ID: 212302 Prevalence of False Negative Results for Morphine in Oral Fluid Toxicology Compared With Urine Toxicology

Introduction: Urine drug testing has been the standard for monitoring opioid compliance in chronic pain patients. The COVID-19 pandemic created a dilemma for opioid monitoring by severely limiting in-person testing due to safety concerns. Oral fluid toxicology emerged as a feasible, alternative test due to its ability for remote sample collection under virtual supervision while minimizing infringements on patient privacy. However, the efficacy of these two tests for reliably detecting opioids should be explored prior to transitioning to testing only with oral fluids. Method(s): In this study, we compared morphine levels in oral fluid and urine toxicology studies from 5 randomly selected patients from a Chronic Pain Center who were regularly taking high doses (>=90 mEq) of extended-release morphine. Charts from the start of the COVID-19 pandemic until July 2022 were reviewed for urine and oral fluid testing results and medication regimens. All oral fluid and urine test results and collection methods were validated by a nationally recognized toxicology lab. Prescription Monitoring Program (PMP) reports were reviewed for each patient to observe pre-testing prescription trends. Result(s): We found that the overwhelming majority of patients had at least 1 false negative oral fluid test result. The remainder of the oral fluid results were below threshold (10 ng/mL) or ranged from 11.3 to 54 ng/mL of morphine. 80% of patients (n = 5) had at least one negative or positive-but-below-threshold (10 ng/mL) result in their oral fluid sample analyses. In contrast, none of the urine studies had negative results. Urine studies for all patients were positive for morphine and well-above primary cutoff values (100 ng/mL) with levels >6000 ng/mL. PMP reports did not reveal any aberrant drug taking behavior in any of the patients. No unprescribed medications or illicit substances were detected in any of the oral or urine samples. Conclusion(s): The prevalence of false negative results for the detection of morphine metabolites in oral fluid toxicology may be higher than clinicians are currently aware of. Physicians and other providers monitoring opioid compliance in chronic pain patients should keep this possibility in mind when selecting toxicology tests and making conclusions about aberrant drug-taking behavior. Larger scale studies are needed to compare oral fluid and urine levels of morphine with extension to other commonly prescribed opioids. Disclosure: Evan Chung, MD: None, Joseph Valenza, MD: NoneCopyright © 2023

Trends for Opioid Prescriptions and the Impact of the Covid-19 Pandemic among Patients with Rheumatic and Musculoskeletal Diseases between 2006 and 2021

Background/Aims Rheumatic and musculoskeletal diseases (RMDs) are some of the most common indications for prescribed opioids. It is unclear how opioid prescribing has changed in the UK for RMDs, especially during the COVID-19 pandemic with limited healthcare access and cancelled elective-surgical interventions, which could impact prescribing in either direction. We aimed to investigate trends in opioid prescribing in RMDs and assess the impact of the pandemic in the UK. Methods Adult patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (AxSpA), systemic lupus erythematosus (SLE), osteoarthritis (OA) and fibromyalgia with opioid prescriptions between 01/Jan/2006-31/Aug/2021 without prior cancer in the UK Clinical Practice Research Datalink (CPRD) were included. We calculated ageand gender-standardised yearly rates of people with opioid prescriptions between 2006-2021, and identified change points in trends by checking whether the rate of change of standardised rates crossed zero. For people with opioid prescriptions, monthly measures of mean morphine milligram equivalents (MME)/day were calculated between 2006-2021. To assess the impact of the pandemic, we fitted regression models to the monthly number of people with opioid prescriptions between Jan/2015-Aug/2021. The time coefficient reflects the trend pre-pandemic and the interaction term coefficient represents the change in the trend during the pandemic. Results We included 1,313,519 patients: 36,932 with RA, 12,649 with PsA, 6,811 with AxSpA, 6,423 with SLE, 1,255,999 with OA, and 66,944 with fibromyalgia. People with opioid prescriptions increased from 2006 to 2018 for OA, to 2019 for RA, AxSpA and SLE, to 2020 for PsA, and to 2021 for fibromyalgia, and all plateaued/decreased afterwards. OA patients on opioids increased from 466.8/10,000 persons in 2006 to a peak of 703.0 in 2018, followed by a decline to 575.3 in 2021. From 2006 to 2021, there was a 4.5-fold increase in fibromyalgia opioid users (17.7 vs.78.5/10,000 persons). In this period, MME/day increased for all RMDs, with the highest for fibromyalgia (>=35). During COVID-19 lockdowns, RA, PsA and fibromyalgia showed significant changes in the trend of people with opioid prescriptions. With a decreasing trend for RA (-0.001,95%CI=-0.002,-0.001) and a decreasing-to-flat curve for PsA (0.0010,95%CI=0.0006,0.0015) prepandemic until Feb/2020, the trends changed by -0.005 (95%CI=-0.008,-0.002) for RA and -0.003 (95%CI=-0.006,-0.0003) for PsA, leading to steeper decreasing trends during the pandemic (Mar/2020-Aug/2021). Fibromyalgia, conversely, had an increasing trend (0.009,95%CI=0.008,0.009) pre-pandemic, and this trend started decreasing by -0.009 (95%CI=-0.011,-0.006) during the pandemic. Conclusion The plateauing/decreasing trend of people with opioid prescriptions in RMDs after 2018 may reflect the efforts to tackle the rising opioid prescribing in UK primary care. Of all RMDs, fibromyalgia patients had the highest MME/day throughout the study period. COVID-19 lockdowns contribute to fewer people on opioids for most RMDs, reassuring there was no sudden increase in opioid prescribing during the pandemic.

