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9. For each key question, the following sub-questions were addressed:
Opioid Therapy
a. What is the comparative effectiveness of opioid therapy versus: (1) nonopioid pharmacologic therapy (e.g., acetaminophen, nonsteroidal anti-inflammatory drugs [NSAIDs], antidepressants, anticonvulsants) or (2) nonpharmacologic therapy (e.g., exercise, cognitive behavioral therapy, acupuncture) for outcomes related to pain, function, pain relief satisfaction, and quality of life and after followup at the following intervals: less than 1 day;, 1 day to less than 1 week;, 1 week to less than 2 weeks;, 2 weeks to less than 4 weeks,; 4 weeks or longer?
b. How does effectiveness of opioid therapy vary depending on: (1) patient demographics (e.g., age, race, ethnicity, gender); (2) patient medical or psychiatric comorbidities; (3) dose of opioids; (4) duration of opioid therapy, including number of opioid prescription refills and quantity of pills used; (5) opioid use history; (6) substance use history; (7) use of concomitant therapies?
c. What are the harms of opioid therapy versus nonopioid pharmacologic therapy, or nonpharmacologic therapy with respect to: (1) misuse, opioid use disorder, and related outcomes; (2) overdose; (3) other harms, including gastrointestinal-related harms, falls, fractures, motor vehicle accidents, endocrinological harms, infections, cardiovascular events, cognitive harms, and psychological harms (e.g., depression)?
d. How do harms vary depending on: (1) patient demographics (e.g., age, gender); (2) patient medical or psychiatric comorbidities; (3) the dose of opioid used; (4) the duration of opioid therapy; (5) opioid use history; or (6) substance use history?
e. What are the effects of prescribing opioid therapy versus not prescribing opioid therapy for acute pain on (1) short-term (<3 months) continued need for prescription pain relief, such as need for opioid refills, and (2) long-term opioid use (3 months or greater)?
f. For patients with acute pain being considered for opioid therapy, what is the accuracy of instruments for predicting risk of opioid misuse, opioid use disorder, or overdose?
g. For patients with acute pain being considered for opioid therapy, what is the effectiveness of instruments for predicting risk of opioid misuse, opioid use disorder, or overdose?
h. For patients with acute pain being considered for opioid therapy, what is the effect of the following factors on the decision to prescribe opioids: (1) existing opioid management plans; (2) patient education; (3) clinician and patient values and preferences related to opioids; (4) urine drug screening; (5) use of prescription drug monitoring program data; (6) availability of close followup?
Nonopioid Pharmacologic Therapy
i. What is the comparative effectiveness of nonopioid pharmacologic therapy (e.g., acetaminophen, nonsteroidal anti-inflammatory drugs [NSAIDs], antidepressants, anticonvulsants) versus: (1) other nonopioid pharmacologic treatments, such as those in a different medication class;, or (2) nonpharmacologic therapy for outcomes related to pain, function, pain relief satisfaction, and quality of life after followup at the following intervals: less than <1 day;, 1 day to less than <1 week,; 1 week to less than <2 weeks,; 2 weeks to less than 4 weeks,; 4 weeks or longer?
j. How does effectiveness of nonopioid pharmacologic therapy vary depending on: (1) patient demographics (e.g., age, race, ethnicity, gender); (2) patient medical and psychiatric comorbidities; (3) the type of nonopioid medication; (4) dose of medication; (5) duration of treatment?
k. What are the harms of nonopioid pharmacologic therapy versus other nonopioid pharmacologic therapy, or nonpharmacologic therapy with respect to: (1) misuse;, (2) overdose; (3) other harms, including gastrointestinal-related harms, cardiovascular-related harms, kidney-related harms, falls, fractures, motor vehicle accidents, endocrinological harms, infections, cognitive harms, and psychological harms (e.g., depression)?
l. How do harms vary depending on: (1) patient demographics (e.g., age, gender); (2) patient medical comorbidities; (3) the type of nonopioid medication; (4) dose of medication; (5) the duration of therapy?
Nonpharmacologic Therapy
m. What is the comparative effectiveness of nonpharmacologic therapy versus sham treatment, waitlist, usual care, attention control, and no treatment after followup at the following intervals: less than 1 day,; 1 day to less than 1 week,; 1 week to less than 2 weeks,; 2 weeks to less than 4 weeks,; 4 weeks or longer?
n. What is the comparative effectiveness of nonpharmacologic treatments (e.g., exercise, cognitive behavioral therapy, acupuncture) for outcomes related to pain, function, pain relief satisfaction, and quality of life after followup at the following intervals: less than 1 day,; 1 day to less than 1 week,; 1 week to less than 2 weeks,; 2 weeks to less than 4 weeks,; 4 weeks or longer?
o. How does effectiveness of nonpharmacologic therapy vary depending on: (1) patient demographics (e.g., age, gender); (2) patient medical and psychiatric comorbidities?
p. How do harms vary depending on: (1) patient demographics (e.g., age, gender); (2) patient medical and psychiatric comorbidities; (3) the type of treatment used; (4) the frequency of therapy; (5) the duration of therapy?