Publications

The Amami rabbit (Pentalagus furnessi), endemic to the Amami-Oshima and Tokunoshima Islands, is an endangered species that faces habitat disturbance. This study used fecal DNA metabarcoding to analyze the dietary preferences of Amami rabbits. Fecal samples from six rabbits were collected and analyzed for plant DNA. The results revealed the presence of 85 operational taxonomic units (OTUs) representing different plant species, with individual rabbits consuming 17-38 plant species. The dietary composition varied significantly among individuals, with a notable preference for ferns in some cases. Diet diversity, assessed using Simpson's Diversity Index, ranged from 0.328 to 0.889. This study highlights the importance of a diverse plant diet for Amami rabbits and underscores the need for habitat preservation to ensure a stable food supply. Conservation efforts must focus on maintaining a unique subtropical moist forest ecosystem and mitigating human-wildlife conflicts to promote sustainable coexistence.

Opioids pose significant risks of addiction due to the cyclical nature of serum opiate concentration associated with traditional dosing methods. Emerging technologies, including closed-loop feedback control systems, offer a promising solution by enabling dynamic, real-time microdosing that minimizes fluctuations in drug levels and reduces the risk of dependency. Drawing on advancements in biosensors and feedback systems used in other medical applications, these innovations could revolutionize pain management, potentially reducing opioid addiction rates by up to 87 percent compared to current oral administration methods.

OBJECTIVES: To evaluate the effectiveness of transitioning patients from methadone to buprenorphine/naloxone (BUP/NLX) using morphine milligram equivalent (MME) dosing, with a focus on treatment adherence, withdrawal management, and therapeutic response, as illustrated through two patient case studies.

METHODS: Two participants (male, 33 years; female 42 years) were treated between June 2023 to January 2024 for opioid use disorder, undergoing BUP/NLX induction from methadone in an opioid treatment program. MME low-dose initiations were utilized for dosage conversion. Data collected included patient demographics, vital signs, Clinical Opiate Withdrawal Scale assessment, MME low-dose initiation calculations, adverse events, treatment adherence, and outcomes.

RESULTS: MME dosing was based on initial methadone dosage and standard MME conversion ratios. Case 1: Sublingual BUP/NLX was started at 0.5 mg, increased to 0.5 mg twice daily by day 3, and titrated until day 17; methadone (24 mg) was tapered off by day 17. Case 2: A similar initiation and tapering process was followed; methadone (11 mg) was discontinued by day 12. Both cases achieved stabilization on BUP/NLX without severe adverse events or precipitated withdrawal symptoms.

CONCLUSIONS: MME low-dose initiations appear to be a feasible and safe method for BUP/NLX induction. Further research involving patients on higher methadone doses and larger sample sizes, along prospective designs, is necessary to validate these findings and explore the long-term effectiveness and safety of MME-guided induction protocols across various clinical settings.

Opioid medications have become increasingly prescribed in recent decades due to their sedative and analgesic properties, making them common treatments for pain management. However, prolonged use of these opioids is associated with serious side effects, including respiratory depression, overdose, dependence, and tolerance. In response, research into safer alternatives has focused on opioid-like compounds, particularly endogenous and exogenous opioid peptides, which are produced in the body or derived from the enzymatic digestion of food proteins. These peptides function as neuromodulators, regulating various physiological processes such as pain, emotion, and attachment behavior by interacting with three major G protein-coupled receptors: µ, κ, and δ. Endogenous opioid peptides, such as endorphins, enkephalins, and dynorphins, are generated from precursor molecules through proteolytic cleavage and play key roles in pain modulation and analgesia. Opioid peptides-including both endogenous and exogenous forms from animal or plant sources, as well as synthetic analogs-exhibit complex pharmacology with diverse effects on living systems, often producing complementary or opposing physiological responses. This review highlights significant discoveries regarding the peptide sequences and structural modifications of opioid peptides, emphasizing the need for continued research to fully elucidate their roles in human behavior and their potential as safer therapeutic alternatives to traditional opioids.

INTRODUCTION: Intravenous methadone has shown an opioid-sparing effect in high-risk surgeries. It was hypothesized that intrathecal methadone might provide better effects than intravenous administration due to a direct action on the spinal cord.

