Nefopam Hydrochloride*: New Analgesic Agent

Two dose-levels of nefopam hydrochloride ( i.e. 30 mg and 60 mg) were compared with two dose-levels of aspirin ( i.e. 300 mg and 600 mg) and placebo in 125 male patients having pain associated with muscle disorders. Drugs were given as a single dose and pain intensity and side-effects monitored at thirty minutes and then hourly for four hours. Time-course action of the drugs revealed that aspirin 300 mg failed to achieve statistically significant analgesia at any post-treatment observation, whereas nefopam 60 mg was significantly better than placebo ( p < 0·05) at one and three hours in terms of pain intensity and at one hour in terms of pain intensity difference scores. Aspirin 600 mg was significantly different from placebo ( p < 0·05) at all hourly observations for both efficacy parameters, as was nefopam 30 mg ( p < 0·01). Summation of pain intensity difference scores showed aspirin 600 mg and nefopam 30 mg to be significantly different from placebo at the 0·025 and 0·005 levels respectively.

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The efficacy, tolerability, and speed of onset of fentanyl pectin nasal spray (FPNS) in the treatment of breakthrough cancer pain (BTCP): A multicenter, placebo-controlled, double-blind, two-phase crossover study

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.9535 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 9535-9535

Author(s):

N. Y. Gabrail ◽

A. W. Burton ◽

E. Reyes ◽

A. Nguyen ◽

D. R. Taylor

Keyword(s):

Cancer Pain ◽

Pain Intensity ◽

Nasal Spray ◽

Time Course ◽

Oral Morphine ◽

Nasal Delivery ◽

Intensity Difference ◽

Double Blind ◽

Pain Intensity Difference ◽

Breakthrough Cancer Pain

9535 Background: Breakthrough cancer pain (BTCP) affects up to 95% of patients with cancer pain but oral fentanyl formulations do not consistently match the typical time course of BTCP, which is rapid in onset and lasts for 30–60 min. To tailor fentanyl delivery for the treatment of BTCP, a new nasal formulation of fentanyl (fentanyl pectin nasal spray [FPNS]) has been developed to provide both rapid and controlled nasal delivery of fentanyl. Methods: A randomised, placebo-controlled, double-blind (DB) study assessing the efficacy and tolerability of FPNS was conducted in 114 cancer patients experiencing 1–4 BTCP episodes/day while taking ≥60 mg/day of oral morphine (or equivalent) for cancer pain. Patients who completed a titration phase (N=83) continued to a DB phase where 10 episodes of BTCP were treated with the effective dose identified during titration (7) or placebo (3). Pain intensity (PI) was measured using an 11-point categorical scale and pain relief (PR) using a 5-point scale, both PI and PR were measured at 5, 10, 15, 45 and 60 min post-dose. The primary endpoint was the Summed Pain Intensity Difference at 30 min (SPID30min). Secondary efficacy endpoints included Pain Intensity Difference (PID) from baseline, PI and PR. Safety was assessed by adverse events (AEs) and both objective and subjective nasal assessments. Results: Compared with placebo, FPNS significantly improved mean SPID30min scores (P<0.0001) and significantly improved SPID scores as early as 10 min (P<0.05) and up to 60 min (P<0.0001). Significant differences in favour of FPNS were found in PI as early as 5 min (P<0.05). Similar benefits were also seen with PID, with a trend at 5 min (P=0.07) that was significant from 10 min onward (P<0.01). PR was significant from 10 min (P<0.001) and at all time points to 60 min (P<0.001). Only 5.3% of patients withdrew from titration due to AEs; no significant nasal effects were reported. Conclusions: FPNS provided rapid and effective analgesia in BTCP and was generally safe and well tolerated. [Table: see text]

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Dreierkombination (Thomapyrin®) ist wirksamer bei Kopfschmerzen als Monosubstanzen und Zweierkombination

Nervenheilkunde ◽

10.1055/s-0038-1629992 ◽

2005 ◽

Vol 24 (07) ◽

pp. 626-639 ◽

Cited By ~ 1

Author(s):

V. Pfaffenrath ◽

L. Pageler ◽

H. Peil ◽

B. Aicher ◽

H. C. Diener

Keyword(s):