Impacts of the COVID-19 pandemic on enrollment in medications for opioid use disorder (MOUD) in Vancouver, Canada: An interrupted time series analysis.

BACKGROUND: In anticipation of COVID-19 related disruptions to opioid use disorder (OUD) care, new provincial and federal guidance for the management of OUD and risk mitigation guidance (RMG) for prescription of pharmaceutical opioids were introduced in British Columbia, Canada, in March 2020. This study evaluated the combined impacts of the COVID-19 pandemic and counteracting OUD policies on enrollment in medications for OUD (MOUD). METHODS: Using data from three cohorts of people with presumed OUD in Vancouver, we conducted an interrupted time series analysis to estimate the combined effects impact of the COVID-19 pandemic and counteracting OUD policies on the prevalence of enrollment in MOUD overall, as well as in individual MOUDs (methadone, buprenorphine/naloxone, slow-release oral morphine) between November 2018 and November 2021, controlling for pre-existing trends. In sub-analysis we considered RMG opioids together with MOUD. RESULTS: We included 760 participants with presumed OUD. In the post-COVID-19 period, MOUD and slow-release oral morphine prevalence rates showed an estimated immediate increase in level (+7.6%, 95% CI: 0.6%, 14.6% and 1.8%, 95% CI: 0.3%, 3.3%, respectively), followed by a decline in the monthly trend (-0.8% per month, 95% CI: -1.4%, -0.2% and -0.2% per month, 95% CI: -0.4, -0.1, respectively). There were no significant changes in the prevalence trends of enrollment in methadone, buprenorphine/naloxone, or when RMG opioids were considered together with MOUD. CONCLUSIONS: Despite immediate improvements in MOUD enrollment in the post-COVID-19 period, this beneficial trend reversed over time. RMG opioids appeared to have provided additional benefits to sustain retention in OUD care.

Quality of life of palliative care cancer patients during COVID-19 lockdown phase

Background: Coronavirus pandemic in 2019 led India to implement a complete lockdown except for essential services. Cancer patients faced hindrances in seeking medical help. This caused stress and worry, leading to reduced quality of life (QoL). This study evaluated QoL and pain management in palliative care cancer patients during the lockdown. Patients and Methods: This was a cross-sectional observational study at a tertiary cancer hospital, over one month period with convenience sampling. Participants included all who were unable to visit the palliative outpatient department during the lockdown during the COVID-19 pandemic. They were contacted telephonically and a valid QoL questionnaire was filled out. Disease, demographic details and pain were assessed. Result(s): A total of 51 were interviewed, 45% (n = 23) patients reported difficult access to medication during the lockdown;18 (35.3%) required morphine to alleviate pain and 6 (33.33%) faced difficulty in acquiring morphine tablets. QoL scores did not differ based on access to morphine (p = 0.648). Mean QoL scores were 12.7 +/- 3.76 and 15.0 +/- 3.60 amongst patients who did not have access to other medications and those who did have access, respectively (p = 0.03). Overall QoL FACT G7 mean score was 14 +/- 3.8. The variables NRS (pain intensity) and QoL scores were found to be negatively correlated (Pearson's Correlation Coefficient: r (49) = -0.69, p < 0.00001). Conclusion(s): Evaluation of QoL of palliative care cancer patients during global crises plays an important role in the assessment of patients' overall condition as well as to maintain a continuum of care.Copyright © Via Medica.

