The health care sector is not immune from cybersecurity attacks (malicious attempts to access or damage a computer or network system). Between October 2019 and October 2021, 857 data breaches were reported to the United States Department of Health and Human Services.¹ The 3 main types of breaches reported were theft, hacking/IT incident, or unauthorized access/disclosure.¹ Health care has become a common target due to the availability of valuable patient information (health, personal, and financial), the industry’s financial stability and resource capacity, and network susceptibility.² The top 2 cybersecurity threats facing physician practices are:

• ransomware attacks, in which an external party uses a type of malicious software (malware) that prevents you from accessing your computer files, systems, or networks, and demands you pay a ransom for their return.
• employee-related threats, such as the theft or destruction of sensitive information by a disgruntled employee.³

The financial implications of health care–related cybersecurity threats coupled with exposure to potential litigation associated with breaches of confidentiality result in a need to “cybersecure” your practice.² In this article, I outline steps to take to protect your practice against such threats. Although the recommendations I provide will increase your practice’s cybersecurity fortification, they are not exhaustive, and you may need to consult with an IT specialist to help protect your data and network.

Improve your network protection. A broadband internet connection is always operating, which makes it continuously susceptible to cybersecurity attacks. Install a firewall (a network security system that monitors and controls network traffic and permits or blocks traffic based on a defined set of rules) between your practice’s internal computer network and the internet.⁴ For maximum protection, enable all available firewall settings in your operating software.² Prevent unauthorized access by ensuring that all network passwords are strong (ie, they include a combination of uppercase and lowercase letters, numbers, and symbols). Consider using different networks for online communication and for storing sensitive information.² Create separate Wi-Fi networks for your practice and for your patients, and use unique passwords for each that are not easily guessed.⁴ If you or your employees use a virtual private network (VPN) to remotely access your practice’s network, ensure that all devices used to do so (cell phones, tablets, etc) are encrypted and secured with strong passwords.

Reduce employee-related threats. Not every employee in your practice will need to access to your patients’ clinical or financial data. Limiting employee access to sensitive clinical or financial data can reduce the risks of employee-related cybersecurity threats.³ In addition, restrict an employee’s ability to install software on computers and other devices that belong to your practice.²

Frequently incorporate cybersecurity training, such as teaching your employees about the risks of clicking on links and attachments in emails and how to identify phishing attacks (in which an individual sends a fraudulent communication that appears to come from a reputable source in order to trick the recipient into revealing financial information, system credentials, or other sensitive data).^2,3 Use multifactor authentication to verify an employee’s login identity, and change passwords often. Reinforce these policies at staff meetings and educate new employees about this process.³ If you need to fire an employee, consider deploying cybersurveillance software to monitor the behavior of all employees before the employee is terminated.³ Once the employee has been terminated, change all logins and passwords.

The health care sector is not immune from cybersecurity attacks (malicious attempts to access or damage a computer or network system). Between October 2019 and October 2021, 857 data breaches were reported to the United States Department of Health and Human Services.¹ The 3 main types of breaches reported were theft, hacking/IT incident, or unauthorized access/disclosure.¹ Health care has become a common target due to the availability of valuable patient information (health, personal, and financial), the industry’s financial stability and resource capacity, and network susceptibility.² The top 2 cybersecurity threats facing physician practices are:

• ransomware attacks, in which an external party uses a type of malicious software (malware) that prevents you from accessing your computer files, systems, or networks, and demands you pay a ransom for their return.
• employee-related threats, such as the theft or destruction of sensitive information by a disgruntled employee.³

The financial implications of health care–related cybersecurity threats coupled with exposure to potential litigation associated with breaches of confidentiality result in a need to “cybersecure” your practice.² In this article, I outline steps to take to protect your practice against such threats. Although the recommendations I provide will increase your practice’s cybersecurity fortification, they are not exhaustive, and you may need to consult with an IT specialist to help protect your data and network.

Improve your network protection. A broadband internet connection is always operating, which makes it continuously susceptible to cybersecurity attacks. Install a firewall (a network security system that monitors and controls network traffic and permits or blocks traffic based on a defined set of rules) between your practice’s internal computer network and the internet.⁴ For maximum protection, enable all available firewall settings in your operating software.² Prevent unauthorized access by ensuring that all network passwords are strong (ie, they include a combination of uppercase and lowercase letters, numbers, and symbols). Consider using different networks for online communication and for storing sensitive information.² Create separate Wi-Fi networks for your practice and for your patients, and use unique passwords for each that are not easily guessed.⁴ If you or your employees use a virtual private network (VPN) to remotely access your practice’s network, ensure that all devices used to do so (cell phones, tablets, etc) are encrypted and secured with strong passwords.

Reduce employee-related threats. Not every employee in your practice will need to access to your patients’ clinical or financial data. Limiting employee access to sensitive clinical or financial data can reduce the risks of employee-related cybersecurity threats.³ In addition, restrict an employee’s ability to install software on computers and other devices that belong to your practice.²

Frequently incorporate cybersecurity training, such as teaching your employees about the risks of clicking on links and attachments in emails and how to identify phishing attacks (in which an individual sends a fraudulent communication that appears to come from a reputable source in order to trick the recipient into revealing financial information, system credentials, or other sensitive data).^2,3 Use multifactor authentication to verify an employee’s login identity, and change passwords often. Reinforce these policies at staff meetings and educate new employees about this process.³ If you need to fire an employee, consider deploying cybersurveillance software to monitor the behavior of all employees before the employee is terminated.³ Once the employee has been terminated, change all logins and passwords.

The health care sector is not immune from cybersecurity attacks (malicious attempts to access or damage a computer or network system). Between October 2019 and October 2021, 857 data breaches were reported to the United States Department of Health and Human Services.¹ The 3 main types of breaches reported were theft, hacking/IT incident, or unauthorized access/disclosure.¹ Health care has become a common target due to the availability of valuable patient information (health, personal, and financial), the industry’s financial stability and resource capacity, and network susceptibility.² The top 2 cybersecurity threats facing physician practices are:

• ransomware attacks, in which an external party uses a type of malicious software (malware) that prevents you from accessing your computer files, systems, or networks, and demands you pay a ransom for their return.
• employee-related threats, such as the theft or destruction of sensitive information by a disgruntled employee.³

The financial implications of health care–related cybersecurity threats coupled with exposure to potential litigation associated with breaches of confidentiality result in a need to “cybersecure” your practice.² In this article, I outline steps to take to protect your practice against such threats. Although the recommendations I provide will increase your practice’s cybersecurity fortification, they are not exhaustive, and you may need to consult with an IT specialist to help protect your data and network.

Improve your network protection. A broadband internet connection is always operating, which makes it continuously susceptible to cybersecurity attacks. Install a firewall (a network security system that monitors and controls network traffic and permits or blocks traffic based on a defined set of rules) between your practice’s internal computer network and the internet.⁴ For maximum protection, enable all available firewall settings in your operating software.² Prevent unauthorized access by ensuring that all network passwords are strong (ie, they include a combination of uppercase and lowercase letters, numbers, and symbols). Consider using different networks for online communication and for storing sensitive information.² Create separate Wi-Fi networks for your practice and for your patients, and use unique passwords for each that are not easily guessed.⁴ If you or your employees use a virtual private network (VPN) to remotely access your practice’s network, ensure that all devices used to do so (cell phones, tablets, etc) are encrypted and secured with strong passwords.

Reduce employee-related threats. Not every employee in your practice will need to access to your patients’ clinical or financial data. Limiting employee access to sensitive clinical or financial data can reduce the risks of employee-related cybersecurity threats.³ In addition, restrict an employee’s ability to install software on computers and other devices that belong to your practice.²

Frequently incorporate cybersecurity training, such as teaching your employees about the risks of clicking on links and attachments in emails and how to identify phishing attacks (in which an individual sends a fraudulent communication that appears to come from a reputable source in order to trick the recipient into revealing financial information, system credentials, or other sensitive data).^2,3 Use multifactor authentication to verify an employee’s login identity, and change passwords often. Reinforce these policies at staff meetings and educate new employees about this process.³ If you need to fire an employee, consider deploying cybersurveillance software to monitor the behavior of all employees before the employee is terminated.³ Once the employee has been terminated, change all logins and passwords.

Psychiatrists who treat women of childbearing age should consider that those women may become pregnant, and that women with psychiatric illness are more likely to have unplanned pregnancies.¹ Thus, thoughtful perinatal medication choices should begin before pregnancy. Pregnancy is a time of vulnerability to psychiatric illness for many reasons, including physiologic changes that can affect mental status; changes in medication efficacy; and numerous stressors, such as new responsibilities and limited sleep.^1,2 For the treatment of pregnant—or potentially pregnant—patients, we recommend the following.

Do not panic! Knee-jerk medication changes in response to learning a patient is pregnant can lead to an exacerbation of psychiatric symptoms, as well as decrease trust in clinicians.² Switching to a medication with a purportedly “safer” reproductive profile may worsen psychiatric illness, while also exposing the fetus to a medication of unknown benefit. ²

Recognize the risk of untreated or undertreated psychiatric illness, either of which has the potential to harm both the woman and her fetus. For example, a pregnant woman in a manic state may be more likely to engage in risky behaviors, such as drug use or risky sexual activity, which can lead to adverse fetal outcomes. They may also present with a higher risk of suicide. Compared to nonpregnant women, pregnant women for whom lithium was discontinued were equally likely to experience illness recurrence and significantly more likely to experience postpartum illness recurrence.³ In addition, the risk of recurrence was greater after rapid discontinuation compared with gradual discontinuation.³

Accurately communicate research findings. Pregnancy risk categories are no longer used. A nuanced interpretation of the potential adverse effects of a medication, such as malformations, impaired fetal growth, birth outcomes (such as preterm birth), and neurodevelopmental sequelae is necessary. Physicians must accurately convey information about risks to their patients, including both the absolute risk of an adverse event and the possible range of severity. For example, lithium use during pregnancy confers a higher relative risk of Ebstein’s anomaly (a cardiac defect).⁴ However, the absolute incidence of this risk remains low: 0.6% of lithium-exposed infants vs 0.18% among unexposed infants.⁴ Ebstein’s anomaly also varies significantly in severity—serious cases may require surgery, but less serious cases need only monitoring. A reliable database that compiles the latest evidence may help in staying abreast of the latest data.

Treat the psychiatric illness. Consider the optimal treatment for the psychiatric illness. Lithium remains the gold standard treatment for bipolar I disorder, regardless of reproductive status. Olanzapine and quetiapine are also commonly used and effective during pregnancy. This is an opportunity to conduct a detailed review of the patient’s previous medication regimens, including a review of medication trials and efficacy. Keep in mind that untreated bipolar disorder also carries an increased risk of adverse pregnancy outcomes.⁵

Consider pregnancy timing. Most organs form between weeks 3 to 8 of pregnancy. For example, if a medication potentially affects heart formation, but the patient is in the third trimester, explain to her that the heart has already been formed. Consider that medication may be required long-term and affect future pregnancies. Pregnant women require more frequent monitoring, because blood volume changes in pregnancy and postpartum can affect medication levels and efficacy. In addition, note whether a woman plans to breastfeed and be mindful of a medication’s profile in breastfeeding.

Ensure the patient can provide informed consent. Communicate your diagnostic formulation and treatment options. Consider involving the patient’s partner and/or support system in the discussion, if the patient consents. If a patient cannot provide informed consent, a surrogate decision-maker should be identified.⁶

Continue to: Collaborate with other clinicians

Collaborate with other clinicians, such as the patient’s OB/GYN and family medicine physician when possible. This will ensure that all clinicians are on the same page.

Plan for future pregnancies. Psychiatric medications can be long-term. Even patients who say they do not wish to become pregnant may someday become pregnant. Having discussions about medication choices, and their reproductive implications, prior to pregnancy allows patients to take an active role in their health.^1,2

Consult a reproductive psychiatrist when indicated, and as early in the pregnancy as possible.

Psychiatrists who treat women of childbearing age should consider that those women may become pregnant, and that women with psychiatric illness are more likely to have unplanned pregnancies.¹ Thus, thoughtful perinatal medication choices should begin before pregnancy. Pregnancy is a time of vulnerability to psychiatric illness for many reasons, including physiologic changes that can affect mental status; changes in medication efficacy; and numerous stressors, such as new responsibilities and limited sleep.^1,2 For the treatment of pregnant—or potentially pregnant—patients, we recommend the following.

Do not panic! Knee-jerk medication changes in response to learning a patient is pregnant can lead to an exacerbation of psychiatric symptoms, as well as decrease trust in clinicians.² Switching to a medication with a purportedly “safer” reproductive profile may worsen psychiatric illness, while also exposing the fetus to a medication of unknown benefit. ²

Recognize the risk of untreated or undertreated psychiatric illness, either of which has the potential to harm both the woman and her fetus. For example, a pregnant woman in a manic state may be more likely to engage in risky behaviors, such as drug use or risky sexual activity, which can lead to adverse fetal outcomes. They may also present with a higher risk of suicide. Compared to nonpregnant women, pregnant women for whom lithium was discontinued were equally likely to experience illness recurrence and significantly more likely to experience postpartum illness recurrence.³ In addition, the risk of recurrence was greater after rapid discontinuation compared with gradual discontinuation.³

Accurately communicate research findings. Pregnancy risk categories are no longer used. A nuanced interpretation of the potential adverse effects of a medication, such as malformations, impaired fetal growth, birth outcomes (such as preterm birth), and neurodevelopmental sequelae is necessary. Physicians must accurately convey information about risks to their patients, including both the absolute risk of an adverse event and the possible range of severity. For example, lithium use during pregnancy confers a higher relative risk of Ebstein’s anomaly (a cardiac defect).⁴ However, the absolute incidence of this risk remains low: 0.6% of lithium-exposed infants vs 0.18% among unexposed infants.⁴ Ebstein’s anomaly also varies significantly in severity—serious cases may require surgery, but less serious cases need only monitoring. A reliable database that compiles the latest evidence may help in staying abreast of the latest data.

