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Journal of Pain and Symptom Management Jun 2024Strong opioids are the cornerstone in the treatment of cancer-related pain.
CONTEXT
Strong opioids are the cornerstone in the treatment of cancer-related pain.
OBJECTIVES
This study aims to compare analgesic effectiveness of different strong opioids for the treatment of cancer-related pain.
METHODS
PubMed and Embase were searched for RCTs that compared strong opioids for treatment of cancer-related pain against one another. A network meta-analysis was conducted and the related Surface Under the Cumulative RAnking (SUCRA)-based treatment ranks were calculated. Primary outcome was pain intensity (numerical rating scale (NRS)) and/or the percentage of patients with ≥50% pain reduction, after 1 and 2-4 weeks.
RESULTS
Sixteen RCTs (1813 patients) were included. Methadone showed, with a high certainty of evidence, increased ORs for treatment success at 1 week, compared with morphine, buprenorphine, fentanyl, and oxycodone, range 3.230-36.833. Methadone had the highest likelihood to be the treatment of preference (ToP) (SUCRA 0.9720). For fentanyl, ORs were lower, however significant and with high certainty. After 2-4 weeks, methadone again showed the highest likelihood for ToP, however, with moderate certainty and non-significant ORs. The combination of morphine/methadone, compared with morphine, buprenorphine, fentanyl, hydromorphone, methadone, and oxycodone achieved a treatment effect of mean NRS difference after 2-4 weeks between -1.100 and -1.528 and had the highest likelihood for ToP.
CONCLUSION
The results suggest that methadone possibly deserves further promotion as first-line treatment for the treatment of cancer-related pain.
PubMed: 38838946
DOI: 10.1016/j.jpainsymman.2024.05.022 -
PloS One 2024In 2017, a university-based academic healthcare system changed the opioid default pill count from 30 to 12 pills. Modifying the electronic default pill count influences...
BACKGROUND
In 2017, a university-based academic healthcare system changed the opioid default pill count from 30 to 12 pills. Modifying the electronic default pill count influences short-term clinician prescribing practices. We sought to understand the long-term impact on postoperative opioid prescribing habits after an opioid default pill count reduction.
MATERIALS AND METHODS
A retrospective electronic medical record system (EMRS) review was conducted in a healthcare system comprised of seven affiliated hospitals. Patients who underwent a surgical procedure and were prescribed an opioid on discharge between 2017-2021 were evaluated. All prescriptions were converted into morphine equivalents (MME). Analyses were performed with the chi-square test and Bonferonni adjusted t-test.
RESULTS
191,379 surgical procedures were studied. The average quantity of opioids prescribed decreased from 32 oxycodone 5 mg tablets in 2017 to 21 oxycodone 5 mg tablets in 2021 (236 MME to 154 MME, p<0.001). The percentage of patients obtaining a refill within 90 days of surgery varied between 18.3% and 19.9% (p<0.001). Patients with a pre-existing opioid prescription and opioid-naïve patients both had significant reductions in prescription quantities above the default MME (79.7% to 60.6% vs. 65.3% to 36.9%, p<0.001). There was no significant change in refills for both groups (pre-existing 36.7% to 38.3% (p = 0.1) vs naïve 15.0% to 15.3% (p = 0.29)).
CONCLUSIONS
The benefits of decreasing the default opioid pill count continue to accumulate long after the original change. Physician uptake of small changes to default EMRS practices represents a sustainable and effective intervention to reduce the quantities of postoperative opioids prescribed without deleterious effects on outpatient opiate requirements.
Topics: Humans; Male; Female; Analgesics, Opioid; Middle Aged; Retrospective Studies; Pain, Postoperative; Drug Prescriptions; Practice Patterns, Physicians'; Adult; Aged; Electronic Health Records; Oxycodone
PubMed: 38833500
DOI: 10.1371/journal.pone.0304100 -
Drug Design, Development and Therapy 2024Oxycodone is a potent μ- and κ-opioid receptor agonist that can relieve both somatic and visceral pain. We assessed oxycodone- vs sufentanil-based multimodal analgesia... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
PURPOSE
Oxycodone is a potent μ- and κ-opioid receptor agonist that can relieve both somatic and visceral pain. We assessed oxycodone- vs sufentanil-based multimodal analgesia on postoperative pain following major laparoscopic gastrointestinal surgery.
