Injection Pain Research Articles

Sterile water injections for relief of labour pain (the SATURN trial): study protocol for a randomised controlled trial

BackgroundUp to 80% of women use some form of pharmacological analgesia during labour and birth. The side effects of pharmacological agents are often incompatible with the concurrent use of non-pharmacological pain relieving strategies, such as water immersion, ambulation and upright positioning, or may have negative effects on both the mother and fetus. Sterile water injections given into the skin of the lumbar region have been demonstrated to reduce back pain during labour. However, the injections given for back pain have no effect on abdominal contraction pain. The analgesic efficacy of sterile water injections for abdominal pain during childbirth is unknown. The injections cause an immediate, brief but significant pain that deters some women from using the procedure. This study aims to investigate the use of water injections given intradermally into the abdomen to relieve labour contraction pain. A vapocoolant spray will be applied to the skin immediately prior to the injections to reduce the injection pain.MethodsIn this pragmatic, placebo controlled trial 154 low-risk women in labour at term with a labour pain score ≥ 60 on a 100 millimitre visual analogue scale (VAS) will be randomly allocated to receive either six injections of sterile water or a sodium chloride 0.9% solution as a placebo (0.1–.0.3 ml per injection). Three injections are given along the midline from the fundus to the supra-pubis and three laterally across the supra-pubis. The primary outcome will be the difference in VAS score 30 min post injection between groups. Secondary outcomes include VAS score of the injection pain on administration, VAS score of labour pain at 60 and 90 min, maternal and neonatal birth outcomes.DiscussionAccess to effective pain relief during labour is fundamental to respectful and safe maternity care. Pharmacological analgesics should support rather than limit other non-pharmacological strategies. Sterile water injections have the potential to provide an alternative form of labour pain relief that is easy to administer in any labour and birth setting, and compatible with other non-pharmacological choices.Trial registrationANZCTR (ACTRN12621001036808) Date submitted: 22/06/2021. Date registered: 05/08/2021. https://www.anzctr.org.au/

Effects of low level laser therapy on injection pain and anesthesia efficacy during local anesthesia in children: Arandomized clinical trial.

The use of low level laser therapy (LLLT) to reduce injection pain associated with dental local anesthesia is reported in a limited number of studies in adults, but research on the effects of LLLT in children is needed. This study aimed to evaluate the effects of topical anesthesia+LLLT on injection pain, anesthesia efficacy, and duration in local anesthesia of children who are undergoing pulpotomy treatment. The study was conducted as a randomized, controlled-crossover, double-blind clinical trial with 60 children aged 6-9years. Before local infiltration anesthesia was administered, only topical anesthesia was applied in one side (control group/CG), and topical anesthesia plus LLLT (a diode laser: 810nm; continuous mode; 0.3W; 20s; 69J/cm2 ) was applied in the contralateral side (LG) as pre-anesthesia. The injection pain and anesthesia efficacy were evaluated subjectively and objectively using the Wong-Baker Faces Pain Rating Scale (PRS) and the Face, Legs, Activity, Cry, Consolability (FLACC) scale respectively. Data were analyzed for statistical significance (p<.05). The "no pain" and "severe pain" rates in the PRS were 41.7% and 3.3% for the LG and 21.7% and 11.7% for the CG, respectively, during injection. Similarly, in the FLACC data, the number of "no pain" responses was higher for the LG than the CG (40%, 33.3%) and no "severe pain" rate was observed in both groups. The only statistically significant difference found for the PRS was p<.05. The median pain score was "0" for the LG and the CG in the FLACC data for the evaluation of anesthesia efficacy, and there was no statistically significant difference between the groups in terms of pain and anesthesia duration (p>.05). Also, most of the children preferred injection with topical anesthesia+LLLT (66.7%). It has been determined that the application of topical anesthesia+LLLT with an 810-nm diode laser before local infiltration anesthesia reduced injection pain and did not have an effect on anesthesia efficacy and duration in children.

