Bleeding complications following intramuscular injections among hospitalized anticoagulated patients: a retrospective observational comparative study.

BACKGROUND: Bleeding complications following intramuscular (IM) injections are generally considered rare with reported incidence of 0.06%. However, evidence on safety of IM injections among anticoagulated hospitalized patients is lacking. The objective of the current study was to examine the incidence of injection site bleeding complications following IM injection among anticoagulated hospitalized patients. METHODS: A retrospective comparative study comprised of all hospitalized patients ≥ 18 years old that were treated with ≥ 1 IM injection between 2009 and 2019 in a large tertiary medical center. Bleeding complications were defined as focal hematoma, local bleeding, intramuscular bleeding or compartment syndrome. Each case with IM injection was searched for ICD9 codes (e.g., hematoma, hemorrhage or compartment syndrome) and for indirect evidence suggestive of potential bleeding: hemoglobin drop ≥ 2 g/dl, AST or CPK increase, packed red blood cell transfusion, or abrupt cessation of the anticoagulation. These case were then verified for true injection-site bleeding by natural language processing model and manual review of the electronic medical record. RESULTS: A total of 71,710 patients were treated with 236,406 IM injections. Mean age 53 (± 22) and 63% were females. Concomitant anticoagulation (Heparins: 90.3%, warfarin: 6.8% and DOACs: 4.7%) occurred in 40,819 IM injections (8189 patients). Suspected bleeding complications at the IM injection site were identified among 7,111 patients following 23,089 IM injections, the majority were unrelated to the IM injection-site (e.g., gastrointestinal bleeding, retroperitoneal, etc.). Two cases were verified as true injection site bleeding complication, both in the anticoagulated group (2/8189, 0.02%). CONCLUSION: Bleeding complications at site of IM injections among anticoagulated hospitalized patients are rare, and their risk is probably not higher compared to patients without anticoagulation.

Sensory assessment of intramuscular quadratus lumborum block at the L2 level in open inguinal hernia repair patients.

BACKGROUND: The effectiveness of the quadratus lumborum block (QLB) for postoperative pain management depends on the injection pathway used. There is limited research on the block area produced by intramuscular injection of local anesthesia in the quadratus lumborum muscle. This study aimed to determine the cutaneous sensory blockade area produced by an intramuscular quadratus lumborum block (QLBi) at the L2 level. METHODS: Twenty patients aged 18-60 years with ASA grade I-II and a BMI of 18-30 kg/m2 who were scheduled for open inguinal hernia repair with mesh underwent ultrasound-guided QLBi injection of 20 ml of 0.5% ropivacaine. The cutaneous sensory blockade area was measured by applying a cold stimulus 1 h after the block and then measured every hour after surgery until the sensation returned to normal. The duration of a blockade is defined as the time it takes for all affected areas to fully regain normal sensation following a blockade. Pain scores (numeric rating scale, NRS) were recorded at 2, 4, 8, 12, and 24 h after surgery. Adverse reactions to QLBi were recorded 24 h after surgery. RESULTS: All 20 patients had reduced or lost cold sensation areas. The greatest extent of cold sensation reduction occurred at T7 (10%), and the least amount of cold sensation reduction occurred at L3 (10%). The block level covered T8 (20%), T9 (30%), T10 (45%), T11 (90%), T12 (95%), L1 (100%), and L2 (15%). Eighteen patients experienced areas of sensory loss, with the highest range at T11 and the lowest at L2. The duration of the blockade was 8.9 ± 3.8 h, with a maximum of 24 h and a minimum of 5 h. One patient experienced quadriceps weakness after surgery. CONCLUSION: Quadratus lumborum block of intramuscular pathway can produce effective cutaneous sensory blockade, which can be used for postoperative analgesia of indirect inguinal hernia operation, and may also be beneficial to analgesia of other lower abdominal operations. However, the best method needs further confirmation to determine specific anesthesia methods for various operations. CHINESE CLINICAL TRIAL REGISTRY: June 2, 2018; ChiCTR1800016457.

The effect of lavender oil use on pain and comfort level in intramuscular injection administration: A single blind randomized controlled study.

