Pharmacological management of secondary chronic spinal cord injury: a systematic review.

INTRODUCTION: Spinal cord injury (SCI) may bring lifelong consequences for affected patients and a high financial burden to the health care system. SOURCE OF DATA: Published peer-reviewed scientific articles identified from EMBASE, Google Scholar, PubMed and Scopus. AREAS OF AGREEMENT: Surgery and blood pressure management are the main targets in acute SCI to avoid secondary damage. AREAS OF CONTROVERSY: The management of secondary chronic SCI is challenging, with unpredictable outcomes. GROWING POINTS: Given the lack of consensus on pharmacological therapy for acute and secondary chronic SCI, the present study analyses the currently available drugs and treatment options to manage secondary chronic SCI. AREAS TIMELY FOR DEVELOPING RESEARCH: Different approaches exist for the pharmacological management of secondary chronic SCI. One of the most investigated drugs, 4-aminopyridine, improves central motor conduction and shows improvement in neurological signs. Positive results in different areas have been observed in patients receiving the anti-spastic drugs tizanidine and baclofen or Granulocyte colony-stimulating factor. Growth hormone showed only minimal or no significant effects, and the therapy of secondary chronic SCI with riluzole has been poorly researched to date.

Efficacy of Clonidine Adhesive Patch for Patients With Tourette Syndrome: A Randomized, Double-blind, Placebo-Controlled, Multicenter Clinical Trial.

OBJECTIVE: This study aimed to explore the efficacy of the clonidine adhesive patch for participants with Tourette syndrome (TS). METHODS: This randomized, double-blind, placebo-controlled, multicenter phase IV clinical trial included participants with TS at 20 centers between May 2012 and March 2015. Treatment efficacy at week 8 was the primary outcome. The Clinical Global Impression-Severity scale and Improvement scale were the secondary endpoints. RESULTS: This trial included 488 participants, with 121 participants in the 2.0-mg/wk group, 119 participants in the 1.5-mg/wk group, 126 participants in the 1.0-mg/wk group, and 122 participants in the placebo group. For Yale Global Tic Severity Scale score reduction rate, compared with the placebo group (39.60 ± 25.56), those of the 2.0-mg/wk group (63.21 ± 32.60) and the 1.5-mg/wk group (68.16 ± 25.88) were statistically significantly different (all P < 0.001). For total Yale Global Tic Severity Scale score, compared with the placebo group (17.0 ± 8.03), the score for the 2.0-mg/wk group was 9.9 ± 8.36 ( P < 0.001); 1.5-mg/wk group, 9.6 ± 8.03 ( P < 0.001); and 1.0-mg/wk group, 10.5 ± 9.28 ( P < 0.001). The Clinical Global Impression-Severity scale and Improvement scale scores were statistically significantly different in the 3 clonidine (or experimental) groups compared with the placebo group (all P < 0.001). CONCLUSIONS: Larger doses of the clonidine adhesive patch such as 1.5 and 2.0 mg/wk are effective in improving the symptoms and overall function of participants with TS.

Involvement of posterior hypothalamic CaMKII-positive neurons in ADHD-like behaviors in mice.

This study explores the behavioral effects of modulating CaMKII-positive (CaMKII+) neurons in the posterior hypothalamus (PH). Utilizing a chemogenetic approach in mice, we discovered that the activation of CaMKII + neurons within the PH is associated with heightened locomotor activity, reduced social interaction, and impulsive behavior unrelated to anxiety or avoidance. These observed behaviors share a significant resemblance with characteristics commonly found in attention deficit and hyperactivity disorder (ADHD). Notably, treatment with clonidine, which is frequently prescribed for ADHD, effectively reduced impulsive behaviors in our mouse model. Our findings uncover the role of the PH that has not been previously explored and suggest a possible involvement of the PH in the manifestation of ADHD-like behaviors.

Physicochemical and Microbiological Stability of Compounded Clonidine Hydrochloride Oral Liquid Dosage Forms in PCCA Base, SuspendIt®.

