ORLANDO – Early evidence suggests that OpenNotes is helping to engage patients and improve health outcomes while not creating undue burden for physicians.

A 2010 pilot project at Beth Israel Deaconess Medical Center in Boston, Geisinger Health System in Pennsylvania, and Harborview Medical Center in Seattle tested OpenNotes, a program that allows patients to see the entirety of a physician’s notes within their medical record and not just a summarized version.

Homer Chin, MD, of the department of medical informatics and outcomes research at Oregon Health & Science University, Portland, an associate with the OpenNotes Program, and physician champion for the Northwest OpenNotes Consortium, noted that a survey of the 105 primary care physicians participating in the pilot revealed they were apprehensive when they heard their visit notes would be completely available to patients.

Prior to the launch of the pilot, 24% of physicians expected significantly longer visits because of the availability of OpenNotes, 42% said they expected to spend more time addressing patient questions outside of visits, and 39% said they expected to spend more time writing/editing/dictating notes, Dr. Chin said at the annual meeting of the Healthcare Information and Management Systems Society.

Their concerns never quite materialized.

According to a survey of the participating physicians after the yearlong pilot, only 2% reported visits took significantly longer, 3% said they spent more time addressing patient questions outside of visits, and 11% said they spent more time writing/editing/dictating notes.

With regard to writing notes, “what we are finding is that most physicians are saying they are changing the way they write the note a little bit, but it is not taking more time,” Dr. Chin said. “They are just watching for certain terms and writing them in a different way, but it is not necessarily taking more time.”

More than 70% of patients who participated in the trial reported they are taking better care of themselves, more than 77% said they have a better understanding of their medical condition, more than 69% said they are better prepared for visits and more than 60% said they are more adherent to their prescription medication regimens.

Importantly, 85% said the availability of OpenNotes would affect their future choice of providers.

Dr. Chin also discussed the results of a survey of patients using OpenNotes in the Virginia Commonwealth University Health System in Richmond, noting that of roughly 420 respondents, 70% said their contact with their providers did not change, with nearly 20% saying they were contacting their provider less. Just over 40% said that reading their notes made them less worried about something health related, while a little more than 50% said there was no change. Nearly 85% said they thought seeing the notes helped them take better care of themselves. Nearly 90% of patients said that they understood some or all of their doctors’ notes.

Gregory Twachtman/Frontline Medical News

John Kravitz, senior vice president and chief information officer at the Geisinger Health System in Danville, Pa., also touted the positive impact of OpenNotes.

It has been incredibly valuable “when the patients use the portal to prepare themselves for the visit with the provider,” Mr. Kravitz said. “They will review their case. They’ll look at past x-rays or reports, any kind of information, the results for laboratory and anything else, but they will message their provider. They are very heavy into messaging. It’s secure messaging within the portal and any type of questions, especially after they’ve had an appointment, they’ve thought of something they didn’t think about in the appointment, they have the opportunity to message back to the provider’s office.”

Geisinger saw 620,000 encounter reviews in OpenNotes out of 2 million patient visits in its last fiscal year, with virtually no complaints about the information in the OpenNotes.

Dr. Chin stressed that the implemented OpenNotes needs to be driven by physicians.

“I would emphasize that this has to be a clinician operational leader supported effort, and not an IT effort, so that when clinicians complain, you can point them to their department head, the chief medical officer, and not the IT people,” he said. “You’ve got to have good communication to providers. Our advice is to start with one department. You might do a pilot for a very short period of time, but there is enough evidence now to really implement it throughout the organization. We encourage people not to allow individual providers to opt out on their own, to make their own decision to opt out, to do it as an organizational effort.”

Michael Day, chief information officer of Ascension Health and Columbia St. Mary’s Health System of Milwaukee, offered the same advice.

“You’ve got to have leadership commitment up front,” Mr. Day said. “This really has to have good, strong physician leadership. The key executive in charge of all of this was the president of our medical group which drove a lot of the change with a lot of support from other areas.”

He noted that at his organization there was “a lot of physician grumbling” when OpenNotes was announced. However, there has been “relatively no impact. I think they’ve all agreed that this has made care better. We’ve also seen an actual improvement in the quality of the documentation.”

None of the presenters reported any conflicts of interest.
 

 

[email protected]

 

ORLANDO – Early evidence suggests that OpenNotes is helping to engage patients and improve health outcomes while not creating undue burden for physicians.

A 2010 pilot project at Beth Israel Deaconess Medical Center in Boston, Geisinger Health System in Pennsylvania, and Harborview Medical Center in Seattle tested OpenNotes, a program that allows patients to see the entirety of a physician’s notes within their medical record and not just a summarized version.

Homer Chin, MD, of the department of medical informatics and outcomes research at Oregon Health & Science University, Portland, an associate with the OpenNotes Program, and physician champion for the Northwest OpenNotes Consortium, noted that a survey of the 105 primary care physicians participating in the pilot revealed they were apprehensive when they heard their visit notes would be completely available to patients.

Prior to the launch of the pilot, 24% of physicians expected significantly longer visits because of the availability of OpenNotes, 42% said they expected to spend more time addressing patient questions outside of visits, and 39% said they expected to spend more time writing/editing/dictating notes, Dr. Chin said at the annual meeting of the Healthcare Information and Management Systems Society.

Their concerns never quite materialized.

According to a survey of the participating physicians after the yearlong pilot, only 2% reported visits took significantly longer, 3% said they spent more time addressing patient questions outside of visits, and 11% said they spent more time writing/editing/dictating notes.

With regard to writing notes, “what we are finding is that most physicians are saying they are changing the way they write the note a little bit, but it is not taking more time,” Dr. Chin said. “They are just watching for certain terms and writing them in a different way, but it is not necessarily taking more time.”

More than 70% of patients who participated in the trial reported they are taking better care of themselves, more than 77% said they have a better understanding of their medical condition, more than 69% said they are better prepared for visits and more than 60% said they are more adherent to their prescription medication regimens.

Importantly, 85% said the availability of OpenNotes would affect their future choice of providers.

Dr. Chin also discussed the results of a survey of patients using OpenNotes in the Virginia Commonwealth University Health System in Richmond, noting that of roughly 420 respondents, 70% said their contact with their providers did not change, with nearly 20% saying they were contacting their provider less. Just over 40% said that reading their notes made them less worried about something health related, while a little more than 50% said there was no change. Nearly 85% said they thought seeing the notes helped them take better care of themselves. Nearly 90% of patients said that they understood some or all of their doctors’ notes.

Gregory Twachtman/Frontline Medical News

John Kravitz, senior vice president and chief information officer at the Geisinger Health System in Danville, Pa., also touted the positive impact of OpenNotes.

It has been incredibly valuable “when the patients use the portal to prepare themselves for the visit with the provider,” Mr. Kravitz said. “They will review their case. They’ll look at past x-rays or reports, any kind of information, the results for laboratory and anything else, but they will message their provider. They are very heavy into messaging. It’s secure messaging within the portal and any type of questions, especially after they’ve had an appointment, they’ve thought of something they didn’t think about in the appointment, they have the opportunity to message back to the provider’s office.”

Geisinger saw 620,000 encounter reviews in OpenNotes out of 2 million patient visits in its last fiscal year, with virtually no complaints about the information in the OpenNotes.

Dr. Chin stressed that the implemented OpenNotes needs to be driven by physicians.

“I would emphasize that this has to be a clinician operational leader supported effort, and not an IT effort, so that when clinicians complain, you can point them to their department head, the chief medical officer, and not the IT people,” he said. “You’ve got to have good communication to providers. Our advice is to start with one department. You might do a pilot for a very short period of time, but there is enough evidence now to really implement it throughout the organization. We encourage people not to allow individual providers to opt out on their own, to make their own decision to opt out, to do it as an organizational effort.”

Michael Day, chief information officer of Ascension Health and Columbia St. Mary’s Health System of Milwaukee, offered the same advice.

“You’ve got to have leadership commitment up front,” Mr. Day said. “This really has to have good, strong physician leadership. The key executive in charge of all of this was the president of our medical group which drove a lot of the change with a lot of support from other areas.”

He noted that at his organization there was “a lot of physician grumbling” when OpenNotes was announced. However, there has been “relatively no impact. I think they’ve all agreed that this has made care better. We’ve also seen an actual improvement in the quality of the documentation.”

None of the presenters reported any conflicts of interest.
 

 

[email protected]

 

ORLANDO – Early evidence suggests that OpenNotes is helping to engage patients and improve health outcomes while not creating undue burden for physicians.

A 2010 pilot project at Beth Israel Deaconess Medical Center in Boston, Geisinger Health System in Pennsylvania, and Harborview Medical Center in Seattle tested OpenNotes, a program that allows patients to see the entirety of a physician’s notes within their medical record and not just a summarized version.

Homer Chin, MD, of the department of medical informatics and outcomes research at Oregon Health & Science University, Portland, an associate with the OpenNotes Program, and physician champion for the Northwest OpenNotes Consortium, noted that a survey of the 105 primary care physicians participating in the pilot revealed they were apprehensive when they heard their visit notes would be completely available to patients.

Prior to the launch of the pilot, 24% of physicians expected significantly longer visits because of the availability of OpenNotes, 42% said they expected to spend more time addressing patient questions outside of visits, and 39% said they expected to spend more time writing/editing/dictating notes, Dr. Chin said at the annual meeting of the Healthcare Information and Management Systems Society.

Their concerns never quite materialized.

According to a survey of the participating physicians after the yearlong pilot, only 2% reported visits took significantly longer, 3% said they spent more time addressing patient questions outside of visits, and 11% said they spent more time writing/editing/dictating notes.

With regard to writing notes, “what we are finding is that most physicians are saying they are changing the way they write the note a little bit, but it is not taking more time,” Dr. Chin said. “They are just watching for certain terms and writing them in a different way, but it is not necessarily taking more time.”

More than 70% of patients who participated in the trial reported they are taking better care of themselves, more than 77% said they have a better understanding of their medical condition, more than 69% said they are better prepared for visits and more than 60% said they are more adherent to their prescription medication regimens.

Importantly, 85% said the availability of OpenNotes would affect their future choice of providers.

Dr. Chin also discussed the results of a survey of patients using OpenNotes in the Virginia Commonwealth University Health System in Richmond, noting that of roughly 420 respondents, 70% said their contact with their providers did not change, with nearly 20% saying they were contacting their provider less. Just over 40% said that reading their notes made them less worried about something health related, while a little more than 50% said there was no change. Nearly 85% said they thought seeing the notes helped them take better care of themselves. Nearly 90% of patients said that they understood some or all of their doctors’ notes.

Gregory Twachtman/Frontline Medical News

John Kravitz, senior vice president and chief information officer at the Geisinger Health System in Danville, Pa., also touted the positive impact of OpenNotes.

It has been incredibly valuable “when the patients use the portal to prepare themselves for the visit with the provider,” Mr. Kravitz said. “They will review their case. They’ll look at past x-rays or reports, any kind of information, the results for laboratory and anything else, but they will message their provider. They are very heavy into messaging. It’s secure messaging within the portal and any type of questions, especially after they’ve had an appointment, they’ve thought of something they didn’t think about in the appointment, they have the opportunity to message back to the provider’s office.”

Geisinger saw 620,000 encounter reviews in OpenNotes out of 2 million patient visits in its last fiscal year, with virtually no complaints about the information in the OpenNotes.

Dr. Chin stressed that the implemented OpenNotes needs to be driven by physicians.

“I would emphasize that this has to be a clinician operational leader supported effort, and not an IT effort, so that when clinicians complain, you can point them to their department head, the chief medical officer, and not the IT people,” he said. “You’ve got to have good communication to providers. Our advice is to start with one department. You might do a pilot for a very short period of time, but there is enough evidence now to really implement it throughout the organization. We encourage people not to allow individual providers to opt out on their own, to make their own decision to opt out, to do it as an organizational effort.”

Michael Day, chief information officer of Ascension Health and Columbia St. Mary’s Health System of Milwaukee, offered the same advice.

“You’ve got to have leadership commitment up front,” Mr. Day said. “This really has to have good, strong physician leadership. The key executive in charge of all of this was the president of our medical group which drove a lot of the change with a lot of support from other areas.”

He noted that at his organization there was “a lot of physician grumbling” when OpenNotes was announced. However, there has been “relatively no impact. I think they’ve all agreed that this has made care better. We’ve also seen an actual improvement in the quality of the documentation.”

None of the presenters reported any conflicts of interest.
 

 

[email protected]

NATIONAL HARBOR, MD. – Patient-reported outcomes from a prospective cohort study of minimally invasive versus open surgery for women with endometrial cancer showed that the disability from open surgery persisted for longer than had previously been recognized. Further, for a subset of patients, impairment in sexual functioning was significant, and persistent, regardless of the type of surgery.

At 3 weeks after surgery, patients who had open surgery had greater pain as measured by the Brief Pain Inventory (minimally important difference greater than 1, P = .0004). By 3 months post surgery, responses on the Functional Assessment of Cancer Therapy–General were still significantly lower for the open-surgery group, compared with the minimally invasive group (P = .0011).

Although patients’ pain and overall state of health were better at 3 weeks post surgery, regardless of whether women had open, laparoscopic, or robotic surgery, the reduced overall quality of life experienced by patients who had open surgery persisted.