CONTEXT: The fact that the concept of quality in health care services has come to the fore and that evidence-based practices have become widespread made such concepts as patient satisfaction and comfort important and priority parameters in determining the quality of health services. OBJECTIVES: The aim of the study is to determine the effects of using lavender oil in intramuscular injection on injection pain, comfort level, blood pressure, pulse rate and respiratory rate. METHODS: The study was designed as a prospective, single-blind randomized controlled trial. The research was conducted in accordance with the CONSORT Checklist guide. In our study, a total of 160 individuals were included in the sample, 80 of whom were control and 80 were intervention. Structured Information Form, Visual Analog Scale and Comfort Scale were used to collect the data of the research. Mann Whitney U, Kruskal Wallis test and Wilcoxon test were used to evaluate the data. RESULTS: It was determined that the mean pain scores of the individuals who received intramuscular injection by applying lavender oil were statistically significantly lower than the individuals in the control group. Again, the comfort score averages of the individuals who were applied lavender oil were found to be statistically significantly higher than the control group. It was determined that the blood pressure, pulse rate and respiratory rate before the injection of the individuals in the control group increased statistically significantly according to the post-injection measurements, while the blood pressure, pulse rate and respiratory rate in the lavender oil group decreased significantly after the injection and remained within their normal values. CONCLUSION: As a result, it was determined that the application of lavender oil in intramuscular injection had a positive and significant effect on the blood pressure, pulse rate and respiratory rate of the individuals on the injection pain and comfort level.

Immune Response of Inactivated Rabies Vaccine Inoculated via Intraperitoneal, Intramuscular, Subcutaneous and Needle-Free Injection Technology-Based Intradermal Routes in Mice.

Inoculation routes may significantly affect vaccine performance due to the local microenvironment, antigen localization and presentation, and, therefore, final immune responses. In this study, we conducted a head-to-head comparison of immune response and safety of inactivated rabies vaccine inoculated via intraperitoneal (IP), intramuscular (IM), subcutaneous (SC) and needle-free injection technology-based intradermal (ID) routes in ICR mice. Immune response was assessed in terms of antigen-specific antibodies, antibody subtypes and neutralizing antibodies for up to 28 weeks. A live rabies virus challenge was also carried out to evaluate vaccine potency. The dynamics of inflammatory cell infiltration at the skin and muscle levels were determined via histopathological examination. The kinetics and distribution of a model antigen were also determined by using in vivo fluorescence imaging. Evidence is presented that the vaccine inoculated via the ID route resulted in the highest antigen-specific antibody and neutralizing antibody titers among all administration routes, while IP and IM routes were comparable, followed by the SC route. Antibody subtype analysis shows that the IP route elicited a Th1-biased immune response, while SC and IM administration elicited a prominent Th2-type immune response. Unexpectedly, the ID route leads to a balanced Th1 and Th2 immune response. In addition, the ID route conferred effective protection against lethal challenge with 40 LD50 of the rabies CVS strain, which was followed by IP and IM routes. Moreover, a one-third dose of the vaccine inoculated via the ID route provided comparable or higher efficacy to a full dose of the vaccine via the other three routes. The superior performance of ID inoculation over other routes is related to longer local retention at injection sites and higher lymphatic drainage. Histopathology examination reveals a transient inflammatory cell infiltration at ID and IM injection sites which peaked at 48 h and 24 h, respectively, after immunization, with all side effects disappearing within one week. These results suggest that needle-free injection technology-based ID inoculation is a promising strategy for rabies vaccination in regard to safety and efficacy.

Considering skin-to-muscle depth for successful intramuscular injections in an increasingly obese population.

BACKGROUND: Intramuscular (IM) injection practice is an essential nursing skill. Current practice relies on clinical judgement to determine needle length (unless specified in the medicine's product licence). Obesity is increasing in the global population, but guidelines have largely ignored how to select needle length to meet individual patient need. AIM: The aim of this review was to systematically review the skin-to-muscle depth required to achieve injection into muscle in adults. The objectives were to identify any implications of obesity status when selecting an appropriate needle length and site in clinical practice. Search and review methodology: Studies of subjects above the age of 18 years using observational or experimental designs where the distance from the skin to muscle had been measured at any IM injection site, and obesity status was reported, were included in the search strategy. The primary outcome of interest was the distance from skin surface to muscle penetration. FINDINGS: 14 studies were identified that investigated the dorsogluteal, ventrogluteal, deltoid and vastus lateralis sites, all used cross-sectional observational designs. Ten used ultrasound, three used computed tomography (CT) and one used magnetic resonance imaging. Obesity status was reported as BMI or hip-to-waist ratio. In all studies there was a correlation between obesity status and the distance from skin surface to muscle. In females this exceeded 37 mm at both gluteal sites, independent of obesity status. CONCLUSIONS: There should be an assessment of obesity status before selecting needle length for IM injections in both genders. Needles longer than the standard 37 mm are recommended for all females, whatever their obesity status, for any gluteal site. Injections into gluteal sites should be avoided in females who are obese. Deltoid injections are more likely to achieve muscle penetration in both genders, and in patients who are overweight or obese. Further research is required.

