The Importance of the Treatment Rationale for Pain in Animal-Assisted Interventions: A Randomized Controlled Trial in Healthy Participants.

Animal-assisted interventions (AAIs) is a promising treatment approach for pain, but possible mechanisms still need to be elucidated. This study set out to investigate the analgesic effects of an animal provided with a treatment rationale in a randomized controlled trial employing a standardized experimental heat-pain paradigm. We randomly assigned 128 healthy participants to: dog treatment (DT), placebo treatment (PT), dog and placebo treatment (DPT), and no treatment (NT). Primary outcomes were heat-pain tolerance and the corresponding self-reported ratings of pain unpleasantness and intensity. Results revealed no differences in heat-pain tolerance between the conditions. However, participants in the DT condition experienced heat-pain as significantly less unpleasant at the limit of their tolerance compared to participants in the NT condition (estimate = -0.96, CI = -1.58 to 0.34, P = .010). Participants in the DT condition also showed lower ratings of pain intensity at the limit of their tolerance compared to participants in the NT condition (estimate = -0.44, CI = -0.89 to 0.02, P = .060). This study indicates that a dog has analgesic effects on pain perception when integrated into the treatment rationale. We assume that providing a treatment rationale regarding the animal is important in AAIs for pain. PERSPECTIVE: This study shows that the presence of an animal is not sufficient for animal-assisted interventions (AAIs) to have an analgesic effect on pain unless they are provided with a treatment rationale. This could imply that not only the animal but also contextual factors are important in AAIs. TRIAL REGISTRATION: Clinical Trials NCT04361968.

The use of analgesics for intentional self-poisoning: Trends in U.S. poison center data.

In the U.S., intentional self-poisonings with analgesics that are available without a prescription increased from 2000 to 2018. Given concerns regarding mental health outcomes during the COVID-19 pandemic, we examined and compared trends in pediatric and adult intentional self-poisoning with acetaminophen, aspirin, ibuprofen, and naproxen from 2016 to 2021 using the National Poison Data System (NPDS) to see if these trends have continued. We extracted annual case counts of all suspected suicide attempts from intentional poisoning, and of suspected suicide attempts resulting in major effects or death, from the NPDS for non-prescription single ingredient adult formulation acetaminophen, non-prescription single ingredient adult formulation aspirin, single ingredient formulation ibuprofen, and single ingredient formulation naproxen. We enumerated the cases by year, age, and gender. Most cases of intentional self-poisoning within the review period involved acetaminophen and ibuprofen and the 13-19-year-olds constituted the highest proportion of intentional self-poisoning cases across age groups for all four analgesics. Cases involving females predominated cases involving males by 3:1 or greater. The 13-19-year-old age group also represented the largest proportion of cases that resulted in major clinical effects or deaths. An increasing trend in suicide poisoning cases with acetaminophen and ibuprofen was observed in the 6-19-years age group and this trend appeared to exacerbate from 2020 to 2021 corresponding with the start of the COVID-19 pandemic period.

Chronic pain and continuity of analgesic treatment during the COVID-19 pandemic.

INTRODUCTION: Chronic pain can trigger both physical and mental health complications. During the COVID-19 pandemic, patients with chronic diseases have had reduced access to some medications. OBJECTIVE: To determine the pharmacological management of patients with chronic pain and its continuity during the COVID-19 pandemic. METHODS: This was a retrospective longitudinal study of the continuity of analgesic use in patients with chronic pain between September 1, 2019 and February 28, 2021 based on a drug dispensing database. Survival analysis was performed until the discontinuation of chronic analgesics. RESULTS: A total of 12,701 patients who were being treated for chronic pain were identified. Their median age was 70.3 years, and 74.4% were women. The pain of rheumatological origin was the most frequent etiology (46.1%); the most used medications were nonopioid analgesics (78.9%), pain modulators (24.8%) and opioid analgesics (23.3%). A total of 76.1% of the patients experienced interruptions in their management during the study period. The median time to the first interruption of treatment was 5.0 months (95% CI: 4.8-5.2). Those who were treated for oncological pain experienced a greater number of interruptions in their management. CONCLUSIONS: The pharmacological management of patients with chronic pain is heterogeneous, and this real-world study showed that a high proportion of patients experienced an interruption of pain management during the 12 months following the onset of the COVID-19 pandemic.

