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

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

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

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.

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.

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.

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.

[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.

[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.

[email protected]

Up to two-thirds of the mutations that drive human cancers may be due to DNA replication errors in normally dividing stem cells, not by inherited or environmentally induced mutations, according to a mathematical modeling study.

The proportion of replication error-driven mutations varied widely among 17 cancers analyzed, but the overall attributable risk of these errors was remarkably consistent among 69 countries included in the study, said Cristian Tomasetti, PhD, a coauthor of the paper and a biostatistician at Johns Hopkins University, Baltimore.

The findings should be a game-changer in the cancer field, Dr. Tomasetti said during a press briefing sponsored by the American Association for the Advancement of Science. Research dogma has long held that most cancers are related to lifestyle and environmental exposure, with a few primarily due to genetic factors.

“We have now determined that there is a third factor, and that it causes most of the mutations that drive cancer,” Dr. Tomasetti said. “We cannot ignore it and pretend it doesn’t exist. This is a complete paradigm shift in how we think of cancer and what causes it.”

The finding that 66% of cancer-driving mutations are based on unavoidable replication errors doesn’t challenge well-established epidemiology, said Dr. Tomasetti and his coauthor, Bert Vogelstein, MD. Rather, it fits perfectly with several key understandings of cancer: that about 40% of cases are preventable, that rapidly dividing tissues are more prone to develop cancers, and that cancer incidence rises exponentially as humans age.

“If we have as our starting point the assumption that 42% of cancers are preventable, we are completely consistent with that,” in finding that about 60% of cancers are unavoidable, Dr. Tomasetti said. “Those two numbers go perfectly together.”

The study also found that replication-error mutations (R) were most likely to drive cancers in tissues with rapid turnover, such as colorectal tissue. This makes intuitive sense, given that basal mutation rates hover at about three errors per cell replication cycle regardless of tissue type.

“The basal mutation rate in all cells is pretty even,” said Dr. Vogelstein, the Clayton Professor of Oncology and Pathology at John Hopkins University, Baltimore. “The difference is the number of stem cells. The more cells, the more divisions, and the more mistakes.”

R-mutations also contribute to age-related cancer incidence. As a person ages, more cell divisions accumulate, thus increasing the risk of a cancer-driving R-error. But these mutations also occur in children, who have rapid cell division in all their tissues. In fact, the colleagues suspect that R-errors are the main drivers of almost all pediatric cancers.

The new study bolsters the duo’s controversial 2015 work.

Courtesy Dr. Cristian Tomasetti and Dr. Bert Vogelstein

[email protected]

On Twitter @Alz_gal

Up to two-thirds of the mutations that drive human cancers may be due to DNA replication errors in normally dividing stem cells, not by inherited or environmentally induced mutations, according to a mathematical modeling study.

The proportion of replication error-driven mutations varied widely among 17 cancers analyzed, but the overall attributable risk of these errors was remarkably consistent among 69 countries included in the study, said Cristian Tomasetti, PhD, a coauthor of the paper and a biostatistician at Johns Hopkins University, Baltimore.

The findings should be a game-changer in the cancer field, Dr. Tomasetti said during a press briefing sponsored by the American Association for the Advancement of Science. Research dogma has long held that most cancers are related to lifestyle and environmental exposure, with a few primarily due to genetic factors.

“We have now determined that there is a third factor, and that it causes most of the mutations that drive cancer,” Dr. Tomasetti said. “We cannot ignore it and pretend it doesn’t exist. This is a complete paradigm shift in how we think of cancer and what causes it.”

The finding that 66% of cancer-driving mutations are based on unavoidable replication errors doesn’t challenge well-established epidemiology, said Dr. Tomasetti and his coauthor, Bert Vogelstein, MD. Rather, it fits perfectly with several key understandings of cancer: that about 40% of cases are preventable, that rapidly dividing tissues are more prone to develop cancers, and that cancer incidence rises exponentially as humans age.

“If we have as our starting point the assumption that 42% of cancers are preventable, we are completely consistent with that,” in finding that about 60% of cancers are unavoidable, Dr. Tomasetti said. “Those two numbers go perfectly together.”

The study also found that replication-error mutations (R) were most likely to drive cancers in tissues with rapid turnover, such as colorectal tissue. This makes intuitive sense, given that basal mutation rates hover at about three errors per cell replication cycle regardless of tissue type.

“The basal mutation rate in all cells is pretty even,” said Dr. Vogelstein, the Clayton Professor of Oncology and Pathology at John Hopkins University, Baltimore. “The difference is the number of stem cells. The more cells, the more divisions, and the more mistakes.”

R-mutations also contribute to age-related cancer incidence. As a person ages, more cell divisions accumulate, thus increasing the risk of a cancer-driving R-error. But these mutations also occur in children, who have rapid cell division in all their tissues. In fact, the colleagues suspect that R-errors are the main drivers of almost all pediatric cancers.

The new study bolsters the duo’s controversial 2015 work.

