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Drugs Jun 2024Although paracetamol (acetaminophen) combined with other analgesics can reduce pain intensity in some pain conditions, its effectiveness in managing low back pain and...
BACKGROUND AND OBJECTIVE
Although paracetamol (acetaminophen) combined with other analgesics can reduce pain intensity in some pain conditions, its effectiveness in managing low back pain and osteoarthritis is unclear. This systematic review investigated whether paracetamol combination therapy is more effective and safer than monotherapy or placebo in low back pain and osteoarthritis.
METHODS
Online database searches were conducted for randomised trials that evaluated paracetamol combined with another analgesic compared to a placebo or the non-paracetamol ingredient in the combination (monotherapy) in low back pain and osteoarthritis. The primary outcome was a change in pain. Secondary outcomes were (serious) adverse events, changes in disability and quality of life. Follow-up was immediate (≤ 2 weeks), short (> 2 weeks but ≤ 3 months), intermediate (> 3 months but < 12 months) or long term (≥ 12 months). A random-effects meta-analysis was conducted. Risk of bias was assessed using the original Cochrane tool, and quality of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE).
RESULTS
Twenty-two studies were included. Pain was reduced with oral paracetamol plus a non-steroidal anti-inflammatory drug (NSAID) at immediate term in low back pain (paracetamol plus ibuprofen vs ibuprofen [mean difference (MD) - 6.2, 95% confidence interval (CI) -10.4 to -2.0, moderate evidence]) and in osteoarthritis (paracetamol plus aceclofenac vs aceclofenac [MD - 4.7, 95% CI - 8.3 to - 1.2, moderate certainty evidence] and paracetamol plus etodolac vs etodolac [MD - 15.1, 95% CI - 18.5 to - 11.8; moderate certainty evidence]). Paracetamol plus oral tramadol reduced pain compared with placebo at intermediate term for low back pain (MD - 11.7, 95% CI - 19.2 to - 4.3; very low certainty evidence) and osteoarthritis (MD - 6.8, 95% CI - 12.7 to -0.9; moderate certainty evidence). Disability scores improved in half the comparisons. Quality of life was infrequently measured. All paracetamol plus NSAID combinations did not increase the risk of adverse events compared to NSAID monotherapy.
CONCLUSIONS
Low-to-moderate quality evidence supports the oral use of some paracetamol plus NSAID combinations for short-term pain relief with no increased risk of harm for low back pain and osteoarthritis compared to its non-paracetamol monotherapy comparator.
PubMed: 38937394
DOI: 10.1007/s40265-024-02065-w -
Naunyn-Schmiedeberg's Archives of... Jun 2024Pain management is a primary goal after oral surgeries, but little is known about sex differences in the sensitivity to analgesics. This study aimed to compare the...
Pain management is a primary goal after oral surgeries, but little is known about sex differences in the sensitivity to analgesics. This study aimed to compare the efficacy of three drugs with analgesic potential on heat and mechanical hyperalgesia, spontaneous pain and locomotion on male and female rats subjected to a model of orofacial postoperative pain. Male and female Wistar rats were submitted to intraoral incision or sham surgery, and on postoperative day 3, the effect of the ibuprofen (30 and 100 mg/kg), acetaminophen (100 and 300 mg/kg) and codeine (3 and 10 mg/kg) was assessed on responses to heat and mechanical facial stimulation, facial grooming, and locomotion. Ibuprofen reduced heat and mechanical hyperalgesia and grooming behavior in male and female rats in a non-sedative dose; acetaminophen dose-dependently reduced the mechanical hyperalgesia and abolished the heat hyperalgesia and the grooming behavior but caused sedation in both sexes; codeine dose-dependently reduced the mechanical hyperalgesia in male and female rats, and reduced the heat hyperalgesia, but females were less sensitive than males. It reduced spontaneous facial grooming in both sexes, but induced hyperlocomotion in females. Ibuprofen presented the most favorable profile, since it reduced over 50% heat and mechanical hyperalgesia in male and female rats, and significantly reduced spontaneous pain, without causing sedation or affecting locomotion. The identification of sex differences in the sensitivity and safety profile of frequently used analgesics can help guide the choice of more effective individualized therapies for pain control.
