The Recommended Deltoid Intramuscular Injection Sites in the Adult Population: A Cadaveric Pilot Study With an Orthopedic Perspective.

Background and aim The deltoid is a common site for intramuscular injections, but guidelines for administration lack standardization. Global researchers propose various techniques, and recent study reports indicate a 1.5-15% incidence of nerve palsies due to injections. This pilot cadaveric study aimed to standardize the deltoid intramuscular injection sites in the Southeast Asian population. Methods This cadaveric study of a two-year duration was conducted in the Department of Anatomy as an intramural research project in collaboration with the Departments of Anatomy and Orthopedics. In the first year of study, which was the pilot phase of the project, the available six cadavers, i.e., 12 upper extremity specimens were dissected. Anthropometric measurements of deltoid muscle along with the distance of underlying neurovascular structures like the axillary nerve and posterior circumflex humeral artery were measured from neighboring bony landmarks. This article presents the observations of the six cadavers studied in the pilot phase and shall be followed up by another article after the project. Results In adults, in anatomical position, the mean distances of the axillary nerve and posterior circumflex humeral artery from the mid-acromial point are 8.19±0.616 and 8.66±0.968 cm, respectively. The deltoid thickness at 3, 5, and 7 cm from mid-acromial point was observed to be 1.079±0.13 cm (0.5-1.78 cm), 1.599±0.12 cm (1-2.96 cm), and 1.815±1.0 cm (1.2-2.5 cm), respectively. The acquired qualitative and quantitative data were tabulated, graphically represented, and statistically analyzed. Conclusions The deltoid intramuscular injection (IMI) must be given at or below the level of the midpoint of the deltoid muscle, but never in the upper half. We recommend a site, 4 fingerbreadths/9 cm below the mid-acromion point as the safest site to avoid injury to any underlying neurovascular structures.

Evaluation of Combined Strategy to Reduce the Pain of Penicillin G Benzathine Injection in Primary Syphilis.

Background: Intramuscular (IM) injection of penicillin G Benzathine (PGB) is widely recognized as the primary treatment for patients at all stages of syphilis. However, the discomfort and induration associated with PGB injections are often a challenge for patients. While lidocaine is already known to reduce injection pain and is standard practice in some countries, the added value of combining lidocaine with the z-track technique has not been thoroughly investigated. This study aims to observe the use of combining lidocaine with the Z-track technique in the treatment of syphilis, and to explore less painful methods of administering IM PGB for the treatment of syphilis in adult patients. Methods: 32 syphilis patients requiring penicillin treatment were injected with 1.2 million units of penicillin on both sides of the buttocks. The left side was injected using the traditional method with 0.9% saline as the solvent (control Group), while the right side was injected using a "z" injection method with 0.2% lidocaine as the solvent (experimental Group). The success rate of the single injection, the intensity and duration of the post-injection pain and the induration reaction were observed and recorded. Results: There was no statistically significant difference in single injection success rate and immediate post injection pain score between the two sides (P>0.05). However, the right side had a lower pain score at 30 minutes post injection and fewer induration reactions, showing a statistically significant difference between the two sides (P<0.05). Chi-squared analysis showed that age, gender and BMI had no significant effect on pain scores 30 minutes after injection in either the control or intervention groups. (P>0.05). Conclusion: The lidocaine + Z-track penicillin method can reduce delayed pain and induration reactions in patients with syphilis, and provides an additional approach to improving patient comfort beyond the standard use of lidocaine alone. This method merits clinical promotion.

Comparison of Systemic Exposure Between Epinephrine Delivered via Metered-Dose Inhalation and Intramuscular Injection.

