UNASSIGNED: Needle pain due to routine vaccination is an important factor contributing to low vaccine adherence and immunization coverage. Prophylactic oral analgesics can address this important issue of needle pain related to vaccination. Paracetamol and mefenamic acid are commonly used nonsteroidal anti-inflammatory drugs for pain relief, but there is little published literature on whether the same can be used for needle pain related to vaccination.
UNASSIGNED: This study was planned to compare the efficacy of oral mefenamic acid and paracetamol over placebo as a prophylactic analgesic during vaccination and prophylactic antipyretic during the post-vaccination period.
UNASSIGNED: Three-arm, triple-blind, randomized controlled trial.
UNASSIGNED: This study was conducted at the outpatient department of a tertiary-level medical college in South India from January 2021 to June 2022. In this three-arm interventional trial, each arm had either a single dose of placebo or mefenamic acid (4 mg/kg/dose) or paracetamol (10 mg/kg/dose). These medicines were administered orally 30 min before vaccination to reduce needle pain.
UNASSIGNED: Outcome was measured with the change of FLACC (Face, Leg, Activity, Cry, Consolability) scoring at the time of vaccination, subsequently at 15 and 30 min of vaccination in all three groups. Appearance of fever, grade of fever, and need for antipyretics 24 h after vaccination were also noted.
UNASSIGNED: There was a significant difference in FLACC scores at the time of administration (p = 0.010) and at 15 min (p = 0.014) with mefenamic acid compared to placebo. Although the paracetamol group showed a difference when compared to the placebo, it was not significant at the time of administration (p = 0.401), at 15 min (p = 0.451), or 30 min (p = 0.892) post-vaccination. The appearance of fever, grade of fever, and use of antipyretic up to 24 h post-vaccination had no significant difference among any of the three groups.
UNASSIGNED: Mefenamic acid was more potent than placebo for pre-vaccination pain prophylaxis in children. There was no difference in the appearance of fever and its grade among the three groups. The promising results from this trial warrant further large-scale studies to recommend a single oral dose of mefenamic acid to tackle needle pain related to vaccination in children to improve vaccine adherence and coverage.
UNASSIGNED: CTRI (Clinical trials registry-India) (CTRI/2021/01/030239). [Date of Commencement: 13 Jan 2021, Date of last recruitment: 30 June 2022 (now closed for new participants)].

UNASSIGNED: Abnormal uterine bleeding (AUB) is a common problem in reproductive age group and perimenopausal age group being responsible for many outpatient visits. Traditional management of AUB consists of giving mefenamic acid, tranexamic acid, or their combination with progestogens or hormonal intrauterine deviced levonorgestrel intrauterine system (LNG-IUS) for severe or nonresponsive cases. The objective of the current study was to study the efficacy and safety of adding diosmin along with tranexamic acid and mefenamic acid in reducing menstrual blood loss in AUB patients.
UNASSIGNED: It was a prospective double-blind randomized controlled trial in which 900 mg of diosmin was given once daily along with 500 mg tranexamic acid and 250 mg mefenamic acid during menstruation (Group I-92 patients), or only tranexamic acid and mefenamic acid during menstruation (Group II-92 patients).
UNASSIGNED: Mean age, parity, body mass index, and socioeconomic status were similar in the two groups. It was 35.68 years versus 36.78 years, 2.2 versus 2.3, 23.68 kg/m2 versus 24.62 kg/m2 respectively. Mean days of bleeding before this treatment were 6.8 versus 6.6 (P = 0.33) and were 3.5 versus 5.2 (P = 0.02) after treatment. There was a significant reduction in both groups as compared to before treatment (P = 0.021 in Group I, 0.027 in Group II) but the reduction was greater in Group I (P = 0.02). The amount of blood loss was 385 ml versus 390 ml (P = 0.7) before treatment which was significantly reduced in both groups to 68 ml versus 112 ml (P = 0.02 in Group I, 0.03 in Group II) with more decrease in Group I than in Group II (P = 0.01). Mean hemoglobin at beginning of the study was 8.4 versus 8.5 g/dl in Group I and Group II (P = 0.02) and significantly increased in both groups posttreatment to 10.9 and 9.8 g/dl in Group I and Group II (P = 0.012 in Group I, 0.011 in Group II) with increase being more in Group I than Group II (P = 0.03). Pictorial blood assessment chart score was 398 versus 406 (P = 0.35) before treatment and decreased significantly to 86.5 and 110.5 (P = 0.001 in Group I, 0.001 in Group II) with more decrease being in Group I than II (P = 0.01). There was significant decrease in dysmenorrhea with both treatments with no difference in the two groups. Various adverse effects such as nausea, vomiting, abdominal pain, diarrhea, constipation, and headache were equal in the two groups.
UNASSIGNED: Both the group\'s diosmin with tranexamic acid and mefenamic acid (Group I) and tranexamic acid and mefenamic acid (Group II) were efficacious in reducing menstrual blood loss, number of menstrual days and dysmenorrhea with effect being more by addition of diosmin. Adverse effects were equal in both the two groups.

