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Pediatric Hematology and Oncology Jun 2024This study aimed to evaluate the utilization of drugs with pharmacogenomic guidelines (PGx-drugs) for personalized dosing in pediatric leukemia. A retrospective...
This study aimed to evaluate the utilization of drugs with pharmacogenomic guidelines (PGx-drugs) for personalized dosing in pediatric leukemia. A retrospective observational study of pediatric leukemia patients admitted between 2009-2019 at a single-center academic children's hospital was conducted to determine PGx-drug exposure within 3 years of diagnosis. Along with baseline demographic and clinical characteristics of these patients, data regarding dates of diagnosis, relapse, death were collected. During the study period, inclusion criteria were met by 714 patients. The most frequently given medications were ondansetron (96.1%), morphine (92.2%), and allopurinol (85.3%) during the study period. In this cohort, 82% of patients received five or more PGx-drugs. Patients diagnosed with acute myeloid leukemia and leukemia unspecified were prescribed more PGx-drugs than other types of leukemia. There was a significant relationship between age at diagnosis and the number of PGx-drugs prescribed. Adolescents and adults both received a median of 10 PGx-drugs, children received a median of 6 PGx-drugs, and infants received a median of 7 PGx-drugs ( < 0.001). Patients with recurrent leukemia had significantly more PGx-drugs prescribed compared to those without recurrent disease, 10 drugs and 6 drugs, respectively ( < 0.001). Patients diagnosed with childhood leukemia are high utilizers of PGx-drugs. There is a vital need to understand how PGx testing may be utilized to optimize treatment and enhance quality of life. Preemptive PGx testing is a tool that aids in optimization of drug therapy and decreases the need for later treatment modifications. This can result in financial savings from decreased health-care encounters.
PubMed: 38904214
DOI: 10.1080/08880018.2024.2368007 -
The Journal of Arthroplasty Jun 2024Successful revision hip arthroplasty (rTHA) requires major resource allocation and a surgical team adept at managing these complex cases. The purpose of this study was...
INTRODUCTION
Successful revision hip arthroplasty (rTHA) requires major resource allocation and a surgical team adept at managing these complex cases. The purpose of this study was to compare the results of rTHA performed by fellowship-trained and non-fellowship-trained surgeons.
METHODS
A national administrative database was utilized to identify 5,880 patients who underwent aseptic rTHA and 1,622 patients who underwent head-liner exchange for infection by fellowship- and non-fellowship-trained surgeons from 2010 to 2020 with a 5-year follow-up. Postoperative opioid and anticoagulant prescriptions were compared among surgeons. Patients treated by fellowship- and non-fellowship-trained surgeons had propensity scores matched based on age, sex, comorbidity index, and diagnosis. The five-year surgical complications were compared using descriptive statistics. Multivariable analysis was performed to determine the odds of failure following head-liner exchange when performed by a fellowship-trained versus non-fellowship-trained surgeon.
RESULTS
Aseptic rTHA patients treated by fellowship-trained surgeons received fewer opioids (132 versus 165 milligram morphine equivalents per patient) and non-aspirin anticoagulants (21.4 versus 32.0%, P < 0.001). Fellowship-training was associated with lower dislocation rates (9.9 versus 14.2%, P = 0.011), fewer postoperative infections, and fewer periprosthetic fractures and re-revisions (15.2 versus 21.3%, P < 0.001). Head-liner exchange for infection performed by fellowship-trained surgeons was associated with lower odds of failure (31.2 versus 45.7%, odds ratio (OR) 0.76, 95% confidence interval (CI) 0.62 to 0.91, P < 0.001).
CONCLUSIONS
Revision THA performed by adult reconstruction fellowship-trained surgeons results in fewer re-revisions in aseptic cases and head-liner exchanges. Variations in resources, volumes, and perioperative protocols may account for some of the differences.
PubMed: 38901710
DOI: 10.1016/j.arth.2024.06.029 -
Redox Biology Jun 2024Morphine, a typical opiate, is widely used for controlling pain but can lead to various side effects with long-term use, including addiction, analgesic tolerance, and...