Effect of Hydroxychloroquine, Favipiravir, Lopinavir/Ritonavir, Remdesivir, Umifenovir, and Interferon beta-1a in Covid-19 patients: A systematic review of Randomized Clinical Trials

Background: Coronavirus disease 2019 (COVID-19) was recognized by the World Health Organization (WHO) as a global pandemic on March 11, 2020. Since then, researchers worldwide have focused their attention on identifying effective treatments and developing vaccines to combat this disease. Aim: To report the effectiveness of the drugs employed in the COVID-19 treatment protocols based on data from clinical trial studies conducted from the beginning of the pandemic until December 10, 2020. Methods: Following the PRISMA guidelines, we conducted an advanced search in several electronic databases. A total of 13553 studies was screened by two people simultaneously and separately based on the article title, and full-text. The quality of the studies was evaluated using the Cochrane criteria. Results: Of the 13553 studies identified, 50 clinical trials were included in this systematic review. Of these, three studies explored the use of remdesivir, nine studies the use of hydroxychloroquine, five studies the use of lopinavir/ritonavir, six studies the use of favipiravir, one study the use of tocilizumab, two studies the use of interferon beta-1a and two studies the use of umifenovir.

Prolonged Cessation of Chronic Opioid Analgesic Therapy: A Multidisciplinary Intervention

Am J Manag Care. 2022;28(2):60-65. https://doi.org/10.37765/ajmc.2022.88785 _____ Takeaway Points Building on articles previously published in this journal, this research suggests a potential path toward an effective and sustained clinical approach to decrease chronic opioid analgesic therapy use in the population of patients with chronic, noncancer pain. * We retrospectively examine the initial and sustained success rates of full mu agonist chronic opioid analgesic therapy (COAT) cessation in the setting of chronic, noncancer pain (CNCP) through voluntary participation in a pilot program—implemented via 2 sites and care teams—that provided a standardized, multidisciplinary curriculum containing robust complementary care. * This study provides unusually lengthy follow-up for postintervention COAT cessation monitoring of up to 24 months. * Initial COAT cessation success rates were high, and sustained success at 6 months and beyond was even higher (90%, 95%, and 97%, respectively), indicating that the program curriculum may be an effective strategy for broader application for sustainable COAT cessation in the setting of CNCP. _____ A recent CDC report suggests that years of nationwide medical and managed care regulations to limit prescription opioid access, dose, and time exposure have had minimal positive impact on life expectancy in the United States.1 Despite the wide abandonment of opioid prescriptions by the medical community, opioid-related mortality and morbidity have continued to rise, a trajectory that has accelerated due to the COVID-19 pandemic.1-3 Aside from being a contributor to overdose-related death, full mu agonist chronic opioid analgesic therapy (COAT) has been shown to impede vocational and social return to function and to increase length of disability.1,3,4 Managed care charges for patients with opioid dependency are more than 550% higher than the average annual per-patient charge.5 Also, the population of "opioid refugees" is gaining numbers—patients who were made dependent upon opioids by recent, but now out-of-favor, prescribing practices for the management of chronic pain and are now abruptly unable to find a medical source for the same medications.6 This has moved many patients with chronic pain dependent upon opioids to drastic measures such as seeking new or multiple prescribers, emergency medical care, or even illicit opioid sources.7 The medical community has been trialing and comparing several approaches to combat the ineffective use of COAT for chronic, noncancer pain (CNCP). Some managed care institutions have attempted a model of coverage cessation for these medications, resulting in paradoxically increased costs as patients struggle to cope.3 Clinicians have reported varying levels of success to promote COAT cessation through outpatient weaning8-12 and single-modality approaches of cognitive behavioral therapy (CBT),13,14 acupuncture,10 interdisciplinary programing,15-24 and buprenorphine substitution.20,25-27 None of the data present a definitive, best-practice approach to the challenge of the opioid epidemic in the setting of chronic pain. Every activity was designed for home exercise and was led by a licensed or credentialed expert in that field, such as a physician, nurse practitioner, psychologist, licensed acupuncturist, physical therapist, or licensed physical therapy assistant. Because the PDMP is ubiquitous as a record of presence and volume of prescribed controlled substances in California, with few exceptions (see Discussion), lack of an entry in the PDMP was interpreted as that subject not using opioids.

