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Cureus May 2024Background Adjuvants have been discovered to prolong the analgesic impact of local anesthetics (LA), while the transversus abdominis plane (TAP) block offers sufficient...
Comparative Study of Levobupivacaine Versus Levobupivacaine With Dexmedetomidine as an Adjuvant in Transversus Abdominis Block for Postoperative Pain Relief in Abdominal Hysterectomy Patients: A Randomized, Double-Blind Study.
Background Adjuvants have been discovered to prolong the analgesic impact of local anesthetics (LA), while the transversus abdominis plane (TAP) block offers sufficient postoperative pain relief after various abdominal procedures. Nevertheless, the impact of the given LA will determine the duration of the TAP block. Thus, in this investigation, we aimed to estimate the analgesic impact of combining dexmedetomidine (DEX) with levobupivacaine in the TAP block for patients having an infraumbilical incision for an abdominal hysterectomy while under spinal anesthetic. Aim This study aimed to determine the analgesic effect of DEX (0.5 mcg/kg) to 20 ml of 0.25% levobupivacaine on each side in the TAP block in patients undergoing total abdominal hysterectomy (TAH). Materials and methods Two groups of 30 patients each, with ASA grades 1 and 2, were randomly selected from patients. Group N, comprising 30 patients, had a bilateral TAP block using 2 mL of normal saline and 20 mL of 0.25% levobupivacaine. Group D (n = 30 patients) was given DEX at a dose of 0.5 mcg/kg (2 mL) in addition to 20 mL of 0.25% levobupivacaine given bilaterally. The TAP block was administered just after skin closure. Time of the initial analgesic dose administration; total fentanyl doses utilized as rescue analgesia; pain scores (numerical rating scale (NRS)) at 2, 4, 6, 8, 12, and 24 hours; and pre- and postoperative cortisol levels were also noted. For each group, 1 gram IV paracetamol was administered every eight hours. Drugs used for rescue analgesia (RA) were diclofenac 75 mg IV stat and fentanyl 1 mcg/kg. Results and discussion In addition to Group N having lower NRS scores at rest, Group D had a considerably longer time for initial rescue analgesia than Group N. There was also a significant decrease in the total fentanyl consumption and postoperative serum cortisol levels in Group D in contrast to Group N. Conclusion Potential adjuvant DEX prolongs postoperative analgesia in patients experiencing abdominal hysterectomy when used alongside LA in TAP.
PubMed: 38826898
DOI: 10.7759/cureus.59523 -
Cureus Apr 2024The objective of this case report is to describe and document a case of respiratory syncytial virus (RSV) in a pediatric patient with Dravet syndrome (DS), also known as...
The objective of this case report is to describe and document a case of respiratory syncytial virus (RSV) in a pediatric patient with Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy. Febrile seizures are often a complication in a patient with DS and can lead to status epilepticus, necessitating measures to prevent triggers such as fever, electrolyte imbalance, or dehydration. An increased awareness and understanding of DS can facilitate the identification of warning signs. A two-year-old female with a past medical history of DS with focal and generalized features presented to the pediatric emergency department (ED) with a five-day history of cough, fever, and decreased oral intake. The patient's parents accompanied her and expressed concerns regarding the risk of seizures associated with a rise in body temperature, as they had been alternating between acetaminophen and ibuprofen to manage her fever with a maximum recorded temperature of 101.5℉. She exhibited signs of increased work of breathing, necessitating the administration of supplemental oxygen via nasal cannula. Blood samples were obtained and resulted in the development of metabolic acidosis. A respiratory panel confirmed the presence of an RSV infection, promoting the administration of breathing treatment with albuterol and ipratropium bromide. The patient was admitted for dehydration and was started on ½ normal saline/potassium chloride 20 mEq at 40 mL/hr. Additionally, her home medication regimen was resumed to minimize the risk of seizures. Given the patient's complications and increased risk of seizure, she was transferred to higher-level care where her status improved after the placement of a percutaneous endoscopic gastrostomy (PEG). This case underscores the complexities involved in managing patients with DS, particularly when complicated by respiratory illness and electrolyte imbalances that can lower the seizure threshold. This patient received a combination of diet and medications to prevent seizures, as well as allow for recovery and correction of the underlying metabolic acidosis. The transfer to a higher level of care in this case was necessary to allow for the specialized resources and expertise needed to handle this case.