Background: Primatene® MIST, an epinephrine metered-dose inhaler (MDI), has long been questioned by some medical professionals for asthma treatment despite having been approved by the Food and Drug Administration. One of the primary reasons for their concerns stemmed from potential cardiovascular complications following epinephrine administration. However, the majority of documented cardiovascular complications seemed to occur following the injection route of the epinephrine. The aim of this study was to evaluate the systemic exposure of epinephrine delivered through different administration routes and to understand its relationship with cardiovascular effects. Since albuterol inhalers are commonly recommended for asthma, albuterol was also studied as a comparator drug. Method: A randomized, evaluator-blinded, three-arm crossover study was conducted in 28 healthy adult subjects to compare the profiles of systemic exposure for epinephrine delivered by MDI versus epinephrine intramuscular (IM) injection and albuterol MDI. Serially sampled plasma epinephrine and albuterol levels were measured and compared between treatment groups. Safety was assessed by adverse events, serial vital signs, electrocardiograms (ECGs), and clinical laboratory tests obtained at each crossover dosing visit. Results: Systemic exogenous drug exposure for inhaled epinephrine MDI (39 pg/mL × hour) was ∼9 times lower than that of epinephrine IM (435 pg/mL × hour) and 122 times lower than that of albuterol MDI (3453 pg/mL × hour) after dose normalization. The Cmax in epinephrine MDI (345 pg/mL) was approximately half of that of epinephrine IM (816 pg/mL) and that of albuterol MDI (681 pg/mL). Plasma drug concentrations for epinephrine MDI dropped rapidly to baseline (∼0.6 hour), while epinephrine IM took ∼8 hours, and albuterol MDI required more than 24 hours. Epinephrine MDI and albuterol MDI resulted in minimal, clinically insignificant changes in vital signs and ECGs, whereas epinephrine IM led to mild transient increases in systolic blood pressure, heart rate, and corrected QT interval. Conclusion: Epinephrine MDI (Primatene MIST) had ∼9 times lower systemic drug exposure (SDE) than that of epinephrine IM and ∼122 times lower than that of albuterol MDI. The lower SDE of inhaled epinephrine also correlated with reassuring safety findings, with no significant cardiovascular adverse effects found, compared with transient effects seen after IM epinephrine. Clinical trial registration number: NCT04207840.

Relative vaccine effectiveness of ChAdOx1/AZD1222 vaccines as booster dose via intradermal injection with a one-fifth dose compared with the intramuscular injection in the prevention of SAR-CoV-2 infections in Phuket: A retrospective cohort study.

OBJECTIVES: This study assessed the real-world relative vaccine effectiveness of the ChAdOx1/AZD1222 vaccine given intradermally at one-fifth dose compared to the standard intramuscular injection, following the completion of 2 doses of CoronaVac, due to limited vaccine availability in Thailand during the Coronavirus disease 2019 (COVID-19) pandemic. METHOD: This retrospective cohort study used 138,264 records from Vachira Phuket Hospital, Phuket, Thailand. The records were divided into 2 groups: 49,387 recipients received one-fifth doses via intradermal injections, and 88,877 recipients received standard-dose intramuscular injections from September 14 to October 3, 2021, with follow-up until December 31, 2021. Relative vaccine effectiveness for the cohorts was estimated using Cox regression, adjusting for demographic and clinical risk factors. RESULTS: The adjusted hazard ratio between the intradermal and intramuscular groups was 0.88 (95% Confidence Interval 0.76-1.02, P = 0.09), indicating a nonsignificant protective factor for the intradermal group. Further stratified analysis revealed no significant difference between the 2 groups. The 21 and 28-day postvaccination periods minimized the possibility of confounding due to differences in the cohorts' timeframes. CONCLUSION: A booster dose of ChAdOx1/AZD1222 given intradermally at one-fifth dose did not show a significant difference compared to the standard intramuscular injection.

Tricaprylin-based drug crystalline suspension for intramuscular long-acting delivery of entecavir with alleviated local inflammation.

