Lornng/cpgQA huggingface dataset:
Background information

Pain is defined as “an unpleasant sensory and emotional experience associated with actual or potential  tissue damage, or described in terms of such damage…Pain is always subjective…It is unquestionably a  sensation in a part or parts of the body, but it is also always unpleasant and therefore also an emotional  experience.” All of these facets signify the complexity of pain as a condition by itself and how it  relates to both the brain and the body. Pain as a symptom is multifaceted and is described and  characterized by many factors such as its quality (e.g., sharp versus dull), intensity, timing, location, and  whether it is associated with position or movement.

Question: Define pain according to the VA/DoD CPG.
Answer: an unpleasant sensory and emotional experience associated with actual or potential  tissue damage, or described in terms of such damage…Pain is always subjective…It is unquestionably a  sensation in a part or parts of the body, but it is also always unpleasant and therefore also an emotional  experience.

Question: How to characterize pain as a symptom?
Answer: multifaceted

Question: Which factors can describe and characterize pain as a symptom?
Answer: quality (e.g., sharp versus dull), intensity, timing, location, and  whether it is associated with position or movement
Background information

Chronic pain is defined as pain lasting three months or more. It is often associated with changes in the  central nervous system (CNS) known as central sensitization. Whereas acute and subacute pain are  thought to involve primarily nociceptive processing areas in the CNS, chronic pain is thought to be  associated with alterations in brain centers involved with emotions, reward, and executive function as well  as central sensitization of nociceptive pathways across several CNS areas.

Question: Define chronic pain according to the VA/DoD CPG.
Answer: pain lasting three months or more. It is often associated with changes in the  central nervous system (CNS) known as central sensitization.

Question: Which areas in the CNS are involved in the acute and subacute pain?
Answer: primarily nociceptive processing areas

Question: What is CNS?
Answer: central nervous system

Question: Which areas in the CNS are involved in the chronic pain?
Answer: chronic pain is thought to be  associated with alterations in brain centers involved with emotions, reward, and executive function as well  as central sensitization of nociceptive pathways across several CNS areas.
Background information

There are many causes of chronic pain. Pain arising from persistent peripheral stimulation could be  mechanical or chemical/inflammatory in nature typically leading to well-localized nociceptive mechanism pain. Mechanical or inflammatory pain with a visceral origin may produce a less localized pain.  Neuropathic pain due to injury or disease of the central or peripheral nervous system (e.g., spinal cord  injury, diabetic neuropathy, radiculopathy) may lead to poorly localized symptoms such as diffuse pain,  burning, numbness, or a feeling of skin sensitivity.

Question: What are the causes of chronic pain?
Answer: Pain arising from persistent peripheral stimulation could be  mechanical or chemical/inflammatory in nature typically leading to well-localized nociceptive mechanism pain. Mechanical or inflammatory pain with a visceral origin may produce a less localized pain.  Neuropathic pain due to injury or disease of the central or peripheral nervous system (e.g., spinal cord  injury, diabetic neuropathy, radiculopathy) may lead to poorly localized symptoms such as diffuse pain,  burning, numbness, or a feeling of skin sensitivity.

Question: Which pain can lead to well-localized nociceptive mechanism pain?
Answer: Pain arising from persistent peripheral stimulation

Question: Which pain could be mechanical or chemical/inflammatory in nature?
Answer: Pain arising from persistent peripheral stimulation

Question: Which pain may produce a less localized pain?
Answer: Mechanical or inflammatory pain with a visceral origin

Question: Which pain may lead to poorly localized symptoms?
Answer: Neuropathic pain due to injury or disease of the central or peripheral nervous system (e.g., spinal cord  injury, diabetic neuropathy, radiculopathy)

Question: What are some examples of poorly localized symptoms?
Answer: diffuse pain,  burning, numbness, or a feeling of skin sensitivity
Background information

