Lornng/cpgQA huggingface dataset:
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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

In addition to benzodiazepines, the addition of other psychoactive medications to LOT must be made with  caution. While the evidence for harm associated with the combination of opioids and Z-drugs (e.g.,  zolpidem, eszopiclone) is not as strong as the evidence for harm associated with the combination of  opioids and benzodiazepines, we suggest not prescribing Z-drugs to patients who are on LOT, as moderate  quality evidence demonstrates that the combination of zolpidem and opioids increases the AOR of  overdose.[66] The evidence reviewed also identifies potential adverse outcomes (e.g., risk of overdose)  with the combined use of antidepressants and opioids in patients who do not have depression.[66] This  particular study did not differentiate between classes of antidepressants, limiting the ability of the Work  Group to recommend for or against prescribing opioids and a specific class of antidepressants. As such,  there is no recommendation in this guideline with respect to using specific classes of antidepressants and  LOT.

Question: In addition to benzodiazepines, what to do with caution?
Answer: the addition of other psychoactive medications to LOT

Question: What is not as strong as the evidence for harm associated with the combination of  opioids and benzodiazepines?
Answer: the evidence for harm associated with the combination of opioids and Z-drugs (e.g.,  zolpidem, eszopiclone)

Question: What does increase the AOR of  overdose?
Answer: the combination of zolpidem and opioids

Question: The combination of zolpidem and opioids increases what?
Answer: the AOR of  overdose

Question: What can happen with the combined use of antidepressants and opioids in patients who do not have depression?
Answer: potential adverse outcomes (e.g., risk of overdose)

Question: What can have potential adverse outcomes in patients who do not have depression?
Answer: the combined use of antidepressants and opioids

Question: Who can have potential adverse outcomes with the combined use of antidepressants and opioids?
Answer: patients who do not have depression
Recommendations

a) We recommend against long-term opioid therapy for patients less than 30 years of age  secondary to higher risk of opioid use disorder and overdose. (Strong against) b) For patients less than 30 years of age currently on long-term opioid therapy, we recommend  close monitoring and consideration for tapering when risks exceed benefits (see Recommendation  14 and Recommendation 17). (Strong for) (Reviewed, New-replaced)

Question: What is the stance regarding long-term opioid therapy for patients less than 30 years of age  secondary to higher risk of opioid use disorder and overdose?
Answer: recommend against

Question: What is recommended for patients less than 30 years of age currently on long-term opioid therapy?
Answer: close monitoring and consideration for tapering when risks exceed benefits
Recommendations

All patients who take opioids chronically are at risk for OUD and overdose, but especially those who are  younger than 30 years of age. Seven studies were identified that examined age as a predictor of OUD,  respiratory/CNS depression, and/or overdose. Four of the seven studies were rated as fair quality  evidence,[59,86,88,92] while three were rated as poor quality evidence.[58,62,87] Six of the seven studies  demonstrated that age was inversely associated with the risk of OUD and overdose.[59,62,86-88,92] One  of the three low quality studies showed that older subjects had a higher HR of overdose.[58] The Work  Group’s overall confidence in the quality of the evidence was moderate.

Question: Who are at risk for OUD and overdose?
Answer: All patients who take opioids chronically

Question: Which patients are especially at risk for OUD and overdose?
Answer: those who are  younger than 30 years of age

Question: All patients who take opioids chronically are at risk for what?
Answer: OUD and overdose

Question: How many studies examined age as a predictor of OUD,  respiratory/CNS depression, and/or overdose?
Answer: Seven
Recommendations

Similar to other risk factors, age <30 years should be weighed heavily in the risk-benefit determination for  initiating LOT. Age <30 years is not an absolute contraindication to LOT. There may be some situations  where the benefits of LOT clearly outweigh the risks of OUD and overdose. Hospitalized patients  recovering from battlefield injuries, for example, are known to have less chronic pain, depression, and  PTSD when their pain is aggressively managed starting soon after injury.[93] In those cases, LOT may be  appropriate only if risk mitigation strategies are employed and patients are titrated off LOT as soon as it is  appropriate (see Recommendations 14 and 15).