“What was a bit different from other studies … is that we found that this is maintained even at 3 months, and it was clinically and statistically different,” Sarah Ferguson, MD, said in a video interview at the annual meeting of the Society of Gynecologic Oncology. “So that was really, I think, an interesting finding, that this doesn’t just impact the very short term. Three months is a fairly long time after a primary surgery, and [it’s] important for women to know this.”

Patients in the eight-center study had histologically confirmed clinical stage I or II endometrial cancer. The open-surgery arm of the study involved 106 patients, and 414 had minimally invasive surgery (168 laparascopic, 246 robotic).

The robotic and laparoscopic arms showed no statistically significant differences for any patient-reported outcome, even after adjusting for potentially confounding variables, said Dr. Ferguson of Princess Margaret Cancer Centre at the University of Toronto. Accordingly, investigators compared both minimally invasive arms grouped together against open surgery.

Overall, about 80% of patients completed the quality-of-life questionnaires. The response rate for the sexual-functioning questionnaires, however, was much lower, ranging from about a quarter to a half of the participants.

When Dr. Ferguson and her colleagues examined the characteristics of the patients who did complete the sexual-functioning questionnaires, they found that these women were more likely to be younger, partnered, premenopausal and sexually active at the time of diagnosis. Both of the surgical groups “met the clinical cutoff for sexual dysfunction” on the Female Sexual Function Index questionnaire, she said.

For the sexual function questionnaires, differences between the open and minimally invasive groups were not significant at any time point throughout the 26 weeks that patients were studied. “Though it’s a small population, I think these results are important,” said Dr. Ferguson. “These variables may be helpful for us to target patients in our practice, or in future studies, who require intervention.”

Though the study was not randomized, Dr. Ferguson said that the baseline characteristics were similar between groups, and the investigators’ intention-to-treat analysis used a statistical model that adjusted for many potential confounding variables.

Dr. Ferguson reported having no conflicts of interest.

[email protected]
On Twitter @karioakes

NATIONAL HARBOR, MD. – Patient-reported outcomes from a prospective cohort study of minimally invasive versus open surgery for women with endometrial cancer showed that the disability from open surgery persisted for longer than had previously been recognized. Further, for a subset of patients, impairment in sexual functioning was significant, and persistent, regardless of the type of surgery.

At 3 weeks after surgery, patients who had open surgery had greater pain as measured by the Brief Pain Inventory (minimally important difference greater than 1, P = .0004). By 3 months post surgery, responses on the Functional Assessment of Cancer Therapy–General were still significantly lower for the open-surgery group, compared with the minimally invasive group (P = .0011).

Although patients’ pain and overall state of health were better at 3 weeks post surgery, regardless of whether women had open, laparoscopic, or robotic surgery, the reduced overall quality of life experienced by patients who had open surgery persisted.

“What was a bit different from other studies … is that we found that this is maintained even at 3 months, and it was clinically and statistically different,” Sarah Ferguson, MD, said in a video interview at the annual meeting of the Society of Gynecologic Oncology. “So that was really, I think, an interesting finding, that this doesn’t just impact the very short term. Three months is a fairly long time after a primary surgery, and [it’s] important for women to know this.”

Patients in the eight-center study had histologically confirmed clinical stage I or II endometrial cancer. The open-surgery arm of the study involved 106 patients, and 414 had minimally invasive surgery (168 laparascopic, 246 robotic).

The robotic and laparoscopic arms showed no statistically significant differences for any patient-reported outcome, even after adjusting for potentially confounding variables, said Dr. Ferguson of Princess Margaret Cancer Centre at the University of Toronto. Accordingly, investigators compared both minimally invasive arms grouped together against open surgery.

Overall, about 80% of patients completed the quality-of-life questionnaires. The response rate for the sexual-functioning questionnaires, however, was much lower, ranging from about a quarter to a half of the participants.

When Dr. Ferguson and her colleagues examined the characteristics of the patients who did complete the sexual-functioning questionnaires, they found that these women were more likely to be younger, partnered, premenopausal and sexually active at the time of diagnosis. Both of the surgical groups “met the clinical cutoff for sexual dysfunction” on the Female Sexual Function Index questionnaire, she said.

For the sexual function questionnaires, differences between the open and minimally invasive groups were not significant at any time point throughout the 26 weeks that patients were studied. “Though it’s a small population, I think these results are important,” said Dr. Ferguson. “These variables may be helpful for us to target patients in our practice, or in future studies, who require intervention.”

Though the study was not randomized, Dr. Ferguson said that the baseline characteristics were similar between groups, and the investigators’ intention-to-treat analysis used a statistical model that adjusted for many potential confounding variables.

Dr. Ferguson reported having no conflicts of interest.

[email protected]
On Twitter @karioakes

NATIONAL HARBOR, MD. – Patient-reported outcomes from a prospective cohort study of minimally invasive versus open surgery for women with endometrial cancer showed that the disability from open surgery persisted for longer than had previously been recognized. Further, for a subset of patients, impairment in sexual functioning was significant, and persistent, regardless of the type of surgery.

At 3 weeks after surgery, patients who had open surgery had greater pain as measured by the Brief Pain Inventory (minimally important difference greater than 1, P = .0004). By 3 months post surgery, responses on the Functional Assessment of Cancer Therapy–General were still significantly lower for the open-surgery group, compared with the minimally invasive group (P = .0011).

Although patients’ pain and overall state of health were better at 3 weeks post surgery, regardless of whether women had open, laparoscopic, or robotic surgery, the reduced overall quality of life experienced by patients who had open surgery persisted.

“What was a bit different from other studies … is that we found that this is maintained even at 3 months, and it was clinically and statistically different,” Sarah Ferguson, MD, said in a video interview at the annual meeting of the Society of Gynecologic Oncology. “So that was really, I think, an interesting finding, that this doesn’t just impact the very short term. Three months is a fairly long time after a primary surgery, and [it’s] important for women to know this.”

Patients in the eight-center study had histologically confirmed clinical stage I or II endometrial cancer. The open-surgery arm of the study involved 106 patients, and 414 had minimally invasive surgery (168 laparascopic, 246 robotic).

The robotic and laparoscopic arms showed no statistically significant differences for any patient-reported outcome, even after adjusting for potentially confounding variables, said Dr. Ferguson of Princess Margaret Cancer Centre at the University of Toronto. Accordingly, investigators compared both minimally invasive arms grouped together against open surgery.

Overall, about 80% of patients completed the quality-of-life questionnaires. The response rate for the sexual-functioning questionnaires, however, was much lower, ranging from about a quarter to a half of the participants.

When Dr. Ferguson and her colleagues examined the characteristics of the patients who did complete the sexual-functioning questionnaires, they found that these women were more likely to be younger, partnered, premenopausal and sexually active at the time of diagnosis. Both of the surgical groups “met the clinical cutoff for sexual dysfunction” on the Female Sexual Function Index questionnaire, she said.

For the sexual function questionnaires, differences between the open and minimally invasive groups were not significant at any time point throughout the 26 weeks that patients were studied. “Though it’s a small population, I think these results are important,” said Dr. Ferguson. “These variables may be helpful for us to target patients in our practice, or in future studies, who require intervention.”

Though the study was not randomized, Dr. Ferguson said that the baseline characteristics were similar between groups, and the investigators’ intention-to-treat analysis used a statistical model that adjusted for many potential confounding variables.

Dr. Ferguson reported having no conflicts of interest.

[email protected]
On Twitter @karioakes

The course of chronic psychiatric conditions, such as schizophrenia, differs from chronic medical conditions, such as diabetes. Some patients with chronic psychiatric conditions achieve remission and become symptom-free, while others continue to have lingering signs of disease for life.

Residual symptoms of schizophrenia are not fully defined in the literature, which poses a challenge because they are central in the overall treatment of schizophrenia spectrum disorders.¹ During this phase of schizophrenia, patients continue to have symptoms after psychosis has subsided. These patients might continue to have negative symptoms such as social and emotional withdrawal and low energy. Although frank psychotic behavior has disappeared, the patient might continue to hold strange beliefs. Pharmacotherapy is the primary treatment option for psychiatric conditions, but the psychosocial aspect may have greater importance when treating residual symptoms and patients with chronic psychiatric illness.²

A naturalistic study in Germany evaluated the occurrence and characteristics of residual symptoms in patients with schizophrenia.³ The authors used a Positive and Negative Syndrome Scale symptom severity score >1 for those purposes, which is possibly a stringent criterion to define residual symptoms. This multicenter study enrolled 399 individuals age 18 to 65 with a DSM-IV-TR diagnosis of schizophrenia, schizophreniform disorder, delusional disorder, or schizoaffective disorder.³ Of the 236 patients achieving remission at discharge, 94% had at least 1 residual symptom and 69% had at least 4 residual symptoms. Therefore, residual symptoms were highly prevalent in remitted patients. The most frequent residual symptoms were:

• blunted affect
• conceptual disorganization
• passive or apathetic social withdrawal
• emotional withdrawal
• lack of judgment and insight
• poor attention
• somatic concern
• difficulty with abstract thinking
• anxiety
• poor rapport.³

Of note, positive symptoms, such as delusions and hallucinatory behavior, were found in remitted patients at discharge (17% and 10%, respectively). The study concluded that the severity of residual symptoms was associated with relapse risk and had an overall negative impact on the outcome of patients with schizophrenia.³ The study noted that residual symptoms may be greater in number or volume than negative symptoms and questioned the origins of residual symptoms because most were present at baseline in more than two-third of patients.

Patients with residual symptoms of schizophrenia usually are older and therefore present specific management challenges for clinicians. Changes associated with aging, such as medical problems, cognitive deficits, and lack of social support, could create new care needs for this patient population. Although the biopsycho­social model used to treat chronic psychiatric conditions, especially schizophrenia, is preferred, older schizophrenia patients with residual symptoms often need more psychosocial interventions compared with young adults with schizophrenia.

 

 

Managing residual symptoms in schizophrenia

Few studies are devoted to pharmacological treatment of older adults with schizophrenia, likely because pharmacotherapy for older patients with schizophrenia can be challenging. Evidence-based treatment is based primarily on findings from younger patients who survived into later life. Clinicians often use the adage of geriatric psychiatry, “start low, go slow,” because older patients are susceptible to adverse effects associated with psychiatric medications, including cardiovascular, metabolic, anticholinergic, and extrapyramidal effects, orthostasis, sedation, falls, and neuroleptic malignant syndrome.

Older patients with schizophrenia are at an increased risk for extrapyramidal symptoms (EPS) and anticholinergic adverse effects, perhaps because of degeneration of dopaminergic and cholinergic neurons.⁴ Lowering the anticholinergic load by discontinuing or reducing the dosage of medications with anticholinergic properties, when possible, is a key principle when treating these patients. This tactic could help improve cognition and quality of life by decreasing the risk of other anticholinergic adverse effects, including delirium, constipation, urinary retention, and blurred vision.

Patients treated with typical antipsychotics are nearly twice as likely to develop tardive dyskinesia compared with those receiving atypical antipsychotics.⁵ Sedation, orthostatic hypotension, and anticholinergic effects can cause cognitive clouding, worsen cognitive impairment, and increase the risk of falls, especially in older patients.⁶ Clozapine and olanzapine have the strongest association with clinically significant weight gain and treatment-induced type 2 diabetes mellitus.⁷

The appropriate starting dosage of antipsychotics in older patients with schizophrenia is one-fourth of the starting adult dosage. Total daily maintenance dosages may be one-third to one-half of the adult dosage.⁶ Consensus guidelines for dosing atypical antipsychotics for older patients with schizophrenia are as shown in Table 1.⁸

To ensure safety, patients should be regularly monitored with a complete blood count, comprehensive metabolic panel, lipid panel, hemoglobin A_1C, electrocardiogram, orthostatic vital signs, Abnormal Involuntary Movement Scale, and weight check.^7,9

When negative symptoms remain after a patient has achieved remission, it is important to evaluate whether the symptoms are related to adverse effects of medication (eg, parkinsonism syndrome), untreated depressive symptoms, or persistent positive symptoms, such as paranoia. Management of these symptoms consists of treating the cause, for example, using antipsychotics for primary positive symptoms, antidepressants for depression, anxiolytics for anxiety, and anti-parkinsonian agents or antipsychotic dosage reduction for EPS.

It is important to differentiate between negative symptoms of schizophrenia and depression in these patients. Negative symptoms of schizophrenia include affective flattening, alogia, avolition, and anhedonia. In depression, patients could have depressed mood, cognitive problems, sleep disturbances, and loss of appetite. Also, long-term symptoms are more consistent with negative symptomatology.

Keep in mind the potential for pharmacokinetic drug–drug interaction when using a combination of selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, paroxetine, and fluvoxamine (to treat negative/depressive symptoms), because all are significant inhibitors of cytochrome P450 enzymes and increase antipsychotic plasma level. The Expert Treatment Guidelines for Patients with Schizophrenia recommends SSRIs, followed by venlafaxine then bupropion to treat depressive symptoms after optimizing second-generation antipsychotics.⁹
 

 

Another point to consider when treating residual symptoms in patients with schizophrenia is to not discontinue antipsychotic medications. Relapse rates for these patients can occur up to 5 times higher than for those who continue treatment.¹⁰ A way to address this problem could be the use of depot antipsychotic medications, but there are no set recommendations for the use of long-acting injectable antipsychotics in older patients. These medications should be used with caution and at lowest effective dosages to offset potential adverse effects.