In order to ensure prolonged pharmacokinetic profile along with local tolerability at the injection site, tricaprylin-based drug crystalline suspension (TS) was designed and its local distribution, pharmacokinetics, and inflammatory response, were evaluated with conventional aqueous suspension (AS). As model drug particles, entecavir 3-palmitate (EV-P), an ester lipidic prodrug for entecavir (EV), was employed. The EV-P-loaded TS was prepared by ultra-sonication method. Prepared TS and conventional AS exhibited comparable morphology (rod or rectangular), median diameter (2.7 and 2.6 µm), crystallinity (melting point of 160-165°C), and in vitro dissolution profile. However, in vivo performances of drug microparticles were markedly different, depending on delivery vehicle. At AS-injected site, drug aggregates of up to 500 µm were formed upon intramuscular injection, and were surrounded with inflammatory cells and fibroblastic bands. In contrast, no distinct particle aggregation and adjacent granulation was observed at TS-injected site, with >4 weeks remaining of the oily vehicle in micro-computed tomographic observation. Surprisingly, TS exhibited markedly alleviated local inflammation compared to AS, endowing markedly lessened necrosis, fibrosis thickness, inflammatory area, and macrophage infiltration. The higher initial systemic exposure was observed with TS compared to AS, but TS provided prolonged delivery of EV for 3 weeks. Therefore, we suggest that the novel TS system can be a promising tool in designing parenteral long-acting delivery, with improved local tolerability.

Novel use of local analgesia prior to intramuscular magnesium sulphate injection compared to mixed local analgesia with magnesium sulphate to reduce pain: a randomised crossover study in patients being managed for eclampsia and preeclampsia.

Objective: The World Health Organization (WHO) recommended addition of local anesthetic to reduce the intense pain of intramuscular injection of 50% Magnesium Sulphate (MgSO4) salt solution has been found to be ineffective. We tested whether giving the local anesthetic 5 min before the MgSO4 injection would reduce pain. Methods: We conducted a prospective cross-over trial where each participant with pre-eclampsia or eclampsia received sequential and mixed injection methods in random sequence during sequential MgSO4 administrations. Pain and preference were assessed using descriptive words, a numeric pain scale and direct comparison between the two injection methods. Differences were measured using the Wilcoxon signed rank test, risk ratios with 95% confidence intervals and the Chi squared or Fisher's test. The administration techniques were refined based on an initial pilot of 8 participants. Results: We enrolled 49 consented participants and analysed data from 41 post-pilot participants The sequential injection method had a non-significantly lower mean pain score than the mixed injection method (3.1 vs. 3.3, p = 0.44). Severe pain was reported for 3/41 vs. 9/41, p = 0.12. The sequential injection method was perceived to be more painful by 13 (37%) vs. 22 (63%) participants (p = 0.03). The sequential injection was preferred by 21(60%) vs. 14 participants (40%) (p = 0.1). Conclusion: Our results consistently favoured the novel sequential injection method. The lack of statistical significance for most results is not surprising given the small sample size. Given the potential for clinically important benefits to women, a larger study to confirm these results is justified. Clinical Trial Registration: https://pactr.samrc.ac.za/, Identifier (PACTR202201521544765).

Long-acting intramuscular injections of ELQ-331, an antimalarial agent.

The overarching premise of this investigation is that injectable, long-acting antimalarial medication would encourage adherence to a dosage regimen for populations at risk of contracting the disease. To advance support for this goal, we have developed oil-based formulations of ELQ-331 (a prodrug of ELQ-300) that perform as long-acting, injectable chemoprophylactics with drug loading as high as 160 mg/ml of ELQ-331. In a pharmacokinetic study performed with rats, a single intramuscular injection of 12.14 mg/kg maintained higher plasma levels than the previously established minimum fully protective plasma concentration (33.25 ng/ml) of ELQ-300 for more than 4 weeks. The formulations were well tolerated by the rats and the tested dose produced no adverse reactions. We believe that by extending the length of time between subsequent injections, these injectable oil-based solutions of ELQ-331 can offer a more accessible, low-cost option for long-acting disease prevention and reduced transmission in malaria-endemic regions and may also be of use to travelers.

