Regulatory bodies and professional societies have encouraged or mandated written pain treatment agreements for over a decade as a way to establish informed consent, improve adherence, and mitigate risk. Unfortunately, the content of these agreements varies, their efficacy is uncertain, and some are stigmatizing or coercive and jeopardize trust. Additionally, many are written at reading levels beyond most patients’ understanding. However, we believe a well-written agreement is still an important tool in chronic pain management.

In this article, we explore common limitations of current pain treatment “contracts” and propose strategies to improve their usefulness and acceptance.

PAIN AND ITS TREATMENT HAVE COSTS

Chronic pain affects 100 million US adults and is estimated to cost $635 billion each year in treatment, lost wages, and reduced productivity.¹

Opioid therapy for chronic noncancer pain is being called into question,^2–5 and a 2016 guideline from the US Centers for Disease Control and Prevention has called for more limited and judicious use of opioids in primary care.⁶ Nevertheless, long-term opioid therapy is probably helpful in some circumstances and will likely continue to have a role in chronic pain management for the foreseeable future.⁷

Concerns about opioids include risks of overdose and death. Unintentional drug overdoses, typically with opioids, exceeded motor vehicle accidents in 2009 as the leading cause of accidental death in the United States⁸; by 2014, nearly one and a half times as many people were dying of a drug overdose than of a car accident.⁹ Even when used appropriately, opioids are associated with sedation, falls, motor vehicle accidents, addiction, and unintended overdose.¹⁰

The potential harm extends beyond the patient to the community at large. Diversion of prescription drugs for nonmedical use is common¹¹ and, after marijuana and alcohol abuse, is the most common form of drug abuse in the United States.¹² Misuse of prescription drugs costs health insurers an estimated $72.5 billion each year—a cost largely passed on to consumers through higher premiums.¹³ Most individuals who abuse prescription opioids get them from friends and family, sometimes by stealing them.¹⁴

THE SPECIAL ROLE OF THE PRIMARY CARE PHYSICIAN

Chronic pain is extremely prevalent in general internal medicine and primary care practice.^15,16 It has tremendous associated medical, social, and economic costs.¹

In light of the risks and complexity of opioid use and the increasing regulatory requirements for safe prescribing, some primary care physicians have stopped prescribing opioids altogether and refer patients elsewhere for pain management.

This does a disservice to patients. Primary care physicians cannot entirely avoid chronic pain management or absolutely refuse to prescribe opioids in all circumstances and still provide quality care. And although some primary care physicians may need more training in prescribing opioids, their comprehensive understanding of the patient’s other health issues enables them to address the psychosocial generators and consequences of the patient’s chronic pain more fully than a specialist can.

Furthermore, access to board-certified pain specialists is limited. There are only four such specialists for every 100,000 patients with chronic pain,¹⁷ and those who are available often restrict the types of insurance they accept, disproportionately excluding Medicaid patients.

We encourage primary care physicians to undertake continuing medical education and professional development as needed to prescribe opioids as safely and effectively as possible.

A CONTROLLED-SUBSTANCE AGREEMENT INSTEAD OF A ‘NARCOTIC CONTRACT’

To address the challenges of long-term opioid therapy, many state officials, medical licensing boards, professional societies, and other regulatory bodies recommend proactive monitoring and management of prescribing risks. Often promoted and sometimes mandated is the use of a written pain treatment agreement, sometimes called a “pain contract” or “narcotic contract,” in which the patient and the physician ostensibly agree to various conditions under which opioids will be prescribed or discontinued. Although well-intentioned, these documents can cause several problems.

Contracts were being advocated in treating opiate addiction as early as 1981.¹⁸ Since then, the term “narcotic contract” has become widely used, even as most professional guidelines have now moved away from using it. A Google search for the term on November 27, 2015, yielded 2,000 results, with numerous examples of the documents in clinical use.

But the phrase is misleading, and we believe physicians should avoid using it. Clinically, the word “narcotic” is imprecise and can refer to substances other than opioids. For example, the US Controlled Substances Act lists cocaine as a narcotic.¹⁹ The word also carries a stigma, as law enforcement agencies and drug abuse programs commonly use phrases such as “narcotic task force” or “narcotic treatment program.” On the other hand, the more accurate term “opioid” may be unfamiliar to patients. We recommend using the term “controlled substance” instead.

Similarly, the word “contract” can be perceived as coercive, can erode physician-patient trust, and implies that failure to agree to it will result in loss of access to pain medications.^20–23

For these reasons, we encourage physicians to adopt the phrase “controlled-substance agreement” or something similar. This label accurately reflects the specificity of the treatment and connotes a partnership between patient and physician. Furthermore, it allows the physician to use the agreement when prescribing other controlled substances such as benzodiazepines and stimulants that also carry a risk of addiction, misuse, and adverse effects.

STIGMATIZING THE PATIENT

Although no studies have systematically assessed the style and tone of available treatment agreements, many of the agreements seem to stigmatize the patient, using language that is mistrustful, accusatory, and even confrontational and that implies that the patient will misuse or abuse the medications.^21,24 For example, “Failure to comply with the terms of the contract will risk loss of medication or discharge from the medical practice” is inflammatory and coercive, but variations of this phrase appear in many of the results of the aforementioned Google search.

Such language defeats attempts to communicate openly and implies a deprecatory attitude towards patients. Stigmatization may result in undertreatment of pain, physician refusal to prescribe opioids, and patient refusal to submit to the terms of a one-sided agreement perceived as unfair. Therefore, poorly written opioid agreements impair the trust necessary for a therapeutic physician-patient relationship and can interfere with optimal pain management.^20–23

Some physicians stigmatize inadvertently. Believing that they can identify which patients will misuse their prescriptions, they use controlled-substance agreements only in this subgroup. But in fact, physicians are notoriously poor at predicting which patients will misuse prescription opioids or suffer adverse effects.²⁵ Therefore, it is important to be transparent and consistent with monitoring practices for all patients on chronic opioid therapy.²⁶

Framing the controlled-substance agreement in terms of safety and using it universally can minimize miscommunication and unintentional stigmatization.

SHARED DECISION-MAKING AND CHRONIC OPIOID THERAPY

We recommend using controlled-substance agreements only in the context of personalized patient counseling and shared decision-making.

Shared decision-making promotes mutual respect between patients and physicians, is feasible to implement in primary care, and may improve health outcomes.^27,28 A study found that physicians who received 2 hours of training in shared decision-making for chronic opioid therapy were more likely to complete treatment agreements and set mutually agreed-upon functional goals with patients, and they felt more confident, competent, and comfortable treating chronic pain.²⁹ Additionally, after learning about the risks, some patients may choose to forgo opioid therapy.

To be consistent with shared decision-making, the controlled-substance agreement must:

• Engage the patient, emphasizing the shared, reciprocal obligations of physician and patient
• Address goals of treatment that are personalized and mutually agreed-upon and that incorporate the patient’s values and preferences
• Explain treatment options in a way that is understandable and informative for the patient.

Table 1 outlines other key elements in detail.^27,30,31

Shared decision-making is especially useful when the balance between the risks and benefits of a treatment plan is uncertain. It is not a substitute for medical expertise, and a patient’s preferences do not override the physician’s clinical judgment. A physician should not offer or implement chronic opioid therapy if he or she believes it is not indicated or is contraindicated, or that the risks for that patient clearly outweigh the benefits.³²

THE CONTROLLED-SUBSTANCE AGREEMENT: FOUR OBJECTIVES

Stigmatizing language in the controlled-substance agreement may result from physician ambivalence regarding its intent and objectives. For example, some may perceive the agreement as a way to facilitate communication, while others may use it in a possibly unethical manner to control patient behavior with the threat of cutting off access to pain medication.³³

Controlled-substance agreements have four commonly identified objectives,³⁴ explored further below:

• To improve adherence with the safe use of controlled substances while reducing aberrant behaviors
• To obtain informed consent
• To outline the prescribing policies of the practice
• To mitigate the prescriber’s legal risk.

Improving adherence

Many authors say that the primary goal of the controlled-substance agreement is to promote the use of the medication as prescribed, without variance, and from one physician only.^35–38 This goal seems reasonable. However, many other classes of medications are also risky when used aberrantly, and we do not ask the patient to sign an agreement when we prescribe them. This double standard may reflect both the inherently higher risks associated with controlled substances and physician ambivalence regarding their use.

Regardless, the efficacy of controlled­substance agreements in improving safe-use adherence and reducing aberrant medication-taking behaviors is uncertain. A 2010 systematic review based on observational and largely poor-quality studies concluded that using treatment agreements along with urine drug testing modestly reduced opioid misuse,³⁹ while other reports have called their efficacy into question.⁴⁰ We remain optimistic that well-written controlled-substance agreements can advance this objective, and that absence of evidence is not evidence of absence—ie, lack of efficacy. However, the data are not yet clear.

Interestingly, a 2014 survey found that most primary care physicians thought that controlled-substance agreements do not meaningfully reduce opioid misuse but do give a sense of protection against liability.⁴¹ Additionally, these documents are associated with a greater sense of physician satisfaction and mastery,⁴² and for some physicians these reasons may be enough to justify their use.

Somewhat alarmingly though, one study suggests that many patients do not even know that they signed a treatment agreement.⁴³ Using a controlled-substance agreement without the full awareness and engagement of the patient cannot promote adherence and is likely counterproductive.

Obtaining informed consent

It is essential to discuss possible benefits and risks so that informed and shared decision-making can occur.

Controlled-substance agreements may advance this aim if carefully written, although medical practices often design them for use across a spectrum of patients with varying indications, contraindications, and risks, making these documents inherently inflexible. A one-size-fits-all document does not allow for meaningful personalization and is insufficient without patient-centered counseling.

We strongly recommend that treatment agreements complement but not replace personalized patient-centered counseling about individual risks and benefits. Well-written controlled-substance agreements may reduce the chance of overlooking key risks and launch further customized discussion. Additionally, they can be written in a manner that allows patients and physicians to agree on and document personalized goals (Table 2).

Furthermore, when crafted within a risk-benefit framework, a controlled-substance agreement can help to clarify an ethically important concept, ie, that the physician is judging the safety and appropriateness of the treatment, not the character of the patient.⁴⁴ The prescriber can focus on evaluating the risks and benefits of treatment choices, not being a police officer or a judge of how “deserving” of opioid therapy the patient is.

Importantly, for patients to provide meaningful informed consent, the agreement must be understandable. A study of 162 opioid treatment agreements found that on average, they were written at a 14th grade level, which is beyond the reading comprehension of most patients.⁴⁵ Another study evaluated patients’ ability to understand and follow instructions on labels for common prescriptions; even though 70% of the patients could read the labels, only 34.7% could demonstrate the instructions “take two tablets by mouth twice daily.”⁴⁶

We recommend analyzing all controlled- substance agreements for readability by assessing their Flesch-Kincaid grade level or a similar literacy assessment, using readily available computer apps. The average education level of the patients cared for in each practice will vary based on the demographic served, and the controlled-substance agreement can be modified accordingly, but typically writing the document at the 6th- to 7th-grade reading level is suggested.