With the introduction of typical and atypical antipsychotics, the use of electroconvulsive therapy in older patients with schizophrenia has declined. In a 2009 meta-analysis of studies that included patients with refractory schizophrenia and repetitive transcranial magnetic stimulation (rTMS), results revealed a mixed effect size for controlled and uncontrolled studies. The authors stated the need for further controlled trials, assessing the efficacy of rTMS on negative and positive symptoms of schizophrenia.¹¹

Psychotherapy and psychosocial interventions

Patients with schizophrenia who have persistent psychotic symptoms while receiving adequate pharmacotherapy should be offered adjunctive cognitive, behaviorally oriented psychotherapy to reduce symptom severity. Cognitive-behavioral therapy (CBT) has been shown to help reduce relapse rates, reduce psychotic symptoms, and improve patients’ mental state.¹² Amotivation and lack of insight can be particularly troublesome, which CBT can help address.¹² Psychoeducation can:

• empower patients to understand their illness
• help them cope with their disease
• be aware of symptom relapse
• seek help sooner rather than later.

Also, counseling and supportive therapy are recommended by the American Psychiatric Association guidelines. Providers should involve family and loved ones in this discussion, so that they can help collaborate with care and provide a supportive and non-judgmental environment.

Older patients with residual symptoms of schizophrenia are less likely to have completed their education, pursued a career, or developed long-lasting relationships. Family members who were their support system earlier in life, such as parents, often are unable to provide care for them by the time patients with schizophrenia become older. These patients also are less likely to get married or have children, meaning that they are more likely to live alone. The advent of the interdisciplinary team, integration of several therapeutic modalities, the provision of case managers, and assertive community treatment (ACT) teams has provided help with social support, relapses, and hospitalizations, for older patients with schizophrenia.¹³ Key elements of ACT include:

• a multidisciplinary team, including a medication prescriber
• a shared caseload among team members
• direct service provision by team members
• frequent patient contact
• low patient to staff ratios
• outreach to patients in the community.

Medical care

Patients with schizophrenia are at higher risk for several comorbid medical conditions, such as diabetes, coronary artery disease, and digestive and liver disorders, compared with individuals without schizophrenia. This risk is associated with numerous factors, including sedentary lifestyle, high rates of lifetime cigarette use (70% to 80% of schizophrenia outpatients age <67 smoke), poor self-management skills, frequent homelessness, and unhealthy diet.

Although substantial attention is devoted to the psychiatric and behavioral management of patients with schizophrenia, many barriers impede the detection and treatment of their medical conditions. Patients with schizophrenia could experience delays in diagnosing a medical disorder, leading to more acute comorbidities at the time of diagnosis and premature mortality. Studies have confirmed that cardiovascular diseases are the leading cause of premature death among psychiatric patients in the United States.¹⁴ Key risk factors include smoking, obesity, hypertension, dyslipidemia, diabetes, and lack of physical activity, all of which are more common among patients with schizophrenia compared with the general population.¹⁵ In addition, antipsychotics are associated with adverse metabolic effects.¹⁶

 

 

What are realistic treatment goals to manage residual symptoms in schizophrenia?

We believe that because remission in schizophrenia has been defined consensually, the bar for treatment expectations is set higher than it was 20 years ago. There can be patient-, family-, and system-related variables affecting the feasibility of treating residual symptoms. Providers who treat patients with schizophrenia should consider the following treatment goals:

• Prevent relapse and acute psychiatric hospitalization
• Use evidence-based strategies to minimize or monitor adverse effects
• Monitor compliance and consider use of depot antipsychotics combined with patients’ preference
• Facilitate ongoing safety assessment, including suicide risk
• Monitor negative and cognitive symptoms in addition to positive symptoms, using evidence-based management
• Encourage collaboration of care with family, caretakers, and other members of the treatment team
• Empower patients by providing psycho­education and social skills training and assisting in their vocational rehabilitation 
• Educate the patient and family about healthy lifestyle interventions and medical comorbidities common with schizophrenia
• Perform baseline screening and follow-up for early detection and treatment of medical comorbidities in patients with schizophrenia
• Improve functional status and quality of life.

In addition to meeting these treatment goals, a measurement-based method can be implemented to monitor improvement and status of the independent treatment domains. A collection of rating instruments can be found in Table 2.^17-30

Summing up

The clinical presentation of patients with residual symptoms of schizophrenia differs from that of other patients with schizophrenia. Our understanding of residual symptoms in schizophrenia has come a long way in the last decade; however, we are still far from pinning the complex nature of these symptoms, let alone their management. Given the risk of morbidity and disability, there clearly is a need for further investigation and investment of time and resources to support developing novel pharmacological treatment options to manage residual symptoms in patients with schizophrenia.

Because patients with residual symptoms of schizophrenia usually are older, psychiatrists should be responsible for implementing necessary screening assessments and should closely collaborate with primary care practitioners and other specialists, and when necessary, treat comorbid medical conditions. The importance of educating patients, their families, and the treatment team cannot be overlooked. Further, psychiatric treatment facilities should offer and promote healthy lifestyle interventions.

The course of chronic psychiatric conditions, such as schizophrenia, differs from chronic medical conditions, such as diabetes. Some patients with chronic psychiatric conditions achieve remission and become symptom-free, while others continue to have lingering signs of disease for life.

Residual symptoms of schizophrenia are not fully defined in the literature, which poses a challenge because they are central in the overall treatment of schizophrenia spectrum disorders.¹ During this phase of schizophrenia, patients continue to have symptoms after psychosis has subsided. These patients might continue to have negative symptoms such as social and emotional withdrawal and low energy. Although frank psychotic behavior has disappeared, the patient might continue to hold strange beliefs. Pharmacotherapy is the primary treatment option for psychiatric conditions, but the psychosocial aspect may have greater importance when treating residual symptoms and patients with chronic psychiatric illness.²

A naturalistic study in Germany evaluated the occurrence and characteristics of residual symptoms in patients with schizophrenia.³ The authors used a Positive and Negative Syndrome Scale symptom severity score >1 for those purposes, which is possibly a stringent criterion to define residual symptoms. This multicenter study enrolled 399 individuals age 18 to 65 with a DSM-IV-TR diagnosis of schizophrenia, schizophreniform disorder, delusional disorder, or schizoaffective disorder.³ Of the 236 patients achieving remission at discharge, 94% had at least 1 residual symptom and 69% had at least 4 residual symptoms. Therefore, residual symptoms were highly prevalent in remitted patients. The most frequent residual symptoms were:

• blunted affect
• conceptual disorganization
• passive or apathetic social withdrawal
• emotional withdrawal
• lack of judgment and insight
• poor attention
• somatic concern
• difficulty with abstract thinking
• anxiety
• poor rapport.³

Of note, positive symptoms, such as delusions and hallucinatory behavior, were found in remitted patients at discharge (17% and 10%, respectively). The study concluded that the severity of residual symptoms was associated with relapse risk and had an overall negative impact on the outcome of patients with schizophrenia.³ The study noted that residual symptoms may be greater in number or volume than negative symptoms and questioned the origins of residual symptoms because most were present at baseline in more than two-third of patients.

Patients with residual symptoms of schizophrenia usually are older and therefore present specific management challenges for clinicians. Changes associated with aging, such as medical problems, cognitive deficits, and lack of social support, could create new care needs for this patient population. Although the biopsycho­social model used to treat chronic psychiatric conditions, especially schizophrenia, is preferred, older schizophrenia patients with residual symptoms often need more psychosocial interventions compared with young adults with schizophrenia.

 

 

Managing residual symptoms in schizophrenia

Few studies are devoted to pharmacological treatment of older adults with schizophrenia, likely because pharmacotherapy for older patients with schizophrenia can be challenging. Evidence-based treatment is based primarily on findings from younger patients who survived into later life. Clinicians often use the adage of geriatric psychiatry, “start low, go slow,” because older patients are susceptible to adverse effects associated with psychiatric medications, including cardiovascular, metabolic, anticholinergic, and extrapyramidal effects, orthostasis, sedation, falls, and neuroleptic malignant syndrome.

Older patients with schizophrenia are at an increased risk for extrapyramidal symptoms (EPS) and anticholinergic adverse effects, perhaps because of degeneration of dopaminergic and cholinergic neurons.⁴ Lowering the anticholinergic load by discontinuing or reducing the dosage of medications with anticholinergic properties, when possible, is a key principle when treating these patients. This tactic could help improve cognition and quality of life by decreasing the risk of other anticholinergic adverse effects, including delirium, constipation, urinary retention, and blurred vision.

Patients treated with typical antipsychotics are nearly twice as likely to develop tardive dyskinesia compared with those receiving atypical antipsychotics.⁵ Sedation, orthostatic hypotension, and anticholinergic effects can cause cognitive clouding, worsen cognitive impairment, and increase the risk of falls, especially in older patients.⁶ Clozapine and olanzapine have the strongest association with clinically significant weight gain and treatment-induced type 2 diabetes mellitus.⁷

The appropriate starting dosage of antipsychotics in older patients with schizophrenia is one-fourth of the starting adult dosage. Total daily maintenance dosages may be one-third to one-half of the adult dosage.⁶ Consensus guidelines for dosing atypical antipsychotics for older patients with schizophrenia are as shown in Table 1.⁸

To ensure safety, patients should be regularly monitored with a complete blood count, comprehensive metabolic panel, lipid panel, hemoglobin A_1C, electrocardiogram, orthostatic vital signs, Abnormal Involuntary Movement Scale, and weight check.^7,9

When negative symptoms remain after a patient has achieved remission, it is important to evaluate whether the symptoms are related to adverse effects of medication (eg, parkinsonism syndrome), untreated depressive symptoms, or persistent positive symptoms, such as paranoia. Management of these symptoms consists of treating the cause, for example, using antipsychotics for primary positive symptoms, antidepressants for depression, anxiolytics for anxiety, and anti-parkinsonian agents or antipsychotic dosage reduction for EPS.

It is important to differentiate between negative symptoms of schizophrenia and depression in these patients. Negative symptoms of schizophrenia include affective flattening, alogia, avolition, and anhedonia. In depression, patients could have depressed mood, cognitive problems, sleep disturbances, and loss of appetite. Also, long-term symptoms are more consistent with negative symptomatology.

Keep in mind the potential for pharmacokinetic drug–drug interaction when using a combination of selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, paroxetine, and fluvoxamine (to treat negative/depressive symptoms), because all are significant inhibitors of cytochrome P450 enzymes and increase antipsychotic plasma level. The Expert Treatment Guidelines for Patients with Schizophrenia recommends SSRIs, followed by venlafaxine then bupropion to treat depressive symptoms after optimizing second-generation antipsychotics.⁹
 

 

Another point to consider when treating residual symptoms in patients with schizophrenia is to not discontinue antipsychotic medications. Relapse rates for these patients can occur up to 5 times higher than for those who continue treatment.¹⁰ A way to address this problem could be the use of depot antipsychotic medications, but there are no set recommendations for the use of long-acting injectable antipsychotics in older patients. These medications should be used with caution and at lowest effective dosages to offset potential adverse effects.

With the introduction of typical and atypical antipsychotics, the use of electroconvulsive therapy in older patients with schizophrenia has declined. In a 2009 meta-analysis of studies that included patients with refractory schizophrenia and repetitive transcranial magnetic stimulation (rTMS), results revealed a mixed effect size for controlled and uncontrolled studies. The authors stated the need for further controlled trials, assessing the efficacy of rTMS on negative and positive symptoms of schizophrenia.¹¹

Psychotherapy and psychosocial interventions

Patients with schizophrenia who have persistent psychotic symptoms while receiving adequate pharmacotherapy should be offered adjunctive cognitive, behaviorally oriented psychotherapy to reduce symptom severity. Cognitive-behavioral therapy (CBT) has been shown to help reduce relapse rates, reduce psychotic symptoms, and improve patients’ mental state.¹² Amotivation and lack of insight can be particularly troublesome, which CBT can help address.¹² Psychoeducation can:

• empower patients to understand their illness
• help them cope with their disease
• be aware of symptom relapse
• seek help sooner rather than later.

Also, counseling and supportive therapy are recommended by the American Psychiatric Association guidelines. Providers should involve family and loved ones in this discussion, so that they can help collaborate with care and provide a supportive and non-judgmental environment.

Older patients with residual symptoms of schizophrenia are less likely to have completed their education, pursued a career, or developed long-lasting relationships. Family members who were their support system earlier in life, such as parents, often are unable to provide care for them by the time patients with schizophrenia become older. These patients also are less likely to get married or have children, meaning that they are more likely to live alone. The advent of the interdisciplinary team, integration of several therapeutic modalities, the provision of case managers, and assertive community treatment (ACT) teams has provided help with social support, relapses, and hospitalizations, for older patients with schizophrenia.¹³ Key elements of ACT include:

• a multidisciplinary team, including a medication prescriber
• a shared caseload among team members
• direct service provision by team members
• frequent patient contact
• low patient to staff ratios
• outreach to patients in the community.