MAS-1, a novel water-in-oil adjuvant/delivery system, with reduced seasonal influenza vaccine hemagglutinin dose may enhance potency, durability and cross-reactivity of antibody responses in the elderly

BackgroundIncreased influenza vaccine efficacy is needed in the elderly at high-risk for morbidity and mortality due to influenza infection. Adjuvants may allow hemagglutinin (HA) dose-sparing with enhanced immunogenicity. MAS-1 is an investigational water-in-oil emulsion-based adjuvant/delivery system comprised of stable nanoglobular aqueous droplets. MethodsA phase 1, randomized, double-blind, safety and immunogenicity, adjuvant dose escalation trial was conducted in persons aged 65 years and older. MAS-1 adjuvant dose volumes at 0.3 mL or 0.5 mL containing 9 µg per HA derived from licensed seasonal trivalent influenza vaccine (IIV, Fluzone HD 60 µg per HA, Sanofi Pasteur) were compared to high dose (HD) IIV (Fluzone HD). Safety was measured by reactogenicity, adverse events, and safety laboratory measures. Immunogenicity was assessed by serum hemagglutination inhibition (HAI) antibody titers. ResultsForty-five subjects, aged 65–83 years, were randomly assigned to receive 9 µg per HA in 0.3 mL MAS-1 (15 subjects) or HD IIV (15 subjects) followed by groups randomly assigned to receive 9 µg per HA in 0.5 mL MAS-1 (10 subjects) or HD IIV (5 subjects). Injection site tenderness, induration, and pain, and headache, myalgia, malaise and fatigue were common, resolving before day 14 post-vaccination. Clinically significant late-onset injection site reactions occurred in four of ten subjects at the 0.5 mL adjuvant dose. Safety laboratory measures were within acceptable limits. MAS-1-adjuvanted IIV enhanced mean antibody titers, mean-fold increases in antibody titer, and seroconversion rates against vaccine strains for at least 168 days post-vaccination and enhanced cross-reactive antibodies against some non-study vaccine influenza viruses. ConclusionMAS-1 adjuvant provided HA dose-sparing without safety concerns at the 0.3 mL dose, but the 0.5 mL dose caused late injection site reactions. MAS-1-adjuvanted IIV induced higher HAI antibody responses with prolonged durability including against historical strains, thereby providing greater potential vaccine efficacy in the elderly throughout an influenza season.Clinical Trial Registry: ClinicalTrials.gov # NCT02500680.

Effect of 6% hydroxyethyl starch pre-administration for reduction of pain on propofol injection: A placebo-controlled randomised study.

Background and Aims:Colloids modify the vascular endothelium and prevent contact activation of various substances. Pre-administration of colloids may prevent contact activation of vascular endothelium by propofol. The objective of this study was to evaluate the effect of 6% hydroxyethyl starch (HES) 130/0.4 pre-administration on propofol injection pain.Methods:Adult patients of the American Society of Anesthesiologists physical status I and II patients, 18-65 years old, of either gender and undergoing elective surgery were randomised into two groups. 100 mL bolus of HES or 0.9% normal saline (NS) was administered over three to five minutes through an 18 G cannula placed in the hand or forearm vein, followed by induction with 1% propofol premixed with 2% lidocaine. Pain during propofol injection was assessed every 10 seconds before the loss of verbal contact as 0- no pain; 1- mild pain evident only on questioning after 10 seconds without any obvious discomfort; 2-moderate pain self-reported by patients within 10 seconds with some discomfort; and 3- severe pain accompanied by withdrawing of hand, and behavioural signs.Results:126 patients completed the study. Overall incidence of pain was significantly higher in the NS group vs HES group (53% vs 28%; P = 0.004; relative risk 1.54, 95% confidence interval 1.13-2.09). Incidence of severe (8% vs 0%) and moderate pain (16% vs 5%) was higher in the NS group, while the incidence of mild pain was comparable (29% vs 23%; NS vs HES). A significant difference was seen in the severity of pain between the groups (P = 0.002).Conclusion:Pre-administration of 100 mL bolus of 6% HES 130/0.4 significantly reduced propofol injection pain.