Botulinum Toxin in Chronic Lateral Epicondylitis, from Tendon to Muscle Approach-A Review.

BACKGROUND: Chronic lateral epicondylitis challenges the therapeutical approach; underlying mechanisms are incompletely understood; neuropathic pain and central and peripheral sensitization may explain the fact that botulinum toxin has been found to play a role in pain and function management. METHODS: We searched the literature for MeSH terms: lateral epicondylitis or synonyms and botulinum toxin. RESULTS: We found 14 papers containing trials on botulinum toxin injection into the tendon or into the extensor muscles (specifically, extensor carpi radialis brevis and extensor communis digitorum). We followed the administration pathways, doses, timing, and side effects. CONCLUSIONS: With a chronic course, the focus of the therapy shifts from the afflicted tendon to the inserting muscles, as muscle contracture may create a vicious loop to perpetuate and aggravate the disease. Doses, timing, and side effects are discussed.

Conventional Method of Cardiac Ischemia/Reperfusion Injury in Mice.

Myocardial ischemia-reperfusion injury (IRI) after myocardial ischemia, cardiac surgery, or circulatory arrest leads to adverse cardiovascular outcomes. Primarily, no blood flow to the heart causes an imbalance between oxygen demand and supply, namely, ischemia, resulting in damage or dysfunction of the cardiac tissue. Early restoration of blood flow has been established to be the treatment of choice to prevent further tissue injury. Indeed, the use of thrombolytic therapy or primary percutaneous coronary intervention is the most effective strategy for reducing the size of a myocardial infarct and improving the clinical outcome. Unfortunately, restoring blood flow to the ischemic myocardium, named reperfusion, can also contribute to injury. This phenomenon was therefore termed myocardial IRI. Subsequent studies in animal models of acute myocardial infarction suggest that myocardial IRI accounts for up to 50% of the final size of a myocardial infarct. Consequently, many researchers aim to understand the underlying molecular mechanism of myocardial IRI to find therapeutic strategies that ultimately reduce the final infarct size. Despite numerous therapeutic strategies identified in laboratories, no clinical medicine specifically targeting IRI has yet been approved. Therefore, more relevant research is needed to develop promising therapeutic agents. In this respect, we will introduce a solid and reproducible experimental protocol to induce myocardial IRI in mice and test potent drug transfer during this surgical procedure.

The effect of simultaneous administration of occipital nerve block and cervical myofascial trigger point injection (MTrPI) on headache parameters in chronic migraine patients.

