Search results for: opioid withdrawal management

Authors: Raquel R. Soares-Santos, Daniel P. Machado, Thiago L. Romero, Igor D. G. Duarte

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Tramadol, an analgesic classified as an 'atypical opioid,' exhibits both opioid and non-opioid mechanisms of action. This study aimed to explore these mechanisms, specifically the opioid-, cannabinoid-, nitric oxide-, and potassium channel-based mechanisms, which contribute to the peripheral antinociception effect of tramadol, in an experimental rat model. The nociceptive threshold was determined using paw pressure withdrawal. To examine the mechanisms of action, several substances were administered intraplantarly: naloxone, a non-selective opioid antagonist (50 μg/paw); AM251 (80 μg/paw) and AM630 (100 μg/paw) as the selective antagonists for type 1 and type 2 cannabinoid receptors, respectively; nitric oxide synthase inhibitors L-NOArg, L-NIO, L-NPA, and L-NIL (24 μg/paw); and the enzyme inhibitors of guanylatocyclase and phosphodiesterase of cGMP, ODQ and zaprinast. Additionally, potassium channel blockers glibenclamide, tetraethylammonium, dequalinium, and paxillin were used. The results showed that opioid and cannabinoid receptor antagonists did not reverse tramadol’s effects. L-NOarg, L-NIO, and L-NPA partially reversed antinociception, while ODQ completely reversed, and zaprinast enhanced tramadol’s antinociception effect. Notably, glibenclamide blocked tramadol’s antinociception in a dose-dependent manner. These findings suggest that tramadol’s peripheral antinociception effect is likely mediated by the nitrergic pathway and sensitive ATP potassium channels, rather than the opioid and cannabinoid pathways.

Keywords: tramadol, nitric oxide, potassium channels, peripheral analgesia, opioid

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Authors: Sean Hall

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Prior to COVID-19, the world was preoccupied with opioids, effectiveness versus risk, and specifically toxicity versus abuse. Historically underpinning opioid use was a concept of safety. As use over time and real-world data evolved, a pursuit for efficacy associated with non-opioid alternatives became mainstream. On January 8, 2021, the US signed back into the opioid problem, with these two fundamental questions still unresolved. The author will share the current progression of a lead non-opioid cancer bone pain candidate, NanaBis™. NanaBis™ represents two innovative factors: The active ingredients are from cannabinoids; these ingredients are in a proprietary sub-micron delivery platform, NanoCelle®. The author will offer an opinion piece, potentiating the future role of delivery platforms in medicine to increase both patient safety and compliance.

Keywords: NanaBis, nanoCelle, opioids, toxicity

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Authors: Kyung Min Kwom, Young Joo Lee

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Purpose: Up to 90% of pancreatic cancer patient suffer from neuropathic pain. In palliative care setting, pain control in a pancreatic cancer patient is one of the major goals. Ketamine is a NMDA receptor antagonist effective in neuropathic pain. Also, there have been studies about opioid sparing effect of ketamine. This study was held in palliative care unit among pancreatic cancer patients to find out the factors related to ketamine use and the opioid sparing effect. Methods: Medical records of pancreatic cancer patients admitted to St. Mary’s hospital palliative care unit from 2013.1 to 2014.12 were reviewed. Patients were divided into two categories according to ketamine use. Also, opioid use before and after ketamine use was compared in ketamine group. Results: Compared to non ketamine use group, patients in ketamine group required a higher dose of opioid. Total opioid dose, daily opioid dose, number of daily rescue medication, daily average rescue dose were statistically significantly higher in ketamine group. Opioid requirement was increased after ketamine administration. Conclusion: In this study, ketamine group required more opioid. Ketamine is frequently considered in patients with severe pain, requiring high amount of opioid. Also, ketamine did not have an opioid sparing effect. Future studies about palliative use of ketamine in a larger number of patients are required.

Keywords: ketamine, opioid sparing, palliative care, pancreatic cancer

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Authors: Kristina De Milt, Nicole Huang, Jihye Park

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Opioids have been a mainstay of the treatment of chronic pain, but their overprescription and misuse have led to an opioid epidemic. Recently, as an attempt to decrease the number of opioids prescribed, the use of cannabinoid therapy has become an increasingly popular adjunctive chronic pain management choice among providers. This review of literature investigates the effects of adjunctive cannabinoids to opioids in the management of chronic pain. The nine articles are included in the literature review range from observational studies to meta-analyses published in the year 2016 and after. A majority of the studies showed a decrease in the need for opioids after adjunctive cannabinoids were introduced and, in some instances, the cessation of opioid consumption. More high-quality evidence is needed to further support this stance and providers should weigh the benefits and risks of adjunctive cannabinoids according to the clinical picture.