Outlining practice policies

Opioids are federally controlled substances with prescribing restrictions that vary based on the drug’s Drug Enforcement Agency schedule. State laws and regulations also govern opioid prescribing and are constantly evolving.⁴⁷

Refilling opioid prescriptions should be a deliberate process during which the prescriber reviews the appropriateness of the medication and issues the prescription as safely as possible.

To promote practice consistency and to share expectations transparently with patients, we recommend spelling out in the agreement your policies on:

• Who can manage this patient’s opioid therapy
• How to handle refill requests after hours and on weekends
• When and how patients should request opioid refills
• Which pharmacies patients will use
• Whether the practice allows others to pick up refills for the patient.

This not only serves as a reference for patients, who keep a copy for their records, it also reduces the risk of inconsistent processes within the office, which will quickly lead to chaos and confusion among patients and physicians alike. Inconsistent prescription and refill practices can give the impression that a double standard exists and that some patients get more leeway than others, without apparent justification.

There is little evidence that this approach truly improves practice efficiency,^34,48 but we believe that it may avert future confusion and conflict.

Mitigating the prescriber’s risk

Most licensing boards and clinical guidelines recommend controlled-substance agreements as part of opioid risk mitigation. These documents are now the standard of care, with many bodies recommending or mandating them, including the Federation of State Medical Boards,⁴⁹ many states,⁵⁰ Physicians for Responsible Opioid Prescribing,⁵¹ the American Academy of Pain Management,⁵² and the American Pain Society along with the American Academy of Pain Medicine.⁵³

Historically, primary care physicians have used controlled-substance agreements inconsistently and primarily for patients believed to be at high risk of misuse.⁵⁴ However, because physicians cannot accurately predict who will misuse or divert medications,²⁵ controlled-substance agreements should be used universally, ie, for all patients prescribed controlled substances.

A controlled-substance agreement can serve as documentation. The patient can keep a copy for future reference, and a cosigned document is evidence that a discussion took place and may lower the risk of malpractice litigation.⁵⁵ Further, if a state requires physicians to check their prescription monitoring database before prescribing opioids, the controlled-substance agreement can serve to both inform patients about this obligation and to obtain their consent when required.

At a minimum, we recommend that prescribers learn about the regulatory framework in their state and use controlled-substance agreements as legislatively mandated.

A CHECKLIST FOR THE PHYSICIAN AND PATIENT

To facilitate the development and use of ethically appropriate controlled-substance agreements with a focus on shared decision-making, we offer a sample tool in the form of a checklist (Table 2). It can be modified and implemented instead of a traditional controlled-substance agreement or can be used alongside other more comprehensive documents to facilitate discussion.

The model presents critical information for the patient and physician to discuss and acknowledge (initial) in writing. It is divided into three sections: shared responsibilities, patient responsibilities, and physician responsibilities. Each contains an approximately equal number of items; this is deliberate and visually conveys the notion of equivalent and shared responsibilities for patient and physician. The patient, physician, or both should initial each item to indicate their agreement.

The document is customizable for the specific treatment prescribed. It is written at a Flesch-Kincaid grade level of 6.8, consistent with current health literacy recommendations, and avoids medical jargon and complex compound sentences as much as possible.

We indicate key elements of shared decision-making^27,30,31 in parentheses in Table 2 and cross-reference them with Table 1, which describes them more fully.

A BETTER TOOL

Both chronic pain and prescription drug abuse are highly prevalent and carry serious consequences. These overlapping epidemics put the prescriber in the difficult position of trying to prevent misuse, abuse, and diversion while simultaneously adequately treating pain.

Physicians and policy makers look to controlled-substance agreements as tools to help them balance the benefits and risks, but frequently at the expense of eroding trust between the patient and physician, stigmatizing the patient, using pejorative and coercive language, not adhering to health literacy guidelines, and failing to share decisions.

We believe a better tool is possible and suggest that controlled-substance agreements be universally applied, use deliberate and understandable language, be framed in terms of safety, and be implemented according to the principles of shared decision-making.

Regulatory bodies and professional societies have encouraged or mandated written pain treatment agreements for over a decade as a way to establish informed consent, improve adherence, and mitigate risk. Unfortunately, the content of these agreements varies, their efficacy is uncertain, and some are stigmatizing or coercive and jeopardize trust. Additionally, many are written at reading levels beyond most patients’ understanding. However, we believe a well-written agreement is still an important tool in chronic pain management.

In this article, we explore common limitations of current pain treatment “contracts” and propose strategies to improve their usefulness and acceptance.

PAIN AND ITS TREATMENT HAVE COSTS

Chronic pain affects 100 million US adults and is estimated to cost $635 billion each year in treatment, lost wages, and reduced productivity.¹

Opioid therapy for chronic noncancer pain is being called into question,^2–5 and a 2016 guideline from the US Centers for Disease Control and Prevention has called for more limited and judicious use of opioids in primary care.⁶ Nevertheless, long-term opioid therapy is probably helpful in some circumstances and will likely continue to have a role in chronic pain management for the foreseeable future.⁷

Concerns about opioids include risks of overdose and death. Unintentional drug overdoses, typically with opioids, exceeded motor vehicle accidents in 2009 as the leading cause of accidental death in the United States⁸; by 2014, nearly one and a half times as many people were dying of a drug overdose than of a car accident.⁹ Even when used appropriately, opioids are associated with sedation, falls, motor vehicle accidents, addiction, and unintended overdose.¹⁰

The potential harm extends beyond the patient to the community at large. Diversion of prescription drugs for nonmedical use is common¹¹ and, after marijuana and alcohol abuse, is the most common form of drug abuse in the United States.¹² Misuse of prescription drugs costs health insurers an estimated $72.5 billion each year—a cost largely passed on to consumers through higher premiums.¹³ Most individuals who abuse prescription opioids get them from friends and family, sometimes by stealing them.¹⁴

THE SPECIAL ROLE OF THE PRIMARY CARE PHYSICIAN

Chronic pain is extremely prevalent in general internal medicine and primary care practice.^15,16 It has tremendous associated medical, social, and economic costs.¹

In light of the risks and complexity of opioid use and the increasing regulatory requirements for safe prescribing, some primary care physicians have stopped prescribing opioids altogether and refer patients elsewhere for pain management.

This does a disservice to patients. Primary care physicians cannot entirely avoid chronic pain management or absolutely refuse to prescribe opioids in all circumstances and still provide quality care. And although some primary care physicians may need more training in prescribing opioids, their comprehensive understanding of the patient’s other health issues enables them to address the psychosocial generators and consequences of the patient’s chronic pain more fully than a specialist can.

Furthermore, access to board-certified pain specialists is limited. There are only four such specialists for every 100,000 patients with chronic pain,¹⁷ and those who are available often restrict the types of insurance they accept, disproportionately excluding Medicaid patients.

We encourage primary care physicians to undertake continuing medical education and professional development as needed to prescribe opioids as safely and effectively as possible.

A CONTROLLED-SUBSTANCE AGREEMENT INSTEAD OF A ‘NARCOTIC CONTRACT’

To address the challenges of long-term opioid therapy, many state officials, medical licensing boards, professional societies, and other regulatory bodies recommend proactive monitoring and management of prescribing risks. Often promoted and sometimes mandated is the use of a written pain treatment agreement, sometimes called a “pain contract” or “narcotic contract,” in which the patient and the physician ostensibly agree to various conditions under which opioids will be prescribed or discontinued. Although well-intentioned, these documents can cause several problems.

Contracts were being advocated in treating opiate addiction as early as 1981.¹⁸ Since then, the term “narcotic contract” has become widely used, even as most professional guidelines have now moved away from using it. A Google search for the term on November 27, 2015, yielded 2,000 results, with numerous examples of the documents in clinical use.

But the phrase is misleading, and we believe physicians should avoid using it. Clinically, the word “narcotic” is imprecise and can refer to substances other than opioids. For example, the US Controlled Substances Act lists cocaine as a narcotic.¹⁹ The word also carries a stigma, as law enforcement agencies and drug abuse programs commonly use phrases such as “narcotic task force” or “narcotic treatment program.” On the other hand, the more accurate term “opioid” may be unfamiliar to patients. We recommend using the term “controlled substance” instead.

Similarly, the word “contract” can be perceived as coercive, can erode physician-patient trust, and implies that failure to agree to it will result in loss of access to pain medications.^20–23

For these reasons, we encourage physicians to adopt the phrase “controlled-substance agreement” or something similar. This label accurately reflects the specificity of the treatment and connotes a partnership between patient and physician. Furthermore, it allows the physician to use the agreement when prescribing other controlled substances such as benzodiazepines and stimulants that also carry a risk of addiction, misuse, and adverse effects.

STIGMATIZING THE PATIENT

Although no studies have systematically assessed the style and tone of available treatment agreements, many of the agreements seem to stigmatize the patient, using language that is mistrustful, accusatory, and even confrontational and that implies that the patient will misuse or abuse the medications.^21,24 For example, “Failure to comply with the terms of the contract will risk loss of medication or discharge from the medical practice” is inflammatory and coercive, but variations of this phrase appear in many of the results of the aforementioned Google search.

Such language defeats attempts to communicate openly and implies a deprecatory attitude towards patients. Stigmatization may result in undertreatment of pain, physician refusal to prescribe opioids, and patient refusal to submit to the terms of a one-sided agreement perceived as unfair. Therefore, poorly written opioid agreements impair the trust necessary for a therapeutic physician-patient relationship and can interfere with optimal pain management.^20–23

Some physicians stigmatize inadvertently. Believing that they can identify which patients will misuse their prescriptions, they use controlled-substance agreements only in this subgroup. But in fact, physicians are notoriously poor at predicting which patients will misuse prescription opioids or suffer adverse effects.²⁵ Therefore, it is important to be transparent and consistent with monitoring practices for all patients on chronic opioid therapy.²⁶

Framing the controlled-substance agreement in terms of safety and using it universally can minimize miscommunication and unintentional stigmatization.

SHARED DECISION-MAKING AND CHRONIC OPIOID THERAPY

We recommend using controlled-substance agreements only in the context of personalized patient counseling and shared decision-making.

Shared decision-making promotes mutual respect between patients and physicians, is feasible to implement in primary care, and may improve health outcomes.^27,28 A study found that physicians who received 2 hours of training in shared decision-making for chronic opioid therapy were more likely to complete treatment agreements and set mutually agreed-upon functional goals with patients, and they felt more confident, competent, and comfortable treating chronic pain.²⁹ Additionally, after learning about the risks, some patients may choose to forgo opioid therapy.

To be consistent with shared decision-making, the controlled-substance agreement must:

• Engage the patient, emphasizing the shared, reciprocal obligations of physician and patient
• Address goals of treatment that are personalized and mutually agreed-upon and that incorporate the patient’s values and preferences
• Explain treatment options in a way that is understandable and informative for the patient.

