Hieu-Pham/cpgQA huggingface dataset:
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 is necessary to more accurately determine how long it takes for OUD to occur?
Answer: Research
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 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
Recommendations

We recommend against long-term opioid therapy for pain in patients with untreated substance use disorder. (Strong against) For patients currently on long-term opioid therapy with evidence of untreated substance use  disorder, we recommend close monitoring, including engagement in substance use disorder treatment, and discontinuation of opioid therapy for pain with appropriate tapering (see  Recommendation 14 and Recommendation 17). (Strong for) (Reviewed, Amended) 

Question: What is the stance regarding long-term opioid therapy for pain in patients with untreated substance use disorder?
Answer: recommend against
Recommendations

We recommend against long-term opioid therapy for pain in patients with untreated substance use disorder. (Strong against) For patients currently on long-term opioid therapy with evidence of untreated substance use  disorder, we recommend close monitoring, including engagement in substance use disorder treatment, and discontinuation of opioid therapy for pain with appropriate tapering (see  Recommendation 14 and Recommendation 17). (Strong for) (Reviewed, Amended) 

Question: For which patients close monitoring, including engagement in substance use disorder treatment, and discontinuation of opioid therapy for pain with appropriate tapering are recommended?
Answer: patients currently on long-term opioid therapy with evidence of untreated substance use  disorder
Recommendations

We recommend against long-term opioid therapy for pain in patients with untreated substance use disorder. (Strong against) For patients currently on long-term opioid therapy with evidence of untreated substance use  disorder, we recommend close monitoring, including engagement in substance use disorder treatment, and discontinuation of opioid therapy for pain with appropriate tapering (see  Recommendation 14 and Recommendation 17). (Strong for) (Reviewed, Amended) 

Question: What is recommended for patients currently on long-term opioid therapy with evidence of untreated substance use  disorder?
Answer: close monitoring, including engagement in substance use disorder treatment, and discontinuation of opioid therapy for pain with appropriate tapering
Recommendations

Opioids carry a significant risk for OUD, overdose, and death, especially among patients with untreated  SUD. The recommendation against LOT for patients with SUD is supported by five large studies (four  retrospective case cohort studies and one case cohort study).[59,61,66,86,87] Individually, these studies  are of moderate strength; however, the combined weight of their results is strongly supportive of this  recommendation. Clinicians should note that this recommendation does not refer to patients whose sole  SUD relates to tobacco misuse. 

Question: Opioids carry a significant risk for what?
Answer: OUD, overdose, and death, especially among patients with untreated  SUD
Recommendations

Opioids carry a significant risk for OUD, overdose, and death, especially among patients with untreated  SUD. The recommendation against LOT for patients with SUD is supported by five large studies (four  retrospective case cohort studies and one case cohort study).[59,61,66,86,87] Individually, these studies  are of moderate strength; however, the combined weight of their results is strongly supportive of this  recommendation. Clinicians should note that this recommendation does not refer to patients whose sole  SUD relates to tobacco misuse. 

Question: What does carry a significant risk for OUD, overdose, and death, especially among patients with untreated  SUD?
Answer: Opioids
Recommendations

Opioids carry a significant risk for OUD, overdose, and death, especially among patients with untreated  SUD. The recommendation against LOT for patients with SUD is supported by five large studies (four  retrospective case cohort studies and one case cohort study).[59,61,66,86,87] Individually, these studies  are of moderate strength; however, the combined weight of their results is strongly supportive of this  recommendation. Clinicians should note that this recommendation does not refer to patients whose sole  SUD relates to tobacco misuse. 

Question: The recommendation against LOT for patients with SUD does not refer to which patients?
Answer: patients whose sole  SUD relates to tobacco misuse
Recommendations

The Edlund et al. (2014) study of 568,640 commercial health plan patients (see Recommendation 2 and 3)  found that those diagnosed with CNCP and an alcohol use or non-opioid drug use disorder had higher rates  of OUD (OR: 3.22, 95% CI: 1.79-5.80 for patients with pre-index alcohol use disorder compared to no  alcohol use disorder; OR: 8.26, 95% CI: 4.74-14.39 for patients with pre-index non-opioid drug use  disorders compared to no non-opioid drug use disorders).[86] Moreover, Huffman et al. (2015) found that  the presence of a lifetime history of SUD for patients with CNCP was associated with 28 times increased  odds of therapeutic opioid addiction compared to patients with CNCP without a lifetime history of SUD (OR: 28.58, 95% CI: 10.86-75.27).[87]  

Question: Who had higher rates  of OUD?
Answer: those diagnosed with CNCP and an alcohol use or non-opioid drug use disorder
Recommendations