Primary proximal hypospadias repair in in toilet-trained males is associated with a higher risk of post-operative complications and parental dissatisfaction

Introduction & Objectives: Hypospadias is the most common congenital malformation of the penis. There has been a lot of recent controversy in certain countries as to whether operating on distal hypospadias is warranted, and when this should occur. Proximal hypospadias, however, is much less common, with a putative aetiology within the male programming window of the first trimester. It has an association with differences of sexual development (DSD) when diagnosed alongside cryptorchidism and the operative approach is technically more challenging. The European Association of Urology (EAU) recommends initial repair between 6-18 months of age. Material(s) and Method(s): We prospectively gathered data from 24 consecutive toilet-trained children (3-7 years) who were initially listed for proximal hypospadias repair, but who were delayed as a result of resource limitations and the ongoing supply chain effects of COVID-19. The patients were operated between July 2020 and July 2022 with a mean follow-up of 7 months (3-24months). These were compared with a cohort of 16 patients who underwent proximal hypospadias repair between 12-18 months of age in the same institution. Both single and staged procedures were included. Institutional review board approval was obtained. Patients who had previously been operated on as an infant, or who were diagnosed with a DSD, or had an associated diagnosed neuropsychiatric developmental disorder were excluded. Pre-, peri- and post-operative data were statistically compared. Result(s): Overall, 40 children underwent a total of 75 primary procedures for their proximal hypospadias (7x single stage;31 x 2-stage;2 x 3-stage). All patients had an indwelling catheter placed post-operatively, were on antibiotic prophylaxis and oxybutynin for bladder spasms. Morphine was not used post-operatively in any case. Apart from age, there were no significant demographic or racial differences between these groups. The toilettrained cohort was associated with a higher rate of urethrocutaneous fistulas (58% vs. 31%;p=0.11), catheter/stent trauma (79% vs. 6%;p<0.001), pain (54% vs. 12%;p<0.01), constipation (75% vs. 37%;p=0.02). Both Likert Scales (4 vs. 8) and parental net promoter scores (-25 vs. +68.75) were worse for the toilet trained cohort compared to the infant cohort. There were no differences in glans dehiscence, or residual chordee between both groups. Conclusion(s): Primary proximal hypospadias repair is associated with a higher degree of perioperative complications in toilet-trained kids and lower levels of parental satisfaction. These cases are not deemed to be suitable to be managed conservatively and should be offered treatment within the 6-18 months window adjusted for gestational age as endorsed by the EAU.Copyright © 2023.

Probing different paradigms of morphine withdrawal on sleep behavior in male and female C57BL/6J mice.

Opioid misuse has dramatically increased over the last few decades resulting in many people suffering from opioid use disorder (OUD). The prevalence of opioid overdose has been driven by the development of new synthetic opioids, increased availability of prescription opioids, and more recently, the COVID-19 pandemic. Coinciding with increases in exposure to opioids, the United States has also observed increases in multiple Narcan (naloxone) administrations as a life-saving measures for respiratory depression, and, thus, consequently, naloxone-precipitated withdrawal. Sleep dysregulation is a main symptom of OUD and opioid withdrawal syndrome, and therefore, should be a key facet of animal models of OUD. Here we examine the effect of precipitated and spontaneous morphine withdrawal on sleep behaviors in C57BL/6 J mice. We find that morphine administration and withdrawal dysregulate sleep, but not equally across morphine exposure paradigms. Furthermore, many environmental triggers promote relapse to drug-seeking/taking behavior, and the stress of disrupted sleep may fall into that category. We find that sleep deprivation dysregulates sleep in mice that had previous opioid withdrawal experience. Our data suggest that the 3-day precipitated withdrawal paradigm has the most profound effects on opioid-induced sleep dysregulation and further validates the construct of this model for opioid dependence and OUD.