Table 1 outlines other key elements in detail.^27,30,31

Shared decision-making is especially useful when the balance between the risks and benefits of a treatment plan is uncertain. It is not a substitute for medical expertise, and a patient’s preferences do not override the physician’s clinical judgment. A physician should not offer or implement chronic opioid therapy if he or she believes it is not indicated or is contraindicated, or that the risks for that patient clearly outweigh the benefits.³²

THE CONTROLLED-SUBSTANCE AGREEMENT: FOUR OBJECTIVES

Stigmatizing language in the controlled-substance agreement may result from physician ambivalence regarding its intent and objectives. For example, some may perceive the agreement as a way to facilitate communication, while others may use it in a possibly unethical manner to control patient behavior with the threat of cutting off access to pain medication.³³

Controlled-substance agreements have four commonly identified objectives,³⁴ explored further below:

• To improve adherence with the safe use of controlled substances while reducing aberrant behaviors
• To obtain informed consent
• To outline the prescribing policies of the practice
• To mitigate the prescriber’s legal risk.

Improving adherence

Many authors say that the primary goal of the controlled-substance agreement is to promote the use of the medication as prescribed, without variance, and from one physician only.^35–38 This goal seems reasonable. However, many other classes of medications are also risky when used aberrantly, and we do not ask the patient to sign an agreement when we prescribe them. This double standard may reflect both the inherently higher risks associated with controlled substances and physician ambivalence regarding their use.

Regardless, the efficacy of controlled­substance agreements in improving safe-use adherence and reducing aberrant medication-taking behaviors is uncertain. A 2010 systematic review based on observational and largely poor-quality studies concluded that using treatment agreements along with urine drug testing modestly reduced opioid misuse,³⁹ while other reports have called their efficacy into question.⁴⁰ We remain optimistic that well-written controlled-substance agreements can advance this objective, and that absence of evidence is not evidence of absence—ie, lack of efficacy. However, the data are not yet clear.

Interestingly, a 2014 survey found that most primary care physicians thought that controlled-substance agreements do not meaningfully reduce opioid misuse but do give a sense of protection against liability.⁴¹ Additionally, these documents are associated with a greater sense of physician satisfaction and mastery,⁴² and for some physicians these reasons may be enough to justify their use.

Somewhat alarmingly though, one study suggests that many patients do not even know that they signed a treatment agreement.⁴³ Using a controlled-substance agreement without the full awareness and engagement of the patient cannot promote adherence and is likely counterproductive.

Obtaining informed consent

It is essential to discuss possible benefits and risks so that informed and shared decision-making can occur.

Controlled-substance agreements may advance this aim if carefully written, although medical practices often design them for use across a spectrum of patients with varying indications, contraindications, and risks, making these documents inherently inflexible. A one-size-fits-all document does not allow for meaningful personalization and is insufficient without patient-centered counseling.

We strongly recommend that treatment agreements complement but not replace personalized patient-centered counseling about individual risks and benefits. Well-written controlled-substance agreements may reduce the chance of overlooking key risks and launch further customized discussion. Additionally, they can be written in a manner that allows patients and physicians to agree on and document personalized goals (Table 2).

Furthermore, when crafted within a risk-benefit framework, a controlled-substance agreement can help to clarify an ethically important concept, ie, that the physician is judging the safety and appropriateness of the treatment, not the character of the patient.⁴⁴ The prescriber can focus on evaluating the risks and benefits of treatment choices, not being a police officer or a judge of how “deserving” of opioid therapy the patient is.

Importantly, for patients to provide meaningful informed consent, the agreement must be understandable. A study of 162 opioid treatment agreements found that on average, they were written at a 14th grade level, which is beyond the reading comprehension of most patients.⁴⁵ Another study evaluated patients’ ability to understand and follow instructions on labels for common prescriptions; even though 70% of the patients could read the labels, only 34.7% could demonstrate the instructions “take two tablets by mouth twice daily.”⁴⁶

We recommend analyzing all controlled- substance agreements for readability by assessing their Flesch-Kincaid grade level or a similar literacy assessment, using readily available computer apps. The average education level of the patients cared for in each practice will vary based on the demographic served, and the controlled-substance agreement can be modified accordingly, but typically writing the document at the 6th- to 7th-grade reading level is suggested.

Outlining practice policies

Opioids are federally controlled substances with prescribing restrictions that vary based on the drug’s Drug Enforcement Agency schedule. State laws and regulations also govern opioid prescribing and are constantly evolving.⁴⁷

Refilling opioid prescriptions should be a deliberate process during which the prescriber reviews the appropriateness of the medication and issues the prescription as safely as possible.

To promote practice consistency and to share expectations transparently with patients, we recommend spelling out in the agreement your policies on:

• Who can manage this patient’s opioid therapy
• How to handle refill requests after hours and on weekends
• When and how patients should request opioid refills
• Which pharmacies patients will use
• Whether the practice allows others to pick up refills for the patient.

This not only serves as a reference for patients, who keep a copy for their records, it also reduces the risk of inconsistent processes within the office, which will quickly lead to chaos and confusion among patients and physicians alike. Inconsistent prescription and refill practices can give the impression that a double standard exists and that some patients get more leeway than others, without apparent justification.

There is little evidence that this approach truly improves practice efficiency,^34,48 but we believe that it may avert future confusion and conflict.

Mitigating the prescriber’s risk

Most licensing boards and clinical guidelines recommend controlled-substance agreements as part of opioid risk mitigation. These documents are now the standard of care, with many bodies recommending or mandating them, including the Federation of State Medical Boards,⁴⁹ many states,⁵⁰ Physicians for Responsible Opioid Prescribing,⁵¹ the American Academy of Pain Management,⁵² and the American Pain Society along with the American Academy of Pain Medicine.⁵³

Historically, primary care physicians have used controlled-substance agreements inconsistently and primarily for patients believed to be at high risk of misuse.⁵⁴ However, because physicians cannot accurately predict who will misuse or divert medications,²⁵ controlled-substance agreements should be used universally, ie, for all patients prescribed controlled substances.

A controlled-substance agreement can serve as documentation. The patient can keep a copy for future reference, and a cosigned document is evidence that a discussion took place and may lower the risk of malpractice litigation.⁵⁵ Further, if a state requires physicians to check their prescription monitoring database before prescribing opioids, the controlled-substance agreement can serve to both inform patients about this obligation and to obtain their consent when required.

At a minimum, we recommend that prescribers learn about the regulatory framework in their state and use controlled-substance agreements as legislatively mandated.

A CHECKLIST FOR THE PHYSICIAN AND PATIENT

To facilitate the development and use of ethically appropriate controlled-substance agreements with a focus on shared decision-making, we offer a sample tool in the form of a checklist (Table 2). It can be modified and implemented instead of a traditional controlled-substance agreement or can be used alongside other more comprehensive documents to facilitate discussion.

The model presents critical information for the patient and physician to discuss and acknowledge (initial) in writing. It is divided into three sections: shared responsibilities, patient responsibilities, and physician responsibilities. Each contains an approximately equal number of items; this is deliberate and visually conveys the notion of equivalent and shared responsibilities for patient and physician. The patient, physician, or both should initial each item to indicate their agreement.

The document is customizable for the specific treatment prescribed. It is written at a Flesch-Kincaid grade level of 6.8, consistent with current health literacy recommendations, and avoids medical jargon and complex compound sentences as much as possible.

We indicate key elements of shared decision-making^27,30,31 in parentheses in Table 2 and cross-reference them with Table 1, which describes them more fully.

A BETTER TOOL

Both chronic pain and prescription drug abuse are highly prevalent and carry serious consequences. These overlapping epidemics put the prescriber in the difficult position of trying to prevent misuse, abuse, and diversion while simultaneously adequately treating pain.

Physicians and policy makers look to controlled-substance agreements as tools to help them balance the benefits and risks, but frequently at the expense of eroding trust between the patient and physician, stigmatizing the patient, using pejorative and coercive language, not adhering to health literacy guidelines, and failing to share decisions.

We believe a better tool is possible and suggest that controlled-substance agreements be universally applied, use deliberate and understandable language, be framed in terms of safety, and be implemented according to the principles of shared decision-making.

Regulatory bodies and professional societies have encouraged or mandated written pain treatment agreements for over a decade as a way to establish informed consent, improve adherence, and mitigate risk. Unfortunately, the content of these agreements varies, their efficacy is uncertain, and some are stigmatizing or coercive and jeopardize trust. Additionally, many are written at reading levels beyond most patients’ understanding. However, we believe a well-written agreement is still an important tool in chronic pain management.

In this article, we explore common limitations of current pain treatment “contracts” and propose strategies to improve their usefulness and acceptance.

PAIN AND ITS TREATMENT HAVE COSTS

Chronic pain affects 100 million US adults and is estimated to cost $635 billion each year in treatment, lost wages, and reduced productivity.¹

Opioid therapy for chronic noncancer pain is being called into question,^2–5 and a 2016 guideline from the US Centers for Disease Control and Prevention has called for more limited and judicious use of opioids in primary care.⁶ Nevertheless, long-term opioid therapy is probably helpful in some circumstances and will likely continue to have a role in chronic pain management for the foreseeable future.⁷

Concerns about opioids include risks of overdose and death. Unintentional drug overdoses, typically with opioids, exceeded motor vehicle accidents in 2009 as the leading cause of accidental death in the United States⁸; by 2014, nearly one and a half times as many people were dying of a drug overdose than of a car accident.⁹ Even when used appropriately, opioids are associated with sedation, falls, motor vehicle accidents, addiction, and unintended overdose.¹⁰

The potential harm extends beyond the patient to the community at large. Diversion of prescription drugs for nonmedical use is common¹¹ and, after marijuana and alcohol abuse, is the most common form of drug abuse in the United States.¹² Misuse of prescription drugs costs health insurers an estimated $72.5 billion each year—a cost largely passed on to consumers through higher premiums.¹³ Most individuals who abuse prescription opioids get them from friends and family, sometimes by stealing them.¹⁴

THE SPECIAL ROLE OF THE PRIMARY CARE PHYSICIAN

Chronic pain is extremely prevalent in general internal medicine and primary care practice.^15,16 It has tremendous associated medical, social, and economic costs.¹

In light of the risks and complexity of opioid use and the increasing regulatory requirements for safe prescribing, some primary care physicians have stopped prescribing opioids altogether and refer patients elsewhere for pain management.

This does a disservice to patients. Primary care physicians cannot entirely avoid chronic pain management or absolutely refuse to prescribe opioids in all circumstances and still provide quality care. And although some primary care physicians may need more training in prescribing opioids, their comprehensive understanding of the patient’s other health issues enables them to address the psychosocial generators and consequences of the patient’s chronic pain more fully than a specialist can.

Furthermore, access to board-certified pain specialists is limited. There are only four such specialists for every 100,000 patients with chronic pain,¹⁷ and those who are available often restrict the types of insurance they accept, disproportionately excluding Medicaid patients.

We encourage primary care physicians to undertake continuing medical education and professional development as needed to prescribe opioids as safely and effectively as possible.

A CONTROLLED-SUBSTANCE AGREEMENT INSTEAD OF A ‘NARCOTIC CONTRACT’

To address the challenges of long-term opioid therapy, many state officials, medical licensing boards, professional societies, and other regulatory bodies recommend proactive monitoring and management of prescribing risks. Often promoted and sometimes mandated is the use of a written pain treatment agreement, sometimes called a “pain contract” or “narcotic contract,” in which the patient and the physician ostensibly agree to various conditions under which opioids will be prescribed or discontinued. Although well-intentioned, these documents can cause several problems.