Keywords: cannabis, chronic pain, opioids, pain management

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Authors: Agnes Simone

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A 52-year-old male with unknown psychiatric and medical history was brought to the Psychiatric Emergency Room by ambulance directly from jail. He had been detained for three weeks for possession of a firearm while intoxicated. On initial evaluation, the patient was unable to provide a reliable history. He presented with odd jerking movements of his extremities and catatonic features, including mutism and stupor. His vital signs were stable. Patient was transferred to the medical emergency department for work-up of altered mental status. Due to suspicion for opioid overdose, the patient was given naloxone (Narcan) with no improvement. Laboratory work-up included complete blood count, comprehensive metabolic panel, thyroid stimulating hormone, vitamin B12, folate, magnesium, rapid plasma reagin, HIV, blood alcohol level, aspirin, and Tylenol blood levels, urine drug screen, and urinalysis, which were all negative. CT head and chest X-Ray were also negative. With this negative work-up, the medical team concluded there was no organic etiology and requested inpatient psychiatric admission. Upon re-evaluation by psychiatry, it was evident that the patient continued to have an altered mental status. Of note, the medical team did not include substance withdrawal in the differential diagnosis due to stable vital signs and a negative urine drug screen. The psychiatry team decided to check California's prescription drug monitoring program (CURES) and discovered that the patient was prescribed benzodiazepine alprazolam (Xanax) 2mg BID, a sedative-hypnotic, and hydrocodone/acetaminophen 10mg/325mg (Norco) QID, an opioid. After a thorough chart review, his daughter's contact information was found, and she confirmed his benzodiazepine and opioid use, with recent escalation and misuse. It was determined that the patient was experiencing alprazolam withdrawal, given this collateral information, his current symptoms, negative urine drug screen, and recent abrupt discontinuation of medications while incarcerated. After admission to the medical unit and two doses of alprazolam 2mg, the patient's mental status, alertness, and orientation improved, but he had no memory of the events that led to his hospitalization. He was discharged with a limited supply of alprazolam and a close follow-up to arrange a taper. Accompanying this case report, a qualitative review of presentations with alprazolam withdrawal was completed. This case and the review highlights: (1) Alprazolam withdrawal can occur at low doses and within just one week of use. (2) Alprazolam withdrawal can present without any vital sign instability. (3) Alprazolam withdrawal does not respond to short-acting benzodiazepines but does respond to certain long-acting benzodiazepines due to its unique chemical structure. (4) Alprazolam withdrawal is distinct from and more severe than other benzodiazepine withdrawals. This case highlights (1) the importance of physician utilization of drug-monitoring programs. This case, in particular, relied on California's drug monitoring program. (2) The importance of obtaining collateral information, especially in cases in which the patient is unable to provide a reliable history. (3) The importance of including substance intoxication and withdrawal in the differential diagnosis even when there is a negative urine drug screen. Toxidrome of withdrawal can be delayed. (4) The importance of discussing addiction and withdrawal risks of medications with patients.

Keywords: addiction risk of benzodiazepines, alprazolam withdrawal, altered mental status, benzodiazepines, drug monitoring programs, sedative-hypnotics, substance use disorder

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Authors: Les Moncrieff

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In a world awash with potent opioids flaming an international crisis, the need to explore safe alternatives has never been more urgent. Bio-electrode Therapy is a novel adjunctive treatment method for relieving acute opioid withdrawal symptoms and many types of complex acute and chronic pain (often the underlying cause of opioid dependence). By combining the science of developmental bioelectricity with Traditional Chinese Medicine’s theory of meridians, rapid relief from pain is routinely being achieved in the clinical setting. Human body functions are dependent on electrical factors, and acupuncture points on the body are known to have higher electrical conductivity than surrounding skin tissue. When tiny gold- and silver-plated electrodes are secured to the skin at specific acupuncture points using established Chinese Medicine principles and protocols, an enhanced microcurrent and electrical field are created between the electrodes, influencing the entire meridian and connecting meridians. No external power source or electrical devices are required. Endogenous DC electric fields are an essential fundamental component for development, regeneration, and wound healing. Disruptions in the normal ion-charge in the meridians and circulation of blood will manifest as pain and development of disease. With the application of these simple electrodes (gold acting as cathode and silver as anode) according to protocols, the resulting microcurrent is directed along the selected meridians to target injured or diseased organs and tissues. When injured or diseased cells have been stimulated by the microcurrent and electrical fields, the permeability of the cell membrane is affected, resulting in an immediate relief of pain, a rapid balancing of positive and negative ions (sodium, potassium, etc.) in the cells, the restoration of intracellular fluid levels, replenishment of electrolyte levels, pH balance, removal of toxins, and a re-establishment of homeostasis.

Keywords: bioelectricity, electrodes, electrical fields, acupuncture meridians, complex pain, opioid withdrawal management

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Authors: Adam J. Carinci

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Background: The opioid epidemic is the most pressing healthcare crisis of our time. There is increasing recognition that opioids have limited long-term efficacy and are associated with hyperalgesia, addiction, and increased morbidity and mortality. Therefore, alternative strategies to combat chronic pain are paramount. We initiated a multicenter retrospective case series to review the efficacy of DRG stimulation in facilitating opioid tapering, opioid discontinuation and as a viable alternative to chronic opioid therapy. Purpose: The dorsal root ganglion (DRG) plays a key role in the development and maintenance of pain. Recent innovations in neuromodulation, specifically, dorsal root ganglion stimulation, offers an effective alternative to opioids in the treatment of chronic pain. This retrospective case series demonstrates preliminary evidence that DRG stimulation facilitates opioid tapering, opioid discontinuation and presents a viable alternative to chronic opioid therapy. Procedure: This small multicenter retrospective case series provides preliminary evidence that DRG stimulation facilitates opioid weaning, opioid tapering and is a viable option to opioid therapy in the treatment of chronic pain. A retrospective analysis was completed. Visual analog scale pain scores and pain medication usage were collected at the baseline visit and after four weeks, 3 months and 6 months of treatment. Ten consecutive patients across two study centers were included. The pain was rated 7.38 at baseline and decreased to 1.50 at the 4-week follow-up, a reduction of 79.5%. All patients significantly decreased their opioid pain medication use with an average > 30% reduction in morphine equivalents and four were able to discontinue their medications entirely. Conclusion: This Retrospective case series demonstrates preliminary evidence that DRG stimulation facilitates opioid tapering, opioid discontinuation and presents a viable alternative to chronic opioid therapy.