Clinical applications of transcutaneous auricular neurostimulation for opioid use disorder and pain

Symposium title: Addressing chronic pain and the opioid epidemic using auricular neuromodulation Symposium description: Our proposed symposium integrates a diverse group of scientist and clinician experts (Drs. Cunningham, Wilkes, Khodaparast, Badran) who have committed to exploring the anti-nociceptive and opioid sparing effects of auricular neuromodulation to progress toward non-opioid interventions for chronic pain and opioid use disorders. The demand for chronic pain therapies has increased at an unprecedented rate over the last several decades, contributing in part to a surge in prescription and illicit opioid demand. Countless patients were escalated to prolonged, high-dose opioid regimens over years of treatment. By 2014, 5.4% of U.S. adults were estimated to use prescription opioids on a long-term basis. As the harms of opioid proliferation became increasingly clear, a dramatic paradigm shift occurred in which these drugs are now perceived as more dangerous than beneficial for chronic pain. New clinical guidelines highlight the risks of high-dose regimens as well as the limited benefits, particularly insufficient analgesia and hyperalgesia, associated with long-term use. According to this new perspective, the preferred therapeutic modality for many patients is to safely taper, or even completely stop, using opioids. Transcutaneous auricular neurostimulation (tAN) is a novel therapeutic paradigm that includes stimulation of both the auricular branch of the vagus nerve and auriculotemporal nerve (branch of trigeminal). tAN therapy results in clinically significant reductions in opioid withdrawal symptoms associated with opioid detoxification and tapering. Either adjunctive vagal or trigeminal stimulation modulates pain transmission suggesting overlapping common effector pathways, possibly targeting the endogenous opioid system, which could lead to a synergistic therapeutic benefit for pain. This symposium will explore the scientific basis for this hypothesis across targeted and interconnected topics, including fundamental neuropharmacological mechanisms underlying pain and opioids, clinical challenges of tapering opioids, managing opioid withdrawal symptoms with tAN, and the prospects for tAN to deliver a safe alternative treatment option for pain disorders. The United States is experiencing an epidemic for prescription and non-prescription opioids, which have continued to rise since the 1990s. During 2015, approximately 2.1 million people were severely dependent on prescription opioids, and 513,000 on heroin. In 2020, the Centers for Disease Control reported 93,331 substance use overdose deaths. The continuing increase in opioid-related deaths from 2015 (18%) to 2020 (60%) is partly attributed to the mental health crisis during the Covid-19 pandemic. Aside from pain mitigation, individuals with opioid use disorder (OUD) may be motivated to continue drug-seeking by both the positive reinforcement of the euphoric effects of opioids and the negative reinforcement of opioid withdrawal symptoms due to cessation. Alternative approaches for OUD are a major priority for government agencies given the substantial impact on health, social, and economic welfare. Transcutaneous auricular neurostimulation (tAN) is a non-invasive form of vagus and trigeminal neuromodulation that was recently proven to be an efficacious non-pharmacologic based treatment for reducing opioid withdrawal symptoms. In 2021, tAN therapy received FDA clearance as an adjunctive treatment for opioid withdrawal symptoms in adults. tAN therapy was also proven safe and effective in reducing symptoms of neonatal opioid withdrawal syndrome (NOWS) in neonates. tAN as an adjuvant was safe, well-tolerated, while facilitating the successful rapid weaning of oral morphine and decreasing length of stay in the neonatal ICU. Based on these preliminary findings, tAN therapy is currently in two NIH-funded pivotal clinical trials to: 1) evaluate the long-term effects of tAN on opioid use relapse prevention and cravings in adults with OUD, and 2) determine f tAN therapy can reduce withdrawal symptoms and reduce morphine length of treatment for neonates with NOWS. Lastly, we will explore how tAN could be utilized as neuromodulatory approach for opioid sparing, and ultimately pain mitigation. Research Category and Technology and Methods Clinical Research: 12. Vagus Nerve Stimulation (VNS) Keywords: Vagus Nerve Stimulation, Opioid Use Disorder, Pain, NeurostimulationCopyright © 2023