Morphine, a typical opiate, is widely used for controlling pain but can lead to various side effects with long-term use, including addiction, analgesic tolerance, and hyperalgesia. At present, however, the mechanisms underlying the development of morphine analgesic tolerance are not fully understood. This tolerance is influenced by various opioid receptor and kinase protein modifications, such as phosphorylation and ubiquitination. Here, we established a murine morphine tolerance model to investigate whether and how S-nitrosoglutathione reductase (GSNOR) is involved in morphine tolerance. Repeated administration of morphine resulted in the down-regulation of GSNOR, which increased excessive total protein S-nitrosation in the prefrontal cortex. Knockout or chemical inhibition of GSNOR promoted the development of morphine analgesic tolerance and neuron-specific overexpression of GSNOR alleviated morphine analgesic tolerance. Mechanistically, GSNOR deficiency enhanced S-nitrosation of cellular protein kinase alpha (PKCα) at the Cys78 and Cys132 sites, leading to inhibition of PKCα kinase activity, which ultimately promoted the development of morphine analgesic tolerance. Our study highlighted the significant role of GSNOR as a key regulator of PKCα S-nitrosation and its involvement in morphine analgesic tolerance, thus providing a potential therapeutic target for morphine tolerance.
PubMed: 38901102
DOI: 10.1016/j.redox.2024.103239 -
European Journal of Orthopaedic Surgery... Jun 2024Nalbuphine, a synthetic k-agonist and µ-antagonist, provides efficient pain relief while reducing opioid-related adverse effects. This study aims to compare the...
BACKGROUND
Nalbuphine, a synthetic k-agonist and µ-antagonist, provides efficient pain relief while reducing opioid-related adverse effects. This study aims to compare the efficacy of intrathecal nalbuphine (ITN) with intrathecal morphine (ITM) for post-TKA pain.
METHODS
A retrospective cohort analysis of 131 patients who underwent TKA with spinal anesthesia (SA), a single shot of adductor canal block, and periarticular injections was conducted. The patients were divided into 2 groups, Group N received 0.8 mg nalbuphine, and Group M received 0.2 mg morphine as an adjuvant to SA. Propensity-score matching was employed to compare the visual analog scales (VAS) of postoperative pain intensity, cumulative morphine use (CMU), maximum knee flexion angle, straight leg raise (SLR) ability, incidence of postoperative nausea and vomiting (PONV), and length of hospital stay (LHS).
RESULTS
The mean VAS of group M were significantly lower than group N at 6, 12, 18, and 24 h (P < 0.01). Group M had lower CMU than group N at 24 h (P < 0.01) and 48 h (P < 0.01), while there was no significant difference between groups in terms of knee flexion angle and SLR at any time point. Additionally, 29.3 and 57.9% of patients in group N and M experienced PONV, respectively (p = 0.04), and group N had significantly shorter LHS compared to group M (P < 0.001).
CONCLUSION
Although, intrathecal morphine (ITM) still provides better pain control particularly in the first 24 h, patients who received intrathecal nalbuphine (ITN) had significantly fewer incidence of PONV, and shorter LHS.
PubMed: 38900159
DOI: 10.1007/s00590-024-04022-5 -
Urology Practice Jul 2024Gabapentin has been used in enhanced recovery after surgery (ERAS) pathways for pain control for patients undergoing ambulatory uro-oncologic surgery; however, it may...
INTRODUCTION
Gabapentin has been used in enhanced recovery after surgery (ERAS) pathways for pain control for patients undergoing ambulatory uro-oncologic surgery; however, it may cause undesirable side effects. We studied the causal association between gabapentin and rapidity of recovery and perioperative pain management after minimally invasive uro-oncologic surgery.
METHODS
We identified 2397 patients ≤ 65 years undergoing prostatectomies or nephrectomies between 2018 and 2022; 131 (5.5%) did not receive gabapentin. We tested the effect of gabapentin use on time of discharge and perioperative opioid consumption, respectively, using multivariable linear regression adjusting for potential confounders including age, gender, BMI, American Society of Anesthesiologists score, and surgery type.
RESULTS
On adjusted analysis, we found no evidence of a difference in discharge time among those who did vs did not receive gabapentin (adjusted difference 0.07 hours shorter on gabapentin; 95% CI -0.17, 0.31; = .6). There was no evidence of a difference in intraoperative opioid consumption by gabapentin receipt (adjusted difference -1.5 morphine milligram equivalents; 95% CI -4.2, 1.1; = .3) or probability of being in the top quartile of postoperative opioid consumption within 24 hours (adjusted difference 4.2%; 95% CI -4.8%, 13%; = .4). We saw no important differences in confounders by gabapentin receipt suggesting causal conclusions are justified.
CONCLUSIONS
Our confidence intervals did not include clinically meaningful benefits from gabapentin, when used with an ERAS protocol, in terms of length of stay or perioperative opioid use. These results support the omission of gabapentin from ERAS protocols for minimally invasive uro-oncologic surgeries.