MAIN OBJECTIVE: To search the currently published literature on the intraoperative use of intrathecal methadone in humans, a systematic review was conducted.

DESIGN: Studies from PubMed, Scopus, OVID, EMBASE, LILACS, Google Scholar, ELSERVIER, REDALYC, SciELO, Europe PubMed Central, and the Cochrane Library were searched from 1980 to June 2024. Search terms included "intrathecal methadone or spinal methadone," "methadone and spinal anesthesia," "spinal anesthesia," "intraoperative period," and "perioperative period." Randomized controlled trials (RCTs) published in English and Spanish involving human participants were considered.

MAIN OUTCOME: The quality of post-operative analgesia measured by the Visual Analog Scale (VAS).

SECONDARY OUTCOMES: Time to first opioid analgesic rescue, post-operative daily needs of morphine equivalents, and side effects.

RESULTS: Forty-one articles were identified. Good agreement intra- and intergroup was found. Four full-text articles met the inclusion criteria. Quality assessment showed an overall low to "some concern" risk of bias. Intrathecal methadone 5-10 mg provided post-operative pain for about 6 hours (VAS average of 2.4/10) after knee and hip replacements, urological, and gynecological surgeries showing minimal side effects. Twenty milligram of intrathecal methadone can produce remarkable side effects. Intrathecal morphine at 0.5-1.0 mg showed significantly lower VAS levels during the 24 hours post-operatively (p < 0.05) but showed more side effects. Intrathecal anesthesia with methadone as adjuvant showed a longer analgesic effect than fentanyl, and better effect than placebo, without differences in side effects (p < 0.05).

CONCLUSIONS: Due to the limited sample size and the small number of selected RCTs showing significant methodological differences, a meta-analysis could not be completed. Therefore, overall statistical significance was not established between the four studies, and there is not enough evidence to give recommendations. Further research is needed to evaluate whether the doses found in this review retain comparable efficacy and safety profiles in a broader range of patient cohorts. In the reviewed literature, no objective or conclusive evidence of neurotoxicity was found from the use of a single dose of perioperative intrathecal methadone.

The effect of chronic marijuana use on patients is unknown, including in the surgical setting. Marijuana produces many effects on the body, which should be considered when providing medical care. Chronic marijuana use may affect surgical opioid requirements. To explore this possibility, an observational study was completed by conducting a retrospective chart review of patients who underwent surgery with general anesthesia. Patients were identified in the electronic medical record via self-reporting as marijuana users (users) or nonmarijuana users (nonusers). Users and nonusers were case-matched based on age, gender, weight, and procedure. After case matching, 570 patients' charts were analyzed, and intraoperative opioid, intraoperative propofol, and post-anesthesia care unit opioid requirements were compared. Marijuana users required less intraoperative opioids (mean [standard deviation (SD)] 27.2 [20.5] morphine milligram equivalents [MMEs]) compared to those who were marijuana nonusers (31.3 [22.1] MME). These results show a statistically significant difference in the intraoperative opioid requirement between case-matched users and nonusers (p = 0.02), with p = 0.013 after statistical adjustment for racial differences between the marijuana user and nonuser cohorts. Users and nonusers required similar amounts of intraoperative propofol (242.2 [220.2] and 257.8 [250.9], respectively) and post-operative opioids (7.3 [6.0] and 8.0 [9.0], respectively). The differences in intraoperative propofol and post-operative opioid requirements were not different statistically with p-values of 0.43 and 0.31, respectively. Based on this study population, marijuana users required less intraoperative opioids when compared to case-matched marijuana nonusers, with no difference in intraoperative propofol or post-operative opioid requirements. Perspective: Typical preoperative screening includes queries about patient substance use including marijuana, but details such as frequency and length of use are infrequently asked. The addition of these details to the assessment may provide improved understanding of a patient's surgical opioid requirements.

OBJECTIVE: This study evaluated the efficacy of weekly shared medical appointments (SMAs) for opioid prescribing in addressing adherence, aberrance, and noncompliance in chronic pain patients receiving long-term opioid therapy (LTOT).

DESIGN: A retrospective observational study.