METHODS
In this randomised double-blind controlled trial, 40 adult patients were randomised (1:1, stratified by type of surgery) to receive oxycodone- or sufentanil-based multimodal analgesia, comprising bilateral transverse abdominis plane blocks, intraoperative dexmedetomidine infusion, flurbiprofen axetil, and oxycodone- or sufentanil-based patient-controlled analgesia. The co-primary outcomes were time-weighted average (TWA) of visceral pain (defined as intra-abdominal deep and dull pain) at rest and on coughing during 0-24 h postoperatively, assessed using the numerical rating scale (0-10) with a minimal clinically important difference of 1.
RESULTS
All patients completed the study (median age, 64 years; 65% male) and had adequate postoperative pain control. The mean (SD) 24-h TWA of visceral pain at rest was 1.40 (0.77) in the oxycodone group vs 2.00 (0.98) in the sufentanil group (mean difference=-0.60, 95% CI, -1.16 to -0.03; =0.039). Patients in the oxycodone group had a significantly lower 24-h TWA of visceral pain on coughing (2.00 [0.83] vs 2.98 [1.26]; mean difference=-0.98, 95% CI, -1.66 to -0.30; =0.006). In the subgroup analyses, the treatment effect of oxycodone vs sufentanil on the co-primary outcomes did not differ in terms of age (18-65 years or >65 years), sex (female or male), or type of surgery (colorectal or gastric). Secondary outcomes (24-h TWA of incisional and shoulder pain, postoperative analgesic usage, rescue analgesia, adverse events, and patient satisfaction) were comparable between groups.
CONCLUSION
For patients undergoing major laparoscopic gastrointestinal surgery, oxycodone-based multimodal analgesia reduced postoperative visceral pain in a statistically significant but not clinically important manner.
TRIAL REGISTRATION
Chinese Clinical Trial Registry (ChiCTR2100052085).
Topics: Humans; Oxycodone; Double-Blind Method; Middle Aged; Male; Female; Laparoscopy; Pain, Postoperative; Visceral Pain; Aged; Analgesics, Opioid; Adult; Digestive System Surgical Procedures; Dexmedetomidine; Sufentanil; Analgesia, Patient-Controlled; Flurbiprofen
PubMed: 38828025
DOI: 10.2147/DDDT.S464518 -
PeerJ 2024To compare the impact of erector spinae plane block (ESPB) and paravertebral block (PVB) on the quality of postoperative recovery (QoR) of patients following... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Erector spinae plane block versus paravertebral block on postoperative quality of recovery in obese patients undergoing laparoscopic sleeve gastrectomy: a randomized controlled trial.
PURPOSE
To compare the impact of erector spinae plane block (ESPB) and paravertebral block (PVB) on the quality of postoperative recovery (QoR) of patients following laparoscopic sleeve gastrectomy (LSG).
METHODS
A total of 110 patients who underwent elective LSG under general anesthesia were randomly assigned to receive either ultrasound-guided bilateral ESPB or PVB at T8 levels. Before anesthesia induction, 40 mL of 0.33% ropivacaine was administered. The primary outcome was the QoR-15 score at 24 hours postoperatively.
RESULTS
At 24 hours postoperatively, the QoR-15 score was comparable between the ESPB and PVB groups (131 (112-140) 124 (111-142.5), = 0.525). Consistently, there was no significant difference in QoR-15 scores at 48 hours postoperatively, numerical rating scale (NRS) pain scores at any postoperative time points, time to first ambulation, time to first anal exhaust, postoperative cumulative oxycodone consumption, and incidence of postoperative nausea and vomiting (PONV) between the two groups (all > 0.05). No nerve block-related complications were observed in either group.