Treat the psychiatric illness. Consider the optimal treatment for the psychiatric illness. Lithium remains the gold standard treatment for bipolar I disorder, regardless of reproductive status. Olanzapine and quetiapine are also commonly used and effective during pregnancy. This is an opportunity to conduct a detailed review of the patient’s previous medication regimens, including a review of medication trials and efficacy. Keep in mind that untreated bipolar disorder also carries an increased risk of adverse pregnancy outcomes.⁵

Consider pregnancy timing. Most organs form between weeks 3 to 8 of pregnancy. For example, if a medication potentially affects heart formation, but the patient is in the third trimester, explain to her that the heart has already been formed. Consider that medication may be required long-term and affect future pregnancies. Pregnant women require more frequent monitoring, because blood volume changes in pregnancy and postpartum can affect medication levels and efficacy. In addition, note whether a woman plans to breastfeed and be mindful of a medication’s profile in breastfeeding.

Ensure the patient can provide informed consent. Communicate your diagnostic formulation and treatment options. Consider involving the patient’s partner and/or support system in the discussion, if the patient consents. If a patient cannot provide informed consent, a surrogate decision-maker should be identified.⁶

Continue to: Collaborate with other clinicians

Collaborate with other clinicians, such as the patient’s OB/GYN and family medicine physician when possible. This will ensure that all clinicians are on the same page.

Plan for future pregnancies. Psychiatric medications can be long-term. Even patients who say they do not wish to become pregnant may someday become pregnant. Having discussions about medication choices, and their reproductive implications, prior to pregnancy allows patients to take an active role in their health.^1,2

Consult a reproductive psychiatrist when indicated, and as early in the pregnancy as possible.

Psychiatrists who treat women of childbearing age should consider that those women may become pregnant, and that women with psychiatric illness are more likely to have unplanned pregnancies.¹ Thus, thoughtful perinatal medication choices should begin before pregnancy. Pregnancy is a time of vulnerability to psychiatric illness for many reasons, including physiologic changes that can affect mental status; changes in medication efficacy; and numerous stressors, such as new responsibilities and limited sleep.^1,2 For the treatment of pregnant—or potentially pregnant—patients, we recommend the following.

Do not panic! Knee-jerk medication changes in response to learning a patient is pregnant can lead to an exacerbation of psychiatric symptoms, as well as decrease trust in clinicians.² Switching to a medication with a purportedly “safer” reproductive profile may worsen psychiatric illness, while also exposing the fetus to a medication of unknown benefit. ²

Recognize the risk of untreated or undertreated psychiatric illness, either of which has the potential to harm both the woman and her fetus. For example, a pregnant woman in a manic state may be more likely to engage in risky behaviors, such as drug use or risky sexual activity, which can lead to adverse fetal outcomes. They may also present with a higher risk of suicide. Compared to nonpregnant women, pregnant women for whom lithium was discontinued were equally likely to experience illness recurrence and significantly more likely to experience postpartum illness recurrence.³ In addition, the risk of recurrence was greater after rapid discontinuation compared with gradual discontinuation.³

Accurately communicate research findings. Pregnancy risk categories are no longer used. A nuanced interpretation of the potential adverse effects of a medication, such as malformations, impaired fetal growth, birth outcomes (such as preterm birth), and neurodevelopmental sequelae is necessary. Physicians must accurately convey information about risks to their patients, including both the absolute risk of an adverse event and the possible range of severity. For example, lithium use during pregnancy confers a higher relative risk of Ebstein’s anomaly (a cardiac defect).⁴ However, the absolute incidence of this risk remains low: 0.6% of lithium-exposed infants vs 0.18% among unexposed infants.⁴ Ebstein’s anomaly also varies significantly in severity—serious cases may require surgery, but less serious cases need only monitoring. A reliable database that compiles the latest evidence may help in staying abreast of the latest data.

Treat the psychiatric illness. Consider the optimal treatment for the psychiatric illness. Lithium remains the gold standard treatment for bipolar I disorder, regardless of reproductive status. Olanzapine and quetiapine are also commonly used and effective during pregnancy. This is an opportunity to conduct a detailed review of the patient’s previous medication regimens, including a review of medication trials and efficacy. Keep in mind that untreated bipolar disorder also carries an increased risk of adverse pregnancy outcomes.⁵

Consider pregnancy timing. Most organs form between weeks 3 to 8 of pregnancy. For example, if a medication potentially affects heart formation, but the patient is in the third trimester, explain to her that the heart has already been formed. Consider that medication may be required long-term and affect future pregnancies. Pregnant women require more frequent monitoring, because blood volume changes in pregnancy and postpartum can affect medication levels and efficacy. In addition, note whether a woman plans to breastfeed and be mindful of a medication’s profile in breastfeeding.

Ensure the patient can provide informed consent. Communicate your diagnostic formulation and treatment options. Consider involving the patient’s partner and/or support system in the discussion, if the patient consents. If a patient cannot provide informed consent, a surrogate decision-maker should be identified.⁶

Continue to: Collaborate with other clinicians

Collaborate with other clinicians, such as the patient’s OB/GYN and family medicine physician when possible. This will ensure that all clinicians are on the same page.

Plan for future pregnancies. Psychiatric medications can be long-term. Even patients who say they do not wish to become pregnant may someday become pregnant. Having discussions about medication choices, and their reproductive implications, prior to pregnancy allows patients to take an active role in their health.^1,2

Consult a reproductive psychiatrist when indicated, and as early in the pregnancy as possible.

Loneliness is distress that occurs when the quality or quantity of social relationships are less than desired.¹ It is a symptom of many psychiatric disorders, and can lead to multiple negative health consequences, including depression, sleep deprivation, executive dysfunction, accelerated cognitive decline, and hypertension. Loneliness can increase the likelihood of immunocompromising conditions, including (but not limited to) stroke, anxiety, and depression, resulting in frequent emergency department visits and costly health expenses.² Up to 80% of individuals younger than age 18 and 40% of adults older than age 65 report being lonely at least sometimes, with levels of loneliness gradually diminishing during middle age and then increasing in older adults.¹ Loneliness is such a common and pervasive problem that in 2017, the government of the United Kingdom created a commission on loneliness and developed a Minister of Loneliness to find solutions to reduce it.³ In this article, I discuss the detrimental impact loneliness can have on our patients, and steps we can take to address it.

What contributes to loneliness?

Most people prefer the company of others, but some psychiatric disorders can cause individuals to become antisocial. For example, patients with schizoid personality disorder avoid social activities and interaction with others. Other patients may want to form bonds with others but their psychiatric disorder hinders this. For example, those with paranoia and social anxiety may avoid interacting with people due to their mistrust of others or their actions. Patients with substance use disorders can drive away those closest to them and lose familial bonds as a result of their behaviors. Patients with depression might not have the energy to pursue relationships and often have faulty cognitive patterns that lead them to believe they are unloved and unwanted.

Situational factors play a significant role in feelings of loneliness. Loss of a job or friends, ending a relationship, death of a loved one, or social isolation as experienced by COVID-19 or other illnesses can lead to loneliness. Social factors such as lack of income or transportation can make it difficult to attend or take part in social activities and events.

Some patients with dementia express feeling lonely, even after a visit from loved ones, because they forget the visit occurred. Nursing home residents often experience loneliness. Children may feel lonely after being subjected to bullying. College students, especially freshmen who are away from home for the first time, report significant levels of loneliness. Members of the LGBTQ+ community are often lonely due to familial rejection, prejudice, and religious beliefs. Anyone can experience loneliness, even married individuals if the marriage is unsatisfying.

What can psychiatry do to help?

Fortunately, psychiatric clinicians can play a large role in helping patients with loneliness.

Assessment. Ask the patient about the status of their present relationships and if they are feeling lonely. If yes, ask additional questions to identify possible causes. Are there conflicts that can be resolved? Is there abuse? What do they believe is the cause of their loneliness, and what might be the solution? How would their life be different if they weren’t lonely?

Treatment. When indicated, pharmacologic interventions might relieve symptoms that interfere with relationships and social interactions. For example, several types of antidepressants can improve mood and reduce anxiety, and selective serotonin reuptake inhibitors may relieve panic symptoms. Benzodiazepines and beta-blockers can reduce symptoms of social anxiety. Antipsychotics can reduce paranoia. Stimulants can aid patients with attention-deficit/hyperactivity disorder by improving their ability to interact with others.

Continue to: Psychotherapy and counseling...

Psychotherapy and counseling can specifically target loneliness. Solution-focused therapy, for example, involves solving the problem by deciding which actions the patient needs to take to relieve symptoms of loneliness. Dialectal behavior therapy can help patients with borderline and other personality disorders regulate their emotions and accept their feelings. Cognitive therapy and rational emotive therapy use various techniques to assist patients in changing their negative thought patterns. For example, a therapist might assign a patient to introduce themselves to a stranger or attend an event with others. The assignment is then discussed at the next session. Client-centered, psychodynamic, and behavior therapies also may be appropriate for a patient experiencing loneliness. Positive psychology can aid patients by helping them appreciate and not discount others in their lives. Meditation and mindfulness can motivate individuals to live in the present and enjoy those around them.

Referral and psychosocial support can be offered to direct patients to social services for help in improving their living circumstances. For example, a patient with an alcohol use disorder may benefit from a referral to a self-help organization such as Alcoholics Anonymous, where they can receive additional support and develop friendships. Other resources might offer patients the ability to discuss solutions, such as the benefits of owning a pet, attending a class, or volunteering opportunities, to combat loneliness.

Living a purposeful life is essential to engaging with others and avoiding isolation. Many people have turned to online support rooms, chat rooms, gaming, and social media to maintain relationships and meet others. Excessive computer use can be detrimental, however, if used in a manner that doesn’t involve interaction with others.

Regardless of the specific intervention, psychiatrists and other psychiatric clinicians can play a major role in reducing a patient’s loneliness. Simply by being present, you are showing the patient that at least one person in their life listens and cares.

Loneliness is distress that occurs when the quality or quantity of social relationships are less than desired.¹ It is a symptom of many psychiatric disorders, and can lead to multiple negative health consequences, including depression, sleep deprivation, executive dysfunction, accelerated cognitive decline, and hypertension. Loneliness can increase the likelihood of immunocompromising conditions, including (but not limited to) stroke, anxiety, and depression, resulting in frequent emergency department visits and costly health expenses.² Up to 80% of individuals younger than age 18 and 40% of adults older than age 65 report being lonely at least sometimes, with levels of loneliness gradually diminishing during middle age and then increasing in older adults.¹ Loneliness is such a common and pervasive problem that in 2017, the government of the United Kingdom created a commission on loneliness and developed a Minister of Loneliness to find solutions to reduce it.³ In this article, I discuss the detrimental impact loneliness can have on our patients, and steps we can take to address it.

What contributes to loneliness?

Most people prefer the company of others, but some psychiatric disorders can cause individuals to become antisocial. For example, patients with schizoid personality disorder avoid social activities and interaction with others. Other patients may want to form bonds with others but their psychiatric disorder hinders this. For example, those with paranoia and social anxiety may avoid interacting with people due to their mistrust of others or their actions. Patients with substance use disorders can drive away those closest to them and lose familial bonds as a result of their behaviors. Patients with depression might not have the energy to pursue relationships and often have faulty cognitive patterns that lead them to believe they are unloved and unwanted.

Situational factors play a significant role in feelings of loneliness. Loss of a job or friends, ending a relationship, death of a loved one, or social isolation as experienced by COVID-19 or other illnesses can lead to loneliness. Social factors such as lack of income or transportation can make it difficult to attend or take part in social activities and events.

Some patients with dementia express feeling lonely, even after a visit from loved ones, because they forget the visit occurred. Nursing home residents often experience loneliness. Children may feel lonely after being subjected to bullying. College students, especially freshmen who are away from home for the first time, report significant levels of loneliness. Members of the LGBTQ+ community are often lonely due to familial rejection, prejudice, and religious beliefs. Anyone can experience loneliness, even married individuals if the marriage is unsatisfying.

What can psychiatry do to help?

Fortunately, psychiatric clinicians can play a large role in helping patients with loneliness.

Assessment. Ask the patient about the status of their present relationships and if they are feeling lonely. If yes, ask additional questions to identify possible causes. Are there conflicts that can be resolved? Is there abuse? What do they believe is the cause of their loneliness, and what might be the solution? How would their life be different if they weren’t lonely?