PubMed: 38826591
DOI: 10.7759/cureus.59405 -
Perioperative Medicine (London, England) May 2024Multimodal analgesia regimens are recommended for the postoperative period after hip and knee replacement surgeries. However, there are no data on practice patterns for...
BACKGROUND
Multimodal analgesia regimens are recommended for the postoperative period after hip and knee replacement surgeries. However, there are no data on practice patterns for analgesic use in the immediate postoperative period after hip and knee replacements in Australia.
OBJECTIVES
To describe analgesic prescribing patterns in the inpatient postoperative phase for patients undergoing hip and knee replacement.
METHODS
Retrospective study of electronic medical record data from two major hospitals in Sydney, Australia. We identified analgesic medication prescriptions for all patients aged 18 years and older who underwent hip or knee replacement surgery in 2019. We extracted data on pain medications prescribed while in the ward up until discharge. These were grouped into distinct categories based on the Anatomical Therapeutic Chemical classification. We described the frequency (%) of pain medications used by category and computed the average oral morphine equivalent daily dose (OMEDD) during hospitalisation.
RESULTS
We identified 1282 surgeries in 1225 patients. Patients had a mean (SD) age of 69 (11.8) years; most (57.1%) were female. Over 99% of patients were prescribed opioid analgesics and paracetamol during their hospital stay. Most patients (61.4%) were managed with paracetamol and opioids only. The most common prescribed opioid was oxycodone (87.3% of patients). Only 19% of patients were prescribed nonsteroidal anti-inflammatories (NSAIDs). The median (IQR) average daily OMEDD was 50.2 mg (30.3-77.9).
CONCLUSION
We identified high use of opioids analgesics as the main strategies for pain control after hip and knee replacement in hospital. Other analgesics were much less frequently used, such as NSAIDs, and always in combination with opioids and paracetamol.
PubMed: 38822448
DOI: 10.1186/s13741-024-00403-w -
Journal of Translational Medicine May 2024Acetaminophen (APAP)-induced liver injury (AILI) is a pressing public health concern. Although evidence suggests that Bifidobacterium adolescentis (B. adolescentis) can...
Acetaminophen (APAP)-induced liver injury (AILI) is a pressing public health concern. Although evidence suggests that Bifidobacterium adolescentis (B. adolescentis) can be used to treat liver disease, it is unclear if it can prevent AILI. In this report, we prove that B. adolescentis significantly attenuated AILI in mice, as demonstrated through biochemical analysis, histopathology, and enzyme-linked immunosorbent assays. Based on untargeted metabolomics and in vitro cultures, we found that B. adolescentis generates microbial metabolite hypaphorine. Functionally, hypaphorine inhibits the inflammatory response and hepatic oxidative stress to alleviate AILI in mice. Transcriptomic analysis indicates that Cry1 expression is increased in APAP-treated mice after hypaphorine treatment. Overexpression of Cry1 by its stabilizer KL001 effectively mitigates liver damage arising from oxidative stress in APAP-treated mice. Using the gene expression omnibus (GEO) database, we verified that Cry1 gene expression was also decreased in patients with APAP-induced acute liver failure. In conclusion, this study demonstrates that B. adolescentis inhibits APAP-induced liver injury by generating hypaphorine, which subsequently upregulates Cry1 to decrease inflammation and oxidative stress.
Topics: Animals; Acetaminophen; Chemical and Drug Induced Liver Injury; Liver; Mice, Inbred C57BL; Male; Bifidobacterium adolescentis; Humans; Oxidative Stress; Mice; Gene Expression Regulation; Pyridines
PubMed: 38822329
DOI: 10.1186/s12967-024-05312-6 -
JMIR Research Protocols May 2024A dietary supplement containing Pelargonium sidoides extract, propolis, zinc, and honey has been recently developed and proven to be an effective adjuvant in clinical...
The Effects of a Dietary Supplement (PediaFlù) Plus Standard of Care in Children With Acute Tonsillopharyngitis/Rhinopharyngitis: Protocol for a Randomized Controlled Trial.