BACKGROUND AND AIM: Peripheral myofascial mechanisms have been identified as contributors to migraine pathophysiology. The specific comorbid relationship between migraine and cervical trigger points may exacerbate the occurrence and severity of migraine attacks. Trigger point injections (TPIs) are frequently employed to address headaches and alleviate migraine symptoms. The current study explores the impact of concurrent myofascial trigger point injection (MTrPI) and occipital nerve block (greater occipital nerve block [GONB] + lesser occipital nerve block [LONB]) on the severity of headaches and the number of migraine attacks in individuals with chronic migraine (CM) and cervical myofascial trigger points (MTrPs), with a comparison of occipital nerve block alone (GONB + LONB). During trigger point examination and injection, trapezius, levator scapulae, splenius capitis, temporalis, and sternocleidomastoid muscles were targeted. We planned the treatment based on whether they were in the muscle groups we determined, rather than the number of trigger points. MATERIALS AND METHOD: This study enrolled 62 individuals experiencing CM with bilateral headache and cervical MTrP who sought care at the Algology Unit within the Departments of Neurology and Physical Therapy and Rehabilitation at Siirt Training and Research Hospital between 2020 and 2022. The CM cohort was stratified into two groups: group 1 received trigger point injections (TrPI), while group 2 underwent concurrent bilateral occipital nerve block (GONB + LONB) and TrPI. Both groups underwent three treatment sessions with bupivacaine 0.5% (1 ml = 5 mg) in weeks 1, 2, and 4. Visual analog scale (VAS) was used to measure the patients' pain intensity. The evaluation included the assessment of the monthly migraine frequency and visual analog scale (VAS) p score for pain before treatment (BT) and after treatment (AT), conducted at baseline and during follow-up visits. Analysis of the data was conducted utilizing IBM SPSS Statistics for Windows version 28.0 software. RESULTS: Among patients diagnosed with CM and MTrPs, 32 individuals (51.6%) underwent GONB and LONB, while 30 patients (48.4%) received simultaneous GONB, LONB, and cervical MTrPI. Within the entire sample, 51 participants (82.3%) were female, and 11 (17.7%) were male, with a mean age of 32.81 ± 10.75 years. With an average age of 32.81 ± 10.75 years, there was no statistically significant variance between the two groups (p = 0.516). Of the total cohort, 45 individuals (72.6%) reported experiencing headaches persisting for 12 months or longer. Among CM patients, 80% had active trigger points, while 20% had latent trigger points. No statistically significant difference was observed between the groups concerning TrPs (p = 0.158), and the distribution of TrPs was homogenous across the two groups. In group 1, the median (min-max) monthly frequency of migraines reduced from 18.5 days (range: 15.0 to 25.0 days) before treatment to 12.0 days (range: 7.0 to 17.0 days) after treatment (p = 0.000). In group 2, the median monthly frequency of migraines reduced from 16.5 days (range: 15.0 to 22.0 days) before treatment to 4.0 days (range: 2.0 to 8.0 days) after treatment (p = 0.000). The median (min-max) VAS score in group 1 was 8.0 (range: 5.0 to 9.0) before treatment, 4.0 (range: 2.0 to 6.0) at week 1, and 5.0 (range: 4.0 to 8.0) at week 4 (p = 0.000). In group 2, the median VAS score was 7.0 (range: 5.0 to 9.0) before treatment, 0.0 (range: 0.0 to 0.3) at week 1, and 2.0 (range: 0.0 to 0.3) at week 4 (p = 0.000). There were significant distinctions between the groups in terms of both the monthly count of migraine days and the severity of headaches (p = 0.000). CONCLUSION: The combination of repeated MTrPIs and ONB proves more effective than ONB alone in managing patients with CM and cervical MTrP. In patients with CM, performing TrPs examination and adding treatments for this may contribute to the treatment. In cases where patients endure prolonged episodes of headache associated with chronic migraine, the inclusion of trigger point injections alongside peripheral nerve blocks may offer enhanced therapeutic benefits.

Intramuscular injection of palmitic acid-conjugated Exendin-4 loaded multivesicular liposomes for long-acting and improving in-situ stability.

BACKGROUND: Exendin-4 (Ex4) is a promising drug for diabetes mellitus with a half-life of 2.4 h in human bodies. Besides, the Ex4 formulations currently employed in the clinic or under development have problems pertaining to stability. In this study, palmitic acid-modified Ex4 (Pal-Ex4) was prepared and purified to extend the half-life of Ex4. In addition, Pal-Ex4-MVLs were further designed and optimized as a long-acting delivery system for intramuscular injection. METHODS: Pal-Ex4 was encapsulated within multivesicular liposomes (MVLs) via a two-step double emulsification process. The formulated products were then assessed for their vesicle size, encapsulation efficiency, and in vitro and in vivo. RESULTS: Pal-Ex4-MVLs with a notable encapsulation efficiency of 99.18% were successfully prepared. Pal-Ex4-MVLs, administered via a single intramuscular injection in Sprague-Dawley rats, sustained stable plasma concentrations for 168 h, presenting extended half-life (77.28 ± 12.919 h) and enhanced relative bioavailability (664.18%). MVLs protected Ex4 through providing stable retention and slow release. This approach considerably improved the in-situ stability of the drug for intramuscular administration. CONCLUSIONS: The combination of palmitic acid modification process with MVLs provides dual protection for Ex4 and can be a promising strategy for other hydrophilic protein/polypeptide-loaded sustained-release delivery systems with high drug bioactivity.