Treatment. When indicated, pharmacologic interventions might relieve symptoms that interfere with relationships and social interactions. For example, several types of antidepressants can improve mood and reduce anxiety, and selective serotonin reuptake inhibitors may relieve panic symptoms. Benzodiazepines and beta-blockers can reduce symptoms of social anxiety. Antipsychotics can reduce paranoia. Stimulants can aid patients with attention-deficit/hyperactivity disorder by improving their ability to interact with others.

Continue to: Psychotherapy and counseling...

Psychotherapy and counseling can specifically target loneliness. Solution-focused therapy, for example, involves solving the problem by deciding which actions the patient needs to take to relieve symptoms of loneliness. Dialectal behavior therapy can help patients with borderline and other personality disorders regulate their emotions and accept their feelings. Cognitive therapy and rational emotive therapy use various techniques to assist patients in changing their negative thought patterns. For example, a therapist might assign a patient to introduce themselves to a stranger or attend an event with others. The assignment is then discussed at the next session. Client-centered, psychodynamic, and behavior therapies also may be appropriate for a patient experiencing loneliness. Positive psychology can aid patients by helping them appreciate and not discount others in their lives. Meditation and mindfulness can motivate individuals to live in the present and enjoy those around them.

Referral and psychosocial support can be offered to direct patients to social services for help in improving their living circumstances. For example, a patient with an alcohol use disorder may benefit from a referral to a self-help organization such as Alcoholics Anonymous, where they can receive additional support and develop friendships. Other resources might offer patients the ability to discuss solutions, such as the benefits of owning a pet, attending a class, or volunteering opportunities, to combat loneliness.

Living a purposeful life is essential to engaging with others and avoiding isolation. Many people have turned to online support rooms, chat rooms, gaming, and social media to maintain relationships and meet others. Excessive computer use can be detrimental, however, if used in a manner that doesn’t involve interaction with others.

Regardless of the specific intervention, psychiatrists and other psychiatric clinicians can play a major role in reducing a patient’s loneliness. Simply by being present, you are showing the patient that at least one person in their life listens and cares.

Loneliness is distress that occurs when the quality or quantity of social relationships are less than desired.¹ It is a symptom of many psychiatric disorders, and can lead to multiple negative health consequences, including depression, sleep deprivation, executive dysfunction, accelerated cognitive decline, and hypertension. Loneliness can increase the likelihood of immunocompromising conditions, including (but not limited to) stroke, anxiety, and depression, resulting in frequent emergency department visits and costly health expenses.² Up to 80% of individuals younger than age 18 and 40% of adults older than age 65 report being lonely at least sometimes, with levels of loneliness gradually diminishing during middle age and then increasing in older adults.¹ Loneliness is such a common and pervasive problem that in 2017, the government of the United Kingdom created a commission on loneliness and developed a Minister of Loneliness to find solutions to reduce it.³ In this article, I discuss the detrimental impact loneliness can have on our patients, and steps we can take to address it.

What contributes to loneliness?

Most people prefer the company of others, but some psychiatric disorders can cause individuals to become antisocial. For example, patients with schizoid personality disorder avoid social activities and interaction with others. Other patients may want to form bonds with others but their psychiatric disorder hinders this. For example, those with paranoia and social anxiety may avoid interacting with people due to their mistrust of others or their actions. Patients with substance use disorders can drive away those closest to them and lose familial bonds as a result of their behaviors. Patients with depression might not have the energy to pursue relationships and often have faulty cognitive patterns that lead them to believe they are unloved and unwanted.

Situational factors play a significant role in feelings of loneliness. Loss of a job or friends, ending a relationship, death of a loved one, or social isolation as experienced by COVID-19 or other illnesses can lead to loneliness. Social factors such as lack of income or transportation can make it difficult to attend or take part in social activities and events.

Some patients with dementia express feeling lonely, even after a visit from loved ones, because they forget the visit occurred. Nursing home residents often experience loneliness. Children may feel lonely after being subjected to bullying. College students, especially freshmen who are away from home for the first time, report significant levels of loneliness. Members of the LGBTQ+ community are often lonely due to familial rejection, prejudice, and religious beliefs. Anyone can experience loneliness, even married individuals if the marriage is unsatisfying.

What can psychiatry do to help?

Fortunately, psychiatric clinicians can play a large role in helping patients with loneliness.

Assessment. Ask the patient about the status of their present relationships and if they are feeling lonely. If yes, ask additional questions to identify possible causes. Are there conflicts that can be resolved? Is there abuse? What do they believe is the cause of their loneliness, and what might be the solution? How would their life be different if they weren’t lonely?

Treatment. When indicated, pharmacologic interventions might relieve symptoms that interfere with relationships and social interactions. For example, several types of antidepressants can improve mood and reduce anxiety, and selective serotonin reuptake inhibitors may relieve panic symptoms. Benzodiazepines and beta-blockers can reduce symptoms of social anxiety. Antipsychotics can reduce paranoia. Stimulants can aid patients with attention-deficit/hyperactivity disorder by improving their ability to interact with others.

Continue to: Psychotherapy and counseling...

Psychotherapy and counseling can specifically target loneliness. Solution-focused therapy, for example, involves solving the problem by deciding which actions the patient needs to take to relieve symptoms of loneliness. Dialectal behavior therapy can help patients with borderline and other personality disorders regulate their emotions and accept their feelings. Cognitive therapy and rational emotive therapy use various techniques to assist patients in changing their negative thought patterns. For example, a therapist might assign a patient to introduce themselves to a stranger or attend an event with others. The assignment is then discussed at the next session. Client-centered, psychodynamic, and behavior therapies also may be appropriate for a patient experiencing loneliness. Positive psychology can aid patients by helping them appreciate and not discount others in their lives. Meditation and mindfulness can motivate individuals to live in the present and enjoy those around them.

Referral and psychosocial support can be offered to direct patients to social services for help in improving their living circumstances. For example, a patient with an alcohol use disorder may benefit from a referral to a self-help organization such as Alcoholics Anonymous, where they can receive additional support and develop friendships. Other resources might offer patients the ability to discuss solutions, such as the benefits of owning a pet, attending a class, or volunteering opportunities, to combat loneliness.

Living a purposeful life is essential to engaging with others and avoiding isolation. Many people have turned to online support rooms, chat rooms, gaming, and social media to maintain relationships and meet others. Excessive computer use can be detrimental, however, if used in a manner that doesn’t involve interaction with others.

Regardless of the specific intervention, psychiatrists and other psychiatric clinicians can play a major role in reducing a patient’s loneliness. Simply by being present, you are showing the patient that at least one person in their life listens and cares.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact letters@currentpsychiatry.com.

As we see the end of the COVID-19 era through a collective windshield, there is hope and optimism at the exit ramps ahead of us. This unforeseen era has brought not only unprecedented change to the practice of medicine, but also a resurgent focus on the impact of medical care. The rapid adoption of telemedicine, the medical heroism lauded in the press during the early days of the pandemic, and the subsequent psychosocial impact of quarantines and lockdowns have brought increased attention to our citizens’ mental health, and not just during a crisis, but in a more holistic sense.

In fact, with the most recent annual Presidential State of the Union Address, mental health has finally received an invitation to the national agenda.  This is an admirable achievement, a nod from Uncle Sam that says, “Here’s your seat at the table.” Now that we have earned this seat, have we improved our understanding of mental illness, treatment options, and our access to them? Or have we lost sight of our real challenges? Shouldn’t achieving national prominence have resulted in newfound treatments and strategies to increase access and understanding?

Instead, we are still touting the same (although perhaps nuanced) monoamine hypothesis underlying most of our conditions, as we have for decades.  Vast areas of the country are out of reach of a local psychiatrist. Our treatments, largely centered on medications, though hopeful and promising at times, would fall short of the hurdle to become mainstay treatments in other medical specialties. Of course, the counterpoints are obvious: there are novel treatments (eg, ketamine, transcranial magnetic stimulation) and new understandings of glutamate and gamma aminobutyric acid systems in mood regulation and addiction. We also can use telemedicine to improve access to psychiatric care in underserved areas. But the overarching truth remains: an understanding of psychiatric illnesses, specifically the pathophysiology underlying those conditions, remains elusive or partially understood. Until we have a pathophysiology to treat, we can only continue to describe phenomenology and treat symptomatology.

Since we are treating symptoms, we must rely on verbal descriptions of psychiatric conditions. Descriptions and discussions of mental illness have pervaded the airwaves and media. It is not uncommon or unusual to hear people talk about depression, anxiety, insomnia, addiction, or even psychosis in a very normal, unjarring way.  These words, which represent severe medical conditions, have now become part of the national nosology and colloquial description of individuals’ day-to-day lives.  Have we stripped the severity and seriousness of our conditions from their descriptors in order to increase awareness and make mental health care a more “normal” part of health care?

We see it in clinics, the media, our schools, and our workplaces. Children and teens are talking about social anxiety because they feel a bit nervous on stage as their part in a school play begins. Teens are asking for extra time on a difficult test in a challenging class that is supposed to be strenuous. Employees are asking for mental health leave when a demanding new boss arrives on the scene.

Has our own campaign to increase awareness and destigmatize mental illness caused it to become diluted? Have we raised awareness by diluting its severity and seriousness, by making our nosology equivalent to everyday stressors? Was this a marketing strategy, a failure of our own nosology, or an inadvertent fallout of a decades-long campaign to raise mental health awareness?

Continue to: Until we have clear...

Until we have clear, delineated pathophysiology to treat, we will remain wed to our descriptive nosology. This nosology is flawed, at times ambiguous and overlapping, and now has become diluted to be more palatable to a national and consumer audience.  

So yes, let’s grab a chair at the national table, but let’s make sure we’re not just chairwarmers. It’s time we redouble our focus on unraveling the pathophysiology of psychiatric illnesses, and to focus on a new scientific nosology, as opposed to our current, almost colloquial and now diluted descriptors that may raise awareness but do little to advance a real understanding of mental illness.  A more holistic understanding of the pathophysiology of psychiatric disorders may provide us with a more scientific nosology. Ultimately, we can hope for more effective, and perhaps even curative treatments. That, my colleagues, is what will give us not just a seat at the table, but maybe even a table of our own.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact letters@currentpsychiatry.com.

As we see the end of the COVID-19 era through a collective windshield, there is hope and optimism at the exit ramps ahead of us. This unforeseen era has brought not only unprecedented change to the practice of medicine, but also a resurgent focus on the impact of medical care. The rapid adoption of telemedicine, the medical heroism lauded in the press during the early days of the pandemic, and the subsequent psychosocial impact of quarantines and lockdowns have brought increased attention to our citizens’ mental health, and not just during a crisis, but in a more holistic sense.

In fact, with the most recent annual Presidential State of the Union Address, mental health has finally received an invitation to the national agenda.  This is an admirable achievement, a nod from Uncle Sam that says, “Here’s your seat at the table.” Now that we have earned this seat, have we improved our understanding of mental illness, treatment options, and our access to them? Or have we lost sight of our real challenges? Shouldn’t achieving national prominence have resulted in newfound treatments and strategies to increase access and understanding?

Instead, we are still touting the same (although perhaps nuanced) monoamine hypothesis underlying most of our conditions, as we have for decades.  Vast areas of the country are out of reach of a local psychiatrist. Our treatments, largely centered on medications, though hopeful and promising at times, would fall short of the hurdle to become mainstay treatments in other medical specialties. Of course, the counterpoints are obvious: there are novel treatments (eg, ketamine, transcranial magnetic stimulation) and new understandings of glutamate and gamma aminobutyric acid systems in mood regulation and addiction. We also can use telemedicine to improve access to psychiatric care in underserved areas. But the overarching truth remains: an understanding of psychiatric illnesses, specifically the pathophysiology underlying those conditions, remains elusive or partially understood. Until we have a pathophysiology to treat, we can only continue to describe phenomenology and treat symptomatology.

Since we are treating symptoms, we must rely on verbal descriptions of psychiatric conditions. Descriptions and discussions of mental illness have pervaded the airwaves and media. It is not uncommon or unusual to hear people talk about depression, anxiety, insomnia, addiction, or even psychosis in a very normal, unjarring way.  These words, which represent severe medical conditions, have now become part of the national nosology and colloquial description of individuals’ day-to-day lives.  Have we stripped the severity and seriousness of our conditions from their descriptors in order to increase awareness and make mental health care a more “normal” part of health care?

We see it in clinics, the media, our schools, and our workplaces. Children and teens are talking about social anxiety because they feel a bit nervous on stage as their part in a school play begins. Teens are asking for extra time on a difficult test in a challenging class that is supposed to be strenuous. Employees are asking for mental health leave when a demanding new boss arrives on the scene.

Has our own campaign to increase awareness and destigmatize mental illness caused it to become diluted? Have we raised awareness by diluting its severity and seriousness, by making our nosology equivalent to everyday stressors? Was this a marketing strategy, a failure of our own nosology, or an inadvertent fallout of a decades-long campaign to raise mental health awareness?

Continue to: Until we have clear...

Until we have clear, delineated pathophysiology to treat, we will remain wed to our descriptive nosology. This nosology is flawed, at times ambiguous and overlapping, and now has become diluted to be more palatable to a national and consumer audience.  