Medical care

Patients with schizophrenia are at higher risk for several comorbid medical conditions, such as diabetes, coronary artery disease, and digestive and liver disorders, compared with individuals without schizophrenia. This risk is associated with numerous factors, including sedentary lifestyle, high rates of lifetime cigarette use (70% to 80% of schizophrenia outpatients age <67 smoke), poor self-management skills, frequent homelessness, and unhealthy diet.

Although substantial attention is devoted to the psychiatric and behavioral management of patients with schizophrenia, many barriers impede the detection and treatment of their medical conditions. Patients with schizophrenia could experience delays in diagnosing a medical disorder, leading to more acute comorbidities at the time of diagnosis and premature mortality. Studies have confirmed that cardiovascular diseases are the leading cause of premature death among psychiatric patients in the United States.¹⁴ Key risk factors include smoking, obesity, hypertension, dyslipidemia, diabetes, and lack of physical activity, all of which are more common among patients with schizophrenia compared with the general population.¹⁵ In addition, antipsychotics are associated with adverse metabolic effects.¹⁶

 

 

What are realistic treatment goals to manage residual symptoms in schizophrenia?

We believe that because remission in schizophrenia has been defined consensually, the bar for treatment expectations is set higher than it was 20 years ago. There can be patient-, family-, and system-related variables affecting the feasibility of treating residual symptoms. Providers who treat patients with schizophrenia should consider the following treatment goals:

• Prevent relapse and acute psychiatric hospitalization
• Use evidence-based strategies to minimize or monitor adverse effects
• Monitor compliance and consider use of depot antipsychotics combined with patients’ preference
• Facilitate ongoing safety assessment, including suicide risk
• Monitor negative and cognitive symptoms in addition to positive symptoms, using evidence-based management
• Encourage collaboration of care with family, caretakers, and other members of the treatment team
• Empower patients by providing psycho­education and social skills training and assisting in their vocational rehabilitation 
• Educate the patient and family about healthy lifestyle interventions and medical comorbidities common with schizophrenia
• Perform baseline screening and follow-up for early detection and treatment of medical comorbidities in patients with schizophrenia
• Improve functional status and quality of life.

In addition to meeting these treatment goals, a measurement-based method can be implemented to monitor improvement and status of the independent treatment domains. A collection of rating instruments can be found in Table 2.^17-30

Summing up

The clinical presentation of patients with residual symptoms of schizophrenia differs from that of other patients with schizophrenia. Our understanding of residual symptoms in schizophrenia has come a long way in the last decade; however, we are still far from pinning the complex nature of these symptoms, let alone their management. Given the risk of morbidity and disability, there clearly is a need for further investigation and investment of time and resources to support developing novel pharmacological treatment options to manage residual symptoms in patients with schizophrenia.

Because patients with residual symptoms of schizophrenia usually are older, psychiatrists should be responsible for implementing necessary screening assessments and should closely collaborate with primary care practitioners and other specialists, and when necessary, treat comorbid medical conditions. The importance of educating patients, their families, and the treatment team cannot be overlooked. Further, psychiatric treatment facilities should offer and promote healthy lifestyle interventions.

The course of chronic psychiatric conditions, such as schizophrenia, differs from chronic medical conditions, such as diabetes. Some patients with chronic psychiatric conditions achieve remission and become symptom-free, while others continue to have lingering signs of disease for life.

Residual symptoms of schizophrenia are not fully defined in the literature, which poses a challenge because they are central in the overall treatment of schizophrenia spectrum disorders.¹ During this phase of schizophrenia, patients continue to have symptoms after psychosis has subsided. These patients might continue to have negative symptoms such as social and emotional withdrawal and low energy. Although frank psychotic behavior has disappeared, the patient might continue to hold strange beliefs. Pharmacotherapy is the primary treatment option for psychiatric conditions, but the psychosocial aspect may have greater importance when treating residual symptoms and patients with chronic psychiatric illness.²

A naturalistic study in Germany evaluated the occurrence and characteristics of residual symptoms in patients with schizophrenia.³ The authors used a Positive and Negative Syndrome Scale symptom severity score >1 for those purposes, which is possibly a stringent criterion to define residual symptoms. This multicenter study enrolled 399 individuals age 18 to 65 with a DSM-IV-TR diagnosis of schizophrenia, schizophreniform disorder, delusional disorder, or schizoaffective disorder.³ Of the 236 patients achieving remission at discharge, 94% had at least 1 residual symptom and 69% had at least 4 residual symptoms. Therefore, residual symptoms were highly prevalent in remitted patients. The most frequent residual symptoms were:

• blunted affect
• conceptual disorganization
• passive or apathetic social withdrawal
• emotional withdrawal
• lack of judgment and insight
• poor attention
• somatic concern
• difficulty with abstract thinking
• anxiety
• poor rapport.³

Of note, positive symptoms, such as delusions and hallucinatory behavior, were found in remitted patients at discharge (17% and 10%, respectively). The study concluded that the severity of residual symptoms was associated with relapse risk and had an overall negative impact on the outcome of patients with schizophrenia.³ The study noted that residual symptoms may be greater in number or volume than negative symptoms and questioned the origins of residual symptoms because most were present at baseline in more than two-third of patients.

Patients with residual symptoms of schizophrenia usually are older and therefore present specific management challenges for clinicians. Changes associated with aging, such as medical problems, cognitive deficits, and lack of social support, could create new care needs for this patient population. Although the biopsycho­social model used to treat chronic psychiatric conditions, especially schizophrenia, is preferred, older schizophrenia patients with residual symptoms often need more psychosocial interventions compared with young adults with schizophrenia.

 

 

Managing residual symptoms in schizophrenia

Few studies are devoted to pharmacological treatment of older adults with schizophrenia, likely because pharmacotherapy for older patients with schizophrenia can be challenging. Evidence-based treatment is based primarily on findings from younger patients who survived into later life. Clinicians often use the adage of geriatric psychiatry, “start low, go slow,” because older patients are susceptible to adverse effects associated with psychiatric medications, including cardiovascular, metabolic, anticholinergic, and extrapyramidal effects, orthostasis, sedation, falls, and neuroleptic malignant syndrome.

Older patients with schizophrenia are at an increased risk for extrapyramidal symptoms (EPS) and anticholinergic adverse effects, perhaps because of degeneration of dopaminergic and cholinergic neurons.⁴ Lowering the anticholinergic load by discontinuing or reducing the dosage of medications with anticholinergic properties, when possible, is a key principle when treating these patients. This tactic could help improve cognition and quality of life by decreasing the risk of other anticholinergic adverse effects, including delirium, constipation, urinary retention, and blurred vision.

Patients treated with typical antipsychotics are nearly twice as likely to develop tardive dyskinesia compared with those receiving atypical antipsychotics.⁵ Sedation, orthostatic hypotension, and anticholinergic effects can cause cognitive clouding, worsen cognitive impairment, and increase the risk of falls, especially in older patients.⁶ Clozapine and olanzapine have the strongest association with clinically significant weight gain and treatment-induced type 2 diabetes mellitus.⁷

The appropriate starting dosage of antipsychotics in older patients with schizophrenia is one-fourth of the starting adult dosage. Total daily maintenance dosages may be one-third to one-half of the adult dosage.⁶ Consensus guidelines for dosing atypical antipsychotics for older patients with schizophrenia are as shown in Table 1.⁸

To ensure safety, patients should be regularly monitored with a complete blood count, comprehensive metabolic panel, lipid panel, hemoglobin A_1C, electrocardiogram, orthostatic vital signs, Abnormal Involuntary Movement Scale, and weight check.^7,9

When negative symptoms remain after a patient has achieved remission, it is important to evaluate whether the symptoms are related to adverse effects of medication (eg, parkinsonism syndrome), untreated depressive symptoms, or persistent positive symptoms, such as paranoia. Management of these symptoms consists of treating the cause, for example, using antipsychotics for primary positive symptoms, antidepressants for depression, anxiolytics for anxiety, and anti-parkinsonian agents or antipsychotic dosage reduction for EPS.

It is important to differentiate between negative symptoms of schizophrenia and depression in these patients. Negative symptoms of schizophrenia include affective flattening, alogia, avolition, and anhedonia. In depression, patients could have depressed mood, cognitive problems, sleep disturbances, and loss of appetite. Also, long-term symptoms are more consistent with negative symptomatology.

Keep in mind the potential for pharmacokinetic drug–drug interaction when using a combination of selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, paroxetine, and fluvoxamine (to treat negative/depressive symptoms), because all are significant inhibitors of cytochrome P450 enzymes and increase antipsychotic plasma level. The Expert Treatment Guidelines for Patients with Schizophrenia recommends SSRIs, followed by venlafaxine then bupropion to treat depressive symptoms after optimizing second-generation antipsychotics.⁹
 

 

Another point to consider when treating residual symptoms in patients with schizophrenia is to not discontinue antipsychotic medications. Relapse rates for these patients can occur up to 5 times higher than for those who continue treatment.¹⁰ A way to address this problem could be the use of depot antipsychotic medications, but there are no set recommendations for the use of long-acting injectable antipsychotics in older patients. These medications should be used with caution and at lowest effective dosages to offset potential adverse effects.

With the introduction of typical and atypical antipsychotics, the use of electroconvulsive therapy in older patients with schizophrenia has declined. In a 2009 meta-analysis of studies that included patients with refractory schizophrenia and repetitive transcranial magnetic stimulation (rTMS), results revealed a mixed effect size for controlled and uncontrolled studies. The authors stated the need for further controlled trials, assessing the efficacy of rTMS on negative and positive symptoms of schizophrenia.¹¹

Psychotherapy and psychosocial interventions

Patients with schizophrenia who have persistent psychotic symptoms while receiving adequate pharmacotherapy should be offered adjunctive cognitive, behaviorally oriented psychotherapy to reduce symptom severity. Cognitive-behavioral therapy (CBT) has been shown to help reduce relapse rates, reduce psychotic symptoms, and improve patients’ mental state.¹² Amotivation and lack of insight can be particularly troublesome, which CBT can help address.¹² Psychoeducation can:

• empower patients to understand their illness
• help them cope with their disease
• be aware of symptom relapse
• seek help sooner rather than later.

Also, counseling and supportive therapy are recommended by the American Psychiatric Association guidelines. Providers should involve family and loved ones in this discussion, so that they can help collaborate with care and provide a supportive and non-judgmental environment.

Older patients with residual symptoms of schizophrenia are less likely to have completed their education, pursued a career, or developed long-lasting relationships. Family members who were their support system earlier in life, such as parents, often are unable to provide care for them by the time patients with schizophrenia become older. These patients also are less likely to get married or have children, meaning that they are more likely to live alone. The advent of the interdisciplinary team, integration of several therapeutic modalities, the provision of case managers, and assertive community treatment (ACT) teams has provided help with social support, relapses, and hospitalizations, for older patients with schizophrenia.¹³ Key elements of ACT include:

• a multidisciplinary team, including a medication prescriber
• a shared caseload among team members
• direct service provision by team members
• frequent patient contact
• low patient to staff ratios
• outreach to patients in the community.

Medical care

Patients with schizophrenia are at higher risk for several comorbid medical conditions, such as diabetes, coronary artery disease, and digestive and liver disorders, compared with individuals without schizophrenia. This risk is associated with numerous factors, including sedentary lifestyle, high rates of lifetime cigarette use (70% to 80% of schizophrenia outpatients age <67 smoke), poor self-management skills, frequent homelessness, and unhealthy diet.

Although substantial attention is devoted to the psychiatric and behavioral management of patients with schizophrenia, many barriers impede the detection and treatment of their medical conditions. Patients with schizophrenia could experience delays in diagnosing a medical disorder, leading to more acute comorbidities at the time of diagnosis and premature mortality. Studies have confirmed that cardiovascular diseases are the leading cause of premature death among psychiatric patients in the United States.¹⁴ Key risk factors include smoking, obesity, hypertension, dyslipidemia, diabetes, and lack of physical activity, all of which are more common among patients with schizophrenia compared with the general population.¹⁵ In addition, antipsychotics are associated with adverse metabolic effects.¹⁶

 

 

What are realistic treatment goals to manage residual symptoms in schizophrenia?

We believe that because remission in schizophrenia has been defined consensually, the bar for treatment expectations is set higher than it was 20 years ago. There can be patient-, family-, and system-related variables affecting the feasibility of treating residual symptoms. Providers who treat patients with schizophrenia should consider the following treatment goals:

• Prevent relapse and acute psychiatric hospitalization
• Use evidence-based strategies to minimize or monitor adverse effects
• Monitor compliance and consider use of depot antipsychotics combined with patients’ preference
• Facilitate ongoing safety assessment, including suicide risk
• Monitor negative and cognitive symptoms in addition to positive symptoms, using evidence-based management
• Encourage collaboration of care with family, caretakers, and other members of the treatment team
• Empower patients by providing psycho­education and social skills training and assisting in their vocational rehabilitation 
• Educate the patient and family about healthy lifestyle interventions and medical comorbidities common with schizophrenia
• Perform baseline screening and follow-up for early detection and treatment of medical comorbidities in patients with schizophrenia
• Improve functional status and quality of life.