SETTING: This study was conducted as a structured intervention within a community pain specialty clinic that introduced a monitoring system over 12 months.

PARTICIPANTS: A total of 355 patients on LTOT were included, of whom 70 were identified as high-risk (Red status) due to noncompliance with opioid use policies.

INTERVENTIONS: Patients attended monthly telemedicine shared medical opioid education appointments delivered by pain specialists that aimed to increase adherence to practice standards. A stratified risk management approach was used, with patients categorized as Green, Yellow, or Red based on adherence behavior.

MAIN OUTCOME MEASURE(S): Primary outcome measures were changes in compliance status (Red to Yellow or Green), opioid prescription changes (morphine milligram equivalent, MME), and overall patient adherence improvement.

RESULTS: Of the 70 patients in Red status, 54 percent transitioned to Green status after weekly SMA participation. The median MME was reduced from 200 to 32. The most significant changes occurred among Red status patients, with 54 percent tapering off opioids completely. Compliance improved from 80 to 90 percent across all LTOT patients.

CONCLUSIONS: Weekly shared medical appointments significantly improved adherence and compliance among LTOT patients. The program highlights the utility of frequent touchpoints in managing high-risk patients and offers an adaptable model for other pain management clinics.

BACKGROUND: The World Health Organization pain ladder treatment is recognized as the gold standard for moderate and severe chronic cancer pain palliation in hospitalized patients. The third step of this treatment includes powerful opioid agents, which in our case are morphine and fentanyl.

METHODS: The primary purpose of our study is to measure pain symptom relief by evaluating the pain scores after intravenous continuous infusion of these opioids in palliative care unit to ensure pain control of the patients. Our second main goal is to compare the morphine equivalent dose (MED) administered to both groups within 72 hours. Our study aimed to compare the frequency of side effects in both groups within 72 hours. The prospective observational study included 67 patients, who included inclusion and exclusion criteria. In respect of the opioid being infused, patients were distributed into Fentanyl (n = 33) and Morphine (n = 34) groups. Patients who were admitted to the palliative care unit were administered a continuous intravenous infusion of morphine or fentanyl. Continuous infusion was administered for 3 days in the hospital. An elastomeric intravenous pump was used for infusion. Taking into account the opioid agents and their doses, consumed by the patient prior to hospital admission, equal doses were calculated for both fentanyl and morphine consumers. For the management of breakthrough pain, 5-15 percent of the daily opioid dose was administered in both groups. Daily pain scores, breakthrough pain scores, basal infusion doses, breakthrough pain doses, laboratory tests, and hemodynamic parameters of the patients were recorded.

RESULTS: Total opioid dose as well as MED and visual analogue scale/numerical rating scale (VAS/NRS) reduction was statistically lower in the fentanyl group (p: 0.000; p < 0.05). There was no significant difference in terms of adverse effects.

CONCLUSION: The study demonstrates that the total consumption of opioids is approximately 70 times higher in the morphine group. The total MED in the fentanyl group is seven times lower than that in the morphine group. Thus, we suggest parenteral administration of fentanyl as a more advantageous alternative to morphine, and we believe that larger, randomized prospective research studies should be conducted on this subject.

OBJECTIVE: To evaluate the percentage of family medicine providers in our institution on completing the 8-hour required training on opioid and substance use disorders 14 months after introduction of the Medication Access and Training Expansion (MATE) Act and to evaluate buprenorphine prescribing attitudes.

DESIGN/SETTING: An anonymized survey was electronically sent to all family medicine providers in a single institution in Minnesota, spanning five outpatient and two express care clinics. Survey was deployed for 2 weeks, August 26-September 8, 2024.

OUTCOME MEASURES: Provider completion of MATE Act training and comfort level in prescribing buprenorphine for opioid use disorder (OUD).

RESULTS: A total of 41 out of 127 providers completed the survey (31.5 percent). Although 76 percent respondents completed the training, only half felt comfortable seeing patients with OUD on buprenorphine, writing a bridge prescription, or initiating buprenorphine.

CONCLUSIONS: Findings suggest that elimination of the x-waiver and enactment of required training are insufficient to positively affect buprenorphine prescribing comfort level.