The Edlund et al. (2014) study of 568,640 commercial health plan patients (see Recommendation 2 and 3)  found that those diagnosed with CNCP and an alcohol use or non-opioid drug use disorder had higher rates  of OUD (OR: 3.22, 95% CI: 1.79-5.80 for patients with pre-index alcohol use disorder compared to no  alcohol use disorder; OR: 8.26, 95% CI: 4.74-14.39 for patients with pre-index non-opioid drug use  disorders compared to no non-opioid drug use disorders).[86] Moreover, Huffman et al. (2015) found that  the presence of a lifetime history of SUD for patients with CNCP was associated with 28 times increased  odds of therapeutic opioid addiction compared to patients with CNCP without a lifetime history of SUD (OR: 28.58, 95% CI: 10.86-75.27).[87]  

Question: What was associated with 28 times increased  odds of therapeutic opioid addiction compared to patients with CNCP without a lifetime history of SUD?
Answer: the presence of a lifetime history of SUD for patients with CNCP
Recommendations

The Edlund et al. (2014) study of 568,640 commercial health plan patients (see Recommendation 2 and 3)  found that those diagnosed with CNCP and an alcohol use or non-opioid drug use disorder had higher rates  of OUD (OR: 3.22, 95% CI: 1.79-5.80 for patients with pre-index alcohol use disorder compared to no  alcohol use disorder; OR: 8.26, 95% CI: 4.74-14.39 for patients with pre-index non-opioid drug use  disorders compared to no non-opioid drug use disorders).[86] Moreover, Huffman et al. (2015) found that  the presence of a lifetime history of SUD for patients with CNCP was associated with 28 times increased  odds of therapeutic opioid addiction compared to patients with CNCP without a lifetime history of SUD (OR: 28.58, 95% CI: 10.86-75.27).[87]  

Question: The presence of a lifetime history of SUD for patients with CNCP was associated with what?
Answer: 28 times increased  odds of therapeutic opioid addiction compared to patients with CNCP without a lifetime history of SUD
Recommendations

Some patients with SUD may disagree with the recommendation to use non-opioid modalities in lieu of  LOT to treat their pain. However, the lack of evidence of efficacy of LOT and considerable evidence of  significant harms of overdose, death from overdose, and increased risk of suicide outweigh any potential  modest benefit of prescribing LOT in this population. See Recommendation 7 for additional information regarding UDT and risk mitigation. See the VA/DoD SUD CPG for guidance on management of SUD.

Question: Who may disagree with the recommendation to use non-opioid modalities in lieu of LOT to treat their pain?
Answer: Some patients with SUD
Recommendations

Some patients with SUD may disagree with the recommendation to use non-opioid modalities in lieu of  LOT to treat their pain. However, the lack of evidence of efficacy of LOT and considerable evidence of  significant harms of overdose, death from overdose, and increased risk of suicide outweigh any potential  modest benefit of prescribing LOT in this population. See Recommendation 7 for additional information regarding UDT and risk mitigation. See the VA/DoD SUD CPG for guidance on management of SUD.8

Question: Some patients with SUD may disagree with what?
Answer: the recommendation to use non-opioid modalities in lieu of  LOT to treat their pain
Recommendations

Some patients with SUD may disagree with the recommendation to use non-opioid modalities in lieu of  LOT to treat their pain. However, the lack of evidence of efficacy of LOT and considerable evidence of  significant harms of overdose, death from overdose, and increased risk of suicide outweigh any potential  modest benefit of prescribing LOT in this population. See Recommendation 7 for additional information regarding UDT and risk mitigation. See the VA/DoD SUD CPG for guidance on management of SUD.9

Question: What outweigh any potential  modest benefit of prescribing LOT in this population?
Answer: the lack of evidence of efficacy of LOT and considerable evidence of  significant harms of overdose, death from overdose, and increased risk of suicide
Recommendations

Some patients with SUD may disagree with the recommendation to use non-opioid modalities in lieu of  LOT to treat their pain. However, the lack of evidence of efficacy of LOT and considerable evidence of  significant harms of overdose, death from overdose, and increased risk of suicide outweigh any potential  modest benefit of prescribing LOT in this population. See Recommendation 7 for additional information regarding UDT and risk mitigation. See the VA/DoD SUD CPG for guidance on management of SUD.10

Question: Where can the guidance on management of SUD be found?
Answer: the VA/DoD SUD CPG
Recommendations

Given the increasing use of cannabis among patients with chronic pain and the lack of RCTs comparing  outcomes of prescribing LOT versus other therapies for patients with and without cannabis use and  cannabis use disorder, future research is needed to optimize care for these patients. Research is also  needed to determine which subpopulations of patients with active SUD are at greatest risk of OUD,  overdose, and death. Finally, further research is needed on the efficacy of alternative treatments for pain  and ways to mitigate risks of opioid-related adverse events in patients with SUD and pain.  