In addition to meeting these treatment goals, a measurement-based method can be implemented to monitor improvement and status of the independent treatment domains. A collection of rating instruments can be found in Table 2.^17-30

Summing up

The clinical presentation of patients with residual symptoms of schizophrenia differs from that of other patients with schizophrenia. Our understanding of residual symptoms in schizophrenia has come a long way in the last decade; however, we are still far from pinning the complex nature of these symptoms, let alone their management. Given the risk of morbidity and disability, there clearly is a need for further investigation and investment of time and resources to support developing novel pharmacological treatment options to manage residual symptoms in patients with schizophrenia.

Because patients with residual symptoms of schizophrenia usually are older, psychiatrists should be responsible for implementing necessary screening assessments and should closely collaborate with primary care practitioners and other specialists, and when necessary, treat comorbid medical conditions. The importance of educating patients, their families, and the treatment team cannot be overlooked. Further, psychiatric treatment facilities should offer and promote healthy lifestyle interventions.

General Medical Sciences

A new study supports the idea that most cancer-driving mutations are a result of DNA replication errors, not heredity or lifestyle/environmental factors.

For all 32 cancer types studied, researchers found that 66% of driver mutations resulted from DNA replication errors, 29% could be attributed to lifestyle or environmental factors, and the remaining 5% were inherited.

In hematologic malignancies, the percentage of mutations caused by DNA replication errors was even higher—70% in Hodgkin lymphoma, 85% in leukemias, 96% in non-Hodgkin lymphomas, and 99% in myeloma.

Cristian Tomasetti, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these findings in Science.

“It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting cancer, but it is not as well-known that each time a normal cell divides and copies its DNA to produce 2 new cells, it makes multiple mistakes,” Dr Tomasetti said.

“These copying mistakes are a potent source of cancer mutations that, historically, have been scientifically undervalued, and this new work provides the first estimate of the fraction of mutations caused by these mistakes.”

In 2015, Dr Tomasetti and his colleagues reported that DNA replication errors could explain why certain cancers occur more often than others in the US.

The current study builds upon that research but includes additional cancers and encompasses an international population.

The researchers first studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries representing 4.8 billion people, or more than half of the world’s population.

The team said they observed a strong correlation between cancer incidence and normal stem cell divisions in all countries, regardless of their environment.

Next, the researchers set out to determine the percentage of driver mutations caused by DNA replication errors in 32 cancer types. The team developed a mathematical model using DNA sequencing data from The Cancer Genome Atlas and epidemiologic data from the Cancer Research UK database.

According to the researchers, it generally takes 2 or more critical mutations for cancer to occur. In an individual, these mutations can be due to random DNA replication errors, the environment, or inherited genes.

Knowing this, the researchers used their mathematical model to show, for example, that when critical mutations in leukemia are added together, 85.2% of them are due to random DNA replication errors, 14.3% to environmental factors, and 0.5% to heredity.

In Hodgkin lymphoma, 69.5% are due to DNA replication errors, 30% to environmental factors, and 0.5% to heredity. In non-Hodgkin lymphoma, 95.6% are due to random DNA replication errors, 3.9% to environmental factors, and 0.5% to heredity.

In myeloma, 99.3% are due to DNA replication errors, 0.2% to environmental factors, and 0.5% to heredity.

Dr Tomasetti said these random DNA replication errors will only get more important as aging populations continue to grow, prolonging the opportunity for cells to make more and more errors.

“We need to continue to encourage people to avoid environmental agents and lifestyles that increase their risk of developing cancer mutations,” said study author Bert Vogelstein, MD, of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University.

“However, many people will still develop cancers due to these random DNA copying errors, and better methods to detect all cancers earlier, while they are still curable, are urgently needed.”

General Medical Sciences

A new study supports the idea that most cancer-driving mutations are a result of DNA replication errors, not heredity or lifestyle/environmental factors.

For all 32 cancer types studied, researchers found that 66% of driver mutations resulted from DNA replication errors, 29% could be attributed to lifestyle or environmental factors, and the remaining 5% were inherited.

In hematologic malignancies, the percentage of mutations caused by DNA replication errors was even higher—70% in Hodgkin lymphoma, 85% in leukemias, 96% in non-Hodgkin lymphomas, and 99% in myeloma.

Cristian Tomasetti, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these findings in Science.

“It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting cancer, but it is not as well-known that each time a normal cell divides and copies its DNA to produce 2 new cells, it makes multiple mistakes,” Dr Tomasetti said.

“These copying mistakes are a potent source of cancer mutations that, historically, have been scientifically undervalued, and this new work provides the first estimate of the fraction of mutations caused by these mistakes.”

In 2015, Dr Tomasetti and his colleagues reported that DNA replication errors could explain why certain cancers occur more often than others in the US.

The current study builds upon that research but includes additional cancers and encompasses an international population.

The researchers first studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries representing 4.8 billion people, or more than half of the world’s population.

The team said they observed a strong correlation between cancer incidence and normal stem cell divisions in all countries, regardless of their environment.

Next, the researchers set out to determine the percentage of driver mutations caused by DNA replication errors in 32 cancer types. The team developed a mathematical model using DNA sequencing data from The Cancer Genome Atlas and epidemiologic data from the Cancer Research UK database.

According to the researchers, it generally takes 2 or more critical mutations for cancer to occur. In an individual, these mutations can be due to random DNA replication errors, the environment, or inherited genes.

Knowing this, the researchers used their mathematical model to show, for example, that when critical mutations in leukemia are added together, 85.2% of them are due to random DNA replication errors, 14.3% to environmental factors, and 0.5% to heredity.

In Hodgkin lymphoma, 69.5% are due to DNA replication errors, 30% to environmental factors, and 0.5% to heredity. In non-Hodgkin lymphoma, 95.6% are due to random DNA replication errors, 3.9% to environmental factors, and 0.5% to heredity.

In myeloma, 99.3% are due to DNA replication errors, 0.2% to environmental factors, and 0.5% to heredity.

Dr Tomasetti said these random DNA replication errors will only get more important as aging populations continue to grow, prolonging the opportunity for cells to make more and more errors.

“We need to continue to encourage people to avoid environmental agents and lifestyles that increase their risk of developing cancer mutations,” said study author Bert Vogelstein, MD, of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University.

“However, many people will still develop cancers due to these random DNA copying errors, and better methods to detect all cancers earlier, while they are still curable, are urgently needed.”

General Medical Sciences

A new study supports the idea that most cancer-driving mutations are a result of DNA replication errors, not heredity or lifestyle/environmental factors.

For all 32 cancer types studied, researchers found that 66% of driver mutations resulted from DNA replication errors, 29% could be attributed to lifestyle or environmental factors, and the remaining 5% were inherited.

In hematologic malignancies, the percentage of mutations caused by DNA replication errors was even higher—70% in Hodgkin lymphoma, 85% in leukemias, 96% in non-Hodgkin lymphomas, and 99% in myeloma.

Cristian Tomasetti, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these findings in Science.

“It is well-known that we must avoid environmental factors such as smoking to decrease our risk of getting cancer, but it is not as well-known that each time a normal cell divides and copies its DNA to produce 2 new cells, it makes multiple mistakes,” Dr Tomasetti said.

“These copying mistakes are a potent source of cancer mutations that, historically, have been scientifically undervalued, and this new work provides the first estimate of the fraction of mutations caused by these mistakes.”

In 2015, Dr Tomasetti and his colleagues reported that DNA replication errors could explain why certain cancers occur more often than others in the US.

The current study builds upon that research but includes additional cancers and encompasses an international population.

The researchers first studied the relationship between the number of normal stem cell divisions and the risk of 17 cancer types in 69 countries representing 4.8 billion people, or more than half of the world’s population.

The team said they observed a strong correlation between cancer incidence and normal stem cell divisions in all countries, regardless of their environment.

Next, the researchers set out to determine the percentage of driver mutations caused by DNA replication errors in 32 cancer types. The team developed a mathematical model using DNA sequencing data from The Cancer Genome Atlas and epidemiologic data from the Cancer Research UK database.

According to the researchers, it generally takes 2 or more critical mutations for cancer to occur. In an individual, these mutations can be due to random DNA replication errors, the environment, or inherited genes.

Knowing this, the researchers used their mathematical model to show, for example, that when critical mutations in leukemia are added together, 85.2% of them are due to random DNA replication errors, 14.3% to environmental factors, and 0.5% to heredity.

In Hodgkin lymphoma, 69.5% are due to DNA replication errors, 30% to environmental factors, and 0.5% to heredity. In non-Hodgkin lymphoma, 95.6% are due to random DNA replication errors, 3.9% to environmental factors, and 0.5% to heredity.

In myeloma, 99.3% are due to DNA replication errors, 0.2% to environmental factors, and 0.5% to heredity.

Dr Tomasetti said these random DNA replication errors will only get more important as aging populations continue to grow, prolonging the opportunity for cells to make more and more errors.

“We need to continue to encourage people to avoid environmental agents and lifestyles that increase their risk of developing cancer mutations,” said study author Bert Vogelstein, MD, of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University.

“However, many people will still develop cancers due to these random DNA copying errors, and better methods to detect all cancers earlier, while they are still curable, are urgently needed.”

Photo by Nina Matthews

Women diagnosed with cancer during their childbearing years have an increased risk of preterm births, according to research published in JAMA Oncology.

The study showed that cancer survivors were more likely than women who never had cancer to give birth prematurely, have underweight babies, and undergo cesarean section deliveries.

The researchers said women diagnosed with cancer during pregnancy may be delivering early in order to start their cancer treatment, but that does not fully explain these findings.

The team also detected an increased risk of preterm delivery in women who had already received cancer treatment.

“We found that women were more likely to deliver preterm if they’ve been treated for cancer overall, with greater risks for women who had chemotherapy,” said study author Hazel B. Nichols, PhD, of University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill.

“While we believe these findings are something women should be aware of, we still have a lot of work to do to understand why this risk is becoming apparent and whether or not the children who are born preterm to these women go on to develop any health concerns.”

Dr Nichols and her colleagues analyzed data on 2598 births to female adolescent and young adult cancer survivors (ages 15 to 39) and 12,990 births to women without a cancer diagnosis.

Among cancer survivors, there was a significantly increased prevalence of preterm birth (prevalence ratio [PR]=1.52), low birth weight (PR=1.59), and cesarean delivery (PR=1.08), compared to women without a cancer diagnosis.

Timing of diagnosis and cancer type

When the researchers broke the data down by cancer diagnosis, they found a higher risk of preterm birth and low birth weight for women with lymphoma as well as breast and gynecologic cancers.

The PR for preterm birth was 1.59 for Hodgkin lymphoma, 1.98 for breast cancer, 2.11 for non-Hodgkin lymphoma, and 2.58 for gynecologic cancer. The PR for low birth weight was 1.59 for breast cancer, 2.41 for non-Hodgkin lymphoma, and 2.74 for gynecologic cancer.

The researchers found an increased risk of adverse birth outcomes among women who were diagnosed with cancer while pregnant and before pregnancy.

Among women diagnosed while pregnant, the PR was 2.97 for preterm birth, 2.82 for low birth weight, 1.21 for cesarean delivery, and 1.90 for low Apgar score. Among women diagnosed before pregnancy, the PR was 1.23 for preterm birth and 1.36 for low birth weight.

Role of treatment

Compared to women without a cancer diagnosis, cancer survivors who received chemotherapy but no radiation were more likely to have preterm births (PR=2.11), infants with low birth weight (PR=2.36), and cesarean deliveries (PR=1.16).

There was no significant increase in adverse birth outcomes among cancer survivors who received radiation but not chemotherapy.

Among the cancer survivors, women who received chemotherapy without radiation were more likely to have preterm births (PR=2.12), infants with low birth weight (PR=2.13), and infants who were small for their gestational age (PR=1.43) when compared to women treated with surgery only.

Dr Nichols said the role of treatment is an area of possible future research.

“We’d like to get better information about the types of chemotherapy women receive,” she said. “Chemotherapy is a very broad category, and the agents have very different effects on the body. In the future, we’d like to get more detailed information on the types of drugs that were involved in treatment.”

Photo by Nina Matthews

Women diagnosed with cancer during their childbearing years have an increased risk of preterm births, according to research published in JAMA Oncology.

The study showed that cancer survivors were more likely than women who never had cancer to give birth prematurely, have underweight babies, and undergo cesarean section deliveries.

The researchers said women diagnosed with cancer during pregnancy may be delivering early in order to start their cancer treatment, but that does not fully explain these findings.

The team also detected an increased risk of preterm delivery in women who had already received cancer treatment.

“We found that women were more likely to deliver preterm if they’ve been treated for cancer overall, with greater risks for women who had chemotherapy,” said study author Hazel B. Nichols, PhD, of University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill.

“While we believe these findings are something women should be aware of, we still have a lot of work to do to understand why this risk is becoming apparent and whether or not the children who are born preterm to these women go on to develop any health concerns.”

Dr Nichols and her colleagues analyzed data on 2598 births to female adolescent and young adult cancer survivors (ages 15 to 39) and 12,990 births to women without a cancer diagnosis.

Among cancer survivors, there was a significantly increased prevalence of preterm birth (prevalence ratio [PR]=1.52), low birth weight (PR=1.59), and cesarean delivery (PR=1.08), compared to women without a cancer diagnosis.

Timing of diagnosis and cancer type

When the researchers broke the data down by cancer diagnosis, they found a higher risk of preterm birth and low birth weight for women with lymphoma as well as breast and gynecologic cancers.