A comprehensive pain assessment includes a biopsychosocial interview and focused physical exam. Elements of the biopsychosocial pain interview include a pain-related history, assessment of pertinent  medical and psychiatric comorbidities including personal and family history of SUD, functional status and  functional goals, coping strategies, and a variety of psychosocial factors such as the patient’s beliefs and  expectations about chronic pain and its treatment. Patients with chronic pain may also experience  worsened quality of life, mental health, immune system function, physical function, sleep, employment  status, and impaired personal relationships. Worsening of some of these factors (e.g., quality of  life, change in employment status) seems to also be associated with pain severity and the presence of  psychiatric comorbidities. Patients with chronic pain report psychological complaints (e.g.,  depression, anxiety, poor self-efficacy, poor general emotional functioning) more often than patients  without chronic pain. Further, there can be social and psychological consequences such as decreased  ability to successfully maintain relationship and career roles and increased depression, fear, and anxiety as  a result of pain.

Question: What does a comprehensive pain assessment include?
Answer: a biopsychosocial interview and focused physical exam

Question: What are the elements of the biopsychosocial pain interview?
Answer: a pain-related history, assessment of pertinent  medical and psychiatric comorbidities including personal and family history of SUD, functional status and  functional goals, coping strategies, and a variety of psychosocial factors such as the patient’s beliefs and  expectations about chronic pain and its treatment

Question: What may be experienced by the patients with chronic pain?
Answer: worsened quality of life, mental health, immune system function, physical function, sleep, employment  status, and impaired personal relationships

Question: What can be associated with pain severity and the presence of  psychiatric comorbidities?
Answer: Worsening of some of these factors (e.g., quality of  life, change in employment status)

Question: Who report psychological complaints more often?
Answer: Patients with chronic pain

Question: What is reported more often by the patients with chronic pain than patients without chronic pain?
Answer: psychological complaints (e.g.,  depression, anxiety, poor self-efficacy, poor general emotional functioning)

Question: What are some examples of psychological complaints made by patients with chronic pain?
Answer: depression, anxiety, poor self-efficacy, poor general emotional functioning

Question: What are some examples of social and psychological consequences on account of chronic pain?
Answer: decreased  ability to successfully maintain relationship and career roles and increased depression, fear, and anxiety as  a result of pain
Background information

Chronic pain is among the most common, costly, and disabling chronic medical conditions in the U.S. In the U.S., approximately 100 million adults experience chronic pain, and pain is associated with  approximately 20% of ambulatory primary care and specialty visits. Since the late 1990s and early 2000s, the proportion of pain visits during which patients  received opioids has increased significantly, as have opioid-related morbidity, mortality, overdose death,  and SUD treatment admissions. Approximately one in five patients with non-cancer pain or pain related diagnoses is prescribed opioids in office-based settings. According to the CDC, sales of  prescription opioids U.S. quadrupled from 1999 and 2014. The absolute number of deaths associated  with use of opioids has increased four-fold since 2000, including by 14% from 2013 to 2014 alone.  Between 1999 and 2015, more than 183,000 people died from overdoses related to prescription  opioids. In one survey, approximately one-third of patients receiving OT for CNCP (or their family  members) indicated thinking that they were “addicted” to or “dependent” on the medication or used the  medication for “fun” or to “get high.” From 2000 through 2013, the rate of heroin overdose deaths  increased nearly four-fold. In the 2000s, the majority of people entering treatment for heroin use used  prescription opioids as their first opioid.

Question: What is one of the most common chronic medical conditions in the U.S.?
Answer: Chronic pain

Question: What is one of the most costly chronic medical conditions in the U.S.?
Answer: Chronic pain

Question: What is one of the most disabling chronic medical conditions in the U.S.?
Answer: Chronic pain

Question: How many adults in the U.S. experience chronic pain?
Answer: approximately 100 million

Question: Since when has there been a significant increment of opioid prescriptions during pain visits?
Answer: the late 1990s and early 2000s

Question: Since when has there been a significant increment of opioid-related morbidity, mortality, overdose death, and SUD treatment admissions?
Answer: the late 1990s and early 2000s