Contracts were being advocated in treating opiate addiction as early as 1981.¹⁸ Since then, the term “narcotic contract” has become widely used, even as most professional guidelines have now moved away from using it. A Google search for the term on November 27, 2015, yielded 2,000 results, with numerous examples of the documents in clinical use.

But the phrase is misleading, and we believe physicians should avoid using it. Clinically, the word “narcotic” is imprecise and can refer to substances other than opioids. For example, the US Controlled Substances Act lists cocaine as a narcotic.¹⁹ The word also carries a stigma, as law enforcement agencies and drug abuse programs commonly use phrases such as “narcotic task force” or “narcotic treatment program.” On the other hand, the more accurate term “opioid” may be unfamiliar to patients. We recommend using the term “controlled substance” instead.

Similarly, the word “contract” can be perceived as coercive, can erode physician-patient trust, and implies that failure to agree to it will result in loss of access to pain medications.^20–23

For these reasons, we encourage physicians to adopt the phrase “controlled-substance agreement” or something similar. This label accurately reflects the specificity of the treatment and connotes a partnership between patient and physician. Furthermore, it allows the physician to use the agreement when prescribing other controlled substances such as benzodiazepines and stimulants that also carry a risk of addiction, misuse, and adverse effects.

STIGMATIZING THE PATIENT

Although no studies have systematically assessed the style and tone of available treatment agreements, many of the agreements seem to stigmatize the patient, using language that is mistrustful, accusatory, and even confrontational and that implies that the patient will misuse or abuse the medications.^21,24 For example, “Failure to comply with the terms of the contract will risk loss of medication or discharge from the medical practice” is inflammatory and coercive, but variations of this phrase appear in many of the results of the aforementioned Google search.

Such language defeats attempts to communicate openly and implies a deprecatory attitude towards patients. Stigmatization may result in undertreatment of pain, physician refusal to prescribe opioids, and patient refusal to submit to the terms of a one-sided agreement perceived as unfair. Therefore, poorly written opioid agreements impair the trust necessary for a therapeutic physician-patient relationship and can interfere with optimal pain management.^20–23

Some physicians stigmatize inadvertently. Believing that they can identify which patients will misuse their prescriptions, they use controlled-substance agreements only in this subgroup. But in fact, physicians are notoriously poor at predicting which patients will misuse prescription opioids or suffer adverse effects.²⁵ Therefore, it is important to be transparent and consistent with monitoring practices for all patients on chronic opioid therapy.²⁶

Framing the controlled-substance agreement in terms of safety and using it universally can minimize miscommunication and unintentional stigmatization.

SHARED DECISION-MAKING AND CHRONIC OPIOID THERAPY

We recommend using controlled-substance agreements only in the context of personalized patient counseling and shared decision-making.

Shared decision-making promotes mutual respect between patients and physicians, is feasible to implement in primary care, and may improve health outcomes.^27,28 A study found that physicians who received 2 hours of training in shared decision-making for chronic opioid therapy were more likely to complete treatment agreements and set mutually agreed-upon functional goals with patients, and they felt more confident, competent, and comfortable treating chronic pain.²⁹ Additionally, after learning about the risks, some patients may choose to forgo opioid therapy.

To be consistent with shared decision-making, the controlled-substance agreement must:

• Engage the patient, emphasizing the shared, reciprocal obligations of physician and patient
• Address goals of treatment that are personalized and mutually agreed-upon and that incorporate the patient’s values and preferences
• Explain treatment options in a way that is understandable and informative for the patient.

Table 1 outlines other key elements in detail.^27,30,31

Shared decision-making is especially useful when the balance between the risks and benefits of a treatment plan is uncertain. It is not a substitute for medical expertise, and a patient’s preferences do not override the physician’s clinical judgment. A physician should not offer or implement chronic opioid therapy if he or she believes it is not indicated or is contraindicated, or that the risks for that patient clearly outweigh the benefits.³²

THE CONTROLLED-SUBSTANCE AGREEMENT: FOUR OBJECTIVES

Stigmatizing language in the controlled-substance agreement may result from physician ambivalence regarding its intent and objectives. For example, some may perceive the agreement as a way to facilitate communication, while others may use it in a possibly unethical manner to control patient behavior with the threat of cutting off access to pain medication.³³

Controlled-substance agreements have four commonly identified objectives,³⁴ explored further below:

• To improve adherence with the safe use of controlled substances while reducing aberrant behaviors
• To obtain informed consent
• To outline the prescribing policies of the practice
• To mitigate the prescriber’s legal risk.

Improving adherence

Many authors say that the primary goal of the controlled-substance agreement is to promote the use of the medication as prescribed, without variance, and from one physician only.^35–38 This goal seems reasonable. However, many other classes of medications are also risky when used aberrantly, and we do not ask the patient to sign an agreement when we prescribe them. This double standard may reflect both the inherently higher risks associated with controlled substances and physician ambivalence regarding their use.

Regardless, the efficacy of controlled­substance agreements in improving safe-use adherence and reducing aberrant medication-taking behaviors is uncertain. A 2010 systematic review based on observational and largely poor-quality studies concluded that using treatment agreements along with urine drug testing modestly reduced opioid misuse,³⁹ while other reports have called their efficacy into question.⁴⁰ We remain optimistic that well-written controlled-substance agreements can advance this objective, and that absence of evidence is not evidence of absence—ie, lack of efficacy. However, the data are not yet clear.

Interestingly, a 2014 survey found that most primary care physicians thought that controlled-substance agreements do not meaningfully reduce opioid misuse but do give a sense of protection against liability.⁴¹ Additionally, these documents are associated with a greater sense of physician satisfaction and mastery,⁴² and for some physicians these reasons may be enough to justify their use.

Somewhat alarmingly though, one study suggests that many patients do not even know that they signed a treatment agreement.⁴³ Using a controlled-substance agreement without the full awareness and engagement of the patient cannot promote adherence and is likely counterproductive.

Obtaining informed consent

It is essential to discuss possible benefits and risks so that informed and shared decision-making can occur.

Controlled-substance agreements may advance this aim if carefully written, although medical practices often design them for use across a spectrum of patients with varying indications, contraindications, and risks, making these documents inherently inflexible. A one-size-fits-all document does not allow for meaningful personalization and is insufficient without patient-centered counseling.

We strongly recommend that treatment agreements complement but not replace personalized patient-centered counseling about individual risks and benefits. Well-written controlled-substance agreements may reduce the chance of overlooking key risks and launch further customized discussion. Additionally, they can be written in a manner that allows patients and physicians to agree on and document personalized goals (Table 2).

Furthermore, when crafted within a risk-benefit framework, a controlled-substance agreement can help to clarify an ethically important concept, ie, that the physician is judging the safety and appropriateness of the treatment, not the character of the patient.⁴⁴ The prescriber can focus on evaluating the risks and benefits of treatment choices, not being a police officer or a judge of how “deserving” of opioid therapy the patient is.

Importantly, for patients to provide meaningful informed consent, the agreement must be understandable. A study of 162 opioid treatment agreements found that on average, they were written at a 14th grade level, which is beyond the reading comprehension of most patients.⁴⁵ Another study evaluated patients’ ability to understand and follow instructions on labels for common prescriptions; even though 70% of the patients could read the labels, only 34.7% could demonstrate the instructions “take two tablets by mouth twice daily.”⁴⁶

We recommend analyzing all controlled- substance agreements for readability by assessing their Flesch-Kincaid grade level or a similar literacy assessment, using readily available computer apps. The average education level of the patients cared for in each practice will vary based on the demographic served, and the controlled-substance agreement can be modified accordingly, but typically writing the document at the 6th- to 7th-grade reading level is suggested.

Outlining practice policies

Opioids are federally controlled substances with prescribing restrictions that vary based on the drug’s Drug Enforcement Agency schedule. State laws and regulations also govern opioid prescribing and are constantly evolving.⁴⁷

Refilling opioid prescriptions should be a deliberate process during which the prescriber reviews the appropriateness of the medication and issues the prescription as safely as possible.

To promote practice consistency and to share expectations transparently with patients, we recommend spelling out in the agreement your policies on:

• Who can manage this patient’s opioid therapy
• How to handle refill requests after hours and on weekends
• When and how patients should request opioid refills
• Which pharmacies patients will use
• Whether the practice allows others to pick up refills for the patient.

This not only serves as a reference for patients, who keep a copy for their records, it also reduces the risk of inconsistent processes within the office, which will quickly lead to chaos and confusion among patients and physicians alike. Inconsistent prescription and refill practices can give the impression that a double standard exists and that some patients get more leeway than others, without apparent justification.

There is little evidence that this approach truly improves practice efficiency,^34,48 but we believe that it may avert future confusion and conflict.

Mitigating the prescriber’s risk

Most licensing boards and clinical guidelines recommend controlled-substance agreements as part of opioid risk mitigation. These documents are now the standard of care, with many bodies recommending or mandating them, including the Federation of State Medical Boards,⁴⁹ many states,⁵⁰ Physicians for Responsible Opioid Prescribing,⁵¹ the American Academy of Pain Management,⁵² and the American Pain Society along with the American Academy of Pain Medicine.⁵³

Historically, primary care physicians have used controlled-substance agreements inconsistently and primarily for patients believed to be at high risk of misuse.⁵⁴ However, because physicians cannot accurately predict who will misuse or divert medications,²⁵ controlled-substance agreements should be used universally, ie, for all patients prescribed controlled substances.

A controlled-substance agreement can serve as documentation. The patient can keep a copy for future reference, and a cosigned document is evidence that a discussion took place and may lower the risk of malpractice litigation.⁵⁵ Further, if a state requires physicians to check their prescription monitoring database before prescribing opioids, the controlled-substance agreement can serve to both inform patients about this obligation and to obtain their consent when required.

At a minimum, we recommend that prescribers learn about the regulatory framework in their state and use controlled-substance agreements as legislatively mandated.

A CHECKLIST FOR THE PHYSICIAN AND PATIENT

To facilitate the development and use of ethically appropriate controlled-substance agreements with a focus on shared decision-making, we offer a sample tool in the form of a checklist (Table 2). It can be modified and implemented instead of a traditional controlled-substance agreement or can be used alongside other more comprehensive documents to facilitate discussion.

The model presents critical information for the patient and physician to discuss and acknowledge (initial) in writing. It is divided into three sections: shared responsibilities, patient responsibilities, and physician responsibilities. Each contains an approximately equal number of items; this is deliberate and visually conveys the notion of equivalent and shared responsibilities for patient and physician. The patient, physician, or both should initial each item to indicate their agreement.

The document is customizable for the specific treatment prescribed. It is written at a Flesch-Kincaid grade level of 6.8, consistent with current health literacy recommendations, and avoids medical jargon and complex compound sentences as much as possible.

We indicate key elements of shared decision-making^27,30,31 in parentheses in Table 2 and cross-reference them with Table 1, which describes them more fully.