Factors associated with non-invasive positive pressure ventilation failure in a COVID-19 Intermediate Care Unit

Aim: To evaluate the efficacy of NIPPV (CPAP, HELMET-CPAP or NIV) in COVID-19 patients treated in the dedicated COVID-19 Intermediate Care unit of Coimbra Hospital and University Centre (CHUC), Portugal, and to assess factors associated with NIPPV failure. Method(s): Patients admitted to the Intermediate Care Unit of CHUC, from December 1st 2020 to February 28th 2021, treated with NIPPV due to confirmed COVID-19 were included. The primary outcome was NIPPV failure (orotracheal intubation (OTI) or death during hospital stay). Factors associated with NIPPV failure were included in an univariate binary logistic regression analysis and those with a significance level of p<0.001 were selected to enter a multivariate regression model. Result(s): 163 patients were included, 64.4% were males (n=105) and the median age was 66 years (IQR 56-75). Overall, 97 patients (59.5%) were successfully treated with NIPPV, while failure was observed in 66 (40.5%), of which 26 (39.4%) were intubated and 40 (60.6%) died during hospital stay. Highest CRP during hospital stay (OR 1.164;95%CI 1.036-1.308) and morphine use (OR 24.771;95%CI 1.809-339.241) were identified as independent predictors in the multivariate logistic model. Adherence to prone positioning (OR 0.109;95%CI 0.017-0.700) and a higher value of the lowest platelet count during hospital stay (OR 0.977;95%CI 0.960-0.994) were associated with a favourable outcome. Conclusion(s): Highest CRP and morphine use were independent predictors of OTI or death. Adherence to prone positioning and a higher value of the lowest platelet count during hospital stay were associated with a favourable outcome.

Complex Regional Pain Syndrome (Crps) in a Hemophilia Child with Inhibitor: A Rare Interactable Cause of Joint Pains

Introduction: Joint bleeding is the main cause of joint pain in hemophilia patients and can lead to chronic joint disease which also happens to be one of the significant causes of disability and joint pain in these patients. Furthermore, ComplexRegional Pain Syndrome (CRPS), despite being a very rare complication, should be considered in cases of persistent intractable pain, especially in the pediatric group. Clinical symptoms in CRPS include severe chronic pain, edema, and decreased range of motion. CRPS management is critical to allowing the function and ability of the joint to restore. Method(s): This study aims to report a hemophilia case with intractable pain and his underlying diagnosis. A 14-year-old severe hemophilia A patient with high titer/responder inhibitor was on on-demand treatment by Bypassing Agents (BPAs). Result(s): During the disease course, his right knee became a target joint due to recurrent bleedings. Consequently, he underwent Radiosynoviorthesis (RSO) and treatment with BPAs. After three days of improving, he got an increasing fever and severe right knee pain. The COVID-19 test result was negative, but Staph. Aureus was found in the synovial fluid, and treatment began with Vancomycin and Rifampin. After several days, his condition and laboratory markers were improved, However, intractable disabling pain remained constant regardless of augmented combination therapy with FEIBA and rFVIIa. Parallelly, morphine was prescribed due to the Pain Management counseling. However, the pain began to rise as the morphine dosage declined. As a result, CRPS proposed to be the leading cause of pain, and after several prolonged special physiotherapy sessions, pain reduced significantly, only one BPA was continued and he was ambulated again. Discussion/Conclusion: The current case indicates that CRPS is a rare complication in patients with bleeding disorders which has been reported rarely till now. Nonetheless, it should be considered a diagnosis in complicated patients with recurrent hemarthrosis due to its debilitating and destructive nature.