Effect of topical local anaesthesia on injection pain associated with administration of sterile water injections - a randomized controlled trial

BackgroundSterile water injections can provide effective pain relief during childbirth, particularly for low back pain related to childbirth. However, the pain associated administering the injections can negatively impact women’s impressions of the procedure. It may discourage women from considering repeat doses despite the quality of analgesia experienced. Determining strategies to reduce the pain related to the administration of sterile water injections would improve the acceptability of the technique. Therefore, the aim of this study was to evaluate the effect of topical local anesthesia on the pain associated with administration of sterile water injections.MethodsThe study was designed as a multi-arm single-blind, randomized, controlled trial and 120 female healthy students were randomly divided according to one of four groups. The Intervention group received sterile water injections with topical local anesthesia. Control group 1 received sterile water injections without topical local anesthesia, control group 2 received injections of isotonic saline 0.9% with topical local anesthesia and control group 3 received injections of isotonic saline 0.9% without topical local anesthesia. Pain Immediately after the injections and subsidence in pain were recorded using a visual analogue scale. Sensations in the injection area were reported 15 min and the day after the injections.ResultsThe main finding of this study was that local anesthesia with EMLA® reduces the pain associated with the administration of intracutaneous sterile water injections. There was a significant difference in the self-assessed pain score immediately following the injections between the control (73.3 mm) and intervention groups (50.0 mm), p = 0.001. No adverse side effects were reported.ConclusionLocal anesthesia with EMLA® reduces the pain associated with intracutaneous administration of sterile water injections.Trial registrationThe study was registered 08/07/2014 at ClinicalTrials.gov Identifier: NCT02213185.

Remimazolam: pharmacological characteristics and clinical applications in anesthesiology.

A novel ultra-short-acting benzodiazepine (BDZ), remimazolam (CNS 7056), has been designed by ‘soft drug’ development to achieve a better sedative profile than that of the current drugs. Notably, the esterase linkage in remimazolam permits rapid hydrolysis to inactivate metabolites by non-specific tissue esterase and induces a unique and favorable pharmacological profile, including rapid onset and offset of sedation and a predictable duration of action. Similar to other BDZs, its sedative effects can be reversed using flumazenil, a BDZ antagonist. The pharmacokinetics and pharmacodynamics of remimazolam are characterized by relatively high clearance, small steady-state volume of distribution, short elimination half-life, short context-sensitive half-life, and fast onset and recovery, indicating rapid elimination, minimal tissue accumulation, and good control. In addition, remimazolam possesses a superior safety profile, including low liability for cardiorespiratory depression and injection pain, making it a preferred hypnotic agent in various clinical settings. Early clinical investigations suggest that remimazolam is well tolerated and effective for procedural sedation and for induction and maintenance of general anesthesia. To date, however, the clinical use of remimazolam has been confined to a few volunteer studies and a limited number of clinical investigations. Therefore, further studies regarding its recovery issues or postoperative complications, characteristics of electroencephalogram changes, and cost-benefit analyses are required to facilitate its widespread use.

Comparison and Clinical Value of Ciprofol and Propofol in Intraoperative Adverse Reactions, Operation, Resuscitation, and Satisfaction of Patients under Painless Gastroenteroscopy Anesthesia

Objective To investigate the comparison and clinical value of ciprofol and propofol for painless gastroenteroscopy anesthesia in terms of intraoperative adverse reactions, operation, resuscitation, and satisfaction of patients. Methods A total of 96 patients who underwent painless gastroenteroscopy anesthesia in our hospital from June 2021 to January 2022 were enrolled. The cases were randomly assigned into research group and control group. The control group received propofol anesthesia (n = 49), and the research group received ciprofol anesthesia (n = 47). The patients, physician satisfaction, vital signs, incidence of adverse reactions, anesthetic first dose, additional time, additional dose, total dose, induction time, insertion time, operation time, awake time, orientation recovery time, leaving room time, and injection pain score were compared. Results The overall satisfaction of the study group was higher than that of the control group (p < 0.05). After taking medicine, the score of 1 min and MAP in the study group were higher than those in the control group. The incidence of adverse reactions in the study group was lower than that in the control group (p < 0.05). The satisfaction of doctors in the study group was higher than that in the control group (p < 0.05). The anesthesia induction time, intubation time, operation time, awake time, orientation recovery time, and leaving room time in the study group were significantly longer than those in the control group (p < 0.05). The incidence and degree of injection pain in the propofol group were significantly lower than those in the propofol group (p < 0.05). Conclusion In painless gastroenteroscopy, compared with propofol, ciprofol is equally safe and effective for patients and will not cause early cognitive dysfunction after operation, which is a good choice in painless gastroenteroscopy anesthesia. In addition, ciprofol has significant advantages in patient and physician satisfaction, especially in injection pain. This trial is registered with ChiCTR2100045400.

Effects of different topical anesthetics on pain from needle insertion and injection, and the influence of anxiety in patients awaiting endodontic treatment.