Intramuscularly injected long-acting testosterone-cholesterol prodrug suspension with three different particle sizes: extended in vitro release and enhanced in vivo safety.

The testosterone undecanoate oil solution is the most widely used injection of testosterone for long-acting effects on the market, whereas the formulation carries the potential risk of causing pulmonary vascular embolism, inflammation, and pain at the injection site. Therefore, a sustained-released long-acting injection of testosterone with strong security is urgently exploited. Herein, a poorly water-soluble testosterone-cholesterol prodrug (TST-Chol) was synthesized by esterification. The water solubility of TST-Chol was decreased by 644 folds in comparison to that of testosterone (TST). Moreover, suspensions of TST and TST-Chol were prepared and analyzed in vitro, utilizing three distinct particle sizes: small-sized nanocrystals (SNCs) measuring 300 nm, medium-sized microcrystals (MMCs) measuring 12 µm, and large-sized microcrystals (LMCs) measuring 20 µm. The findings from the in vitro release study indicated that the sustained release of the drug was significantly influenced by the solubility and particle sizes of the suspension. Notably, the suspensions with low water solubility and larger particle sizes exhibited a more desirable sustained-release effect in vitro. Furthermore, the study on pharmacokinetics exhibited that TST-Chol SNCs produced a sustained TST plasma concentration in vivo for up to 40 days and no obvious pathological changes in lung tissue were found. Our study indicated that solubility and particle sizes of suspensions had made a difference in pharmacokinetics and provided a valuable reference for the advancement of long-acting injections.

Falsely elevated serum testosterone measurements resulting from testosterone topical gel contamination of the venipuncture site: Case Series and retrospective review.

Testosterone as replacement therapy for male hypogonadism or as gender-affirming hormone therapy for transgender and non-binary patients has increased worldwide. Commonly used formulations of testosterone include intramuscular, transdermal patch, and topical gel, each of which has differing pharmacokinetics and practical challenges. In monitoring testosterone serum concentrations, contamination of the phlebotomy site by testosterone topical gel can lead to supraphysiologic (>1000 ng/dL or 34.7 nmol/L) serum concentrations of testosterone, as demonstrated in a few published case reports. The frequency of this issue is currently not known. The present study involves a retrospective search over a 13-year period across all clinical sites at an academic medical center. Out of 578 unique patients using testosterone topical gel, a total of 48 patients had at least 1 testosterone serum concentration exceed 1000 ng/dL. Documentation in the electronic health record revealed 7 patients where contamination of the phlebotomy site by topical gel was strongly supported as the cause of supraphysiologic testosterone serum concentrations. These included 5 males with primary hypogonadism, 1 male with panhypopituitarism, and a non-binary patient with gender dysphoria. The high testosterone concentrations prompted further work-up, including retesting and endocrinology consultation. There were additional cases of high testosterone serum concentration that may have been falsely elevated due to gel contamination but without sufficient supporting evidence available in the health record. Overall, we present 7 cases of spuriously high testosterone concentrations strongly suspected to be due to venipuncture performed near or at the location of prior testosterone gel application. Gel contamination should be considered as a possible cause of otherwise unexplained high testosterone serum concentration in patients receiving topical testosterone gel formulations. Patient counseling and provider awareness of this potential cause of spuriously high testosterone serum concentrations is important.

Chronic shoulder injury related to vaccine administration following coronavirus disease 2019 vaccination: a case report.