Question: What should be weighed heavily in the risk-benefit determination for initiating LOT?
Answer: Similar to other risk factors, age <30 years

Question: What is not an absolute contraindication to LOT?
Answer: Age <30 years

Question: Who are known to have less chronic pain, depression, and  PTSD when their pain is aggressively managed starting soon after injury?
Answer: Hospitalized patients  recovering from battlefield injuries

Question: When may LOT be appropriate?
Answer: only if risk mitigation strategies are employed and patients are titrated off LOT as soon as it is  appropriate
Recommendations

The added risk that younger patients using opioids face for OUD and overdose is great. Edlund et al. (2014)  found that, compared to patients ≥65 years old, patients 18-30 years old carried 11 times the odds of OUD  and overdose. Patients 31-40 years old carried 5 times the odds of OUD and overdose compared to those  ≥65 years old.[86] Bohnert et al. (2011) found that, compared to subjects 18-29 years old, patients 30-39  years old had roughly half the risk of developing OUD or overdose (HR: 0.56, 95% CI: 0.27-1.17). Compared  to the subjects 18-29 years old, patients ≥70 years old had a far less risk (nearly 1/17) of developing OUD  or overdose (HR: 0.06, 95% CI: 0.02, 0.18).[59]

Question: Who have an added great risk for OUD and overdose?
Answer: younger patients using opioids

Question: Who did carry 11 times the odds of OUD and overdose compared to patients ≥65 years old?
Answer: patients 18-30 years old

Question: Compared to whom, patients 18-30 years old carried 11 times the odds of OUD  and overdose?
Answer: patients ≥65 years old

Question: Compared to patients ≥65 years old, patients 18-30 years old carried how many times the odds of OUD  and overdose?
Answer: 11

Question: Who did carry 5 times the odds of OUD and overdose compared to patients ≥65 years old?
Answer: Patients 31-40 years

Question: Compared to whom, patients 31-40 years old carried 5 times the odds of OUD and overdose?
Answer: those  ≥65 years old

Question: Compared to patients ≥65 years old, patients 31-40 years old carried how many times the odds of OUD  and overdose?
Answer: 5

Question: Who had roughly half the risk of developing OUD or overdose compared to subjects 18-29 years old?
Answer: patients 30-39  years old

Question: Compared to whom, patients 30-39  years old had roughly half the risk of developing OUD or overdose?
Answer: subjects 18-29 years old

Question: What was the amount of risk of developing OUD or overdose in patients 30-39  years old compared to subjects 18-29 years old?
Answer: roughly half

Question: Who had far less risk of developing OUD or overdose compared to subjects 18-29 years old?
Answer: patients ≥70 years old

Question: Compared to whom, patients ≥70 years old had far less risk of developing OUD or overdose?
Answer: subjects 18-29 years old

Question: What was the amount of risk of developing OUD or overdose in patients ≥70 years old compared to subjects 18-29 years old?
Answer: far less risk (nearly 1/17)
Recommendations

Younger patients are also at a higher risk of opioid misuse (as suggested by a UDT indicating high-risk  medication-related behavior). Turner et al. (2014) showed that patients in the 45-64 year age group were  significantly less likely to have an aberrant UDT (detection of a non-prescribed opioid, non-prescribed  benzodiazepine, illicit drug, or tetrahydrocannabinol [THC]) in comparison to patients in the 20-44 age  group.[94] Patients in the 45-64 and ≥65 age groups were significantly less likely than 20-44 year olds to  have non-detection of a prescribed opioid as well (indicating possible diversion).[94]

Question: Who are at a higher risk of opioid misuse?
Answer: Younger patients

Question: Younger patients are at a higher risk of what?
Answer: opioid misuse (as suggested by a UDT indicating high-risk  medication-related behavior)

Question: Who were significantly less likely to have an aberrant UDT in comparison to patients in the 20-44 age  group?
Answer: patients in the 45-64 year age group

Question: In comparison to patients in the 20-44 age  group, patients in the 45-64 year age group were significantly less likely to have what?
Answer: an aberrant UDT (detection of a non-prescribed opioid, non-prescribed  benzodiazepine, illicit drug, or tetrahydrocannabinol [THC])

Question: Patients in the 45-64 year age group were significantly less likely to have an aberrant UDT (detection of a non-prescribed opioid, non-prescribed  benzodiazepine, illicit drug, or tetrahydrocannabinol [THC]) in comparison to whom?
Answer: patients in the 20-44 age  group

Question: Who were significantly less likely than 20-44 year olds to have non-detection of a prescribed opioid (indicating possible diversion)?
Answer: Patients in the 45-64 and ≥65 age groups

Question: Patients in the 45-64 and ≥65 age groups were significantly less likely than whom to  have non-detection of a prescribed opioid (indicating possible diversion)?
Answer: 20-44 year olds

Question: What are significantly less likely in patients in the 45-64 and ≥65 age groups than 20-44 year olds?
Answer: to  have non-detection of a prescribed opioid as well (indicating possible diversion)
Recommendations

An age of 30 years was chosen based on how age was categorized in the six studies that showed an inverse  relationship between age and OUD or overdose. One of those six studies found that patients with OUD  were younger than patients without OUD, but did not find a statistically significant relationship.[87] Two of  those six studies examined age as a continuous predictor, and neither reported a specific age where the  risk of OUD or overdose changed markedly.[62,92] One study examined age as a dichotomous (<65 and  ≥65) predictor.[88] In the two remaining studies, the highest risk included ages ranging from 18 to 30  years.[59,86] As such, the Work Group chose 30 years of age as a clinically reasonable threshold.

