OBJECTIVE: 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 two doses of CoronaVac, due to limited vaccine availability in Thailand during the Coronavirus disease 2019 (COVID-19) pandemic.
METHODS: This retrospective cohort study used 138,264 records from Vachira Phuket Hospital, Phuket, Thailand. The records were divided into two 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 non-significant protective factor for the intradermal group. Further stratified analysis revealed no significant difference between the two groups. The 21 and 28-day post-vaccination periods minimized the possibility of confounding due to differences in the cohorts\' timeframes.
CONCLUSIONS: A booster dose of ChAdOx1/AZD1222 given intradermally at one-fifth dose did not show a significant difference compared to the standard intramuscular injection.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: https://pactr.samrc.ac.za/, Identifier (PACTR202201521544765).

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.

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.

OBJECTIVE: 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.
METHODS: 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).
CONCLUSIONS: 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.

UNASSIGNED: Gas Gangrene following intramuscular injection is a rare but serious condition that can lead to morbidity and mortality. This case conveys a severe and fatal complication following intramuscular injections of diclofenac and vitamin B12 in a diabetic patient.
UNASSIGNED: The patient developed pain and swelling in the left buttock after the injection of vitamin B12 and Diclofenac one on each buttock which worsened over time. He was diagnosed with gas gangrene when he presented to the emergency department. The blood culture identified Klebsiella pneumonia. The patient\'s condition rapidly deteriorated, leading to sepsis and acute kidney injury. Despite intensive care management, the patient succumbed five days after admission. At autopsy, gas gangrene of the left lower limb was evident on external examination. Histopathological examination confirmed the acute tubular damage in the kidney and the postmortem blood culture also grew Klebsiella pneumonia and Enterobacter cloacae. The cause of death was determined to be acute tubular necrosis as a result of sepsis due to non-clostridial gas gangrene.
UNASSIGNED: This instance of gas gangrene following trivial trauma poses a challenge for the forensic pathologist in establishing the causal association and in determining the causative organism. These are important when medical/surgical intervention is in question to be the cause of a fatal infection like gas gangrene. Ante-mortem/postmortem blood culture can aid in defining the causative organism of gas gangrene but the causal association with the alleged trauma/insult is still a challenge at autopsy. This case report addresses and tries to overcome the diagnostic challenges and dilemmas at autopsy in a case of gas gangrene.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

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.

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.

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.
METHODS: 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.
CONCLUSIONS: 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.