So yes, let’s grab a chair at the national table, but let’s make sure we’re not just chairwarmers. It’s time we redouble our focus on unraveling the pathophysiology of psychiatric illnesses, and to focus on a new scientific nosology, as opposed to our current, almost colloquial and now diluted descriptors that may raise awareness but do little to advance a real understanding of mental illness.  A more holistic understanding of the pathophysiology of psychiatric disorders may provide us with a more scientific nosology. Ultimately, we can hope for more effective, and perhaps even curative treatments. That, my colleagues, is what will give us not just a seat at the table, but maybe even a table of our own.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact letters@currentpsychiatry.com.

As we see the end of the COVID-19 era through a collective windshield, there is hope and optimism at the exit ramps ahead of us. This unforeseen era has brought not only unprecedented change to the practice of medicine, but also a resurgent focus on the impact of medical care. The rapid adoption of telemedicine, the medical heroism lauded in the press during the early days of the pandemic, and the subsequent psychosocial impact of quarantines and lockdowns have brought increased attention to our citizens’ mental health, and not just during a crisis, but in a more holistic sense.

In fact, with the most recent annual Presidential State of the Union Address, mental health has finally received an invitation to the national agenda.  This is an admirable achievement, a nod from Uncle Sam that says, “Here’s your seat at the table.” Now that we have earned this seat, have we improved our understanding of mental illness, treatment options, and our access to them? Or have we lost sight of our real challenges? Shouldn’t achieving national prominence have resulted in newfound treatments and strategies to increase access and understanding?

Instead, we are still touting the same (although perhaps nuanced) monoamine hypothesis underlying most of our conditions, as we have for decades.  Vast areas of the country are out of reach of a local psychiatrist. Our treatments, largely centered on medications, though hopeful and promising at times, would fall short of the hurdle to become mainstay treatments in other medical specialties. Of course, the counterpoints are obvious: there are novel treatments (eg, ketamine, transcranial magnetic stimulation) and new understandings of glutamate and gamma aminobutyric acid systems in mood regulation and addiction. We also can use telemedicine to improve access to psychiatric care in underserved areas. But the overarching truth remains: an understanding of psychiatric illnesses, specifically the pathophysiology underlying those conditions, remains elusive or partially understood. Until we have a pathophysiology to treat, we can only continue to describe phenomenology and treat symptomatology.

Since we are treating symptoms, we must rely on verbal descriptions of psychiatric conditions. Descriptions and discussions of mental illness have pervaded the airwaves and media. It is not uncommon or unusual to hear people talk about depression, anxiety, insomnia, addiction, or even psychosis in a very normal, unjarring way.  These words, which represent severe medical conditions, have now become part of the national nosology and colloquial description of individuals’ day-to-day lives.  Have we stripped the severity and seriousness of our conditions from their descriptors in order to increase awareness and make mental health care a more “normal” part of health care?

We see it in clinics, the media, our schools, and our workplaces. Children and teens are talking about social anxiety because they feel a bit nervous on stage as their part in a school play begins. Teens are asking for extra time on a difficult test in a challenging class that is supposed to be strenuous. Employees are asking for mental health leave when a demanding new boss arrives on the scene.

Has our own campaign to increase awareness and destigmatize mental illness caused it to become diluted? Have we raised awareness by diluting its severity and seriousness, by making our nosology equivalent to everyday stressors? Was this a marketing strategy, a failure of our own nosology, or an inadvertent fallout of a decades-long campaign to raise mental health awareness?

Continue to: Until we have clear...

Until we have clear, delineated pathophysiology to treat, we will remain wed to our descriptive nosology. This nosology is flawed, at times ambiguous and overlapping, and now has become diluted to be more palatable to a national and consumer audience.  

So yes, let’s grab a chair at the national table, but let’s make sure we’re not just chairwarmers. It’s time we redouble our focus on unraveling the pathophysiology of psychiatric illnesses, and to focus on a new scientific nosology, as opposed to our current, almost colloquial and now diluted descriptors that may raise awareness but do little to advance a real understanding of mental illness.  A more holistic understanding of the pathophysiology of psychiatric disorders may provide us with a more scientific nosology. Ultimately, we can hope for more effective, and perhaps even curative treatments. That, my colleagues, is what will give us not just a seat at the table, but maybe even a table of our own.

Oh, great!” a senior resident sardonically remarked with a smirk as they read up on the next patient in the clinic. “A borderline patient. Get ready for a rough one ... Ugh.”

Before ever stepping foot into the patient’s room, this resident had prematurely established and demonstrated an unfortunate dynamic for any student or trainee within earshot. This is an all-too-familiar occurrence when caring for individuals with borderline personality disorder (BPD), or any other patients deemed to be “difficult.” The patient, however, likely walked into the room with a traumatic past that they continue to suffer from, in addition to any other issues for which they were seeking care.

Consider what these patients have experienced

A typical profile of these resilient patients with BPD: They were born emotionally sensitive. They grew up in homes with caretakers who knowingly or unknowingly invalidated their complaints about having their feelings hurt, about being abused emotionally, sexually, or otherwise, or about their worries concerning their interactions with peers at school. These caretakers may have been frightening and unpredictable, randomly showing affection or arbitrarily punishing for any perceived misstep, which led these patients to develop (for their own safety’s sake) a hypersensitivity to the affect of others. Their wariness and distrust of their social surroundings may have led to a skeptical view of kindness from others. Over time, without any guidance from prior demonstrations of healthy coping skills or interpersonal outlets from their caregivers, the emotional pressure builds. This pressure finally erupts in the form of impulsivity, self-harm, desperation, and defensiveness—in other words, survival. This is often followed by these patients’ first experience with receiving some degree of appropriate response to their complaints—their first experience with feeling seen and heard by their caretakers. They learn that their needs are met only when they cry out in desperation.^1-3

These patients typically bring these maladaptive coping skills with them into adulthood, which often leads to a series of intense, unhealthy, and short-lived interpersonal and professional connections. They desire healthy, lasting connections with others, but through no fault of their own are unable to appropriately manage the normal stressors therein.¹ Often, these patients do not know of their eventual BPD diagnosis, or even reject it due to its ever-negative valence. For other patients, receiving a personality disorder diagnosis is incredibly validating because they are no longer alone regarding this type of suffering, and a doctor—a caretaker—is finally making sense of this tumultuous world.

The countertransference of frustration, anxiety, doubt, and annoyance we may feel when caring for patients with BPD pales in comparison to living in their shoes and carrying the weight of what they have had to endure before presenting to our care. As these resilient patients wait in the exam room for the chance to be heard, let this be a reminder to greet them with the patience, understanding, empathy, and compassion that physicians are known to embody.

Suggestions for working with ‘difficult’ patients

The following tips may be helpful for building rapport with patients with BPD or other “difficult” patients:

• validate their complaints, and the difficulties they cause
• be genuine and honest when discussing their complaints
• acknowledge your own mistakes and misunderstandings in their care
• don’t be defensive—accept criticism with an open mind
• practice listening with intent, and reflective listening
• set ground rules and stick to them (eg, time limits, prescribing expectations, patient-physician relationship boundaries)
• educate and support the patient and their loved ones.

Oh, great!” a senior resident sardonically remarked with a smirk as they read up on the next patient in the clinic. “A borderline patient. Get ready for a rough one ... Ugh.”

Before ever stepping foot into the patient’s room, this resident had prematurely established and demonstrated an unfortunate dynamic for any student or trainee within earshot. This is an all-too-familiar occurrence when caring for individuals with borderline personality disorder (BPD), or any other patients deemed to be “difficult.” The patient, however, likely walked into the room with a traumatic past that they continue to suffer from, in addition to any other issues for which they were seeking care.

Consider what these patients have experienced

A typical profile of these resilient patients with BPD: They were born emotionally sensitive. They grew up in homes with caretakers who knowingly or unknowingly invalidated their complaints about having their feelings hurt, about being abused emotionally, sexually, or otherwise, or about their worries concerning their interactions with peers at school. These caretakers may have been frightening and unpredictable, randomly showing affection or arbitrarily punishing for any perceived misstep, which led these patients to develop (for their own safety’s sake) a hypersensitivity to the affect of others. Their wariness and distrust of their social surroundings may have led to a skeptical view of kindness from others. Over time, without any guidance from prior demonstrations of healthy coping skills or interpersonal outlets from their caregivers, the emotional pressure builds. This pressure finally erupts in the form of impulsivity, self-harm, desperation, and defensiveness—in other words, survival. This is often followed by these patients’ first experience with receiving some degree of appropriate response to their complaints—their first experience with feeling seen and heard by their caretakers. They learn that their needs are met only when they cry out in desperation.^1-3

These patients typically bring these maladaptive coping skills with them into adulthood, which often leads to a series of intense, unhealthy, and short-lived interpersonal and professional connections. They desire healthy, lasting connections with others, but through no fault of their own are unable to appropriately manage the normal stressors therein.¹ Often, these patients do not know of their eventual BPD diagnosis, or even reject it due to its ever-negative valence. For other patients, receiving a personality disorder diagnosis is incredibly validating because they are no longer alone regarding this type of suffering, and a doctor—a caretaker—is finally making sense of this tumultuous world.

The countertransference of frustration, anxiety, doubt, and annoyance we may feel when caring for patients with BPD pales in comparison to living in their shoes and carrying the weight of what they have had to endure before presenting to our care. As these resilient patients wait in the exam room for the chance to be heard, let this be a reminder to greet them with the patience, understanding, empathy, and compassion that physicians are known to embody.

Suggestions for working with ‘difficult’ patients

The following tips may be helpful for building rapport with patients with BPD or other “difficult” patients:

• validate their complaints, and the difficulties they cause
• be genuine and honest when discussing their complaints
• acknowledge your own mistakes and misunderstandings in their care
• don’t be defensive—accept criticism with an open mind
• practice listening with intent, and reflective listening
• set ground rules and stick to them (eg, time limits, prescribing expectations, patient-physician relationship boundaries)
• educate and support the patient and their loved ones.

Oh, great!” a senior resident sardonically remarked with a smirk as they read up on the next patient in the clinic. “A borderline patient. Get ready for a rough one ... Ugh.”

Before ever stepping foot into the patient’s room, this resident had prematurely established and demonstrated an unfortunate dynamic for any student or trainee within earshot. This is an all-too-familiar occurrence when caring for individuals with borderline personality disorder (BPD), or any other patients deemed to be “difficult.” The patient, however, likely walked into the room with a traumatic past that they continue to suffer from, in addition to any other issues for which they were seeking care.

Consider what these patients have experienced

A typical profile of these resilient patients with BPD: They were born emotionally sensitive. They grew up in homes with caretakers who knowingly or unknowingly invalidated their complaints about having their feelings hurt, about being abused emotionally, sexually, or otherwise, or about their worries concerning their interactions with peers at school. These caretakers may have been frightening and unpredictable, randomly showing affection or arbitrarily punishing for any perceived misstep, which led these patients to develop (for their own safety’s sake) a hypersensitivity to the affect of others. Their wariness and distrust of their social surroundings may have led to a skeptical view of kindness from others. Over time, without any guidance from prior demonstrations of healthy coping skills or interpersonal outlets from their caregivers, the emotional pressure builds. This pressure finally erupts in the form of impulsivity, self-harm, desperation, and defensiveness—in other words, survival. This is often followed by these patients’ first experience with receiving some degree of appropriate response to their complaints—their first experience with feeling seen and heard by their caretakers. They learn that their needs are met only when they cry out in desperation.^1-3

These patients typically bring these maladaptive coping skills with them into adulthood, which often leads to a series of intense, unhealthy, and short-lived interpersonal and professional connections. They desire healthy, lasting connections with others, but through no fault of their own are unable to appropriately manage the normal stressors therein.¹ Often, these patients do not know of their eventual BPD diagnosis, or even reject it due to its ever-negative valence. For other patients, receiving a personality disorder diagnosis is incredibly validating because they are no longer alone regarding this type of suffering, and a doctor—a caretaker—is finally making sense of this tumultuous world.

The countertransference of frustration, anxiety, doubt, and annoyance we may feel when caring for patients with BPD pales in comparison to living in their shoes and carrying the weight of what they have had to endure before presenting to our care. As these resilient patients wait in the exam room for the chance to be heard, let this be a reminder to greet them with the patience, understanding, empathy, and compassion that physicians are known to embody.

Suggestions for working with ‘difficult’ patients

The following tips may be helpful for building rapport with patients with BPD or other “difficult” patients:

• validate their complaints, and the difficulties they cause
• be genuine and honest when discussing their complaints
• acknowledge your own mistakes and misunderstandings in their care
• don’t be defensive—accept criticism with an open mind
• practice listening with intent, and reflective listening
• set ground rules and stick to them (eg, time limits, prescribing expectations, patient-physician relationship boundaries)
• educate and support the patient and their loved ones.

With more families placing their children on vegetarian diets, the results from a Canadian longitudinal cohort study are reassuring: It found no clinically meaningful differences in height, growth, or biochemical measures of nutrition in young children on vegetarian and nonvegetarian diets.

While z scores (the standard deviation above or below the mean) were similar in both dietary groups, there was a weak association between a vegetarian diet and lower mean z height, as well as slightly higher odds of underweight.

No significant associations were identified between vegetarian and nonvegetarian diets for child z body mass index (BMI), serum ferritin, 25(OH)D, and serum lipids, according to Jonathon L. Maguire, MD. MSc, of St. Michael’s Hospital Pediatric Clinic in Toronto.