Palliative care for Continuous Positive Airway Pressure (CPAP) withdrawal in patients with COVID-19

Introduction: Patients with COVID-19 who require CPAP as ceiling of care have a high mortality. Evidence is lacking for appropriate end of life care for these patients and withdrawal from high CPAP pressures can be distressing for patients and their families. Method(s): We retrospectively reviewed case notes for 36 patients with COVID-19 pneumonitis who were not suitable for intubation and required withdrawal of CPAP at Colchester Hospital, UK from 29th April, 2020 to 13th February, 2021. Result(s): Mean age was 74.14 (SD 9.48) years, 14 patients were female. Decision to withdraw was discussed with family in 91.7% of cases and with the patient in 50% of cases. A family member was present during withdrawal in 38.9% of cases. All patients after CPAP withdrawal died. Mean time to death since withdrawal (known in 30 patients) was 26.06 (SD 43.84) hours. Reasons for withdrawal included patient deterioration (55.6%), patient discomfort (36.1%) and patient wish (8.3%). Sedative drugs were often needed to achieve comfort, high doses were required in some cases. Comfort was achieved with midazolam, morphine and levomepromazine in the majority, however in one case, phenobarbitone was also required. Total doses used from time of decision to withdraw CPAP to death, are summarised in table 1. Conclusion(s): Optimum palliative care is vital for looking after these patients. In our experience, some patients required higher than usual doses of sedation whilst CPAP was withdrawn. (Table Presented).

Anesthetic management of toxic epidermal necrolysis: a report of two cases

Toxic epidermal necrolysis (TEN), is an acute, life-threatening emergent disease involving the skin and mucous membranes with serious systemic complications. It is characterized by widespread epidermal sloughing. Drugs are the most common triggers of TEN, but infection, vaccination, radiation therapy and malignant neoplasms can all induce it in susceptible patients. We report two cases in whom a hair dye and a COVID-19 vaccine (BioNTech, Pfizer) were believed to be the causative agents. These patients have to undergo repeated debridements of the necrotic tissue. In this manuscript the anesthetic management of TEN patients is discussed. Detailed preoperative evaluation, aggressive fluid and electrolyte replacement, avoidance of hypothermia during debridement, minimizing anesthetic agents and limiting traumatic procedures are key points in the management.Copyright © 2023 Faculty of Anaesthesia, Pain and Intensive Care, AFMS. All rights reserved.

Identification of selected earthworm species of Northeast India using DNA barcoding

Aim: This study aimed at the species identification of selected indigenous earthworms of Manipur and Assam, Northeast India along with an exotic species using morpho-anatomical study and DNA barcoding. Methodology: Indigenous species of earthworms were collected from Imphal and Jorhat, North-eastern part of India. The exotic species of earthworm were collected from Indian Council of Agricultural Research Complex, Manipur. The samples were collected by digging and hand sorting method. Identification of samples was done by both conventional and molecular methods. Molecular characterization was accomplished through PCR amplification of the mitochondrial cytochrome oxidase I (COI) genes. Automatic sequencing reactions were performed for the amplified PCR products on ABI3100 Genetic Analyser (Applied Biosystems). Result(s): Out of five specimens (EM1, EM2, EM4, EG5 and EM6) examined through morpho-anatomical studies, three were identified to species level while the other two were identified to their genus level only. Out of EM1 and EM2 specimens in the genus Perionyx as per the morpho-anatomical studies, DNA barcoding could deduce the EM2 specimen up to the species level as P. excavatus. The exotic EM6 specimen morphologically identified as Eisenia fetida showed 99% COI gene sequence similarity with both E. fetida and E. andrei but its sequence divergence with E. andrei was less than 1%, so, it belonged to E. andrei. Interpretation(s): This study shows the reliability of clubbing DNA barcoding experiments with classical taxonomy in supplementing and strengthening the traditional taxonomy for accurate identification of earthworms.Copyright © Triveni Enterprises, Lucknow (India)

Effectiveness of Morphine in Managing Refractory Dyspnoea in Patients with Coronavirus Disease (COVID-19).

Opiates are generally used to relieve dyspnoea in advanced diseases such as cancer and lung diseases. However, little is known regarding the safety and efficacy of morphine for refractory dyspnoea in coronavirus disease 2019 (COVID-19) patients. We retrospectively reviewed records of 18 COVID-19-positive patients who were administered morphine for refractory dyspnoea during hospitalisation between May 2021 and June 2021. Details of morphine usage, vital signs, an 11-point dyspnoea numeric rating scale (DNRS) and adverse events at baseline, 24 h and 72 h after the start of treatment were abstracted from records. The final clinical outcome in terms of death or discharge was noted. All patients had severe refractory dyspnoea (DNRS score ≥7) at the time of administration of morphine and had not been relieved from standard care for the past 3 days. In the results, the mean (standard deviation [SD]) age was 47.1 (12) years, male was 13 (72.20%) patients and modified Medical Research Council Grade 4 was present in all 18 patients. The mean (SD) 1st day dose of morphine was 7.03 (1.53) mg and the mean (SD) duration of morphine use was 5.22 (3.00) days. Significant decreases in DNRS, respiratory rate and oxygen saturation were observed 24 h and 72 h after the start of morphine administration. Meanwhile, blood pressure and heart rate were not significantly altered after treatment. The finding of this single-centre retrospective study indicates that morphine may be considered for use in the management of refractory dyspnoea among COVID-19 patients.

