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Biomolecules Jun 2024Special attention is given to cow's milk and its variants, with ongoing discussions about health-related impacts primarily focusing on the A1 variant in contrast to the...
Special attention is given to cow's milk and its variants, with ongoing discussions about health-related impacts primarily focusing on the A1 variant in contrast to the A2 variant. The difference between these variants lies in a single amino acid alteration at position 67 of β-casein. This alteration is presumed to make the A1 variant more susceptible to enzymatic breakdown during milk digestion, leading to an increased release of the peptide β-casomorphin-7 (BCM-7). BCM-7 is hypothesized to interact with µ-opioid receptors on immune cells in humans. Although BCM-7 has demonstrated both immunosuppressive and inflammatory effects, its direct impact on the immune system remains unclear. Thus, we examined the influence of A1 and A2 milk on Concanavalin A (ConA)-stimulated human peripheral blood mononuclear cells (PBMCs), as well as the effect of experimentally digested A1 and A2 milk, containing different amounts of free BCM-7 from β-casein cleavage. Additionally, we evaluated the effects of pure BCM-7 on the proliferation of ConA-stimulated PBMCs and purified CD4 T cells. Milk fundamentally inhibited PBMC proliferation, independent of the β-casein variant. In contrast, experimentally digested milk of both variants and pure BCM-7 showed no influence on the proliferation of PBMCs or isolated CD4 T cells. Our results indicate that milk exerts an anti-inflammatory effect on PBMCs, regardless of the A1 or A2 β-casein variant, which is nullified after in vitro digestion. Consequently, we deem BCM-7 unsuitable as a biomarker for food-induced inflammation.
Topics: Humans; Leukocytes, Mononuclear; Cell Proliferation; Milk; Endorphins; Animals; Caseins; Peptide Fragments; CD4-Positive T-Lymphocytes; Concanavalin A; Cattle
PubMed: 38927093
DOI: 10.3390/biom14060690 -
Scientific Reports Jun 2024Opioids are the gold standard for the treatment of chronic pain but are limited by adverse side effects. In our earlier work, we showed that Heat shock protein 90...
Opioids are the gold standard for the treatment of chronic pain but are limited by adverse side effects. In our earlier work, we showed that Heat shock protein 90 (Hsp90) has a crucial role in regulating opioid signaling in spinal cord; Hsp90 inhibition in spinal cord enhances opioid anti-nociception. Building on these findings, we injected the non-selective Hsp90 inhibitor KU-32 by the intrathecal route into male and female CD-1 mice, showing that morphine anti-nociceptive potency was boosted by 1.9-3.5-fold in acute and chronic pain models. At the same time, tolerance was reduced from 21-fold to 2.9 fold and established tolerance was rescued, while the potency of constipation and reward was unchanged. These results demonstrate that spinal Hsp90 inhibition can improve the therapeutic index of morphine. However, we also found that systemic non-selective Hsp90 inhibition blocked opioid pain relief. To avoid this effect, we used selective small molecule inhibitors and CRISPR gene editing to identify 3 Hsp90 isoforms active in spinal cord (Hsp90α, Hsp90β, and Grp94) while only Hsp90α was active in brain. We thus hypothesized that a systemically delivered selective inhibitor to Hsp90β or Grp94 could selectively inhibit spinal cord Hsp90 activity, resulting in enhanced opioid therapy. We tested this hypothesis using intravenous delivery of KUNB106 (Hsp90β) and KUNG65 (Grp94), showing that both drugs enhanced morphine anti-nociceptive potency while rescuing tolerance. Together, these results suggest that selective inhibition of spinal cord Hsp90 isoforms is a novel, translationally feasible strategy to improve the therapeutic index of opioids.
Topics: Animals; HSP90 Heat-Shock Proteins; Spinal Cord; Mice; Analgesics, Opioid; Male; Female; Morphine; Protein Isoforms; Drug Tolerance; Chronic Pain; Disease Models, Animal; Injections, Spinal
PubMed: 38926482
DOI: 10.1038/s41598-024-65637-6 -
Regional Anesthesia and Pain Medicine Jun 2024Hip arthroscopy causes severe pain during the first few hours in the postoperative care unit. This is probably due to the intraoperative stretching of the hip joint...