A BETTER TOOL

Both chronic pain and prescription drug abuse are highly prevalent and carry serious consequences. These overlapping epidemics put the prescriber in the difficult position of trying to prevent misuse, abuse, and diversion while simultaneously adequately treating pain.

Physicians and policy makers look to controlled-substance agreements as tools to help them balance the benefits and risks, but frequently at the expense of eroding trust between the patient and physician, stigmatizing the patient, using pejorative and coercive language, not adhering to health literacy guidelines, and failing to share decisions.

We believe a better tool is possible and suggest that controlled-substance agreements be universally applied, use deliberate and understandable language, be framed in terms of safety, and be implemented according to the principles of shared decision-making.

To the Editor: I much enjoyed the important article by Drs. Lipold, Batur, and Kagan on whether there is a time limit for systemic menopausal hormone therapy.¹ The simple answer is no. The authors did a good job of reviewing the factors to consider in terms of contraindications and precautions when prescribing menopausal hormone therapy.

An important part of the discussion regarding stopping hormone therapy is the recent evidence from Finland that has shown increased risks of myocardial infarction and stroke, especially in women under age 60, when taken off hormone therapy.² This fact is quite ironic, as many clinicians are trying to rush to get women off hormone therapy in order to protect the heart, when the evidence does not suggest this. Just as with other hormone-deficiency conditions, the status needs to be periodically reviewed, and doses may need to be adjusted. However, after age 60 or 65, women do not automatically start producing the sex hormone that they have been deficient in. While menopause is not a definite endocrinopathy, it is a potential endocrinopathy; and for some women, such as young women who are oophorectomized, it is an absolute endocrinopathy.

The International Menopause Society has published updated guidelines emphasizing that new data and reanalysis of older data show that for most women the benefits of menopausal hormone therapy are much greater than the risks, particularly when started within a few years of menopause.³

To the Editor: I much enjoyed the important article by Drs. Lipold, Batur, and Kagan on whether there is a time limit for systemic menopausal hormone therapy.¹ The simple answer is no. The authors did a good job of reviewing the factors to consider in terms of contraindications and precautions when prescribing menopausal hormone therapy.

An important part of the discussion regarding stopping hormone therapy is the recent evidence from Finland that has shown increased risks of myocardial infarction and stroke, especially in women under age 60, when taken off hormone therapy.² This fact is quite ironic, as many clinicians are trying to rush to get women off hormone therapy in order to protect the heart, when the evidence does not suggest this. Just as with other hormone-deficiency conditions, the status needs to be periodically reviewed, and doses may need to be adjusted. However, after age 60 or 65, women do not automatically start producing the sex hormone that they have been deficient in. While menopause is not a definite endocrinopathy, it is a potential endocrinopathy; and for some women, such as young women who are oophorectomized, it is an absolute endocrinopathy.

The International Menopause Society has published updated guidelines emphasizing that new data and reanalysis of older data show that for most women the benefits of menopausal hormone therapy are much greater than the risks, particularly when started within a few years of menopause.³

To the Editor: I much enjoyed the important article by Drs. Lipold, Batur, and Kagan on whether there is a time limit for systemic menopausal hormone therapy.¹ The simple answer is no. The authors did a good job of reviewing the factors to consider in terms of contraindications and precautions when prescribing menopausal hormone therapy.

An important part of the discussion regarding stopping hormone therapy is the recent evidence from Finland that has shown increased risks of myocardial infarction and stroke, especially in women under age 60, when taken off hormone therapy.² This fact is quite ironic, as many clinicians are trying to rush to get women off hormone therapy in order to protect the heart, when the evidence does not suggest this. Just as with other hormone-deficiency conditions, the status needs to be periodically reviewed, and doses may need to be adjusted. However, after age 60 or 65, women do not automatically start producing the sex hormone that they have been deficient in. While menopause is not a definite endocrinopathy, it is a potential endocrinopathy; and for some women, such as young women who are oophorectomized, it is an absolute endocrinopathy.

The International Menopause Society has published updated guidelines emphasizing that new data and reanalysis of older data show that for most women the benefits of menopausal hormone therapy are much greater than the risks, particularly when started within a few years of menopause.³

In Reply: We would like to thank Dr. Thacker for her interest in our article on the clinical considerations regarding optimal duration of hormone therapy.¹ We agree that the simple answer to whether there is there a time limit for systemic menopausal hormone therapy is no, emphasizing an individualized approach to each patient. After appropriate counseling and shared decision-making, some women may elect a short duration of therapy while others prefer longer-term use.

As Dr. Thacker mentioned, Mikkola et al² performed an observational study of more than 300,000 Finnish women who discontinued hormone therapy. Data on the number of deaths in this group were gathered from a national database and compared with the expected number of deaths in the background population; 30% of the listed causes of death were confirmed by autopsy. In women who had started hormone therapy before age 60, the risk of cardiac death was elevated within the first year after stopping it (standardized mortality ratio [SMR] 1.74; 95% confidence interval [CI] 1.37–2.19), as was the risk of stroke (SMR 2.59, 95% CI 2.08–3.19). This was not true in women who started hormone therapy at age 60 and older. These findings are consistent with our contemporary understanding that for many women younger than age 60 the benefits of hormone therapy outweigh the risks.

The study had several important limitations:

• A healthy-woman bias may have contributed to the reduction in cardiovascular risk.
• No dates for the myocardial infarctions or strokes were available, and the dates hormone therapy was discontined potentially had a 3-month error.
• No data were available on important confounding factors such as smoking, body mass index, blood pressure, lipid levels, and family history.
• Hormone therapy users were compared with an age-standardized background population, which also included hormone therapy users.
• Long-term follow-up data were also perplexing: although more women than expected died of stroke or coronary heart disease within the first year of stopping hormone therapy, after 1 year, significantly fewer women died of these conditions than expected, regardless of how long they had been on hormone therapy before stopping.

These observations highlight the need for long-term, randomized, prospective controlled studies that adequately assess all long-term outcomes (cardiovascular events, mortality, cancer, fracture) in women who initiate hormone therapy before age 60 and within 10 years of menopause, including long-term follow-up after discontinuation. Though future randomized controlled trials will be beneficial to help guide women to a more balanced understanding of long-term hormone therapy and the risks of discontinuation, the current evidence supports continuing hormone therapy in women who derive a net benefit.

In Reply: We would like to thank Dr. Thacker for her interest in our article on the clinical considerations regarding optimal duration of hormone therapy.¹ We agree that the simple answer to whether there is there a time limit for systemic menopausal hormone therapy is no, emphasizing an individualized approach to each patient. After appropriate counseling and shared decision-making, some women may elect a short duration of therapy while others prefer longer-term use.

As Dr. Thacker mentioned, Mikkola et al² performed an observational study of more than 300,000 Finnish women who discontinued hormone therapy. Data on the number of deaths in this group were gathered from a national database and compared with the expected number of deaths in the background population; 30% of the listed causes of death were confirmed by autopsy. In women who had started hormone therapy before age 60, the risk of cardiac death was elevated within the first year after stopping it (standardized mortality ratio [SMR] 1.74; 95% confidence interval [CI] 1.37–2.19), as was the risk of stroke (SMR 2.59, 95% CI 2.08–3.19). This was not true in women who started hormone therapy at age 60 and older. These findings are consistent with our contemporary understanding that for many women younger than age 60 the benefits of hormone therapy outweigh the risks.

The study had several important limitations:

• A healthy-woman bias may have contributed to the reduction in cardiovascular risk.
• No dates for the myocardial infarctions or strokes were available, and the dates hormone therapy was discontined potentially had a 3-month error.
• No data were available on important confounding factors such as smoking, body mass index, blood pressure, lipid levels, and family history.
• Hormone therapy users were compared with an age-standardized background population, which also included hormone therapy users.
• Long-term follow-up data were also perplexing: although more women than expected died of stroke or coronary heart disease within the first year of stopping hormone therapy, after 1 year, significantly fewer women died of these conditions than expected, regardless of how long they had been on hormone therapy before stopping.

These observations highlight the need for long-term, randomized, prospective controlled studies that adequately assess all long-term outcomes (cardiovascular events, mortality, cancer, fracture) in women who initiate hormone therapy before age 60 and within 10 years of menopause, including long-term follow-up after discontinuation. Though future randomized controlled trials will be beneficial to help guide women to a more balanced understanding of long-term hormone therapy and the risks of discontinuation, the current evidence supports continuing hormone therapy in women who derive a net benefit.

In Reply: We would like to thank Dr. Thacker for her interest in our article on the clinical considerations regarding optimal duration of hormone therapy.¹ We agree that the simple answer to whether there is there a time limit for systemic menopausal hormone therapy is no, emphasizing an individualized approach to each patient. After appropriate counseling and shared decision-making, some women may elect a short duration of therapy while others prefer longer-term use.

As Dr. Thacker mentioned, Mikkola et al² performed an observational study of more than 300,000 Finnish women who discontinued hormone therapy. Data on the number of deaths in this group were gathered from a national database and compared with the expected number of deaths in the background population; 30% of the listed causes of death were confirmed by autopsy. In women who had started hormone therapy before age 60, the risk of cardiac death was elevated within the first year after stopping it (standardized mortality ratio [SMR] 1.74; 95% confidence interval [CI] 1.37–2.19), as was the risk of stroke (SMR 2.59, 95% CI 2.08–3.19). This was not true in women who started hormone therapy at age 60 and older. These findings are consistent with our contemporary understanding that for many women younger than age 60 the benefits of hormone therapy outweigh the risks.

The study had several important limitations:

• A healthy-woman bias may have contributed to the reduction in cardiovascular risk.
• No dates for the myocardial infarctions or strokes were available, and the dates hormone therapy was discontined potentially had a 3-month error.
• No data were available on important confounding factors such as smoking, body mass index, blood pressure, lipid levels, and family history.
• Hormone therapy users were compared with an age-standardized background population, which also included hormone therapy users.
• Long-term follow-up data were also perplexing: although more women than expected died of stroke or coronary heart disease within the first year of stopping hormone therapy, after 1 year, significantly fewer women died of these conditions than expected, regardless of how long they had been on hormone therapy before stopping.

These observations highlight the need for long-term, randomized, prospective controlled studies that adequately assess all long-term outcomes (cardiovascular events, mortality, cancer, fracture) in women who initiate hormone therapy before age 60 and within 10 years of menopause, including long-term follow-up after discontinuation. Though future randomized controlled trials will be beneficial to help guide women to a more balanced understanding of long-term hormone therapy and the risks of discontinuation, the current evidence supports continuing hormone therapy in women who derive a net benefit.

Routine follow-up coronary angiography after percutaneous coronary intervention leads to increased rates of coronary revascularization but without any significant benefits for outcomes, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously on Nov. 1 in the Journal of the American College of Cardiology: Cardiovascular Interventions.

Hiroki Shiomi, MD, from Kyoto University, and his coauthors reported on ReACT, a prospective, open-label randomized controlled trial of routine follow-up coronary angiography in 700 patients who underwent successful percutaneous coronary intervention (PCI).