BACKGROUND: Shoulder injury related to vaccine administration, defined as shoulder pain and limited range of motion occurring after administration in the upper arm, has been previously reported. The symptom resolved completely after treatment with oral nonsteroidal anti-inflammatory drugs or an intraarticular steroid injection, however there have been few reports of long-term symptoms following coronavirus disease 2019 vaccination. This case report describes a healthy, middle-aged, healthcare worker who developed post-vaccination subacromial-subdeltoid bursitis that lasted for more than 6 months after Pfizer-BioNTech coronavirus disease 2019 vaccination. CASE PRESENTATION: A 55-year-old Japanese woman with no significant medical history was vaccinated in the standard site, with the needle direction perpendicular to the skin. Within a few hours after the second vaccination, severe shoulder pain and limited range of motion appeared. Although shoulder range of motion improved, her shoulder pain did not improved for several months, and she consulted an orthopedic doctor 5 months later. Radiographs of her left shoulder did not provide helpful diagnostic information. High intensity in the subacromial-subdeltoid space was seen on short TI inversion recovery of magnetic resonance imaging, showing subacromial-subdeltoid bursitis. She was diagnosed with a shoulder injury related to vaccine administration. The patient was started on an oral anti-inflammatory drug, and the left subacromial space was injected with 2.5 mg of betamethasone with 3 ml of 1% lidocaine without epinephrine every 2 weeks. One month after starting this treatment, since her shoulder pain had not improved, the oral anti-inflammatory drug was switched to tramadol hydrochloride acetaminophen. However, 3 months after switching medication, the shoulder pain continued, and she worked so as to have minimal impact on her shoulder. CONCLUSION: A case of subacromial-subdeltoid bursitis following a second dose of the Pfizer-BioNTech coronavirus disease 2019 vaccine that lasted many months is reported. Injection technique is a modifiable risk factor, the adverse effects of which could potentially be mitigated with appropriate and relevant training of healthcare providers. To prevent this type of case, the appropriate landmark, needle length, and direction should be confirmed.

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.

The prevalence and clinical course of shoulder injury related to vaccine administration (SIRVA) after COVID-19 vaccines in Dutch hospital workers.

INTRODUCTION: Shoulder Injury Related to Vaccine Administration (SIRVA) is a rare disorder characterized by persistent shoulder pain and limited range of motion presenting within 48 h after vaccine administration. With the widespread distribution of the COVID-19 vaccine, the incidence of SIRVA is expected to rise. This sudden rise in vaccine administration presents an ideal opportunity to estimate the prevalence of SIRVA and to better characterize SIRVA. OBJECTIVE: This study aims to investigate the prevalence of SIRVA following COVID-19 vaccine administration among hospital workers in the Netherlands. METHODS: A questionnaire was sent to all hospital workers from a single non-academic hospital in the Netherlands. Respondents who had active SIRVA complaints were invited for an outpatient orthopaedic clinic assessment. Data was collected on participant characteristics and physical examination including assessment of active and passive range of motion (ROM). An ultrasound was performed to identify potential abnormalities. RESULTS: 32 out of 981 (3.3%) respondents reported shoulder pain with limited ROM occurring within 48 h after vaccine administration lasting for at least 7 days. Of these 32 respondents with SIRVA, 18 (56.2%) still reported active symptoms at the time of the survey. Clinical examination of 13 (72.2%) respondents with active SIRVA complaints showed limited glenohumeral ROM, limitations in activities of daily living and injection site pain. Twelve out of thirteen (92.3%) respondents with active SIRVA complaints showed abnormalities of the soft-tissue of the shoulder on ultrasound. Physiotherapy was the most common treatment modality for persistent SIRVA complaints (38.9%). CONCLUSIONS: The prevalence of SIRVA is estimated at 3% in the adult working population. Signs and symptoms of SIRVA are variable in severity, localization and timing. Soft-tissue abnormalities is the most common clinical sign. This study contributes to clinician's knowledge on SIRVA, aiding in early recognition and treatment, which are imperative for prevention of persistent and severe shoulder pathology.

Development of Retroperitoneal Abscess Following Routine Injection of Triamcinolone for Musculoskeletal Pain.