Clonidine Hydrochloride is a centrally acting alpha-agonist hypotensive agent available as tablets for oral administration in three dosage strengths: 0.1 mg, 0.2 mg and 0.3 mg. A review of the therapeutic uses of clonidine hydrochloride reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of clonidine hydrochloride currently exists. An extemporaneously compounded suspension from pure drug powder would provide a flexible, customizable option to meet unique patient needs with convenient and accurate dosing options. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded clonidine hydrochloride suspensions in the PCCA Base, SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two clonidine hydrochloride concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating high-performance liquid chromatographic assay for the determination of the chemical stability of clonidine hydrochloride in PCCA SuspendIt was developed and validated. Suspensions of clonidine hydrochloride were prepared in PCCA SuspendIt at 20-mcg/mL and 100-mcg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Given the potent nature of the drug, a 2% triturate of clonidine hydrochloride in microcrystalline cellulose was used to prepare the samples. Samples were stored in amber plastic prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially, and on the following time points (days): 7, 14, 28, 42, 63, 91, 119 and 182. Physical data such as pH, viscosity and appearance were also noted. Microbiological stability was tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. Using this criterion, no significant degradation of the clonidine hydrochloride was observed over the 182-day test period for either concentration under refrigerated conditions. Drug concentrations were at, or above 94.6% of initial values. However, at room temperature the concentration of the 20-mcg/mL samples dropped below 90% after 119 days. No microbial growth was observed. pH values remained fairly constant. The viscosity of the suspensions allowed easy re-dispersal of the drug particles upon shaking. This study demonstrates that clonidine hydrochloride is physically, chemically, and microbiologically stable in PCCA SuspendIt for 182 days in the refrigerator and for 119 days at room temperature at both concentrations studied, thus providing a viable, compounded alternative for clonidine hydrochloride in a liquid dosage form, with an extended BUD to meet patient needs.

The analgetic effect of adjuvants in local infiltration analgesia - a systematic review with network meta-analysis of randomized trials.

BACKGROUND: Local infiltration analgesia is commonly used for postoperative pain control after several surgical procedures including intra- and peri-articular as well as wound infiltration. Even though, various adjuvants injected with the local anesthetic have been studied in pairwise comparison or compared to peripheral nerve blocks, the question which adjuvant or combination of adjuvants is the most effective in prolonging the duration of different types of local infiltration analgesia (LIA) has not been answered conclusively. OBJECTIVE: The objective of this network meta-analysis was to determine the analgesic effectiveness and safety of adjuvants in local infiltration analgesia. DESIGN: Systematic review of randomized controlled trials with network meta-analyses. DATA SOURCES: A comprehensive literature search in Embase, CENTRAL, MEDLINE and Web of Science was performed up to March 2023. RESULTS: The best interventions to prolong the duration of analgesia were dexamethasone (Ratio of Means (ROM) 3.33) followed by the combinations of clonidine + morphine (ROM 3.35) and morphine + magnesium sulfate (ROM 2.92), fentanyl (ROM 2.27), ketorolac (ROM 2.26), buprenorphine (ROM 2.04), morphine (ROM 1.93), magnesium sulfate (ROM 1.91), clonidine (ROM 1.89), dexmedetomidine (ROM 1.74) and tramadol (ROM 1.58). Serious adverse events were not reported with either investigated adjuvant. CONCLUSION: There is moderate evidence that dexamethasone is the most effective adjuvant to prolong the duration of analgesia in LIA. The evidence for the alpha-2 agonists dexmedetomidine and clonidine is also moderate, but their effectivity to prolong analgesia stays behind dexamethasone. Clonidine and dexmedetomidine had a small detectable effect on pain scores, yet below clinical relevance, but the largest effect on MEQ consumption. The effects of different opioids were homogenous for all endpoints. The prespecified subgroup analysis of LIA of the knee did not show significantly different results than the pooled analysis. STUDY REGISTRATION: PROSPERO 2020 CRD42020176154 (28.04.2020).

Development of RP-HPLC Method of Tizanidine HCL with Some Validation Parameter.