Question: Why is future research needed to optimize care for chronic-pain patients with and without cannabis use?
Answer: Given the increasing use of cannabis among patients with chronic pain and the lack of RCTs comparing  outcomes of prescribing LOT versus other therapies for patients with and without cannabis use and  cannabis use disorder
Recommendations

We recommend against the concurrent use of benzodiazepines and opioids. (Strong against | Reviewed, New-added) Note: For patients currently on long-term opioid therapy and benzodiazepines, consider tapering one or both when risks exceed benefits and obtaining specialty consultation as appropriate (see Recommendation 14 and the VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders). 

Question: What is the stance regarding the concurrent use of benzodiazepines and opioids?
Answer: recommend against
Recommendations

We recommend against the concurrent use of benzodiazepines and opioids. (Strong against | Reviewed, New-added) Note: For patients currently on long-term opioid therapy and benzodiazepines, consider tapering one or both when risks exceed benefits and obtaining specialty consultation as appropriate (see Recommendation 14 and the VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders). 

Question: For whom to consider tapering one or both benzodiazepines and opioids when risks exceed benefits and obtaining specialty consultation as appropriate?
Answer: patients currently on long-term opioid therapy and benzodiazepines
Recommendations

We recommend against the concurrent use of benzodiazepines and opioids. (Strong against | Reviewed, New-added) Note: For patients currently on long-term opioid therapy and benzodiazepines, consider tapering one or both when risks exceed benefits and obtaining specialty consultation as appropriate (see Recommendation 14 and the VA/DoD Clinical Practice Guideline for the Management of Substance Use Disorders). 

Question: What to consider for patients currently on long-term opioid therapy and benzodiazepines?
Answer: tapering one or both when risks exceed benefits and obtaining specialty consultation as appropriate
Recommendations

Harms may outweigh benefits for the concurrent use of benzodiazepines and LOT. There is moderate quality evidence that concurrent use of benzodiazepines with prescription opioids increases the risk of  overdose and overdose death.[66] In a retrospective cohort study, the adjusted odds ratio (AOR) for drug  overdose was highest for individuals on LOT for chronic pain (without anxiety or PTSD) who also received  concurrent long-term benzodiazepine therapy.[66] In another retrospective study that involved over  200,000 participants (not included in the evidence review), Veterans receiving both opioids and  benzodiazepines were at an increased risk of death from drug overdose.[90] Furthermore, there is a lack of  evidence in favor of long-term therapy with benzodiazepines and opioids for chronic pain.[91]  

Question: What is the relationship between harms and benefits for the concurrent use of benzodiazepines and LOT?
Answer: Harms may outweigh benefits
Recommendations

Harms may outweigh benefits for the concurrent use of benzodiazepines and LOT. There is moderate quality evidence that concurrent use of benzodiazepines with prescription opioids increases the risk of  overdose and overdose death.[66] In a retrospective cohort study, the adjusted odds ratio (AOR) for drug  overdose was highest for individuals on LOT for chronic pain (without anxiety or PTSD) who also received  concurrent long-term benzodiazepine therapy.[66] In another retrospective study that involved over  200,000 participants (not included in the evidence review), Veterans receiving both opioids and  benzodiazepines were at an increased risk of death from drug overdose.[90] Furthermore, there is a lack of  evidence in favor of long-term therapy with benzodiazepines and opioids for chronic pain.[91]  

Question: What increases the risk of overdose and overdose death?
Answer: concurrent use of benzodiazepines with prescription opioids
Recommendations

Harms may outweigh benefits for the concurrent use of benzodiazepines and LOT. There is moderate quality evidence that concurrent use of benzodiazepines with prescription opioids increases the risk of  overdose and overdose death.[66] In a retrospective cohort study, the adjusted odds ratio (AOR) for drug  overdose was highest for individuals on LOT for chronic pain (without anxiety or PTSD) who also received  concurrent long-term benzodiazepine therapy.[66] In another retrospective study that involved over  200,000 participants (not included in the evidence review), Veterans receiving both opioids and  benzodiazepines were at an increased risk of death from drug overdose.[90] Furthermore, there is a lack of  evidence in favor of long-term therapy with benzodiazepines and opioids for chronic pain.[91]  

Question: What is the effect of concurrent use of benzodiazepines with prescription opioids?
Answer: increases the risk of  overdose and overdose death
Recommendations

Harms may outweigh benefits for the concurrent use of benzodiazepines and LOT. There is moderate quality evidence that concurrent use of benzodiazepines with prescription opioids increases the risk of  overdose and overdose death.[66] In a retrospective cohort study, the adjusted odds ratio (AOR) for drug  overdose was highest for individuals on LOT for chronic pain (without anxiety or PTSD) who also received  concurrent long-term benzodiazepine therapy.[66] In another retrospective study that involved over  200,000 participants (not included in the evidence review), Veterans receiving both opioids and  benzodiazepines were at an increased risk of death from drug overdose.[90] Furthermore, there is a lack of  evidence in favor of long-term therapy with benzodiazepines and opioids for chronic pain.[91]  