ObjectivesThis study aimed to evaluate the effects of 5% lidocaine and 2.5% lidocaine/2.5% prilocaine topical anesthetic on pain during needle insertion and infiltration injection in the labial mucosa of anterior maxillary teeth, and to assess the relationship between patients’ anxiety and pain scores.Materials and MethodsThe Modified Dental Anxiety Scale questionnaire was applied and recorded. Patients were randomly divided into 4 groups (n = 30), as follows: G1 group: 5% lidocaine and placebo for 1 minute, G2 group: 2.5% lidocaine/2.5% prilocaine and placebo for 1 minute, G3 group: 5% lidocaine and placebo for 3 minutes, and G4 group: 2.5% lidocaine/2.5% prilocaine and placebo for 3 minutes. Before the application of topical anesthesia, one side was randomly selected as the topical anesthesia and the contralateral side as the placebo. The pain levels were measured with Visual Analog Scale (VAS) immediately after needle insertion and injection and were compared. The correlation between anxiety and pain scores was analyzed.ResultsAdministration of 5% lidocaine for 1 minute had significantly higher pain scores for both insertion and infiltration injection than the other groups (p < 0.05). There was a significant moderate positive correlation between dental anxiety and the injection-induced VAS pain score in the placebo side in all groups (p < 0.05).ConclusionsTopical anesthetics significantly reduced the pain caused by both needle insertion and injection pain in comparison to the placebo side. The pain scores of patients with dental anxiety were lower on the topical anesthesia compared to the placebo side.Trial RegistrationThai Clinical Trials Registry Identifier: TCTR20201217002

A randomized controlled trial of three different local anesthetic methods for minor hand surgery.

Purpose: Hemostasis and local anesthetic injection are essential for minor hand surgeries under local anesthesia (LA). Wide awake local anesthesia no tourniquet (WALANT) became popular for achieving hemostasis without a tourniquet. However, a recent study reported that injection is more painful than tourniquet use in minor hand surgery. Therefore, this study aimed to compare three LA methods that differ according to injection and hemostasis, namely, the combination of a tourniquet and buffered lidocaine solution (CTB), WALANT, and conventional LA. Methods: This randomized prospective single-center study included 169 patients who underwent minor hand surgery between 2017 and 2020. We randomly allocated the patients to each group and recorded the pain and anxiety score during the surgery, as well as satisfaction after the surgery. Results: Pure lidocaine injection was significantly more painful than buffered lidocaine and WALANT solution injection (p < 0.001). Local anesthesia injection was significantly more painful than tourniquet use in all groups (p < 0.001). The intraoperative anxiety score was significantly lower in the CTB group than in the conventional LA and WALANT groups (p < 0.001). The satisfaction score was significantly higher in the CTB and WALANT groups than in the conventional LA group (p < 0.001). Conclusion: CTB for minor hand surgery under LA is associated with less injection pain and patient anxiety. The tourniquet is tolerable without much pain and waiting time. Thus, CTB in minor hand surgery is a good alternative to WALANT and conventional LA.

Effect of cold application on intramuscular injection pain among patients with fractures

Background Intramuscular injection (IMI) is an invasive and painful procedure that is routinely used in health care settings. The knowledge regarding the efficiency of nonpharmacological methods of pain management, including cold application, is limited and needs further research studies. Aim The aim of the study was to evaluate the effect of cold application on IMI pain among patients with fractures. Design A quasi-experimental design (pre-posttest nonequivalent control group design) was used. Setting This study was conducted in the inpatient clinic of Orthopedic Surgical Department in Beni Suef University Hospital. Sample A convenient consecutive sample of 64 adult male and female patients was enrolled in the study. Tools Two tools were used for data collection: (a) structured interview assessment form, including sociodemographic and medical-related data, and (b) pain assessment forms. Results The study findings revealed that the mean age of the study and control groups was 39.2±11.1 and 34.8±11.9 years, respectively. When analyzing the numerical pain scale, a statistically significant difference was found between both groups, with higher reduction in the total mean score of pain from 6.78±1.6 to 2.34±0.9 among the group that received cold application before IMI. It also showed that there were highly statistically significant differences in the total mean score of the observational checklist of nonverbal pain indicators of the study group between preintervention and postintervention results during movement and at rest (P≤0.001). Conclusion This study concluded that cold application was an effective nursing measure in reducing the pain intensity associated with IMI. Recommendations Continuous education for nurses must be provided to improve their knowledge and practice regarding nonpharmacological methods such as cold application and its effect on relieving pain arising from IMI into the vastus lateralis muscle.