This study compiles the information for the development of analytical methods for estimation of the Tizanidine HCl that will be helpful for further research work on this drug and its impurity. The present Literature survey provides information about the Analytical methods like UV,TLC,RP-HPLC,HPTLC,UHPLC and other methods have been reported for Tizanidine HCl drug individually and along with other drugs. The analysis of published data revealed that, there was only UV spectroscopic method (calibration curve metod) is reported for estimation of Tizanidine HCl fixed dose combination. Estimation of Tizanidine HCl by superlative RP-HPLC method i.e. Mobile phase- Acetonitrile: phosphate buffer (pH: 7.5) (50:50%v/v), Column C18 (250mm*4mm*5µm), Flow rate- 1.0 ml/min, Wavelength: 318 nm. Optimized HPLC condition was validated by assessing validation parameters and it meet the acceptance criteria set by ICH. It was showed method was linear and precise. The validated RP-HPLC-PDA method can be used for routine analysis of Tizanidine HCl in tablet.

Effects of Thymbra spicata extract and Thymol on morphine withdrawal syndrome in mice (insights to the liver function, antioxidant, and behavioral responses).

Safe chemicals for drug withdrawal can be extracted from natural sources. This study investigates the effects of clonidine and Thymbra spicata extract (TSE) on mice suffering from morphine withdrawal syndrome. Thymol, which is the active constituent in TSE, was also tested. A total of 90 mice were divided into nine groups. Group 1 was the control group, while Group 2 was given only morphine, and Group 3 received morphine and 0.2 mg/kg of clonidine. Groups 4-6 were given morphine along with 100, 200, and 300 mg/kg of TSE, respectively. Groups 7-9 received morphine plus 30, 60, and 90 mg/kg of Thymol, respectively, for 7 days. An oral naloxone challenge of 3 mg/kg was used to induce withdrawal syndrome in all groups. Improvement of liver enzyme levels (aspartate aminotransferase, alkaline phosphatase, and alanine transaminase) (p < .01) and behavioral responses (frequencies of jumping, frequencies of two-legged standing, Straub tail reaction) (p < .01) were significantly observed in the groups receiving TSE and Thymol (Groups 4-9) compared to Group 2. Additionally, antioxidant activity in these groups was improved compared to Group 2. Nitric oxide significantly decreased in Groups 4 and 6 compared to Groups 2 and 3 (p < .01). Superoxide dismutase increased dramatically in Groups 5, 8, and 9 compared to Groups 2 and 3 (p < .01). Groups 5-9 were significantly different from Group 2 in terms of malondialdehyde levels (p < .01). Certain doses of TSE and Thymol were found to alleviate the narcotics withdrawal symptoms. This similar effect to clonidine can pave the way for their administration in humans.

Effectiveness of pharmacological interventions for managing ADHD symptoms in individuals with autism spectrum disorder: A systematic review and meta-analysis.

OBJECTIVES: This systematic review sought to provide evidence for the effectiveness of common pharmacological interventions used for treating attention deficit hyperactivity disorder (ADHD) symptoms in the autism spectrum disorder (ASD) population, considering studies attempting to find safe and effective drugs. METHODS: We searched for randomized controlled trials describing the effectiveness and/or safety profile of pharmacological interventions for treating ASD and ADHD or ASD with ADHD symptoms using three bibliographic databases: PubMed, Cochrane Library, and Embase. We have chosen ADHD symptoms measured by any clinical scale as the primary outcome. As additional outcomes, we have used other symptoms of aberrant behavior measured by the aberrant behavior checklist, satisfaction with treatment, and peer satisfaction. RESULTS: Twenty-two publications met the inclusion criteria for the systematic review and eight for the meta-analysis. In our investigation, we found a few articles using clonidine, modafinil, and bupropion as interventions when compared to methylphenidate (MPH). Our meta-analysis showed that MPH had positive changes compared to placebo in symptoms such as hyperactivity, irritability, or inattention. However, no effect was found in stereotyped symptoms, and our data's quantitative analysis revealed a large effect of MPH-induced adverse effects on the dropout rate. On the other hand, atomoxetine initiation had positive effects when compared to placebo on symptoms of hyperactivity and inattention. We have found no effect of atomoxetine on stereotypes or irritability. Furthermore, atomoxetine did not influence side effects that caused dropouts from studies. CONCLUSION: Our results indicated that atomoxetine has a modest effect on hyperactivity and inattention symptoms, with a relatively benign profile of side effects. MPH appears to be effective in handling hyperactivity, inattention, and irritability symptoms. However, our results on atomoxetine revealed increased dropouts due to adverse effects when compared to MPH or placebo. Evidence for other substances such as guanfacine, clonidine, bupropion, or modafinil is either preliminary or nonexistent.