Pain Intensity ◽

Visual Analog Scale ◽

A Priori ◽

Intensity Difference ◽

Visuelle Analogskala ◽

Analog Scale ◽

Pain Intensity Difference

ZusammenfassungDie Wirksamkeit, Sicherheit und Verträglichkeit einer Einzelgabe von zwei Tabletten der fixen Dreierkombination mit 250 mg Azetylsalizylsäure (ASS) plus 200 mg Paracetamol plus 50 mg Koffein (Thomapyrin®) gegenüber zwei Tabletten mit 500 mg ASS, oder zwei Tabletten mit 500 mg Paracetamol, oder zwei Tabletten mit 50 mg Koffein beziehungsweise Plazebo wurde in einer klinischen Studie an 1 743 Patienten geprüft, die ihre episodischen Kopfschmerzen vom Spannungstyp oder ihre Migräne mit und ohne Aura üblicherweise erfolgreich mit verschreibungsfreien Analgetika behandeln. Die Dreierkombination war im a priori definierten primären Endpunkt “Zeit bis zu 50% Schmerzreduktion” sowohl der Zweierkombination aus ASS plus Paracetamol (p = 0,0181), als auch den Monoanalgetika ASS (p = 0,0398) und Paracetamol (p = 0,0016), sowie auch der Monotherapie mit Koffein (p < 0,0001) und Plazebo (p < 0,0001) überlegen. Alle Behandlungen außer der Koffein-Monotherapie waren der Plazebobehandlung überlegen (p < 0,0001). Die überlegene Wirksamkeit der Dreierkombination gilt auch für alle sekundären Endpunkte wie beispielsweise der “Verringerung der Kopfschmerzen auf 10 mm VAS (visual analog scale = visuelle Analogskala zur Schmerzmessung), dem gewichteten % SPID (sum of pain intensity difference = aufsummierte Schmerzintensitätsdifferenz gegenüber dem Ausgangsschmerz in Prozent), dem Ausmaß der Beeinträchtigung der alltäglichen Aktivitäten und der globalen Beurteilung der Wirksamkeit durch die Patienten. Alle Behandlungen waren gut verträglich, die Inzidenz von unerwünschten Begleiterscheinungen war gering.

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Efficacy of non-opioid analgesics to control postoperative pain: a network meta-analysis

BMC Anesthesiology ◽

10.1186/s12871-020-01147-y ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

John A. Carter ◽

Libby K. Black ◽

Dolly Sharma ◽

Tarun Bhagnani ◽

Jonathan S. Jahr

Keyword(s):

Postoperative Pain ◽

Pain Intensity ◽

Human Subjects ◽

Meta Analysis ◽

Opioid Analgesics ◽

Abdominal Hysterectomy ◽

Orthopedic Procedures ◽

Intensity Difference ◽

Cumulative Probability ◽

Pain Intensity Difference

Abstract Background The aim of this network meta-analysis (NMA) was to evaluate the safety and efficacy of intravenous (IV) Meloxicam 30 mg (MIV), an investigational non-steroidal anti-inflammatory drug (NSAID), and certain other IV non-opioid analgesics for moderate-severe acute postoperative pain. Methods We searched PubMed and CENTRAL for Randomized Controlled Trials (RCT) (years 2000–2019, adult human subjects) of IV non-opioid analgesics (IV NSAIDs or IV Acetaminophen) used to treat acute pain after abdominal, hysterectomy, bunionectomy or orthopedic procedures. A Bayesian NMA was conducted in R to rank treatments based on the standardized mean differences in sum of pain intensity difference from baseline up to 24 h postoperatively (sum of pain intensity difference: SPID 24). The probability and the cumulative probability of rank for each treatment were calculated, and the surface under the cumulative ranking curve (SUCRA) was applied to distinguish treatments on the basis of their outcomes such that higher SUCRA values indicate better outcomes. The study protocol was prospectively registered with by PROSPERO (CRD42019117360). Results Out of 2313 screened studies, 27 studies with 36 comparative observations were included, producing a treatment network that included the four non-opioid IV pain medications of interest (MIV, ketorolac, acetaminophen, and ibuprofen). MIV was associated with the largest SPID 24 for all procedure categories and comparators. The SUCRA ranking table indicated that MIV had the highest probability for the most effective treatment for abdominal (89.5%), bunionectomy (100%), and hysterectomy (99.8%). MIV was associated with significantly less MME utilization versus all comparators for abdominal procedures, hysterectomy, and versus acetaminophen in orthopedic procedures. Elsewhere MME utilization outcomes for MIV were largely equivalent or nominally better than other comparators. Odds of ORADEs were significantly higher for all comparators vs MIV for orthopedic (gastrointestinal) and hysterectomy (respiratory). Conclusions MIV 30 mg may provide better pain reduction with similar or better safety compared to other approved IV non-opioid analgesics. Caution is warranted in interpreting these results as all comparisons involving MIV were indirect.