2021 Annual Report of the National Poison Data System© (NPDS) from America's Poison Centers: 39th Annual Report.

ABSTRACTINTRODUCTION: This is the 39th Annual Report of America's Poison Centers' National Poison Data System (NPDS). As of 1 January, 2021, all 55 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 4.87 [4.38, 8.62] (median [25%, 75%]) minutes, effectuating a near real-time national exposure and information database and surveillance system. METHODS: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Cases with medical outcomes of death were evaluated by a team of medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality (RCF) of the exposure. RESULTS: In 2021, 2,851,166 closed encounters were logged by NPDS: 2,080,917 human exposures, 62,189 animal exposures, 703,086 information requests, 4,920 human confirmed nonexposures, and 54 animal confirmed nonexposures. Total encounters showed a 14.0% decrease from 2020, and human exposure cases decreased by 2.22%, while health care facility (HCF) human exposure cases increased by 7.20%. All information requests decreased by 37.0%, medication identification (Drug ID) requests decreased by 20.8%, and medical information requests showed a 61.1% decrease, although these remain about 13-fold higher than before the COVID-19 pandemic. Drug Information requests showed a 146% increase, reflecting COVID-19 vaccine calls to PCs. Human exposures with less serious outcomes have decreased 1.80% per year since 2008, while those with more serious outcomes (moderate, major or death) have increased 4.56% per year since 2000.Consistent with the previous year, the top 5 substance classes most frequently involved in all human exposures were analgesics (11.2%), household cleaning substances (7.49%), cosmetics/personal care products (5.88%), antidepressants (5.61%), and sedatives/hypnotics/antipsychotics (4.73%). As a class, antidepressant exposures increased most rapidly, by 1,663 cases/year (5.30%/year) over the past 10 years for cases with more serious outcomes.The top 5 most common exposures in children age 5 years or less were cosmetics/personal care products (10.8%), household cleaning substances (10.7%), analgesics (8.16%), dietary supplements/herbals/homeopathic (7.00%), and foreign bodies/toys/miscellaneous (6.51%). Drug identification requests comprised 3.64% of all information contacts. NPDS documented 4,497 human exposures resulting in death; 3,809 (84.7%) of these were judged as related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory). CONCLUSIONS: These data support the continued value of PC expertise and the need for specialized medical toxicology information to manage more serious exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time status of NPDS represents a national public health resource to collect and monitor US exposure cases and information contacts. The continuing mission of NPDS is to provide a nationwide infrastructure for surveillance for all types of exposures (e.g., foreign body, infectious, venomous, chemical agent, or commercial product), and the identification and tracking of significant public health events. NPDS is a model system for the near real-time surveillance of national and global public health.

Current Insights on Bioactive Molecules, Antioxidant, Anti-Inflammatory, and Other Pharmacological Activities of Cinnamomum camphora Linn.

C. camphora is a renowned traditional Unani medicinal herb and belongs to the family Lauraceae. It has therapeutic applications in various ailments and prophylactic properties to prevent flu-like epidemic symptoms and COVID-19. This comprehensive appraisal is to familiarize the reader with the traditional, broad applications of camphor both in Unani and modern medicine and its effects on bioactive molecules. Electronic databases such as Web of Science, PubMed, Google Scholar, Scopus, and Research Gate were searched for bioactive molecules, and preclinical/clinical research and including 59 research and review papers up to 2022 were retrieved. Additionally, 21 classical Unani and English herbal pharmacopeia books with ethnomedicinal properties and therapeutic applications were explored. Oxidative stress significantly impacts aging, obesity, diabetes mellitus, depression, and neurodegenerative diseases. The polyphenolic bioactive compounds such as linalool, borneol, and nerolidol of C. camphora have antioxidant activity and have the potential to remove free radicals. Its other major bioactive molecules are camphor, cineole, limelol, safrole, limonene, alpha-pinene, and cineole with anti-inflammatory, antibacterial, anxiolytic, analgesic, immunomodulatory, antihyperlipidemic, and many other pharmacological properties have been established in vitro or in vivo preclinical research. Natural bioactive molecules and their mechanisms of action and applications in diseases have been highlighted, with future prospects, gaps, and priorities that need to be addressed.