Moreover, the magnitude of the height and vegetarian diet association was small at just 0.3 cm for a 3-year-old child and unlikely to be clinically meaningful, Dr. Maguire and colleagues wrote online in Pediatrics.

In a secondary study outcome, cow’s milk consumption was associated with higher serum lipid levels for both diets. Serum lipids were similar among those who did or did not consume a vegetarian diet and consumed the recommended 2 cups of cow’s milk per day.

“The vast majority of children with vegetarian diets have similar growth and nutrition as children without vegetarian diets,” said Dr. Maguire, who is also a professor of pediatrics and nutritional sciences at the University of Toronto, in an interview. “But, I think we should be mindful to carefully plan vegetarian diets for children [who are] underweight.”

The study conclusion was based on 8,907 children, 6 months to 8 years of age, including 248 vegetarian and 25 vegan children, at baseline. They were part of theTARGet Kids! practice-based research network in Toronto.

The mean age of children at baseline was 2.2 years (standard deviation, 1.5), and 52.4% were male. Participants were followed for an average of 2.8 years (SD, 1.7).

Those with a vegetarian diet had longer breastfeeding duration: 12.6 months (SD, 9.5) versus 10.0 months (SD, 7.0). They were also more likely to be of Asian ethnicity: 33.8% versus 19.0%. Otherwise, children with and without a vegetarian diet were similar at baseline.

In study outcomes, vegetarian children had higher odds of underweight: body mass index z score less than –2 (odds ratio 1.87; 95% confidence interval, 1.19-2.96, P = .007), while no association with overweight or obesity was found.

In a secondary outcome, cow’s milk consumption was associated with higher levels of non–high-density lipoprotein cholesterol (P = .03), total cholesterol (P = .04), and low-density lipoprotein cholesterol (P = .02) in young children on a vegetarian diet. Levels were similar in children with and without a vegetarian diet who consumed the recommended 2 cups of cow’s milk per day.

Previous studies have found that vegetarian children have normal growth and development but tend to be leaner than their omnivore peers.

As for the potential effect of following a fully vegan diet on these nutritional measures, Dr. Maguire said, “Unfortunately, there were not enough children with vegan diets to make meaningful conclusions.”

Would results likely be similar in older children who have more independence and engage more with their peers?“ I don’t know, but we will be following these children for many years to come through the TARGet Kids! research network, Dr. Maguire said.

Studies such as this are timely as plant-based eating becomes more widespread in the United States. The 2007-2010 National Health and Nutrition Examination Surveys found that 2.1% of American adults followed a vegetarian diet, and that figure appears to have increased, with 5% of American adults self-identifying as vegetarian in a 2019 Gallup poll.

Offering her perspective on the Canadian study but not involved in it, Stephanie Di Figlia-Peck, MS, RDN, agreed the results indicate that “a vegetarian diet is not a negative thing for growth and development.” She is a lead registered dietitian in the division of adolescent medicine at Cohen Children’s Medical Center in New Hyde Park, N.Y. She noted, however, that the study looked only at very young children on average.

She stressed that vegetarian regimens require family commitment and agreed on the need for planning. “For these diets to work, a lot has to go into it. But if they’re carefully planned, there is adequate protein and micro- and macronutrients and there’s a nonnegative effect on growth and development.”

The study results mirror what she sees in clinical practice, with vegetarian children tending to weigh less. “Some obese and overweight children will adopt vegetarian diets to lose weight,” Ms. Di Figlia-Peck said.

And perseverance has rewards. “When people follow a vegetarian diet, they tend to have lower blood pressure and cholesterol. A plant-based diet can favorably impact diseases for an entire lifetime.”

This study was supported by the Canadian Institutes of Health Research and the St. Michael’s Hospital and SickKids Hospital foundations. Dr. Maguire received an unrestricted research grant for a previous investigator-initiated study from Dairy Farmers of Canada, and D drops provided nonfinancial support (vitamin D supplements) for a previous investigator-initiated study on vitamin D and respiratory tract infections. Coauthor David Jenkins, MD, PhD, DSc, reported research support from multiple private-sector and nonprivate organizations; several of his family members are involved in the promotion of vegetarian diets. Ms. Di Figlia-Peck had no competing interests to declare.

With more families placing their children on vegetarian diets, the results from a Canadian longitudinal cohort study are reassuring: It found no clinically meaningful differences in height, growth, or biochemical measures of nutrition in young children on vegetarian and nonvegetarian diets.

While z scores (the standard deviation above or below the mean) were similar in both dietary groups, there was a weak association between a vegetarian diet and lower mean z height, as well as slightly higher odds of underweight.

No significant associations were identified between vegetarian and nonvegetarian diets for child z body mass index (BMI), serum ferritin, 25(OH)D, and serum lipids, according to Jonathon L. Maguire, MD. MSc, of St. Michael’s Hospital Pediatric Clinic in Toronto.

Moreover, the magnitude of the height and vegetarian diet association was small at just 0.3 cm for a 3-year-old child and unlikely to be clinically meaningful, Dr. Maguire and colleagues wrote online in Pediatrics.

In a secondary study outcome, cow’s milk consumption was associated with higher serum lipid levels for both diets. Serum lipids were similar among those who did or did not consume a vegetarian diet and consumed the recommended 2 cups of cow’s milk per day.

“The vast majority of children with vegetarian diets have similar growth and nutrition as children without vegetarian diets,” said Dr. Maguire, who is also a professor of pediatrics and nutritional sciences at the University of Toronto, in an interview. “But, I think we should be mindful to carefully plan vegetarian diets for children [who are] underweight.”

The study conclusion was based on 8,907 children, 6 months to 8 years of age, including 248 vegetarian and 25 vegan children, at baseline. They were part of theTARGet Kids! practice-based research network in Toronto.

The mean age of children at baseline was 2.2 years (standard deviation, 1.5), and 52.4% were male. Participants were followed for an average of 2.8 years (SD, 1.7).

Those with a vegetarian diet had longer breastfeeding duration: 12.6 months (SD, 9.5) versus 10.0 months (SD, 7.0). They were also more likely to be of Asian ethnicity: 33.8% versus 19.0%. Otherwise, children with and without a vegetarian diet were similar at baseline.

In study outcomes, vegetarian children had higher odds of underweight: body mass index z score less than –2 (odds ratio 1.87; 95% confidence interval, 1.19-2.96, P = .007), while no association with overweight or obesity was found.

In a secondary outcome, cow’s milk consumption was associated with higher levels of non–high-density lipoprotein cholesterol (P = .03), total cholesterol (P = .04), and low-density lipoprotein cholesterol (P = .02) in young children on a vegetarian diet. Levels were similar in children with and without a vegetarian diet who consumed the recommended 2 cups of cow’s milk per day.

Previous studies have found that vegetarian children have normal growth and development but tend to be leaner than their omnivore peers.

As for the potential effect of following a fully vegan diet on these nutritional measures, Dr. Maguire said, “Unfortunately, there were not enough children with vegan diets to make meaningful conclusions.”

Would results likely be similar in older children who have more independence and engage more with their peers?“ I don’t know, but we will be following these children for many years to come through the TARGet Kids! research network, Dr. Maguire said.

Studies such as this are timely as plant-based eating becomes more widespread in the United States. The 2007-2010 National Health and Nutrition Examination Surveys found that 2.1% of American adults followed a vegetarian diet, and that figure appears to have increased, with 5% of American adults self-identifying as vegetarian in a 2019 Gallup poll.

Offering her perspective on the Canadian study but not involved in it, Stephanie Di Figlia-Peck, MS, RDN, agreed the results indicate that “a vegetarian diet is not a negative thing for growth and development.” She is a lead registered dietitian in the division of adolescent medicine at Cohen Children’s Medical Center in New Hyde Park, N.Y. She noted, however, that the study looked only at very young children on average.

She stressed that vegetarian regimens require family commitment and agreed on the need for planning. “For these diets to work, a lot has to go into it. But if they’re carefully planned, there is adequate protein and micro- and macronutrients and there’s a nonnegative effect on growth and development.”

The study results mirror what she sees in clinical practice, with vegetarian children tending to weigh less. “Some obese and overweight children will adopt vegetarian diets to lose weight,” Ms. Di Figlia-Peck said.

And perseverance has rewards. “When people follow a vegetarian diet, they tend to have lower blood pressure and cholesterol. A plant-based diet can favorably impact diseases for an entire lifetime.”

This study was supported by the Canadian Institutes of Health Research and the St. Michael’s Hospital and SickKids Hospital foundations. Dr. Maguire received an unrestricted research grant for a previous investigator-initiated study from Dairy Farmers of Canada, and D drops provided nonfinancial support (vitamin D supplements) for a previous investigator-initiated study on vitamin D and respiratory tract infections. Coauthor David Jenkins, MD, PhD, DSc, reported research support from multiple private-sector and nonprivate organizations; several of his family members are involved in the promotion of vegetarian diets. Ms. Di Figlia-Peck had no competing interests to declare.

With more families placing their children on vegetarian diets, the results from a Canadian longitudinal cohort study are reassuring: It found no clinically meaningful differences in height, growth, or biochemical measures of nutrition in young children on vegetarian and nonvegetarian diets.

While z scores (the standard deviation above or below the mean) were similar in both dietary groups, there was a weak association between a vegetarian diet and lower mean z height, as well as slightly higher odds of underweight.

No significant associations were identified between vegetarian and nonvegetarian diets for child z body mass index (BMI), serum ferritin, 25(OH)D, and serum lipids, according to Jonathon L. Maguire, MD. MSc, of St. Michael’s Hospital Pediatric Clinic in Toronto.

Moreover, the magnitude of the height and vegetarian diet association was small at just 0.3 cm for a 3-year-old child and unlikely to be clinically meaningful, Dr. Maguire and colleagues wrote online in Pediatrics.

In a secondary study outcome, cow’s milk consumption was associated with higher serum lipid levels for both diets. Serum lipids were similar among those who did or did not consume a vegetarian diet and consumed the recommended 2 cups of cow’s milk per day.

“The vast majority of children with vegetarian diets have similar growth and nutrition as children without vegetarian diets,” said Dr. Maguire, who is also a professor of pediatrics and nutritional sciences at the University of Toronto, in an interview. “But, I think we should be mindful to carefully plan vegetarian diets for children [who are] underweight.”

The study conclusion was based on 8,907 children, 6 months to 8 years of age, including 248 vegetarian and 25 vegan children, at baseline. They were part of theTARGet Kids! practice-based research network in Toronto.

The mean age of children at baseline was 2.2 years (standard deviation, 1.5), and 52.4% were male. Participants were followed for an average of 2.8 years (SD, 1.7).

Those with a vegetarian diet had longer breastfeeding duration: 12.6 months (SD, 9.5) versus 10.0 months (SD, 7.0). They were also more likely to be of Asian ethnicity: 33.8% versus 19.0%. Otherwise, children with and without a vegetarian diet were similar at baseline.

In study outcomes, vegetarian children had higher odds of underweight: body mass index z score less than –2 (odds ratio 1.87; 95% confidence interval, 1.19-2.96, P = .007), while no association with overweight or obesity was found.

In a secondary outcome, cow’s milk consumption was associated with higher levels of non–high-density lipoprotein cholesterol (P = .03), total cholesterol (P = .04), and low-density lipoprotein cholesterol (P = .02) in young children on a vegetarian diet. Levels were similar in children with and without a vegetarian diet who consumed the recommended 2 cups of cow’s milk per day.

Previous studies have found that vegetarian children have normal growth and development but tend to be leaner than their omnivore peers.

As for the potential effect of following a fully vegan diet on these nutritional measures, Dr. Maguire said, “Unfortunately, there were not enough children with vegan diets to make meaningful conclusions.”

Would results likely be similar in older children who have more independence and engage more with their peers?“ I don’t know, but we will be following these children for many years to come through the TARGet Kids! research network, Dr. Maguire said.

Studies such as this are timely as plant-based eating becomes more widespread in the United States. The 2007-2010 National Health and Nutrition Examination Surveys found that 2.1% of American adults followed a vegetarian diet, and that figure appears to have increased, with 5% of American adults self-identifying as vegetarian in a 2019 Gallup poll.

Offering her perspective on the Canadian study but not involved in it, Stephanie Di Figlia-Peck, MS, RDN, agreed the results indicate that “a vegetarian diet is not a negative thing for growth and development.” She is a lead registered dietitian in the division of adolescent medicine at Cohen Children’s Medical Center in New Hyde Park, N.Y. She noted, however, that the study looked only at very young children on average.

She stressed that vegetarian regimens require family commitment and agreed on the need for planning. “For these diets to work, a lot has to go into it. But if they’re carefully planned, there is adequate protein and micro- and macronutrients and there’s a nonnegative effect on growth and development.”

The study results mirror what she sees in clinical practice, with vegetarian children tending to weigh less. “Some obese and overweight children will adopt vegetarian diets to lose weight,” Ms. Di Figlia-Peck said.

And perseverance has rewards. “When people follow a vegetarian diet, they tend to have lower blood pressure and cholesterol. A plant-based diet can favorably impact diseases for an entire lifetime.”