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Sum of Pain Intensity Differences (Spid) in Migraine Trials. A Comment Based on Four Rizatriptan Trials

Cephalalgia ◽

10.1046/j.1468-2982.2002.00402.x ◽

2002 ◽

Vol 22 (8) ◽

pp. 664-666 ◽

Cited By ~ 8

Author(s):

P Tfelt-Hansen ◽

K McCarroll ◽

C Lines

Keyword(s):

Clinical Trials ◽

Pain Intensity ◽

Treatment Response ◽

Outcome Measure ◽

Intensity Difference ◽

Pain Intensity Difference ◽

Treatment Dose ◽

Headache Relief ◽

Dose Effects ◽

Using Data

Sum of Pain Intensity Difference (SPID) is an outcome measure that summarizes treatment response over a clinically relevant period. SPID is widely reported in clinical trials of analgesics but has been little used in migraine trials. We compared SPID over 2 h with the standard migraine outcome measures of pain-free at 2 h and headache relief at 2 h using data from four published clinical trials of rizatriptan in migraine patients. In assessing treatment response (rizatriptan and sumatriptan versus placebo, rizatriptan versus sumatriptan, within-treatment dose effects), SPID usually yielded similar results to the more easily understood pain-free measure.

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Efficacy of non-opioid analgesics to control postoperative pain: A network meta-analysis

10.21203/rs.3.rs-29083/v2 ◽

2020 ◽

Author(s):

John A Carter ◽

Libby K Black ◽

Dolly Sharma ◽

Tarun Bhagnani ◽

Jonathan Jahr

Keyword(s):

Postoperative Pain ◽

Pain Intensity ◽

Human Subjects ◽

Meta Analysis ◽

Opioid Analgesics ◽

Abdominal Hysterectomy ◽

Orthopedic Procedures ◽

Intensity Difference ◽

Cumulative Probability ◽

Pain Intensity Difference

Abstract BACKGROUND The aim of this network meta-analysis (NMA) was to evaluate the safety and efficacy of intravenous (IV) Meloxicam 30mg (MIV), an investigational non-steroidal anti-inflammatory drug (NSAID), and certain other IV non-opioid analgesics for moderate-severe acute postoperative pain. METHODS We searched PubMed and CENTRAL for Randomized Controlled Trials (RCT) (years 2000-2019, adult human subjects) of IV non-opioid analgesics (IV NSAIDs or IV Acetaminophen) used to treat acute pain after abdominal, hysterectomy, bunionectomy or orthopedic procedures. A Bayesian NMA was conducted in STATA (v15.0) to rank treatments based on the standardized mean differences in sum of pain intensity difference from baseline up to 24 hours postoperatively (Sum of pain intensity difference: SPID 24). The probability and the cumulative probability of rank for each treatment were calculated, and the surface under the cumulative ranking curve (SUCRA) was applied to distinguish each treatment by efficacy and safety where higher SUCRA values indicated better outcomes. Treatments were also compared by frequency of opioid-related adverse events (ORADEs) including gastrointestinal and respiratory and reduction in morphine milligram equivalents (MME). The study protocol was prospectively registered with by PROSPERO (CRD42019117360). RESULTS Out of 2,313 screened studies, 27 studies with 36 comparative observations were included, producing a treatment network that included the four non-opioid IV pain medications of interest (MIV, ketorolac, acetaminophen, and ibuprofen). MIV was associated with the largest SPID 24 for all procedure categories and comparators. The SUCRA ranking table indicated that MIV had the highest probability for the most effective treatment for abdominal (89.5%), bunionectomy (100%), and hysterectomy (99.8%). Significantly lower MME was associated with MIV for abdominal (vs acetaminophen, ibuprofen and ketorolac), bunionectomy (vs acetaminophen), hysterectomy (vs acetaminophen and ketorolac) and orthopedic procedures (vs acetaminophen and ibuprofen). Odds of ORADEs were significantly higher for all comparators vs MIV for orthopedic (gastrointestinal) and hysterectomy (respiratory). CONCLUSIONS MIV 30mg may provide better pain reduction with similar or better safety compared to other approved IV non-opioid analgesics. Caution is warranted in interpreting these results, as all comparisons involving MIV were indirect.