Keywords: dorsal root ganglion, neuromodulation, opioid sparing, stimulation

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Authors: Shannon Rappe, Elizabeth Morse, David Phillippi

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Postpartum women with an opioid use disorder (OUD) are at high risk for treatment disengagement, leaving them vulnerable to overdose and death between seven and twelve months postpartum. Intensive case management programs have been proposed as an effective strategy to reduce barriers and increase treatment engagement among postpartum women. The purpose of this project is to determine the effects of early engagement in an intensive case management program on postpartum engagement and infant health outcomes among postpartum women with opioid use. This retrospective review of secondary data was collected on 225 infants, and 221 postpartum women enrolled in an intensive case management program in Tennessee between May 1, 2019, and May 5, 2020. Chi-squares were computed to examine the timing of engagement during pregnancy, maternal treatment outcomes, and infant health outcomes, including neonatal abstinence syndrome (NAS), birth weight, gestational age, and length of stay. The mean prenatal program engagement was 109 days (SD = 67.6); 16.7% (n = 37) enrolled during the first trimester, 37.6% (n = 83) in the second trimester, and 45.7% (n = 101) in the third trimester. Of the 221 women engaged, 45.2% (n = 100) remained engaged in the case of management at the time of data collection, and 40% (n = 89) remained engaged in MAT at the time of data collection. Twenty- five percent (n = 25) of mothers who graduated sustained engagement in MAT. Of 225 infants 28.9% (n = 65) had a positive NAS status, mean birth weight was 6.5 lbs. (SD = 19.3); mean gestational age was 38.3 weeks (SD = 19.3) and mean length of stay was 8.19 days (SD = 9.8). This study's findings identified that engaging mothers during pregnancy in a program designed to meet their unique challenges positively impacts both the mother and infant outcomes, regardless of their timing.

Keywords: intensive case management, neonatal abstinence syndrome, opioid addiction, opioid crisis, opioid use in pregnant women, postpartum addiction

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Authors: Sandip Tambare, Revati Ghadge

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Alcohol withdrawal syndrome continue to be concerning health issue worldwide in alcoholics. Many current option for treating alcohol withdrawal signs are habit forming causing dependency of sedatives. The divine science of Ayurveda recommends Nasya for improvement of alcohol withdrawal signs. As per the latest reports 1/3 of the Indian population is using alcohol in an unhealthy manner, the complication being wide and varied among which, the Alcohol Withdrawal Syndrome is the dominant one. The presentation varies from mild sleep loss or anxiety to delirium. Ayurveda has given utmost in the context of Madatyaya(Alcoholism). Various protocols based on the identification of the status of tridoshas are explained which includes sodhana, samana and satwavachaya chikitsa. Various medications are being used, with appreciated effects in the clinical practice. As per reports, the panchakarma procedure nasya seems highly effective, in managing of the alcohol withdrawal syndrome. Nasya with Ksheerabala Taila is given for 7 days in the condition of Alcohol Withdrawal syndrome and it was the non Randomized trial with 30 subjects satisfying the DSM V criteria for alcohol withdrawl and the assessment was done using the Clinical Institute Withdrawal Assessment for Alcohol Scale revised (CIWA-Ar). Conclusion: Among the symptoms which were studied after the interventions, it was found that there was high significant response in almost all the symptoms in the given subjects. The eternal science of Ayurveda is able to answer the existing problem of alcohol and its abuse in the society.

Keywords: nasya, alcohol withdrawal, madatyaya, ksheerabala taila

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Authors: Seyed Abdol Mohammad Rezavand, Mohammad Nikbakhsh

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Withdrawal resistance of screws driven into HDPE/Sugarcane Bagasse injection molded parts was investigated. After chemical treatment and drying, SCB was pre-mixed with HDPE using twin extruder. The resulting granules are used in producing samples in injection molding machine. SCB with the quantity of %10, %20, and %30 was used. By using a suitable fixture, screw heads can take with tensile test machine grips. Parts with screws in the center and edge were fasten together. Then, withdrawal resistance was measured with tensile test machine. Injection gate is at the one edge of the part. The results show that by increasing SCB content in composite, the withdrawal resistance is decreased. Furthermore, the withdrawal resistance at the edges (near injection gate and the end of the filling path of mold cavity) is more than that of the center.

Keywords: polyethylene, sugarcane bagasse, wood plastic, screw, withdrawal resistance

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Authors: Santosh Sharma Parajuli, Diwas Manandhar

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Background: Perioperative pain management plays an integral part in patients undergoing cardiac surgery. We studied the effect of Erector Spinae Plane block on acute postoperative pain reduction and 24 hours opioid consumption in adult cardiac surgical patients. Methods: Twenty-five adult cardiac surgical patients who underwent cardiac surgery with sternotomy in whom ESP catheters were placed preoperatively were kept in group E, and the other 25 patients who had undergone cardiac surgery without ESP catheter and pain management done with conventional opioid injection were placed in group C. Fentanyl was used for pain management. The primary study endpoint was to compare the consumption of fentanyl and to assess the numeric rating scale in the postoperative period in the first 24 hours in both groups. Results: The 24 hours fentanyl consumption was 43.00±51.29 micrograms in the Erector Spinae Plane catheter group and 147.00±60.94 micrograms in the control group postoperatively which was statistically significant (p <0.001). The numeric rating scale was also significantly reduced in the Erector Spinae Plane group compared to the control group in the first 24 hours postoperatively. Conclusion: Erector Spinae Plane block is superior to the conventional opioid injection method for postoperative pain management in CABG patients. Erector Spinae Plane block not only decreases the overall opioid consumption but also the NRS score in these patients.

Keywords: erector, spinae, plane, numerical rating scale

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Authors: Jared Cheves, Amanda DeChent, Joyce Pan

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Total knee replacements (TKAs) are one of the most common but painful surgical procedures performed in the United States. Currently, the gold standard for postoperative pain management is the utilization of opioids. However, in the wake of the opioid epidemic, the healthcare system is attempting to reduce opioid consumption by trialing innovative opioid sparing analgesic techniques such as continuous peripheral nerve blocks (CPNB) and continuous periarticular infiltration (CPAI). The alleviation of pain, particularly during the first 72 hours postoperatively, is of utmost importance due to its association with delayed recovery, impaired rehabilitation, immunosuppression, the development of chronic pain, the development of rebound pain, and decreased patient satisfaction. While both CPNB and CPAI are being used today, there is limited evidence comparing the two to the current standard of care or to each other. An extensive literature review was performed to explore the safety profiles and effectiveness of CPNB and CPAI in reducing reported pain scores and decreasing opioid consumption. The literature revealed the usage of CPNB contributed to lower pain scores and decreased opioid use when compared to opioid-only control groups. Additionally, CPAI did not improve pain scores or decrease opioid consumption when combined with a multimodal analgesic (MMA) regimen. When comparing CPNB and CPAI to each other, neither unanimously lowered pain scores to a greater degree, but the literature indicates that CPNB decreased opioid consumption more than CPAI. More research is needed to further cement the efficacy of CPNB and CPAI as standard components of MMA in TKA procedures. In addition, future research can also focus on novel catheter-free applications to reduce the complications of continuous catheter analgesics.