A Randomized Triple-Blind Clinical Trial of the Effect of Low-Level Laser Therapy on Infiltration Injection Pain in the Anterior Maxilla

Objective: To evaluate the level of pain experienced during infiltration anesthesia of the anterior maxilla following low-level laser therapy (LLLT) with 810-980 nm wavelengths. Material and Methods: In the current triple-blind clinical trial, 84 patients received a total of 168 infiltration anesthesia injections (1.8 mL of 2% lidocaine plus 1:100,000 epinephrine) in the anterior maxilla. Each patient received two injections into the buccal mucosa of the right and left central incisors with a two-week interval. One injection was performed after LLLT, while the other injection was administered conventionally without laser. The pain level was measured immediately after injection using a visual analog scale (VAS). Results: There was a significant difference in the pain level experienced with and without LLLT, such that the mean pain score following LLLT was significantly lower than that without LLLT (p<0.05). No significant difference was found in the pain level between laser and no laser groups in males, but the difference in this regard was significant in females (p<0.05) and female patients experienced a significantly lower level of pain following LLLT. Conclusion: The low-level laser therapy can be successfully used to decrease the level of pain experienced during infiltration anesthesia of the anterior maxilla.

Analyzing the U.S. Post-marketing safety surveillance of COVID-19 vaccines

IntroductionSince December 2020, three COVID-19 vaccines have been authorized in the United States (U.S.) and were proceeded by large immunization programs. The aim of this study was to characterize the U.S. post-marketing safety (PMS) profiles of these vaccines with an in-depth analysis of mortality data. MethodsThis was a retrospective database analysis study. Details of the U.S. PMS reports (15 December 2020 to 19 March 2021) of the three vaccines (Pfizer-BioNTech, Moderna, and Janssen Ad26.COV2.S) were retrieved from the U.S. Vaccine Adverse Event Reporting System (VAERS). A descriptive analysis was conducted to characterize the reported adverse events (AEs). A comparative (Pfizer-BioNTech vs. Moderna) analysis of mortality was conducted. The mean count ratio of death between the two vaccines was estimated using a negative binomial regression model adjusting for the measured confounders. ResultsA total of 44,451 AE reports were retrieved (corresponding to 0.05% of the U.S. population who received at least one dose). The most commonly reported AEs were injection site reactions (30.4% of the reports), pain (reported in 26.7% of the reports), and headache (18.6% of the reports). Serious AEs were reported in only 14.6% of the reports with 4,108 hospitalizations. The total number of deaths was 1,919 with a mean count ratio of Moderna (n = 997) vs. Pfizer-BioNTech (n = 899) of 1.07 (95% confidence interval 0.86 to 1.33). ConclusionsThe vast majority of PMS AEs in the U.S. were non-serious, and the number of serious AEs is very low given the total number of vaccinated U.S. population.

Pain, Drug Leakage and Inflammation Associated with Intramuscular Injections of Magnesium Sulfate in Preeclamptic Women: A Descriptive Study

Introduction: Magnesium sulfate (MgSO4) is the drug of choice for preventing and treating convulsions in severe preeclampsia and eclampsia by intramuscular (IM) and IV (IV) regimen. Repeated IM injections of MgSO4 at the same site causes pain, drug leakage, and injection site inflammation. To manage IM injection-related complications, it is important to have an estimation of these adverse effects. Objective: To evaluate the pain, drug leakage, and inflammation associated with IM injections of MgSO4. Material and Methods: A longitudinal descriptive study was carried out in the labor room, PGIMER, Chandigarh. Thirty study participants diagnosed and admitted with preeclampsia were recruited by the total enumeration sampling technique. Each patient received eight IM injections of MgSO4 on the dorsogluteal site as prescribed by the obstetrician. Identification details, clinical, and biophysical characteristics were collected. The pain was assessed by a numerical rating scale (NRS). Sterile blotting paper was used to assess the drug leakage by measuring the wet area of the blotting paper and recording in cm2. A gridded transparent sheet was used for measuring inflammation. The area of the swelling marked and measured by placing the gridded transparent sheet over the swelling and recording in cm2. Results: Pain and drug leakage was significantly increased from the first injection to the eighth injection ( P &lt; .05) and inflammation of 100.60 ± 21.23 (Right), 102.07 ± 21.23 (left) cm2 recorded over the buttocks. Conclusion: Significant increase in pain, drug leakage, and inflammation were recorded during the IM administration of MgSO4. For reducing the pain, drug leakage, and inflammation, nonpharmacological interventions and different techniques of IM injections are recommended.