Question: What is the ratio of patients with non-cancer pain or pain-related diagnoses who receive opioid prescriptions in office-based settings?
Answer: Approximately one in five

Question: What were the changes in the sales of prescription opioids in the U.S. from 1999 and 2014, according to CDC?
Answer: quadrupled

Question: How much has the absolute number of deaths associated with the use of opioids increased since 2000?
Answer: four-fold

Question: How much has the absolute number of deaths associated with the use of opioids increased from 2013 to 2014?
Answer: 14%

Question: How many people died between 1999 and 2015 from overdoses related to prescription opioids?
Answer: more than 183,000
Background information

Individuals with conditions that result in or co-occur with chronic pain may have different needs or respond to treatment differently than individuals with chronic pain alone. Many different physical and psychological conditions have a pain component that can be difficult to distinguish from the underlying mechanism of illness. Furthermore, the treatment of co-occurring pain and other conditions may vary or require special considerations during their management. Readers are encouraged to consult other VA/DoD  CPGs for further information (see VA/DoD Clinical Practice Guidelines website: www.healthquality.va.gov).

Question: Who may have different needs or respond to treatment differently than individuals with chronic pain alone?
Answer: Individuals with conditions that result in or co-occur with chronic pain

Question: What can be difficult to distinguish from the underlying mechanism of illness?
Answer: Many different physical and psychological conditions have a pain component
Background information

The risk factors with the greatest impact on the development of opioid-related adverse events are the duration and dose of opioid analgesic use. Beyond duration and dose of OT, many factors increase the risk of adverse outcomes and must be considered prior to initiating or continuing OT (Box 1). Given the insufficient evidence of benefit for LOT, the clinician must carefully weigh harms and benefits and educate the patient as well as his or her family or caregiver prior to proceeding with treatment. As patient values and preferences may be impacted by other clinical considerations, some patients with one or more risk factors for adverse outcomes may differ with the clinician’s assessment that the risks of OT  outweigh the potential for modest short-term benefits. Thus, it is important to consider patients’ values and concerns, address misconceptions, express empathy, and fully explain to patients with one or more risk factors that they may not benefit from, and may even be harmed by, treatment with OT. Conditions that significantly increase the risk of adverse outcomes from LOT are listed below. Patients for whom LOT is initiated should be carefully monitored, and ongoing assessment of risk should be performed with vigilance for the development of additional risk factors and adverse outcomes (see Recommendations  7-9). Consider consultation with appropriate specialty care providers if there is uncertainty about whether the benefits of OT, such as improved function (e.g., return-to-work), outweigh the risks.

Question: What are the risk factors with the greatest impact on the development of opioid-related adverse events?
Answer: the duration and dose of opioid analgesic use

Question: Why must the clinician carefully weigh harms and benefits and educate the patient as well as his or her family or caregiver prior to proceeding with treatment?
Answer: Given the insufficient evidence of benefit for LOT

Question: Why is it important to consider patients’ values and concerns, address misconceptions, express empathy, and fully explain to patients with one or more risk factors that they may not benefit from, and may even be harmed by, treatment with OT?
Answer: As patient values and preferences may be impacted by other clinical considerations, some patients with one or more risk factors for adverse outcomes may differ with the clinician’s assessment that the risks of OT  outweigh the potential for modest short-term benefits.

Question: What should be done for patients for whom LOT is initiated?
Answer: should be carefully monitored, and ongoing assessment of risk should be performed with vigilance for the development of additional risk factors and adverse outcomes

Question: What to do if there is uncertainty about whether the benefits of OT, such as improved function (e.g., return-to-work), outweigh the risks?
Answer: Consider consultation with appropriate specialty care providers
Background information