Keywords: total knee arthroplasty, continuous peripheral nerve blocks, continuous periarticular infiltration, opioid, multimodal analgesia

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Authors: Yuanjin Liu

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Retirement withdrawal strategies are very important to minimize the probability of ruin in retirement. The ruin probability is modeled as a function of initial withdrawal age, gender, asset allocation, inflation rate, and initial withdrawal rate. The ruin probability is obtained based on the 2019 period life table for the Social Security, IRS Required Minimum Distribution (RMD) Worksheets, US historical bond and equity returns, and inflation rates using simulation. Several popular machine learning algorithms of the generalized additive model, random forest, support vector machine, extreme gradient boosting, and artificial neural network are built. The model validation and selection are based on the test errors using hyperparameter tuning and train-test split. The optimal model is recommended for retirees to monitor the ruin probability. The optimal withdrawal strategy can be obtained based on the optimal predictive model.

Keywords: ruin probability, retirement withdrawal strategies, predictive models, optimal model

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Authors: Mengjia Zhi, Xingmei Wei, Xiang Gao, Shiyang Liu, Zhiran Huang, Li Yang, Jing Sun

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Background: To understand the consumption trend of opioid analgesics and the consumption adequacy of opioid analgesic treatment for moderate to severe pain in China, as well as the pain control level of China with international perspective. Importance: To author’s best knowledge, this is the first study in China to measure the adequacy of opioid analgesic treatment for moderate to severe pain considering disease pattern and with the standardized pain treatment guideline. Methods: A retrospective analysis was carried out to show the consumption frequency (daily defined doses, DDDs) of opioid analgesics and its trend in China from 2006 to 2016. Adequacy of consumption measure (ACM) was used to measure the number of needed morphine equivalents and the overall adequacy of opioid analgesic treatment of moderate to severe pain in China, and compared with international data. Results: The consumption frequency of opioid analgesics (DDDs) in China increased from 13,200,000 DDDs in 2006 to 44,200,000 DDDs in 2016, and showed an increasing trend. The growth rate was faster at first, especially in 2013, then slowed down, decreased slightly in 2015. The ACM of China increased from 0.0032 in 2006 to 0.0074 in 2016, with an overall trend of growth. The ACM level of China has been always a very poor level during 2006-2016. Conclusion: The consumption of opioid analgesics for the treatment of moderate to severe pain in China has always been inadequate. There is a huge gap between China and the international level. There are many reasons behind this problem, which lie in different aspects, including medical staff, patients and the public, health systems and social & cultural aspects. It is necessary to strengthen the training and education of medical staff and the patients, to use mass media to disseminate scientific knowledge of pain management, to encourage communications between doctors and patients, to improve regulatory system for the controlled medicines and the overall health systems, and to balance the regulatory goal for avoidance of abuse, and the social goal of meeting the increasing needs of the people for better life.

Keywords: opioid analgesics, adequate consumption measure, pain control, China

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Authors: Mani Mofidi, Neda Valizadeh, Ali Hashemaghaee, Mona Hashemaghaee, Soudabeh Shafiee Ardestani

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Background: Acute pain and its management remained the most complaint of emergency service admission. Diagnostic and therapeutic procedures add to patients’ pain. Diminishing the pain increases the quality of patient’s feeling and improves the patient-physician relationship. Aim: The aim of this study was to evaluate the outcomes and side effects of opioid administration in emergency patients. Material and Methods: patients admitted to ward II emergency service of Imam Khomeini hospital, who received one of the opioids: morphine, pethidine, methadone or fentanyl as an analgesic were evaluated. Their vital signs and general condition were examined before and after drug injection. Also, patient’s pain experience were recorded as numerical rating score (NRS) before and after analgesic administration. Results: 268 patients were studied. 34 patients were addicted to opioid drugs. Morphine had the highest rate of prescription (86.2%), followed by pethidine (8.5%), methadone (3.3%) and fentanyl (1.68). While initial NRS did not show significant difference between addicted patients and non-addicted ones, NRS decline and its score after drug injection were significantly lower in addicted patients. All patients had slight but statistically significant lower respiratory rate, heart rate, blood pressure and O2 saturation. There was no significant difference between different kind of opioid prescription and its outcomes or side effects. Conclusion: Pain management should be always in physicians’ mind during emergency admissions. It should not be assumed that an addicted patient complaining of pain is malingering to receive drug. Titration of drug and close monitoring must be in the curriculum to prevent any hazardous side effects.

Keywords: numerical rating score, opioid, pain, emergency department

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Authors: Rebar Mohammed Hussein

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Enhanced Recovery After Surgery (ERAS) protocols have transformed perioperative care, aiming to reduce surgical stress, optimize pain management, and accelerate recovery. This study evaluates the impact of ERAS on anesthesia management in high-risk surgical patients, focusing on opioid-sparing techniques and multimodal analgesia. A retrospective analysis was conducted on patients undergoing major surgeries within an ERAS program, comparing outcomes with a historical cohort receiving standard care. Key metrics included postoperative pain scores, opioid consumption, length of hospital stay, and complication rates. Results indicated that the implementation of ERAS protocols significantly reduced postoperative opioid use by 40% and improved pain management outcomes, with 70% of patients reporting satisfactory pain control on postoperative day one. Additionally, patients in the ERAS group experienced a 30% reduction in length of stay and a 20% decrease in complication rates. These findings underscore the importance of integrating ERAS principles into anesthesia practice, particularly for high-risk patients, to enhance recovery, improve patient satisfaction, and reduce healthcare costs. Future directions include prospective studies to further refine anesthesia techniques within ERAS frameworks and explore their applicability across various surgical specialties.

