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Cureus May 2024Introduction Pain after orthopedic surgeries represents a special concern in patients with fractures. The use of multimodal analgesia significantly reduced the opioid...
Introduction Pain after orthopedic surgeries represents a special concern in patients with fractures. The use of multimodal analgesia significantly reduced the opioid need and reduced the risk of their side effects. Objectives This study compared the effectiveness and safety of methocarbamol and nefopam in the reduction of post-operative pain for patients undergoing orthopedic surgeries. Method This prospective, double-blind, randomized controlled trial took place at Al-Sader Teaching Hospital in Basrah, Iraq, from the first of February 2022 to the end of October 2023. The study aimed to assess the post-operative pain relief efficacy and safety of intramuscular nefopam (20 mg) and intravenous methocarbamol (1 g) in 110 adults (aged 18-65) undergoing elective orthopedic surgeries. Exclusions were made for allergies to the drugs, substance abuse history, and severe hepatic or renal impairment. Participants were randomized into two groups, with pain intensity measured at one hour, six hours, and 12 hours post-operation using the visual analog scale (VAS). Side effects were also evaluated. Statistical analysis was done using SPSS 27, with a significance level set at p<0.05 and a 95% confidence interval (CI). Results In this study, we conducted a rigorous comparison between two groups, methocarbamol and nefopam, to evaluate their efficacy and safety in post-operative pain management. We started by ensuring that the groups were well-matched in terms of age, gender distribution, and body mass index (BMI). The results showed remarkable similarities in mean age, gender distribution, and BMI, supported by robust p-values, affirming the effective matching of the two groups. Moving to pain management, we observed a significant advantage in favor of methocarbamol. At all-time intervals (one hour, six hours, and 12 hours post-operation), methocarbamol consistently demonstrated lower mean VAS scores compared to nefopam. These differences were highly statistically significant, underscoring the superior pain relief efficacy of methocarbamol. Exploring side effects, we found no statistically significant disparities in the occurrence of nausea and vomiting between the two groups. However, there was a noticeable trend toward higher tachycardia incidence in the nefopam group, though it did not reach statistical significance. Conclusion The present study showed a higher efficacy of methocarbamol in post-operative pain reduction in comparison to nefopam. No serious side effects were observed with both drugs.
PubMed: 38707756
DOI: 10.7759/cureus.59533 -
Journal of Clinical and Experimental... 2022Muscle cramps are witnessed in 22-88% of patients with cirrhosis of liver and frequently lead to sleep disturbance with an appalling impact on quality of life. Despite... (Review)
Review
BACKGROUND
Muscle cramps are witnessed in 22-88% of patients with cirrhosis of liver and frequently lead to sleep disturbance with an appalling impact on quality of life. Despite such a high prevalence, there is lack of evidence-based management protocol due to scarcity of trials on treatment options in the literature. This study aimed to review systematically the available therapeutic options for muscle cramps in patients with cirrhosis of liver.
METHODS
A systematic review of the relevant databases (PubMed, Scopus, Embase, and Web of Science) to identify treatments for muscle cramps in patients with hepatic cirrhosis was performed. Studies meeting the selection criteria were reviewed and assessed for risk of bias and analyzed.
RESULTS
Twenty-four publications were identified as eligible for inclusion in this systematic review. Seven randomized controlled trials (RCTs) and 17 prospective studies were included. Taurine, methocarbamol, baclofen, and orphenadrine are relatively safer and effective treatment option for muscle cramps in cirrhosis on the basis of recently conducted RCTs. Moreover, l-carnitine, branched-chain amino acids (BCAAs), pregabalin, zinc, and vitamin D are also safe and showed beneficial effects on muscle cramps. However, studies on vitamin E revealed contradictory results.
CONCLUSION
Taurine, BCAAs, orphenadrine, and baclofen are safe and well-tolerated treatment options for muscle cramps in cirrhosis. However, well-designed randomized controlled clinical trials are the need of the hour to determine the most suitable treatment options for skeletal muscle cramps in patients with cirrhosis of liver.
PubMed: 35677500
DOI: 10.1016/j.jceh.2021.10.147 -
BMC Chemistry Dec 2022An isocratic RP-HPLC method has been developed for the separation and determination of methocarbamol (MTL), indomethacin (IND), and betamethasone (BET) in combined...