BACKGROUND
A dietary supplement containing Pelargonium sidoides extract, propolis, zinc, and honey has been recently developed and proven to be an effective adjuvant in clinical practice for seasonal diseases and the treatment of respiratory tract disorders.
OBJECTIVE
This trial aims to verify the efficacy of the tested dietary supplement in a pediatric population with acute tonsillopharyngitis/rhinopharyngitis (ATR).
METHODS
The trial includes children aged between 3 and 10 years with ATR ≤48 h, a negative rapid test for beta-hemolytic streptococcus or culture identification of nasal and/or pharyngeal exudates, and SARS-CoV-2 infection. The dietary supplement tested is an oral solution already on the market based on Pelagon P-70 (equivalent to Pelargonium sidoides d.e. 133.3 mg/100 ml), propolis, zinc, and honey. The product is administered at 5 ml 3 times a day for 6 days for children younger than 6 years and 10 ml 3 times a day for 6 days for children older than 6 years. The study design is open label, randomized, and controlled, with the tested dietary supplement plus standard of care (SoC) versus SoC alone. Patients are enrolled from 3 sites in Romania. The change in Tonsillitis Severity Score and number of treatment failures (using ibuprofen or high-dose paracetamol as rescue medication) are the primary end points. Based on the Tonsillitis Severity Score and the 2-sample comparison of the means formula with a 5% significance level, 80% power, and a minimally clinically important difference of 2 (SD 3.85) points, 120 patients are required. To account for potential screening failures and dropouts, we need to screen a population of approximately 150 children.
RESULTS
Patient enrollment began on June 3, 2021 (first patient's first visit), and ended on August 12, 2021 (last patient's last visit). The data collection period was from June 3, 2021, to September 16, 2021. The study was funded in February 2023. Data analysis is currently ongoing (April 2024). We expect the results to be published in a peer-reviewed clinical journal in the third quarter of 2024 and presented at scientific meetings in the last quarter of 2024.
CONCLUSIONS
The data from this trial may help identify new adjuvant treatments for children with ATR when streptococcal infection is excluded by a negative rapid test, thereby avoiding unnecessary antibiotic administration.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04899401 https://clinicaltrials.gov/study/NCT04899401.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/53703.
Topics: Child; Child, Preschool; Female; Humans; Male; Acute Disease; COVID-19; Dietary Supplements; Honey; Pharyngitis; Plant Extracts; Propolis; Randomized Controlled Trials as Topic; Standard of Care; Tonsillitis; Zinc
PubMed: 38819917
DOI: 10.2196/53703 -
Cureus Apr 2024Stiff Person Syndrome (SPS) is a rare autoimmune condition marked by extremely painful muscle spasms, stiffness, and rigidity throughout the body. Its rarity often...
Stiff Person Syndrome (SPS) is a rare autoimmune condition marked by extremely painful muscle spasms, stiffness, and rigidity throughout the body. Its rarity often translates to limited treatment options for patients and, occasionally, challenges in obtaining a definitive diagnosis. SPS also impacts patients' mental health, social and economic involvement, and overall quality of life. A 43-year-old man was initially being seen for lumbar radicular pain. A clinical diagnosis of SPS was made by a neurologist and confirmed by in-clinic follow-ups and anti-glutamic acid decarboxylase (anti-GAD) antibody testing. The Pain Management doctor agreed with this diagnosis and offered intravenous (IV) ketamine treatment, which he has found to positively impact the treatment of similar disorders. After an initial 10-day infusion, the patient reported improvement in pain and function. For almost two years, the patient received intravenous immunoglobulin (IVIg) and IV ketamine treatments to manage their condition and maintain pain control as well as quality of life. When the patient's symptoms began worsening after IVIg infusions, the decision to withdraw IVIg infusions and continue ketamine infusions was made. After discontinuing IVIg infusions, the patient reported improvement in function and pain level and continues to receive monthly two-day ketamine boosters. Outside of the infusions, the patient was able to discontinue the use of fentanyl patches and continued taking ketamine lozenges, oxycodone-acetaminophen, and dextromethorphan for at-home pain management. The patient's symptoms continue to be managed effectively with their current regimen, enabling their return to work and experiencing an enhanced quality of life. This case illustrates the potential benefits of IV ketamine treatment for patients with treatment-resistant SPS and similar neurologic and autoimmune disorders. Understanding and examining treatment alternatives for rare syndromes is crucial for achieving optimal patient outcomes. Additionally, documenting such cases offers valuable insights into the mechanism of ketamine, extending beyond these syndromes.