The PR for preterm birth was 1.59 for Hodgkin lymphoma, 1.98 for breast cancer, 2.11 for non-Hodgkin lymphoma, and 2.58 for gynecologic cancer. The PR for low birth weight was 1.59 for breast cancer, 2.41 for non-Hodgkin lymphoma, and 2.74 for gynecologic cancer.

The researchers found an increased risk of adverse birth outcomes among women who were diagnosed with cancer while pregnant and before pregnancy.

Among women diagnosed while pregnant, the PR was 2.97 for preterm birth, 2.82 for low birth weight, 1.21 for cesarean delivery, and 1.90 for low Apgar score. Among women diagnosed before pregnancy, the PR was 1.23 for preterm birth and 1.36 for low birth weight.

Role of treatment

Compared to women without a cancer diagnosis, cancer survivors who received chemotherapy but no radiation were more likely to have preterm births (PR=2.11), infants with low birth weight (PR=2.36), and cesarean deliveries (PR=1.16).

There was no significant increase in adverse birth outcomes among cancer survivors who received radiation but not chemotherapy.

Among the cancer survivors, women who received chemotherapy without radiation were more likely to have preterm births (PR=2.12), infants with low birth weight (PR=2.13), and infants who were small for their gestational age (PR=1.43) when compared to women treated with surgery only.

Dr Nichols said the role of treatment is an area of possible future research.

“We’d like to get better information about the types of chemotherapy women receive,” she said. “Chemotherapy is a very broad category, and the agents have very different effects on the body. In the future, we’d like to get more detailed information on the types of drugs that were involved in treatment.”

Photo by Nina Matthews

Women diagnosed with cancer during their childbearing years have an increased risk of preterm births, according to research published in JAMA Oncology.

The study showed that cancer survivors were more likely than women who never had cancer to give birth prematurely, have underweight babies, and undergo cesarean section deliveries.

The researchers said women diagnosed with cancer during pregnancy may be delivering early in order to start their cancer treatment, but that does not fully explain these findings.

The team also detected an increased risk of preterm delivery in women who had already received cancer treatment.

“We found that women were more likely to deliver preterm if they’ve been treated for cancer overall, with greater risks for women who had chemotherapy,” said study author Hazel B. Nichols, PhD, of University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill.

“While we believe these findings are something women should be aware of, we still have a lot of work to do to understand why this risk is becoming apparent and whether or not the children who are born preterm to these women go on to develop any health concerns.”

Dr Nichols and her colleagues analyzed data on 2598 births to female adolescent and young adult cancer survivors (ages 15 to 39) and 12,990 births to women without a cancer diagnosis.

Among cancer survivors, there was a significantly increased prevalence of preterm birth (prevalence ratio [PR]=1.52), low birth weight (PR=1.59), and cesarean delivery (PR=1.08), compared to women without a cancer diagnosis.

Timing of diagnosis and cancer type

When the researchers broke the data down by cancer diagnosis, they found a higher risk of preterm birth and low birth weight for women with lymphoma as well as breast and gynecologic cancers.

The PR for preterm birth was 1.59 for Hodgkin lymphoma, 1.98 for breast cancer, 2.11 for non-Hodgkin lymphoma, and 2.58 for gynecologic cancer. The PR for low birth weight was 1.59 for breast cancer, 2.41 for non-Hodgkin lymphoma, and 2.74 for gynecologic cancer.

The researchers found an increased risk of adverse birth outcomes among women who were diagnosed with cancer while pregnant and before pregnancy.

Among women diagnosed while pregnant, the PR was 2.97 for preterm birth, 2.82 for low birth weight, 1.21 for cesarean delivery, and 1.90 for low Apgar score. Among women diagnosed before pregnancy, the PR was 1.23 for preterm birth and 1.36 for low birth weight.

Role of treatment

Compared to women without a cancer diagnosis, cancer survivors who received chemotherapy but no radiation were more likely to have preterm births (PR=2.11), infants with low birth weight (PR=2.36), and cesarean deliveries (PR=1.16).

There was no significant increase in adverse birth outcomes among cancer survivors who received radiation but not chemotherapy.

Among the cancer survivors, women who received chemotherapy without radiation were more likely to have preterm births (PR=2.12), infants with low birth weight (PR=2.13), and infants who were small for their gestational age (PR=1.43) when compared to women treated with surgery only.

Dr Nichols said the role of treatment is an area of possible future research.

“We’d like to get better information about the types of chemotherapy women receive,” she said. “Chemotherapy is a very broad category, and the agents have very different effects on the body. In the future, we’d like to get more detailed information on the types of drugs that were involved in treatment.”

Photo by Rhoda Baer

The US cancer care delivery system is undergoing changes to better meet the needs of cancer patients, but persistent hurdles threaten to slow progress, according to the American Society of Clinical Oncology (ASCO).

ASCO’s “The State of Cancer Care in America, 2017” report describes areas of progress, including new approaches for cancer diagnosis and treatment, improved data sharing to drive innovation, and an increased focus on value-based healthcare.

However, the report also suggests that access and affordability challenges, along with increased practice burdens, continue to pose barriers to high-value, high-quality cancer care.

The report was published in the Journal of Oncology Practice.

Challenges

The report notes that the US population is growing rapidly, changing demographically, and living longer. And all of these factors contribute to a record number of cancer cases/survivors.

It has been estimated that the number of cancer survivors in the US will grow from 15.5 million to 20.3 million by 2026.

Unfortunately, the report says, cancer care is unaffordable for many patients, even those with health insurance.

And significant health disparities persist that are independent of insurance status. Socioeconomic status, geography, and race/ethnicity all impact patient health outcomes.

The report also suggests that oncology practices are facing increased administrative burdens that divert time and resources from their patients.

Progress

Despite the aforementioned challenges, the report paints an optimistic vision about the future of cancer care and highlights activity in the past year aimed at improving care.

For instance, the Food and Drug Administration approved 5 new anticancer therapies, expanded the use of 13, and approved several diagnostic tests in 2016.

In addition, overall cancer incidence and mortality rates were lower in 2016 than in previous decades.

“Since 1991, we’ve been able to save 2.1 million lives because of significant advances in prevention, diagnosis, and treatment—something unimaginable even a decade ago,” said ASCO President Daniel F. Hayes, MD.

“But there’s still more work to be done to ensure that every patient with cancer, no matter who they are or where they live, has access to high-quality, high-value cancer care.”

The report includes a list of recommendations that, ASCO believes, could help bring the US closer to achieving that goal.

Photo by Rhoda Baer

The US cancer care delivery system is undergoing changes to better meet the needs of cancer patients, but persistent hurdles threaten to slow progress, according to the American Society of Clinical Oncology (ASCO).

ASCO’s “The State of Cancer Care in America, 2017” report describes areas of progress, including new approaches for cancer diagnosis and treatment, improved data sharing to drive innovation, and an increased focus on value-based healthcare.

However, the report also suggests that access and affordability challenges, along with increased practice burdens, continue to pose barriers to high-value, high-quality cancer care.

The report was published in the Journal of Oncology Practice.

Challenges

The report notes that the US population is growing rapidly, changing demographically, and living longer. And all of these factors contribute to a record number of cancer cases/survivors.

It has been estimated that the number of cancer survivors in the US will grow from 15.5 million to 20.3 million by 2026.

Unfortunately, the report says, cancer care is unaffordable for many patients, even those with health insurance.

And significant health disparities persist that are independent of insurance status. Socioeconomic status, geography, and race/ethnicity all impact patient health outcomes.

The report also suggests that oncology practices are facing increased administrative burdens that divert time and resources from their patients.

Progress

Despite the aforementioned challenges, the report paints an optimistic vision about the future of cancer care and highlights activity in the past year aimed at improving care.

For instance, the Food and Drug Administration approved 5 new anticancer therapies, expanded the use of 13, and approved several diagnostic tests in 2016.

In addition, overall cancer incidence and mortality rates were lower in 2016 than in previous decades.

“Since 1991, we’ve been able to save 2.1 million lives because of significant advances in prevention, diagnosis, and treatment—something unimaginable even a decade ago,” said ASCO President Daniel F. Hayes, MD.

“But there’s still more work to be done to ensure that every patient with cancer, no matter who they are or where they live, has access to high-quality, high-value cancer care.”

The report includes a list of recommendations that, ASCO believes, could help bring the US closer to achieving that goal.

Photo by Rhoda Baer

The US cancer care delivery system is undergoing changes to better meet the needs of cancer patients, but persistent hurdles threaten to slow progress, according to the American Society of Clinical Oncology (ASCO).

ASCO’s “The State of Cancer Care in America, 2017” report describes areas of progress, including new approaches for cancer diagnosis and treatment, improved data sharing to drive innovation, and an increased focus on value-based healthcare.

However, the report also suggests that access and affordability challenges, along with increased practice burdens, continue to pose barriers to high-value, high-quality cancer care.

The report was published in the Journal of Oncology Practice.

Challenges

The report notes that the US population is growing rapidly, changing demographically, and living longer. And all of these factors contribute to a record number of cancer cases/survivors.

It has been estimated that the number of cancer survivors in the US will grow from 15.5 million to 20.3 million by 2026.

Unfortunately, the report says, cancer care is unaffordable for many patients, even those with health insurance.

And significant health disparities persist that are independent of insurance status. Socioeconomic status, geography, and race/ethnicity all impact patient health outcomes.

The report also suggests that oncology practices are facing increased administrative burdens that divert time and resources from their patients.

Progress

Despite the aforementioned challenges, the report paints an optimistic vision about the future of cancer care and highlights activity in the past year aimed at improving care.

For instance, the Food and Drug Administration approved 5 new anticancer therapies, expanded the use of 13, and approved several diagnostic tests in 2016.

In addition, overall cancer incidence and mortality rates were lower in 2016 than in previous decades.

“Since 1991, we’ve been able to save 2.1 million lives because of significant advances in prevention, diagnosis, and treatment—something unimaginable even a decade ago,” said ASCO President Daniel F. Hayes, MD.

“But there’s still more work to be done to ensure that every patient with cancer, no matter who they are or where they live, has access to high-quality, high-value cancer care.”

The report includes a list of recommendations that, ASCO believes, could help bring the US closer to achieving that goal.

Photo courtesy of NHS

The European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products has recommended that NiCord® receive orphan designation as a treatment for patients who require a hematopoietic stem cell transplant.

NiCord is a stand-alone graft derived from a single umbilical cord blood unit that has been expanded in culture and enriched with stem and progenitor cells.

NiCord already has orphan designation in the European Union as a treatment for patients with acute myeloid leukemia.

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.

NiCord also has orphan designation and breakthrough designation from the US Food and Drug Administration for the treatment of hematologic malignancies.

NiCord research

Data from the pilot study of NiCord suggested the therapy can provide a clinically meaningful improvement in time to neutrophil engraftment over traditional cord blood transplant.

And research presented at EBMT 2016 showed that patients who received NiCord had fewer infections, shorter hospital stays, quicker platelet engraftment, and improved non-relapse mortality when compared to patients who received a traditional cord blood transplant.

NiCord is currently being studied in a phase 3 registration study as a graft for patients with hematologic malignancies who do not have a rapidly available, fully matched donor.

Gamida Cell, the company developing NiCord, announced last month that the first patient in the study had been transplanted.

Photo courtesy of NHS

The European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products has recommended that NiCord® receive orphan designation as a treatment for patients who require a hematopoietic stem cell transplant.

NiCord is a stand-alone graft derived from a single umbilical cord blood unit that has been expanded in culture and enriched with stem and progenitor cells.

NiCord already has orphan designation in the European Union as a treatment for patients with acute myeloid leukemia.

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.

NiCord also has orphan designation and breakthrough designation from the US Food and Drug Administration for the treatment of hematologic malignancies.

NiCord research

Data from the pilot study of NiCord suggested the therapy can provide a clinically meaningful improvement in time to neutrophil engraftment over traditional cord blood transplant.

And research presented at EBMT 2016 showed that patients who received NiCord had fewer infections, shorter hospital stays, quicker platelet engraftment, and improved non-relapse mortality when compared to patients who received a traditional cord blood transplant.

NiCord is currently being studied in a phase 3 registration study as a graft for patients with hematologic malignancies who do not have a rapidly available, fully matched donor.

Gamida Cell, the company developing NiCord, announced last month that the first patient in the study had been transplanted.

Photo courtesy of NHS

The European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products has recommended that NiCord® receive orphan designation as a treatment for patients who require a hematopoietic stem cell transplant.

NiCord is a stand-alone graft derived from a single umbilical cord blood unit that has been expanded in culture and enriched with stem and progenitor cells.

NiCord already has orphan designation in the European Union as a treatment for patients with acute myeloid leukemia.

Orphan designation provides regulatory and financial incentives for companies to develop and market therapies that treat life-threatening or chronically debilitating conditions affecting no more than 5 in 10,000 people in the European Union, and where no satisfactory treatment is available.

Orphan designation provides a 10-year period of marketing exclusivity if the drug receives regulatory approval. The designation also provides incentives for companies seeking protocol assistance from the EMA during the product development phase and direct access to the centralized authorization procedure.

The EMA adopts an opinion on the granting of orphan drug designation, and that opinion is submitted to the European Commission for a final decision. The European Commission typically makes a decision within 30 days.

