Lornng/cpgQA huggingface dataset:
Background information

QTc interval >450 ms for using methadone: Unlike most other commonly used opioids, methadone has unique pharmacodynamic properties that can prolong the QTc interval (the heart rate’s corrected time interval from the start of the Q wave to the end of the T wave) and precipitate torsades de pointes, a dangerous or fatal cardiac arrhythmia. Patients who may be at risk include those with other risk factors for QTc prolongation, current or prior electrocardiograms (ECGs) with a prolonged QTc >450 ms, or a history of syncope. Therefore, ECGs before and after initiating methadone are highly advised (see Methadone Dosing Guidance).

Question: Which opioid has unique pharmacodynamic properties that can prolong the QTc interval and precipitate torsades de pointes, a dangerous or fatal cardiac arrhythmia?
Answer: methadone

Question: What is QTc interval?
Answer: the heart rate’s corrected time interval from the start of the Q wave to the end of the T wave

Question: What is torsades de pointes?
Answer: a dangerous or fatal cardiac arrhythmia

Question: Which one is a dangerous or fatal cardiac arrhythmia?
Answer: torsades de pointes

Question: What unique properties does methadone have?
Answer: unique pharmacodynamic properties that can prolong the QTc interval (the heart rate’s corrected time interval from the start of the Q wave to the end of the T wave) and precipitate torsades de pointes, a dangerous or fatal cardiac arrhythmia

Question: Why are ECGs highly advised before and after initiating methadone?
Answer: Patients who may be at risk include those with other risk factors for QTc prolongation, current or prior electrocardiograms (ECGs) with a prolonged QTc >450 ms, or a history of syncope.

Question: Which patients may be at risk?
Answer: those with other risk factors for QTc prolongation, current or prior electrocardiograms (ECGs) with a prolonged QTc >450 ms, or a history of syncope
Background information

Intolerance, serious adverse effects, or a history of inadequate beneficial response to opioids: Serious harm may occur should patients be prescribed additional (or different) opioids if prior administration of opioids led to serious adverse effects or was not tolerated. It is also inadvisable to prescribe opioids to patients who already have had an adequate opioid trial (of sufficient dose and duration to determine whether or not it will optimize benefit) without a  positive response.

Question: When may serious harm occur in patients?
Answer: should patients be prescribed additional (or different) opioids if prior administration of opioids led to serious adverse effects or was not tolerated

Question: It is inadvisable to prescribe opioids to which patients?
Answer: patients who already have had an adequate opioid trial (of sufficient dose and duration to determine whether or not it will optimize benefit) without a  positive response
Background information

Impaired bowel motility unresponsive to therapy: Opioids inhibit bowel peristalsis. Their use with patients with impaired bowel motility can increase the risk of severe constipation/impaction or possible obstruction.

Question: What do opioids do to the bowel?
Answer: inhibit bowel peristalsis

Question: How can the use of opioids affect patients with impaired bowel motility?
Answer: can increase the risk of severe constipation/impaction or possible obstruction
Background information

Headache not responsive to other pain treatment modalities: LOT is an ineffective treatment  modality for patients with migraine headaches (with or without aura), tension-type headaches,  occipital neuralgia, or myofascial pain and may result in worsening of the underlying headache  condition through factors such as central sensitization and withdrawal.

Question: What is an ineffective treatment modality for patients with migraine headaches (with or without aura)?
Answer: LOT

Question: What is an ineffective treatment modality for patients with tension-type headaches?
Answer: LOT

Question: What is an ineffective treatment modality for patients with occipital neuralgia?
Answer: LOT

Question: What is an ineffective treatment modality for patients with myofascial pain?
Answer: LOT

Question: What is an ineffective treatment modality for patients with migraine headaches (with or without aura), tension-type headaches, occipital neuralgia, or myofascial pain?
Answer: LOT

Question: LOT is an ineffective treatment modality for patients with what kind of headaches?
Answer: migraine headaches (with or without aura), tension-type headaches,  occipital neuralgia, or myofascial pain