This study was supported by the Canadian Institutes of Health Research and the St. Michael’s Hospital and SickKids Hospital foundations. Dr. Maguire received an unrestricted research grant for a previous investigator-initiated study from Dairy Farmers of Canada, and D drops provided nonfinancial support (vitamin D supplements) for a previous investigator-initiated study on vitamin D and respiratory tract infections. Coauthor David Jenkins, MD, PhD, DSc, reported research support from multiple private-sector and nonprivate organizations; several of his family members are involved in the promotion of vegetarian diets. Ms. Di Figlia-Peck had no competing interests to declare.

Until recently, chronic hepatitis C virus (HCV) treatment had poor efficacy and was provided only by specialists such as hepatologists and gastroenterologists. However, the introduction of safe, effective direct-acting antivirals (DAAs) has revolutionized HCV treatment.

One pivotal transformation has been the expansion of treatment to nonspecialist physicians. Nevertheless, various factors must be considered when initiating treatment for HCV.

Dr Elizabeth Verna, director of hepatology research at Columbia University in New York City, examines the essential treatment considerations for chronic HCV in treatment-naive patients.

First, she outlines recommended first-line therapies and the simplified HCV treatment algorithm recently issued by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America. She then discusses patient-specific factors, such as cirrhosis, co-infections, age, and pregnancy, that can create treatment challenges and change the algorithm.

In closing, she talks about changes in HCV screening recommendations and how diagnosis and treatment of this infectious disease largely rest in the hands of general practitioners who are the first line of defense in controlling HCV spread.

--

Associate Professor of Medicine, Director of Hepatology Research, Associate Physician, Department of Medicine, Columbia University, New York, NY

Elizabeth Verna, MD, has disclosed the following relevant financial relationships:

Received research grant from: Salix

Until recently, chronic hepatitis C virus (HCV) treatment had poor efficacy and was provided only by specialists such as hepatologists and gastroenterologists. However, the introduction of safe, effective direct-acting antivirals (DAAs) has revolutionized HCV treatment.

One pivotal transformation has been the expansion of treatment to nonspecialist physicians. Nevertheless, various factors must be considered when initiating treatment for HCV.

Dr Elizabeth Verna, director of hepatology research at Columbia University in New York City, examines the essential treatment considerations for chronic HCV in treatment-naive patients.

First, she outlines recommended first-line therapies and the simplified HCV treatment algorithm recently issued by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America. She then discusses patient-specific factors, such as cirrhosis, co-infections, age, and pregnancy, that can create treatment challenges and change the algorithm.

In closing, she talks about changes in HCV screening recommendations and how diagnosis and treatment of this infectious disease largely rest in the hands of general practitioners who are the first line of defense in controlling HCV spread.

--

Associate Professor of Medicine, Director of Hepatology Research, Associate Physician, Department of Medicine, Columbia University, New York, NY

Elizabeth Verna, MD, has disclosed the following relevant financial relationships:

Received research grant from: Salix

Until recently, chronic hepatitis C virus (HCV) treatment had poor efficacy and was provided only by specialists such as hepatologists and gastroenterologists. However, the introduction of safe, effective direct-acting antivirals (DAAs) has revolutionized HCV treatment.

One pivotal transformation has been the expansion of treatment to nonspecialist physicians. Nevertheless, various factors must be considered when initiating treatment for HCV.

Dr Elizabeth Verna, director of hepatology research at Columbia University in New York City, examines the essential treatment considerations for chronic HCV in treatment-naive patients.

First, she outlines recommended first-line therapies and the simplified HCV treatment algorithm recently issued by the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America. She then discusses patient-specific factors, such as cirrhosis, co-infections, age, and pregnancy, that can create treatment challenges and change the algorithm.

In closing, she talks about changes in HCV screening recommendations and how diagnosis and treatment of this infectious disease largely rest in the hands of general practitioners who are the first line of defense in controlling HCV spread.

--

Associate Professor of Medicine, Director of Hepatology Research, Associate Physician, Department of Medicine, Columbia University, New York, NY

Elizabeth Verna, MD, has disclosed the following relevant financial relationships:

Received research grant from: Salix

In early-stage disease, perioperative chemotherapy plays a critical role. The triple-chemotherapy FLOT regimen is now the standard treatment in patients who are able to tolerate it. However, it is associated with significant toxicities, and modifications frequently are needed. In clinical practice, FOLFOX chemotherapy can be used in patients who are not candidates for FLOT. A phase 2 OGSG 1601 study enrolled 37 patients with clinical stage T3/T4a N1-3 M0 gastric cancer who received perioperative doublet chemotherapy with capecitabine and oxaliplatin. At the 3-year follow-up, this study continues to demonstrate good activity of this doublet chemotherapy, with an overall survival rate of 83.8% at 3 years and relapse-free rate of 73%. These results support the use of this doublet in patients who cannot tolerate a more intense chemotherapy regimen. The interpretation of this study is limited by its small size and nonrandomized design. Given what we know about the activity of this regimen in advanced disease, however, these results add to the body of evidence that supports the use of this doublet in select patients.

There have been efforts to augment the activity of perioperative chemotherapy using antiangiogenic agents. In the advanced setting, studies with antiangiogenic agents have had mixed results. Ramucirumab in combination with paclitaxel is FDA-approved in the second-line setting, but a subsequent study in the first line-setting showed no improvement from the addition of ramucirumab.^4,7 In the preoperative setting, the role of ramucirumab in combination with chemotherapy was evaluated in a phase 2 study. Although a hint of activity was seen, there was increased toxicity, especially in Siewert type I tumors.⁸ The phase 2 study by Tang and colleagues enrolled 32 patients with resectable gastric and gastroesophageal juncture adenocarcinoma who received neoadjuvant oxaliplatin, capecitabine, and apatinib. Apatinib is a small-molecule tyrosine kinase inhibitor with highly selective affinity to vascular endothelial growth factor receptor 2. The treatment had manageable toxicity, with hypertension being the most common adverse event, as expected. Early signs of potential clinical efficacy were seen (pathologic complete response and pathologic response were achieved in 6.3% and 34.4% of the patients, respectively), but the true contribution from the addition of apatinib can be established only in a prospective randomized study. For now, chemotherapy alone remains the standard perioperative treatment, although ongoing studies are evaluating the addition of immune checkpoint inhibitors in this setting (NCT03221426, NCT04592913). These types of agents are probably more likely than antiangiogenic agents to become part of standard treatment in the perioperative setting.

Additional References

1. Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): A randomised, open-label, phase 3 trial. Lancet. 2021;398:27-40. Doi: 10.1016/S0140-6736(21)00797-2 Source
2. Van Cutsem E, Moiseyenko VM, Tjulandin S, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: A report of the V325 Study Group. J Clin Oncol. 2006;24:4991-4997. Doi:  10.1200/JCO.2006.06.8429 Source
3. Al-Batran S-E, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): A randomised, phase 2/3 trial. Lancet. 2019;393:1948-1957. Doi: 10.1016/S0140-6736(18)32557-1 Source0
4. Wilke H, Van Cutsem E, Cheul Oh S, et al. RAINBOW: A global, phase 3, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy: Results of a multiple Cox regression analysis adjusting for prognostic factors. J Clin Oncol. 2014;32(15, suppl):1076. Doi: 10.1200/jco.2014.32.15_suppl.4076 Source
5. Elimova E, Janjigian YY, Mulcahy M, et al. It is time to stop using epirubicin to treat any patient with gastroesophageal adenocarcinoma. J Clin Oncol. 2017;35:475-477. Doi: 10.1200/JCO.2016.69.7276 Source
6. Park H, Jin RU, Wang-Gillam A, et al. FOLFIRINOX for the treatment of advanced gastroesophageal cancers: A phase 2 nonrandomized clinical trial. JAMA Oncol. 2020;6:1231-1240. Doi: 10.1001/jamaoncol.2020.2020 Source
7. Fuchs CS, Shitara K, Di Bartolomeo M, et al. RAINFALL: A randomized, double-blind, placebo-controlled phase III study of cisplatin (Cis) plus capecitabine (Cape) or 5FU with or without ramucirumab (RAM) as first-line therapy in patients with metastatic gastric or gastroesophageal junction (G-GEJ) adenocarcinoma. J Clin Oncol. 2018;36(4, suppl):5. Doi: 10.1200/JCO.2018.36.4_suppl.5 Source
8. Al-Batran S-E, Hofheinz RD, Schmalenberg H, et al. Perioperative ramucirumab in combination with FLOT versus FLOT alone for resectable esophagogastric adenocarcinoma (RAMSES/FLOT7): Results of the phase II-portion—A multicenter, randomized phase II/III trial of the German AIO and Italian GOIM. J Clin Oncol. 2020;38(15, suppl):4501. Doi: 10.1200/JCO.2020.38.15_suppl.4501 Source

In early-stage disease, perioperative chemotherapy plays a critical role. The triple-chemotherapy FLOT regimen is now the standard treatment in patients who are able to tolerate it. However, it is associated with significant toxicities, and modifications frequently are needed. In clinical practice, FOLFOX chemotherapy can be used in patients who are not candidates for FLOT. A phase 2 OGSG 1601 study enrolled 37 patients with clinical stage T3/T4a N1-3 M0 gastric cancer who received perioperative doublet chemotherapy with capecitabine and oxaliplatin. At the 3-year follow-up, this study continues to demonstrate good activity of this doublet chemotherapy, with an overall survival rate of 83.8% at 3 years and relapse-free rate of 73%. These results support the use of this doublet in patients who cannot tolerate a more intense chemotherapy regimen. The interpretation of this study is limited by its small size and nonrandomized design. Given what we know about the activity of this regimen in advanced disease, however, these results add to the body of evidence that supports the use of this doublet in select patients.

There have been efforts to augment the activity of perioperative chemotherapy using antiangiogenic agents. In the advanced setting, studies with antiangiogenic agents have had mixed results. Ramucirumab in combination with paclitaxel is FDA-approved in the second-line setting, but a subsequent study in the first line-setting showed no improvement from the addition of ramucirumab.^4,7 In the preoperative setting, the role of ramucirumab in combination with chemotherapy was evaluated in a phase 2 study. Although a hint of activity was seen, there was increased toxicity, especially in Siewert type I tumors.⁸ The phase 2 study by Tang and colleagues enrolled 32 patients with resectable gastric and gastroesophageal juncture adenocarcinoma who received neoadjuvant oxaliplatin, capecitabine, and apatinib. Apatinib is a small-molecule tyrosine kinase inhibitor with highly selective affinity to vascular endothelial growth factor receptor 2. The treatment had manageable toxicity, with hypertension being the most common adverse event, as expected. Early signs of potential clinical efficacy were seen (pathologic complete response and pathologic response were achieved in 6.3% and 34.4% of the patients, respectively), but the true contribution from the addition of apatinib can be established only in a prospective randomized study. For now, chemotherapy alone remains the standard perioperative treatment, although ongoing studies are evaluating the addition of immune checkpoint inhibitors in this setting (NCT03221426, NCT04592913). These types of agents are probably more likely than antiangiogenic agents to become part of standard treatment in the perioperative setting.

Additional References

1. Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): A randomised, open-label, phase 3 trial. Lancet. 2021;398:27-40. Doi: 10.1016/S0140-6736(21)00797-2 Source
2. Van Cutsem E, Moiseyenko VM, Tjulandin S, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: A report of the V325 Study Group. J Clin Oncol. 2006;24:4991-4997. Doi:  10.1200/JCO.2006.06.8429 Source
3. Al-Batran S-E, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): A randomised, phase 2/3 trial. Lancet. 2019;393:1948-1957. Doi: 10.1016/S0140-6736(18)32557-1 Source0
4. Wilke H, Van Cutsem E, Cheul Oh S, et al. RAINBOW: A global, phase 3, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy: Results of a multiple Cox regression analysis adjusting for prognostic factors. J Clin Oncol. 2014;32(15, suppl):1076. Doi: 10.1200/jco.2014.32.15_suppl.4076 Source
5. Elimova E, Janjigian YY, Mulcahy M, et al. It is time to stop using epirubicin to treat any patient with gastroesophageal adenocarcinoma. J Clin Oncol. 2017;35:475-477. Doi: 10.1200/JCO.2016.69.7276 Source
6. Park H, Jin RU, Wang-Gillam A, et al. FOLFIRINOX for the treatment of advanced gastroesophageal cancers: A phase 2 nonrandomized clinical trial. JAMA Oncol. 2020;6:1231-1240. Doi: 10.1001/jamaoncol.2020.2020 Source
7. Fuchs CS, Shitara K, Di Bartolomeo M, et al. RAINFALL: A randomized, double-blind, placebo-controlled phase III study of cisplatin (Cis) plus capecitabine (Cape) or 5FU with or without ramucirumab (RAM) as first-line therapy in patients with metastatic gastric or gastroesophageal junction (G-GEJ) adenocarcinoma. J Clin Oncol. 2018;36(4, suppl):5. Doi: 10.1200/JCO.2018.36.4_suppl.5 Source
8. Al-Batran S-E, Hofheinz RD, Schmalenberg H, et al. Perioperative ramucirumab in combination with FLOT versus FLOT alone for resectable esophagogastric adenocarcinoma (RAMSES/FLOT7): Results of the phase II-portion—A multicenter, randomized phase II/III trial of the German AIO and Italian GOIM. J Clin Oncol. 2020;38(15, suppl):4501. Doi: 10.1200/JCO.2020.38.15_suppl.4501 Source

In early-stage disease, perioperative chemotherapy plays a critical role. The triple-chemotherapy FLOT regimen is now the standard treatment in patients who are able to tolerate it. However, it is associated with significant toxicities, and modifications frequently are needed. In clinical practice, FOLFOX chemotherapy can be used in patients who are not candidates for FLOT. A phase 2 OGSG 1601 study enrolled 37 patients with clinical stage T3/T4a N1-3 M0 gastric cancer who received perioperative doublet chemotherapy with capecitabine and oxaliplatin. At the 3-year follow-up, this study continues to demonstrate good activity of this doublet chemotherapy, with an overall survival rate of 83.8% at 3 years and relapse-free rate of 73%. These results support the use of this doublet in patients who cannot tolerate a more intense chemotherapy regimen. The interpretation of this study is limited by its small size and nonrandomized design. Given what we know about the activity of this regimen in advanced disease, however, these results add to the body of evidence that supports the use of this doublet in select patients.