Duration and dose of OT: See Recommendation 2 for more guidance on duration of OT and Recommendations 10-12 for more guidance on dosing of OT. Severe respiratory instability or sleep disordered breathing: This would include any co-occurring condition that significantly affects respiratory rate or function such as chronic obstructive pulmonary disease (COPD), asthma, pneumonia, sleep apnea, or a neuromuscular condition (e.g., amyotrophic lateral sclerosis). Two large observational studies of patients with a  history of COPD and sleep apnea who were prescribed opioids showed a weak but positive association with opioid-related toxicity/overdose and overdose-related death.[58,59]

Question: What does include severe respiratory instability or sleep disordered breathing?
Answer: any co-occurring condition that significantly affects respiratory rate or function such as chronic obstructive pulmonary disease (COPD), asthma, pneumonia, sleep apnea, or a neuromuscular condition (e.g., amyotrophic lateral sclerosis)

Question: Who showed a weak but positive association with opioid-related toxicity/overdose and overdose-related death?
Answer: Two large observational studies of patients with a  history of COPD and sleep apnea who were prescribed opioids
Background information

Acute psychiatric instability or intermediate to high acute suicide risk: Intermediate to high acute suicide risk, severe depression, unstable bipolar disorder, or unstable psychotic disorder precludes the safe use of self-administered LOT.[60] Im et al. (2015) (n=487,462) found that a  diagnosis of a mood disorder was significantly associated with suicide attempts for the chronic use of short-acting and long-acting opioids compared with no diagnosis of a mood disorder.[61] In a study of patients on opioids, Campbell et al. (2015) reported that those with bipolar disorder had 2.9 times the odds of suicidal ideation within the past 12 months as well as 3.2  times the odds of a lifetime suicide attempt compared to those with no bipolar disorder.[62] See  Recommendation 8 and the VA/DoD Suicide CPG2 for more information on suicidality. See the  VA/DoD Clinical Practice Guideline for Management of Bipolar Disorder in Adults (VA/DoD BD  CPG) for more information on bipolar disorder.3 Merrill and colleagues found that high dose chronic opioid therapy for pain was associated with depressed mood.[63] Treatment for chronic pain with movement, exercise, and cognitive-behavioral therapy for pain may have benefits in treating depression, PTSD, and in reducing suicide risk.[64]

Question: What does preclude the safe use of self-administered LOT?
Answer: Intermediate to high acute suicide risk, severe depression, unstable bipolar disorder, or unstable psychotic disorder

Question: What was significantly associated with suicide attempts for the chronic use of short-acting and long-acting opioids?
Answer: a  diagnosis of a mood disorder

Question: In a study of patients on opioids, who had 2.9 times the odds of suicidal ideation within the past 12 months as well as 3.2  times the odds of a lifetime suicide attempt compared to those with no bipolar disorder?
Answer: those with bipolar disorder

Question: What are the odds of suicidal ideation within the past 12 months in those with bipolar disorder compared to those with no bipolar disorder?
Answer: 2.9 times

Question: What are the odds of a lifetime suicide attempt in those with bipolar disorder compared to those with no bipolar disorder?
Answer: 3.2  times

Question: Where can more information on suicidality be found?
Answer: the VA/DoD Suicide CPG

Question: Where can more information on bipolar disorder be found?
Answer: the  VA/DoD Clinical Practice Guideline for Management of Bipolar Disorder in Adults (VA/DoD BD  CPG)

Question: What was associated with depressed mood?
Answer: high dose chronic opioid therapy for pain

Question: Which treatment for chronic pain may have benefits in treating depression, PTSD, and in reducing suicide risk?
Answer: Treatment for chronic pain with movement, exercise, and cognitive-behavioral therapy for pain
Background information