NiCord also has orphan designation and breakthrough designation from the US Food and Drug Administration for the treatment of hematologic malignancies.

NiCord research

Data from the pilot study of NiCord suggested the therapy can provide a clinically meaningful improvement in time to neutrophil engraftment over traditional cord blood transplant.

And research presented at EBMT 2016 showed that patients who received NiCord had fewer infections, shorter hospital stays, quicker platelet engraftment, and improved non-relapse mortality when compared to patients who received a traditional cord blood transplant.

NiCord is currently being studied in a phase 3 registration study as a graft for patients with hematologic malignancies who do not have a rapidly available, fully matched donor.

Gamida Cell, the company developing NiCord, announced last month that the first patient in the study had been transplanted.

 

BACKGROUND: Readmissions after hospitalization for pneumonia are common, but the few risk-prediction models have poor to modest predictive ability. Data routinely collected in the EHR may improve prediction.

OBJECTIVE: To develop pneumonia-specific readmission risk-prediction models using EHR data from the first day and from the entire hospital stay (“full stay”).

DESIGN: Observational cohort study using backward-stepwise selection and cross validation.

SUBJECTS: Consecutive pneumonia hospitalizations from six diverse hospitals in north Texas from 2009 to 2010.

MEASURES: All-cause, nonelective, 30-day readmissions, ascertained from 75 regional hospitals.

 

RESULTS: Of 1,463 patients, 13.6% were readmitted. The first-day, pneumonia-specific model included sociodemographic factors, prior hospitalizations, thrombocytosis, and a modified pneumonia severity index. The full-stay model included disposition status, vital sign instabilities on discharge, and an updated pneumonia severity index calculated using values from the day of discharge as additional predictors. The full-stay, pneumonia-specific model outperformed the first-day model (C-statistic, 0.731 vs. 0.695; P = .02; net reclassification index = 0.08). Compared with a validated multicondition readmission model, the Centers for Medicare & Medicaid Services pneumonia model, and two commonly used pneumonia severity of illness scores, the full-stay pneumonia-specific model had better discrimination (C-statistic, 0.604-0.681; P less than 0.01 for all comparisons), predicted a broader range of risk, and better reclassified individuals by their true risk (net reclassification index range, 0.09-0.18).

CONCLUSIONS: EHR data collected from the entire hospitalization can accurately predict readmission risk among patients hospitalized for pneumonia. This approach outperforms a first-day, pneumonia-specific model, the Centers for Medicare & Medicaid Services pneumonia model, and two commonly used pneumonia severity of illness scores.
 

Also In JHM This Month

Evaluating automated rules for rapid response system alarm triggers in medical and surgical patients
AUTHORS: Santiago Romero-Brufau, MD; Bruce W. Morlan, MS; Matthew Johnson, MPH; Joel Hickman; Lisa L. Kirkland, MD; James M. Naessens, ScD; Jeanne Huddleston, MD, FACP, FHM

Prognosticating with the Hospital-Patient One-year Mortality Risk score using information abstracted from the medical record
AUTHORS: Genevieve Casey, MD, and Carl van Walraven, MD, FRCPC, MSc

Automating venous thromboembolism risk calculation using electronic health record data upon hospital admission: The Automated Padua Prediction Score
AUTHORS: Pierre Elias, MD; Raman Khanna, MD; Adams Dudley, MD, MBA; Jason Davies, MD, PhD; Ronald Jacolbia, MSN; Kara McArthur, BA; Andrew D. Auerbach, MD, MPH, SFHM

The value of ultrasound in cellulitis to rule out deep venous thrombosis
AUTHORS: Hyung J. Cho, MD, and Andrew S. Dunn, MD, SFHM

Hospital medicine and perioperative care: A framework for high quality, high value collaborative care
AUTHORS: Rachel E. Thompson, MD, MPH, SFHM; Kurt Pfeifer, MD, FHM; Paul Grant, MD, SFHM; Cornelia Taylor, MD; Barbara Slawski, MD, FACP, MS, SFHM; Christopher Whinney, MD, FACP, FHM; Laurence Wellikson, MD, MHM; Amir K. Jaffer, MD, MBA, SFHM
 

 

BACKGROUND: Readmissions after hospitalization for pneumonia are common, but the few risk-prediction models have poor to modest predictive ability. Data routinely collected in the EHR may improve prediction.

OBJECTIVE: To develop pneumonia-specific readmission risk-prediction models using EHR data from the first day and from the entire hospital stay (“full stay”).

DESIGN: Observational cohort study using backward-stepwise selection and cross validation.

SUBJECTS: Consecutive pneumonia hospitalizations from six diverse hospitals in north Texas from 2009 to 2010.

MEASURES: All-cause, nonelective, 30-day readmissions, ascertained from 75 regional hospitals.

 

RESULTS: Of 1,463 patients, 13.6% were readmitted. The first-day, pneumonia-specific model included sociodemographic factors, prior hospitalizations, thrombocytosis, and a modified pneumonia severity index. The full-stay model included disposition status, vital sign instabilities on discharge, and an updated pneumonia severity index calculated using values from the day of discharge as additional predictors. The full-stay, pneumonia-specific model outperformed the first-day model (C-statistic, 0.731 vs. 0.695; P = .02; net reclassification index = 0.08). Compared with a validated multicondition readmission model, the Centers for Medicare & Medicaid Services pneumonia model, and two commonly used pneumonia severity of illness scores, the full-stay pneumonia-specific model had better discrimination (C-statistic, 0.604-0.681; P less than 0.01 for all comparisons), predicted a broader range of risk, and better reclassified individuals by their true risk (net reclassification index range, 0.09-0.18).

CONCLUSIONS: EHR data collected from the entire hospitalization can accurately predict readmission risk among patients hospitalized for pneumonia. This approach outperforms a first-day, pneumonia-specific model, the Centers for Medicare & Medicaid Services pneumonia model, and two commonly used pneumonia severity of illness scores.
 

Also In JHM This Month

Evaluating automated rules for rapid response system alarm triggers in medical and surgical patients
AUTHORS: Santiago Romero-Brufau, MD; Bruce W. Morlan, MS; Matthew Johnson, MPH; Joel Hickman; Lisa L. Kirkland, MD; James M. Naessens, ScD; Jeanne Huddleston, MD, FACP, FHM

Prognosticating with the Hospital-Patient One-year Mortality Risk score using information abstracted from the medical record
AUTHORS: Genevieve Casey, MD, and Carl van Walraven, MD, FRCPC, MSc

Automating venous thromboembolism risk calculation using electronic health record data upon hospital admission: The Automated Padua Prediction Score
AUTHORS: Pierre Elias, MD; Raman Khanna, MD; Adams Dudley, MD, MBA; Jason Davies, MD, PhD; Ronald Jacolbia, MSN; Kara McArthur, BA; Andrew D. Auerbach, MD, MPH, SFHM

The value of ultrasound in cellulitis to rule out deep venous thrombosis
AUTHORS: Hyung J. Cho, MD, and Andrew S. Dunn, MD, SFHM

Hospital medicine and perioperative care: A framework for high quality, high value collaborative care
AUTHORS: Rachel E. Thompson, MD, MPH, SFHM; Kurt Pfeifer, MD, FHM; Paul Grant, MD, SFHM; Cornelia Taylor, MD; Barbara Slawski, MD, FACP, MS, SFHM; Christopher Whinney, MD, FACP, FHM; Laurence Wellikson, MD, MHM; Amir K. Jaffer, MD, MBA, SFHM
 

 

BACKGROUND: Readmissions after hospitalization for pneumonia are common, but the few risk-prediction models have poor to modest predictive ability. Data routinely collected in the EHR may improve prediction.

OBJECTIVE: To develop pneumonia-specific readmission risk-prediction models using EHR data from the first day and from the entire hospital stay (“full stay”).

DESIGN: Observational cohort study using backward-stepwise selection and cross validation.

SUBJECTS: Consecutive pneumonia hospitalizations from six diverse hospitals in north Texas from 2009 to 2010.

MEASURES: All-cause, nonelective, 30-day readmissions, ascertained from 75 regional hospitals.

 

RESULTS: Of 1,463 patients, 13.6% were readmitted. The first-day, pneumonia-specific model included sociodemographic factors, prior hospitalizations, thrombocytosis, and a modified pneumonia severity index. The full-stay model included disposition status, vital sign instabilities on discharge, and an updated pneumonia severity index calculated using values from the day of discharge as additional predictors. The full-stay, pneumonia-specific model outperformed the first-day model (C-statistic, 0.731 vs. 0.695; P = .02; net reclassification index = 0.08). Compared with a validated multicondition readmission model, the Centers for Medicare & Medicaid Services pneumonia model, and two commonly used pneumonia severity of illness scores, the full-stay pneumonia-specific model had better discrimination (C-statistic, 0.604-0.681; P less than 0.01 for all comparisons), predicted a broader range of risk, and better reclassified individuals by their true risk (net reclassification index range, 0.09-0.18).

CONCLUSIONS: EHR data collected from the entire hospitalization can accurately predict readmission risk among patients hospitalized for pneumonia. This approach outperforms a first-day, pneumonia-specific model, the Centers for Medicare & Medicaid Services pneumonia model, and two commonly used pneumonia severity of illness scores.
 

Also In JHM This Month

Evaluating automated rules for rapid response system alarm triggers in medical and surgical patients
AUTHORS: Santiago Romero-Brufau, MD; Bruce W. Morlan, MS; Matthew Johnson, MPH; Joel Hickman; Lisa L. Kirkland, MD; James M. Naessens, ScD; Jeanne Huddleston, MD, FACP, FHM

Prognosticating with the Hospital-Patient One-year Mortality Risk score using information abstracted from the medical record
AUTHORS: Genevieve Casey, MD, and Carl van Walraven, MD, FRCPC, MSc

Automating venous thromboembolism risk calculation using electronic health record data upon hospital admission: The Automated Padua Prediction Score
AUTHORS: Pierre Elias, MD; Raman Khanna, MD; Adams Dudley, MD, MBA; Jason Davies, MD, PhD; Ronald Jacolbia, MSN; Kara McArthur, BA; Andrew D. Auerbach, MD, MPH, SFHM

The value of ultrasound in cellulitis to rule out deep venous thrombosis
AUTHORS: Hyung J. Cho, MD, and Andrew S. Dunn, MD, SFHM

Hospital medicine and perioperative care: A framework for high quality, high value collaborative care
AUTHORS: Rachel E. Thompson, MD, MPH, SFHM; Kurt Pfeifer, MD, FHM; Paul Grant, MD, SFHM; Cornelia Taylor, MD; Barbara Slawski, MD, FACP, MS, SFHM; Christopher Whinney, MD, FACP, FHM; Laurence Wellikson, MD, MHM; Amir K. Jaffer, MD, MBA, SFHM
 

 

Washington – Uninterrupted dabigatran for periprocedural anticoagulation in patients undergoing catheter ablation for atrial fibrillation proved far superior to uninterrupted warfarin – the current standard – in the randomized multicenter RE-CIRCUIT trial, Hugh Calkins, MD, reported at the annual meeting of the American College of Cardiology.

The primary study endpoint – the incidence of major bleeding events from the time of the first femoral puncture at the procedure’s start through the subsequent 8 weeks – occurred in 1.6% of the dabigatran (Pradaxa) group and 6.9% of the warfarin group, for an absolute 5.9% reduction in risk and a 77% relative risk reduction favoring the novel anticoagulant.

“This trial will definitely affect my own practice, and I think it will quickly affect the practices of electrophysiologists around the world,” declared Dr. Calkins, professor of cardiology and medicine and director of the clinical electrophysiology laboratory and the arrhythmia service at Johns Hopkins University, Baltimore.

RE-CIRCUIT (Randomized Evaluation of Dabigatran Etexilate Compared to Warfarin in Pulmonary Vein Ablation: Assessment of an Uninterrupted Periprocedural Anticoagulation Strategy) was a multicenter, prospective, international trial conducted in 635 atrial fibrillation (AF) patients who underwent catheter ablation at 104 sites. The trial was of necessity open label because of the need for frequent adjustments of warfarin dosing; however, outcome assessment was carried out by a blinded panel of six cardiologists and three neurologists.

Standard practice among AF ablationists is to continue oral anticoagulation periprocedurally because prior studies have convincingly shown that periprocedural interruption of warfarin in an effort to reduce bleeding results in a sharply increased risk of periprocedural stroke. So participants in RE-CIRCUIT were randomized to 4-8 weeks of uninterrupted anticoagulation with either dabigatran at 150 mg b.i.d. or warfarin with a target international normalized ratio (INR) of 2.0-3.0 prior to the ablation procedure, during it, and for 8 weeks afterward, at which time an individualized decision was made as to whether to stop or continue the drug.

Major bleeding events were defined by the International Society on Thrombosis and Hemostatis criteria. Most of these bleeds occurred within the first day or two after the procedure. Pericardial tamponades and groin hematomas were significantly less common with dabigatran.

The incidence of minor bleeding events was similar, at around 18% in the two treatment arms. No strokes or systemic embolisms occurred in the study. One patient on warfarin experienced a transient ischemic attack.

Dr. Calkins elaborated on why RE-CIRCUIT will change clinical practice: “A stroke is a terrible thing during an AF procedure and cardiac tamponade is the most common cause of death from the procedure. And now we have high-quality data showing that if you perform this procedure on uninterrupted dabigatran, the risk of stroke and other systemic embolic events is extremely low, and the rate of major bleeding was 77% less.