Impact of COVID-19 Pandemic Lockdown on Migraine Patients in Latin America.

The coronavirus (COVID-19) pandemic, confinement, fear, lifestyle changes, and worldwide health care impacted almost all diseases. Reports from countries outside Latin America revealed differences in migraine patients. In this study, we describe and compare the immediate changes in migraine symptoms associated with COVID-19 quarantine in patients from Argentina, Mexico, and Peru. An online survey was conducted from May to July 2020. The survey was answered by 243 migraine patients, with questions related to sociodemographic data, quarantine conditions, changes in working conditions, physical activity, coffee intake, healthcare access, acute migraine medication use, symptoms of anxiety, depression, and fear of COVID-19. The results show that 48.6% of migraine patients experienced worsened symptoms, 15.6% improved, and 35.8% remained unchanged. Worsening migraine symptoms were associated with staying at home during the lockdown. Intake of analgesics was associated with an increase in migraine symptoms of 18 times relative to those who did not increase their intake. Migraine symptoms improved when the number of sleep hours was increased, and we observed an improvement when patients decreased analgesic intake. The uncertainty about the end of the pandemic, the news, and social media are three items that contributed to the worsening of migraine symptoms in patients in the three investigated countries. Confinement during the first pandemic wave in Latin America harmed migraine patients who stayed home during the lockdown.

Modulation of transient receptor potential (TRP) channels by plant derived substances used in over-the-counter cough and cold remedies.

BACKGROUND: Upper respiratory tract infections (URTIs) impact all age groups and have a significant economic and social burden on society, worldwide. Most URTIs are mild and self-limiting, but due to the wide range of possible causative agents, including Rhinovirus (hRV), Adenovirus, Respiratory Syncytial Virus (RSV), Coronavirus and Influenza, there is no single and effective treatment. Over-the-counter (OTC) remedies, including traditional medicines and those containing plant derived substances, help to alleviate symptoms including inflammation, pain, fever and cough. PURPOSE: This systematic review focuses on the role of the major plant derived substances in several OTC remedies used to treat cold symptoms, with a particular focus on the transient receptor potential (TRP) channels involved in pain and cough. METHODS: Literature searches were done using Pubmed and Web of Science, with no date limitations, using the principles of the PRISMA statement. The search terms used were 'TRP channel AND plant compound', 'cough AND plant compound', 'cough AND TRP channels AND plant compound', 'cough AND P2X3 AND plant compound' and 'P2X3 AND plant compound' where plant compound represents menthol or camphor or eucalyptus or turpentine or thymol. RESULTS: The literature reviewed showed that menthol activates TRPM8 and may inhibit respiratory reflexes reducing irritation and cough. Menthol has a bimodal action on TRPA1, but inhibition may have an analgesic effect. Eucalyptus also activates TRPM8 and inhibits TRPA1 whilst down regulating P2X3, aiding in the reduction of cough, pain and airway irritation. Camphor inhibits TRPA1 and the activation of TRPM8 may add to the effects of menthol. Activation of TRPV1 by camphor, may also have an analgesic effect. CONCLUSIONS: The literature suggests that these plant derived substances have multifaceted actions and can interact with the TRP 'cough' receptors. The plant derived substances used in cough and cold medicines have the potential to target multiple symptoms experienced during a cold.

Norwegian adolescents' use of energy drinks and painkillers and misuse of prescription drugs prior to and during the initial COVID-19 pandemic year: Evidence from the MyLife study.

