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Background and Objective PSD502 is a metered-dose spray for premature ejaculation. The two trials aimed to evaluate the safety and pharmacokinetics of PSD502 in healthy Chinese male and female individuals. Methods Two phase I, randomized, double-blind, placebo-controlled trials were conducted in men (Trial 1) and women (Trial 2). The participants were randomized 3:1 to receive PSD502 (7.5 mg of lidocaine and 2.5 mg of prilocaine per spray) or a placebo. For male individuals, a single dose (three sprays) once daily was applied to the glans penis for 21 days except for nine sprays (three doses) on days 7 and 14, 4 h apart for each dose. For female individuals, two sprays were applied to the vagina and one to the cervix once daily for 7 days. The primary endpoint was safety. Pharmacokinetics analysis was also performed. Results Twenty-four male and 24 female individuals were recruited. Treatment-emergent adverse events occurred in 38.9% (7/18) of male individuals and 66.7% (12/18) of female individuals in the PSD502 group, respectively. Both trials reported 50.0% (3/6) treatment-emergent adverse events for the placebo. No grade ≥ 3 treatment-emergent adverse events, serious adverse events, or treatment-emergent adverse events leading to early withdrawal or discontinuation occurred. After consecutive applications, lidocaine and prilocaine cleared rapidly in both trials. Plasma concentrations exhibited high inter-individual variability. The maximum plasma concentrations of active ingredients were far below the anticipated minimum toxic concentrations. The area under the plasma concentration–time curve of metabolites were ≤ 20% of the parent drugs. No clinically significant accumulations were observed in the two trials. Conclusions PSD502 was well tolerated and showed low plasma concentrations in healthy Chinese male and female individuals.

ObjectiveIntravenous cannulation is a routine procedure in the ED. Different methods are being used to reduce the pain of intravenous cannulation. Among them, there are studies which have shown the efficacy of vapocoolant spray and lidocaine–prilocaine combination topical cream. This study aimed to compare the efficacy of these methods in pain management.MethodThis was a randomised clinical trial study including adult (18–65 year) patients admitted to the ED of an academic hospital in Iran between February 2024 and May 2024 and who required peripheral intravenous catheter. Patients were assigned randomly to vapocoolant spray or lidocaine–prilocaine cream. The spray was applied for 30 s immediately before intravenous cannulation and the cream 45 min before intravenous cannulation. Patients’ pain scores were assessed by Numeric Rating Scale (NRS) immediately after cannulation along with adverse effects. Patients’ willingness to use the same anaesthetic method was also recorded.ResultThis study included 77 patients; median age was 39 (IQR: 29.75–55.39) and 48% were men. The median cannulation pain score was 2 (IQR: 2–3) in the vapocoolant group and 3 (IQR: 2–3) in the lidocaine–prilocaine cream group (p value=0.09). Overall, adverse events occurred in 24 (31%) patients; 21 patients in the lidocaine–prilocaine group experienced transient paleness (p value=0.03). 33 (43%) patients who received vapocoolant and 21 (27%) patients who used the cream selected to use their assigned method again (p value=0.02).ConclusionThis study demonstrated that the vapocoolant spray was not statistically more effective than lidocaine–prilocaine cream in pain reduction during intravenous cannulation. Although all these side effects were generally considered clinically insignificant, the spray group exhibited significantly fewer side effects compared with the cream group.Trial registration number NCT04473820.