Among the 349 patients randomized to follow-up coronary angiography (FUCAG), 12.8% underwent any coronary revascularization within the first year after PCI, compared with 3.8% of the 351 patients randomized to standard clinical follow-up. The routine angiography group also had a higher incidence of target lesion revascularization in the first year after the index PCI (7.0% vs. 1.7%).

In both these cases, the cumulative 5-year incidence of coronary or target lesion revascularization was not significantly different between the routine angiography and control groups. However researchers saw no significant benefit from routine FUCAG in terms of the cumulative 5-year incidence of all-cause death, myocardial infarction, stroke, or emergency hospitalizations for acute coronary syndrome or heart failure, compared with clinical follow-up (22.4% vs. 24.7%; P = 0.70).

Nor were there any significant differences between the two groups in these individual components, or in the cumulative 5-year incidence of major bleeding (JACC Cardiovasc Interv. 2016 Nov 1.)

The authors commented that several previous studies have shown that routine FUCAG does not improve clinical outcomes, although it is still commonly performed in Japan after PCI.

“However, previous studies in the drug-eluting stents (DES) era were conducted in the context of pivotal randomized trials of DES and there have been no randomized clinical trials evaluating long-term clinical impact of routine FUCAG after PCI in the real world clinical practice including high-risk patients for cardiovascular events risk such as complex coronary artery disease and acute myocardial infarction (AMI) presentation,” the authors wrote.

Overall, 85.4% of patients in the routine angiography group and 12% of those in the clinical care group underwent coronary angiography in the first year, including for clinical reasons.

In the clinical follow-up group, coronary angiography was performed because of acute coronary syndrome (14%), recurrence of angina (60%), other clinical reasons (14%), or no clinical reason (12%). The control group also had more noninvasive physiological stress testing such as treadmill exercise test and stress nuclear study.

“Considering the invasive nature of coronary angiography and increased medical expenses, routine FUCAG after PCI would not be allowed as the usual clinical practice, unless patients have recurrent symptoms or objective evidence of ischemia,” the authors wrote.

“On the other hand, there was no excess of adverse clinical events with routine angiographic follow-up strategy except for the increased rate of 1-year repeat coronary revascularization.”

Given this, they suggested that scheduled angiographic follow-up might still be considered acceptable for early in vivo or significant coronary device trials.

While the authors said the trial ended up being underpowered because of a reduced final sample size and lower-than-anticipated event rate, it did warrant further larger-scale studies. In particular, they highlighted the question of what impact routine follow-up angiography might have in higher-risk patients, such as those with left main or multivessel coronary artery disease.

“Finally, because patient demographics, practice patterns including the indication of coronary revascularization, and clinical outcomes in Japan may be different from those outside Japan, generalizing the present study results to populations outside Japan should be done with caution.”

This study was supported by an educational grant from the Research Institute for Production Development (Kyoto). One author declared honoraria for education consulting from Boston Scientific Corporation.
 

Routine follow-up coronary angiography after percutaneous coronary intervention leads to increased rates of coronary revascularization but without any significant benefits for outcomes, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously on Nov. 1 in the Journal of the American College of Cardiology: Cardiovascular Interventions.

Hiroki Shiomi, MD, from Kyoto University, and his coauthors reported on ReACT, a prospective, open-label randomized controlled trial of routine follow-up coronary angiography in 700 patients who underwent successful percutaneous coronary intervention (PCI).

Among the 349 patients randomized to follow-up coronary angiography (FUCAG), 12.8% underwent any coronary revascularization within the first year after PCI, compared with 3.8% of the 351 patients randomized to standard clinical follow-up. The routine angiography group also had a higher incidence of target lesion revascularization in the first year after the index PCI (7.0% vs. 1.7%).

In both these cases, the cumulative 5-year incidence of coronary or target lesion revascularization was not significantly different between the routine angiography and control groups. However researchers saw no significant benefit from routine FUCAG in terms of the cumulative 5-year incidence of all-cause death, myocardial infarction, stroke, or emergency hospitalizations for acute coronary syndrome or heart failure, compared with clinical follow-up (22.4% vs. 24.7%; P = 0.70).

Nor were there any significant differences between the two groups in these individual components, or in the cumulative 5-year incidence of major bleeding (JACC Cardiovasc Interv. 2016 Nov 1.)

The authors commented that several previous studies have shown that routine FUCAG does not improve clinical outcomes, although it is still commonly performed in Japan after PCI.

“However, previous studies in the drug-eluting stents (DES) era were conducted in the context of pivotal randomized trials of DES and there have been no randomized clinical trials evaluating long-term clinical impact of routine FUCAG after PCI in the real world clinical practice including high-risk patients for cardiovascular events risk such as complex coronary artery disease and acute myocardial infarction (AMI) presentation,” the authors wrote.

Overall, 85.4% of patients in the routine angiography group and 12% of those in the clinical care group underwent coronary angiography in the first year, including for clinical reasons.

In the clinical follow-up group, coronary angiography was performed because of acute coronary syndrome (14%), recurrence of angina (60%), other clinical reasons (14%), or no clinical reason (12%). The control group also had more noninvasive physiological stress testing such as treadmill exercise test and stress nuclear study.

“Considering the invasive nature of coronary angiography and increased medical expenses, routine FUCAG after PCI would not be allowed as the usual clinical practice, unless patients have recurrent symptoms or objective evidence of ischemia,” the authors wrote.

“On the other hand, there was no excess of adverse clinical events with routine angiographic follow-up strategy except for the increased rate of 1-year repeat coronary revascularization.”

Given this, they suggested that scheduled angiographic follow-up might still be considered acceptable for early in vivo or significant coronary device trials.

While the authors said the trial ended up being underpowered because of a reduced final sample size and lower-than-anticipated event rate, it did warrant further larger-scale studies. In particular, they highlighted the question of what impact routine follow-up angiography might have in higher-risk patients, such as those with left main or multivessel coronary artery disease.

“Finally, because patient demographics, practice patterns including the indication of coronary revascularization, and clinical outcomes in Japan may be different from those outside Japan, generalizing the present study results to populations outside Japan should be done with caution.”

This study was supported by an educational grant from the Research Institute for Production Development (Kyoto). One author declared honoraria for education consulting from Boston Scientific Corporation.
 

Routine follow-up coronary angiography after percutaneous coronary intervention leads to increased rates of coronary revascularization but without any significant benefits for outcomes, according to a study presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously on Nov. 1 in the Journal of the American College of Cardiology: Cardiovascular Interventions.

Hiroki Shiomi, MD, from Kyoto University, and his coauthors reported on ReACT, a prospective, open-label randomized controlled trial of routine follow-up coronary angiography in 700 patients who underwent successful percutaneous coronary intervention (PCI).

Among the 349 patients randomized to follow-up coronary angiography (FUCAG), 12.8% underwent any coronary revascularization within the first year after PCI, compared with 3.8% of the 351 patients randomized to standard clinical follow-up. The routine angiography group also had a higher incidence of target lesion revascularization in the first year after the index PCI (7.0% vs. 1.7%).

In both these cases, the cumulative 5-year incidence of coronary or target lesion revascularization was not significantly different between the routine angiography and control groups. However researchers saw no significant benefit from routine FUCAG in terms of the cumulative 5-year incidence of all-cause death, myocardial infarction, stroke, or emergency hospitalizations for acute coronary syndrome or heart failure, compared with clinical follow-up (22.4% vs. 24.7%; P = 0.70).

Nor were there any significant differences between the two groups in these individual components, or in the cumulative 5-year incidence of major bleeding (JACC Cardiovasc Interv. 2016 Nov 1.)

The authors commented that several previous studies have shown that routine FUCAG does not improve clinical outcomes, although it is still commonly performed in Japan after PCI.

“However, previous studies in the drug-eluting stents (DES) era were conducted in the context of pivotal randomized trials of DES and there have been no randomized clinical trials evaluating long-term clinical impact of routine FUCAG after PCI in the real world clinical practice including high-risk patients for cardiovascular events risk such as complex coronary artery disease and acute myocardial infarction (AMI) presentation,” the authors wrote.

Overall, 85.4% of patients in the routine angiography group and 12% of those in the clinical care group underwent coronary angiography in the first year, including for clinical reasons.

In the clinical follow-up group, coronary angiography was performed because of acute coronary syndrome (14%), recurrence of angina (60%), other clinical reasons (14%), or no clinical reason (12%). The control group also had more noninvasive physiological stress testing such as treadmill exercise test and stress nuclear study.

“Considering the invasive nature of coronary angiography and increased medical expenses, routine FUCAG after PCI would not be allowed as the usual clinical practice, unless patients have recurrent symptoms or objective evidence of ischemia,” the authors wrote.

“On the other hand, there was no excess of adverse clinical events with routine angiographic follow-up strategy except for the increased rate of 1-year repeat coronary revascularization.”

Given this, they suggested that scheduled angiographic follow-up might still be considered acceptable for early in vivo or significant coronary device trials.

While the authors said the trial ended up being underpowered because of a reduced final sample size and lower-than-anticipated event rate, it did warrant further larger-scale studies. In particular, they highlighted the question of what impact routine follow-up angiography might have in higher-risk patients, such as those with left main or multivessel coronary artery disease.

“Finally, because patient demographics, practice patterns including the indication of coronary revascularization, and clinical outcomes in Japan may be different from those outside Japan, generalizing the present study results to populations outside Japan should be done with caution.”

This study was supported by an educational grant from the Research Institute for Production Development (Kyoto). One author declared honoraria for education consulting from Boston Scientific Corporation.
 

ROME – Temporary interruption of oral anticoagulation for stroke prevention in patients with atrial fibrillation occurs often and is associated with substantially increased risk of both cardioembolic events and all-cause mortality, according to a new prespecified secondary analysis of the ENGAGE-AF TIMI 48 trial.

The analysis showed that many of these treatment interruptions occur in response to nonserious adverse events such as minor bleeding, planned dental procedures, or simply because of patient wishes. The new ENGAGE-AF TIMI 48 findings should encourage physicians and patients to think twice before interrupting anticoagulant therapy for such reasons, which look pretty flimsy in light of the new evidence of the potentially serious consequences, Ilaria Cavallari, MD, said at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

bjancin@frontlinemedcom.com

ROME – Temporary interruption of oral anticoagulation for stroke prevention in patients with atrial fibrillation occurs often and is associated with substantially increased risk of both cardioembolic events and all-cause mortality, according to a new prespecified secondary analysis of the ENGAGE-AF TIMI 48 trial.

The analysis showed that many of these treatment interruptions occur in response to nonserious adverse events such as minor bleeding, planned dental procedures, or simply because of patient wishes. The new ENGAGE-AF TIMI 48 findings should encourage physicians and patients to think twice before interrupting anticoagulant therapy for such reasons, which look pretty flimsy in light of the new evidence of the potentially serious consequences, Ilaria Cavallari, MD, said at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

bjancin@frontlinemedcom.com

ROME – Temporary interruption of oral anticoagulation for stroke prevention in patients with atrial fibrillation occurs often and is associated with substantially increased risk of both cardioembolic events and all-cause mortality, according to a new prespecified secondary analysis of the ENGAGE-AF TIMI 48 trial.