CONCLUSION
In patients undergoing LSG, preoperative bilateral ultrasound-guided ESPB yields comparable postoperative recovery to preoperative bilateral ultrasound-guided PVB.
Topics: Humans; Female; Nerve Block; Male; Gastrectomy; Laparoscopy; Adult; Pain, Postoperative; Middle Aged; Anesthetics, Local; Ropivacaine; Ultrasonography, Interventional; Pain Measurement; Paraspinal Muscles; Treatment Outcome; Obesity, Morbid; Postoperative Nausea and Vomiting; Anesthesia, General
PubMed: 38827293
DOI: 10.7717/peerj.17431 -
Perioperative Medicine (London, England) May 2024Multimodal analgesia regimens are recommended for the postoperative period after hip and knee replacement surgeries. However, there are no data on practice patterns for...
BACKGROUND
Multimodal analgesia regimens are recommended for the postoperative period after hip and knee replacement surgeries. However, there are no data on practice patterns for analgesic use in the immediate postoperative period after hip and knee replacements in Australia.
OBJECTIVES
To describe analgesic prescribing patterns in the inpatient postoperative phase for patients undergoing hip and knee replacement.
METHODS
Retrospective study of electronic medical record data from two major hospitals in Sydney, Australia. We identified analgesic medication prescriptions for all patients aged 18 years and older who underwent hip or knee replacement surgery in 2019. We extracted data on pain medications prescribed while in the ward up until discharge. These were grouped into distinct categories based on the Anatomical Therapeutic Chemical classification. We described the frequency (%) of pain medications used by category and computed the average oral morphine equivalent daily dose (OMEDD) during hospitalisation.
RESULTS
We identified 1282 surgeries in 1225 patients. Patients had a mean (SD) age of 69 (11.8) years; most (57.1%) were female. Over 99% of patients were prescribed opioid analgesics and paracetamol during their hospital stay. Most patients (61.4%) were managed with paracetamol and opioids only. The most common prescribed opioid was oxycodone (87.3% of patients). Only 19% of patients were prescribed nonsteroidal anti-inflammatories (NSAIDs). The median (IQR) average daily OMEDD was 50.2 mg (30.3-77.9).
CONCLUSION
We identified high use of opioids analgesics as the main strategies for pain control after hip and knee replacement in hospital. Other analgesics were much less frequently used, such as NSAIDs, and always in combination with opioids and paracetamol.
PubMed: 38822448
DOI: 10.1186/s13741-024-00403-w -
Cureus Apr 2024Stiff Person Syndrome (SPS) is a rare autoimmune condition marked by extremely painful muscle spasms, stiffness, and rigidity throughout the body. Its rarity often...
Stiff Person Syndrome (SPS) is a rare autoimmune condition marked by extremely painful muscle spasms, stiffness, and rigidity throughout the body. Its rarity often translates to limited treatment options for patients and, occasionally, challenges in obtaining a definitive diagnosis. SPS also impacts patients' mental health, social and economic involvement, and overall quality of life. A 43-year-old man was initially being seen for lumbar radicular pain. A clinical diagnosis of SPS was made by a neurologist and confirmed by in-clinic follow-ups and anti-glutamic acid decarboxylase (anti-GAD) antibody testing. The Pain Management doctor agreed with this diagnosis and offered intravenous (IV) ketamine treatment, which he has found to positively impact the treatment of similar disorders. After an initial 10-day infusion, the patient reported improvement in pain and function. For almost two years, the patient received intravenous immunoglobulin (IVIg) and IV ketamine treatments to manage their condition and maintain pain control as well as quality of life. When the patient's symptoms began worsening after IVIg infusions, the decision to withdraw IVIg infusions and continue ketamine infusions was made. After discontinuing IVIg infusions, the patient reported improvement in function and pain level and continues to receive monthly two-day ketamine boosters. Outside of the infusions, the patient was able to discontinue the use of fentanyl patches and continued taking ketamine lozenges, oxycodone-acetaminophen, and dextromethorphan for at-home pain management. The patient's symptoms continue to be managed effectively with their current regimen, enabling their return to work and experiencing an enhanced quality of life. This case illustrates the potential benefits of IV ketamine treatment for patients with treatment-resistant SPS and similar neurologic and autoimmune disorders. Understanding and examining treatment alternatives for rare syndromes is crucial for achieving optimal patient outcomes. Additionally, documenting such cases offers valuable insights into the mechanism of ketamine, extending beyond these syndromes.