BACKGROUND: This work aimed to prepare niosomal formulations of an anticancer agent [mefenamic acid (MEF)] to enhance its cancer targeting. 131I was utilized as a radiolabeling isotope to study the radio-kinetics of MEF niosomes.
METHODS: niosomal formulations were prepared by the ether injection method and assessed for entrapment efficiency (EE%), zeta potential (ZP), polydispersity index (PDI) and particle size (PS). MEF was labeled with 131I by direct electrophilic substitution reaction through optimization of radiolabeling-related parameters. In the radio-kinetic study, the optimal 131I-MEF niosomal formula was administered intravenously (I.V.) to solid tumor-bearing mice and compared to I.V. 131I-MEF solution as a control.
RESULTS: the average PS and ZP values of the optimal formulation were 247.23 ± 2.32 nm and - 28.3 ± 1.21, respectively. The highest 131I-MEF labeling yield was 98.7 ± 0.8%. The biodistribution study revealed that the highest tumor uptake of 131I-MEF niosomal formula and 131I-MEF solution at 60 min post-injection were 2.73 and 1.94% ID/g, respectively.
CONCLUSIONS: MEF-loaded niosomes could be a hopeful candidate in cancer treatment due to their potent tumor uptake. Such high targeting was attributed to passive targeting of the nanosized niosomes and confirmed by radiokinetic evaluation.

UNASSIGNED: This study aimed to compare the efficacy of ibuprofen, Novafen, mefenamic acid (MA), and celecoxib for pain relief in patients with symptomatic irreversible pulpitis prior to emergency endodontic treatment.
UNASSIGNED: This clinical trial was conducted on 120 patients with moderate to severe pain due to symptomatic irreversible pulpitis seeking emergency endodontic treatment. The patients were randomly divided into 4 groups to receive Novafen, MA, Celecoxib, and ibuprofen. The pain score of patients was measured before and 1 hour after analgesic intake using a visual analog scale (VAS). The success of analgesic treatment was analyzed by the binary logistic regression model.
UNASSIGNED: A total of 117 patients including 76 females and 41 males with a mean age of 30.29 years completed the study and were statistically analyzed. Ibuprofen had the highest analgesic efficacy followed by Novafen, and caused a significantly greater reduction in pain score compared with MA and celecoxib [OR (Ibuprofen vs MA)=1.28, OR (Ibuprofen vs Celecoxib)=3.74, OR (Novafen vs MA)=2.94, OR (Novafen vs Celecoxib)=2.94, P<0.05]. Ibuprofen and Novafen had no significant difference in analgesic efficacy (P>0.05). Baseline pain score was a predictive factor for the success of analgesics (P<0.05). The success of analgesic treatment decreased by 0.68 times with each unit increase in pain score (P<0.05). Gender and age of patients had no significant effect on success of analgesics (P>0.05).
UNASSIGNED: Both ibuprofen and Novafen can serve as the analgesics of choice for pain relief in patients with symptomatic irreversible pulpitis with moderate to severe pain when emergency endodontic treatment cannot be immediately performed.