The analysis showed that many of these treatment interruptions occur in response to nonserious adverse events such as minor bleeding, planned dental procedures, or simply because of patient wishes. The new ENGAGE-AF TIMI 48 findings should encourage physicians and patients to think twice before interrupting anticoagulant therapy for such reasons, which look pretty flimsy in light of the new evidence of the potentially serious consequences, Ilaria Cavallari, MD, said at the annual congress of the European Society of Cardiology.

Bruce Jancin/Frontline Medical News

bjancin@frontlinemedcom.com

PORTLAND, OR—Combining trans­cranial direct current stimulation (tDCS) and cognitive training resulted in an improvement in a greater number of cognitive outcomes than either intervention alone in a small, randomized, controlled trial of patients with Parkinson’s disease and mild cognitive impairment.

Researchers at Curtin University in Perth, Australia, conducted the trial comparing the effects of standard (ie, not individualized) cognitive training (SCT), tailored (ie, individualized) cognitive training (TCT), tDCS, and a combination of tDCS with either form of cognitive training on cognitive outcomes, activities of daily living, and quality of life. Previously, it was not known whether either form of cognitive training, tDCS, or a combination of the two would be most efficacious in improving cognition.

“Executive function, attention and working memory, memory, and language were the cognitive domains that improved for some groups, and we also found that activities of daily living and quality of life improved for the different groups as well,” PhD candidate Blake Lawrence said at the Fourth World Parkinson Congress.

Patients had cognitive deficits that did not interfere with functional independence and were responding to stable doses of antiparkinsonian medication. Forty-two eligible participants underwent neuropsychologic testing at baseline and were randomly and equally assigned to one of the following six groups: SCT, TCT, tDCS, SCT+tDCS, TCT+tDCS, or control.

Cognitive training consisted of three 45-minute sessions per week for four weeks using Smartbrain Pro software in participants’ homes. tDCS involved constant 1.5-mA stimulation for 20 minutes in one session per week for four weeks at the university, with the anode placed over area F3 to stimulate the left dorsal lateral prefrontal cortex. Neuropsychologic testing was conducted post intervention (ie, at five weeks). Follow-up evaluations were at 12 weeks.

The researchers administered tests to evaluate executive function (Stockings of Cambridge), attention and working memory (Stroop test), memory (paragraph recall), quality of life (Parkinson’s Disease Questionnaire), activities of daily living (Unified Parkinson’s Disease Rating Scale-II), and language (similarities test). In general, combining tDCS with either form of cognitive training resulted in significantly greater improvements in more outcomes than any of the modalities alone. SCT showed positive results when compared against the control group in memory improvement at follow-up (effect size, 1.30), as well as in quality of life and activities of daily living post intervention (effect sizes, 0.24 and 0.33, respectively). TCT showed benefits on quality of life at both time points (effect sizes, 0.26 and 0.12, respectively).

When combined with tDCS, SCT produced improvements in attention and working memory both post intervention and at 12-week follow-up (effect sizes, 0.60 and 0.24, respectively), and executive function at post intervention and follow-up (0.41 and 0.23, respectively). Improvement in activities of daily living and language were statistically significant only immediately post intervention.

Combining tDCS with TCT resulted in improvements post intervention and at follow-up on measures of memory (1.36 and 1.75, respectively) and executive function (0.19 and 0.92, respectively), as well as in language post intervention (1.06).

“The groups that completed both cognitive training and brain stimulation improved to a greater extent and in more outcomes than the groups that just completed the brain training or the stimulation individually,” Mr. Lawrence said. “The majority of the effects were shown immediately after the intervention, but some of the promising results ... actually maintained improvement at the 12-week follow-up, so that was after about eight weeks, when they did not complete any intervention whatsoever.”

The improvements are probably clinically meaningful to patients, since they themselves reported the outcomes on quality of life and activities of daily living scales, he said.

—Daniel M. Keller

PORTLAND, OR—Combining trans­cranial direct current stimulation (tDCS) and cognitive training resulted in an improvement in a greater number of cognitive outcomes than either intervention alone in a small, randomized, controlled trial of patients with Parkinson’s disease and mild cognitive impairment.

Researchers at Curtin University in Perth, Australia, conducted the trial comparing the effects of standard (ie, not individualized) cognitive training (SCT), tailored (ie, individualized) cognitive training (TCT), tDCS, and a combination of tDCS with either form of cognitive training on cognitive outcomes, activities of daily living, and quality of life. Previously, it was not known whether either form of cognitive training, tDCS, or a combination of the two would be most efficacious in improving cognition.

“Executive function, attention and working memory, memory, and language were the cognitive domains that improved for some groups, and we also found that activities of daily living and quality of life improved for the different groups as well,” PhD candidate Blake Lawrence said at the Fourth World Parkinson Congress.

Patients had cognitive deficits that did not interfere with functional independence and were responding to stable doses of antiparkinsonian medication. Forty-two eligible participants underwent neuropsychologic testing at baseline and were randomly and equally assigned to one of the following six groups: SCT, TCT, tDCS, SCT+tDCS, TCT+tDCS, or control.

Cognitive training consisted of three 45-minute sessions per week for four weeks using Smartbrain Pro software in participants’ homes. tDCS involved constant 1.5-mA stimulation for 20 minutes in one session per week for four weeks at the university, with the anode placed over area F3 to stimulate the left dorsal lateral prefrontal cortex. Neuropsychologic testing was conducted post intervention (ie, at five weeks). Follow-up evaluations were at 12 weeks.

The researchers administered tests to evaluate executive function (Stockings of Cambridge), attention and working memory (Stroop test), memory (paragraph recall), quality of life (Parkinson’s Disease Questionnaire), activities of daily living (Unified Parkinson’s Disease Rating Scale-II), and language (similarities test). In general, combining tDCS with either form of cognitive training resulted in significantly greater improvements in more outcomes than any of the modalities alone. SCT showed positive results when compared against the control group in memory improvement at follow-up (effect size, 1.30), as well as in quality of life and activities of daily living post intervention (effect sizes, 0.24 and 0.33, respectively). TCT showed benefits on quality of life at both time points (effect sizes, 0.26 and 0.12, respectively).

When combined with tDCS, SCT produced improvements in attention and working memory both post intervention and at 12-week follow-up (effect sizes, 0.60 and 0.24, respectively), and executive function at post intervention and follow-up (0.41 and 0.23, respectively). Improvement in activities of daily living and language were statistically significant only immediately post intervention.

Combining tDCS with TCT resulted in improvements post intervention and at follow-up on measures of memory (1.36 and 1.75, respectively) and executive function (0.19 and 0.92, respectively), as well as in language post intervention (1.06).

“The groups that completed both cognitive training and brain stimulation improved to a greater extent and in more outcomes than the groups that just completed the brain training or the stimulation individually,” Mr. Lawrence said. “The majority of the effects were shown immediately after the intervention, but some of the promising results ... actually maintained improvement at the 12-week follow-up, so that was after about eight weeks, when they did not complete any intervention whatsoever.”

The improvements are probably clinically meaningful to patients, since they themselves reported the outcomes on quality of life and activities of daily living scales, he said.

—Daniel M. Keller

PORTLAND, OR—Combining trans­cranial direct current stimulation (tDCS) and cognitive training resulted in an improvement in a greater number of cognitive outcomes than either intervention alone in a small, randomized, controlled trial of patients with Parkinson’s disease and mild cognitive impairment.

Researchers at Curtin University in Perth, Australia, conducted the trial comparing the effects of standard (ie, not individualized) cognitive training (SCT), tailored (ie, individualized) cognitive training (TCT), tDCS, and a combination of tDCS with either form of cognitive training on cognitive outcomes, activities of daily living, and quality of life. Previously, it was not known whether either form of cognitive training, tDCS, or a combination of the two would be most efficacious in improving cognition.

“Executive function, attention and working memory, memory, and language were the cognitive domains that improved for some groups, and we also found that activities of daily living and quality of life improved for the different groups as well,” PhD candidate Blake Lawrence said at the Fourth World Parkinson Congress.

Patients had cognitive deficits that did not interfere with functional independence and were responding to stable doses of antiparkinsonian medication. Forty-two eligible participants underwent neuropsychologic testing at baseline and were randomly and equally assigned to one of the following six groups: SCT, TCT, tDCS, SCT+tDCS, TCT+tDCS, or control.

Cognitive training consisted of three 45-minute sessions per week for four weeks using Smartbrain Pro software in participants’ homes. tDCS involved constant 1.5-mA stimulation for 20 minutes in one session per week for four weeks at the university, with the anode placed over area F3 to stimulate the left dorsal lateral prefrontal cortex. Neuropsychologic testing was conducted post intervention (ie, at five weeks). Follow-up evaluations were at 12 weeks.

The researchers administered tests to evaluate executive function (Stockings of Cambridge), attention and working memory (Stroop test), memory (paragraph recall), quality of life (Parkinson’s Disease Questionnaire), activities of daily living (Unified Parkinson’s Disease Rating Scale-II), and language (similarities test). In general, combining tDCS with either form of cognitive training resulted in significantly greater improvements in more outcomes than any of the modalities alone. SCT showed positive results when compared against the control group in memory improvement at follow-up (effect size, 1.30), as well as in quality of life and activities of daily living post intervention (effect sizes, 0.24 and 0.33, respectively). TCT showed benefits on quality of life at both time points (effect sizes, 0.26 and 0.12, respectively).

When combined with tDCS, SCT produced improvements in attention and working memory both post intervention and at 12-week follow-up (effect sizes, 0.60 and 0.24, respectively), and executive function at post intervention and follow-up (0.41 and 0.23, respectively). Improvement in activities of daily living and language were statistically significant only immediately post intervention.

Combining tDCS with TCT resulted in improvements post intervention and at follow-up on measures of memory (1.36 and 1.75, respectively) and executive function (0.19 and 0.92, respectively), as well as in language post intervention (1.06).

“The groups that completed both cognitive training and brain stimulation improved to a greater extent and in more outcomes than the groups that just completed the brain training or the stimulation individually,” Mr. Lawrence said. “The majority of the effects were shown immediately after the intervention, but some of the promising results ... actually maintained improvement at the 12-week follow-up, so that was after about eight weeks, when they did not complete any intervention whatsoever.”

The improvements are probably clinically meaningful to patients, since they themselves reported the outcomes on quality of life and activities of daily living scales, he said.

—Daniel M. Keller

Patients with advanced cancer should receive dedicated palliative care services early in the disease course, concurrently with active treatment, according to the American Society of Clinical Oncology’s new guidelines on the integration of palliative care into standard oncology care.

Ideally, patients should be referred to interdisciplinary palliative care teams within 8 weeks of cancer diagnosis, and palliative care should be available in both the inpatient and outpatient setting, recommended ASCO.

The guidelines, which updated and expanded the 2012 ASCO provisional clinical opinion, were developed by a multidisciplinary expert panel that systematically reviewed phase III randomized controlled trials, secondary analyses of those trials, and meta-analyses that were published between March 2010 and January 2016.

According to the panel, essential components of palliative care include:
 

• Rapport and relationship building with patient and family caregivers.

• Symptom, distress, and functional status management.