PubMed: 38817534
DOI: 10.7759/cureus.59397 -
Reproductive Toxicology (Elmsford, N.Y.) Aug 2024Paracetamol is suggested to have endocrine disrupting properties possibly affecting fetal programming of reproductive health that might lead to impaired semen quality...
Paracetamol is suggested to have endocrine disrupting properties possibly affecting fetal programming of reproductive health that might lead to impaired semen quality and changes in reproductive hormones. In this longitudinal study, we included 1058 young adult men born 1998-2000 into the Danish National Birth Cohort with follow-up at 18-21 years of age. The exposure, maternal intake of paracetamol, was modelled in three ways: dichotomized, trimester-specific, and as duration of exposure categorized into: short (1-2 weeks), medium (3-9 weeks) or long duration (>9 weeks) vs. no intake. Outcomes included semen characteristics, self-measured testis volume, and reproductive hormone levels. We used negative binominal regression to estimate the percentage difference and 95% confidence interval (CI) for each outcome. In total, 547 (48%) sons were prenatally exposed to paracetamol due to maternal intake at least once. Maternal intake of paracetamol during pregnancy was not associated with any of the biomarkers in the dichotomized or trimester-specific exposure models. For duration of exposure, sons of mothers with long duration of maternal intake of paracetamol showed tendencies towards lower semen concentration (-14% [95% CI: -31%; 8%]), a higher proportion of nonprogressive and immotile spermatozoa (8% [95% CI: -4%; 21%]) and higher DNA Fragmentation Index (16% [95% CI: -1%; 36%]) compared to son of mothers with no intake. Maternal intake of paracetamol during pregnancy was not clearly associated with biomarkers of male fecundity in adult sons. However, it cannot be ruled out that long duration of maternal intake of paracetamol might be associated with impaired semen characteristics.
Topics: Acetaminophen; Humans; Male; Female; Pregnancy; Young Adult; Biomarkers; Adolescent; Prenatal Exposure Delayed Effects; Fertility; Analgesics, Non-Narcotic; Longitudinal Studies; Denmark; Testis; Semen Analysis
PubMed: 38815769
DOI: 10.1016/j.reprotox.2024.108626 -
Acta Pharmaceutica (Zagreb, Croatia) Jun 2024Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its...
Oral solid dosage forms are most frequently administered with a glass of water which empties from the stomach relatively fast, but with a certain variability in its emptying kinetics. The purpose of this study was thus to simulate different individual water gastric emptying (GE) patterns in an glass-bead flow-through dissolution system. Further, the effect of GE on the dissolution of model drugs from immediate-release tablets was assessed by determining the amount of dissolved drug in the samples pumped out of the stomach compartment. Additionally, different HCl solutions were used as dissolution media to assess the effect of the variability of pH of the gastric fluid on the dissolution of three model drugs: paracetamol, diclofenac sodium, and dipyridamole. The difference in fast and slow GE kinetics resulted in different dissolution profiles of paracetamol in all studied media. For diclofenac sodium and dipyridamole tablets, the effect of GE kinetics was well observed only in media, where the solubility was not a limiting factor. Therefore, GE kinetics of co-ingested water influences the drug release from immediate-release tablets, however, in certain cases, other parameters influencing drug dissolution can partly or fully hinder the expression of this effect.
Topics: Gastric Emptying; Drug Liberation; Diclofenac; Water; Solubility; Tablets; Dipyridamole; Acetaminophen; Hydrogen-Ion Concentration; Kinetics; Administration, Oral; Glass
PubMed: 38815199
DOI: 10.2478/acph-2024-0016 -
Annals of Medicine Dec 2024Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the efficacy and safety of simple analgesics for the treatment of episodic tension-type headache (ETTH) in adults.