Chewing Gum for Prevention of Nausea and Vomiting After Elective Caesarean Section: a Pilot Randomised Controlled Trial.

Nausea and vomiting are common complications in patients undergoing caesarean delivery under regional anaesthesia. When experienced after surgery, they may delay recovery, reduce patient satisfaction and affect the bonding between mother and baby. Various pharmacological and non-pharmacological approaches for prophylaxis and treatment of postoperative nausea and vomiting (PONV) have been employed with different degree of efficacy. In this pilot randomised controlled trial, we aimed to determine the possible preventative effects of chewing gum on the rate of PONV in expectant mothers undergoing neuraxial anaesthesia for elective lower segment caesarean section. All participants underwent spinal anaesthesia with administration of 10-11.5 mg of intrathecal heavy Bupivicaine 0.5% according to anaesthetists' preference, Morphine 100 µg and Fentanyl 25 µg. Postoperative analgesia regimen was also standardised. Two hundred ninety-six patients were randomised to an intervention arm to receive chewing gum in addition to standard therapy and to a non-intervention arm to receive standard therapy. After exclusions, 258 patients were followed up 24 h postoperatively. Standard therapy is defined as Ondansetron 4 mg IV intra-operatively. The primary outcomes were the incidences of nausea and vomiting in the first 24 h postoperatively. Secondary outcomes were the number of episodes of nausea or vomiting in the recovery room and on the ward 24 h postoperatively, use of anti-emetics postoperatively, severity of nausea and patient satisfaction with the intervention. Our study revealed no significant differences in rates of postoperative nausea and vomiting between the intervention and standard therapy groups (41.4% v 36.9% p = 0.461). There were no significant differences in secondary outcomes between groups. Chewing gum does not reduce the incidence of PONV after elective LSCS under spinal anaesthesia. Our trial was registered with clinicaltrials.org (NCT04191694).

Hippocampal and amygdalar increased BDNF expression in the extinction of opioid-induced place preference.

The opioid crisis was exacerbated during the COVID-19 pandemic in the United States with alarming statistics about overdose-related deaths. Current treatment options, such as medication assisted treatments, have been unable to prevent relapse in many patients, whereas cue-based exposure therapy have had mixed results in human trials. To improve patient outcomes, it is imperative to develop animal models of addiction to understand molecular mechanisms and identify potential therapeutic targets. We previously found increased brain derived neurotrophic factor (bdnf) transcript in the ventral striatum/nucleus accumbens (VS/NAc) of rats that extinguished morphine-induced place preference. Here, we expand our study to determine whether BDNF protein expression was modulated in mesolimbic brain regions of the reward system in animals exposed to extinction training. Drug conditioning and extinction sessions were followed by Western blots for BDNF in the hippocampus (HPC), amygdala (AMY) and VS/NAc. Rears, as a measure of withdrawal-induced anxiety were also measured to determine their impact on extinction. Results showed that animals who received extinction training and successfully extinguished morphine CPP significantly increased BDNF in the HPC when compared to animals deprived of extinction training (sham-extinction). This increase was not significant in animals who failed to extinguish (extinction-resistant). In AMY, all extinction-trained animals showed increased BDNF, regardless of behavior phenotype. No BDNF modulation was observed in the VS/NAc. Finally, extinction-trained animals showed no difference in rears regardless of extinction outcome, suggesting that anxiety elicited by drug withdrawal did not significantly impact extinction of morphine CPP. Our results suggest that BDNF expression in brain regions of the mesolimbic reward system could play a key role in extinction of opioid-induced maladaptive behaviors and represents a potential therapeutic target for future combined pharmacological and extinction-based therapies.