BACKGROUND: Renal transplants are often prescribed non-steroidal anti-inflammatory drugs (NSAIDs) for analgesic purposes.
OBJECTIVE: Considering the dearth of data, we carried out the present study to evaluate the use of various NSAIDs and the incidence of acute kidney injury (AKI) in transplant patients.
METHODS: A retrospective study amongst renal transplant patients prescribed at least one dose of NSAID was carried between January and December 2020 at the Department of Nephrology, Salmaniya Medical Complex, Kingdom of Bahrain. The patients\' demographic details, serum creatinine values, and drug-related details were obtained. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used for defining AKI.
RESULTS: Eighty-seven patients were included. Forty-three patients were prescribed diclofenac, 60 received ibuprofen, six received indomethacin, 10 were administered mefenamic acid, and 11 received naproxen. Due to multiple courses of NSAID prescription, a total of 70 prescriptions were identified for diclofenac, 80 for ibuprofen, six for indomethacin, 11 for mefenamic acid, and 16 for naproxen. No significant differences were observed in the absolute (p = 0.08) and percent changes in serum creatinine (p = 0.1) between the NSAIDs. Twenty-eight (15.2%) courses of NSAID therapy met the KDIGO criteria for AKI. Age (OR: 1.1, 95% CI: 1.007, 1.2; p = 0.02), concomitant everolimus (OR: 483, 95% CI: 4.3, 54407; p = 0.01), and mycophenolate + cyclosporine + azathioprine (OR: 63.4E+006, 95% CI: 203.2157 to 19.8E+012; p = 0.005) administration were observed with significant risk of NSAID-induced AKI.
CONCLUSIONS: We observed possible NSAID-induced AKI to an extent of around 15.2% in our renal transplant patients. No significant differences were observed in the incidence of AKI between various NSAIDs and none of them had either graft failure or death.

Recently, Chemometric calibration methods in spectrophotometric analysis are achieving significant attention in the quality control of resolving drug mixtures and pharmaceutical formulations containing two or more drugs with overlapping spectra. The simple univariate methods have been used over the last few decades and has proven to be highly efficient and easy to apply. In this study, a comparative study was performed between some univariate and multivariate methods to determine if chemometric methods can substitute univariate methods in pharmaceutical analysis. In this study, three chemometric techniques were compared to seven univariate techniques to resolve a mixture of mefenamic acid and febuxostat in their raw materials, dosage forms and spiked human plasma. Mefenamic acid and febuxostat were used together for treatment of gout. The applied chemometric methods are partial least squares (PLS), artificial neural network (ANN) and genetic algorithm partial least squares (GA-PLS), while the used univariate methods include first derivative, second derivative, ratio spectra, derivative ratio spectra, ratio subtraction, Q-Absorbance ratio and mean centering spectrophotometric methods. The ten proposed methods were found to be green, sensitive, and rapid. They are simple and did not require any pre-separation steps. The results of both univariate and multivariate approaches were statistically compared with the reported spectrophotometric methods using student\'s t test and ratio variance F-test. They were also compared with each other, using one-way analysis of variance (ANOVA). These methods were assessed and validated according to ICH guidelines. The studied drugs were analyzed in their pharmaceutical dosage forms and spiked human plasma with good recoveries using the developed methods, which qualify them for routine quality control of the studied drugs.