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Efficacy of non-opioid analgesics to control postoperative pain: A network meta-analysis

10.21203/rs.3.rs-29083/v1 ◽

2020 ◽

Author(s):

John A Carter ◽

Libby K Black ◽

Dolly Sharma ◽

Tarun Bhagnani ◽

Jonathan Jahr

Keyword(s):

Postoperative Pain ◽

Pain Intensity ◽

Human Subjects ◽

Meta Analysis ◽

Opioid Analgesics ◽

Abdominal Hysterectomy ◽

Orthopedic Procedures ◽

Intensity Difference ◽

Cumulative Probability ◽

Pain Intensity Difference

Abstract BACKGROUND The aim of this network meta-analysis (NMA) was to evaluate the safety and efficacy of intravenous (IV) Meloxicam 30 mg (MIV), an investigational non-steroidal anti-inflammatory drug (NSAID), and certain other IV non-opioid analgesics for moderate-severe acute postoperative pain. METHODS We searched PubMed and CENTRAL for Randomized Controlled Trials (RCT) (years 2000–2019, adult human subjects) of IV nonopioids (IV NSAIDs or IV Acetaminophen) used to treat acute pain after abdominal, hysterectomy, bunionectomy or orthopedic procedures. A Bayesian NMA was conducted in STATA (v13.0) to rank treatments based on the standardized mean differences in sum of pain intensity difference from baseline up to 24 hours postoperatively (Sum of pain intensity difference: SPID 24). The probability and the cumulative probability of rank for each treatment were calculated, and the surface under the cumulative ranking curve (SUCRA) was applied to distinguish each treatment by efficacy and safety where higher SUCRA values indicated better outcomes. Treatments were also compared by frequency of opioid-related adverse events (ORADEs) including gastrointestinal and respiratory and reduction in morphine milligram equivalents (MME). The study protocol was prospectively registered with by PROSPERO (CRD42019117360). RESULTS Out of 2,313 screened studies, 27 studies with 36 comparative observations were included, producing a treatment network that included the four non-opioid IV pain medications of interest (MIV, ketorolac, acetaminophen, and ibuprofen). MIV was associated with the largest SPID 24 for all procedure categories and comparators. The SUCRA ranking table indicated that MIV had the highest probability for the most effective treatment for abdominal (89.5%), bunionectomy (100%), and hysterectomy (99.8%). Significantly lower MME was associated with MIV for abdominal (vs acetaminophen, ibuprofen and ketorolac), bunionectomy (vs acetaminophen), hysterectomy (vs acetaminophen and ketorolac) and orthopedic procedures (vs acetaminophen and ibuprofen). Odds of ORADEs were significantly higher for all comparators vs MIV for orthopedic (gastrointestinal) and hysterectomy (respiratory). CONCLUSIONS MIV 30 mg may provide better pain reduction with similar or better safety compared to other approved IV non-opioid analgesics. Caution is warranted in interpreting these results, as all comparisons involving MIV were indirect.

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Analgesic effect of oral ibuprofen 400, 600, and 800 mg; paracetamol 500 and 1000 mg; and paracetamol 1000 mg plus 60 mg codeine in acute postoperative pain: a single-dose, randomized, placebo-controlled, and double-blind study

European Journal of Clinical Pharmacology ◽

10.1007/s00228-021-03231-9 ◽

2021 ◽

Author(s):

Gaute Lyngstad ◽

Per Skjelbred ◽

David M. Swanson ◽

Lasse A. Skoglund

Keyword(s):