• Exploration of understanding and education about illness and prognosis.

• Clarification of treatment goals.

• Assessment and support of coping needs.

• Assistance with medical decision making.

The panel makes the case that not only does palliative care improve care for patients and families, it also likely reduces the total cost of care, often substantially. However, “race, poverty and low socioeconomic and/or immigration status are determinants of barriers to palliative care,” wrote the expert panel, which was cochaired by Betty Ferrell, PhD, of the City of Hope Medical Center, Duarte, Calif., and Thomas Smith, MD, of the Sidney Kimmel Comprehensive Cancer Center in Baltimore.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

Patients with advanced cancer should receive dedicated palliative care services early in the disease course, concurrently with active treatment, according to the American Society of Clinical Oncology’s new guidelines on the integration of palliative care into standard oncology care.

Ideally, patients should be referred to interdisciplinary palliative care teams within 8 weeks of cancer diagnosis, and palliative care should be available in both the inpatient and outpatient setting, recommended ASCO.

The guidelines, which updated and expanded the 2012 ASCO provisional clinical opinion, were developed by a multidisciplinary expert panel that systematically reviewed phase III randomized controlled trials, secondary analyses of those trials, and meta-analyses that were published between March 2010 and January 2016.

According to the panel, essential components of palliative care include:
 

• Rapport and relationship building with patient and family caregivers.

• Symptom, distress, and functional status management.

• Exploration of understanding and education about illness and prognosis.

• Clarification of treatment goals.

• Assessment and support of coping needs.

• Assistance with medical decision making.

The panel makes the case that not only does palliative care improve care for patients and families, it also likely reduces the total cost of care, often substantially. However, “race, poverty and low socioeconomic and/or immigration status are determinants of barriers to palliative care,” wrote the expert panel, which was cochaired by Betty Ferrell, PhD, of the City of Hope Medical Center, Duarte, Calif., and Thomas Smith, MD, of the Sidney Kimmel Comprehensive Cancer Center in Baltimore.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

Patients with advanced cancer should receive dedicated palliative care services early in the disease course, concurrently with active treatment, according to the American Society of Clinical Oncology’s new guidelines on the integration of palliative care into standard oncology care.

Ideally, patients should be referred to interdisciplinary palliative care teams within 8 weeks of cancer diagnosis, and palliative care should be available in both the inpatient and outpatient setting, recommended ASCO.

The guidelines, which updated and expanded the 2012 ASCO provisional clinical opinion, were developed by a multidisciplinary expert panel that systematically reviewed phase III randomized controlled trials, secondary analyses of those trials, and meta-analyses that were published between March 2010 and January 2016.

According to the panel, essential components of palliative care include:
 

• Rapport and relationship building with patient and family caregivers.

• Symptom, distress, and functional status management.

• Exploration of understanding and education about illness and prognosis.

• Clarification of treatment goals.

• Assessment and support of coping needs.

• Assistance with medical decision making.

The panel makes the case that not only does palliative care improve care for patients and families, it also likely reduces the total cost of care, often substantially. However, “race, poverty and low socioeconomic and/or immigration status are determinants of barriers to palliative care,” wrote the expert panel, which was cochaired by Betty Ferrell, PhD, of the City of Hope Medical Center, Duarte, Calif., and Thomas Smith, MD, of the Sidney Kimmel Comprehensive Cancer Center in Baltimore.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

Each year the American Academy of Pediatrics National Conference and Exhibition fills a huge convention hall with the latest products that can improve health and generate practice revenue.

Some products are solutions to the minor annoyances of everyday practice. For instance, there are ear curettes equipped with their own LED light and a magnifying lens. There are countless creams to treat rashes. There are new automated devices for testing hearing, vision, and attention. And at the far extreme, there are products with the potential to revolutionize clinical care or to bankrupt it. The latest technology in that category is whole exome sequencing.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis.

Each year the American Academy of Pediatrics National Conference and Exhibition fills a huge convention hall with the latest products that can improve health and generate practice revenue.

Some products are solutions to the minor annoyances of everyday practice. For instance, there are ear curettes equipped with their own LED light and a magnifying lens. There are countless creams to treat rashes. There are new automated devices for testing hearing, vision, and attention. And at the far extreme, there are products with the potential to revolutionize clinical care or to bankrupt it. The latest technology in that category is whole exome sequencing.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis.

Each year the American Academy of Pediatrics National Conference and Exhibition fills a huge convention hall with the latest products that can improve health and generate practice revenue.

Some products are solutions to the minor annoyances of everyday practice. For instance, there are ear curettes equipped with their own LED light and a magnifying lens. There are countless creams to treat rashes. There are new automated devices for testing hearing, vision, and attention. And at the far extreme, there are products with the potential to revolutionize clinical care or to bankrupt it. The latest technology in that category is whole exome sequencing.

Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis.

Answer to “What’s your diagnosis?” on page X: Collagenous gastritis and collagenous sprue

Recent studies have also shown the importance of obtaining at least 1 biopsy from the duodenal bulb to avoid missing the diagnosis of celiac disease. In 126 patients with newly established celiac disease and 85 patients with a previous diagnosis on a gluten-free diet presenting for reevaluation, villous atrophy was limited to the duodenal bulb in 9% and 14% of cases, respectively.3

References

1. Brain, O., Rajaguru, C., Warren, B. et al. Collagenous gastritis: reports and systematic review. Eur J Gastroenterol Hepatol. 2009;21:1419-24.

2. Gopal, P., McKenna, B.J. The collagenous gastroenteritides: similarities and differences. Arch Pathol Lab Med. 2010;134:1485-9.

3. Evans, K.E., Aziz, I., Cross, S.S. et al. A prospective study of duodenal bulb biopsy in newly diagnosed and established adult celiac disease. Am J Gastroenterol. 2011;106:1837-742.

Answer to “What’s your diagnosis?” on page X: Collagenous gastritis and collagenous sprue

Recent studies have also shown the importance of obtaining at least 1 biopsy from the duodenal bulb to avoid missing the diagnosis of celiac disease. In 126 patients with newly established celiac disease and 85 patients with a previous diagnosis on a gluten-free diet presenting for reevaluation, villous atrophy was limited to the duodenal bulb in 9% and 14% of cases, respectively.3

References

1. Brain, O., Rajaguru, C., Warren, B. et al. Collagenous gastritis: reports and systematic review. Eur J Gastroenterol Hepatol. 2009;21:1419-24.

2. Gopal, P., McKenna, B.J. The collagenous gastroenteritides: similarities and differences. Arch Pathol Lab Med. 2010;134:1485-9.

3. Evans, K.E., Aziz, I., Cross, S.S. et al. A prospective study of duodenal bulb biopsy in newly diagnosed and established adult celiac disease. Am J Gastroenterol. 2011;106:1837-742.

Answer to “What’s your diagnosis?” on page X: Collagenous gastritis and collagenous sprue

Recent studies have also shown the importance of obtaining at least 1 biopsy from the duodenal bulb to avoid missing the diagnosis of celiac disease. In 126 patients with newly established celiac disease and 85 patients with a previous diagnosis on a gluten-free diet presenting for reevaluation, villous atrophy was limited to the duodenal bulb in 9% and 14% of cases, respectively.3

References

1. Brain, O., Rajaguru, C., Warren, B. et al. Collagenous gastritis: reports and systematic review. Eur J Gastroenterol Hepatol. 2009;21:1419-24.

2. Gopal, P., McKenna, B.J. The collagenous gastroenteritides: similarities and differences. Arch Pathol Lab Med. 2010;134:1485-9.

3. Evans, K.E., Aziz, I., Cross, S.S. et al. A prospective study of duodenal bulb biopsy in newly diagnosed and established adult celiac disease. Am J Gastroenterol. 2011;106:1837-742.

The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during transcatheter aortic valve replacement yielded puzzling and somewhat contradictory results, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.

Virtually every device in this industry-sponsored study involving 363 elderly patients (mean age, 83.4 years) with severe aortic stenosis trapped particulate debris as intended, the mean volume of new lesions in the protected areas of the brain was reduced by 42%, and the number and volume of new lesions correlated with neurocognitive outcomes at 30 days.

However, the reduction in lesion volume did not achieve statistical significance, and the improvement in neurocognitive function also did not reach statistical significance.

In addition, “the sample size was clearly too low to assess clinical outcomes, and in retrospect, was also too low to evaluate follow-up MRI findings or neurocognitive outcomes.” Nevertheless, the trial “provides reassuring evidence of device safety,” said Samir R. Kapadia, MD, of the Cleveland Clinic (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.023).

In this prospective study, the investigators assessed patients at 17 medical centers in the United States and 2 in Germany. In addition to being elderly, the study patients were at high risk because of frequent comorbidities, including atrial fibrillation (31.7%) and prior stroke (5.8%).

cardnews@frontlinemedcom.com

The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during transcatheter aortic valve replacement yielded puzzling and somewhat contradictory results, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.

Virtually every device in this industry-sponsored study involving 363 elderly patients (mean age, 83.4 years) with severe aortic stenosis trapped particulate debris as intended, the mean volume of new lesions in the protected areas of the brain was reduced by 42%, and the number and volume of new lesions correlated with neurocognitive outcomes at 30 days.

However, the reduction in lesion volume did not achieve statistical significance, and the improvement in neurocognitive function also did not reach statistical significance.

In addition, “the sample size was clearly too low to assess clinical outcomes, and in retrospect, was also too low to evaluate follow-up MRI findings or neurocognitive outcomes.” Nevertheless, the trial “provides reassuring evidence of device safety,” said Samir R. Kapadia, MD, of the Cleveland Clinic (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.023).

In this prospective study, the investigators assessed patients at 17 medical centers in the United States and 2 in Germany. In addition to being elderly, the study patients were at high risk because of frequent comorbidities, including atrial fibrillation (31.7%) and prior stroke (5.8%).

cardnews@frontlinemedcom.com

The largest randomized clinical trial to assess the safety and efficacy of cerebral embolic protection systems during transcatheter aortic valve replacement yielded puzzling and somewhat contradictory results, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the Journal of the American College of Cardiology.

Virtually every device in this industry-sponsored study involving 363 elderly patients (mean age, 83.4 years) with severe aortic stenosis trapped particulate debris as intended, the mean volume of new lesions in the protected areas of the brain was reduced by 42%, and the number and volume of new lesions correlated with neurocognitive outcomes at 30 days.

However, the reduction in lesion volume did not achieve statistical significance, and the improvement in neurocognitive function also did not reach statistical significance.

In addition, “the sample size was clearly too low to assess clinical outcomes, and in retrospect, was also too low to evaluate follow-up MRI findings or neurocognitive outcomes.” Nevertheless, the trial “provides reassuring evidence of device safety,” said Samir R. Kapadia, MD, of the Cleveland Clinic (J Am Coll Cardiol. 2016 Nov 1. doi: 10.1016/j.jacc.2016.10.023).

In this prospective study, the investigators assessed patients at 17 medical centers in the United States and 2 in Germany. In addition to being elderly, the study patients were at high risk because of frequent comorbidities, including atrial fibrillation (31.7%) and prior stroke (5.8%).

cardnews@frontlinemedcom.com