PubMed: 38935129
DOI: 10.1007/s00210-024-03254-w -
Acta Anaesthesiologica Scandinavica Jun 2024Inadequate pain relief with moderate to severe pain remains a challenge after cesarean section and may significantly impair postoperative recovery. However, detailed...
BACKGROUND
Inadequate pain relief with moderate to severe pain remains a challenge after cesarean section and may significantly impair postoperative recovery. However, detailed assessment on the timing of severe pain, opioid consumption, influence on activities such as mobilization, breastfeeding, and caring for the infant are difficult to conduct, especially after discharge. Short message services (SMS)-based questionnaires may offer a low-cost way of providing such data but with the risk of insufficient response rates. We assessed the feasibility of collecting detailed, prospective data on postoperative pain and recovery during the initial hours and days following cesarean section using SMS-based questionnaires.
METHODS
Prospective Danish single-center cohort study involving elective cesarean sections under spinal anesthesia with fentanyl and bupivacaine. The postoperative pain regimen consisted of paracetamol, NSAID and oral morphine by request. Patients received an SMS-based questionnaire at 6, 12, 18, 24, and 48 h postoperatively, as well as on days 7 and 30.
PRIMARY OUTCOME
Response rate and time from receiving the SMS to completion of the questionnaires.
SECONDARY OUTCOMES
Opioid consumption and Patient Reported Outcomes Measures on pain and recovery.
RESULTS
From December 2022 to June 2023; 100 patients were included. The response rate was 78% at 6 h postoperatively, decreasing to 63% at 24 h. The median response time from receiving to answering the SMS-based questionnaire at 6 h after cesarean section was 23 min (IQR 2-72), decreasing to 20 min (IQR 2-78) after 24 h. Severe pain, corresponding to a Numeric Rating Scale (NRS) score >6, was reported by 57% (95% CI 65-84) at 6 h, decreasing to 28% (95% CI 34-58) at 24 h. Median opioid consumption within the first 24 h was 30 mg (IQR 20-50).
CONCLUSION
SMS-based questionnaires on Patient Reported Outcome Measures are a feasible and cost-effective way of prospectively collecting frequent data with acceptable response rates, even shortly after cesarean section. Secondarily 66% of patients reported severe pain during the first 24 h following cesarean section, with the highest pain scores within the initial 12 h. Future studies should focus on optimizing pain-management within this timeframe.
PubMed: 38934683
DOI: 10.1111/aas.14477 -
Current Pediatric Reviews Jun 2024An off-label medication involves the use of an approved drug for an unapproved indication, population, route of administration, or dosage.The physiological state of...
Awareness, Practice, and Views of Pediatricians, General Physicians, and Pharmacists about Prescribing Off-label Medication in Pediatric Patients in Eastern Province, Saudi Arabia.
BACKGROUND
An off-label medication involves the use of an approved drug for an unapproved indication, population, route of administration, or dosage.The physiological state of children differs from that of adults, making the adult formulation potentially dangerous to children. Off-label prescribing is quite common in children due to challenges in the development of pediatric formulations. The current study was conducted to determine the awareness, practice, and views of pediatricians, general physicians, and pharmacists about prescribing Off-label medication to pediatric patients in Eastern Province, Saudi Arabia.
METHODS
A cross-sectional study based on a questionnaire was conducted among pediatricians, general physicians, and pharmacists (clinical and community) in Eastern Province, Saudi Arabia. Statistical analysis was conducted using the data exported from Google Forms (Mountain View, California, USA) and Microsoft Excel (Version 2016) and then exported into Statistical Package for Social Sciences (SPSS) version 26.0 (IBM, Inc., Armonk, NY, USA). Chi-square was deemed suitable. The level of significance was set at 0.05.