AIMS: This study aimed to examine and compare the use of energy drinks, over-the-counter (OTC) painkillers and misuse of prescription drugs in two cohorts of Norwegian adolescents entering high school (i.e. grade 11) immediately prior to and during the initial year of the COVID-19 pandemic. METHODS: Accelerated longitudinal design and multi-cohort sampling enabled identification of the two socio-demographically comparable cohorts of grade 11 students: (a) COVID-19 cohort assessed in the autumn of 2020 (n=915) and (b) pre-COVID-19 cohort assessed in the autumn of 2018/19 (n=1621). Unadjusted and adjusted logistic and Poisson models were used to estimate the proportion of (mis)users and use frequencies among (mis)users in two cohorts. RESULTS: Energy drinks use was both more common in the COVID-19 cohort (60.8% vs. 52.5%; adjusted odds ratio=1.40, 95% confidence interval (CI) 1.18-1.66, p<0.001) and more frequent among users from this cohort than among their pre-COVID-19 counterparts (9.58 vs. 7.79 days past month, adjusted incidence risk ratio (aIRR)=1.23, 95% CI 1.14-1.32, p<0.001). No cohort differences were observed in OTC painkillers use. Prescription drugs misuse was equally common in the two cohorts but was more frequent among misusers from the COVID-19 cohort than among their pre-COVID-19 counterparts (18.94 vs. 12.45 times past year, aIRR=1.52, 95% CI 1.10-2.10, p<0.001). CONCLUSIONS: Norwegian adolescents from the COVID-19 cohort were more likely to use energy drinks and, once engaged in these behaviours, to use energy drinks and misuse prescription drugs more frequently than their pre-COVID-19 counterparts.

Pain management recommendations during the progression of SARS-CoV-2 infection.

COVID-19, an infection caused by SARS-CoV-2, had a devastating impact on people's lives. The pandemic placed a heavy burden on healthcare systems and impacted the care of patients, including those with pain. This narrative review aims to highlight the challenges in managing pain and fever resulting from COVID-19 and pre-existing conditions, and to discuss the role of over the counter analgesics as a key part of the COVID-19 treatment regimen. As most patients with COVID-19 are being managed in the outpatient setting, lifestyle interventions and over the counter analgesics are readily available options to effectively treat pain and fever, which can help to decrease the burden on the healthcare system during the COVID-19 pandemic.

COVID-19 is an infection caused by SARS-CoV-2. The COVID-19 pandemic not only affects patient lives, but also heavily impacts healthcare systems. This review aims to discuss the available literature on how to manage pain from COVID-19 and encourage a consensus meeting for recommendations. As most patients with COVID-19 are being managed in the outpatient setting, lifestyle interventions and over the counter analgesics are readily available options to effectively treat pain and fever, which can help to decrease the demand on the healthcare system during the COVID-19 pandemic.

Geographic Accessibility of Retail Cannabis in Northern California and Prenatal Cannabis Use During the COVID-19 Pandemic.