PubMed: 38817534
DOI: 10.7759/cureus.59397 -
BioRxiv : the Preprint Server For... May 202430% of people in the United States have diabetes or pre-diabetes. Many of these individuals will develop diabetic neuropathy as a comorbidity, which is often treated...
30% of people in the United States have diabetes or pre-diabetes. Many of these individuals will develop diabetic neuropathy as a comorbidity, which is often treated with exogenous opioids like morphine, oxycodone, or tramadol. Although these opioids are effective analgesics, growing evidence indicates that they may directly impact the endocrine pancreas function in human and preclinical models. One common feature of these exogenous opioid ligands is their preference for the mu opioid receptor (MOPR), so we aimed to determine if endogenous MOPRs directly regulate pancreatic islet metabolism and hormone secretion. We show that pharmacological antagonism of MOPRs enhances glucagon secretion, but not insulin secretion, from human islets under high glucose conditions. This increased secretion is accompanied by increased cAMP signaling. mRNA expression of MOPRs is enriched in human islet α-cells, but downregulated in T2D islet donors, suggesting a link between metabolism and MOPR expression. Conditional genetic knockout of MOPRs in murine α-cells increases glucagon secretion in high glucose conditions without increasing glucagon content. Consistent with downregulation of MOPRs during metabolic disease, conditional MOPR knockout mice treated with a high fat diet show impaired glucose tolerance, increased glucagon secretion, increased insulin content, and increased islet size. Finally, we show that MOPR-mediated changes in glucagon secretion are driven, in part, by KATP channel activity. Together, these results demonstrate a direct mechanism of action for endogenous opioid regulation of endocrine pancreas.
PubMed: 38798528
DOI: 10.1101/2024.05.13.593899 -
BioRxiv : the Preprint Server For... Apr 2024Opioid use disorder is heritable, yet its genetic etiology is largely unknown. Analysis of addiction model traits in rodents (e.g., opioid behavioral sensitivity and...
Opioid use disorder is heritable, yet its genetic etiology is largely unknown. Analysis of addiction model traits in rodents (e.g., opioid behavioral sensitivity and withdrawal) can facilitate genetic and mechanistic discovery. C57BL/6J and C57BL/6NJ substrains have extremely limited genetic diversity, yet can show reliable phenotypic diversity which together, can facilitate gene discovery. The C57BL/6NJ substrain was less sensitive to oxycodone (OXY)-induced locomotor activity compared to the C57BL/6J substrain. Quantitative trait locus (QTL) mapping in an F2 cross identified a distal chromosome 1 QTL explaining 7-12% of the variance in OXY locomotor sensitivity and anxiety-like withdrawal in the elevated plus maze. We identified a second QTL for withdrawal on chromosome 5 near the candidate gene Gabra2 (alpha-2 subunit of GABA-A receptor) explaining 9% of the variance. Next, we generated recombinant lines from an F2 founder spanning the distal chromosome 1 locus (163-181 Mb), captured the QTL for OXY sensitivity and withdrawal, and fine-mapped a 2.45-Mb region (170.16-172.61 Mb). There were five striatal cis-eQTL transcripts in this region (Pcp4l1, Ncstn, Atp1a2, Kcnj9, Igsf9), two of which were confirmed at the protein level (KCNJ9, ATP1A2). Kcnj9, a.k.a., GIRK3, codes for a potassium channel that is a major effector of mu opioid receptor signaling. Atp1a2 codes for a subunit of a Na+/K+ ATPase enzyme that regulates neuronal excitability and shows adaptations following chronic opioid administration. To summarize, we identified genetic sources of opioid behavioral differences in C57BL/6 substrains, two of the most widely and often interchangeably used substrains in opioid addiction research.
