Hieu-Pham/cpgQA huggingface dataset:
Recommendations

At follow-up visits, a clinician should re-examine the rationale for continuing the patient on OT. Clinicians should take into account changes in co-occurring conditions, diagnoses/medications, and functional status when conducting the risk/benefit analysis for LOT. Alcohol use, pregnancy, nursing of infants, and lab abnormalities may change the risk/benefit calculus for LOT. Ongoing OT prescribing practice may include pharmacy review, informed consent, UDTs, and checking state PDMPs. A clinician should also be mindful of signs of diversion during follow-up (see Risk Factors for Adverse Outcomes of Opioid Therapy). The longer the patient is on opioids, the greater the potential for change in patient status and development of opioid-related harms. 

Question: What to consider at the time of re-examining at a follow-up visit?
Answer: changes in co-occurring conditions, diagnoses/medications, and functional status when conducting the risk/benefit analysis for LOT
Recommendations

At follow-up visits, a clinician should re-examine the rationale for continuing the patient on OT. Clinicians should take into account changes in co-occurring conditions, diagnoses/medications, and functional status when conducting the risk/benefit analysis for LOT. Alcohol use, pregnancy, nursing of infants, and lab abnormalities may change the risk/benefit calculus for LOT. Ongoing OT prescribing practice may include pharmacy review, informed consent, UDTs, and checking state PDMPs. A clinician should also be mindful of signs of diversion during follow-up (see Risk Factors for Adverse Outcomes of Opioid Therapy). The longer the patient is on opioids, the greater the potential for change in patient status and development of opioid-related harms. 

Question: What may change the risk/benefit calculus for LOT?
Answer: Alcohol use, pregnancy, nursing of infants, and lab abnormalities
Recommendations

At follow-up visits, a clinician should re-examine the rationale for continuing the patient on OT. Clinicians should take into account changes in co-occurring conditions, diagnoses/medications, and functional status when conducting the risk/benefit analysis for LOT. Alcohol use, pregnancy, nursing of infants, and lab abnormalities may change the risk/benefit calculus for LOT. Ongoing OT prescribing practice may include pharmacy review, informed consent, UDTs, and checking state PDMPs. A clinician should also be mindful of signs of diversion during follow-up (see Risk Factors for Adverse Outcomes of Opioid Therapy). The longer the patient is on opioids, the greater the potential for change in patient status and development of opioid-related harms. 

Question: What is included in the ongoing OT prescribing practice?
Answer: pharmacy review, informed consent, UDTs, and checking state PDMPs
Recommendations

At follow-up visits, a clinician should re-examine the rationale for continuing the patient on OT. Clinicians should take into account changes in co-occurring conditions, diagnoses/medications, and functional status when conducting the risk/benefit analysis for LOT. Alcohol use, pregnancy, nursing of infants, and lab abnormalities may change the risk/benefit calculus for LOT. Ongoing OT prescribing practice may include pharmacy review, informed consent, UDTs, and checking state PDMPs. A clinician should also be mindful of signs of diversion during follow-up (see Risk Factors for Adverse Outcomes of Opioid Therapy). The longer the patient is on opioids, the greater the potential for change in patient status and development of opioid-related harms. 

Question: What to be aware of during follow-ups?
Answer: signs of diversion
Recommendations

At follow-up visits, a clinician should re-examine the rationale for continuing the patient on OT. Clinicians should take into account changes in co-occurring conditions, diagnoses/medications, and functional status when conducting the risk/benefit analysis for LOT. Alcohol use, pregnancy, nursing of infants, and lab abnormalities may change the risk/benefit calculus for LOT. Ongoing OT prescribing practice may include pharmacy review, informed consent, UDTs, and checking state PDMPs. A clinician should also be mindful of signs of diversion during follow-up (see Risk Factors for Adverse Outcomes of Opioid Therapy). The longer the patient is on opioids, the greater the potential for change in patient status and development of opioid-related harms. 