Keywords: ERAS protocols, high-risk surgical patients, anesthesia management, recovery

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Authors: Sheng-Yu Lee

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Aim: Opioid use disorder is often characterized by repetitive drug-seeking and drug-taking behaviors with severe public health consequences. Animal model showed that opioid-induced perturbations in the gut microbiota causally relate to neuroinflammation, deficits in reward responding, and opioid tolerance, possibly due to changes in gut microbiota. Therefore, we propose that the dysbiosis of gut microbiota can be associated with pathogenesis of opioid dependence. In this current study, we explored the differences in gut microbiota between patients and normal controls and in patients before and after initiation of methadone treatment program for 12 weeks. Methods: Patients with opioid use disorder between 20 and 65 years were recruited from the methadone maintenance outpatient clinic in 2 medical centers in the Southern Taiwan. Healthy controls without any family history of major psychiatric disorders (schizophrenia, bipolar disorder and major depressive disorder) were recruited from the community. After initial screening, 15 patients with opioid use disorder joined the study for initial evaluation (Week 0), 12 of them completed the 12-week follow-up while receiving methadone treatment and ceased heroin use (Week 12). Fecal samples were collected from the patients at baseline and the end of 12th week. A one-time fecal sample was collected from the healthy controls. The microbiota of fecal samples were investigated using 16S rRNA V3V4 amplicon sequencing, followed by bioinformatics and statistical analyses. Results: We found no significant differences in species diversity in opioid dependent patients between Week 0 and Week 12, nor compared between patients at both points and controls. For beta diversity, using principal component analysis, we found no significant differences between patients at Week 0 and Week 12, however, both patient groups showed significant differences compared to control (P=0.011). Furthermore, the linear discriminant analysis effect size (LEfSe) analysis was used to identify differentially enriched bacteria between opioid use patients and healthy controls. Compared to controls, the relative abundance of Lactobacillaceae Lactobacillus (L. Lactobacillus), Megasphaera Megasphaerahexanoica (M. Megasphaerahexanoica) and Caecibacter Caecibactermassiliensis (C Caecibactermassiliensis) were increased in patients at Week 0, while Coriobacteriales Atopobiaceae (C. Atopobiaceae), Acidaminococcus Acidaminococcusintestini (A. Acidaminococcusintestini) and Tractidigestivibacter Tractidigestivibacterscatoligenes (T. Tractidigestivibacterscatoligenes) were increased in patients at Week 12. Conclusion: In conclusion, we suggest that the gut microbiome community maybe linked to opioid use disorder, such differences may not be altered even after 12-week of cessation of opioid use.

Keywords: opioid use disorder, gut microbiota, methadone treatment, follow up study

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Authors: Donna L. Roberts

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Heroin has appeared on the drug scene before. Yet the current opioid crisis differs in significant ways. In order to address the grave challenges, this epidemic poses, the unique precipitating and sustaining conditions must be thoroughly examined. This research explored the various aspects of the political, economic, and social conditions that created a 'perfect storm' for the evolution and maintenance of the current opioid crisis. Specifically, the epidemiology, demographics, and progression of addiction inherent in the current crisis were compared to the patterns of past opioid use. Additionally, the role of pharmaceutical companies and prescribing physicians, the nature and pharmaceutical properties of the available substances and the changing socioeconomic climate were considered. Results indicated that the current crisis differs significantly with respect to its evolution, magnitude, prevalence, and widespread societal effects. Precipitated by a proliferation of prescription medication and sustained by the availability of cheaper, more potent street drugs, including new versions of synthetic opioids, the current crisis presents unprecedented challenges affecting a wider and more diverse segment of society. The unique aspects of this epidemic demand unique approaches to addressing the problem. Understanding these differences is a key step in working toward a practical and enduring solution.

Keywords: addiction, drug abuse, opioids, opioid crisis

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Authors: Daniele Zullino, Gabriel Thorens, Léonice Furtado, Federico Seragnoli, Radu Iuga, Louise Penzenstadler

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Context: Since the start of the 21st century, there has been a resurgence of interest in psychedelics, marked by a renewed focus on scientific investigations into their therapeutic potential. While psychedelic therapy has gained recognition for effectively treating depression and anxiety disorders, notable progress has been made in the clinical development of substances like psilocybin. Moreover, mounting evidence suggests promising applications of Lysergic acid diethylamide (LSD) and psilocybin in the field of addiction medicine. In Switzerland, compassionate treatment with LSD and psilocybin has been permitted since 2014 through exceptional licenses granted by the Federal Office of Public Health. This treatment approach is also available within the Geneva treatment program, extending its accessibility to patients undergoing opioid-assisted treatment involving substances like morphine and diacetylmorphine. The aim of this study is to assess the feasibility of psychedelic-assisted therapy in patients with opioid use disorder who are undergoing opioid-assisted treatment. This study addresses the question of whether psychedelic-assisted therapy can be successfully implemented in patients with opioid use disorder. It also explores the effects of psychedelic therapy on the patient's experiences and outcomes. Methodology: This is an open case series on six patients who have undergone at least one session with either LSD (100-200 micrograms) or psilocybin (20-40 mg). The patients were assessed using the Five Dimensional Altered States of Consciousness (5D-ASC)-Scale. The data were analyzed descriptively to identify patterns and trends in the patients' experiences. Results: The patients experienced substantial positive psychedelic effects during the psychedelic sessions without significant adverse effects. The patients reported positive experiences and improvements in their condition. Conclusion: The findings of this study support the feasibility and potential efficacy of psychedelic-assisted therapy in patients undergoing opioid-assisted treatment.