Question: What was highest for individuals on LOT for chronic pain (without anxiety or PTSD) who also received  concurrent long-term benzodiazepine therapy?
Answer: the adjusted odds ratio (AOR) for drug  overdose
Recommendations

Harms may outweigh benefits for the concurrent use of benzodiazepines and LOT. There is moderate quality evidence that concurrent use of benzodiazepines with prescription opioids increases the risk of  overdose and overdose death.[66] In a retrospective cohort study, the adjusted odds ratio (AOR) for drug  overdose was highest for individuals on LOT for chronic pain (without anxiety or PTSD) who also received  concurrent long-term benzodiazepine therapy.[66] In another retrospective study that involved over  200,000 participants (not included in the evidence review), Veterans receiving both opioids and  benzodiazepines were at an increased risk of death from drug overdose.[90] Furthermore, there is a lack of  evidence in favor of long-term therapy with benzodiazepines and opioids for chronic pain.[91]  

Question: Who has the highest adjusted odds ratio (AOR) for drug  overdose?
Answer: individuals on LOT for chronic pain (without anxiety or PTSD) who also received  concurrent long-term benzodiazepine therapy
Recommendations

Harms may outweigh benefits for the concurrent use of benzodiazepines and LOT. There is moderate quality evidence that concurrent use of benzodiazepines with prescription opioids increases the risk of  overdose and overdose death.[66] In a retrospective cohort study, the adjusted odds ratio (AOR) for drug  overdose was highest for individuals on LOT for chronic pain (without anxiety or PTSD) who also received  concurrent long-term benzodiazepine therapy.[66] In another retrospective study that involved over  200,000 participants (not included in the evidence review), Veterans receiving both opioids and  benzodiazepines were at an increased risk of death from drug overdose.[90] Furthermore, there is a lack of  evidence in favor of long-term therapy with benzodiazepines and opioids for chronic pain.[91]  

Question: Who were at an increased risk of death from drug overdose?
Answer: Veterans receiving both opioids and  benzodiazepines
Recommendations

Harms may outweigh benefits for the concurrent use of benzodiazepines and LOT. There is moderate quality evidence that concurrent use of benzodiazepines with prescription opioids increases the risk of  overdose and overdose death.[66] In a retrospective cohort study, the adjusted odds ratio (AOR) for drug  overdose was highest for individuals on LOT for chronic pain (without anxiety or PTSD) who also received  concurrent long-term benzodiazepine therapy.[66] In another retrospective study that involved over  200,000 participants (not included in the evidence review), Veterans receiving both opioids and  benzodiazepines were at an increased risk of death from drug overdose.[90] Furthermore, there is a lack of  evidence in favor of long-term therapy with benzodiazepines and opioids for chronic pain.[91]  

Question: Veterans receiving both opioids and benzodiazepines were at an increased risk of what?
Answer: death from drug overdose
Recommendations

There is a large variation in patient preference regarding the concurrent use of benzodiazepines and LOT.  This is especially true for patients who are already accustomed to receiving both medications (see Patient  Focus Group Methods and Findings). Concurrent benzodiazepine and LOT use is a serious risk factor for  unintentional overdose death and should be weighed heavily in the risk-benefit evaluation for tapering  versus continuing one or both agents. Once initiated, benzodiazepines can be challenging to discontinue due to symptoms related to benzodiazepine dependence, exacerbations of PTSD, and/or anxiety.[91]  Moreover, abrupt discontinuation of benzodiazepines should be avoided, as it can lead to serious adverse  effects including seizures and death. Tapering benzodiazepines should be performed with caution and  within a team environment when possible (see Recommendation 26 in the VA/DoD SUD CPG).7 Due to the  difficulty of tapering or discontinuing benzodiazepines, particular caution should be used when considering initiating benzodiazepines for Veterans with PTSD who have co-occurring chronic pain. The VA/DoD PTSD  CPG recommends against benzodiazepines for the prevention of PTSD and cautions against their use in  treatment of PTSD. Benzodiazepines to treat acute anxiety symptoms after trauma are associated with a  higher incidence of PTSD symptoms. For treatment of PTSD, there is evidence of lack of efficacy from small  clinical trials and evidence of harm from observational studies of benzodiazepines for PTSD. Although  anxiety may initially improve with benzodiazepines, the improvement is short-lived and may result in  tolerance to increasing doses and eventual failure of the treatment. Even gradual benzodiazepine taper  may result in exacerbation of severe PTSD symptoms. Concomitant use of benzodiazepines is considered a  contraindication to initiation of OT.  

Question: What is a serious risk factor for unintentional overdose death?
Answer: Concurrent benzodiazepine and LOT use