BACKGROUND
Hip arthroscopy causes severe pain during the first few hours in the postoperative care unit. This is probably due to the intraoperative stretching of the hip joint capsule. Pain relief requires high doses of opioids which may prolong recovery and may cause opioid-related adverse events.The majority of hip joint capsule nociceptors are located anteriorly. The obturator nerve innervates the anteromedial part of the hip joint capsule. We hypothesized that a subpectineal obturator nerve block using 15 ml bupivacaine 5 mg/mL with added epinephrine 5 μg/mL would reduce the opioid consumption after hip arthroscopy.
METHODS
40 ambulatory hip arthroscopy patients were enrolled in this randomized, triple-blind controlled trial. All patients were allocated to a preoperative active or placebo subpectineal obturator nerve block. The primary outcome was opioid consumption for the first 3 hours in the postanesthesia care unit. Secondary outcomes were pain, nausea, and hip adductor strength.
RESULTS
34 patients were analyzed for the primary outcome. The mean intravenous morphine equivalent consumption in the subpectineal obturator nerve block group was 11.9 mg vs 19.7 mg in the placebo group (p<0.001). The hip adductor strength was significantly reduced in the active group. No other intergroup differences were observed regarding the secondary outcomes.
CONCLUSION
We found a significant reduction in the opioid consumption for patients receiving an active subpectineal obturator nerve block. The postoperative intravenous morphine equivalent reduction the first painful 3 hours was reduced by 40% for patients receiving a subpectineal obturator nerve block in this randomized, triple-blind trial.
TRIAL REGISTRATION NUMBER
EudraCT database 2021-006575-42.
PubMed: 38925710
DOI: 10.1136/rapm-2024-105638 -
Anaesthesia Jun 2024Intrathecal diamorphine is believed to provide postoperative analgesia but is associated with adverse effects such as nausea and vomiting. There is little evidence of... (Review)
Review
BACKGROUND
Intrathecal diamorphine is believed to provide postoperative analgesia but is associated with adverse effects such as nausea and vomiting. There is little evidence of synthesis regarding intrathecal diamorphine in the contemporary literature. We performed a systematic review, meta-analysis with meta-regression and trial sequential analysis to determine the magnitude of intrathecal diamorphine efficacy and safety.
METHODS
We systematically searched the literature for trials comparing intrathecal diamorphine with a control group in patients undergoing all types of surgery. The primary efficacy and safety outcomes were intravenous morphine consumption and incidence of postoperative nausea and vomiting at 24 h following surgery, respectively.
RESULTS
Twelve trials were identified, which included data for 712 patients. Intrathecal doses of diamorphine ranged from 100 μg to 2500 μg. Intravenous morphine consumption at 24 h postoperatively was significantly reduced in the intrathecal diamorphine group, with a mean difference (95%CI) of -8 mg (-11 to -6), I = 93%, p < 0.001. There was a significant difference between three intrathecal diamorphine dosing subgroups but without correlation: mean differences (95%CI) -1 mg (-3-0), -26 mg (-40 to -11) and -6 mg (-15-4) in patients receiving doses of 0-200 μg, 201-400 μg and > 400 μg, respectively (p = 0.003). Intrathecal diamorphine increased postoperative nausea and vomiting with a risk ratio (95%CI) of 1.37 (1.19-1.58), I = 7%, p < 0.001. There were no differences in postoperative nausea and vomiting between the three intrathecal diamorphine dosing subgroups. There was no correlation observed with meta-regression of the primary efficacy and safety outcomes. The quality of evidence for all outcomes was very low.
CONCLUSION
There is very low level of evidence that intrathecal diamorphine provides effective analgesia after surgery, while increasing postoperative nausea and vomiting with doses > 200 μg.
PubMed: 38922818
DOI: 10.1111/anae.16359 -
JAMA Network Open Jun 2024Opioid medications are commonly prescribed for the management of acute postoperative pain. In light of increasing awareness of the potential risks of opioid prescribing,...
IMPORTANCE
Opioid medications are commonly prescribed for the management of acute postoperative pain. In light of increasing awareness of the potential risks of opioid prescribing, data are needed to define the procedures and populations for which most opioid prescribing occurs.
