure pulls a retracted TM forward when I was pretty sure the TM more likely was bulging. There are specula with a semisoft sleeve midway down the shaft, but I have not found they are any less likely to cause the child to cry, because as anyone knows who has stuck a Q-tip swab into their ear canal, it is sensitive skin.

Then there is the wax! Clinical studies show that about half of children have wax in their external auditory canal blocking 25% of the view, and one-quarter have wax blocking 50% of the view. The best tool I have found to clear the wax is a plastic cerumen spoon (called a safe ear curette) made by Bionix Medical Technologies (Toledo, Ohio). I use the white ones as they are the most flexible. Ninety percent of the time I can scoop the wax out of the way and get a good view. For the remaining difficult cases, the ear canal needs to be irrigated with warm water (code 69210), and then the remaining wax can be scooped out.

Tympanometry (code 92567) is another tool to aid in accurate diagnosis and follow-up of otitis media. A key aspect of the diagnostic algorithm advocated by the American Academy of Pediatrics is a determination of whether the TM is bulging (AOM) or not (no AOM). A retracted TM is inconsistent with the diagnosis of AOM. Tympanometry requires a seal with the external auditory canal because a pressure is applied to the TM to determine TM movement. After positive and negative pressure are applied by the instrument, the readout will be a positive peaked curve (bulging), a negative peaked curve (retracted), a normal peaked curve (normal), or flat, no curve (stiff TM).

The first three readouts are very helpful in distinguishing AOM from no AOM. The flat curve indicates three possibilities: The TM is stiff, perhaps due to thickening; the TM is not moving because the middle ear space is filled with pus behind it, meaning it is AOM; or the TM is not moving because the middle ear space is filled with effusion fluid behind it, meaning the patient has otitis media with effusion. In the case of a flat readout, the tie breaker should come from the visual exam and/or the use of spectral gradient acoustic reflectometry (code 92567).

These better tools and techniques should improve your diagnosis of otitis media.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester General Hospital, N.Y. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said he had no financial disclosures relevant to this article. To comment, e-mail him at [email protected].

The diagnosis of otitis media absolutely requires visualization of the tympanic membrane. So it may be time to upgrade your tools to do a better job in diagnosing. Think about how often you use your otoscope. Are you using the best available technology, or are you using the otoscope you got in medical school, perhaps quite a few years ago? It may be time for an upgrade. Considering how often you might use an otoscope, you can afford it. You deserve it.

The improved features of new otoscopes include remarkably better illumination. The quality of the light not only has to do with the lumens, but also the color of the light. Also there is a version of an otoscope called a Macro View (Welch Allyn, Skaneateles Falls, N.Y.). It allows you to increase the magnification on the tympanic membrane (TM) as needed. There is an option to purchase a lighter and smaller handle for the scope, and that can improve ease of use for persons with small hands.

For all otoscopes, the bulb should be replaced when illumination begins to fade and you cannot get back the intensity of light with a battery recharge. For most primary care practitioners, bulbs usually require replacement annually.

Speculum size is key to getting the most light onto the TM; the bigger the speculum, the better. Advancing the speculum as far into the external ear canal as you can without causing discomfort helps improve the intensity of the light shone on the TM. While it is convenient to use disposable specula, they are not as good as reusable ones because the finish on the inside of disposable specula is duller than on reusable specula, thus decreasing the amount of light shone on the TM. Also, disposable specula often are too short, and that too reduces the light shone on the TM.

Many clinicians have not been trained on using pneumatic otoscopy, or even if trained, they find it inconvenient and/or problematic to use because it requires a seal of the speculum against the external auditory canal; this makes children cry. The problem is that you really need to use pneumatic otoscopy in some cases to determine if the TM is retracted (no acute infection) or bulging (acute infection, or AOM). I use pneumatic otoscopy in about one-third of cases, and to this day I am surprised sometimes when the negative pressure pulls a retracted TM forward when I was pretty sure the TM more likely was bulging. There are specula with a semisoft sleeve midway down the shaft, but I have not found they are any less likely to cause the child to cry, because as anyone knows who has stuck a Q-tip swab into their ear canal, it is sensitive skin.

Then there is the wax! Clinical studies show that about half of children have wax in their external auditory canal blocking 25% of the view, and one-quarter have wax blocking 50% of the view. The best tool I have found to clear the wax is a plastic cerumen spoon (called a safe ear curette) made by Bionix Medical Technologies (Toledo, Ohio). I use the white ones as they are the most flexible. Ninety percent of the time I can scoop the wax out of the way and get a good view. For the remaining difficult cases, the ear canal needs to be irrigated with warm water (code 69210), and then the remaining wax can be scooped out.