RESULTS
Among the study participants, 53(35.09%) were pharmacists, followed by 24(15.89%) others, 22(14.565) pediatricians, 19(12.58%) other specialists, 17(11.25%) general physicians, and 16(10.59%) were clinical pharmacist. About 73(48.34%) described the definition of off-label correctly. About 114(75.49%) believed that parents and guardians must be informed about off-label medicine prescribed to their children. About 52(34.43%) had concerns about the safety of the medication, and 98(64.90%) believed they should be tested in pediatrics during clinical trials. Further, 97(64.23%) considered themselves not enough knowledgeable about off-label medications. The barriers reported by the participants were as follows: 89(58.945%) said lack of information resources, 71(47.01%) said lack of training, 56(37.08%) said lack of information on the safety of excipients used in pediatrics, 47(31.12%) said lack of formulary, 44(29.13%) said lack of guidelines, and 58(5.29%) said lack of information related to the safety of excipient concentration in pediatrics. The proportion of healthcare professionals who agreed that excipients in adult medication may be harmful to pediatrics was 103(68.21%). The drugs most often prescribed as off-label were paracetamol 54(21.68%), followed by Phenobarbital 35(14%), and Amoxicillin 33(13.25%).
CONCLUSION
There are a considerable number of healthcare professionals unaware of the description of off-label medication. The majority have concerns over the safety and efficacy of the off-label drugs and believe that most frequently used off-label drugs in pediatrics must be tested in pediatrics during clinical trials. In addition, excipient safety data are of considerable importance to ensure off-label drug safety in pediatrics, who believe their knowledge is inadequate and need proper guidelines and training on this issue.
PubMed: 38934287
DOI: 10.2174/0115733963298903240614072717 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Physicians are currently finding products for pediatric respiratory diseases of viral etiology to reduce the inappropriate use of antibiotic therapy. This study...
The Effectiveness of a Dietary Supplement with Honey, Propolis, Extract, and Zinc in Children Affected by Acute Tonsillopharyngitis: An Open, Randomized, and Controlled Trial.
Physicians are currently finding products for pediatric respiratory diseases of viral etiology to reduce the inappropriate use of antibiotic therapy. This study evaluated PediaFlù (Pediatrica S.r.l.), a dietary supplement already on the market composed of honey, propolis, extract, and zinc (DSHPP), in children affected by acute tonsillopharyngitis (ATR). The open-label, randomized, and controlled study compared DSHPP + standard of care (SoC) versus SoC alone for six days. Children between 3 and 10 years with an ATR ≤ 48 h, a negative rapid test for beta-hemolytic , or a culture identification of nasal and/or pharyngeal exudates were included. A tonsillitis severity score (TSS) and the number of treatment failures (using ibuprofen or high-dose paracetamol as rescue medication) were the primary endpoints. DSHPP+ SoC showed better performance than SoC alone for TSS sub-scores: throat pain and erythema on day 6 ( < 0.001 and < 0.05), swallowing ( < 0.01 on day 4), and TSS total score on days 4 and 6 ( < 0.05 and < 0.001). Only one patient (SoC group) had treatment failure for ibuprofen administration. No adverse events were reported. DSHPP is an optimal adjuvant in the treatment of URTI and could potentially be useful in the daily clinical practice of paediatricians evaluating the correct antibiotic prescription.
PubMed: 38931472
DOI: 10.3390/ph17060804 -
Pharmaceuticals (Basel, Switzerland) Jun 2024() is a prominent plant used in Moroccan traditional medicine. This study investigated the phenolic composition and the anti-inflammatory, the hepatoprotective, and the...