Question: What is the relationship between the length of OT and opioid-related harms?
Answer: The longer the patient is on opioids, the greater the potential for change in patient status and development of opioid-related harms.
Recommendations

If prescribing opioids, we recommend prescribing the lowest dose of opioids as indicated by patient-specific risks and benefits. (Strong for | Reviewed, New-replaced) Note: There is no absolutely safe dose of opioids. As opioid dosage and risk increase, we recommend more frequent monitoring for adverse events including opioid use disorder and overdose. Risks for opioid use disorder start at any dose and increase in a dose-dependent manner. • Risks for overdose and death significantly increase at a range of 20-50 mg morphine equivalent daily dose. (Strong for | Reviewed, New- replaced)  We recommend against opioid doses over 90 mg morphine equivalent daily dose for treating chronic pain. (Strong against | Reviewed, New-replaced) Note: For patients who are currently prescribed doses over 90 mg morphine equivalent daily dose, evaluate for tapering to reduced dose or to discontinuation (see Recommendations 14 and 15). 

Question: What is the recommended dose of opioids?
Answer: the lowest dose of opioids as indicated by patient-specific risks and benefits
Recommendations

If prescribing opioids, we recommend prescribing the lowest dose of opioids as indicated by patient-specific risks and benefits. (Strong for | Reviewed, New-replaced) Note: There is no absolutely safe dose of opioids. As opioid dosage and risk increase, we recommend more frequent monitoring for adverse events including opioid use disorder and overdose. Risks for opioid use disorder start at any dose and increase in a dose-dependent manner. • Risks for overdose and death significantly increase at a range of 20-50 mg morphine equivalent daily dose. (Strong for | Reviewed, New- replaced)  We recommend against opioid doses over 90 mg morphine equivalent daily dose for treating chronic pain. (Strong against | Reviewed, New-replaced) Note: For patients who are currently prescribed doses over 90 mg morphine equivalent daily dose, evaluate for tapering to reduced dose or to discontinuation (see Recommendations 14 and 15). 

Question: Is there any absolutely safe dose of opioids?
Answer: no
Recommendations

If prescribing opioids, we recommend prescribing the lowest dose of opioids as indicated by patient-specific risks and benefits. (Strong for | Reviewed, New-replaced) Note: There is no absolutely safe dose of opioids. As opioid dosage and risk increase, we recommend more frequent monitoring for adverse events including opioid use disorder and overdose. Risks for opioid use disorder start at any dose and increase in a dose-dependent manner. • Risks for overdose and death significantly increase at a range of 20-50 mg morphine equivalent daily dose. (Strong for | Reviewed, New- replaced)  We recommend against opioid doses over 90 mg morphine equivalent daily dose for treating chronic pain. (Strong against | Reviewed, New-replaced) Note: For patients who are currently prescribed doses over 90 mg morphine equivalent daily dose, evaluate for tapering to reduced dose or to discontinuation (see Recommendations 14 and 15). 

Question: What to do with the increment of opioid dosage and risk?
Answer: more frequent monitoring for adverse events including opioid use disorder and overdose
Recommendations

If prescribing opioids, we recommend prescribing the lowest dose of opioids as indicated by patient-specific risks and benefits. (Strong for | Reviewed, New-replaced) Note: There is no absolutely safe dose of opioids. As opioid dosage and risk increase, we recommend more frequent monitoring for adverse events including opioid use disorder and overdose. Risks for opioid use disorder start at any dose and increase in a dose-dependent manner. • Risks for overdose and death significantly increase at a range of 20-50 mg morphine equivalent daily dose. (Strong for | Reviewed, New- replaced)  We recommend against opioid doses over 90 mg morphine equivalent daily dose for treating chronic pain. (Strong against | Reviewed, New-replaced) Note: For patients who are currently prescribed doses over 90 mg morphine equivalent daily dose, evaluate for tapering to reduced dose or to discontinuation (see Recommendations 14 and 15). 

Question: At what dose do risks for opioid use disorder begin?
Answer: any
Recommendations

If prescribing opioids, we recommend prescribing the lowest dose of opioids as indicated by patient-specific risks and benefits. (Strong for | Reviewed, New-replaced) Note: There is no absolutely safe dose of opioids. As opioid dosage and risk increase, we recommend more frequent monitoring for adverse events including opioid use disorder and overdose. Risks for opioid use disorder start at any dose and increase in a dose-dependent manner. • Risks for overdose and death significantly increase at a range of 20-50 mg morphine equivalent daily dose. (Strong for | Reviewed, New- replaced)  We recommend against opioid doses over 90 mg morphine equivalent daily dose for treating chronic pain. (Strong against | Reviewed, New-replaced) Note: For patients who are currently prescribed doses over 90 mg morphine equivalent daily dose, evaluate for tapering to reduced dose or to discontinuation (see Recommendations 14 and 15). 