Palatal injections are considered to be one of the most painful dental procedures. As a result, it was important to find alternatives to this painful injection to improve children's cooperation. The dental literature mentioned using EMLA cream as a possible alternative to conventional injections, but its anesthetic effect was debated. Therefore, it was valuable to research the impact of microneedle patches to enhance the effectiveness of this cream. The purpose of this randomized controlled clinical trial was to compare the effectiveness of different methods of anesthesia and pain levels in children aged 7–11 years. The study compared the use of EMLA cream, EMLA with microneedles, and conventional palatal injections. A total of 90 children were randomly assigned to three groups: Group 1 received conventional palatal anesthesia (control), Group 2 received EMLA cream only, and Group 3 received EMLA with microneedles. Pain levels were assessed using the FLACC and Wong-Baker scales at three different time points: T1(during anesthesia), T2(on palatal probing), and T3(during extraction). The FLACC scale revealed a significant difference in pain between groups only at T1 ( P value = 0.000). It was found that the conventional palatal injection group had a higher pain level than the EMLA cream-only group and the group using microneedle patches with EMLA cream ( P value = 0.000). However, the other groups did not show significant differences in pain levels during the anesthesia ( P value  = 1.00). Similarly, the Wong-Baker scale also demonstrated a statistically significant difference in pain between groups only at T1 ( P value  = 0.000). It was found that the conventional palatal injection group had a higher pain level than the EMLA cream-only group and the group using microneedle patches with EMLA cream ( P value  = 0.000). However, the other groups did not show significant differences in pain levels during the anesthesia ( P value  = 0.091). The study concludes that both EMLA cream alone and EMLA with microneedles can be used as an alternative to conventional palatal anesthesia for children.

Background The injection of local anesthetics, an extremely painful procedure, leads to a reduction of patients’ acceptance. Objective To investigate the efficacy and adverse reactions of 4% tetracaine gel (TG) and lidocaine-prilocaine cream (LPC) on reducing the local anesthetic injection pain for upper eyelid blepharoplasty. Methods Sixty participants were equally divided into three groups. Each patient in two treatment groups was assigned a pair of eutectic mixture of local anesthetics (EMLA) and 4% TG, and the blank control group did not receive any topical anesthetic. The primary outcome was the pain score associated with anesthetic injection. The secondary outcomes included the local cutaneous reactions and eyelid edema in 24 h postoperatively. Results The NRS score in the control group was 6.65 ± 1.60, in the 4% TG and EMLA sides of 5.75 ± 1.62 and 6.25 ± 1.48 in group A, without statistically significant ( p  = 0.334, 0.067, respectively). While in group B, the injection pain scores in 4% TG and EMLA sides were 4.65 ± 1.66 and 5.5 ± 1.73 ( p  < 0.001 and p  = 0.031, respectively). A negative correlation was observed between age and LAIP (regression coefficient = -0.022), whereas gender had almost no impact (regression coefficient = 0.368). The administration duration of 4%TG and EMLA had no statistically significant effect on the cutaneous reactions observed on the patients’ eyelids ( p  = 0.723, p  = 0.507, respectively). However, the incidence of cutaneous reactions was 35% for EMLA, significantly lower than 72.5% for 4% TG ( p  < 0.001). The postoperative edema score of the control group was 1.5 (1.0,2.0), while in group A both 4% TG and EMLA sides scored 2.0 (1.0,2.0) and in group B they scored 2.0 (1.0,2.0) and 1.0 (1.0,2.0), respectively. Neither group showed significant differences in postoperative edema score compared to the control group, and there’s also no significant difference was revealed comparing the 4% TG or EMLA side with the paired side in one group or the same side in the other group. Conclusion In comparison to LPC, 4% TG showed a stronger anesthetic effect on reducing injection pain after 60-minute application. It also generally presented a higher frequency of cutaneous reactions but didn’t affect the eyelid edema 24 h postoperatively. Trial registration This study was registered at chictr.org (the first registration date is 03/04/2023, and the registration number is ChiCTR2300070153).