There have been efforts to augment the activity of perioperative chemotherapy using antiangiogenic agents. In the advanced setting, studies with antiangiogenic agents have had mixed results. Ramucirumab in combination with paclitaxel is FDA-approved in the second-line setting, but a subsequent study in the first line-setting showed no improvement from the addition of ramucirumab.^4,7 In the preoperative setting, the role of ramucirumab in combination with chemotherapy was evaluated in a phase 2 study. Although a hint of activity was seen, there was increased toxicity, especially in Siewert type I tumors.⁸ The phase 2 study by Tang and colleagues enrolled 32 patients with resectable gastric and gastroesophageal juncture adenocarcinoma who received neoadjuvant oxaliplatin, capecitabine, and apatinib. Apatinib is a small-molecule tyrosine kinase inhibitor with highly selective affinity to vascular endothelial growth factor receptor 2. The treatment had manageable toxicity, with hypertension being the most common adverse event, as expected. Early signs of potential clinical efficacy were seen (pathologic complete response and pathologic response were achieved in 6.3% and 34.4% of the patients, respectively), but the true contribution from the addition of apatinib can be established only in a prospective randomized study. For now, chemotherapy alone remains the standard perioperative treatment, although ongoing studies are evaluating the addition of immune checkpoint inhibitors in this setting (NCT03221426, NCT04592913). These types of agents are probably more likely than antiangiogenic agents to become part of standard treatment in the perioperative setting.

Additional References

1. Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): A randomised, open-label, phase 3 trial. Lancet. 2021;398:27-40. Doi: 10.1016/S0140-6736(21)00797-2 Source
2. Van Cutsem E, Moiseyenko VM, Tjulandin S, et al. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: A report of the V325 Study Group. J Clin Oncol. 2006;24:4991-4997. Doi:  10.1200/JCO.2006.06.8429 Source
3. Al-Batran S-E, Homann N, Pauligk C, et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): A randomised, phase 2/3 trial. Lancet. 2019;393:1948-1957. Doi: 10.1016/S0140-6736(18)32557-1 Source0
4. Wilke H, Van Cutsem E, Cheul Oh S, et al. RAINBOW: A global, phase 3, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy: Results of a multiple Cox regression analysis adjusting for prognostic factors. J Clin Oncol. 2014;32(15, suppl):1076. Doi: 10.1200/jco.2014.32.15_suppl.4076 Source
5. Elimova E, Janjigian YY, Mulcahy M, et al. It is time to stop using epirubicin to treat any patient with gastroesophageal adenocarcinoma. J Clin Oncol. 2017;35:475-477. Doi: 10.1200/JCO.2016.69.7276 Source
6. Park H, Jin RU, Wang-Gillam A, et al. FOLFIRINOX for the treatment of advanced gastroesophageal cancers: A phase 2 nonrandomized clinical trial. JAMA Oncol. 2020;6:1231-1240. Doi: 10.1001/jamaoncol.2020.2020 Source
7. Fuchs CS, Shitara K, Di Bartolomeo M, et al. RAINFALL: A randomized, double-blind, placebo-controlled phase III study of cisplatin (Cis) plus capecitabine (Cape) or 5FU with or without ramucirumab (RAM) as first-line therapy in patients with metastatic gastric or gastroesophageal junction (G-GEJ) adenocarcinoma. J Clin Oncol. 2018;36(4, suppl):5. Doi: 10.1200/JCO.2018.36.4_suppl.5 Source
8. Al-Batran S-E, Hofheinz RD, Schmalenberg H, et al. Perioperative ramucirumab in combination with FLOT versus FLOT alone for resectable esophagogastric adenocarcinoma (RAMSES/FLOT7): Results of the phase II-portion—A multicenter, randomized phase II/III trial of the German AIO and Italian GOIM. J Clin Oncol. 2020;38(15, suppl):4501. Doi: 10.1200/JCO.2020.38.15_suppl.4501 Source

Although most patients with psoriatic arthritis (PsA) have concomitant psoriasis, many with PsA who are enrolled in clinic trials as well as in rheumatology clinic do not have severe psoriasis. Therefore, an unanswered question is how much psoriasis symptoms contribute to impaired quality of life (QOL) in PsA patients. This question was addressed in a recent study by Taylor and colleagues. This post hoc analysis of two phase 3 studies, OPAL Broaden and OPAL Beyond, included 816 patients with active PsA and an inadequate response to previous therapies who received tofacitinib, adalimumab, or placebo. The analyses demonstrated that Itch Severity Item (ISI) scores of 7-10, Physician's Global Assessment of Psoriasis (PGA-PsO) scores of 4, and Patient's Global Joint and Skin Assessment-Visual Analog Scale (PGJS-VAS) scores of 90-100 mm corresponded with Dermatology Life Quality Index (DLQI) scores categorized as having a very large effect on a patient's life. An improvement of ≥ 3 points in ISI, ≥ 2 points in PGA-PsO, and ≥ 40 mm in PGJS-VAS translated to a clinically meaningful improvement in DLQI scores; improvements from baseline of ≥4/≥3/≥40-mm in the above scores, respectively, were also associated with clinically meaningful improvements across SF-36v2 (Short-Form Health Survey) domains. Thus, dermatologic symptoms are substantially associated with QOL in patients with active PsA, and improvements in skin measures could translate to clinically meaningful improvements in their QOL.

There is also increasing scrutiny on sex differences in PsA. Eder and colleagues conducted a post hoc analysis of two phase 3 trials that included 679 patients with active PsA who were either biologic-naive (SPIRIT-P1) or showed an inadequate response to one or two tumor necrosis factor inhibitors (TNFi) (SPIRIT-P2) and were randomly assigned to receive ixekizumab, an IL-17A inhibitor (IL-17Ai), or placebo. They demonstrated that at baseline female vs male patients had significantly higher Health Assessment Questionnaire Disability Index scores (P ≤ .003), with a significantly higher proportion of male vs female patients in the ixekizumab every-4-weeks treatment arm (53.8% vs 38.3%) and ixekizumab every-2-weeks treatment arm(41.2% vs 28.1%) achieving ≥50% and ≥70% improvement in the American College of Rheumatology response criteria, respectively (both P < .05). Thus, female patients with PsA exhibited significantly higher disease activity at baseline and a poorer response to ixekizumab.

Janus kinase (JAK) inhibitors have been shown to improve inflammatory and other types of pain in rheumatoid arthritis. To further evaluate the effect of inhibition of JAK1 on pain, McInnes and colleagues aimed to evaluate the effect of upadacitinib on pain outcomes in patients with active PsA or ankylosing spondylitis across three randomized trials (SELECT-PsA-1 and -2 for PsA; SELECT-AXIS 1 for ankylosing spondylitis). A significantly higher proportion of patients receiving 15 mg upadacitinib vs placebo achieved ≥30%, ≥50%, and ≥70% reductions in pain as early as 2 weeks (P < .05), with improvements sustained up to week 56. Further research on whether improvement in pain is at least partially independent of improvement in musculoskeletal inflammation is required.

Persistence of drug treatment is an important outcome and is a surrogate measure of safety and effectiveness. Vegas and colleagues assessed the long-term persistence of different biologic classes in a nationwide cohort study that included 16,892 adults with psoriasis and 6531 adults with PsA who initiated first-line treatment with a TNFi, IL-12/23 inhibitors (IL-12/23i), or an IL-17i. Treatment persistence was higher with IL-17i than with TNFi (weighted hazard ratio [HR] 0.70; P < .001) or IL-12/23i (weighted HR 0.69; P < .001); however, IL-12/23i and TNFi showed similar persistence (P = .70). Thus, IL-17i may be associated with higher treatment persistence in PsA compared with TNFi.

Although most patients with psoriatic arthritis (PsA) have concomitant psoriasis, many with PsA who are enrolled in clinic trials as well as in rheumatology clinic do not have severe psoriasis. Therefore, an unanswered question is how much psoriasis symptoms contribute to impaired quality of life (QOL) in PsA patients. This question was addressed in a recent study by Taylor and colleagues. This post hoc analysis of two phase 3 studies, OPAL Broaden and OPAL Beyond, included 816 patients with active PsA and an inadequate response to previous therapies who received tofacitinib, adalimumab, or placebo. The analyses demonstrated that Itch Severity Item (ISI) scores of 7-10, Physician's Global Assessment of Psoriasis (PGA-PsO) scores of 4, and Patient's Global Joint and Skin Assessment-Visual Analog Scale (PGJS-VAS) scores of 90-100 mm corresponded with Dermatology Life Quality Index (DLQI) scores categorized as having a very large effect on a patient's life. An improvement of ≥ 3 points in ISI, ≥ 2 points in PGA-PsO, and ≥ 40 mm in PGJS-VAS translated to a clinically meaningful improvement in DLQI scores; improvements from baseline of ≥4/≥3/≥40-mm in the above scores, respectively, were also associated with clinically meaningful improvements across SF-36v2 (Short-Form Health Survey) domains. Thus, dermatologic symptoms are substantially associated with QOL in patients with active PsA, and improvements in skin measures could translate to clinically meaningful improvements in their QOL.

There is also increasing scrutiny on sex differences in PsA. Eder and colleagues conducted a post hoc analysis of two phase 3 trials that included 679 patients with active PsA who were either biologic-naive (SPIRIT-P1) or showed an inadequate response to one or two tumor necrosis factor inhibitors (TNFi) (SPIRIT-P2) and were randomly assigned to receive ixekizumab, an IL-17A inhibitor (IL-17Ai), or placebo. They demonstrated that at baseline female vs male patients had significantly higher Health Assessment Questionnaire Disability Index scores (P ≤ .003), with a significantly higher proportion of male vs female patients in the ixekizumab every-4-weeks treatment arm (53.8% vs 38.3%) and ixekizumab every-2-weeks treatment arm(41.2% vs 28.1%) achieving ≥50% and ≥70% improvement in the American College of Rheumatology response criteria, respectively (both P < .05). Thus, female patients with PsA exhibited significantly higher disease activity at baseline and a poorer response to ixekizumab.

Janus kinase (JAK) inhibitors have been shown to improve inflammatory and other types of pain in rheumatoid arthritis. To further evaluate the effect of inhibition of JAK1 on pain, McInnes and colleagues aimed to evaluate the effect of upadacitinib on pain outcomes in patients with active PsA or ankylosing spondylitis across three randomized trials (SELECT-PsA-1 and -2 for PsA; SELECT-AXIS 1 for ankylosing spondylitis). A significantly higher proportion of patients receiving 15 mg upadacitinib vs placebo achieved ≥30%, ≥50%, and ≥70% reductions in pain as early as 2 weeks (P < .05), with improvements sustained up to week 56. Further research on whether improvement in pain is at least partially independent of improvement in musculoskeletal inflammation is required.

Persistence of drug treatment is an important outcome and is a surrogate measure of safety and effectiveness. Vegas and colleagues assessed the long-term persistence of different biologic classes in a nationwide cohort study that included 16,892 adults with psoriasis and 6531 adults with PsA who initiated first-line treatment with a TNFi, IL-12/23 inhibitors (IL-12/23i), or an IL-17i. Treatment persistence was higher with IL-17i than with TNFi (weighted hazard ratio [HR] 0.70; P < .001) or IL-12/23i (weighted HR 0.69; P < .001); however, IL-12/23i and TNFi showed similar persistence (P = .70). Thus, IL-17i may be associated with higher treatment persistence in PsA compared with TNFi.

Although most patients with psoriatic arthritis (PsA) have concomitant psoriasis, many with PsA who are enrolled in clinic trials as well as in rheumatology clinic do not have severe psoriasis. Therefore, an unanswered question is how much psoriasis symptoms contribute to impaired quality of life (QOL) in PsA patients. This question was addressed in a recent study by Taylor and colleagues. This post hoc analysis of two phase 3 studies, OPAL Broaden and OPAL Beyond, included 816 patients with active PsA and an inadequate response to previous therapies who received tofacitinib, adalimumab, or placebo. The analyses demonstrated that Itch Severity Item (ISI) scores of 7-10, Physician's Global Assessment of Psoriasis (PGA-PsO) scores of 4, and Patient's Global Joint and Skin Assessment-Visual Analog Scale (PGJS-VAS) scores of 90-100 mm corresponded with Dermatology Life Quality Index (DLQI) scores categorized as having a very large effect on a patient's life. An improvement of ≥ 3 points in ISI, ≥ 2 points in PGA-PsO, and ≥ 40 mm in PGJS-VAS translated to a clinically meaningful improvement in DLQI scores; improvements from baseline of ≥4/≥3/≥40-mm in the above scores, respectively, were also associated with clinically meaningful improvements across SF-36v2 (Short-Form Health Survey) domains. Thus, dermatologic symptoms are substantially associated with QOL in patients with active PsA, and improvements in skin measures could translate to clinically meaningful improvements in their QOL.