() is a prominent plant used in Moroccan traditional medicine. This study investigated the phenolic composition and the anti-inflammatory, the hepatoprotective, and the anticancer activities of a hydroethanolic extract of leaves and stems. Ultra-high-performance liquid chromatography identified the phenolic profile. The in vitro anticancer activity was evaluated using the MTT assay on HL-60 and K-562 myeloleukemia cells and liver (Huh-7) cell lines. The anti-inflammatory effect was assessed in vivo using carrageenan-induced paw edema in rats. The hepatoprotective effect at 300 and 1000 mg/kg doses against the acetaminophen-induced hepatotoxicity on rats was studied for seven days. Additionally, molecular docking simulations were performed to evaluate the extract's inhibitory potential against key targets: lipoxygenase, cytochrome P450, tyrosine kinase, and TRADD. The extract exhibited significant cytotoxic activity against K-562 and HL-60 cells, but not against lung cancer cells (Huh-7 line). The 1000 mg/kg dose demonstrated the most potent anti-inflammatory effect, inhibiting edema by 99.10% after 6 h. extract displayed promising hepatoprotective properties. Procyanidin (-7.27 kcal/mol), quercetin (-8.102 kcal/mol), and catechin (-9.037 kcal/mol) were identified as the most active molecules against lipoxygenase, cytochrome P450, and tyrosine kinase, respectively. These findings highlight the untapped potential of for further exploration in treating liver damage, inflammation, and leukemia.
PubMed: 38931453
DOI: 10.3390/ph17060786 -
Pharmaceuticals (Basel, Switzerland) May 2024(1) Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are extremely severe cutaneous adverse drug reactions which are relatively rare in...
(1) Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are extremely severe cutaneous adverse drug reactions which are relatively rare in routine clinical practice. An analysis of a national pharmacovigilance database may be the most effective method of obtaining information on SJS and TEN. (2) Methods: Design-a retrospective descriptive pharmacoepidemiologic study of spontaneous reports (SRs) with data on SJS and TEN retrieved from the Russian National Pharmacovigilance database for the period from 1 April 2019 to 31 December 2023. Descriptive statistics was used to assess the demographic data of patients and the structure of suspected drugs. (3) Results: A total of 170 SRs on SJS and TEN were identified, of which 32.9% were SJS and 67.1%-TEN. In total, 30% were pediatric SRs, 21.2%-SRs of the elderly. There were 12 lethal cases, and all cases were TEN. The leading culprit drugs were anti-infectives for systemic use and nervous system agents. The top 10 involved drugs are as follows: lamotrigine (23.5%), ibuprofen (12.9%), ceftriaxone (8.8%), amoxicillin and amoxicillin with beta-lactam inhibitors (8.8%), paracetamol (7.6%), carbamazepine (5.9%), azithromycin (4.1%), valproic acid (4.1%), omeprazole (3.5%), and levetiracetam (3.5%). (4) Conclusions: Our study was the first study in Russia aimed at the assessment of the structure of the drugs involved in SJS and TEN on the national level.
PubMed: 38931343
DOI: 10.3390/ph17060675 -
Nutrients Jun 2024The excessive employment of acetaminophen (APAP) is capable of generating oxidative stress and apoptosis, which ultimately result in acute liver injury (ALI)....
The excessive employment of acetaminophen (APAP) is capable of generating oxidative stress and apoptosis, which ultimately result in acute liver injury (ALI). polysaccharides (GLPs) exhibit hepatoprotective activity, yet the protective impact and potential mechanism of GLPs in relation to APAP-induced ALI remain ambiguous. The intention of this research was to scrutinize the effect of GLPs on APAP-induced ALI and to shed light on their potential mechanism. The results demonstrated that GLPs were capable of notably alleviating the oxidative stress triggered by APAP, as shown through a significant drop in the liver index, the activities of serum ALT and AST, and the amounts of ROS and MDA in liver tissue, along with an increase in the levels of SOD, GSH, and GSH-Px. Within these, the hepatoprotective activity at the high dose was the most conspicuous, and its therapeutic efficacy surpassed that of the positive drug (bifendate). The results of histopathological staining (HE) and apoptosis staining (TUNEL) indicated that GLPs could remarkably inhibit the necrosis of hepatocytes, the permeation of inflammatory cells, and the occurrence of apoptosis induced by APAP. Moreover, Western blot analysis manifested that GLPs enhanced the manifestation of Nrf2 and its subsequent HO-1, GCLC, and NQO1 proteins within the Nrf2 pathway. The results of qPCR also indicated that GLPs augmented the expression of antioxidant genes Nrf2, HO-1, GCLC, and NQO1. The results reveal that GLPs are able to set off the Nrf2 signaling path and attenuate ALI-related oxidative stress and apoptosis, which is a potential natural medicine for the therapy of APAP-induced liver injury.