Courtesy Dr. Cristian Tomasetti and Dr. Bert Vogelstein

[email protected]

On Twitter @Alz_gal

Up to two-thirds of the mutations that drive human cancers may be due to DNA replication errors in normally dividing stem cells, not by inherited or environmentally induced mutations, according to a mathematical modeling study.

The proportion of replication error-driven mutations varied widely among 17 cancers analyzed, but the overall attributable risk of these errors was remarkably consistent among 69 countries included in the study, said Cristian Tomasetti, PhD, a coauthor of the paper and a biostatistician at Johns Hopkins University, Baltimore.

The findings should be a game-changer in the cancer field, Dr. Tomasetti said during a press briefing sponsored by the American Association for the Advancement of Science. Research dogma has long held that most cancers are related to lifestyle and environmental exposure, with a few primarily due to genetic factors.

“We have now determined that there is a third factor, and that it causes most of the mutations that drive cancer,” Dr. Tomasetti said. “We cannot ignore it and pretend it doesn’t exist. This is a complete paradigm shift in how we think of cancer and what causes it.”

The finding that 66% of cancer-driving mutations are based on unavoidable replication errors doesn’t challenge well-established epidemiology, said Dr. Tomasetti and his coauthor, Bert Vogelstein, MD. Rather, it fits perfectly with several key understandings of cancer: that about 40% of cases are preventable, that rapidly dividing tissues are more prone to develop cancers, and that cancer incidence rises exponentially as humans age.

“If we have as our starting point the assumption that 42% of cancers are preventable, we are completely consistent with that,” in finding that about 60% of cancers are unavoidable, Dr. Tomasetti said. “Those two numbers go perfectly together.”

The study also found that replication-error mutations (R) were most likely to drive cancers in tissues with rapid turnover, such as colorectal tissue. This makes intuitive sense, given that basal mutation rates hover at about three errors per cell replication cycle regardless of tissue type.

“The basal mutation rate in all cells is pretty even,” said Dr. Vogelstein, the Clayton Professor of Oncology and Pathology at John Hopkins University, Baltimore. “The difference is the number of stem cells. The more cells, the more divisions, and the more mistakes.”

R-mutations also contribute to age-related cancer incidence. As a person ages, more cell divisions accumulate, thus increasing the risk of a cancer-driving R-error. But these mutations also occur in children, who have rapid cell division in all their tissues. In fact, the colleagues suspect that R-errors are the main drivers of almost all pediatric cancers.

The new study bolsters the duo’s controversial 2015 work.

Courtesy Dr. Cristian Tomasetti and Dr. Bert Vogelstein

[email protected]

On Twitter @Alz_gal

Syndromic and enhanced surveillance employed during a Zika outbreak in American Samoa last year is credited for bringing a quick end to ongoing transmission and could be used to predict when ongoing transmission in similarly small populations will end.

“Establishing a timeline for discontinuing screening of asymptomatic pregnant women allows ASDoH [the American Samoa Department of Health] to allocate resources appropriately toward early interventions for children and families affected by Zika virus,” W. Thane Hancock, MD, of the CDC’s Office of Public Health Preparedness and Response, and his colleagues wrote in the Morbidity and Mortality Weekly Report (2017 Mar 24;66[11]:299-301).

Laboratory-confirmed Zika cases first cropped up in American Samoa in January 2016, prompting the implementation of protocols to reduce the mosquito population, along with syndromic surveillance based on electronic health records to determine which patients may be at higher risk. Routine testing of all asymptomatic pregnant woman, along with individuals with one or more symptoms of Zika virus, also became standard procedure. Real-time, reverse transcription–polymerase chain reaction (rRT-PCR) testing was used to confirm suspected Zika virus cases.

“Early in the response, collection and testing of specimens from pregnant women was prioritized over the collection from symptomatic nonpregnant patients because of limited testing and shipping capacity,” the researchers wrote.

By May 2016, suspected cases had dropped from six per week during January and February, to just one per week, with the last laboratory-confirmed case occurring on June 19, 2016. In August, the ASDoH proposed ending routine screening of asymptomatic pregnant women by Oct. 15, 2016. Transmission data from American Samoa and the CDC were used to determine the Oct. 15 date as an estimate for when active mosquito-borne transmission would end.

To confirm that local transmission was no longer ongoing, enhanced surveillance was implemented from Aug. 31 to Oct. 15, involving free testing at local clinics. Over the course of 45 days, there were a total of 32 patients suspected of having a Zika virus infection.

Two of these subjects’ specimens were not sufficient in sample size to be tested, but the other 30 underwent rRT-PCR testing within 30 days of symptom onset, and all the results were negative. Additionally, 277 asymptomatic pregnant women were tested and 86 (31%) tested anti-Zika IgM–positive or equivocal. All 86 specimens later tested negative by rRT-PCR.

Given the possibility that Zika virus can persist in semen for 6 months, officials recommended permissive testing of asymptomatic pregnant women who conceive through April 15, 2017 “as a conservative approach.”

“The surveillance processes outlined and the timeline established for American Samoa might have implications for jurisdictions where small populations and similar population immunity following widespread Zika virus exposure can facilitate interruption of transmission,” the researchers wrote.