There is also increasing scrutiny on sex differences in PsA. Eder and colleagues conducted a post hoc analysis of two phase 3 trials that included 679 patients with active PsA who were either biologic-naive (SPIRIT-P1) or showed an inadequate response to one or two tumor necrosis factor inhibitors (TNFi) (SPIRIT-P2) and were randomly assigned to receive ixekizumab, an IL-17A inhibitor (IL-17Ai), or placebo. They demonstrated that at baseline female vs male patients had significantly higher Health Assessment Questionnaire Disability Index scores (P ≤ .003), with a significantly higher proportion of male vs female patients in the ixekizumab every-4-weeks treatment arm (53.8% vs 38.3%) and ixekizumab every-2-weeks treatment arm(41.2% vs 28.1%) achieving ≥50% and ≥70% improvement in the American College of Rheumatology response criteria, respectively (both P < .05). Thus, female patients with PsA exhibited significantly higher disease activity at baseline and a poorer response to ixekizumab.

Janus kinase (JAK) inhibitors have been shown to improve inflammatory and other types of pain in rheumatoid arthritis. To further evaluate the effect of inhibition of JAK1 on pain, McInnes and colleagues aimed to evaluate the effect of upadacitinib on pain outcomes in patients with active PsA or ankylosing spondylitis across three randomized trials (SELECT-PsA-1 and -2 for PsA; SELECT-AXIS 1 for ankylosing spondylitis). A significantly higher proportion of patients receiving 15 mg upadacitinib vs placebo achieved ≥30%, ≥50%, and ≥70% reductions in pain as early as 2 weeks (P < .05), with improvements sustained up to week 56. Further research on whether improvement in pain is at least partially independent of improvement in musculoskeletal inflammation is required.

Persistence of drug treatment is an important outcome and is a surrogate measure of safety and effectiveness. Vegas and colleagues assessed the long-term persistence of different biologic classes in a nationwide cohort study that included 16,892 adults with psoriasis and 6531 adults with PsA who initiated first-line treatment with a TNFi, IL-12/23 inhibitors (IL-12/23i), or an IL-17i. Treatment persistence was higher with IL-17i than with TNFi (weighted hazard ratio [HR] 0.70; P < .001) or IL-12/23i (weighted HR 0.69; P < .001); however, IL-12/23i and TNFi showed similar persistence (P = .70). Thus, IL-17i may be associated with higher treatment persistence in PsA compared with TNFi.

Despite the improved outcomes in rheumatoid arthritis (RA) observed in clinical trials from early use of biologic disease-modifying antirheumatic drugs (bDMARD) in a treat-to-target strategy, real-world use may be limited by stopping medications for various reasons. Burkard and colleagues used the Swiss RA registry to examine potential reasons for discontinuation of bDMARD and targeted synthetic disease-modifying antirheumatic drugs (tsDMARD) among over 2500 adults with RA who stopped these medications from 1999 through 2018. In this cohort study, patients were followed from date of discontinuation of their medication until restarting a bDMARD or tsDMARD. The most common reasons for discontinuation were nonresponse and adverse events; of these patients, over 80% restarted a bDMARD or tsDMARD. Only 8% of patients stopped due to remission; of these, nearly half restarted. The authors found a higher proportion of fibromyalgia among patients who stopped due to nonresponse and adverse events vs due to remission. Oddly, though 40%-50% of patients stopped for "unknown reasons" between 2002 and 2006, this proportion dropped to close to 0 after 2010; during the first time period, the proportions stopping medication due to adverse events and nonresponse were also low, suggesting possible misattribution of the reason for treatment cessation. As such, drawing further conclusions on association of different patient characteristics with reasons for treatment cessation is difficult.

The gap between control of inflammatory joint pain in RA and overall patient outcomes has come up frequently in recent studies. Gwinnutt and colleagues looked at patients participating in three European RA registries, comprising over 2500 patients followed over 8-10 years, and classified them as having high or low inflammation on the basis of Disease Activity Score (DAS28) and analyzed Health Assessment Questionnaire (HAQ) score trajectories as low vs high as a measure of disability. Overall, patients in the three registries had different trajectory patterns, though it appears clear, in keeping with other studies, that a subset of patients remain with high HAQ scores despite decreases in DAS28 scores. Older age; being a woman; and more pain, fatigue, and depressive symptoms were associated with higher HAQ trajectory in both the high and low inflammation pairs, suggesting that this phenomenon is not quite "excess disability" solely in patients with low inflammation.

An additional factor that increases morbidity as well as mortality in RA is frailty, which is associated with age as well as with RA (including people < 65 years old). Hanlon and colleagues examined the change in the "frailty phenotype" over time and its association with adverse clinical outcomes in people with early RA in the Scottish Early Rheumatoid Arthritis (SERA) and UK Biobank cohorts. Frailty was defined by different measures in the two cohorts, including elements of the HAQ disability index for SERA and self-reported fatigue, depression, and poor health for UK Biobank. The computed frailty index was higher in people with higher DAS28 scores and increased with age. Of note, frailty index values were higher prior to treatment initiation and improved somewhat with lower disease activity over time, though those with higher baseline frailty index values tended to have poorer physical function and disease activity over time. Understanding frailty in RA may allow us to better predict and prevent functional limitation, disease progression, and mortality in people with RA.

Of current interest is an observational study by van der Togt and colleagues on the response to COVID-19 vaccines in people with RA being treated with rituximab. Of patients who had previously been treated with 200, 500, or 1000 mg of rituximab prior to COVID-19 vaccination, those who received 200 mg  rituximab as well as those who had longer intervals between rituximab dose and vaccination had a better response to vaccination as defined by immunoglobulins (total, IgG, and IgM) against SARS-CoV-2. Although this study lacked a control arm of people being treated with other disease-modifying antirheumatic drugs and did not evaluate COVID-19 infections or outcomes, its findings do suggest that dosage and timing of rituximab in people with RA should be studied further in regard to vaccine response and infection risk.

Despite the improved outcomes in rheumatoid arthritis (RA) observed in clinical trials from early use of biologic disease-modifying antirheumatic drugs (bDMARD) in a treat-to-target strategy, real-world use may be limited by stopping medications for various reasons. Burkard and colleagues used the Swiss RA registry to examine potential reasons for discontinuation of bDMARD and targeted synthetic disease-modifying antirheumatic drugs (tsDMARD) among over 2500 adults with RA who stopped these medications from 1999 through 2018. In this cohort study, patients were followed from date of discontinuation of their medication until restarting a bDMARD or tsDMARD. The most common reasons for discontinuation were nonresponse and adverse events; of these patients, over 80% restarted a bDMARD or tsDMARD. Only 8% of patients stopped due to remission; of these, nearly half restarted. The authors found a higher proportion of fibromyalgia among patients who stopped due to nonresponse and adverse events vs due to remission. Oddly, though 40%-50% of patients stopped for "unknown reasons" between 2002 and 2006, this proportion dropped to close to 0 after 2010; during the first time period, the proportions stopping medication due to adverse events and nonresponse were also low, suggesting possible misattribution of the reason for treatment cessation. As such, drawing further conclusions on association of different patient characteristics with reasons for treatment cessation is difficult.

The gap between control of inflammatory joint pain in RA and overall patient outcomes has come up frequently in recent studies. Gwinnutt and colleagues looked at patients participating in three European RA registries, comprising over 2500 patients followed over 8-10 years, and classified them as having high or low inflammation on the basis of Disease Activity Score (DAS28) and analyzed Health Assessment Questionnaire (HAQ) score trajectories as low vs high as a measure of disability. Overall, patients in the three registries had different trajectory patterns, though it appears clear, in keeping with other studies, that a subset of patients remain with high HAQ scores despite decreases in DAS28 scores. Older age; being a woman; and more pain, fatigue, and depressive symptoms were associated with higher HAQ trajectory in both the high and low inflammation pairs, suggesting that this phenomenon is not quite "excess disability" solely in patients with low inflammation.

An additional factor that increases morbidity as well as mortality in RA is frailty, which is associated with age as well as with RA (including people < 65 years old). Hanlon and colleagues examined the change in the "frailty phenotype" over time and its association with adverse clinical outcomes in people with early RA in the Scottish Early Rheumatoid Arthritis (SERA) and UK Biobank cohorts. Frailty was defined by different measures in the two cohorts, including elements of the HAQ disability index for SERA and self-reported fatigue, depression, and poor health for UK Biobank. The computed frailty index was higher in people with higher DAS28 scores and increased with age. Of note, frailty index values were higher prior to treatment initiation and improved somewhat with lower disease activity over time, though those with higher baseline frailty index values tended to have poorer physical function and disease activity over time. Understanding frailty in RA may allow us to better predict and prevent functional limitation, disease progression, and mortality in people with RA.

Of current interest is an observational study by van der Togt and colleagues on the response to COVID-19 vaccines in people with RA being treated with rituximab. Of patients who had previously been treated with 200, 500, or 1000 mg of rituximab prior to COVID-19 vaccination, those who received 200 mg  rituximab as well as those who had longer intervals between rituximab dose and vaccination had a better response to vaccination as defined by immunoglobulins (total, IgG, and IgM) against SARS-CoV-2. Although this study lacked a control arm of people being treated with other disease-modifying antirheumatic drugs and did not evaluate COVID-19 infections or outcomes, its findings do suggest that dosage and timing of rituximab in people with RA should be studied further in regard to vaccine response and infection risk.

Despite the improved outcomes in rheumatoid arthritis (RA) observed in clinical trials from early use of biologic disease-modifying antirheumatic drugs (bDMARD) in a treat-to-target strategy, real-world use may be limited by stopping medications for various reasons. Burkard and colleagues used the Swiss RA registry to examine potential reasons for discontinuation of bDMARD and targeted synthetic disease-modifying antirheumatic drugs (tsDMARD) among over 2500 adults with RA who stopped these medications from 1999 through 2018. In this cohort study, patients were followed from date of discontinuation of their medication until restarting a bDMARD or tsDMARD. The most common reasons for discontinuation were nonresponse and adverse events; of these patients, over 80% restarted a bDMARD or tsDMARD. Only 8% of patients stopped due to remission; of these, nearly half restarted. The authors found a higher proportion of fibromyalgia among patients who stopped due to nonresponse and adverse events vs due to remission. Oddly, though 40%-50% of patients stopped for "unknown reasons" between 2002 and 2006, this proportion dropped to close to 0 after 2010; during the first time period, the proportions stopping medication due to adverse events and nonresponse were also low, suggesting possible misattribution of the reason for treatment cessation. As such, drawing further conclusions on association of different patient characteristics with reasons for treatment cessation is difficult.

The gap between control of inflammatory joint pain in RA and overall patient outcomes has come up frequently in recent studies. Gwinnutt and colleagues looked at patients participating in three European RA registries, comprising over 2500 patients followed over 8-10 years, and classified them as having high or low inflammation on the basis of Disease Activity Score (DAS28) and analyzed Health Assessment Questionnaire (HAQ) score trajectories as low vs high as a measure of disability. Overall, patients in the three registries had different trajectory patterns, though it appears clear, in keeping with other studies, that a subset of patients remain with high HAQ scores despite decreases in DAS28 scores. Older age; being a woman; and more pain, fatigue, and depressive symptoms were associated with higher HAQ trajectory in both the high and low inflammation pairs, suggesting that this phenomenon is not quite "excess disability" solely in patients with low inflammation.

An additional factor that increases morbidity as well as mortality in RA is frailty, which is associated with age as well as with RA (including people < 65 years old). Hanlon and colleagues examined the change in the "frailty phenotype" over time and its association with adverse clinical outcomes in people with early RA in the Scottish Early Rheumatoid Arthritis (SERA) and UK Biobank cohorts. Frailty was defined by different measures in the two cohorts, including elements of the HAQ disability index for SERA and self-reported fatigue, depression, and poor health for UK Biobank. The computed frailty index was higher in people with higher DAS28 scores and increased with age. Of note, frailty index values were higher prior to treatment initiation and improved somewhat with lower disease activity over time, though those with higher baseline frailty index values tended to have poorer physical function and disease activity over time. Understanding frailty in RA may allow us to better predict and prevent functional limitation, disease progression, and mortality in people with RA.

Of current interest is an observational study by van der Togt and colleagues on the response to COVID-19 vaccines in people with RA being treated with rituximab. Of patients who had previously been treated with 200, 500, or 1000 mg of rituximab prior to COVID-19 vaccination, those who received 200 mg  rituximab as well as those who had longer intervals between rituximab dose and vaccination had a better response to vaccination as defined by immunoglobulins (total, IgG, and IgM) against SARS-CoV-2. Although this study lacked a control arm of people being treated with other disease-modifying antirheumatic drugs and did not evaluate COVID-19 infections or outcomes, its findings do suggest that dosage and timing of rituximab in people with RA should be studied further in regard to vaccine response and infection risk.