Primary dysmenorrhea is considered as one of the women\'s main problems during reproductive age. The present study aimed to investigate the effect of vitamin D on the severity of dysmenorrhea and menstrual blood loss.
This double-blind, randomized, placebo-controlled trial, was performed on 84 single female college students between 18 and 25 years old who living in dormitories. Students with primary dysmenorrhea and vitamin D deficiency were divided into experimental (n = 42) and control (n = 42) groups. Five days before the putative beginning of their next menstrual cycle, the experimental group received 300,000 IU vitamin D (50,000 IU, two tablets every 8 h), and the control group received a placebo (oral paraffin). The effects of the supplement on the severity of dysmenorrhea and menstrual blood loss were evaluated one cycle before and during two successive cycles. Using the visual analog scale (VAS), verbal multidimensional scoring system (VMS), and pictorial blood assessment chart (PBLAC) questionnaires. Fisher\'s exact, Chi-square, independent sample t-test and repeated measurements were used.
In total, 78 of the 84 students completed the study (39 students per group). The intervention resulted in a significant reduction in the mean scores of both the VAS and VMS in the experimental group, in the first and second menstrual cycles (p < 0.001, p < 0.001, respectively), but not in the means score of PBLAC. Mefenamic acid consumption at the first and second menstruation period, in the experimental group was lower than the control group (p = 0.009, p < 0.001, respectively).
The results indicate that vitamin D supplementation could decrease the severity of primary dysmenorrhea and the need to consume pain-relief medications. Contrariwise vitamin D supplementation had no significant effect on menstrual blood loss.
This trial was registered in the Iranian Registry of Clinical Trials with code IRCT201305212324N on 18/1/2014. URL of registry: https://en.irct.ir/trial/1964 .

Introduction Fever is the most common presenting symptom in children and causes distress in patients and parents. Although nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as antipyretics, they should be reserved for pain or chronic inflammatory conditions due to safety concerns. If we can safely achieve the same antipyretic effect using a higher dose (20 mg/kg) of paracetamol, NSAIDs may be avoided for treating fever. There is a paucity of literature comparing the antipyretic effect of mefenamic acid and high-dose paracetamol. We hypothesized that there would be no difference in the antipyretic effect of high-dose paracetamol and mefenamic acid. Methods In this randomized control trial, 165 febrile children were randomly allocated to one of the following three groups: standard-dose (15 mg/kg) paracetamol (SDPCM) as the control group and high-dose (20 mg/kg) paracetamol (HDPCM) and mefenamic acid (6 mg/kg) (MFN) as the intervention groups. The temperature was measured using a digital thermometer at the start of drug dosage and every 15 minutes until it reached normal. One-way between-group analysis of variance (ANOVA) was used to compare outcome measures such as time for temperature to reach normal, fall of temperature in 60 minutes, and time for the next fever. Post hoc analysis was performed to compare mean differences. Patients were monitored for adverse effects. Results Out of 165 enrolled patients, 159 were analyzed. The baseline demographic data were comparable among the groups. There was a statistically significant difference in the mean time taken for the temperature to reach normal (F-value (F) (2,156)=3.184, p<0.05) and the mean reduction in temperature at 60 minutes (F (2,156)=23.40, p<0.001) among the groups. The mean time for temperature to reach normal in the SDPCM group (97.50±26.60 minutes) was longer than that in the HDPCM (85.09±31.43 minutes) and MFN (84.90±30.42 minutes) groups. The decrease in temperature over 60 minutes was greater in the HDPCM (0.46°C±0.19°C) and MFN (0.45°C±0.11°C) groups than in the SDPCM (0.33°C±0.10°C) group. The time to the next fever spike was shorter for the SDPCM group (5.07±2.66 hours) than for the HDPCM (7.20±3.08 hours) and MFN (8.82±3.83 hours) groups. Post hoc analysis demonstrated that high-dose paracetamol and mefenamic acid had similar and faster antipyretic effects than standard-dose paracetamol. Although the duration of action was found to be longer in the mefenamic acid group, the difference was not statistically significant. There were negligible adverse effects in the groups. Conclusion  Standard-dose paracetamol (15 mg/kg/dose) had a slower and shorter antipyretic effect than high-dose paracetamol (20 mg/kg/dose) and mefenamic acid (6 mg/kg/dose). A single dose of high-dose paracetamol was safe and had a similar antipyretic effect as mefenamic acid. Mefenamic acid may be avoided as an antipyretic and spared for pain and anti-inflammatory indications. Multicentered double-blind clinical trials with larger sample sizes and comparisons of other NSAIDs will be required to confirm these findings.