Efficacy of New Vibration Device in Reduction of Injection Pain among Children-A Randomized Control Trial

Needle-related procedures considered as the very crucial sources of pain in children. Pain management during invasive procedure is a challenge to direct health care providers. Unnecessary pain can spoil the nurse-patient relationship. Injections usually reason for some level of pain at the injection site. To develop and validation of the new vibration device for reduction of injection pain and compare the injection pain score among children between experimental and the control group. We will base this study on Analytical intervention approach. A hospital-based Randomized Controlled Trial will consider the effect of a new vibration device in intervention and routine care in the control group for reduction of injection pain. The sample will be children of the age Group 4 years to 12 years. Researcher will take before data collection selection of children as per inclusion criteria, detail explanation about nature and purpose of the study the written consent from the child’s parent. The computerized randomized sampling technique will use for the group formation. The setting of the study will be Hospital Wardha. There will be an efficacy of interventions on children's outcomes reduce injection pain and stable emotional behaviour and stable physiological parameter. Researcher will draw conclusion after the analysis of data collected from the predetermined sample size. Researcher will publish the findings of the study in an open access peer-reviewed Journal.

Long Term Effectiveness and Safety of Intracavernosal Botulinum Toxin A as an Add-on Therapy to Phosphosdiesterase Type 5 Inhibitors or Prostaglandin E1 Injections for Erectile Dysfunction

Some evidence suggests that intracavernosal botulinum toxin A (BTX-A IC) injections administered in addition to phosphodiesterase type 5 inhibitors (PDE5-Is) or prostaglandin E1 intracavernosal injections (PGE1 ICI) could effectively treat erectile dysfunction (ED) in non-responders, or insufficient responders to these pharmacologic treatments. To determine the long-term effectiveness and safety of combined treatment involving a single injection of BTX-A IC as an add on therapy to PDE5-Is or PGE1-ICI for the treatment of ED of different etiologies. A retrospective, uncontrolled, single center study was conducted. Data from 123 consecutive patients with ED who were insufficient responders to PDE5-Is or PGE1-ICI and who received onabotulinumtoxinA 100 U, abobotulinumtoxinA 250 U or 500 U IC as an add on to their current pharmacologic treatment were analyzed. All analyses were exploratory. Qualitative data were compared using the Fisher's exact test. Univariate and multivariate analysis were performed using logistic regression with Odds Ratios (OR). Only variables with P < .05 in the univariate analysis were selected for multivariate analysis. The minimally clinically important difference (relative to baseline severity of ED) in the International Index of Erectile Function-Erectile function domain (IIEF-EF) score was achieved in 50% of patients at 34 (27-42) days and in 41% at 5.9 (3.9 - 8.1) months following BTX-A IC in combination with PDE5-Is or PGE1 ICI. The severity of ED influenced response to BTX-A IC according to the multivariate analysis (OR = 0.3, IC(95%]) = (0.16 - 0.56). Neither being post prostatectomy nor the type of BTX-A affected the response. Effectiveness tended to decrease more over time with abobotulinumtoxinA 250 U than 500 U.The only side-effects were mild penile pain on injection (n = 1) and mild penile pain for 3 days following injection (n = 1); no systemic effects were reported. BTX-A IC (all types) administered as an add on to registered pharmacologic treatments improved erectile function for at least 6 months in 41% of patients with ED of varying etiologies, and was safe. A relatively large cohort of patients with ED was included, with a long follow-up period, however the study was retrospective, and uncontrolled. This study provides preliminary evidence that BTX-A IC administered as an add-on therapy for ED that is insufficiently responsive to standard therapy is effective for at least 6 months, and is safe. Randomized clinical trials are now needed to fully confirm these results.

Sexual rehabilitation with intracavernous alprostadil after radical prostatectomy: Outcomes from a nursing program.