PubMed: 38798314
DOI: 10.1101/2024.04.16.589731 -
Journal of Personalized Medicine May 2024Severe cancer pain substantially affects patients' quality of life, increasing the burden of the disease and reducing the disability-adjusted life years. Although opioid... (Review)
Review
Severe cancer pain substantially affects patients' quality of life, increasing the burden of the disease and reducing the disability-adjusted life years. Although opioid analgesics are effective, they may induce opioid-induced bowel dysfunction (OIBD). Oxycodone/naloxone combination therapy has emerged as a promising approach to mitigate opioid-induced constipation (OIC) while providing effective pain relief. This review provides an updated analysis of the literature of the last decade regarding the use of oxycodone/naloxone in the management of severe cancer pain. Through a comprehensive search of databases, studies focusing on the efficacy, safety, and patient experience of oxycodone/naloxone's prolonged release in severe cancer pain management were identified. Furthermore, the literature discusses the mechanism of action of naloxone in mitigating OIC without compromising opioid analgesia. Overall, the evidence suggests that oxycodone/naloxone combination therapy offers a valuable option for effectively managing severe cancer pain while minimizing opioid-induced constipation, thereby improving patients' quality of life. However, further research is needed to optimize dosing regimens, evaluate long-term safety, and assess patient outcomes in diverse cancer populations.
PubMed: 38793067
DOI: 10.3390/jpm14050483 -
Acta Obstetricia Et Gynecologica... Jul 2024There is a paucity of objectively verified data on substance use among Danish pregnant women. We estimated the prevalence of substance use including alcohol and nicotine...
INTRODUCTION
There is a paucity of objectively verified data on substance use among Danish pregnant women. We estimated the prevalence of substance use including alcohol and nicotine among the general population of Danish pregnant women.
MATERIAL AND METHODS
In this anonymous, national, cross-sectional, descriptive study, pregnant women were invited when attending an ultrasound scan between November 2019 and December 2020 at nine Danish hospitals. Women submitted a urine sample and filled out a questionnaire. Urine samples were screened on-site with a qualitative urine dipstick for 15 substances including alcohol, nicotine, opioids, amphetamines, cannabis, and benzodiazepines. All screen-positive urine samples underwent secondary quantitative analyses with gold standard, liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Results were compared to questionnaire information to analyze the validity of self-reporting and to examine possible cross-reactions.
RESULTS
A total of 1903 of 2154 invited pregnant women participated (88.3%). The prevalence of dipstick-positive urine samples was 25.0%. 44.0% of these were confirmed positive, resulting in a total confirmed prevalence of 10.8%. The prevalence of nicotine use was 10.1%-and for all other substances, <0.5%. Nicotine use was more prevalent among younger pregnant women, while other substance use appeared evenly distributed over age groups. Self-reporting of use of nicotine products was high (71.1%), but low for cannabis and alcohol intake (0% and 33.3%, respectively). Prescription medication explained almost all cases of oxycodone, methylphenidate, and benzodiazepine use.
CONCLUSIONS
Substance use among pregnant women consisted mainly of nicotine. Dipstick screening involved risks of false negatives and false positives. Except for alcohol intake and cannabis use, dipstick analyses did not seem to provide further information than self-reporting. LC-MS/MS analyses remain gold standard, and future role of dipstick screenings should be discussed.
Topics: Humans; Female; Pregnancy; Cross-Sectional Studies; Denmark; Adult; Substance-Related Disorders; Substance Abuse Detection; Prevalence; Pregnancy Complications; Surveys and Questionnaires; Young Adult; Tandem Mass Spectrometry; Chromatography, Liquid
PubMed: 38778571
DOI: 10.1111/aogs.14862