Single Dose ◽

Pain Intensity ◽

Effect Size ◽

Analgesic Effect ◽

Intensity Difference ◽

Double Blind ◽

Pain Intensity Difference ◽

Calculated Effect ◽

Maximum Pain ◽

Size Estimates

Abstract Purpose Effect size estimates of analgesic drugs can be misleading. Ibuprofen (400 mg, 600 mg, 800 mg), paracetamol (1000 mg, 500 mg), paracetamol 1000 mg/codeine 60 mg, and placebo were investigated to establish the multidimensional pharmacodynamic profiles of each drug on acute pain with calculated effect size estimates. Methods A randomized, double-blind, single-dose, placebo-controlled, parallel-group, single-centre, outpatient, and single-dose study used 350 patients (mean age 25 year, range 18 to 30 years) of homogenous ethnicity after third molar surgery. Primary outcome was sum pain intensity over 6 h. Secondary outcomes were time to analgesic onset, duration of analgesia, time to rescue drug intake, number of patients taking rescue drug, sum pain intensity difference, maximum pain intensity difference, time to maximum pain intensity difference, number needed to treat values, adverse effects, overall drug assessment as patient-reported outcome measure (PROM), and the effect size estimates NNT and NNTp. Results Ibuprofen doses above 400 mg do not significantly increase analgesic effect. Paracetamol has a very flat analgesic dose–response profile. Paracetamol 1000/codeine 60 mg gives similar analgesia as ibuprofen from 400 mg, but has a shorter time to analgesic onset. Active drugs show no significant difference in maximal analgesic effect. Other secondary outcomes support these findings. The frequencies of adverse effects were low, mild to moderate in all active groups. NNT and NTTp values did not coincide well with PROMs. Conclusion Ibuprofen doses above 400 mg for acute pain offer limited analgesic gain. Paracetamol 1000 mg/codeine 60 mg is comparable to ibuprofen doses from 400 mg. Calculated effect size estimates and PROM in our study seem not to relate well as clinical analgesic efficacy estimators. Trial registration NCT00699114.

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Sufentanil Sublingual Tablet System for the Management of Postoperative Pain after Knee or Hip Arthroplasty

Anesthesiology ◽

10.1097/aln.0000000000000746 ◽

2015 ◽

Vol 123 (2) ◽

pp. 434-443 ◽

Cited By ~ 38

Author(s):

Maurice Jove ◽

David W. Griffin ◽

Harold S. Minkowitz ◽

Bruce Ben-David ◽

Mark A. Evashenk ◽

...

Keyword(s):

Pain Intensity ◽

Hip Arthroplasty ◽

Intensity Difference ◽

Double Blind Study ◽

Double Blind ◽

Sublingual Tablet ◽

Pain Intensity Difference ◽

Major Orthopedic Surgery ◽

American Society ◽

American Society Of Anesthesiologists

Abstract Background: Complications with IV patient-controlled analgesia include programming errors, invasive access, and impairment of mobility. This study evaluated an investigational sufentanil sublingual tablet system (SSTS) for the management of pain after knee or hip arthroplasty. Methods: This prospective, randomized, parallel-arm, double-blind study randomized postoperative patients at 34 U.S. sites to receive SSTS 15 μg (n = 315) or an identical placebo system (n = 104) and pain scores were recorded for up to 72 h. Adult patients with American Society of Anesthesiologists status 1 to 3 after primary total unilateral knee or hip replacement under general anesthesia or with spinal anesthesia that did not include intrathecal opioids were eligible. Patients were excluded if they were opioid tolerant. The primary endpoint was the time-weighted summed pain intensity difference to baseline over 48 h. Secondary endpoints included total pain relief, patient and healthcare professional global assessments, and patient and nurse ease-of-care questionnaires. Results: Summed pain intensity difference (standard error) was higher (better) in the SSTS group compared with placebo (76 [7] vs. −11 [11], difference 88 [95% CI, 66 to 109]; P < 0.001). In the SSTS group, more patients and nurses responded “good” or “excellent” on the global assessments compared with placebo (P < 0.001). Patient and nurse ease-of-care ratings for the system were high in both groups. There was a higher incidence of nausea and pruritus in the SSTS group. Conclusion: SSTS could be an effective patient-controlled pain management modality in patients after major orthopedic surgery and is easy to use by both patients and healthcare professionals.