Question: How may LOT affect patients with migraine headaches, tension-type headaches, occipital neuralgia, or myofascial pain?
Answer: may result in worsening of the underlying headache  condition through factors such as central sensitization and withdrawal

Question: What treatment modality may result in worsening of the underlying headache condition in patients with migraine headaches, tension-type headaches, occipital neuralgia, or myofascial pain?
Answer: LOT
Background information

Traumatic brain injury (TBI): Patients with a history of TBI who use chronic short-acting and  long-acting opioids are more likely to attempt suicide.[61]

Question: Who are more likely to attempt suicide?
Answer: Patients with a history of TBI who use chronic short-acting and  long-acting opioids
Background information

True allergy to opioid agents: Morphine causes a release of histamine that frequently results in  itching, but this does not constitute an allergic reaction. True allergy to opioid agents  (e.g., anaphylaxis) is not common, but does occur. Generally, allergy to one opioid does not  mean the patient is allergic to other opioids; many times, rotating to a different opioid may be  effective. When an opioid allergy is present and OT is being considered, consultation with an allergist may be helpful.

Question: Why does Morphine frequently cause itching?
Answer: Morphine causes a release of histamine

Question: What is an example of true allergy to opioid agents?
Answer: anaphylaxis

Question: When may a consultation with an allergist be helpful?
Answer: When an opioid allergy is present and OT is being considered

Question: What to do when an opioid allergy is present and OT is being considered?
Answer: consultation with an allergist may be helpful
Recommendations

a) We recommend against initiation of long-term opioid therapy for chronic pain. (Strong against) b) We recommend alternatives to opioid therapy such as self-management strategies and other non-pharmacological treatments. (Strong for) c) When pharmacologic therapies are used, we recommend non-opioids over opioids. (Strong for) (Reviewed, New-replaced)

Question: What is the recommendation regarding initiation of long-term opioid therapy for chronic pain?
Answer: recommend against

Question: What is the stance regarding alternatives to opioid therapy such as self-management strategies and other non-pharmacological treatments?
Answer: recommend

Question: When should non-opioids be recommended over opioids?
Answer: When pharmacologic therapies are used

Question: What are some alternatives to opioid therapy?
Answer: self-management strategies and other non-pharmacological treatments
Recommendations

As outlined in this CPG, there is a rapidly growing understanding of the significant harms of LOT even at  doses lower than 50 mg oral morphine equivalent daily dose [MEDD], including but not limited to  overdose and OUD. At the same time there is a lack of high quality evidence that LOT improves pain,  function, and/or quality of life. The literature review conducted for this CPG identified no studies  evaluating the effectiveness of LOT for outcomes lasting longer than 16 weeks. Given the lack of evidence  showing sustained functional benefit of LOT and moderate evidence outlining harms, non-opioid  treatments are preferred for chronic pain. Patient values, goals, concerns, and preferences must be  factored into clinical decision making on a case-by-case basis. When considering the initiation or  continuation of LOT, it is important to consider whether LOT will result in clinically meaningful  improvements in function such as readiness to return to work/duty and/or measurable improvement in  other areas of function, such that the benefits outweigh the potential harms.

Question: Why non-opioid  treatments are preferred for chronic pain?
Answer: Given the lack of evidence  showing sustained functional benefit of LOT and moderate evidence outlining harms

Question: In the literature review conducted for this CPG, are there any study evaluating the effectiveness of LOT for outcomes lasting longer than 16 weeks?
Answer: no

Question: What must be factored into clinical decision making on a case-by-case basis?
Answer: Patient values, goals, concerns, and preferences

Question: What needs to be considered when considering the initiation or continuation of LOT?
Answer: consider whether LOT will result in clinically meaningful  improvements in function such as readiness to return to work/duty and/or measurable improvement in  other areas of function, such that the benefits outweigh the potential harms
Recommendations

While there is currently no evidence in the literature documenting the benefit of LOT that demonstrates  improvement in pain and function, we recognize that in a rare subset of individuals a decision to initiate  LOT may be considered (e.g., for intermittent severe exacerbations of chronic painful conditions). If a  decision is made to initiate LOT, a careful assessment of benefits and risks should be made to ensure that  the benefits are expected to outweigh the well-documented risks. In addition, prior to this consideration, a  multimodal treatment plan should be integrated into the patient’s care. Once opioid therapy is initiated,  all opioid risk mitigation strategies outlined in this guideline (see Recommendation 7) should be put into  place.