Oral Clonidine-Based Strategy to Reduce Opiate Use During Cooling for Neonatal Encephalopathy: An Observational Study.

OBJECTIVE: To determine whether an enteral, clonidine-based sedation strategy (CLON) during therapeutic hypothermia (TH) for hypoxic-ischemic encephalopathy would decrease opiate use while maintaining similar short-term safety and efficacy profiles to a morphine-based strategy (MOR). STUDY DESIGN: This was a single-center, observational study conducted at a level IV neonatal intensive care unit from January 1, 2017, to October 1, 2021. From April 13, 2020, to August 13, 2020, we transitioned from MOR to CLON. Thus, patients receiving TH for hypoxic-ischemic encephalopathy were grouped to MOR (before April 13, 2020) and CLON (after August 13, 2020). We calculated the total and rescue morphine milligram equivalent/kg (primary outcome) and frequency of hemodynamic changes (secondary outcome) for both groups. RESULTS: The MOR and CLON groups (74 and 25 neonates, respectively) had similar baseline characteristics and need for rescue sedative intravenous infusion (21.6% MOR and 20% CLON). Both morphine milligram equivalent/kg and need for rescue opiates (combined bolus and infusions) were greater in MOR than CLON (P < .001). As days in TH advanced, a lower percentage of patients receiving CLON needed rescue opiates (92% on day 1 to 68% on day 3). Patients receiving MOR received a greater cumulative dose of dopamine and more frequently required a second inotrope and hydrocortisone for hypotension. MOR had a lower respiratory rate during TH (P = .01 vs CLON). CONCLUSIONS: Our CLON protocol is noninferior to MOR, maintaining perceived effectiveness and hemodynamic safety, with an apparently reduced need for opiates and inotropes.

Clonidine for post-traumatic stress disorder: a systematic review of the current evidence.

Background: Clonidine is a centrally acting anti-adrenergic agent that may have applications in post-traumatic stress disorder (PTSD), particularly for sleep.Objective: In this systematic review, we aimed to summarize the effect of clonidine on sleep quality and duration, nightmares, and PTSD symptom severity in adults with PTSD.Method: PubMed (Medline), Embase, PsycINFO, CINAHL, and clinicaltrials.gov were searched up to April 2023. Studies on clonidine use in adult PTSD patients reporting data on the effect on sleep, nightmares, and PTSD symptoms were included. A narrative summary and a meta-analysis of the study findings are presented.Results: Ten reports, accounting for N = 569 patients with PTSD (145 on clonidine and 436 controls), were included in the final selection. There were four case reports, four observational studies, one non-blind clinical trial, and one crossover randomized controlled trial (RCT). Median clonidine dose was 0.15 mg/day (range: 0.1-0.5 mg/day). Median follow-up time was 31 days (range: 3 days to 19 months). The quality of the evidence was rated from very low to low. There was marked between-study heterogeneity and low power in the individual studies, but many reported improved sleep quality, nightmare reduction, and improvement of PTSD symptoms for patients treated with clonidine. Meta-analysis was only possible for two studies reporting the effect of clonidine on nightmares, and showed no difference from the comparator (i.e. prazosin or terazosin) (odds ratio: 1.16; 95% confidence interval: 0.66 to 2.05), potentially pointing towards non-inferiority between these medications.Conclusions: Future research, such as well-powered RCTs, is needed to identify the efficacy in the lower dose range and the most suitable treatment group, and to obtain good evidence on the effects of clonidine in the treatment of sleep disorders related to PTSD.

Post-traumatic stress disorder (PTSD) is associated with hyperarousal and sleep disorders, reflecting adrenergic nervous system involvement.The use of anti-adrenergic drugs to target the sympathetic activation in PTSD is rational. However, previous reports on prazosin, a peripherally acting agent, yielded weak evidence.Clonidine, a central adrenergic antagonist, shows promise in improving sleep, nightmares, and PTSD symptoms, but further research is needed because the quality of the current evidence is low.

A nano-level assay of tizanidine using the fluorogenic character of benzofurazan derivative: Application to plasma, tablets, and content homogeneity evaluation.