Topics: Humans; Gabapentin; Male; Middle Aged; Female; Pain, Postoperative; Analgesics; Ambulatory Surgical Procedures; Prostatectomy; Minimally Invasive Surgical Procedures; Nephrectomy; Retrospective Studies; Analgesics, Opioid; Time Factors
PubMed: 38899668
DOI: 10.1097/UPJ.0000000000000570 -
Preventive Medicine Jun 2024Understanding the clinical and demographic profile of patients on gabapentinoids can highlight areas of prescribing disparities, inform clinical practice, and guide...
OBJECTIVE
Understanding the clinical and demographic profile of patients on gabapentinoids can highlight areas of prescribing disparities, inform clinical practice, and guide future research to optimize effectiveness and safety of gabapentinoids for pain management. We used a national sample of Medicare beneficiaries to examine trends, patterns, and patient-level predictors of gabapentinoid use among long-term opioid users.
METHODS
Using a national Medicare sample between 2014 and 2020, we examined factors associated with gabapentinoid use among long-term opioid users. We included Medicare eligible long-term opioid users with no prior gabapentinoid use. The primary outcome was gabapentinoid use after the long-term opioid use episode. Logistic regression was used to test the association with gabapentinoid use for year, age, sex, race/ethnicity, region, Medicare entitlement, low-income status, frailty, pain locations, anxiety, depression, opioid use disorder, and opioid morphine milligrams equivalent.
RESULTS
Gabapentinoid use among long-term opioid users increased from 12.6% in 2014 to 16.8% in 2019 (p < .0001). Factors associated with increased gabapentinoid use were Hispanic ethnicity, back pain, nerve pain, and moderate or high opioid usage. Factors associated with decreased gabapentinoid use were older age and Medicare entitlement due to old age.
CONCLUSIONS
Variation of gabapentinoid use by socio-demographics and insurance status indicates opportunities to improve pain management and a need for shared therapeutic decision making informed by discussion between pain patients and providers regarding safety and effectiveness of pain therapies. Our findings underscore the need for future research into the comparative effectiveness and safety of gabapentinoids for non-cancer chronic pain in various subpopulations.
PubMed: 38897356
DOI: 10.1016/j.ypmed.2024.108046 -
Journal of Orthopaedic Surgery (Hong... 2024Local infiltration analgesia (LIA), adductor canal block (ACB), and infiltration between the popliteal artery and the capsule of the posterior knee (IPACK) are popular...
Efficacy of adding infiltration between the popliteal artery and the capsule of the posterior knee (IPACK) to adductor canal block and local infiltration analgesia in total knee arthroplasty: A retrospective cohort study.
OBJECTIVE
Local infiltration analgesia (LIA), adductor canal block (ACB), and infiltration between the popliteal artery and the capsule of the posterior knee (IPACK) are popular multimodal analgesia techniques used during total knee arthroplasty (TKA). This study aimed to explore the efficacy of adding the IPACK technique to ACB and LIA in patients undergoing TKA.
METHODS
In this retrospective cohort study, patients who underwent primary unilateral TKA were divided into two groups based on their date of admission. Sixty-three patients underwent IPACK, ACB and LIA (IPACK group) during surgery, while 60 patients underwent ACB and LIA (control group). The primary outcome was the postoperative administration of morphine hydrochloride as a rescue analgesic. Secondary outcomes included time to first rescue analgesia, postoperative pain assessed using the visual analog scale (VAS), functional recovery assessed by knee range of motion and ambulation distance, time until hospital discharge, and complication rates.
RESULTS
The two groups were similar in average postoperative 0-to-24-h morphine consumption (11.8 mg for the control group vs 12.7 mg for the IPACK group, = .428) and average total morphine consumption (18.2 mg vs 18.0 mg, = .983) during hospitalization. There were also no significant differences in the secondary outcomes.
CONCLUSIONS
The addition of IPACK to ACB and LIA did not provide any clinical analgesic benefits. Orthopedic surgeons and anesthesiologists are justified in using ACB and LIA without IPACK for TKA.