Importance: Prenatal cannabis use is associated with health risks for mothers and their children. Prior research suggests that rates of prenatal cannabis use in Northern California increased during the COVID-19 pandemic, but it is unknown whether increases varied with the local cannabis retail and policy environment. Objective: To test whether pandemic-related increases in prenatal cannabis use were greater among pregnant individuals with greater retail availability of cannabis around their homes or among those living in jurisdictions that allowed storefront retailers. Design, Setting, and Participants: A cross-sectional, population-based time series study used data from pregnancies in the Kaiser Permanente Northern California health care system screened for cannabis use before (January 1, 2019, to March 31, 2020) and during (April 1 to December 31, 2020) the early COVID-19 pandemic. Proximity to the nearest retailer and number of retailers within a 15-minute drive from one's home and local cannabis storefront retailer policy (banned vs permitted) were calculated. Interrupted time series models were fit using multiplicative and additive Poisson regression, adjusting for age and race and ethnicity. Exposures: The COVID-19 pandemic. Main Outcomes and Measures: Prenatal cannabis use based on universal urine toxicology tests conducted during early pregnancy at entrance to prenatal care. Results: The sample (n = 99 127 pregnancies) included 26.2% Asian or Pacific Islander, 6.8% Black, 27.6% Hispanic, 34.4% non-Hispanic White, and 4.9% other, unknown, or multiracial individuals, with a mean (SD) age of 30.8 (5.3) years. Prenatal cannabis use before (6.8%) and during (8.2%) the pandemic was associated with closer proximity to a retailer, greater retailer density, and residing in a jurisdiction that permitted vs banned retailers. There was a greater absolute increase in cannabis use from before to during the pandemic among those within a 10-minute drive (<10 minutes: adjusted rate difference [aRD], 0.93 cases/100 patients; 95% CI, 0.56-1.29 cases/100 patients; ≥10 minutes: aRD, 0.40 cases/100 patients; 95% CI, 0.12-0.68 cases/100 patients; interaction P = .02). Otherwise, relative and absolute rates increased similarly across categories of cannabis retailer proximity/density and local policy (interaction P > .05). Conclusions and Relevance: Prenatal cannabis use was more common among individuals living in areas with greater retail availability of cannabis. Although relative rates increased similarly during the pandemic regardless of local cannabis retail and policy environment, there was a larger absolute increase associated with living closer to a storefront cannabis retailer. Continued monitoring of local cannabis policy, the retail environment, and prenatal cannabis use is needed.

Tracheotomy in ventilator-dependent patients with COVID-19: a cross-sectional study of analgesia and sedative requirements.

OBJECTIVE: During March 2020 in the United States, demand for sedatives increased by 91%, that for analgesics rose by 79%, and demand for neuromuscular blockers increased by 105%, all owing to the number of COVID-19 cases requiring invasive mechanical ventilation (MV). We hypothesize that analgesic and sedative requirements decrease following tracheotomy in this patient population. METHODS: In this cross-sectional study, we conducted a retrospective chart review to identify patients with COVID-19 who underwent tracheotomy (T) at an academic medical center between March 2020 and January 2021. We used a paired Student t-test to compare total oral morphine equivalents (OMEs), total lorazepam equivalents, 24-hour average dexmedetomidine dosage in µg/kg/hour, and 24-hour average propofol dosage in µg/kg/minute on days T-1 and T+2 for each patient. RESULTS: Of 50 patients, 46 required opioids before and after tracheotomy (mean decrease of 49.4 mg OMEs). Eight patients required benzodiazepine infusion (mean decrease of 45.1 mg lorazepam equivalents. Fifteen patients required dexmedetomidine infusion (mean decrease 0.34 µg/kg/hour). Seventeen patients required propofol (mean decrease 20.5 µg/kg/minute). CONCLUSIONS: When appropriate personal protective equipment is available, use of tracheotomy in patients with COVID-19 who require MV may help to conserve medication supplies in times of extreme shortages.

Telemedicine Implementation in Pain Medicine: A Survey Evaluation of Pain Medicine Practices in Spring 2020.