Keywords: psychedelics, psychedelic-assisted treatment, opioid use disorder, addiction, LSD, psilocybin

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Authors: Aikaterini Amanatidou

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We describe the case of a 20-year-old female patient diagnosed with Ehlers-Danlos Syndrome (EDS) who was scheduled to undergo a wisdom teeth extraction in outpatient surgery. EDS is a hereditary connective tissue disorder characterized by joint hypermobility, skin hyper-extensibility, and vascular and soft tissue fragility. There are six subtypes of Ehlers-Danlos, and in our case, the patient had EDS hyper-mobility (HT) type disorder. One important clinical feature of this syndrome is chronic pain, which is often poorly understood and treated. Our patient had a long history of articular and lumbar pain when she was diagnosed. She was prescribed analgesic treatment for acute and neuropathic pain and had multiple sessions of psychotherapy and physiotherapy to ease the pain. Unfortunately, her extensive medical history was underrated by our anesthetic team, and no further measures were taken for the operation. Despite an uneventful intra-operative phase, the patient experienced several episodes of hyperalgesia during the immediate post-operative care. Management of pain was challenging for the anesthetic team: initial opioid treatment had only a temporary effect and a paradoxical reaction after a while. Final pain relief was eventually obtained with psycho-physiologic treatment, high doses of ketamine, and patient-controlled analgesia infusion of morphine-ketamine-dehydrobenzperidol. We suspected an episode of Opioid-Induced hyperalgesia. This case report supports the hypothesis that anti-hyperalgesics such as ketamine as well as lidocaine, and dexmedetomidine should be considered intra-operatively to avoid opioid-induced hyperalgesia and may be an alternative solution to manage complex chronic pain like others in neuropathic pain syndromes.

Keywords: Ehlers-Danlos, post-operative management, hyperalgesia, opioid-induced hyperalgesia, rare disease

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Authors: Raheel Shakoor Siddiqui, Shahbaz Malik, Manikandar Srinivas Cheruvu, Sanjay Narayana Murthy, Livio DiMascio

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Background: elderly traumatic hip fracture patients frequently present to trauma services globally. Rising low energy falls amongst an osteoporotic aging population is the commonest cause for injury. Hip fractures in this population are a major cause for severe pain, morbidity and mortality. The term hip fracture is interchangeable with neck of femur fracture, fractured neck of femur or proximal femur fracture. Hip fracture pain management protocols and guidelines suggest conventional analgesia, nerve block and opioid based treatment as rescue analgesia. There is a current global opioid crisis with overuse, abuse and dependence. Adverse opioid related complications in vulnerable elderly patients further adds to morbidity and mortality. Systematic reviews in literature have evidenced superiority of multimodal analgesia in osteoarthritic primary joint replacements compared to opioids however, this has not yet been conducted for elderly traumatic hip fracture patients. Aims: The primary aim of this systematic review is to provide standardised evidence following Cochrane and PRISMA guidance in determining advantages of perioperative multimodal analgesia over conventional opioid based treatments in elderly traumatic hip fractures. Methods: 5 databases were searched from January 2000-2023 which identified 8 randomised controlled trials and 446 total participants. These trials met defined PICOS eligibility criteria of patient mean age ≥ 65 years presenting with a unilateral traumatic fractured neck of femur for operative intervention. Analgesic intervention with perioperative multimodal analgesia has been compared to conventional opioid based analgesia. Outcomes of interest include, primarily, the change in postoperative opioid consumption within a 0-30 postoperative period and secondarily, the change in postoperative adverse events and complications. A qualitative synthesis has been performed due to clinical heterogenicity and variance amongst trials. Results: GRADE evidence of moderate quality supports perioperative multimodal analgesia leads to a reduction in postoperative opioid consumption however, low quality evidence supports a reduction of adverse effects and complications. Conclusion: Perioperative multimodal analgesia whether used preoperative, intraoperative and/or postoperative leads to a reduction in postoperative opioid consumption for elderly traumatic hip fracture patients. This review recommends the use of perioperative multimodal analgesia as part of hip fracture pain protocols however, caution and clinical judgement should be used as the risk of adverse effects may not be lower.

Keywords: trauma, orthopaedics, hip, fracture, neck of femur fracture, analgesia, multimodal analgesia, opioid

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Authors: Heba Kamal Mohamed

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Introduction: Tramadol is a weak -opioid receptor agonist with an analgesic effect because of the inhibition of uptake of norepinephrine and serotonin. Nowadays, tramadol hydrochloride is frequently used as a pain reliever. Tramadol is recommended for the management of acute and chronic pain of moderate to severe intensity associated with a variety of diseases or problems, including osteoarthritis, diabetic neuropathy, neuropathic pain, and even perioperative pain in human patients. In obstetrics and gynecology, tramadol is used extensively to treat postoperative pain. Aim of the study: This study was undertaken to investigate the histological (light and electron microscopic) and immunohistochemical effects of long term tramadol treatment on the ovary of adult rats and the possible recovery after tramadol withdrawal. Design: Experimental study. Materials and methods: Thirty adult female albino rats were used in this study. They were classified into three main groups (10 rats each). Group I served as the control group. Group II, rats were subcutaneously injected with tramadol 40 mg/kg three times per week for 8 weeks. Group III, rats were subcutaneously injected with tramadol 40 mg/kg three times per week for 8 weeks then were kept for another 8 weeks without treatment for recovery. At the end of the experiment rats were sacrificed and bilateral oophorectomy was carried out; the ovaries were processed for histological study (light and electron microscopic) and immunohistochemical reaction for caspase-3 (apoptotic protein). Results: Examination of the ovary of tramadol-treated rats (group II) revealed many atretic ovarian follicles, some follicles showed detachment of the oocyte from surrounding granulosa cells and others showed loss of the oocyte. Many follicles revealed degenerated vacuolated oocytes and vacuolated theca folliculi cells. Granulosa cells appeared shrunken, disrupted and loosely attached with vacuolated cytoplasm and pyknotic nuclei. Some follicles showed separation of granulosa cells from the theca folliculi layer. The ultrastructural study revealed the presence of granulosa cells with electron dense indented nuclei, damaged mitochondria and granular vacuolated cytoplasm. Other cells showed accumulation of large amount of lipid droplets in their cytoplasm. Some follicles revealed rarifaction of the cytoplasm of oocytes and absent zona pellucida. Moreover, apoptotic changes were detected by immunohistochemical staining in the form of increased staining intensity to caspase-3 (apoptotic protein). With Masson's Trichrome stain, there was an increased collagen fibre deposition in the ovarian cortical stroma. The wall of blood vessels appeared thickened. In the withdrawal group (group III), there was a little improvement in the histological and immunohistochemical changes. Conclusion: Tramadol had serious deleterious effects on ovarian structure. Thus, it should be used with caution, especially when a long term treatment is indicated. Withdrawal of tramadol led to a little improvement in the structural impairment of the ovary.