Erectile dysfunction (ED) is a common complication after radical prostatectomy that affects quality of life. There are several therapeutic options, including intracavernous alprostadil injections (IAI). However, no specific recommendations have been made on the optimal rehabilitation strategy. In this study we evaluated a sexual rehabilitation program (SRP) with IAI for patients with ED after radical prostatectomy, assessing the rate of compliance and reasons for dropout. The sexual rehabilitation program (SRP) was offered to all patients who underwent radical prostatectomy from 1 January 2010 to 31 December 2019. The first consultations were performed by a urology specialist nurse, explaining the IAI procedure and possible complications. The program was considered successful when the patients achieved autonomy in the drug preparation with a good injection technique. A medical consultation was performed at 6 months evaluating the IAI usage and adverse events. In case of dropout, a questionnaire about reasons for dropout was performed. The primary endpoint was the rate of compliance and dropout of the program. Secondary endpoints were the reasons for dropout and adverse events. 340 patients underwent radical prostatectomy at our institution, and 123 patients accepted to participate in the rehabilitation program. A total of 96 patients (78%) successfully completed the SRP, and at 6 months 60 (62.5%) still used IAI. Concerning the reasons for dropping out, the most frequent were the need of injectable therapy and pain. Regarding complications, 17 patients (13.8%) reported pain related to the injection and 1 patient (0.8%) had a priapism, managed with conservative treatment. Management of post-radical prostatectomy ED by a nursing program achieved good rates of patients' self-injection accomplishment and treatment compliance. Close monitoring for dose adjustment and management of post-injection penile pain is required during the follow-up.

Intravenous and Intramuscular Allopregnanolone for Early Treatment of Status Epilepticus: Pharmacokinetics, Pharmacodynamics, and Safety in Dogs.

Allopregnanolone (ALLO) is a neurosteroid that modulates synaptic and extrasynaptic GABAA receptors. We hypothesize that ALLO may be useful as first-line treatment of status epilepticus (SE). Our objectives were to (1) characterize ALLO pharmacokinetics-pharmacodynamics PK-PD after intravenous (IV) and intramuscular (IM) administration and (2) compare IV and IM ALLO safety and tolerability. Three healthy dogs and two with a history of epilepsy were used. Single ALLO IV doses ranging from 1-6 mg/kg were infused over 5 minutes or injected IM. Blood samples, vital signs, and sedation assessment were collected up to 8 hours postdose. Intracranial EEG (iEEG) was continuously recorded in one dog. IV ALLO exhibited dose-proportional increases in exposure, which were associated with an increase in absolute power spectral density in all iEEG frequency bands. This relationship was best described by an indirect link PK-PD model where concentration-response was described by a sigmoidal maximum response (Emax) equation. Adverse events included site injection pain with higher IM volumes and ataxia and sedation associated with higher doses. IM administration exhibited incomplete absorption and volume-dependent bioavailability. Robust iEEG changes after IM administration were not observed. Based on PK-PD simulations, a 2 mg/kg dose infused over 5 minutes is predicted to achieve plasma concentrations above the EC50, but below those associated with heavy sedation. This study demonstrates that ALLO is safe and well tolerated when administered at 1-4 mg/kg IV and up to 2 mg/kg IM. The rapid onset of effect after IV infusion suggests that ALLO may be useful in the early treatment of SE. SIGNIFICANCE STATEMENT: The characterization of the pharmacokinetics and pharmacodynamics of allopregnanolone is essential in order to design clinical studies evaluating its effectiveness as an early treatment for status epilepticus in dogs and people. This study has proposed a target dose/therapeutic range for a clinical trial in canine status epilepticus.

Cooling Anesthesia for Intravitreal Injection: Results of the Prospective Open-Label, Dose-Ranging COOL-1 Trial