Question: At what dose do risks for opioid use disorder increase?
Answer: in a dose-dependent manner
Recommendations

If prescribing opioids, we recommend prescribing the lowest dose of opioids as indicated by patient-specific risks and benefits. (Strong for | Reviewed, New-replaced) Note: There is no absolutely safe dose of opioids. As opioid dosage and risk increase, we recommend more frequent monitoring for adverse events including opioid use disorder and overdose. Risks for opioid use disorder start at any dose and increase in a dose-dependent manner. • Risks for overdose and death significantly increase at a range of 20-50 mg morphine equivalent daily dose. (Strong for | Reviewed, New- replaced)  We recommend against opioid doses over 90 mg morphine equivalent daily dose for treating chronic pain. (Strong against | Reviewed, New-replaced) Note: For patients who are currently prescribed doses over 90 mg morphine equivalent daily dose, evaluate for tapering to reduced dose or to discontinuation (see Recommendations 14 and 15). 

Question: At what dose do the risks for overdose and death increase?
Answer: a range of 20-50 mg morphine equivalent daily dose
Recommendations

If prescribing opioids, we recommend prescribing the lowest dose of opioids as indicated by patient-specific risks and benefits. (Strong for | Reviewed, New-replaced) Note: There is no absolutely safe dose of opioids. As opioid dosage and risk increase, we recommend more frequent monitoring for adverse events including opioid use disorder and overdose. Risks for opioid use disorder start at any dose and increase in a dose-dependent manner. • Risks for overdose and death significantly increase at a range of 20-50 mg morphine equivalent daily dose. (Strong for | Reviewed, New- replaced)  We recommend against opioid doses over 90 mg morphine equivalent daily dose for treating chronic pain. (Strong against | Reviewed, New-replaced) Note: For patients who are currently prescribed doses over 90 mg morphine equivalent daily dose, evaluate for tapering to reduced dose or to discontinuation (see Recommendations 14 and 15). 

Question: What opioid dose is not recommended for treating chronic pain?
Answer: over 90 mg morphine equivalent daily dose
Recommendations

If prescribing opioids, we recommend prescribing the lowest dose of opioids as indicated by patient-specific risks and benefits. (Strong for | Reviewed, New-replaced) Note: There is no absolutely safe dose of opioids. As opioid dosage and risk increase, we recommend more frequent monitoring for adverse events including opioid use disorder and overdose. Risks for opioid use disorder start at any dose and increase in a dose-dependent manner. • Risks for overdose and death significantly increase at a range of 20-50 mg morphine equivalent daily dose. (Strong for | Reviewed, New- replaced)  We recommend against opioid doses over 90 mg morphine equivalent daily dose for treating chronic pain. (Strong against | Reviewed, New-replaced) Note: For patients who are currently prescribed doses over 90 mg morphine equivalent daily dose, evaluate for tapering to reduced dose or to discontinuation (see Recommendations 14 and 15). 

Question: What is recommended for patients who are currently prescribed doses over 90 mg morphine equivalent daily dose?
Answer: evaluate for tapering to reduced dose or to discontinuation
Recommendations

There is moderate quality evidence from retrospective cohort and retrospective case-control studies  indicating that risk of prescription opioid overdose and overdose death exists even at low opioid dosage levels and increases with increasing doses. Significant risk (approximately 1.5 times) exists at a daily dosage range of 20 to <50 mg MEDD and further increases (approximately 2.6 times) at a range of 50 to <100 mg MEDD compared to risk at <20 mg MEDD. Risk continues to increase at higher dosage ranges (≥100 mg  MEDD) (Table 2).[58,59,66,133]  

Question: Is there any evidence that risk of prescription opioid overdose and overdose death exists even at low opioid dosage levels and increases with increasing doses?
Answer: There is moderate quality evidence from retrospective cohort and retrospective case-control studies
Recommendations