Topics: Acetaminophen; Oxidative Stress; Apoptosis; Reishi; Chemical and Drug Induced Liver Injury; NF-E2-Related Factor 2; Animals; Male; Polysaccharides; Signal Transduction; Liver; Mice; Fungal Polysaccharides; Antioxidants
PubMed: 38931214
DOI: 10.3390/nu16121859 -
Materials (Basel, Switzerland) Jun 2024In recent years, there has been a significant interest in the advancement of electrochemical sensing platforms to detect antipyretic drugs with high sensitivity and...
In recent years, there has been a significant interest in the advancement of electrochemical sensing platforms to detect antipyretic drugs with high sensitivity and selectivity. The electrochemical determination of acetaminophen (PCT) was studied with strontium molybdate with a functionalized carbon nanotube (SrMoO@f-CNF) nanocomposite. The SrMoO@f-CNF nanocomposite was produced by a facial hydrothermal followed by sonochemical treatment, resulting in a significant enhancement in the PCT determination. The sonochemical process was applied to incorporate SrMoO nanoparticles over f-CNF, enabling a network-like structure. Moreover, the produced SrMoO@f-CNF composite structural, morphological, and spectroscopic properties were confirmed with XRD, TEM, and XPS characterizations. The synergistic effect between SrMoO and f-CNF contributes to the lowering of the charge transfer resistance (Rct=85 Ω·cm2), a redox potential of Epc=0.15 V and Epa=0.30 V (vs. Ag/AgCl), and a significant limit of detection (1.2 nM) with a wide response range of 0.01-28.48 µM towards the PCT determination. The proposed SrMoO@f-CNF sensor was studied with differential pulse voltammetry (DPV) and cyclic voltammetry (CV) techniques and demonstrated remarkable electrochemical properties with a good recovery range in real-sample analysis.
PubMed: 38930256
DOI: 10.3390/ma17122887 -
Materials (Basel, Switzerland) Jun 20243D-printable composites have become an attractive option used for the design and manufacture of electrochemical sensors. However, to ensure proper charge-transfer...
3D-printable composites have become an attractive option used for the design and manufacture of electrochemical sensors. However, to ensure proper charge-transfer kinetics at the electrode/electrolyte interface, activation is often required, with this step consisting of polymer removal to reveal the conductive nanofiller. In this work, we present a novel effective method for the activation of composites consisting of poly(lactic acid) filled with carbon black (CB-PLA) using microwave radiation. A microwave synthesizer used in chemical laboratories (CEM, Matthews, NC, USA) was used for this purpose, establishing that the appropriate activation time for CB-PLA electrodes is 15 min at 70 °C with a microwave power of 100 W. However, the usefulness of an 80 W kitchen microwave oven is also presented for the first time and discussed as a more sustainable approach to CB-PLA electrode activation. It has been established that 10 min in a kitchen microwave oven is adequate to activate the electrode. The electrochemical properties of the microwave-activated electrodes were determined by electrochemical techniques, and their topography was characterized using scanning electron microscopy (SEM), Raman spectroscopy, and contact-angle measurements. This study confirms that during microwave activation, PLAs decompose to uncover the conductive carbon-black filler. We deliver a proof-of-concept of the utility of kitchen microwave-oven activation of a 3D-printed, free-standing electrochemical cell (FSEC) in paracetamol electroanalysis in aqueous electrolyte solution. We established satisfactory limits of linearity for paracetamol detection using voltammetry, ranging from 1.9 μM to 1 mM, with a detection limit (LOD) of 1.31 μM.
PubMed: 38930201
DOI: 10.3390/ma17122833