People frequently administer Tizanidine (TIZ) to treat spasticity resulting from diseases like multiple sclerosis or spinal cord injuries. It also helps prevent muscle spasms. It helps to relax and release tense and stiff muscles by inhibiting specific nerve signals in the brain and spinal cord. The technique employed in this study made use of the unique ability of benzofurazan to confer fluorescent character when reacted with TIZ at specific conditions. This fluorogenic property was harnessed to evolve a remarkably sensitive, affordable, and selective method to quantify TIZ. The resulting yellow fluorescent product was observedat a wavelength beam of 532.9 nm, and an excitation wavelength beam of 474.9 nm was applied. By looking at the response across the TIZ concentration, the calibration chart's linearity was assessed in the range of 40-500 ng/mL. By computation, the approach's detection level (LOD) was determined to be 11.9 ng/mL, while the quantitation level was approximated to be 36 ng/mL. All pertinent factors impacting the strategy's efficacy were thoroughly inspected and adjusted accordingly. The proposed strategy was validated following the guidelines outlined by the ICH. The outcomes confirmed the method's capability for the accurate quantifying of TIZ in tablets, spiked plasma, and pharmaceutical assessing content uniformity.

Recommended dosages of analgesic and sedative drugs in intensive care result in a low incidence of potentially toxic blood concentrations.

Background: Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses need to be better examined. The purpose of this study was to describe daily dosages, measured blood concentrations, and clinical responses in critically ill patients. The purpose was also to contribute to establishing whole blood concentration reference values of the drugs investigated. Methods: A descriptive study of prospectively collected data from 302 admissions to a general intensive care unit (ICU) at a university hospital. Ten drugs (clonidine, fentanyl, morphine, dexmedetomidine, ketamine, ketobemidone, midazolam, paracetamol, propofol, and thiopental) were investigated, and daily dosages recorded. Blood samples were collected twice daily, and drug concentrations were measured. Clinical responses were registered using Richmond agitation-sedation scale (RASS) and Numeric rating scale (NRS). Results: Drug dosages were within recommended dose ranges. Blood concentrations for all 10 drugs showed a wide variation within the cohort, but only 3% were above therapeutic interval where clonidine (57 of 122) and midazolam (38 of 122) dominated. RASS and NRS were not correlated to drug concentrations. Conclusion: Using recommended dose intervals for analgesic and sedative drugs in the ICU setting combined with regular monitoring of clinical responses such as RASS and NRS leads to 97% of concentrations being below the upper limit in the therapeutic interval. This study contributes to whole blood drug concentration reference values regarding these 10 drugs.

The alpha2-adrenergic receptor agonist clonidine protects against cerebral ischemia/reperfusion induced neuronal apoptosis in rats.

Apoptosis is the crucial pathological mechanism following cerebral ischemic injury. Our previous studies demonstrated that clonidine, one agonist of alpha2-adrenergic receptor (α2-AR), could attenuate cerebral ischemic injury in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). However, it's unclear whether clonidine exerts neuroprotective effects by regulating neuronal apoptosis. In this study, we elucidated whether clonidine can exert anti-apoptotic effects in cerebral ischemic injury, and further explored the possible mechanisms. Neurological deficit score was measured to evaluate the neurological function. TTC staining was used for the measurement of brain infarct size. Hematoxylin-Eosin (HE) staining was applied to examine the cell morphology. TUNEL and DAPI fluorescent staining methods were used to analyze the cell apoptosis in brain tissue. Fluorescence quantitative real-time PCR was performed to assess the gene expression of Caspase-3 and P53. Western blotting assay was applied to detect the protein expression of Caspase-3 and P53. The results showed that clonidine improved neurological function, reduced brain infarct size, alleviated neuronal damage, and reduced the ratio of cell apoptosis in the brain with MCAO/R injury. moreover, clonidine down-regulated the gene and protein expression of Caspase-3 and P53 which were over-expressed after MCAO/R injury. Whereas, yohimbine (one selective α2-AR antagonist) mitigated the anti-apoptosis effects of clonidine, accompanied by reversed gene and protein expression changes. The results indicated that clonidine attenuated cerebral MCAO/R injury via suppressing neuronal apoptosis, which may be mediated, at least in part, by activating α2-AR.

Dual-step pharmacological intervention for traumatic-like memories: implications from D-cycloserine and cannabidiol or clonidine in male and female rats.