Keywords: tramadol, ovary, withdrawal, rats

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Authors: Pius Babuna

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Sustainable water use is important for the existence of the human race. Water resources carrying capacity (WRCC) measures the sustainability of water use; however, the calculation and optimization of WRCC remain challenging. This study used a mathematical model (the Logistics Growth of Water Resources -LGWR) and a linear objective function to model water sustainability. We tested the validity of the models using data from Ghana. Total freshwater resources, water withdrawal, and population data were used in MATLAB. The results show that the WRCC remains sustainable until the year 2132 ±18, when half of the total annual water resources will be used. The optimized water treatment cost suggests that Ghana currently wastes GHȼ 1115.782± 50 cedis (~$182.21± 50) per water treatment plant per month or ~ 0.67 million gallons of water in an avoidable loss. Adopting an optimized water treatment scheme and a watershed management approach will help sustain the WRCC.

Keywords: water resources carrying capacity, smart water management, optimization, sustainable water use, water withdrawal

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Authors: Sami Houry

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Complex systems exhibit universal characteristics as they near a tipping point. Among them are common generic early warning signals which precede critical transitions. These signals include: critical slowing down in which the rate of recovery from perturbations decreases over time; an increase in the variance of the state variable; an increase in the skewness of the state variable; an increase in the autocorrelations of the state variable; flickering between different states; and an increase in spatial correlations over time. The presence of the signals has management implications, as the identification of the signals near the tipping point could allow management to identify intervention points. Despite the applications of the generic early warning signals in various scientific fields, such as fisheries, ecology and finance, a review of literature did not identify any applications that address the program student withdrawal problem at the undergraduate distance universities. This area could benefit from the application of generic early warning signals as the program withdrawal rate amongst distance students is higher than the program withdrawal rate at face-to-face conventional universities. This research specifically assessed the generic early warning signals through an intensive case study of undergraduate program student withdrawal at a Canadian distance university. The university is non-cohort based due to its system of continuous course enrollment where students can enroll in a course at the beginning of every month. The assessment of the signals was achieved through the comparison of the incidences of generic early warning signals among students who withdrew or simply became inactive in their undergraduate program of study, the true positives, to the incidences of the generic early warning signals among graduates, the false positives. This was achieved through significance testing. Research findings showed support for the signal pertaining to the rise in flickering which is represented in the increase in the student’s non-pass rates prior to withdrawing from a program; moderate support for the signals of critical slowing down as reflected in the increase in the time a student spends in a course; and moderate support for the signals on increase in autocorrelation and increase in variance in the grade variable. The findings did not support the signal on the increase in skewness of the grade variable. The research also proposes a new signal based on the fractal-like characteristic of student behavior. The research also sought to extend knowledge by investigating whether the emergence of a program withdrawal status is self-similar or fractal-like at multiple levels of observation, specifically the program level and the course level. In other words, whether the act of withdrawal at the program level is also present at the course level. The findings moderately supported self-similarity as a potential signal. Overall, the assessment of the signals suggests that the signals, with the exception with the increase of skewness, could be utilized as a predictive management tool and potentially add one more tool, the fractal-like characteristic of withdrawal, as an additional signal in addressing the student program withdrawal problem.

Keywords: critical transitions, fractals, generic early warning signals, program student withdrawal

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Authors: Widad Kouachi, Nacera Benmouhoub

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Background: Erector spinae plane block (ESP) and thoracic paravertebral block (PVB) are two widely used regional anesthesia techniques in breast cancer surgery. Both techniques aim to improve postoperative pain management and reduce opioid consumption. However, comparative data on their efficacy in oncologic breast surgery remains limited. Objectives: This study aims to compare the efficacy of ESP and PVB in postoperative pain control, patient satisfaction, and opioid consumption in breast cancer surgery. Methods: A randomized, double-blind trial was conducted involving 100 patients undergoing oncologic breast surgery. Patients were randomly assigned to two groups: 50 received ESP, and 50 received PVB. Postoperative pain scores (at rest and during movement), opioid consumption, patient satisfaction, and hospital length of stay were recorded and analyzed. Results: Both ESP and PVB provided effective postoperative analgesia. No significant difference in pain scores was observed between the two groups within the first 24 hours. However, ESP showed a notable advantage in managing chronic postoperative pain at the 6-month follow-up. Opioid consumption was lower in both groups compared to patients without a block. No significant differences in complication rates or hospital stay were noted between the groups. Conclusion: ESP and PVB offer comparable efficacy for immediate postoperative pain control in breast cancer surgery. Nevertheless, ESP may have a superior role in managing long-term pain. Further research is needed to explore the mechanisms behind the observed differences in chronic pain outcomes.

Keywords: pain assessment, brest surgery, bpv block, ESP block

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Authors: Said Fares, Mary Fares

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It is well documented that introductory computer programming courses are difficult and that failure rates are high. The aim of this project was to reduce the high failure and withdrawal rates in learning to program. This paper presents a number of changes in module organization and instructional delivery system in teaching CS1. Daily out of class help sessions and tutoring services were applied, interactive lectures and laboratories, online resources, and timely feedback were introduced. Five years of data of 563 students in 21 sections was collected and analyzed. The primary results show that the failure and withdrawal rates were cut by more than half. Student surveys indicate a positive evaluation of the modified instructional approach, overall satisfaction with the course and consequently, higher success and retention rates.