PurposeTo evaluate the safety and efficacy of a novel medical device to provide cooling anesthesia to the eye as local anesthesia for intravitreal injections.Study DesignFirst in human, open-label study of 43 subjects assessed at three different doses: −10°C for 20 seconds (group 1), −15°C for 15 seconds (group 2), and −15°C for 20 seconds (group 3). Main outcome measures were safety and pain of injection using a numeric rating scale (NRS).ResultsCooling anesthesia did not result in any serious ocular adverse events. One grade 1 adverse event was a vasovagal response during cooling administration which resolved immediately after cooling. Mean NRS scores at the time of injection for each group ranged from 2.5 to 4.3 There was a statistically significant difference between pain scores of the 3 groups at injection in aggregate but not in pairwise comparisons (P value = 0.047). There was a statistically significant decrease in pain from injection to 5 minutes post injection in all groups (P value = 0.00008, 0.003, 0.0005 for groups 1, 2, 3, respectively) as well as from 5 minutes to 24–48 hours (P value = 0.00001, 0.018, and 0.0545 for groups 1, 2, 3, respectively).ConclusionThe rapid cooling anesthesia device was well tolerated for achieving local anesthesia among patients receiving intravitreal injections with no serious ocular adverse events.

Comparison of Effects of Ketamine, Esmolol and Lidocaine on Propofol Injection Pain

Objective: Propofol is the most frequently used agent for intravenous anesthesia administration. However, during propofol injection, pain may develop in the hand and forearm region and cause unwanted situations. Different applications have been used to prevent propofol injection pain. Although lidocaine is often used for proprofol injection pain, anesthetic agent ketamine, which has an analgesic feature, is also preferred. In recent years, the analgesic feature of esmolol, a short-acting beta blocker, has been emphasized. Our aim was to evaluate the effects of three different agents, ketamine, esmolol or lidocaine, on the severity of pain developing by propofol injection. Also, hemodynamic effects were investigated. Methods: Sixty cases in ASA groups I and II, aged from 18 to 80 years old undergoing elective operations included in the study. To reduce the pain due to propofol injection, patients were given either 0.5 mg/kg ketamine, 0.5 mg/kg esmolol HCl or 0.5 mg/kg lidocaine. For induction 1% propofol injection was administered, presence and severity of pain in the arm was questioned and recorded. To evaluate the severity of pain developing due to propofol injection, a 4-point numerical scale was used (no pain: 1, mild pain: 2, moderate pain: 3 and severe pain: 4). Arm pull motion was also recorded. Results: There were no significant differences between the groups according to the severity of pain and pulling arm rates. There was no significant difference between hemodynamic parameters in the groups preoperatively, first, 5th, 10th, 15th, 20th and 30th minute. Conclusion: Ketamine, esmolol, and lidocaine can safely control the severity of pain developing by propofol injection. Esmolol, ketamine and lidocaine provided effective analgesia at the doses used in our study without affecting the hemodynamic findings of the patients.

Comparison of the efficacy and safety of intralesional injection of tranexamic acid and the topical application of Kligman combination drug in the treatment of macular amyloidosis.

Macular amyloidosis (MA) is a common form of cutaneous amyloidosis that manifests as dark spots consisting of brown pigments with a rippled pattern on the skin, and the treatment of this condition is highly challenging. The aim of this study was to compare the efficacy and safety of intralesional injection of tranexamic acid (TXA) and topical application of Kligman combination drug in the treatment of macular amyloidosis. In this double-blind clinical trial, a total of 43 patients, who were diagnosed with MA, were treated with two different methods of intralesional injection of tranexamic acid and topical application of Kligman combination drug. Both therapeutic methods were effective in improving MA and significantly reduced hyperpigmentation of the treated areas, but tranexamic acid was significantly more effective than the Kligman combination drug. Significantly, greater improvements were observed in the group of patients treated with tranexamic acid. In the tranexamic acid treatment group, ΔE was reduced from 11.39 in the first session to 8.53 in the third session, and in the Kligman treatment group, it was reduced from 8.79 in the first session to 6.32 in the third session (p< 0.05). In addition, the pruritus score in patients treated with topical tranexamic acid injection was lower compared to the patients treated with the topical application of the Kligman combination drug. The results of this study demonstrated the significant positive effects of both treatment methods, but in terms of reducing melanin content, intralesional injection of tranexamic acid was a more effective method. Both treatments considered safe for MA. In tranexamic acid group, patients logically experienced a tolerable pain during injection but they significantly had significantly lower local pruritic discomfort during study. So, based on the positive findings of this study we suggest to use tranexamic acid in combination with other effective therapeutic methods for treatment of MA especially use of its topically applied form in combination with non-aggressive needling that results in better drug delivery without the experience of injection pain. Selection of the best administration route of tranexamic acid for hyperpigmented lesions depends on the each patient characteristic and their previous theraputic results that may vary case by case.