Question: What does the literature say about the the benefit of LOT?
Answer: there is currently no evidence in the literature documenting the benefit of LOT that demonstrates  improvement in pain and function

Question: What to do if a  decision is made to initiate LOT?
Answer: a careful assessment of benefits and risks should be made to ensure that  the benefits are expected to outweigh the well-documented risks

Question: What kind of treatment plan should be integrated into the patient’s care prrior to considering LOT?
Answer: multimodal

Question: What to do once opioid therapy is initiated?
Answer: all opioid risk mitigation strategies outlined in this guideline (see Recommendation 7) should be put into  place
Recommendations

In 2011, in response to the recognition of pain and its management as a public health problem, the  National Academy of Medicine investigated and reported on the state of pain research, treatment, and  education in the U.S. The report called for a cultural transformation in the way pain is viewed and  treated.[3] Accordingly, the U.S. Department of Health and Human Services (HHS) National Pain Strategy  (March 2016) recommends a biopsychosocial approach to pain care that is multimodal and  interdisciplinary.[26] The underlying concepts of the biopsychosocial model of pain include the idea that  pain perception and its effects on the patient’s function is mediated by multiple factors (e.g., mood, social  support, prior experience, biomechanical factors), not just biology alone. With this overall change in  construct, a biopsychosocial assessment and treatment plan should be tailored accordingly.

Question: Why did the National Academy of Medicine investigated and reported on the state of pain research, treatment, and  education in the U.S. in 2011?
Answer: in response to the recognition of pain and its management as a public health problem

Question: In response to the recognition of pain and its management as a public health problem in 2011, who investigated and reported on the state of pain research, treatment, and  education in the U.S.?
Answer: the  National Academy of Medicine

Question: In response to the recognition of pain and its management as a public health problem in 2011, what was investigated and reported by the National Academy of Medicine?
Answer: the state of pain research, treatment, and  education in the U.S.

Question: What was the impact of the report on the state of pain research, treatment, and  education in the U.S. by the National Academy of Medicine in 2011?
Answer: The report called for a cultural transformation in the way pain is viewed and  treated.

Question: What does the U.S. Department of Health and Human Services (HHS) National Pain Strategy  (March 2016) recommend?
Answer: a biopsychosocial approach to pain care that is multimodal and  interdisciplinary

Question: Who does recommend a biopsychosocial approach to pain care that is multimodal and interdisciplinary?
Answer: the U.S. Department of Health and Human Services (HHS) National Pain Strategy  (March 2016)

Question: What are included in the underlying concepts of the biopsychosocial model of pain?
Answer: pain perception and its effects on the patient’s function is mediated by multiple factors (e.g., mood, social  support, prior experience, biomechanical factors), not just biology alone
Recommendations

In addition to non-pharmacological therapies (e.g., exercise, CBT), appropriate mechanism and condition specific non-opioid pharmacologic agents should be tried and optimized before consideration of opioid  medications (e.g., gabapentin in neuropathic pain states).[83] Potential contraindications and long-term  risks of use should be considered for non-opioid pharmacologic agents as well, as these also can carry risk  of harm, depending on the specific patient and chosen medication.