Topical anesthetics are widely applied in order to relieve the discomfort and anxiety caused by needle insertion and other painful superficial interventions at the oral cavity. So far, there are no commercially available effective topical anesthetic formulations for that purpose, and the most of developments are related to hydrophilic and low mucoadhesive forms. Therefore, we have prepared different hybrid nanofilms composed of biopolymer matrices (chitosan, pectin, and chitosan-pectin) blended with nanostructured lipid carriers (NLC) loading the eutectic mixture of 5% lidocaine–prilocaine (LDC–PLC), in order to fulfill this gap in the market. These dual systems were processed as hybrid nanofilms by the solvent/casting method, and its mucoadhesive, structural and mechanical properties were detailed. The most appropriate hybrid nanofilm combined the advantages of both pectin (PCT) and NLC components. The resultant material presented sustained LDC–PLC release profile for more than 8 h; permeation across porcine buccal mucosa almost twice higher than control and non-cytotoxicity against 3T3 and HACAT cell lines. Then, the in vivo efficacy of PCT/NLC formulation was compared to biopolymer film and commercial drug, exhibiting the longest-lasting anesthetic effect (> 7 h), assessed by tail flick test in mice. These pectin-based hybrid nanofilms open perspectives for clinical trials and applications beyond Dentistry.

Arteriovenous fistula puncture pain is a serious problem for patients undergoing dialysis and a good indication for topical anesthetics. No previous study has compared lidocaine/prilocaine cream (EMLA) with lidocaine tape for pain relief during arteriovenous fistula puncture in patients undergoing maintenance hemodialysis. To this end, we conducted a multicenter randomized crossover study including 66 patients (mean age, 65.8 years; males, 57.6%) undergoing maintenance hemodialysis thrice/week. Subjects were assigned to Sequence EL (EMLA administration followed by lidocaine, with 1-week wash-out) or Sequence LE (reverse administration, first lidocaine then EMLA). All subjects completed the study. At each puncture site, 1 g EMLA (25 mg lidocaine + 25 mg prilocaine) or one sheet of lidocaine tape (18 mg lidocaine) was applied 1 h or 30 min prior to arteriovenous fistula puncture, respectively. The primary endpoint was puncture pain relief, which was measured using a 100-mm visual analog scale. The secondary endpoints included quality of life, which was measured by SF-36, and safety. EMLA produced a 10.1-mm greater visual analog scale improvement than lidocaine tape (P = 0.00001). However, there was no statistically significant difference in the quality of life between the two groups, and no significant carryover/period effect was observed in any analysis. Further, no drug-related adverse events were observed. Taken together, these results suggest that EMLA cream is superior to lidocaine tape for the relief of arteriovenous fistula puncture pain in patients undergoing maintenance hemodialysis. Trial registration: University Hospital Medical Information Network Clinical Trials Registry (UMIN000027885).

Extracorporeal shock wave lithotripsy-related pain is the largest limiting factor in this technique. Our study aimed to compare the effectiveness of different types of analgesics for pain management used during ESWL sessions. We conducted a prospective study of 300 patients with urinary lithiasis justifying ESWL treatment. The patients were randomized to three groups: group I, included 100 patients who received intramuscular injection of 2cc of physiological saline solution (placebo), group II included 100 patients who received intramuscular injection of ketoprofen 100mg while group III included 100 patients who received lidocaine and prilocaine topical cream. Visual Analog Scale (VAS) was used to assess pain 10 minutes after and at the end of the session. Mean VAS score 10 minutes after and at the end of ESWL session was 3.7 and 4.91 respectively. There was no significant difference among the three groups with respect to: epidemiological data (age, sex, BMI, patient's history) and the characteristics of the renal stone (side, size, location, presence or not of double-J ureteral catheter). Eleven patients in the Group I terminated treatment early, with a significant difference compared to the other groups (p=0.003). VAS score 10 minutes after and at the end of ESWL session was statistically higher in Group I compared to Groups II and III (p < 0.001). Moreover, ESWL session was significantly more effective in Groups (II and III) compared to Group I (p<0.001). Pain treatment is necessary during ESWL sessions. Two painkillers molecules were assessed, which showed good pain control as well as an increase in the effectiveness of lithotripsy.