Application of Box-Behnken experimental design and response surface methodology for selecting the optimum RP-HPLC conditions for the simultaneous determination of methocarbamol, indomethacin and betamethasone in their pharmaceutical dosage form.
An isocratic RP-HPLC method has been developed for the separation and determination of methocarbamol (MTL), indomethacin (IND), and betamethasone (BET) in combined dosage form using an Inertsil ODS-3v C18 (250 × 4.6 mm, 5 μm) column with UV- detection at 235 nm. Experimental design using Box-Behnken design (BBD) was applied to study the response surface during method optimization and to achieve a good separation with a minimum number of experimental runs. The three independent parameters were pH of buffer, % of acetonitrile and flow rate of the mobile phase while the peak resolution of IND from MTL and the peak resolution of BET from IND (R2) were taken as responses to obtain mathematical models. The composite desirability was employed to optimize a set of responses overall (peak resolutions). The predicted optimum assay conditions include a mobile phase composition of acetonitrile and phosphate buffer (pH 5.95) in a ratio of 79:21, v/v, pumped at a flow rate of 1.4 mL min. With this ideal condition, the optimized method was able to achieve baseline separation of the three drugs with good resolution and a total run time of less than 7 min. The linearity of MTL, IND, and BET was determined in the concentration ranges of 5-600 µg mL, 5-300 µg mL, and 5-300 µg mL and the regression coefficients were 0.9994, 0.9998, and 0.9998, respectively. The average percent recoveries for the accuracy were determined to be 100.41 ± 0.60%, 100.86 ± 0.86%, and 100.99 ± 0.65% for MTL, IND, and BET, respectively. The R.S.D.% of the intra-day precision was found to be less than 1%, while the R.S.D.% of the inter-day precision was found to be less than 2%. The RP-HPLC method was fully validated with regard to linearity, accuracy, precision, specificity, and robustness as per ICH recommendations. The proposed method has various applications in quality control and routine analysis of the investigated drugs in their pharmaceutical dosage forms and laboratory-prepared mixtures with the goal of reducing laboratory waste, analysis time, and effort.
PubMed: 36510282
DOI: 10.1186/s13065-022-00908-9 -
Scientific Reports Jan 2023Wound healing is a well-organized dynamic process involving coordinated consecutive phases: homeostasis, inflammation, proliferation and resolution. Fibroblasts play...
Wound healing is a well-organized dynamic process involving coordinated consecutive phases: homeostasis, inflammation, proliferation and resolution. Fibroblasts play major roles in skin wound healing such as in wound contraction and release of growth factors which are of importance in angiogenesis and tissue remodeling. Abnormal fibroblast phenotypes have been identified in patients with chronic wounds. In this work, we analyzed scRNA-seq datasets of normal and wounded skin from mice at day 4 post-wound to investigate fibroblast heterogeneity during the proliferative phase of wound healing. Compositional analysis revealed a specific subset of fibroblast (cluster 3) that primarily increased in wounded skin (14%) compared to normal skin (3.9%). This subset was characterized by a gene signature marked by the plasma membrane proteins Sfrp2 + Sfrp4 + Sfrp1 + and the transcription factors Ebf1 + Prrx1 + Maged1 + . Differential gene expression and enrichment analysis identified epithelial to mesenchymal transition (EMT) and angiogenesis to be upregulated in the emerging subset of fibroblasts of the wounded skin. Using two other datasets for murine wounded skin confirmed the increase in cluster 3-like fibroblasts at days 2, 7 and 14 post-wounding with a peak at day 7. By performing a similarity check between the differential gene expression profile between wounded and normal skin for this emerging fibroblast subset with drug signature from the ConnectivityMap database, we identified drugs capable of mimicking the observed gene expression change in fibroblasts during wound healing. TTNPB, verteprofin and nicotinic acid were identified as candidate drugs capable of inducing fibroblast gene expression profile necessary for wound healing. On the other hand, methocarbamol, ifosfamide and penbutolol were recognized to antagonize the identified fibroblast differential expression profile during wound healing which might cause delay in wound healing. Taken together, analysis of murine transcriptomic skin wound healing datasets suggested a subset of fibroblasts capable of inducing EMT and further inferred drugs that might be tested as potential candidates to induce wound closure.