BACKGROUND: The COVID-19 pandemic resulted in a novel challenge for healthcare delivery and implementation in the United States (US) in 2020 and beyond. Telemedicine arose as a significant and effective medium for safe and efficacious physician-patient interactions. Prior to the COVID-19 pandemic, telemedicine while available, had infrequently been utilized in pain medicine practices due to difficulties with reimbursement, the learning curve associated with new technology usage, and the need for new logistical systems in place to implement telemedicine effectively. Given the unique constraints on the healthcare system during the COVID-19 pandemic, the ubiquitous utilization of telemedicine among pain medicine physicians increased, giving insight into potential future roles for the technology beyond the pandemic. OBJECTIVES: To survey and understand the state of implementation of telemedicine into pain medicine practices across practice settings and geographical areas; to identify potential barriers to the implementation of telemedicine in pain medicine practice; and to identify the likelihood of telemedicine continuing beyond the pandemic in pain medicine practice. STUDY DESIGN: Online questionnaire targeting Pain Medicine physicians in the US. Participants were asked questions related to the use of telemedicine during the first peak of the COVID-19 pandemic. SETTING: Online-based questionnaire distributed to academic and private practice pain medicine physicians nationally in the United States. METHODS: A 34 web-based questionnaires were distributed by the American Society of Regional Anesthesia and Pain Medicine and the Society of Interventional Spine to all active members. Data were analyzed using SAS v9.4. RESULTS: Between December 3, 2020, and February 18, 2021, 164 participants accessed the survey with a response rate of 14.3%. Overall, academic physicians were more likely to implement telemedicine than private practice physicians. Telemedicine was also more frequently utilized for follow-up appointments rather than initial visits. LIMITATIONS: Although our n = 164, the overall low response rate of 14.3% warrants further investigation into the utilization of telemedicine throughout the COVID-19 pandemic. CONCLUSIONS: Telemedicine as an emerging technology for efficient communication played a key role in mitigating the adverse effects of the COVID -19 pandemic on chronic pain patients. The utilization of telemedicine remarkably increased after the start of the pandemic within 1 to 2 weeks. Overall, private hospital-based centers were significantly less likely to implement telemedicine than academic centers, possibly due to limited access to secure telemedicine platforms and high start-up costs. Telemedicine was used more frequently for follow-up visits than initial visit encounters at most centers. In spite of the unforeseen consequences to the healthcare system and chronic pain practices in the US from COVID-19, telehealth has emerged as a unique model of care for patients with chronic pain. Although it has flaws, telehealth has the ability to increase access to care beyond the end of the pandemic. Further identification of barriers to the use of telemedicine platforms in private practices should be addressed from a policy perspective to facilitate increased care access.

Application of network composite module analysis and verification to explore the bidirectional immunomodulatory effect of Zukamu granules on Th1 / Th2 cytokines in lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Zukamu granules (ZKMG), as the preferred drug for the treatment of colds in Uygur medical theory, has been used for 1500 years. It is also widely used in China and included in the National Essential Drugs List (2018 edition). It has unique anti-inflammatory, antitussive and analgesic effects. AIM OF THE STUDY: Aiming at the research of traditional Chinese medicine (TCM) with the characteristics of overall regulation of body diseases and the immune regulation mechanism with the concept of integrity, this paper put forward the integrated application of network composite module analysis and animal experiment verification to study the immune regulation mechanism of TCM. MATERIALS AND METHODS: The active components and targets of ZKMG were predicted, and network module analysis was performed to explore their potential immunomodulatory mechanisms. Then acute lung injury (ALI) mice and idiopathic pulmonary fibrosis (IPF) rats were used as pathological models to observe the effects of ZKMG on the pathological conditions of infected ALI and IPF rats, determine the contents of Th1, Th2 characteristic cytokines and immunoglobulins, and study the intervention of GATA3/STAT6 signal pathway. RESULTS: The results of network composite module analysis showed that ZKMG contained 173 pharmacodynamic components and 249 potential targets, and four key modules were obtained. The immunomodulatory effects of ZKMG were related to T cell receptor signaling pathway. The validation results of bioeffects that ZKMG could carry out bidirectional immune regulation on Th1/Th2 cytokines in the stage of ALI and IPF, so as to play the role of regulating immune homeostasis and organ protection. CONCLUSIONS: The network composite module analysis and verification method is an exploration to study the immune regulation mechanism of TCM by combining the network module prediction analysis with animal experiments, which provides a reference for subsequent research.

GABAA receptors as targets for anaesthetics and analgesics and promising candidates to help treat coronavirus infections: A mini-review.

GABA is a major inhibitory neurotransmitter that regulates the balance between excitatory and inhibitory circuits in the human nervous system. The GABA receptors are divided into three main subtypes, GABAA , GABAB , and GABAC (also termed GABAA rho) receptors. GABAA receptors are pentameric ligand-gated ion channels widely expressed throughout the central and peripheral nervous system. The activation of GABAA receptors results in opening of an anion-selective channel that mainly gates chloride ions and allows them to flow into the neuron, causing hyperpolarization of the cell membrane that dampens neural excitability. This makes GABAA receptors critical anaesthetic and analgesic targets for existing as well as for the development of novel drugs. In this review, we first summarize the biochemical properties of GABAA receptors and the clinical anaesthetics and analgesics targeting the receptors. In a forward-looking section, we summarize the emerging role of GABAergic signalling in treatment of COVID-19 related infections. Finally, we discuss the opportunities arising from targeting specific and unique subunit interfaces for the development of novel anaesthetics and analgesics leading to more efficient therapies.