RATIONALE: Therapeutic approaches to mitigating traumatic memories have often faced resistance. Exploring safe reconsolidation blockers, drugs capable of reducing the emotional valence of the memory upon brief retrieval and reactivation, emerges as a promising pharmacological strategy. Towards this objective, preclinical investigations should focus on aversive memories resulting in maladaptive outcomes and consider sex-related differences to enhance their translatability. OBJECTIVES: After selecting a relatively high training magnitude leading to the formation of a more intense and generalized fear memory in adult female and male rats, we investigated whether two clinically approved drugs disrupting its reconsolidation remain effective. RESULTS: We found resistant reconsolidation impairment by the α2-adrenergic receptor agonist clonidine or cannabidiol, a major non-psychotomimetic Cannabis sativa component. However, pre-retrieval administration of D-cycloserine, a partial agonist at the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor complex, facilitated their impairing effects on reconsolidation. A similar reconsolidation blockade by clonidine or cannabidiol was achieved following exposure to a non-conditioned but generalized context after D-cycloserine administration. This suggests that sufficient memory destabilization can accompany generalized fear expression. Combining clonidine with cannabidiol without potentiating memory destabilization by D-cycloserine was ineffective. CONCLUSIONS: These findings highlight the importance of NMDA receptor signaling in memory destabilization and underscore the efficacy of a dual-step pharmacological intervention in attenuating traumatic-like memories, even in a context different from the original learning environment.

A Comparative Study of the Antiemetic Effects of α2-Adrenergic Receptor Agonists Clonidine and Dexmedetomidine against Diverse Emetogens in the Least Shrew (Cryptotis parva) Model of Emesis.

In contrast to cats and dogs, here we report that the α2-adrenergic receptor antagonist yohimbine is emetic and corresponding agonists clonidine and dexmedetomidine behave as antiemetics in the least shrew model of vomiting. Yohimbine (0, 0.5, 0.75, 1, 1.5, 2, and 3 mg/kg, i.p.) caused vomiting in shrews in a bell-shaped and dose-dependent manner, with a maximum frequency (0.85 ± 0.22) at 1 mg/kg, which was accompanied by a key central contribution as indicated by increased expression of c-fos, serotonin and substance P release in the shrew brainstem emetic nuclei. Our comparative study in shrews demonstrates that clonidine (0, 0.1, 1, 5, and 10 mg/kg, i.p.) and dexmedetomidine (0, 0.01, 0.05, and 0.1 mg/kg, i.p.) not only suppress yohimbine (1 mg/kg, i.p.)-evoked vomiting in a dose-dependent manner, but also display broad-spectrum antiemetic effects against diverse well-known emetogens, including 2-Methyl-5-HT, GR73632, McN-A-343, quinpirole, FPL64176, SR141716A, thapsigargin, rolipram, and ZD7288. The antiemetic inhibitory ID50 values of dexmedetomidine against the evoked emetogens are much lower than those of clonidine. At its antiemetic doses, clonidine decreased shrews' locomotor activity parameters (distance moved and rearing), whereas dexmedetomidine did not do so. The results suggest that dexmedetomidine represents a better candidate for antiemetic potential with advantages over clonidine.

Evaluation of medications used for opioid use disorder in emergency departments: A cross-sectional analysis of the 2020 National Hospital Ambulatory Medical Care Survey.