Topics: Mice; Animals; Skin; Epithelial-Mesenchymal Transition; Wound Healing; Transcription Factors; Fibroblasts; Neoplasm Proteins
PubMed: 36650180
DOI: 10.1038/s41598-022-27152-4 -
Frontiers in Veterinary Science 2023Tetanus is a severe neurologic disease caused by , resulting in spastic paralysis. Canine tetanus is associated with serious complications such as aspiration and a high...
OBJECTIVE
Tetanus is a severe neurologic disease caused by , resulting in spastic paralysis. Canine tetanus is associated with serious complications such as aspiration and a high mortality rate of up to 50%.
MATERIALS AND METHODS
Medical records of all dogs diagnosed with tetanus over 8 years (2014-2022) were analyzed for severity grade, treatment protocols, nutritional management, and complications, as well as outcome, vaccination, and antibody production in some dogs. No medical records were excluded. Normality was analyzed by the D'Agostino-Pearson test. Parametric, normally distributed data were presented as mean ± standard deviation. Non-parametric, non-normally distributed data were presented as median (m) and range (minimum-maximum). The association between tetanus grade, progression of diseases, and duration of hospitalization was analyzed using the -test, Mann-Whitney U test, and Kruskal-Wallis test. A ≤ 0.05 was considered significant.
RESULTS
Eighteen dogs were identified. Most affected dogs were classified into severity grade II (66.7%, 12 of 18). Clinical signs deteriorated in 55.6% of dogs (10 of 18). A source was identified in 88.9% of dogs (16 of 18). Nine dogs required surgical wound revision. A percutaneous endoscopic gastropexy tube was placed in 83.3% of dogs (15 of 18) for nutritional support. Medical treatment included metronidazole, methocarbamol, and combinations of different sedatives adapted to the patient's requirements. Tetanus antitoxin was used in 72.2% of dogs (13 of 18) without reported adverse events. The survival rate was 88.9% (16 of 18). Complications, such as hypertension, aspiration pneumonia, and laryngeal spasm occurred in 12 of 18 dogs. Median hospitalization time (8 days; range 0-16 days) was associated with the maximum tetanus severity grade (p = 0.022). Rapid eye movement behavior disorder was observed in 72.2% of dogs (13 of 18). In 5 dogs, antibodies were measured after recovery, and in 4 of 5 dogs, no antibodies were detectable despite generalized tetanus disease. Vaccination with tetanus toxoid was performed in five dogs following the disease.
CONCLUSION
In the present study, the mortality rate was lower than previously reported. Tetanus is still a life-threatening disease, but the prognosis may be good if adequate management and monitoring can be ensured.
PubMed: 38026664
DOI: 10.3389/fvets.2023.1249833 -
Journal of Research in Pharmacy Practice 2021Acute low back pain is a common ailment and causes pain and disability. Physicians often prescribe nonsteroidal anti-inflammatory drugs (NSAIDs) to treat acute low back...
Efficacy of the Combination of Indomethacin and Methocarbamol versus Indomethacin Alone in Patients with Acute Low Back Pain: A Double-Blind, Randomized Placebo-Controlled Clinical Trial.
OBJECTIVE
Acute low back pain is a common ailment and causes pain and disability. Physicians often prescribe nonsteroidal anti-inflammatory drugs (NSAIDs) to treat acute low back pain; however, due attention has recently been drawn to muscle relaxants to reduce the severity of patients' daily physical dysfunction. Therefore, this study aimed to evaluate the therapeutic effect of the administration of indomethacin alone compared with methocarbamolas a muscle relaxant and indomethacin as an NSAID on the treatment of acute low back pain.
METHODS
The present double-blind clinical trial was performed on 64 patients with acute low back pain. The patients were categorized into two groups and received the treatments as follows. Indomethacin capsules of 25 mg every 8 h and placebo tablets every 8 h were administered in the first group (Group I). Indomethacin capsules of 25 mg every 8 h and methocarbamol tablets of 500 mg every 8 h were administered in the second group (Group I + M). Patient pain intensity and physical function based on Back Pain Function Scale (BPFS) were recorded before and 1 week after the intervention.
FINDINGS
The present study results revealed that the mean pain reduction of patients in Group I + M was significantly higher than that of Group I (3.66 ± 3.17 vs. 1.84 ± 1.53; < 0.001). Moreover, the mean BPFS increase in Group I + M was significantly higher than that of Group I (19.44 ± 8.66 vs. 4.75 ± 4.35; < 0.001).