The efficacy of botulinum toxin a injections in pelvic floor muscles in chronic pelvic pain patients: a systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: Chronic pelvic pain (CPP) is a common multifactorial condition affecting 6 to 27% of women aged 18-50 years worldwide. This study was conducted to review and meta-analyse the current literature on the reduction of chronic pelvic pain after botulinum toxin A (BTA) injection. METHOD: In July 2021 we performed a systematic search in PubMed and EMBASE to assess the benefits of BTA injection in pelvic floor muscles in women with chronic pelvic pain. Primary outcome was reduction in visual analogue scale (VAS) after treatment. Secondary outcomes evaluated were: reduction of dyspareunia, pelvic floor resting pressure and quality of life. Identified reports were assessed on quality of reporting and risk of bias. Standardized mean difference (SMD) was used to combine and analyse outcomes of the included studies. RESULTS: Eight studies with 289 participants were considered eligible to be included in this systematic review and meta-analysis. After recalculating SMD into VAS scores (0-100), long-term follow-up (24-26 weeks) showed a significant 15-point improvement in VAS scores (95% CI: 8.8-21.5) for non-menstrual pelvic pain and a 13-point improvement (95% CI: 2.1-24.0) for dyspareunia. BTA injection had a significant effect on pelvic floor resting pressure and quality of life. CONCLUSION: There is limited scientific evidence on the effectiveness of BTA injections in pelvic floor muscles in women with chronic pelvic pain. The available studies show that BTA injections significantly reduce pain levels and improve quality of life at 6 months follow-up. PROSPERO ID: CRD42018105204.

Epidemiology and treatment outcomes in pediatric patients with post-injection paralysis.

BACKGROUND: Post-injection paralysis (PIP) of the sciatic nerve is an iatrogenic paralysis that occurs after an intramuscular injection, with resultant foot deformity and disability. This study investigates the epidemiology and treatment of PIP in Uganda. METHODS: Health records of pediatric patients surgically treated for PIP at the CoRSU Rehabilitation Hospital from 2013 to 2018 were retrospectively reviewed. Pre-operative demographics, perioperative management, and outcomes were coded and analyzed with descriptive statistics, chi-square for categorical variables, and linear models for continuous variables. RESULTS: Four-hundred and two pediatric patients underwent 491 total procedures. Eighty-three percent of reported injection indications were for febrile illness. Twenty-five percent of reported injections explicitly identified quinine as the agent. Although ten different procedures were performed, achilles tendon lengthening, triple arthrodesis, tibialis posterior and anterior tendon transfers composed 83% of all conducted surgeries. Amongst five different foot deformities, equinus and varus were most likely to undergo soft tissue and bony procedures, respectively (p=0.0223). Ninteen percent of patients received two or more surgeries. Sixty-seven percent of patients achieved a plantigrade outcome; 13.61% had not by the end of the study period; 19.3% had unreported outcomes. Those who lived further from the facility had longer times between the inciting injection and initial hospital presentation (p=0.0216) and were more likely to be lost to follow-up (p=0.0042). CONCLUSION: PIP is a serious iatrogenic disability. Prevention strategies are imperative, as over 400 children required 491 total surgical procedures within just six years at one hospital in Uganda.

Point-of-Care Ultrasound Identifies Pyomyositis Secondary to Intramuscular Testosterone Injection: Report of Two Cases.

BACKGROUND: Intramuscular (i.m.) injections are a commonly utilized route for medication delivery. Intramuscular-associated soft tissue infections are rare and can include pyomyositis and i.m. abscess. Intramuscular testosterone injections have not been previously implicated in causing pyomyositis. Point-of-care ultrasound is an important bedside tool that can identify pyomyositis and differentiate this infection from more common entities such as cellulitis. CASE REPORTS: We present two cases of i.m. testosterone-associated pyomyositis. In both cases, the physical examination features were consistent with simple cellulitis. However, point-of-care ultrasound evaluation revealed changes consistent with pyomyositis in each case. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although uncommon, i.m. injections such as testosterone carry a risk of soft tissue infection. As demonstrated in the above cases, ultrasound can be helpful in making the differentiation between simple cellulitis and pyomyositis. The emergency physician should be cognizant of this complication of therapeutic i.m. injections, as well as the diagnostic efficacy of point-of-care ultrasound in evaluating the extent and location of the soft tissue infection.