INTRODUCTION: Opioid use disorder (OUD) is a significant health issue impacting millions in the United States (US). Medications used for OUD (MOUD) (e.g., buprenorphine, methadone, naltrexone) and medications for overdose and symptom management (e.g., naloxone, clonidine) have been shown to be safe and effective tools in clinical management. MOUD therapy in Emergency Departments (EDs) improves patient outcomes and enhances engagement with formal addiction treatment; however, provider factors and institutional barriers have created hurdles to ED-based MOUD treatment and heterogeneity in ED based OUD care. We used a nationally representative dataset, the National Hospital Ambulatory Medical Care Survey (NHAMCS) to characterize MOUD prescribing practices across patient demographics, geographic regions, payers, providers, and comorbidities in EDs. METHODS: NHAMCS is a survey conducted by the US Census Bureau assessing utilization of ambulatory healthcare services nationally. Survey staff compile encounter records from a nationally representative sample of EDs. We conducted a cross-sectional study using this data to assess visits in 2020 among patients aged 18-64 presenting with an opioid overdose or OUD. We estimated the proportion of patients who had any MOUD, clonidine, or naloxone treatment and 95% confidence intervals (CI). We modeled the association between patient demographic, location, comorbidities, and provider characteristics with receipt of MOUD treatment as unadjusted odds ratios (OR) and 95% CI. RESULTS: There was a weighted frequency of 469,434 patients who were discharged from EDs after being seen for OUD or overdose. Naloxone, clonidine, and buprenorphine were the most frequent treatments administered and/or prescribed for OUDs or overdose. Overall, 54,123 (11.5%, 95%CI 0-128,977) patients who were discharged from the ED for OUDs or overdose received at least one type of MOUD. Hispanic race, (OR 17.9, 95%CI 1.33-241.90) and Western region (OR43.77, 95%CI 2.97-645.27) were associated with increased odds of receiving MOUDs, while arrival by ambulance was associated with decreased odds of receiving MOUDs (OR0.01, 95%CI 0.001-0.19). Being seen by an APP or physician assistant was associated with MOUD treatment (OR 16.68, 95%CI: 1.41-152.33; OR: 13.84, 95%CI: 3.58-53.51, respectively). CONCLUSION: Our study findings suggest that MOUD and other medications for opioid overdose are infrequently used in the ED setting. This finding was especially notable in race, geographic region, mode of arrival, and those seen by APP, underscoring the need for further study into the root causes of these disparities. Our study provides a foundational understanding of MOUD patterns, guiding future research as the landscape of OUD treatment continues to shift.

GH provocative tests stimulate the growth in children with idiopathic short stature.

CONTEXT: Growth hormone (GH) deficiency in a child with short stature is diagnosed by GH secretion provocative tests. When the test response is considered adequate, the short stature is considered idiopathic (ISS). OBJECTIVE: To determine the effect of GH provocative tests on the growth rate in children with idiopathic short stature. DESIGN: Children with short stature with a normal response to at least one GH provocative test were enrolled. Height and growth velocity were measured prior to and after stimulus tests during the follow-up. METHODS: Height, mid-parental height, body weight, and body mass index were measured. The height and growth rate were converted to percentiles and Standard Deviation Scores (SDS) using reference ranges standardized by age and sex. GH provocative tests employed arginine or clonidine as secretagogues. RESULTS: Fourty-six children of both genders were enrolled. In thirty-six children, height was measured at the time of testing and on an average time prior to and after the tests of 210 days and 180 days respectively. After testing the children displayed a 3.4-fold increase in their estimated 90-day growth rate. The median (inter-quartile range, IQR) 90 days growth of children pre-and post-tests were 0.7 (0.2-1.0) cm and 2.4 (1.7-3.1) cm respectively with a mean 3,4-fold increase (p < 0.0001). The median (IQR) 90 days growth of children pre- and post-tests calculated as standard deviation scores (SDS) were -4.0 (-5.4--2.1) SDS and 0.1 (-1.9-1.4) SDS respectively (p < 0.0001). Ten children with ISS were observed for about 5 months before the GH provocative tests. A small increase in the growth rate was seen only in 2 out of 10 children before testing while it increased in all of them after the tests. The difference in the median growth rate at the first and the second observation was not significant (p = 0.219). CONCLUSIONS: Two sequential somatotropic axis provocative tests increase the growth rate in children with idiopathic short stature. The duration of this effect is yet to be determined.

Comparison of diclofenac with tramadol, tizanidine or placebo in the treatment of acute low back pain and sciatica: multi-center randomized controlled trial.