CONCLUSION
According to the results of the present study, concomitant administration of indomethacin and methocarbamol can be more effective in reducing pain intensity and improving the patient's physical function (or performance).
PubMed: 34527615
DOI: 10.4103/jrpp.JRPP_21_31 -
Frontiers in Veterinary Science 2022To define factors associated with survival in dogs with tetanus and to evaluate the prognostic significance of an established severity classification scheme.
OBJECTIVE
To define factors associated with survival in dogs with tetanus and to evaluate the prognostic significance of an established severity classification scheme.
METHODS
Medical records of dogs with the clinical diagnosis of tetanus were retrospectively reviewed with regard to signalment, clinical signs, clinicopathological findings on admission, wound characteristics, complications, therapeutic measures, and survival to discharge. Based on the extracted data, dogs were graded according to a previously published 4-class severity scheme. Non-parametric tests were applied for comparisons between survival categories.
RESULTS
Forty-two dogs fulfilled inclusion criteria, of which 32 survived. Of 10 non-survivors, 4 died and 6 were euthanised. Non-survivors were more often younger than 2 years of age (6/10 vs. 7/32 dogs, = 0.023), had shorter duration of specific signs of tetanus (time from onset of typical signs to presentation) (2 vs. 4 days, = 0.016), were prescribed less often antibiotics prior to presentation ( = 0.006), had higher tetanus severity grade (10/12 dogs in Class III or IV died, < 0.001), more often received acepromazine ( = 0.009) and atropine ( = 0.012), and more often had hyperthermia ( = 0.005) and respiratory complications (pneumonia, laryngeal spasm; = 0.008). Wound characteristics, the use of tube feeding, metronidazole, methocarbamol, magnesium and antitoxin were not significantly different between non-survivors and survivors.
CLINICAL SIGNIFICANCE AND CONCLUSION
Young dogs with a rapid course of severe generalized tetanus have a guarded prognosis. The previously described severity classification scheme proved valuable in predicting survival. Prospective multi-center studies are needed to clarify the prognostic significance of age, sedative usage and modified versions of an established classification scheme, including the presence of respiratory complications.
PubMed: 36590798
DOI: 10.3389/fvets.2022.1015569 -
Veterinary Medicine and Science Mar 2022The number of publications for most common drug violations in racehorses is limited. This study reports the most common medication violations in racehorses at four major...
INTRODUCTION/BACKGROUND
The number of publications for most common drug violations in racehorses is limited. This study reports the most common medication violations in racehorses at four major racetracks in Louisiana between 2016 and 2020.
METHODS
During this 5-year period, 27,237 blood samples and 25,672 urine samples collected during the course of normal race meeting activities were analysed by initial screening procedure utilizing Liquid Chromatography Mass Spectrometry (LC-MS/MS). Following initial screening, suspect samples were subject to quantitative or semi- quantitative confirmation analysis by LC-MS/MS.
RESULTS
The total number of violations reported was 534 (1.01% of the total number of specimens analysed). The total number of violations reported in Thoroughbred horses was 210 while the total number of violations reported in Quarter Horses was 324. The percentage of total violations was %0.59 for all the specimens analysed in Thoroughbred horses while this percentage was %1.9 for all the specimens analysed in Quarter Horses during this 5-year period. The most frequent violations included the overages (concentrations of permitted medications equal to or exceeding the set threshold) of clenbuterol (165 violations), non-steroidal anti-inflammatory drugs (NSAIDs) such as phenylbutazone (73 violations), combination of phenylbutazone with flunixin (45 violations) and muscle relaxant methocarbamol (40 violations).
DISCUSSION/CONCLUSIONS
The total number of violations were relatively low during 5-year period, but wide varieties of medications with different pharmacological actions were confirmed in performance horses in Louisiana. The most frequently reported violations in Louisiana were for permitted therapeutic medications (clenbuterol, phenylbutazone, flunixin methocarbamol) with established threshold and/or withdrawal guidelines in racehorses.
Topics: Animals; Chromatography, Liquid; Clenbuterol; Horses; Methocarbamol; Phenylbutazone; Tandem Mass Spectrometry
PubMed: 34989156
DOI: 10.1002/vms3.724