A Comparison of Two Different Tactile Stimulus Methods on Reducing Pain of Children During Intramuscular Injection: A Randomized Controlled Study.

INTRODUCTION: Pediatric patients in the emergency department often require intramuscular injection procedures, which may lead to pain, fear, and anxiety. The purpose of this study was to test a novel nonpharmacological intervention to reduce needle-related pain in the pediatric emergency department. METHODS: The study was conducted as a parallel-group, randomized controlled design. The study population consisted of 159 children aged 7 to 10 years cared for in the emergency department who received an intramuscular injection of ampicillin/sulbactam. The children were randomly assigned to Palm Stimulator, ShotBlocker, or control groups. The children's preprocedure fear levels were evaluated using the Children's Fear Scale, and their perceived pain levels during the procedure were evaluated using the Faces Pain Scale-Revised and Visual Analog Scale. Parents and observers also completed the pain level scores. RESULTS: According to all raters (child, parent, and observer), the Palm Stimulator group had the lowest mean Faces Pain Scale-Revised score averages (P < .001). The Visual Analog Scale score averages of the children in the Palm Stimulator group (Visual Analog Scale: M = 27.94, standard deviation = 19.13) were statistically significantly lower than the ShotBlocker (Visual Analog Scale: M = 46.07, standard deviation = 24.96) and control group (Visual Analog Scale: M = 53.43, standard deviation = 29.01) score averages (F = 14.94, η2 = 0.16, P = .001). DISCUSSION: The results of this study support the effectiveness of the Palm Stimulator to reduce perceived pain in children during intramuscular injection administration in the pediatric emergency department.

Bifurcation of the sciatic nerve: A descriptive study on a South African cadaver cohort.

BACKGROUND: The sciatic nerve bifurcates into the tibial and common fibular nerves in six different regions: the pelvic region, gluteal region, proximal, middle, or distal third of the posterior thigh, or in the popliteal fossa. Inadequate knowledge of sciatic nerve anatomy could lead to failed nerve blocks, and damage during intramuscular injections. Limited studies have been done on African population groups and lack a quantifiable method to classify the levels of sciatic nerve bifurcation. AIM: Thus, this descriptive cadaver study aimed to assess the bifurcation level of the sciatic nerve in a South African population group using a quantifiable method. METHODS: Three hundred and thirty-eight formalin-fixed limbs from three universities were dissected between March and August 2018. Type A was classified if the sciatic nerve bifurcated within the pelvic region. A sciatic nerve bifurcation level index (SNBLI) was developed for this study to quantitatively classify the region of sciatic nerve bifurcation into types B to F. RESULTS: Type F bifurcation was most common (79.6%), and types B and C were not observed. In 15 (0.04%) specimens, two separate nerves entered the gluteal region and converged to form the sciatic nerve distal to the piriformis, which could bifurcate either in the distal third of the posterior thigh or popliteal fossa. CONCLUSION: This is the first study to provide information on the sciatic nerve bifurcation in a large South African cadaver cohort. Moreover, we created a quantifiable method that can be used to classify the sciatic nerve bifurcation level. This will be beneficial in ensuring accurate comparison between different population groups in future.

[A case of intramuscular injection of methomyl poisoning].

Methomyl is a carbamate insecticide widely used in pesticides. Most of the poisoning methods are through digestive tract, respiratory tract and skin contact. At present, there is no report of poisoning caused by intramuscular injection. A case of poisoning caused by intramuscular injection of methomyl was analyzed retrospectively. About 4 minutes later, cholinergic crisis and central inhibition occurred. Venovenous-Extracorporeal Membrane Oxygenation (VV-ECMO) and atropine were given quickly. Finally, the patient was successfully rescued and had a good prognosis. After intramuscular injection of methomyl, cholinergic crisis can occur rapidly, and the onset rate is significantly faster than that of digestive tract, respiratory tract and skin contact.

Evaluation of vapocoolant spray effect on pain reduction during digital nerve block: A randomized clinical trial.