Topics: Humans; Retrospective Studies; Arthroplasty, Replacement, Knee; Male; Female; Aged; Popliteal Artery; Nerve Block; Pain, Postoperative; Middle Aged; Analgesics, Opioid; Morphine; Anesthetics, Local; Pain Measurement; Anesthesia, Local; Analgesia; Pain Management
PubMed: 38896879
DOI: 10.1177/10225536241265445 -
Journal of Clinical Medicine May 2024: Our understanding of dexmedetomidine, as an adjuvant to nerve blocks in cancer surgery, is characterized by a current lack of compelling evidence, and it remains... (Review)
Review
: Our understanding of dexmedetomidine, as an adjuvant to nerve blocks in cancer surgery, is characterized by a current lack of compelling evidence, and it remains unknown whether the potential benefits of use outweigh the risks. The aim of the study was to evaluate the benefit and safety profiles of dexmedetomidine as an adjuvant to nerve blocks in cancer surgery. : Systematic searches were conducted in MEDLINE, ScienceDirect, Cochrane Library, Springer, medRxiv, and Scopus up to 17 May 2024. Risk ratios (RR) for binary outcomes and standardized mean differences (SMDs) for continuous outcomes were quantified. : Twenty studies were identified. In breast cancer surgery, the use of dexmedetomidine reduced 24 h total morphine consumption (SMD = -1.99 [95% CI -3.01 to -0.98], = 0.0001, I2 = 91%, random effects) and prolonged the requirement for morphine rescue analgesia (SMD = 2.98 [95% CI 0.01 to 5.95], = 0.05, I2 = 98%, random effects). In abdominal cancer surgery, the dexmedetomidine group had lower total sufentanil consumption (SMD = -1.34 [95% CI -2.29 to -0.40], = 0.005, I2 = 84%, random effects). Dexmedetomidine reduced the VAS score and decreased postoperative nausea and vomiting (PONV). No studies using dexmedetomidine reported serious adverse events. : Using dexmedetomidine as an adjuvant to nerve blocks in cancer surgery could lower the VAS pain score and prolong the regional anesthesia duration, which would lead to a decrease in total opioid consumption and possibly contribute to fewer PONV events. Furthermore, the reports of no serious adverse events indicate its good safety profile.
PubMed: 38892876
DOI: 10.3390/jcm13113166 -
Journal of Clinical Medicine May 2024Post-operative urinary retention (POUR) is a common complication following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Spinal anaesthetic has been...
Post-operative urinary retention (POUR) is a common complication following total hip arthroplasty (THA) and total knee arthroplasty (TKA). Spinal anaesthetic has been associated with an increased risk of POUR, whilst other risk factors remain unclear. This study aims to identify modifiable and non-modifiable risk factors of POUR for THA and TKA patients. A single-centre retrospective cohort study of patients admitted to our hospital over the course of 6 weeks from September to October 2021 for a THA or TKA. All patients who underwent elective THA/TKA were included, and trauma cases were excluded. Ninety-two consecutive patients were included in this study. The overall rate of POUR was 17%. A shorter operative duration resulted in a reduced risk of POUR (median duration of non-retention patients, 88 min vs. 100 min POUR patients; odds ratio, 0.97; 95% CI, 0.95-0.99, = 0.018). The median bladder volume of patients with urinary retention at the point of diagnosis was 614 mL (range, 298-999 mL). The arthroplasty type, anaesthetic technique, pre-operative morphine use, body mass index, age, cardiovascular disease, and renal disease were found to have no significant association with POUR. A reduced operative time of arthroplasty surgery is associated with a decreased risk of POUR. Patients with a prolonged operative time should have an increased frequency of micturition monitoring in the immediate post-operative period.
PubMed: 38892812
DOI: 10.3390/jcm13113102 -
Animals : An Open Access Journal From... Jun 2024Noxious chemicals, coupled with morphine treatment, are often used in studies on pain in vertebrates. Here we show that injection of morphine caused several behavioural...
Noxious chemicals, coupled with morphine treatment, are often used in studies on pain in vertebrates. Here we show that injection of morphine caused several behavioural changes in the crab, , including reduced pressing against the sides of the enclosure and more rubbing and picking at the mouth parts and, at least for a short time, more defensive displays. Subsequent injection of acetic acid into one rear leg caused rubbing of the injected leg and the injected leg was held vertically off the ground. These activities directed at or involving the specific leg are consistent with previous observations of directed behaviour following noxious stimuli and are consistent with the idea that decapods experience pain. Further, acetic acid but not injection of water induced autotomy of the injected leg in these animals. Because autotomy is temporally associated with directed behaviour, it is possible that the autotomy is a pain-related response. Acetic acid is clearly a noxious substance when applied to decapods. However, morphine had no effect on the activities associated with acetic acid injection and thus there is no evidence for an analgesic effect. Further, the injection of acetic acid did not interfere with behavioural effects of morphine. The activities directed towards the site of injection are like those observed with injection, or with external application, of various noxious substances and the present study adds to a growing body of knowledge about possible pain in decapods.
PubMed: 38891753
DOI: 10.3390/ani14111705