Keywords: failure rate, interactive learning, student engagement, CS1

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Authors: Conchita Martin de Bustamante, Christopher S. Kung, Brianne Lacy, Eunsol Park, Hien Piotrowski, Mustafa Husain, Waseem Ahmed

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Objective: To explore the comorbidity of mental health conditions (major depressive disorder, borderline personality disorder, generalized anxiety disorder, and schizophrenia) with opioid use disorder in people incarcerated at a large urban jail. Background Schizophrenia, depression, bipolar disorder, and anxiety are all serious mental health conditions that are highly prevalent amongst incarcerated patients. However, it is seldom the only disorder these patients are suffering from. According to the US Department of Justice, about half of US prisoners, both at the state and federal level, suffer from substance use disorders. Although the opioid epidemic has been studied greatly in the recent years amongst the general population, little has been explored on how the opioid crisis has affected incarcerated patients in local jails, particularly regarding which of these patients are most susceptible. Method The cohort consisted of 507 people incarcerated at a large county jail who were evaluated by mental health providers in December 2020. A retrospective review was performed to evaluate associations between mental health diagnoses, substance use disorder, and other demographic variables. Results Participants had been diagnosed with various mental health conditions, including MDD (22.6%, n = 115), GAD (33.7%, n = 171), Schizophrenia (15.2%, n = 77) and BPD (27%, n = 137). Preliminary Chi square tests were conducted for these conditions against marijuana, alcohol, cocaine, opioid, methamphetamine, benzodiazepines, and sedative use disorders. The results showed significant associations between Schizophrenia (p = 0.013), GAD (p M 0.001), and MDD (p = 0.029) with opioid use disorders. Conclusions Determining the extent of these comorbid substance use and mental health disorders within an incarcerated population can help influence treatment plans for future incarcerated patients. Many federal and state jail systems lack pharmacological substance use intervention and the prevalence of these co-morbid conditions can shed light on the importance of treating conditions concurrently upon intake.

Keywords: mental health conditions, opioids, substance use disorder, comorbidity

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Authors: Nancy Wilson

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In utero, fetal drug exposure is prevalent amongst birthing facilities. Assessment tools for neonatal abstinence syndrome (NAS) are often cumbersome and ill-fitting, harboring immense subjectivity. This paradox often leads the clinical assessor to be hypervigilant when assessing the newborn for subtle symptoms of NAS, often mistaken for normal newborn behaviors. As a quality improvement initiative, this project led to a more adaptable NAS tool termed eat, sleep, console (ESC). This function-based NAS assessment scores the infant based on the ability to accomplish three basic newborn necessities- to sleep, to eat, and to be consoled. Literature supports that ESC methodology improves patient and family outcomes while providing more cost-effective care.

Keywords: neonatal abstinence syndrome, neonatal opioid withdrawal, maternal substance abuse, pregnancy, and addiction, Finnegan neonatal abstinence syndrome tool, eat, sleep, console

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Authors: Allwell Uwazuruike

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With the withdrawal, in 2016, of 3 African states from the ICC, the discourse took an interesting twist. African states, or at least some of them, had now shown their resolve to part ways with the ICC and, by implication, focus on further enthroning regional control and governance through an improved continental justice system. A range of views has been expressed over the years on the allegations of bias by some African states and the continued membership of the ICC. While there may be a split on the merits of the allegations of bias, academic analysts have generally not opposed African states’ membership of the ICC nor been particularly optimistic about the prospects of an African criminal court. There is also a degree of ambivalence on whether there are positives to be taken from African states’ withdrawal from the ICC. This article examines the recent developments with the ICC and analyses whether these could be viewed from the positive (or, at least, alternative) spectrum of the AU’s spirited march towards regional sovereignty or entirely negatively from the point of view of African Heads-of-State seeking to enthrone an era of authoritarianism and non-accountability.

Keywords: international criminal court, Africa, regionalism, criminal justice

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Authors: Itee Chowdhury, Shikha Modi

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Introduction: Cancer is beginning to outpace cardiovascular disease as a cause of death affecting every major organ system with profound implications for perioperative management. Breast cancer is the most common cancer in women in India, accounting for 27% of all cancers. The small changes in analgesic management of cancer patients can greatly improve prognosis and reduce the risk of postsurgical cancer recurrence as opioid-based analgesia has a deleterious effect on cancer outcomes. Shortened postsurgical recovery time facilitates earlier return to intended oncological therapy maximising the chance of successful treatment. Literature reveals that the role of BIS since FDA approval has been assessed in various types of surgeries, but clinical data on its use in oncosurgical patients are scanty. Our study focuses on the role of BIS-guided anaesthesia for breast cancer surgery patients. Methods: A prospective randomized controlled study in patients aged 36-55years scheduled for modified radical mastectomy was conducted in 51 patients in each group who met the inclusion and exclusion criteria, and randomization was done by sealed envelope technique. In BIS guided anaesthesia group (B), sevoflurane was titrated to keep the BIS value 45-60, and thereafter if the patient showed hypertension/tachycardia, an opioid was given. In standard anaesthesia care (group C), sevoflurane was titrated to keep MAC in the range of 0.8-1, and fentanyl was given if the patient showed hypertension/tachycardia. Intraoperative opioid consumption was calculated. Postsurgery recovery characteristics, including Aldrete score, were assessed. Patients were questioned for pain, PONV, and recall of the intraoperative event. A comparison of age, BMI, ASA, recovery characteristics, opioid, and VAS score was made using the non-parametric Mann-Whitney U test. Categorical data like intraoperative awareness of surgery and PONV was studied using the Chi-square test. A comparison of heart rate and MAP was made by an independent sample t-test. #ggplot2 package was used to show the trend of the BIS index for all intraoperative time points for each patient. For a statistical test of significance, the cut-off p-value was set as <0.05. Conclusions: BIS monitoring led to reduced opioid consumption and early recovery from anaesthesia in breast cancer patients undergoing MRM resulting in less postoperative nausea and vomiting and less pain intensity in the immediate postoperative period without any recall of the intraoperative event. Thus, the use of a Bispectral index monitor allows for tailoring of anaesthesia administration with a good outcome.

Keywords: bispectral index, depth of anaesthesia, recovery, opioid consumption

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