INTRODUCTION: The digital nerve block is an effective method of anesthesia before minor surgical interventions on the fingers. However, patients may experience a lot of pain and anxiety during this procedure. The efficacy of topical vapocoolant spray during minor procedures has been demonstrated in previous studies. we aimed to evaluate the effectiveness of topical vapocoolant spray in reducing pain during digital nerve block. METHODS: This prospective, randomized clinical study was conducted to evaluate the effectiveness of vapocoolant spray application in reducing pain during digital block. The patients were categorized into 2 groups as spray-treated and control group. A routine digital block process was applied to the control group. Spray application was performed in two groups of 50 each, in a manner of bilateral and unilateral to the finger. Demographic data of the patients, such as gender, age, dominant hand, injury patterns, injection site and injury sites, were recorded. After the application, the patients' visual analog scale (VAS) was evaluated. RESULTS: Of the participants, 100 were randomly assigned to the vapocoolant spray-treated group, and 50 were included in the control group. The VAS pain score during penetration in both spray groups was significantly lower than the control group (p < 0.001). Pain change during penetration was found to be significantly lower in the bilateral spray-treated group compared to the control group (p < 0.001). Pain change during infiltration was significantly lower in both spray groups compared to the control group (p < 0.001). CONCLUSIONS: Spray application prior to digital nerve blocking can be used to reduce needle penetration pain associated with this procedure and pain associated with local anesthetic infiltration.

Efficacy of testosterone replacement therapy plus alternate-day tadalafil for patients with late-onset hypogonadism: An open-label, randomized, crossover study.

OBJECTIVE: To examine the efficacy and safety of combination treatment with testosterone replacement therapy plus alternate-day tadalafil (10 mg) in patients with late-onset hypogonadism. METHODS: In this open-label, randomized, crossover study, 29 patients with late-onset hypogonadism were randomly assigned to receive testosterone replacement therapy for 12 weeks followed by combination treatment for 12 weeks (Group 1) or combination treatment for 12 weeks followed by testosterone replacement therapy (Group 2). Symptom questionnaires were administered and blood tests were performed prior to and following each treatment to assess safety and efficacy. At the end of the study, participants were asked about their treatment preferences. RESULTS: An adverse effect, a rheum symptom, occurred in only one participant, and 26 participants completed the study without any toxicity. Scores on the Aging Male Symptoms scale and the modified short version of the International Index of Erectile Function, and Overactive Bladder Symptom scores were significantly improved in the combination treatment phase of Group 2, whereas no significant difference between the phases were observed in Group 1. In total, 12 out of the 14 participants in Group 1 and 11 out of the 12 participants in Group 2 preferred combination treatment, which reached statistical significance (P = 0.008 and 0.004 for Groups 1 and 2, respectively). CONCLUSIONS: Testosterone replacement therapy with add-on alternate-day tadalafil is a safe and satisfactory treatment for patients with late-onset hypogonadism.

Successful use of long-acting octreotide for protracted gastrointestinal bleeding related to protein-losing enteropathy after the Fontan procedure: a case report.

Gastrointestinal bleeding complicated with protein-losing enteropathy after the Fontan procedure has been often reported in recent years, but there is no established therapy for it.We report the case of an 18-year-old boy who suffered from abdominal pain, melena, and anaemia due to intractable haemorrhagic protein-losing enteropathy after the Fontan procedure. He was successfully treated with octreotide therapy.

Virtual reality and distraction cards to reduce pain during intramuscular benzathine penicillin injection procedure in adults: A randomized controlled trial.

AIM: The aim of this study was to determine the effect of using three-dimensional videos with virtual reality glasses and distraction cards including optical illusion pictures on patients' pain and satisfaction levels during intramuscular benzathine penicillin injection. DESIGN: A randomized controlled trial. METHOD: The study population consisted of 91 patients who were prescribed intramuscular benzathine penicillin medication. The participants were stratified by gender and assigned to three groups (control, virtual reality and distraction cards groups). The visual analogue scale was used to assess pain and patient satisfaction. A one-way analysis of variance and Dunnett's post hoc tests were used to compare the pain and satisfaction levels by group. RESULTS: The mean pain was 6.67 (2.17) in the control group, 4.4 (2.71) in the distraction cards group and 4.93 (3.07) in the virtual reality group and the difference was statistically significant (F = 5.84, p Ë‚ .01). The average of the satisfaction levels in the groups was 3.57 (2.23) in the control group, 7.13 (2.86) in the distraction cards group and 8.07 (2.55) in the virtual reality group. The difference between the satisfaction levels was statistically significant (F = 25.77, p Ë‚ .01). CONCLUSION: The three-dimensional videos with virtual reality glasses and distraction cards including optical illusion pictures were effective in reducing pain associated with intramuscular benzathine penicillin injection and increasing patient satisfaction. IMPACT: The results of this study will contribute to evidence-based nursing practices for the pain associated with intramuscular benzathine penicillin injection. CLINICAL TRIAL REGISTRY: NCT04420559.