BACKGROUND: Low back pain (LBP) is a leading cause of disability worldwide and has posed numerous health and socioeconomic challenges. This study compared whether nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with tramadol, tizanidine or placebo would be the best treatment regime to improve the Roland Morris Disability Questionnaire (RMDQ) scores at 1 week. METHODS: This was a multi-center, double-blind, randomized, and placebo-controlled trial including adult patients with acute LBP and sciatica in three emergency departments in Hong Kong. Patients were randomized to the receive tramadol 50 mg, tizanidine 2 mg, or placebo every 6 hours for 2 weeks in a 1:1:1 ratio. The RMDQ and other secondary outcomes were measured at baseline, Day 2, 7, 14, 21, and 28. Data were analyzed on an intention to treat basis. Crude and adjusted mean differences in the changes of RMDQ and NRS scores from baseline to Day 7 between tizanidine/tramadol and placebo were determined with 95% confidence intervals. RESULTS: Two hundred and ninety-one patients were analyzed with the mean age of 47.4 years and 57.7% were male. The primary outcome of mean difference in RMDQs on Day 7 (compared with baseline) was non-significant for tizanidine compared with placebo (adjusted mean difference - 0.56, 95% CI -2.48 to 1.37) and tramadol compared with placebo (adjusted mean difference - 0.85, 95% CI -2.80 to 1.10). Only 23.7% were fully compliant to the treatment allocated. Complier Average Causal Effect analysis also showed no difference in the primary outcome for the tizanidine and tramadol versus placebo. CONCLUSION: Among patients with acute LBP and sciatica presenting to the ED, adding tramadol or tizanidine to diclofenac did not improve functional recovery.

Novel RP-HPLC method for estimation of a newly developed combination of tizanidine and etoricoxib in rat plasma: Eight criteria for greens evaluation.

A novel environmentally friendly reversed-phase high-performance liquid chromatography (RP-HPLC) method has been effectively validated for simultaneously measuring a prospective conjunction of tizanidine (TIZ) and etoricoxib (ETC), the combined medicine, in rat plasma. The technique employs diclofenac potassium as the internal standard, guaranteeing dependable and precise outcomes. This study aimed to assess the impact of the suggested combination therapy on treating inflammation resulting from rheumatoid arthritis (RA) in a rat model. The procedure was performed using an Agilent series 1200 model HPLC apparatus. The chromatographic conditions consist of isocratic elution mode, C18 column with dimensions of 150 mm × 4.6 mm × 5 µm, flow rate of 1.5 mL/min, wavelength of 230 nm, temperature of 50°C, and injection volume of 10 µL. The elution was performed using a mobile phase consisting of a phosphate buffer with a pH of 3.5 and acetonitrile in a ratio of 80:20 v/v. Calibration curves were conducted for TIZ and ETC within the 1-50 µg/mL range, demonstrating linear trends with R2 values over 0.999. The effectiveness and eco-friendliness of the proposed method were evaluated using eight separate environmentally conscious metrics. The addition of TIZ and ETC to arthritic rodents amplified these effects significantly. Furthermore, TIZ and ETC significantly reduced serum levels in arthritic rodents, and safety investigations revealed normal complete blood count, liver, and renal functions. TIZ and ETC appear to have antiarthritic, anti-inflammatory, and safe combinations, making them viable future treatment options for RA that are also safe and efficacious. Following validation by United States Food and Drug Administration (US-FDA) rules, all goods met the criteria.

Intraoperative clonidine in endometriosis and spine surgery: A protocol for two randomised, blinded, placebo-controlled trials.

BACKGROUND: A high proportion of patients who undergo surgery continue to suffer from moderate to severe pain in the early postoperative period despite advances in pain management strategies. Previous studies suggest that clonidine, an alpha2 adrenergic agonist, administered during the perioperative period could reduce acute postoperative pain intensity and opioid consumption. However, these studies have several limitations related to study design and sample size and hence, further studies are needed. AIM: To investigate the effect of a single intravenous (IV) dose of intraoperative clonidine on postoperative opioid consumption, pain intensity, nausea, vomiting and sedation after endometriosis and spine surgery. METHODS: Two separate randomised, blinded, placebo-controlled trials are planned. Patients scheduled for endometriosis (CLONIPAIN) will be randomised to receive either 150 µg intraoperative IV clonidine or placebo (isotonic saline). Patients undergoing spine surgery (CLONISPINE) will receive 3 µg/kg intraoperative IV clonidine or placebo. We aim to include 120 patients in each trial to achieve power of 90% at an alpha level of 0.05. OUTCOMES: The primary outcome is opioid consumption within the first three postoperative hours. Secondary outcomes include pain intensity at rest and during coughing, nausea, vomiting and sedation within the first two postoperative hours and opioid consumption within the first six postoperative hours. Time to discharge from the PACU will be registered. CONCLUSION: This study is expected to provide valuable information on the efficacy of intraoperative clonidine in acute postoperative pain management in patients undergoing endometriosis and spine surgery.