An Interprofessional Approach to Mobilizing Patients With COVID-19 Receiving Extracorporeal Membrane Oxygenation.

OBJECTIVE: To assess survival outcomes with the intervention of an interprofessional mobilization program for patients with COVID-19 who were receiving venovenous extracorporeal membrane oxygenation (VV-ECMO). DESIGN: Preintervention and postintervention retrospective cohort study. METHODS: Survival outcomes of nonmobilized, adult patients (n = 16) with COVID-19 who were receiving VV-ECMO (May 2020 through December 2020) were compared with those of 26 patients who received a mobility care plan (January 2021 through November 2021). In the preintervention group, full sedation and paralysis were used. In the postintervention group, an early mobilization strategy involving interprofessional collaboration was introduced. RESULTS: The postintervention group had improved survival (73.1% vs 43.8%; P < .04); fewer days of receiving paralytics, fentanyl, and midazolam (P < .01 for all); but more days of dexmedetomidine, morphine, and ketamine administration (P < .01 for all). Concomitantly, more patients in the postintervention cohort received oral or transdermal analgesics, oral anxiolytics, and oral antipsychotics (P < .01 for all), and also required more VV-ECMO cannula adjustments (P = .03). CONCLUSION: Early mobilization of patients with COVID-19 who were receiving VV-ECMO improved survival rates but led to more cannula adjustments.

In the Swim of Cannabis: Developmental Toxicity and Metabolomic Pathway Alterations of Zebrafish Larvae Exposed to THC for the Assessment of Its Potential Environmental and Human Health Impact.

As the pharmacological properties and therapeutic applications of Cannabis sativa L. pace with the upsurge of interest of the scientific community in harnessing its constituent phytocannabinoids, illicit use may raise serious health issues. Tetrahydrocannabinol (THC) is one of the most well-known phytoactive constituents of cannabis and continues to garner scientific and public attention not only because of its pharmacological value but also because over-the-counter products of THC and prescription medications are becoming increasingly available from pharmacies, dispensaries, Internet, local retail stores, or by illicit means. Hence, a multidimensional approach was employed to examine the impact of THC on zebrafish larvae. The acute toxicity, expressed as LC50, was 1.54 mg/L. Adverse effects were observed on the phenotype, such as tail bending, pericardial edema, etc., even at concentrations lower than LC50, and fundamental functions of larvae (e.g., heart rate and cardiac contractility, and rhythm) were significantly affected. Behavioral changes were noticed, which were reflected in locomotor activity and sensitivity to light/dark changes. Finally, an untargeted metabolomic study was carried out to shed light on the metabolic alterations that occurred, providing substantiating evidence of the observed phenotype alterations. Overall, the potentially detrimental effects of THC on a vertebrate model are depicted.

Effective Dose of Prophylactic Oxytocin Infusion During Cesarean Delivery in 90% Population of Nonlaboring Patients With Preeclampsia Receiving Magnesium Sulfate Therapy and Normotensives: An Up-Down Sequential Allocation Dose-Response Study.