OBJECTIVE
To identify the surgical procedures accounting for the highest proportion of opioids dispensed to adults after surgery in the United States.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional analysis of the 2020-2021 Merative MarketScan Commercial and Multi-State Databases, which capture medical and pharmacy claims for 23 million and 14 million annual privately insured patients and Medicaid beneficiaries, respectively, included surgical procedures for individuals aged 18 to 64 years with a discharge date between December 1, 2020, and November 30, 2021. Procedures were identified using a novel crosswalk between 3664 Current Procedural Terminology codes and 1082 procedure types. Data analysis was conducted from November to December 2023.
MAIN OUTCOMES AND MEASURES
The total amount of opioids dispensed within 3 days of discharge from surgery across all procedures in the sample, as measured in morphine milligram equivalents (MMEs), was calculated. The primary outcome was the proportion of total MMEs attributable to each procedure type, calculated separately among procedures for individuals aged 18 to 44 years and those aged 45 to 64 years.
RESULTS
Among 1 040 934 surgical procedures performed (mean [SD] age of patients, 45.5 [13.3] years; 663 609 [63.7%] female patients), 457 016 (43.9%) occurred among individuals aged 18 to 44 years and 583 918 (56.1%) among individuals aged 45 to 64 years. Opioid prescriptions were dispensed for 503 058 procedures (48.3%). Among individuals aged 18 to 44 years, cesarean delivery accounted for the highest proportion of total MMEs dispensed after surgery (19.4% [11 418 658 of 58 825 364 MMEs]). Among individuals aged 45 to 64 years, 4 of the top 5 procedures were common orthopedic procedures (eg, arthroplasty of knee, 9.7% of total MMEs [5 885 305 of 60 591 564 MMEs]; arthroscopy of knee, 6.5% [3 912 616 MMEs]).
CONCLUSIONS AND RELEVANCE
In this cross-sectional study of the distribution of postoperative opioid prescribing in the United States, a small number of common procedures accounted for a large proportion of MMEs dispensed after surgery. These findings suggest that the optimal design and targeting of surgical opioid stewardship initiatives in adults undergoing surgery should focus on the procedures that account for the most opioid dispensed following surgery over the life span, such as childbirth and orthopedic procedures. Going forward, systems that provide periodic surveillance of opioid prescribing and associated harms can direct quality improvement initiatives to reduce opioid-related morbidity and mortality.
Topics: Humans; Analgesics, Opioid; Adult; Female; Middle Aged; Male; Cross-Sectional Studies; Pain, Postoperative; Practice Patterns, Physicians'; Patient Discharge; United States; Adolescent; Young Adult; Drug Prescriptions; Surgical Procedures, Operative
PubMed: 38922619
DOI: 10.1001/jamanetworkopen.2024.17651 -
Pediatrics Jul 2024Surgery is one of the most common indications for opioid prescribing to pediatric patients. We identified which procedures account for the most pediatric surgical opioid...
BACKGROUND AND OBJECTIVES
Surgery is one of the most common indications for opioid prescribing to pediatric patients. We identified which procedures account for the most pediatric surgical opioid prescribing.
METHODS
We conducted a cross-sectional analysis of commercial and Medicaid claims in the Merative MarketScan Commercial and Multi-State Medicaid Databases. Analyses included surgical procedures for patients aged 0 to 21 years from December 1, 2020, to November 30, 2021. Procedures were identified using a novel crosswalk between 3664 procedure codes and 1082 procedure types. For each procedure type in the crosswalk, we calculated the total amount of opioids in prescriptions dispensed within 3 days of discharge from surgery, as measured in morphine milligram equivalents (MMEs). We then calculated the share of all MMEs accounted for by each procedure type. We conducted analyses separately among patients aged 0 to 11 and 12 to 21 years.
RESULTS
Among 107 597 procedures for patients aged 0 to 11 years, the top 3 procedures accounted for 59.1% of MMEs in opioid prescriptions dispensed after surgery: Tonsillectomy and/or adenoidectomy (50.3%), open treatment of upper extremity fracture (5.3%), and removal of deep implants (3.5%). Among 111 406 procedures for patients aged 12 to 21 years, the top 3 procedures accounted for 33.1% of MMEs: Tonsillectomy and/or adenoidectomy (12.7%), knee arthroscopy (12.6%), and cesarean delivery (7.8%).