Question: In addition to non-pharmacological therapies, what should be tried and optimized before consideration of opioid medications?
Answer: appropriate mechanism and condition specific non-opioid pharmacologic agents

Question: What is an example of opioid medications?
Answer: gabapentin in neuropathic pain states

Question: What should be considered for non-opioid pharmacologic agents?
Answer: Potential contraindications and long-term  risks of use

Question: Why should the potential contraindications and long-term  risks of use be considered for non-opioid pharmacologic agents as well?
Answer: these also can carry risk  of harm, depending on the specific patient and chosen medication
Recommendations

Patient access to physical, psychological, and pain rehabilitation modalities should be considered. In some  cases access to care may be limited; all VA and DoD clinics may not have access to multidisciplinary pain  services. Still, all avenues for obtaining these treatments (e.g. Internet based CBT) and all appropriate non opioid medications should be exhausted before consideration of LOT.[82]

Question: To which modalities should the patient have access?
Answer: physical, psychological, and pain rehabilitation modalities

Question: What should be exhausted before consideration of LOT?
Answer: all avenues for obtaining these treatments (e.g. Internet based CBT) and all appropriate non opioid medications
Recommendations

Further studies may help determine earlier in the course of treatment which patients are most likely to  benefit from a specific non-pharmacologic therapy (physical, psychological, and pain rehabilitation) or non opioid pharmacologic therapies alone or as part of a multimodal approach.

Question: What may help determine earlier in the course of treatment which patients are most likely to  benefit from a specific non-pharmacologic therapy or non opioid pharmacologic therapies alone or as part of a multimodal approach?
Answer: Further studies
Recommendations

If prescribing opioid therapy for patients with chronic pain, we recommend a short duration. (Strong for| Reviewed, New-replaced) Note: Consideration of opioid therapy beyond 90 days requires re-evaluation and discussion with patient of risks and benefits. For patients currently on long-term opioid therapy, we recommend ongoing risk mitigation strategies (see Recommendations 7-9), assessment for opioid use disorder, and consideration for tapering when risks exceed benefits (see Recommendation 14). (Strong for| Reviewed, New-replaced)

Question: What timeframe is recommended if prescribing opioid therapy for patients with chronic pain?
Answer: a short duration

Question: What does require re-evaluation and discussion with patient of risks and benefits?
Answer: Consideration of opioid therapy beyond 90 days

Question: What is required when considering opioid therapy beyond 90 days?
Answer: re-evaluation and discussion with patient of risks and benefits

Question: What is recommended for patients currently on long-term opioid therapy?
Answer: ongoing risk mitigation strategies (see Recommendations 7-9), assessment for opioid use disorder, and consideration for tapering when risks exceed benefits (see Recommendation 14)

Question: For whom ongoing risk mitigation strategies are recommended?
Answer: patients currently on long-term opioid therapy

Question: For whom assessment for opioid use disorder is recommended?
Answer: patients currently on long-term opioid therapy

Question: For whom consideration for tapering when risks exceed benefits is recommended?
Answer: patients currently on long-term opioid therapy

Question: For whom ongoing risk mitigation strategies, assessment for opioid use disorder, and consideration for tapering when risks exceed benefits are recommended?
Answer: patients currently on long-term opioid therapy
Recommendations

The support for these recommendations is two-fold: a paucity of research showing benefit for LOT and the strength of the evidence demonstrating the potential for life-threatening harm. Of utmost concern is the heightened risk for developing OUD in patients who receive OT beyond 90 days (see Appendix C for  Diagnostic and Statistical Manual of Mental Disorders [DSM] 5 diagnostic criteria for OUD).

Question: What is the utmost concern for patients who receive OT beyond 90 days?
Answer: the heightened risk for developing OUD
Recommendations

Similar to other risk factors, continuing OT beyond 90 days’ duration should be weighed heavily in the risk benefit calculus for LOT. Continuing OT for longer than 90 days is not an absolute contraindication to LOT.  There may be some situations where the benefits of LOT clearly outweigh the risks. That must be  determined through individual clinical assessment.

Question: What should be weighed heavily in the risk benefit calculus for LOT?
Answer: continuing OT beyond 90 days’ duration

Question: What is not an absolute contraindication to LOT?
Answer: Continuing OT for longer than 90 days

Question: What must be determined through individual clinical assessment?
Answer: There may be some situations where the benefits of LOT clearly outweigh the risks.