BACKGROUND: Oxytocin administration during cesarean delivery is the first-line therapy for the prevention of uterine atony. Patients with preeclampsia may receive magnesium sulfate, a drug with known tocolytic effects, for seizure prophylaxis. However, no study has evaluated the minimum effective dose of oxytocin during cesarean delivery in women with preeclampsia. METHODS: This study compared the effective dose in 90% population (ED90) of oxytocin infusion for achieving satisfactory uterine tone during cesarean delivery in nonlaboring patients with preeclampsia who were receiving magnesium sulfate treatment with a control group of normotensives who were not receiving magnesium sulfate. This prospective dual-arm dose-finding study was based on a 9:1 biased sequential allocation design. Oxytocin infusion was initiated at 13 IU/h, on clamping of the umbilical cord, in the first patient of each group. Uterine tone was graded as satisfactory or unsatisfactory by the obstetrician at 4 minutes after initiation of oxytocin infusion. The dose of oxytocin infusion for subsequent patients was decided according to the response exhibited by the previous patient in the group; it was increased by 2 IU/h after unsatisfactory response or decreased by 2 IU/h or maintained at the same level after satisfactory response, in a ratio of 1:9. Oxytocin-associated side effects were also evaluated. Dose-response data for the groups were evaluated using a log-logistic function and ED90 estimates were derived from fitted equations using the delta method. RESULTS: The ED90 of oxytocin was significantly greater for the preeclampsia group (n = 27) than for the normotensive group (n = 40) (24.9 IU/h [95% confidence interval {CI}, 22.4-27.5] and 13.9 IU/h [95% CI, 12.4-15.5], respectively); the difference in dose requirement was 10.9 IU/h (95% CI, 7.9-14.0; P < .001). The number of patients with oxytocin-related hypotension, defined as a decrease in systolic blood pressure >20% from baseline or to <90 mm Hg, was significantly greater in the preeclampsia group (92.6% vs 62.5%; P = .030), while other side effects such as ST-T depression, nausea/vomiting, headache, and flushing, were not significantly different. There was no significant difference in the need for additional uterotonic or uterine massage, estimated blood loss, and need for re-exploration for uncontrolled bleeding. CONCLUSIONS: Patients with preeclampsia receiving preoperative magnesium therapy need a greater intraoperative dose of oxytocin to achieve satisfactory contraction of the uterus after fetal delivery, as compared to normotensives.

Trauma pain management in the emergency department: use of methoxyflurane as a patient-administered analgesic.

Evidence suggests that pain is highly prevalent among patients with traumatic injuries who attend emergency departments (EDs), yet accurate assessment and management of patients with acute pain can be challenging in this setting. Effective and rapid pain management is beneficial for patients and can support timely discharge from the ED, which is particularly important in the context of the coronavirus disease 2019 (COVID-19) pandemic. This article describes a service development project that introduced the use of a patient-administered analgesic, methoxyflurane, for patients with traumatic injuries with moderate to severe pain in one ED. The author outlines the benefits and rationale for using methoxyflurane as a first-line analgesic in this patient group and describes the main elements of training sessions for emergency nurses and other ED clinicians in the administration and supervision of patient-administered methoxyflurane.

Synthesis of Sugar and Nucleoside Analogs and Evaluation of Their Anticancer and Analgesic Potentials.

Chemical modification of sugars and nucleosides has a long history of producing compounds with improved selectivity and efficacy. In this study, several modified sugars (2-3) and ribonucleoside analogs (4-8) have been synthesized from α-d-glucose in a total of 21 steps. The compounds were tested for peripheral anti-nociceptive characteristics in the acetic acid-induced writhing assay in mice, where compounds 2, 7, and 8 showed a significant reduction in the number of writhes by 56%, 62%, and 63%, respectively. The compounds were also tested for their cytotoxic potential against human HeLa cell line via trypan blue dye exclusion test followed by cell counting kit-8 (CCK-8) assay. Compound 6 demonstrated significant cytotoxic activity with an IC50 value of 54 µg/mL. Molecular docking simulations revealed that compounds 2, 7, and 8 had a comparable binding affinity to cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. Additionally, the bridged nucleoside analogs 7 and 8 potently inhibited adenosine kinase enzyme as well, which indicates an alternate mechanistic pathway behind their anti-nociceptive action. Cytotoxic compound 6 demonstrated strong docking with cancer drug targets human cytidine deaminase, proto-oncogene tyrosine-protein kinase Src, human thymidine kinase 1, human thymidylate synthase, and human adenosine deaminase 2. This is the first ever reporting of the synthesis and analgesic property of compound 8 and the cytotoxic potential of compound 6.