Question: How was an age of 30 years chosen as a clinically reasonable threshold?
Answer: An age of 30 years was chosen based on how age was categorized in the six studies that showed an inverse  relationship between age and OUD or overdose.
Recommendations

Some may interpret the recommendation to limit opioid use by age as arbitrary and potentially  discriminatory when taken out of context; however, there is good neurophysiologic rationale explaining  the relationship between age and OUD and overdose. Studies in other areas (e.g., use of different  substances) indicate that developing brains (age <30 years) are at increased risk of abnormalities and  addiction when exposed to substance use early in life.[95-98]

Question: What kind of rationale is there to explain the the relationship between age and OUD and overdose?
Answer: good neurophysiologic rationale

Question: What indicate that developing brains (age <30 years) are at increased risk of abnormalities and  addiction when exposed to substance use early in life?
Answer: Studies in other areas (e.g., use of different  substances)

Question: What are at increased risk of abnormalities and  addiction when exposed to substance use early in life?
Answer: developing brains (age <30 years)

Question: What are the risks of substance use early in life?
Answer: increased risk of abnormalities and  addiction
Recommendations

We recommend implementing risk mitigation strategies upon initiation of long-term opioid  therapy, starting with an informed consent conversation covering the risks and benefits of opioid  therapy as well as alternative therapies. The strategies and their frequency should be  commensurate with risk factors and include: Ongoing, random urine drug testing (including appropriate confirmatory testing), Checking state prescription drug monitoring programs, Monitoring for overdose potential and suicidality, Providing overdose education, Prescribing of naloxone rescue and accompanying education  (Strong for | Reviewed, New-replaced)

Question: What is recommended upon initiation of long-term opioid  therapy?
Answer: implementing risk mitigation strategies

Question: How to implement risk mitigation strategies upon initiation of long-term opioid  therapy?
Answer: starting with an informed consent conversation covering the risks and benefits of opioid  therapy as well as alternative therapies

Question: What should be commensurate with risk factors?
Answer: The strategies and their frequency

Question: What should be included in the risk mitigation strategies and their frequency?
Answer: Ongoing, random urine drug testing (including appropriate confirmatory testing), Checking state prescription drug monitoring programs, Monitoring for overdose potential and suicidality, Providing overdose education, Prescribing of naloxone rescue and accompanying education
Recommendations

There may be some variation in patient values and preferences. Certain patients may appreciate the use of  risk mitigation strategies and others may not. Participants in the patient focus group expressed an  understanding of why various risk mitigation strategies were used (see Patient Focus Group Methods and  Findings).

Question: What is the relationship between patient values and preferences?
Answer: There may be some variation

Question: There may be some variation in what?
Answer: patient values and preferences
Recommendations

Implementing more extensive risk mitigation strategies entails an investment of resources. Primary care  providers may require more time with patients to allow for shared decision making and treatment planning. More frequent follow-up of patients on LOT can affect access to care for all empaneled patients.  VHA providers must also follow VHA policy regarding education and signature informed consent when  providing LOT for patients with non-cancer pain.[101]

Question: What does implementing more extensive risk mitigation strategies entail?
Answer: an investment of resources

Question: Why may primary care providers require more time with patients?
Answer: to allow for shared decision making and treatment planning

Question: What would happen if there were a more frequent follow-up of patients on LOT?
Answer: can affect access to care for all empaneled patients

Question: What must VHA providers follow when providing LOT for patients with non-cancer pain?
Answer: VHA policy regarding education and signature informed consent

Question: When must VHA providers follow VHA policy regarding education and signature informed consent?
Answer: when  providing LOT for patients with non-cancer pain

Question: Who must follow VHA policy regarding education and signature informed consent when providing LOT for patients with non-cancer pain?
Answer: VHA providers
Recommendations

There is a paradigm shift occurring in approaches to ensuring and documenting patient and provider  understanding and expectations regarding the risks and benefits of LOT. The 2010 OT CPG reflected prior  practice of using opioid treatment (or pain care) agreements. OTAs have been described as coercive rather  than therapeutic, lack respect for individual autonomy, can be a barrier to pain care, and may be harmful  to the patient-provider relationship.[102-105]

Question: What did the 2010 OT CPG reflect?
Answer: prior  practice of using opioid treatment (or pain care) agreements

Question: How have OTAs been described in the 2010 OT CPG?
Answer: as coercive rather  than therapeutic, lack respect for individual autonomy, can be a barrier to pain care, and may be harmful  to the patient-provider relationship