Glucocorticoid intramuscular injections are a quick, routine procedure done in an outpatient setting to relieve musculoskeletal pain quickly. However, despite being a low-risk procedure it can lead to local infections, including abscess and skin necrosis, and even more rarely, bacteraemia and multi-organ failure. In this case, we present a healthy, immunocompetent woman in her 40s diagnosed with a retroperitoneal abscess due to methicillin-resistant Staphylococcus aureus after an intramuscular injection of triamcinolone. LEARNING POINTS: Injections of glucocorticoids are commonly used in medical practice to alleviate musculoskeletal pain in addition to oral non-steroidal anti-inflammatory agents.Complications of injections include abscess formation, skin necrosis and sepsis, typically from Staphylococcus aureus or other skin colonisers.It should be understood that there are risks associated with injections regardless of age or co-morbidities, so these risks should be discussed with the patient in depth before administration.

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.

Prolonged control of insulin-dependent diabetes via intramuscular expression of plasmid-encoded single-strand insulin analogue.

Daily insulin injection is necessary for the treatment of the insulin-dependent diabetes. However, the process is painful and inconvenient. Accordingly, we have made exploratory efforts to establish an alternative method for continuous insulin supply via intramuscular injection of a designed plasmid encoding the single-strand insulin analogue (SIA), which provides safe, effective and prolonged control of insulin-dependent diabetes. To generate a SIA, a short flexible peptide was alternatively introduced into the natural proinsulin to replace its original long and rigid C-peptide. Then, the synthetic promoter SP301 was used to drive potent and specific expression of SIA in skeletal muscle cells. By combining the Pluronic L64 and low-voltage electropulse (L/E), the specialized gene delivery technique was applied to efficiently transfer the constructed plasmid into skeletal muscle cells via intramuscular injection. Through these efforts, a plasmid-based intramuscular gene expression system was established and improved, making it applicable for gene therapy. The plasmid-expressed SIA showed biological functions that were similar to that of natural insulin. A single L/E-pSP301-SIA administration provided sustained SIA expression in vivo for about 1.5 months. In addition, the diabetic mice treated with L/E-pSP301-SIA were much healthier than those with other treatments. This plasmid-based system was safe for the treatment of diabetes and did not cause immune responses or pathological damage. The results confirmed that, in a mouse model, long-term positive effects were achieved by a single intramuscular L/E-pSP301-SIA injection, which consequently provided reliable experimental basis for its clinical application for the treatment of diabetes mellitus with promising prospects.

Gluteal muscle and subcutaneous tissue thicknesses in adults: a systematic review and meta-analysis.

Background: Nurses often administer intramuscular injections at the gluteal site. This study aimed to determine gluteal muscle and subcutaneous tissue thicknesses in adults. Methods: Systematic review and meta-analysis. The databases Turkish Medline, Ulakbim, National Thesis Center, Cochrane, Web of Science, Science Direct, PubMed, CINAHL Plus with Full text (EBSCO host), OVID and SCOPUS were screened using the keywords 'intramuscular injection', 'subcutaneous tissue thickness', 'muscle tissue thickness' and 'needle length' between April and May 2021. The studies were evaluated with ultrasound. This study was reported according to the PRISMA recommendations. Results: Six studies met the eligibility criteria. The total sample size was 734 (women: 432, men: 302). The V method revealed that the ventrogluteal site had a muscle and subcutaneous tissue thickness of 38.071 ± 2.119 and 19.927 ± 2.493 mm, respectively. The geometric method revealed that the ventrogluteal site had a muscle and subcutaneous tissue thickness of 35.989 ± 4.190 and 19.661 ± 3.992 mm, respectively. The geometric method also revealed that the dorsogluteal site had a thickness of 42.560 ± 8.840 mm. According to the V method, females had thicker subcutaneous tissue at the ventrogluteal site than males (Q = 5.37, df = 1, p = 0.0204). Body mass index did not affect the subcutaneous tissue thicknesses at the ventrogluteal site. Conclusion: The results show that gluteal muscle, subcutaneous and total tissue thicknesses vary across injection sites.