Evaluation of the effect of selecting gluteal injection site on the pain injection based on anthropometric indices and body shape pattern: A randomised controlled trial study.

AIMS AND OBJECTIVES: This study was aimed at comparing the effect of injection site selection based on anthropometric indices and body shape pattern on pain injection. BACKGROUND: Pain is one of the common complications of intramuscular injection. Selecting the right place for gluteal injection is one of the challenges of nursing which can increase the safety and success of the injection and thereby reduce the pain severity caused by it. DESIGN: Open-label randomized controlled trial study. METHODS: In this study, 162 eligible subjects referred to the emergency unit of Vasei Hospital of Sabzevar, Iran were randomly assigned to three groups of control, anthropometric indices and body shape pattern. Subjects in the control group received dorsogluteal injection (traditional way). In the anthropometric group, body mass index (BMI), waist circumference (WC) and anterior superior iliac spine to iliac tubercle (ASIS-IT), and in body shape pattern group, observed body shape indices (OBS), BMI and sex were used to select the gluteal injection site. Pain injection was assessed using the Visual Analogue Scale (VAS). The CONSORT checklist was used. RESULTS: The mean age of the participant was 39.43 ± 13.16 and 43.21% (n = 70) were male. Based on multiple linear regression analysis, the mean pain injection was substantially lower in body shape pattern as compared to the control group (r2 : .26; bxy = -0.41; 95% CI: -0.81, -0.01; p = .043). The mean pain injection was significantly greater in the left leg injection than right one (r2 : .26; bxy = 0.44; 95% CI: 0.06, 0.81; p = .021). CONCLUSIONS: Findings of this study suggest that the selection of a gluteal injection site based on body shape pattern in comparison with traditional dorsogluteal injection method has a significant effect on pain injection relief. RELEVANCE TO CLINICAL PRACTICE: Nurses can choose the appropriate gluteal injection site based on the body shape pattern to reduce the pain of the intramuscular (IM) gluteal injections.

Short communication: Influence of intramuscular injection of vitamin B12 in early-lactation dairy cows on Mozzarella cheese quality and vitamin B12 stability.

The current study explored the effect of intramuscular injection of vitamin B12 (VB12) in early-lactation dairy cows on subsequent low-moisture part-skim Mozzarella cheese quality and VB12 levels during cheese processing and storage. Twenty-four peripartum dairy cows were blocked based on parity and milk yield and randomly assigned into 2 treatments: basal diet (CON) and basal diet with an intramuscular injection of 10 mg of VB12 per cow per week (VB12). Raw milk was collected to determine VB12 content and then used to make low-moisture part-skim Mozzarella cheese 8 wk after injection. The VB12 content of raw milk and cheese was determined using ultra-performance liquid chromatography coupled with tandem mass spectrometry. We found that VB12 content was significantly increased in milk (15.43 vs. 3.30 ng/mL) and fresh cheese (3.72 ng/g vs. undetectable) from the VB12 group compared with the CON group. However, approximately 70% of VB12 was lost in the whey during cheese making, and no VB12 was detectable in either cheese treatment after 8 wk of storage. Furthermore, no significant differences were observed in fat and protein contents in the cheese between the 2 groups. For cheese color, the b* value increased and the a* value decreased slightly in fresh VB12 cheese. Functional properties of stretchability, flowability, and meltability of VB12 cheese were initially comparable to that of CON cheese, but higher flowability and meltability was observed in VB12 cheese after 8 wk of storage. In summary, intramuscular injection of VB12 in early-lactation dairy cows increases the content of VB12 in milk and fresh cheese with no adverse effect on cheese quality, but substantial VB12 is lost during cheesemaking and declines rapidly during storage.