Mefenamic acid is a non‑steroidal anti‑inflammatory drug exhibiting a wide range of anti‑inflammatory, antipyretic, analgesic and probable antiviral activities. The present study evaluated the efficacy of treatment with mefenamic acid combined with standard medical care vs. standard medical care plus a placebo in ambulatory patients with coronavirus disease 2019 (COVID‑19; nasal/oropharyngeal swabs reverse transcription‑PCR test results positive for severe acute respiratory syndrome coronavirus 2). The present study is a phase II prospective, two‑arm, parallel‑group, randomized, double‑blind placebo‑controlled clinical trial which analyzed 36 patients. Two aspects were evaluated during the 14‑day follow‑up period: i) The time for reaching a patient acceptable symptom state (PASS), and ii) the last day of each COVID‑19 symptom presentation. Adverse effects were evaluated. The clinical severity for all the patients in the study was mild (88.9%) and moderate (11.1%). The control (placebo) group achieved PASS on day 8.0±1.3, compared with day 4.4±0.8 in the mefenamic acid group (P=0.020, Kaplan‑Meier analyses using log‑rank tests). Patients that received mefenamic acid plus standard medical care had a ~16‑fold higher probability of achieving PASS on day 8 (adjusted RR, 15.57; 95% CI, 1.22‑198.71; P=0.035), compared with the placebo plus standard medical care group. All symptoms lasted for fewer days in the mefenamic acid group, compared with the placebo group; however, only the symptoms of headache (P=0.008), retro‑orbital eye pain (P=0.049), and sore throat (P=0.029) exhibited statistically significant differences. The experimental treatment produced no severe adverse effects. On the whole, the present study demonstrates that the administration of mefenamic acid markedly reduced the symptomatology and time to reach PASS in ambulatory patients with COVID‑19. Due to its probable antiviral effects and potent anti‑inflammatory mechanisms, mefenamic acid may prove to be useful in the treatment of COVID‑19, in combination with other drugs, including the new antivirals (remdesivir, molnupiravir, or favipiravir). However, future studies are also required to confirm these findings.

BACKGROUND: Primary dysmenorrhea (PD) is the most common complaint in young women and adolescents. Side effects of non-steroidal anti-inflammatory drugs can limit their use. Therefore, non-pharmacological pain relief methods such as auriculotherapy may play an important role in PD management. This study was conducted to compare the effect of auriculotherapy and mefenamic acid on the severity and systemic symptoms of PD.
METHODS: In a randomized clinical trial, 83 students were randomized into two groups. In the auriculotherapy group, electrical stimulation of the ear was conducted once a week for two menstrual cycles. In each cycle close to menstruation, ear seeds were inserted on pressure points to be pressed in times of pain. In the mefenamic acid group, subjects took mefenamic acid capsules upon seeing the initial symptoms of menstruation until the pain reduces. The primary outcomes were mean pain intensity and systemic symptoms associated with it. Pain intensity was measured through the visual analog scale (VAS) and the verbal multidimensional scoring system (VMS). Systemic symptoms were assessed using VMS, as well as the yes/no question form.
RESULTS: Mean pain intensity with the VAS was significantly lower in the auriculotherapy group than the mefenamic acid group in the first and second cycles of intervention. There was a significant difference in VMS grade between both groups during the second cycle of intervention. In terms of the systemic symptoms in the second cycle of intervention, no subjects had dysmenorrhea grade 3 (common systemic symptoms) in the auriculotherapy group. Whereas in the mefenamic acid group, 16.7% of the subjects still had dysmenorrhea grade 3. There was no significant difference between the two groups in the frequency of systemic symptoms of PD. There was a significant decrease in the frequency of fatigue and diarrhea in both groups. However, there was a significant reduction in the frequency of nausea, headache, and anger in the auriculotherapy group.
CONCLUSIONS: Mean pain intensity with the VAS was lower with the auriculotherapy. Also, 65.9% of auriculotherapy group subjects were in the dysmenorrhea grades 0 and 1. Therefore, auriculotherapy is recommended because of its fewer complications and more effect on PD.
BACKGROUND: ClinicalTrials.gov IRCT20181207041873N1. Registered on February 24, 2019. https://en.irct.ir/user/trial/35967/view.