Current or history of SUD: For patients with untreated SUD, see Recommendation 4. For  patients with diagnosed OUD, see Recommendation 17. Frequent requests for early refills or atypically large quantities required to control pain can signal an emerging SUD as well as  diversion (see Evidence for or history of diversion of controlled substances). See the VA/DoD  SUD CPG.4 Depression or history of depression: Zedler et al. (2014) reported that among patients  being treated by the VHA system that received opioids, a history of depression was  significantly associated with opioid-related toxicity/overdose compared to no history of  depression.[58] LOT has been associated with worsening depressive symptoms.[63] See the  VA/DoD MDD CPG.5 PTSD: Seal et al. (2012) (n=15,676) noted that among patients on OT, a prevalence of self inflicted injuries was significantly higher among patients with a history of PTSD (with or  without other mental health diagnoses) as compared to patients with other (or no) mental  health diagnoses.[65] For more information, see the VA/DoD PTSD CPG.6 History of drug overdose: A history of overdose is a red flag and providers should proceed with  utmost caution when considering LOT for these patients. Under 30 years of age: See Recommendation 6.

Question: What can signal an emerging SUD as well as  diversion?
Answer: Frequent requests for early refills or atypically large quantities required to control pain

Question: What can be signalled by frequent requests for early refills required to control pain?
Answer: an emerging SUD as well as  diversion

Question: What can be signalled by frequent requests for atypically large quantities required to control pain?
Answer: an emerging SUD as well as  diversion

Question: Among patients  being treated by the VHA system that received opioids, what was significantly associated with opioid-related toxicity/overdose compared to no history of  depression?
Answer: a history of depression

Question: Among patients  being treated by the VHA system that received opioids, a history of depression was  significantly associated with what?
Answer: opioid-related toxicity/overdose

Question: What has been associated with worsening depressive symptoms?
Answer: LOT

Question: LOT has been associated with what kinds of symptoms?
Answer: worsening depressive symptoms

Question: Among patients on OT, a prevalence of self inflicted injuries was significantly higher among which patients?
Answer: patients with a history of PTSD (with or  without other mental health diagnoses) as compared to patients with other (or no) mental  health diagnoses

Question: Among patients on OT, what was significantly higher among patients with a history of PTSD as compared to patients with other (or no) mental  health diagnoses?
Answer: a prevalence of self inflicted injuries

Question: Where can more information be found on PTSD?
Answer: VA/DoD PTSD CPG

Question: What is a red flag in the presence of which providers should proceed with utmost caution when considering LOT for these patients?
Answer: A history of overdose
Background information

Co-administration of a drug capable of inducing fatal drug-drug interactions: Providers should carefully rule out and avoid potential drug interactions prior to initiating LOT. For example, the following combinations are dangerous:[66] i)Opioids with benzodiazepines (compared to patients with no prescription, the odds ratio [OR] and 95% confidence interval [CI] for drug-related death was OR: 14.92, 95% CI: 7.00- 31.77 for patients who filled a prescription for opioids and benzodiazepines; OR: 3.40, 95%  CI: 1.60-7.21 for patients who filled only an opioid prescription, and 7.21, 95% CI: 3.33-15.60 for patients who filled only a benzodiazepine prescription) (see Recommendation 5) [66,67], ii)Fentanyl with CYP3A4 inhibitors, iii) Methadone with drugs that can prolong the QT interval (the heart rate’s corrected time  interval from the start of the Q wave to the end of the T wave) (e.g., CYP450 2B6 inhibitors)

Question: What should providers carefully rule out and avoid?
Answer: potential drug interactions prior to initiating LOT

Question: What combinations of drugs are dangerous?
Answer: i)Opioids with benzodiazepines (compared to patients with no prescription, the odds ratio [OR] and 95% confidence interval [CI] for drug-related death was OR: 14.92, 95% CI: 7.00- 31.77 for patients who filled a prescription for opioids and benzodiazepines; OR: 3.40, 95%  CI: 1.60-7.21 for patients who filled only an opioid prescription, and 7.21, 95% CI: 3.33-15.60 for patients who filled only a benzodiazepine prescription) (see Recommendation 5) [66,67], ii)Fentanyl with CYP3A4 inhibitors, iii) Methadone with drugs that can prolong the QT interval (the heart rate’s corrected time  interval from the start of the Q wave to the end of the T wave) (e.g., CYP450 2B6 inhibitors)