CONCLUSIONS
Pediatric surgical opioid prescribing is concentrated among a small number of procedures. Targeting these procedures in opioid stewardship initiatives could help minimize the risks of opioid prescribing while maintaining effective postoperative pain control.
Topics: Humans; Child; Adolescent; Child, Preschool; Analgesics, Opioid; Infant; Cross-Sectional Studies; Pain, Postoperative; Practice Patterns, Physicians'; Young Adult; Female; Male; United States; Infant, Newborn; Drug Prescriptions; Surgical Procedures, Operative; Medicaid
PubMed: 38919985
DOI: 10.1542/peds.2024-065814 -
Frontiers in Surgery 2024Total knee arthroplasty (TKA) is a common and effective procedure. Optimizing pain control and reducing postoperative discomfort are essential for patient satisfaction....
BACKGROUND
Total knee arthroplasty (TKA) is a common and effective procedure. Optimizing pain control and reducing postoperative discomfort are essential for patient satisfaction. No studies have examined the safety and efficacy of intra-articular corticosteroid injections following TKA. This study aims to examine the safety and efficacy of corticosteroids in intra-articular multimodal analgesic injections.
MATERIALS AND METHODS
This was a historically controlled study conducted at a single academic institution. Before May 2019, patients received an intra-articular cocktail injection without corticosteroids during surgery, referred to as the non-corticosteroid (NC) group. After June 2019, intraoperatively, patients received an intra-articular cocktail injection containing corticosteroids, referred to as the corticosteroid (C) group. Finally, 738 patients were evaluated, 370 in the C cohort and 368 in the NC cohort. The mean follow-up duration was 30.4 months for the C group and 48.4 months for the NC group.
RESULTS
The mean VAS scores at rest on postoperative day (POD) 1 (2.35) and POD3 (3.88) were significantly lower in the C group than those in the NC group, which were 2.86 (POD1) and 5.26 (POD3) ( < 0.05). Walking pain in the C group (4.42) was also significantly lower than that (5.96) in the NC group on POD3 ( < 0.05). Patients in the C group had a significantly higher mean range of motion (ROM) (92.55) on POD3 than that (86.38) in the NC group. The mean time to straight leg raise for group C (2.77) was significantly shorter than that (3.61) for the NC group ( < 0.05). The C group also had significantly fewer rescue morphine (1.9) and metoclopramide (0.21) uses per patient than the NC group, which were 3.1 and 0.24, respectively. No significant differences in fever or vomiting rates between groups were found. Patients in neither group developed periprosthetic joint infections or skin necrosis. One patient in the C group suffered from wound dehiscence, and the wound healed well after debridement. No patient died or had a re-operation in either group.
CONCLUSIONS
This pilot trial found that intra-articular injection of multimodal analgesia (including corticosteroids) reduced initial postoperative pain, increased ROM in the early postoperative days (up to POD3), and did not increase wound complications or infection rates in approximately 30 months of follow-up.
PubMed: 38919978
DOI: 10.3389/fsurg.2024.1279462 -
Frontiers in Medicine 2024This meta-analysis aims to examine how effective ketamine is in the management of acute and preventing chronic post-thoracotomy pain by synthesizing the available...
OBJECTIVE
This meta-analysis aims to examine how effective ketamine is in the management of acute and preventing chronic post-thoracotomy pain by synthesizing the available research.
METHOD
A systematic literature search was conducted across PubMed, Scopus, and Cochrane Library till May 2023. Randomized Controlled Trials (RCT) examining the influence of ketamine on post-thoracotomy pain in adults were included. The intervention group included ketamine plus morphine, while the control group included morphine only. The outcome measures were opioid intake and pain scores at rest and on moving/coughing. Evidence quality was evaluated using the Cochrane Risk of Bias and GRADE assessment.
RESULTS
Nine articles comprising 556 patients were selected for meta-analysis. The intervention group had a significant decrease in pain at rest (Std. Mean Difference (SMD = -0.60 with 95% CI [-0.83, -0.37]) and on movement/cough (SMD = -0.73 [-1.27, -0.18]) in the first postoperative days. Also, the ketamine group had lower opioid consumption (mg) in comparison with controls (SMD = -2.75 [-4.14, -1.36], -value = 0.0001) in postoperative days 1-3. There was no data to assess the long-term effect of ketamine on chronic pain.