[email protected]

Syndromic and enhanced surveillance employed during a Zika outbreak in American Samoa last year is credited for bringing a quick end to ongoing transmission and could be used to predict when ongoing transmission in similarly small populations will end.

“Establishing a timeline for discontinuing screening of asymptomatic pregnant women allows ASDoH [the American Samoa Department of Health] to allocate resources appropriately toward early interventions for children and families affected by Zika virus,” W. Thane Hancock, MD, of the CDC’s Office of Public Health Preparedness and Response, and his colleagues wrote in the Morbidity and Mortality Weekly Report (2017 Mar 24;66[11]:299-301).

Laboratory-confirmed Zika cases first cropped up in American Samoa in January 2016, prompting the implementation of protocols to reduce the mosquito population, along with syndromic surveillance based on electronic health records to determine which patients may be at higher risk. Routine testing of all asymptomatic pregnant woman, along with individuals with one or more symptoms of Zika virus, also became standard procedure. Real-time, reverse transcription–polymerase chain reaction (rRT-PCR) testing was used to confirm suspected Zika virus cases.

“Early in the response, collection and testing of specimens from pregnant women was prioritized over the collection from symptomatic nonpregnant patients because of limited testing and shipping capacity,” the researchers wrote.

By May 2016, suspected cases had dropped from six per week during January and February, to just one per week, with the last laboratory-confirmed case occurring on June 19, 2016. In August, the ASDoH proposed ending routine screening of asymptomatic pregnant women by Oct. 15, 2016. Transmission data from American Samoa and the CDC were used to determine the Oct. 15 date as an estimate for when active mosquito-borne transmission would end.

To confirm that local transmission was no longer ongoing, enhanced surveillance was implemented from Aug. 31 to Oct. 15, involving free testing at local clinics. Over the course of 45 days, there were a total of 32 patients suspected of having a Zika virus infection.

Two of these subjects’ specimens were not sufficient in sample size to be tested, but the other 30 underwent rRT-PCR testing within 30 days of symptom onset, and all the results were negative. Additionally, 277 asymptomatic pregnant women were tested and 86 (31%) tested anti-Zika IgM–positive or equivocal. All 86 specimens later tested negative by rRT-PCR.

Given the possibility that Zika virus can persist in semen for 6 months, officials recommended permissive testing of asymptomatic pregnant women who conceive through April 15, 2017 “as a conservative approach.”

“The surveillance processes outlined and the timeline established for American Samoa might have implications for jurisdictions where small populations and similar population immunity following widespread Zika virus exposure can facilitate interruption of transmission,” the researchers wrote.

[email protected]

Syndromic and enhanced surveillance employed during a Zika outbreak in American Samoa last year is credited for bringing a quick end to ongoing transmission and could be used to predict when ongoing transmission in similarly small populations will end.

“Establishing a timeline for discontinuing screening of asymptomatic pregnant women allows ASDoH [the American Samoa Department of Health] to allocate resources appropriately toward early interventions for children and families affected by Zika virus,” W. Thane Hancock, MD, of the CDC’s Office of Public Health Preparedness and Response, and his colleagues wrote in the Morbidity and Mortality Weekly Report (2017 Mar 24;66[11]:299-301).

Laboratory-confirmed Zika cases first cropped up in American Samoa in January 2016, prompting the implementation of protocols to reduce the mosquito population, along with syndromic surveillance based on electronic health records to determine which patients may be at higher risk. Routine testing of all asymptomatic pregnant woman, along with individuals with one or more symptoms of Zika virus, also became standard procedure. Real-time, reverse transcription–polymerase chain reaction (rRT-PCR) testing was used to confirm suspected Zika virus cases.

“Early in the response, collection and testing of specimens from pregnant women was prioritized over the collection from symptomatic nonpregnant patients because of limited testing and shipping capacity,” the researchers wrote.

By May 2016, suspected cases had dropped from six per week during January and February, to just one per week, with the last laboratory-confirmed case occurring on June 19, 2016. In August, the ASDoH proposed ending routine screening of asymptomatic pregnant women by Oct. 15, 2016. Transmission data from American Samoa and the CDC were used to determine the Oct. 15 date as an estimate for when active mosquito-borne transmission would end.

To confirm that local transmission was no longer ongoing, enhanced surveillance was implemented from Aug. 31 to Oct. 15, involving free testing at local clinics. Over the course of 45 days, there were a total of 32 patients suspected of having a Zika virus infection.

Two of these subjects’ specimens were not sufficient in sample size to be tested, but the other 30 underwent rRT-PCR testing within 30 days of symptom onset, and all the results were negative. Additionally, 277 asymptomatic pregnant women were tested and 86 (31%) tested anti-Zika IgM–positive or equivocal. All 86 specimens later tested negative by rRT-PCR.

Given the possibility that Zika virus can persist in semen for 6 months, officials recommended permissive testing of asymptomatic pregnant women who conceive through April 15, 2017 “as a conservative approach.”

“The surveillance processes outlined and the timeline established for American Samoa might have implications for jurisdictions where small populations and similar population immunity following widespread Zika virus exposure can facilitate interruption of transmission,” the researchers wrote.

[email protected]