A meta-analysis of the effects of intramuscular and intravenous injection of oxytocin on the third stage of labor.

BACKGROUND: Clinical studies and trials have shown that oxytocin can effectively reduce postpartum bleeding, whether by intramuscular (IM) injection or intravenous (IV) injection. These two methods are widely used in the prevention and treatment for the third stage of childbirth. However, it is unclear whether the subtle differences between the mode of these routes have any effect on maternal outcomes. OBJECTIVES: To systematically evaluate the efficacy and safety of oxytocin administered intramuscularly or intravenously for prophylactic management of the third stage of labor after vaginal birth. METHODS: Computerized retrieval of PubMed, the Cochrane Library, Web of Science, Embase, and ClinicalTrials.gov was conducted to collect randomized controlled trials (RCT) on the effects of IM and IV oxytocin on the third stage of labor. After independent literature screening, data extraction and evaluation of the bias risk of included studies by two evaluators, RevMan 5.3 software was used for a meta-analysis. RESULTS: Six studies with 7734 women were included in this study. Meta-analysis results showed that: the severe postpartum hemorrhage (PPH) rate [risk ratio (RR) 1.54, 95% confidence interval (95% CI) 1.08-2.20, P = 0.02], PPH rate (RR 1.31, 95% CI 1.11-1.55, P = 0.001), incidence of blood transfusion (RR 2.30, 95% CI 1.35-3.93, P = 0.002) and the need of manual removal of placenta (RR 1.44, 95% CI 1.05-1.96, P = 0.02) for IM group were higher than IV group, but there were no significant differences in the use of additional uterotonics (P = 0.31) and the incidence of serious maternal morbidity and adverse effects between two groups. None of the included studies reported maternal death. CONCLUSION: For clinical practice, intravenous injection oxytocin 10 IU may be a good, safe option in the management of the third stage of labor. Medical conditions, available resources, adverse effects, and women' s preferences should also be considered. If an IV line is already in place at delivery, IV administration may be preferable to IM injection.

Extracranial activation of ATP-sensitive potassium channels induces vasodilation without nociceptive effects.

INTRODUCTION: Levcromakalim opens ATP-sensitive potassium channels (KATP channel) and induces head pain in healthy volunteers and migraine headache in migraine patients, but no pain in other parts of the body. KATP channels are expressed in C- and Aδ-fibers, and these channels might directly activate nociceptors and thereby evoke pain in humans. METHODS: To assess the local effect of KATP channel opening in trigeminal and extra-trigeminal regions, we performed a crossover, double-blind, placebo-controlled study in healthy volunteers. Participants received intradermal and intramuscular injections of levcromakalim and placebo in the forehead and the forearms. RESULTS: Intradermal and intramuscular injections of levcromakalim did not evoke more pain compared to placebo in the forehead (p > 0.05) and the forearms (p > 0.05). Intradermal injection of levcromakalim caused more flare (p < 0.001), skin temperature increase (p < 0.001), and skin blood flow increase (p < 0.001) compared to placebo in the forehead and the forearms. CONCLUSION: These findings suggest that it is unlikely that levcromakalim induces head pain by direct activation of peripheral neurons.

Reduced variability in tacrolimus pharmacokinetics following intramuscular injection compared to oral administration in cynomolgus monkeys: Investigating optimal dosing regimens.

Tacrolimus is one of the most commonly used immunosuppressive agents in animal models of transplantation. However, in these models, oral administration is often problematic due to the lowered compliance associated with highly invasive surgery and due to malabsorption in the intestinal tract. Therefore, we carried out a study to determine the pharmacokinetics of tacrolimus after intramuscular (IM) injection and to determine the optimal IM dosing regimens in primate models. Six male cynomolgus monkeys (Macaca fascicularis) were used in the study. Doses of 0.1 mg/kg and 5 mg were administered via IM injection and oral administration, respectively, once to determine single-dose pharmacokinetics and once daily for 5 days to determine multiple-dose pharmacokinetics. According to pharmacokinetic model estimates, the inter- and intra-individual variabilities in bioavailability following IM injection were remarkably reduced compared with those following oral administration. Monte Carlo simulations revealed that Cpeak, Ctrough and AUC would also have less variability following IM injection compared with oral administration. In this study, we found that the pharmacokinetic characteristics of tacrolimus were more constant following IM injection compared with oral administration. These results suggest that IM injection can be an alternative route of administration fin non-human primate model studies.