METHODS
We searched the Cochrane Library, PubMed, Web of Science, Embase, Chinese BioMedical Literature database and International Clinical Trials Registry Platform databases for eligible randomized clinical trials reporting the efficacy and/or safety of simple analgesics. A Bayesian NMA was performed to compare relative efficacy and safety. The surface under the cumulative ranking curve (SUCRA) was calculated to rank interventions. PROSPERO registration number: CRD42018090554.
RESULTS
We highlighted six studies including 3507 patients. For the 2 h pain-free rate, the SUCRA ranking was ibuprofen > diclofenac-K > ketoprofen > acetaminophen > naproxen > placebo. All drugs except naproxen reported a higher 2 h pain-free rate than placebo, with a risk ratio (RR) of 2.86 (95% credible interval, CrI: 1.62-5.42) for ibuprofen and 2.61 (1.53-4.88) for diclofenac-K. For adverse events rate, the SUCRA ranking was: metamizol > diclofenac-K > ibuprofen > lumiracoxib > placebo > aspirin > acetaminophen > naproxen > ketoprofen. The adverse event rates of all analgesics were no higher than those of placebo, except for ketoprofen. Moreover, all drugs were superior to placebo in the global assessment of efficacy. In particular, the RR of lumiracoxib was 2.47 (1.57-4.57). Global heterogeneity between the studies was low.
CONCLUSIONS
Simple analgesics are considered more effective and safe as a placebo for ETTH in adults. Our results suggest that ibuprofen and diclofenac-K may be the two best treatment options for patients with ETTH from a comprehensive point of view (both high-quality evidence).
Topics: Humans; Tension-Type Headache; Analgesics; Adult; Network Meta-Analysis; Ibuprofen; Acetaminophen; Bayes Theorem; Treatment Outcome; Diclofenac; Randomized Controlled Trials as Topic; Naproxen; Ketoprofen; Anti-Inflammatory Agents, Non-Steroidal; Female; Male
PubMed: 38813682
DOI: 10.1080/07853890.2024.2357235 -
Heliyon May 2024APAP (Acetaminophen)-induced hepatic injury is a major public health threat that requires continuous searching for new effective therapeutics. KSG...
APAP (Acetaminophen)-induced hepatic injury is a major public health threat that requires continuous searching for new effective therapeutics. KSG (Kaempferol-3-sophoroside-7-glucoside) is a kaempferol derivative that was separated from plant species belonging to different genera. This study explored the protective effects of KSG on ALI (acute liver injury) caused by APAP overdose in mice and elucidated its possible mechanisms. The results showed that KSG pretreatment alleviated APAP-induced hepatic damage as it reduced hepatic pathological lesions as well as the serum parameters of liver injury. Moreover, KSG opposed APAP-associated oxidative stress and augmented hepatic antioxidants. KSG suppressed the inflammatory response as it decreased the genetic and protein expression as well as the levels of inflammatory cytokines. Meanwhile, KSG enhanced the mRNA expression and level of anti-inflammatory cytokine, IL-10 (interleukin-10). KSG repressed the activation of NF-κB (nuclear-factor kappa-B), besides it promoted the activation of Nrf2 signaling. Additionally, KSG markedly hindered the elevation of ASK-1 (apoptosis-signal regulating-kinase-1) and JNK (c-Jun-N-terminal kinase). Furthermore, KSG suppressed APAP-induced apoptosis as it decreased the level and expression of Bax (BCL2-associated X-protein), and caspase-3 concurrent with an enhancement of anti-apoptotic protein, Bcl2 in the liver. More thoroughly, Computational studies reveal indispensable binding affinities between KSG and Keap1 (Kelch-like ECH-associated protein-1), ASK1 (apoptosis signal-regulating kinase-1), and JNK1 (c-Jun N-terminal protein kinase-1) with distinctive tendencies for selective inhibition. Taken together, our data showed the hepatoprotective capacity of KSG against APAP-produced ALI via modulation of Nrf2/NF-κB and JNK/ASK-1/caspase-3 signaling. Henceforth, KSG could be a promising hepatoprotective candidate for ALI.
PubMed: 38813141
DOI: 10.1016/j.heliyon.2024.e31448