There is moderate quality evidence from retrospective cohort and retrospective case-control studies  indicating that risk of prescription opioid overdose and overdose death exists even at low opioid dosage levels and increases with increasing doses. Significant risk (approximately 1.5 times) exists at a daily dosage range of 20 to <50 mg MEDD and further increases (approximately 2.6 times) at a range of 50 to <100 mg MEDD compared to risk at <20 mg MEDD. Risk continues to increase at higher dosage ranges (≥100 mg  MEDD) (Table 2).[58,59,66,133]  

Question: At what dosage there is a significant risk?
Answer: a daily dosage range of 20 to <50 mg MEDD
Recommendations

There is moderate quality evidence from retrospective cohort and retrospective case-control studies  indicating that risk of prescription opioid overdose and overdose death exists even at low opioid dosage levels and increases with increasing doses. Significant risk (approximately 1.5 times) exists at a daily dosage range of 20 to <50 mg MEDD and further increases (approximately 2.6 times) at a range of 50 to <100 mg MEDD compared to risk at <20 mg MEDD. Risk continues to increase at higher dosage ranges (≥100 mg  MEDD) (Table 2).[58,59,66,133]  

Question: At what dosage does the risk increase even further?
Answer: a range of 50 to <100 mg MEDD compared to risk at <20 mg MEDD
Recommendations

There is moderate quality evidence from retrospective cohort and retrospective case-control studies  indicating that risk of prescription opioid overdose and overdose death exists even at low opioid dosage levels and increases with increasing doses. Significant risk (approximately 1.5 times) exists at a daily dosage range of 20 to <50 mg MEDD and further increases (approximately 2.6 times) at a range of 50 to <100 mg MEDD compared to risk at <20 mg MEDD. Risk continues to increase at higher dosage ranges (≥100 mg  MEDD) (Table 2).[58,59,66,133]  

Question: How much does the risk increase at a daily dosage range of 20 to <50 mg MEDD?
Answer: approximately 1.5 times
Recommendations

There is moderate quality evidence from retrospective cohort and retrospective case-control studies  indicating that risk of prescription opioid overdose and overdose death exists even at low opioid dosage levels and increases with increasing doses. Significant risk (approximately 1.5 times) exists at a daily dosage range of 20 to <50 mg MEDD and further increases (approximately 2.6 times) at a range of 50 to <100 mg MEDD compared to risk at <20 mg MEDD. Risk continues to increase at higher dosage ranges (≥100 mg  MEDD) (Table 2).[58,59,66,133]  

Question: How much does the risk increase at a range of 50 to <100 mg MEDD compared to risk at <20 mg MEDD?
Answer: approximately 2.6 times
Recommendations

In a nested case-control study of U.S. Veterans (not included in our evidence review as it was published after the end of the search date range), Bohnert et al. (2016) examined the association between prescribed opioid dose as a continuous measure (in 10 mg MEDD increments) and overdose.[134]  Prescribed opioid dosage was a moderately good predictor of overdose death, but the study did not reveal a specific dosage cut point or threshold above which risk of overdose increased dramatically. Lower prescribed opioid dosages were associated with reduced risk for overdose, but risk was not completely eliminated at lower doses; approximately 40% of overdoses were observed in patients who were prescribed <50 mg MEDD.  

Question: What is a good predictor of overdose death?
Answer: Prescribed opioid dosage
Recommendations

In a prospective cohort study (not included in the evidence review as it did not include information on  acute versus chronic pain in the patient population), Dasgupta et al. (2015) compared residents of North  Carolina who had received an opioid prescription in the last year to residents who had not. The study examined the outcome of population-based rates of opioid overdose mortality by opioid dose, without use of a presupposed threshold (Table 3).[135] There was no safe dose of opioid. Among the over nine million individuals followed for one year, 629 died from opioid overdose. Of these 629 individuals, 151 had no record of having been dispensed an opioid. It is possible these opioids were obtained through illicit channels or social sharing/diversion. Of the 478 patients who died from an opioid overdose who were prescribed opioids, 235 (49%) had been prescribed <80 mg MEDD. Overdose incidence rate ratios (IRRs)  doubled each time the MEDD ranges increase from 60.0-79.9 mg to 80.0-99.9 mg (IRR 2.9 to 6.2), then to  120-139.9 mg (IRR 14.1), 160-179.9 mg (IRR 29.5), and 350-399.9 mg (IRR 63.2). 