Question: How to determine the situations where the benefits of LOT clearly outweigh the risks?
Answer: through individual clinical assessment
Recommendations

Moderate quality evidence demonstrates that the prevalence of OUD in patients with CNCP is related to duration of opioid use as well as dose (see Recommendations 7-9).[86-88] There are two studies of  patients with CNCP which support the current recommendations. Edlund et al. (2014) conducted a large  retrospective cohort study where they examined claims data from a health insurance database between  2000 and 2005 to examine factors predictive of developing OUD.[86] Days’ supply of opioids was  categorized as none, acute duration (1-90 days), or chronic duration (91+ days). Average daily dose was  defined as none, low (1-36 mg MEDD), medium (36-120 mg MEDD), or high (>120 mg MEDD). The OR of  developing OUD ranged based on dose and duration (OR: 3.03, 95% CI: 2.32-3.95 for low dose, acute  opioid prescription; OR: 14.92, 95% CI: 10.38-21.46 for low dose, chronic opioids prescriptions; OR: 3.10,  95% CI: 1.67-5.77 for high dose, acute opioid prescriptions; OR: 122.45, 95% CI: 72.79-205.99 for high  dose, chronic opioid prescriptions). They found that even greater than opioid dose, duration of OT was the  strongest predictor of developing OUD. Additionally, a study by Boscarino et al. (2011) examined medical  records from a large healthcare system.[89] Through interviews with a random sample of patients on LOT,  they examined factors associated with and the prevalence of OUD (using DSM IV and 5 criteria). These  results showed that the prevalence of lifetime OUD for patients on LOT was 34.9% (based on DSM-5  criteria) and 35.5% (based on DSM-IV criteria).

Question: To what the prevalence of OUD in patients with CNCP is related?
Answer: duration of opioid use as well as dose

Question: Which one is the strongest predictor of developing OUD among opioid dose and duration of OT?
Answer: duration of OT
Recommendations

The relationship between OUD and duration of therapy is magnified when patients have a history of  previous opioid or non-opioid SUD. A cross-sectional cohort study found that provision of LOT (four  prescriptions within a 12 month period) to CNCP patients who had a history of severe OUD resulted in  increased odds of developing OUD (OR: 56.36, 95% CI: 32.49-97.76).[88]

Question: When is the relationship between OUD and duration of therapy magnified?
Answer: when patients have a history of  previous opioid or non-opioid SUD
Recommendations

Patients should be informed that progression from acute to long-term OT is associated with little evidence  for sustained analgesic efficacy but a substantial increase in risk for OUD. Providers should discuss this information with patients at initiation of OT and continuously thereafter to ensure that the patient  understands the associated risks and benefits of LOT. Fully informed, some patients may desire  continuation of OT while others may decline its continued provision. Research is necessary to more accurately determine how long it takes for OUD to occur and whether the  nature of the pain is one of the factors that can influence either of this phenomena.

Question: What to inform patient regarding progression from acute to long-term OT?
Answer: progression from acute to long-term OT is associated with little evidence  for sustained analgesic efficacy but a substantial increase in risk for OUD

Question: What is associated with little evidence for sustained analgesic efficacy but a substantial increase in risk for OUD?
Answer: progression from acute to long-term OT

Question: What information should be discussed with patients at initiation of OT and continuously thereafter?
Answer: progression from acute to long-term OT is associated with little evidence  for sustained analgesic efficacy but a substantial increase in risk for OUD

Question: When should the providers discuss with patients that progression from acute to long-term OT is associated with little evidence  for sustained analgesic efficacy but a substantial increase in risk for OUD?
Answer: at initiation of OT and continuously thereafter

Question: Why should the providers discuss with patients that progression from acute to long-term OT is associated with little evidence  for sustained analgesic efficacy but a substantial increase in risk for OUD?
Answer: to ensure that the patient  understands the associated risks and benefits of LOT

Question: What is necessary to more accurately determine how long it takes for OUD to occur and whether the  nature of the pain is one of the factors that can influence either of this phenomena?
Answer: Research

Question: What is necessary to more accurately determine how long it takes for OUD to occur?
Answer: Research

Question: What can be determined more accurately by research?
Answer: how long it takes for OUD to occur and whether the  nature of the pain is one of the factors that can influence either of this phenomena