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Analgesic Efficacy and Tolerability of Tramadol Versus Low Dose Tramadol-Paracetamol in Patients with Gastro Intestinal Surgery

Journal of Universal College of Medical Sciences ◽

10.3126/jucms.v7i2.27136 ◽

2019 ◽

Vol 7 (2) ◽

pp. 39-45

Author(s):

Monica Nepal ◽

Rama Paudel ◽

Rajesh Poudel ◽

Narayan Gautam

Keyword(s):

Pain Intensity ◽

Rescue Medication ◽

Low Dose ◽

Analgesic Efficacy ◽

Intensity Difference ◽

Haemodynamic Parameter ◽

Pain Intensity Difference ◽

Surgery Patient ◽

Efficacy Outcome ◽

Numerical Rating

INTRODUCTION: Analgesic regimens with an improved efficacy and tolerability balance have potential to improve acute pain management, and thus reduce the progression into chronic pain. Hence, an opportunity was gained to compare analgesic efficacy and tolerability of Tramadol (T) 1.5 mg/kg versus low dose Tramadol 1mg/kg-Paracetamol 1000mg (T-P) in patient with Gastro Intestinal (GI) surgery. MATERIAL AND METHODS: The study was a hospital based prospective, observational study conducted in sixty post-operative GI surgery patient at Universal College of Medical Sciences-Teaching Hospital, Ranigaon, Bhairahawa, Nepal. One group received Tramadol 1.5mg/kg (n=30) while the other group received Tramadol 1mg/kg with Paracetamol 1000 mg (n=30). The primary efficacy outcome measures were pain intensity difference (PID) and sum of pain intensity difference (SPID) whereas secondary efficacy measures included number of patient who require rescue medication, haemodynamic parameter, their quality of sleep in the night and satisfaction with their medication. For tolerability, adverse effect was noted that occurred during study time intervals. RESULTS: Mean pain intensity differences assessed on Numerical Rating Scores (NRS) were significantly better for Group T-P compared to Group T at all the points except 0.5, 1 and 6 hrs. The sum of pain intensity difference over 8, 16, 24, 48 hrs for Group T-P was significantly superior to Group T. Two patients in Tramadol group required rescue medication. Satisfaction to the pain medication was comparatively higher for Tramadol-Paracetamol group. CONCLUSION :- Tramadol-Paracetamol had more pronounced analgesic effect with lower incidence of side effect than Tramadol alone. Thus, low dose Tramadol-Paracetamol is better option for management of post-operative pain in patient with GI surgery.

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The Complex Balance between Analgesic Efficacy, Change of Dose and Safety Profile Over Time, in Cancer Patients Treated with Opioids: Providing the Clinicians with an Evaluation Tool

Journal of Clinical Medicine ◽

10.3390/jcm9020502 ◽

2020 ◽

Vol 9 (2) ◽

pp. 502

Author(s):

Oscar Corli ◽

Luca Porcu ◽

Claudia Santucci ◽

Cristina Bosetti

Keyword(s):

Adverse Events ◽

Pain Intensity ◽

Cancer Patients ◽

Dose Escalation ◽

Clinical Aspects ◽

Intensity Difference ◽

High Dose ◽

Pain Intensity Difference ◽

Therapeutic Decisions ◽

Daily Dose

Background: Scanty data exist on the integration between the analgesic effect of opioids, dose changes, and adverse events in cancer patients. Methods: To provide further information on this issue, we analysed data on 498 advanced-stage cancer patients treated with strong opioids. At baseline and three visits (at days 7, 14, and 21), pain intensity, oral morphine-equivalent daily dose, and the prevalence of major adverse events were measured. The proportion of responders (pain intensity decrease ≥30% from baseline) and non-responders, as well as of patients with low or high dose escalation, was calculated. Results: Pain intensity strongly decreased from baseline (pain intensity difference −4.0 at day 7 and −4.2 at day 21) in responders, while it was quite stable in non-responders (pain intensity difference −0.8 at day 7 and −0.9 at day 21). In low dose escalation patients (82.4% at final visit), daily dose changed from 52.3 to 65.3 mg; in high dose escalation patients (17.6%), it varied from 94.1 to 146.7 mg. Among responders, high dose escalation patients experienced significantly more frequent adverse events compared to low or high dose escalation patients, while no differences were observed in non-responders. Conclusions: The response to opioids results from the combination of three clinical aspects, which are strongly interrelated. These results provide some thoughts to help clinical evaluations and therapeutic decisions regarding opioid use.

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