BackgroundEutectic mixtures of lidocaine and prilocaine are used during painful dermatological procedures. Poisoning is rarely reported in adults.Material and methodWe report three cases of women who experienced lidocaine and prilocaine poisoning after laser-assisted hair removal. Plasma levels of local anesthetics were assayed by a fully validated liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method.Case reportsThe rules of application of the anesthetic cream were observed apart from the maximum dose and/or maximum surface area. One patient applied a higher dose than the maximum recommended dose (140 instead of 60 g) and all patients failed to comply with the maximum recommended surface area (600 cm2). The patients presented an unusual clinical pattern as compared with other local anesthetics overdose: signs of cardiac toxicity with no ECG changes or arrhythmia, neurological toxicity without seizures or coma, and methemoglobinemia.DiscussionHealth authorities should publish explicit recommendations targeting users and prescribers with particular emphasis on the maximal surface area of application.

Ear tattooing is a routine procedure performed on laboratory, commercial and companion rabbits for the purpose of identification. Although this procedure is potentially painful, it is usually performed without the provision of analgesia, so compromising animal welfare. Furthermore, current means to assess pain in rabbits are poor and more reliable methods are required. The objectives of this study were to assess the physiological and behavioural effects of ear tattooing on rabbits, evaluate the analgesic efficacy of topical local anaesthetic cream application prior to this procedure, and to develop a scale to assess pain in rabbits based on changes in facial expression. In a crossover study, eight New Zealand White rabbits each underwent four different treatments of actual or sham ear tattooing, with and without prior application of a topical local anaesthetic (lidocaine/prilocaine). Changes in immediate behaviour, heart rate, arterial blood pressure, serum corticosterone concentrations, facial expression and home pen behaviours were assessed. Changes in facial expression were examined to develop the Rabbit Grimace Scale in order to assess acute pain. Tattooing without EMLA cream resulted in significantly greater struggling behaviour and vocalisation, greater facial expression scores of pain, higher peak heart rate, as well as higher systolic and mean arterial blood pressure compared to all other treatments. Physiological and behavioural changes following tattooing with EMLA cream were similar to those in animals receiving sham tattoos with or without EMLA cream. Behavioural changes 1 hour post-treatment were minimal with no pain behaviours identifiable in any group. Serum corticosterone responses did not differ between sham and tattoo treatments. Ear tattooing causes transient and potentially severe pain in rabbits, which is almost completely prevented by prior application of local anaesthetic cream. The Rabbit Grimace Scale developed appears to be a reliable and accurate way to assess acute pain in rabbits.

Background Pediatric patients often receive topical anesthesia before skin procedures in the Emergency Department, with EMLA cream and amethocaine gel being common choices. The most effective option remains a subject of debate. Objective Our goal was to compare EMLA cream with amethocaine gel in pediatric patients undergoing topical anesthesia, focusing on outcomes: first-attempt cannulation success, child-reported visual analogue scale (VAS) score, parent-reported VAS score, observed pain score, child-reported absence of pain, and child-reported acceptable anesthesia. Methods A database search for studies comparing EMLA cream and amethocaine gel in pediatric topical anesthesia was conducted. Two reviewers extracted and cross-verified data, with a third ensuring accuracy. Using R software, a pairwise meta-analysis was performed via the Mantel-Haenszel method. Outcomes were pooled as risk ratios or standard mean differences with 95% confidence intervals using the random-effects model. Results Amethocaine gel surpasses EMLA cream in child-reported pain absence and first cannulation success. No significant differences were found in child-reported acceptable anesthesia or observed pain scores. Similarly, child- and parent-reported VAS scores showed no variations between EMLA and amethocaine. Conclusion This analysis favors amethocaine gel for pediatric topical anesthesia. Further large randomized trials comparing EMLA cream and amethocaine gel in pediatric patients are warranted. Impact Procedural pain is a major concern for pediatric patients, their families, and physicians. Topical anesthesia is routinely given prior to children undergoing skin-related procedures in the Emergency Department. In pediatric patients, topical anesthetics such as eutectic mixture of local anesthetics cream and amethocaine gel have proved to be pioneering in pain reduction, but the most effective method is often disputed. Presently, this is the most comprehensive pooled analysis of trials comparing EMLA cream and amethocaine gel in pediatric patients undergoing topical anesthesia. Amethocaine performed better with regards to child-reported absence of pain and first attempt cannulation success.