CONCLUSION
This meta-analysis shows that ketamine use can lower acute pain levels and morphine use after thoracotomy. In the future, larger RCTs using standardized methods and assessing both short-term and long-term analgesic effects of ketamine are necessary to deepen the understanding of the issue.
PubMed: 38919936
DOI: 10.3389/fmed.2024.1394219 -
Hospital Pharmacy Aug 2024The Updated 2022 Centers for Disease Control (CDC) Clinical Practice Guideline for Prescribing Opioids for Pain highlights the importance of shared decision making and...
The Updated 2022 Centers for Disease Control (CDC) Clinical Practice Guideline for Prescribing Opioids for Pain highlights the importance of shared decision making and provider-patient relationships. Interprofessional teams may be helpful in supporting providers and patients. A large, multi-site primary care department created an interprofessional primary care opioid stewardship team to target high-risk opioid prescribing and improve practice alignment with CDC recommendations through dashboard reporting and education. The primary objective was to assess reduction in morphine milligram equivalents (MME) from baseline to 6 months in patients on opioid doses ≥90 MME daily. The secondary objective assessed change in number of naloxone prescriptions from baseline to 6 months after education. The study was conducted across 30 primary care sites of one health system within Michigan from 2021 to 2022. The opioid stewardship team included 2 physicians, 3 pharmacists, a project operations manager, and IT support. Interventions included creation of a dashboard, provider education, dissemination of policy, and chart audits. Using the electronic health record (EHR) dashboard, patients on chronic opioid doses ≥90 MME daily or missing an active naloxone prescription were identified. Primary care providers (PCP) were provided with an individual list of patients for whom to consider intervention. Support was provided for prescribers, but the team did not interact with patients directly. Baseline analysis identified 290 patients on doses ≥ 90 MME daily. There was reduction in median daily MME from baseline to 6 months in the overall study population (140 [105 240] vs 120 [90 240], < .001). At 6 months 181 (62.4%) of patients had been given a prescription for naloxone versus 108 (37.2%) who had one at baseline, < .001. The initiatives implemented by the opioid stewardship team resulted in statistically significant reductions in MME and an increase in naloxone prescribing from baseline to 6 months post-education.
PubMed: 38919753
DOI: 10.1177/00185787241234241 -
Journal of Anaesthesiology, Clinical... 2024Regional anaesthesia has gained popularity in managing post-operative pain in paediatric patients. Quadratus lumborum block (QLB) is recognised as one of the...
BACKGROUND AND AIMS
Regional anaesthesia has gained popularity in managing post-operative pain in paediatric patients. Quadratus lumborum block (QLB) is recognised as one of the peri-operative pain management techniques used during abdominal surgeries. However, no consensus about the best approach has been reached.
MATERIAL AND METHODS
Sixty paediatric patients with ages ranging from 1 to 6 as well as classification I and II of the American Society of Anesthesiologists, scheduled for laparoscopic inguinal hernia, were allocated to receive either a posterior approach (Group I) or an anterior approach (Group II) QLB. Twenty four-hour morphine consumption, the face, legs, activity, cry, and consolability (FLACC) score, duration of analgesia, performance time, and block-related complications were recorded.
RESULTS
Group II showed significantly lower morphine consumption as well as a longer duration of analgesia ( = 0.039*, 0.020*, respectively), with an equivalent period for block performance being reported in the two groups ( = 0.080). At 2, 4, 6, and 12 hours post-operatively, the FLACC scores were substantially diminished in Group II compared to Group I ( = 0.001*, 0.012*, 0.002*, 0.028*, respectively). However, at twenty-four hours, comparable pain scores were observed between both groups ( = 0.626). In addition, there were no block-related complications.
CONCLUSIONS
In paediatric patients scheduled for laparoscopic inguinal hernia repair, the ultra-sound-guided anterior approach of the QLB was associated with significantly reduced post-operative morphine consumption, a lower FLACC score, and a longer analgesia duration when compared to the posterior approach.
PubMed: 38919434
DOI: 10.4103/joacp.joacp_366_22