“Plus, the logistics of warfarin are a pain,” he continued. “If the patient presents on the day of ablation with an INR that’s too high, the procedure is canceled, and if they present with an INR that’s too low and the procedure is carried out, it’s done so with an increased stroke risk.”

Dr. Calkins said he suspects the sharp reduction in major bleeding events during and after AF catheter ablation is a class effect shared by the other NOACs. Studies with those agents are ongoing. But for now, the unique availability of an immediate reversal agent in the form of idarucizumab (Praxbind) for dabigatran in the event of uncontrolled major bleeding is a source of reassurance for operators and patients alike. The antidote was never required in RE-CIRCUIT, though, the cardiologist noted.

Discussant William G. Stevenson, MD, called the trial “informative and helpful.”

“Something we’ve all been struggling with was that some concern was earlier raised that dabigatran might be associated with more thromboembolic events in this scenario. This study clearly refutes that concern,” observed Dr. Stevenson, director of the clinical cardiac electrophysiology program at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston.

Dr. Stevenson wondered whether the outcome differences between the two study groups could be explained by differences in operator techniques and tools. That’s highly unlikely, Dr. Calkins replied. Randomization was done patient by patient, not center by center.

Then why the big difference in major bleeding complications? Dr. Stevenson asked.

“It may be that, if you poke a hole when a patient is on a more forgiving anticoagulant like dabigatran, the bleeding doesn’t persist and turn into a tamponade, whereas if you poke a hole on warfarin it turns into a bigger problem,” Dr. Calkins responded. “When you think about it, warfarin really impacts the whole coagulation cascade through factors VII, IX, and X, so multiple coagulation factors are rendered impotent, whereas dabigatran is a direct thrombin inhibitor, so you’re selectively knocking out just one component of the coagulation cascade. It provides more leeway in preventing a small hole from turning into a big effusion,” he said.

“This is a fantastic study, which I think will certainly impact clinical practice, because now we have a periprocedural strategy which is associated with minimal bleeding complications and you also have a reversal agent at hand,” said Jagmeet P. Singh, MD, associate chief of cardiology at Massachusetts General Hospital, Boston, and professor of medicine at Harvard Medical School.

The RE-CIRCUIT trial was funded by Boehringer Ingelheim. Dr. Calkins reported receiving lecture fees from that company and from Medtronic, and serving as a consultant to Medtronic, Abbott Medical, and AtriCure.

Simultaneously with Dr. Calkins’ presentation at ACC 17, the RE-CIRCUIT study was published online (N Engl J Med. 2017 Mar 19. doi: 10.1056/NEJMoa1701005).
 

 

[email protected]

 

Washington – Uninterrupted dabigatran for periprocedural anticoagulation in patients undergoing catheter ablation for atrial fibrillation proved far superior to uninterrupted warfarin – the current standard – in the randomized multicenter RE-CIRCUIT trial, Hugh Calkins, MD, reported at the annual meeting of the American College of Cardiology.

The primary study endpoint – the incidence of major bleeding events from the time of the first femoral puncture at the procedure’s start through the subsequent 8 weeks – occurred in 1.6% of the dabigatran (Pradaxa) group and 6.9% of the warfarin group, for an absolute 5.9% reduction in risk and a 77% relative risk reduction favoring the novel anticoagulant.

“This trial will definitely affect my own practice, and I think it will quickly affect the practices of electrophysiologists around the world,” declared Dr. Calkins, professor of cardiology and medicine and director of the clinical electrophysiology laboratory and the arrhythmia service at Johns Hopkins University, Baltimore.

RE-CIRCUIT (Randomized Evaluation of Dabigatran Etexilate Compared to Warfarin in Pulmonary Vein Ablation: Assessment of an Uninterrupted Periprocedural Anticoagulation Strategy) was a multicenter, prospective, international trial conducted in 635 atrial fibrillation (AF) patients who underwent catheter ablation at 104 sites. The trial was of necessity open label because of the need for frequent adjustments of warfarin dosing; however, outcome assessment was carried out by a blinded panel of six cardiologists and three neurologists.

Standard practice among AF ablationists is to continue oral anticoagulation periprocedurally because prior studies have convincingly shown that periprocedural interruption of warfarin in an effort to reduce bleeding results in a sharply increased risk of periprocedural stroke. So participants in RE-CIRCUIT were randomized to 4-8 weeks of uninterrupted anticoagulation with either dabigatran at 150 mg b.i.d. or warfarin with a target international normalized ratio (INR) of 2.0-3.0 prior to the ablation procedure, during it, and for 8 weeks afterward, at which time an individualized decision was made as to whether to stop or continue the drug.

Major bleeding events were defined by the International Society on Thrombosis and Hemostatis criteria. Most of these bleeds occurred within the first day or two after the procedure. Pericardial tamponades and groin hematomas were significantly less common with dabigatran.

The incidence of minor bleeding events was similar, at around 18% in the two treatment arms. No strokes or systemic embolisms occurred in the study. One patient on warfarin experienced a transient ischemic attack.

Dr. Calkins elaborated on why RE-CIRCUIT will change clinical practice: “A stroke is a terrible thing during an AF procedure and cardiac tamponade is the most common cause of death from the procedure. And now we have high-quality data showing that if you perform this procedure on uninterrupted dabigatran, the risk of stroke and other systemic embolic events is extremely low, and the rate of major bleeding was 77% less.

“Plus, the logistics of warfarin are a pain,” he continued. “If the patient presents on the day of ablation with an INR that’s too high, the procedure is canceled, and if they present with an INR that’s too low and the procedure is carried out, it’s done so with an increased stroke risk.”

Dr. Calkins said he suspects the sharp reduction in major bleeding events during and after AF catheter ablation is a class effect shared by the other NOACs. Studies with those agents are ongoing. But for now, the unique availability of an immediate reversal agent in the form of idarucizumab (Praxbind) for dabigatran in the event of uncontrolled major bleeding is a source of reassurance for operators and patients alike. The antidote was never required in RE-CIRCUIT, though, the cardiologist noted.

Discussant William G. Stevenson, MD, called the trial “informative and helpful.”

“Something we’ve all been struggling with was that some concern was earlier raised that dabigatran might be associated with more thromboembolic events in this scenario. This study clearly refutes that concern,” observed Dr. Stevenson, director of the clinical cardiac electrophysiology program at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston.

Dr. Stevenson wondered whether the outcome differences between the two study groups could be explained by differences in operator techniques and tools. That’s highly unlikely, Dr. Calkins replied. Randomization was done patient by patient, not center by center.

Then why the big difference in major bleeding complications? Dr. Stevenson asked.

“It may be that, if you poke a hole when a patient is on a more forgiving anticoagulant like dabigatran, the bleeding doesn’t persist and turn into a tamponade, whereas if you poke a hole on warfarin it turns into a bigger problem,” Dr. Calkins responded. “When you think about it, warfarin really impacts the whole coagulation cascade through factors VII, IX, and X, so multiple coagulation factors are rendered impotent, whereas dabigatran is a direct thrombin inhibitor, so you’re selectively knocking out just one component of the coagulation cascade. It provides more leeway in preventing a small hole from turning into a big effusion,” he said.

“This is a fantastic study, which I think will certainly impact clinical practice, because now we have a periprocedural strategy which is associated with minimal bleeding complications and you also have a reversal agent at hand,” said Jagmeet P. Singh, MD, associate chief of cardiology at Massachusetts General Hospital, Boston, and professor of medicine at Harvard Medical School.

The RE-CIRCUIT trial was funded by Boehringer Ingelheim. Dr. Calkins reported receiving lecture fees from that company and from Medtronic, and serving as a consultant to Medtronic, Abbott Medical, and AtriCure.

Simultaneously with Dr. Calkins’ presentation at ACC 17, the RE-CIRCUIT study was published online (N Engl J Med. 2017 Mar 19. doi: 10.1056/NEJMoa1701005).
 

 

[email protected]

 

Washington – Uninterrupted dabigatran for periprocedural anticoagulation in patients undergoing catheter ablation for atrial fibrillation proved far superior to uninterrupted warfarin – the current standard – in the randomized multicenter RE-CIRCUIT trial, Hugh Calkins, MD, reported at the annual meeting of the American College of Cardiology.

The primary study endpoint – the incidence of major bleeding events from the time of the first femoral puncture at the procedure’s start through the subsequent 8 weeks – occurred in 1.6% of the dabigatran (Pradaxa) group and 6.9% of the warfarin group, for an absolute 5.9% reduction in risk and a 77% relative risk reduction favoring the novel anticoagulant.

“This trial will definitely affect my own practice, and I think it will quickly affect the practices of electrophysiologists around the world,” declared Dr. Calkins, professor of cardiology and medicine and director of the clinical electrophysiology laboratory and the arrhythmia service at Johns Hopkins University, Baltimore.

RE-CIRCUIT (Randomized Evaluation of Dabigatran Etexilate Compared to Warfarin in Pulmonary Vein Ablation: Assessment of an Uninterrupted Periprocedural Anticoagulation Strategy) was a multicenter, prospective, international trial conducted in 635 atrial fibrillation (AF) patients who underwent catheter ablation at 104 sites. The trial was of necessity open label because of the need for frequent adjustments of warfarin dosing; however, outcome assessment was carried out by a blinded panel of six cardiologists and three neurologists.

Standard practice among AF ablationists is to continue oral anticoagulation periprocedurally because prior studies have convincingly shown that periprocedural interruption of warfarin in an effort to reduce bleeding results in a sharply increased risk of periprocedural stroke. So participants in RE-CIRCUIT were randomized to 4-8 weeks of uninterrupted anticoagulation with either dabigatran at 150 mg b.i.d. or warfarin with a target international normalized ratio (INR) of 2.0-3.0 prior to the ablation procedure, during it, and for 8 weeks afterward, at which time an individualized decision was made as to whether to stop or continue the drug.

Major bleeding events were defined by the International Society on Thrombosis and Hemostatis criteria. Most of these bleeds occurred within the first day or two after the procedure. Pericardial tamponades and groin hematomas were significantly less common with dabigatran.

The incidence of minor bleeding events was similar, at around 18% in the two treatment arms. No strokes or systemic embolisms occurred in the study. One patient on warfarin experienced a transient ischemic attack.

Dr. Calkins elaborated on why RE-CIRCUIT will change clinical practice: “A stroke is a terrible thing during an AF procedure and cardiac tamponade is the most common cause of death from the procedure. And now we have high-quality data showing that if you perform this procedure on uninterrupted dabigatran, the risk of stroke and other systemic embolic events is extremely low, and the rate of major bleeding was 77% less.

“Plus, the logistics of warfarin are a pain,” he continued. “If the patient presents on the day of ablation with an INR that’s too high, the procedure is canceled, and if they present with an INR that’s too low and the procedure is carried out, it’s done so with an increased stroke risk.”

Dr. Calkins said he suspects the sharp reduction in major bleeding events during and after AF catheter ablation is a class effect shared by the other NOACs. Studies with those agents are ongoing. But for now, the unique availability of an immediate reversal agent in the form of idarucizumab (Praxbind) for dabigatran in the event of uncontrolled major bleeding is a source of reassurance for operators and patients alike. The antidote was never required in RE-CIRCUIT, though, the cardiologist noted.

Discussant William G. Stevenson, MD, called the trial “informative and helpful.”

“Something we’ve all been struggling with was that some concern was earlier raised that dabigatran might be associated with more thromboembolic events in this scenario. This study clearly refutes that concern,” observed Dr. Stevenson, director of the clinical cardiac electrophysiology program at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston.

Dr. Stevenson wondered whether the outcome differences between the two study groups could be explained by differences in operator techniques and tools. That’s highly unlikely, Dr. Calkins replied. Randomization was done patient by patient, not center by center.

Then why the big difference in major bleeding complications? Dr. Stevenson asked.

“It may be that, if you poke a hole when a patient is on a more forgiving anticoagulant like dabigatran, the bleeding doesn’t persist and turn into a tamponade, whereas if you poke a hole on warfarin it turns into a bigger problem,” Dr. Calkins responded. “When you think about it, warfarin really impacts the whole coagulation cascade through factors VII, IX, and X, so multiple coagulation factors are rendered impotent, whereas dabigatran is a direct thrombin inhibitor, so you’re selectively knocking out just one component of the coagulation cascade. It provides more leeway in preventing a small hole from turning into a big effusion,” he said.

“This is a fantastic study, which I think will certainly impact clinical practice, because now we have a periprocedural strategy which is associated with minimal bleeding complications and you also have a reversal agent at hand,” said Jagmeet P. Singh, MD, associate chief of cardiology at Massachusetts General Hospital, Boston, and professor of medicine at Harvard Medical School.

The RE-CIRCUIT trial was funded by Boehringer Ingelheim. Dr. Calkins reported receiving lecture fees from that company and from Medtronic, and serving as a consultant to Medtronic, Abbott Medical, and AtriCure.

Simultaneously with Dr. Calkins’ presentation at ACC 17, the RE-CIRCUIT study was published online (N Engl J Med. 2017 Mar 19. doi: 10.1056/NEJMoa1701005).
 

 

[email protected]