Question: Is there any study on the outcome of population-based rates of opioid overdose mortality by opioid dose, without the use of a presupposed threshold?
Answer: In a prospective cohort study (not included in the evidence review as it did not include information on  acute versus chronic pain in the patient population), Dasgupta et al. (2015) compared residents of North  Carolina who had received an opioid prescription in the last year to residents who had not.
Recommendations

Achieving an improved understanding of the factors contributing to prescription opioid-related overdose is an essential step toward addressing this epidemic problem. Although it is widely accepted that progressively higher doses of prescribed opioids result in correspondingly higher risks of opioid overdose,  patients using any dose of opioids can still experience life-threatening respiratory or CNS depression,  especially when opioid-naïve. This risk begins to increase with MEDD as low as 20-50 mg. Risk is further increased when certain concomitant demographic factors, co-occurring medical or psychiatric conditions,  or interacting medications or substances exist.  

Question: Which step should be taken to address the problem of opioid-related overdose epidemic?
Answer: Achieving an improved understanding of the factors contributing to prescription opioid-related overdose
Recommendations

Achieving an improved understanding of the factors contributing to prescription opioid-related overdose is an essential step toward addressing this epidemic problem. Although it is widely accepted that progressively higher doses of prescribed opioids result in correspondingly higher risks of opioid overdose,  patients using any dose of opioids can still experience life-threatening respiratory or CNS depression,  especially when opioid-naïve. This risk begins to increase with MEDD as low as 20-50 mg. Risk is further increased when certain concomitant demographic factors, co-occurring medical or psychiatric conditions,  or interacting medications or substances exist.  

Question: What is the relationship between opioid dosage and risks of opioid overdose?
Answer: progressively higher doses of prescribed opioids result in correspondingly higher risks of opioid overdose
Recommendations

Achieving an improved understanding of the factors contributing to prescription opioid-related overdose is an essential step toward addressing this epidemic problem. Although it is widely accepted that progressively higher doses of prescribed opioids result in correspondingly higher risks of opioid overdose,  patients using any dose of opioids can still experience life-threatening respiratory or CNS depression,  especially when opioid-naïve. This risk begins to increase with MEDD as low as 20-50 mg. Risk is further increased when certain concomitant demographic factors, co-occurring medical or psychiatric conditions,  or interacting medications or substances exist.  

Question: Which factors increase the risk of opioid overdose?
Answer: certain concomitant demographic factors, co-occurring medical or psychiatric conditions,  or interacting medications or substances
Recommendations

Recognizing the lack of evidence of long-term benefit associated with LOT used alone and the risks of  harms with use of opioids without risk mitigation, dosing determinations should be individualized based  upon patient characteristics and preferences, with the goal of using the lowest dose of opioids for the  shortest period of time to achieve well-defined functional treatment goals. Understandably, there will be  greater mortality, co-occurring medical conditions, and other adverse events in patients who require  higher doses of opioids, even in those who benefit from such therapy. When closer follow-up is needed,  healthcare resources and patient adherence should be considered.  

Question: What should be individualized based upon patient characteristics and preferences?
Answer: Recognizing the lack of evidence of long-term benefit associated with LOT used alone and the risks of  harms with use of opioids without risk mitigation, dosing determinations
Recommendations

Recognizing the lack of evidence of long-term benefit associated with LOT used alone and the risks of  harms with use of opioids without risk mitigation, dosing determinations should be individualized based  upon patient characteristics and preferences, with the goal of using the lowest dose of opioids for the  shortest period of time to achieve well-defined functional treatment goals. Understandably, there will be  greater mortality, co-occurring medical conditions, and other adverse events in patients who require  higher doses of opioids, even in those who benefit from such therapy. When closer follow-up is needed,  healthcare resources and patient adherence should be considered.  

Question: Who will have greater mortality, co-occurring medical conditions, and other adverse events?
Answer: patients who require  higher doses of opioids, even in those who benefit from such therapy