Tympanometry (code 92567) is another tool to aid in accurate diagnosis and follow-up of otitis media. A key aspect of the diagnostic algorithm advocated by the American Academy of Pediatrics is a determination of whether the TM is bulging (AOM) or not (no AOM). A retracted TM is inconsistent with the diagnosis of AOM. Tympanometry requires a seal with the external auditory canal because a pressure is applied to the TM to determine TM movement. After positive and negative pressure are applied by the instrument, the readout will be a positive peaked curve (bulging), a negative peaked curve (retracted), a normal peaked curve (normal), or flat, no curve (stiff TM).

The first three readouts are very helpful in distinguishing AOM from no AOM. The flat curve indicates three possibilities: The TM is stiff, perhaps due to thickening; the TM is not moving because the middle ear space is filled with pus behind it, meaning it is AOM; or the TM is not moving because the middle ear space is filled with effusion fluid behind it, meaning the patient has otitis media with effusion. In the case of a flat readout, the tie breaker should come from the visual exam and/or the use of spectral gradient acoustic reflectometry (code 92567).

These better tools and techniques should improve your diagnosis of otitis media.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester General Hospital, N.Y. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said he had no financial disclosures relevant to this article. To comment, e-mail him at [email protected].

The diagnosis of otitis media absolutely requires visualization of the tympanic membrane. So it may be time to upgrade your tools to do a better job in diagnosing. Think about how often you use your otoscope. Are you using the best available technology, or are you using the otoscope you got in medical school, perhaps quite a few years ago? It may be time for an upgrade. Considering how often you might use an otoscope, you can afford it. You deserve it.

The improved features of new otoscopes include remarkably better illumination. The quality of the light not only has to do with the lumens, but also the color of the light. Also there is a version of an otoscope called a Macro View (Welch Allyn, Skaneateles Falls, N.Y.). It allows you to increase the magnification on the tympanic membrane (TM) as needed. There is an option to purchase a lighter and smaller handle for the scope, and that can improve ease of use for persons with small hands.

For all otoscopes, the bulb should be replaced when illumination begins to fade and you cannot get back the intensity of light with a battery recharge. For most primary care practitioners, bulbs usually require replacement annually.

Speculum size is key to getting the most light onto the TM; the bigger the speculum, the better. Advancing the speculum as far into the external ear canal as you can without causing discomfort helps improve the intensity of the light shone on the TM. While it is convenient to use disposable specula, they are not as good as reusable ones because the finish on the inside of disposable specula is duller than on reusable specula, thus decreasing the amount of light shone on the TM. Also, disposable specula often are too short, and that too reduces the light shone on the TM.

Many clinicians have not been trained on using pneumatic otoscopy, or even if trained, they find it inconvenient and/or problematic to use because it requires a seal of the speculum against the external auditory canal; this makes children cry. The problem is that you really need to use pneumatic otoscopy in some cases to determine if the TM is retracted (no acute infection) or bulging (acute infection, or AOM). I use pneumatic otoscopy in about one-third of cases, and to this day I am surprised sometimes when the negative pressure pulls a retracted TM forward when I was pretty sure the TM more likely was bulging. There are specula with a semisoft sleeve midway down the shaft, but I have not found they are any less likely to cause the child to cry, because as anyone knows who has stuck a Q-tip swab into their ear canal, it is sensitive skin.

Then there is the wax! Clinical studies show that about half of children have wax in their external auditory canal blocking 25% of the view, and one-quarter have wax blocking 50% of the view. The best tool I have found to clear the wax is a plastic cerumen spoon (called a safe ear curette) made by Bionix Medical Technologies (Toledo, Ohio). I use the white ones as they are the most flexible. Ninety percent of the time I can scoop the wax out of the way and get a good view. For the remaining difficult cases, the ear canal needs to be irrigated with warm water (code 69210), and then the remaining wax can be scooped out.

Tympanometry (code 92567) is another tool to aid in accurate diagnosis and follow-up of otitis media. A key aspect of the diagnostic algorithm advocated by the American Academy of Pediatrics is a determination of whether the TM is bulging (AOM) or not (no AOM). A retracted TM is inconsistent with the diagnosis of AOM. Tympanometry requires a seal with the external auditory canal because a pressure is applied to the TM to determine TM movement. After positive and negative pressure are applied by the instrument, the readout will be a positive peaked curve (bulging), a negative peaked curve (retracted), a normal peaked curve (normal), or flat, no curve (stiff TM).

The first three readouts are very helpful in distinguishing AOM from no AOM. The flat curve indicates three possibilities: The TM is stiff, perhaps due to thickening; the TM is not moving because the middle ear space is filled with pus behind it, meaning it is AOM; or the TM is not moving because the middle ear space is filled with effusion fluid behind it, meaning the patient has otitis media with effusion. In the case of a flat readout, the tie breaker should come from the visual exam and/or the use of spectral gradient acoustic reflectometry (code 92567).

These better tools and techniques should improve your diagnosis of otitis media.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester General Hospital, N.Y. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said he had no financial disclosures relevant to this article. To comment, e-mail him at [email protected].