Injection Of Dose Research Articles

Is Vibration Anesthesia Effective and Safe for Pain Reduction in Botulinum Toxin Injection? A Randomized Split-Face Controlled Trial and Cadaver Experiment.

Pain is an important issue in botulinum toxin injection. Vibration anesthesia is a noninvasive way for pain alleviation, but few study reported its use during botulinum toxin injection. To investigate whether vibration anesthesia is effective and safe for pain reduction during botulinum toxin injection for masseter reduction. A randomized split-face controlled trial was performed in patients who required masseter reduction. Vibration anesthesia was randomly administered on either side. Study outcomes were pain scores on a visual analog scale, duration of effect, satisfaction, and complications. Intergroup comparison and linear regression analyses were performed. In a total of 216 patients, the pain score on the vibration side (2.97 ± 1.44) was significantly lower than that on the non-vibration side (4.72 ± 2.13) (p < 0.0001), with a higher proportion of mild pain. Linear regression showed that history of injection, more injection points and doses increased the pain, while 2 ml syringe reduced the pain compared to 1ml syringe. Side effects were found in 19 patients and 21 sides (7%), but were not associated with vibration. High satisfactions were reported. Cadaver experiment confirmed that vibration did not alter the diffusion radius and depth of injection. Vibration anesthesia could significantly relieve the pain during botulinum toxin injection for masseter reduction, while did not affect adverse effect and effect duration. Therefore, we recommended the use of vibration anesthesia, larger syringe size, and less injection points to improve patient experience and satisfaction.

Hyaluronidase for reducing perineal trauma.

Perineal trauma after vaginal birth is common and can be associated with short- and long-term health problems. Perineal hyaluronidase (HAase) injection has been widely used to reduce perineal trauma, perineal pain and the need for episiotomy since the 1950s. The administration of HAase is considered to be a simple, low risk, low cost and effective way to decrease perineal trauma without causing adverse effects. To assess the effectiveness and safety of perineal HAase injection for reducing perineal trauma, episiotomy and perineal pain during vaginal delivery. To identify studies for inclusion in this review, we searched the Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Embase, CINAHL (EBSCOhost), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) in November 2023. Randomised and quasi-randomised controlled trials comparing women giving birth to their first baby receiving perineal HAase injection compared to placebo injection or no intervention during vaginal delivery of a single foetus with vertex foetal presentation (foetus with head engaging the maternal pelvis). We used standard methodological procedures expected by Cochrane. Two review authors independently assessed trials for inclusion, extracted and checked data, and evaluated the risk of bias in the studies. Our primary outcomes were perineal trauma (tears or episiotomy, or both), episiotomy and perineal pain. Our secondary outcomes were first and second degree perineal lacerations, third and fourth degree perineal lacerations, perineal oedema 1 hour after vaginal delivery, perineal oedema 24 hours after vaginal delivery and neonatal Apgar scores of less than 7 at five minutes after birth (Apgar score is a measure of the health status of a newborn). We assessed the certainty of the evidence using the GRADE approach. We included five randomised controlled trials involving a total of 747 women (data were available for 743 women). The dosage of HAase used in the perineal injection varied from 750 turbidity-reducing units to 5000 international units. The certainty of the evidence was largely low (ranging from very low to moderate). Perineal HAase injection versus placebo injection Data from three trials involving 426 women provided low-certainty evidence that there may be no difference between the HAase and placebo groups in the incidence of perineal trauma (tears or episiotomy, or both) (RR 0.94, 95% CI 0.87 to 1.03; 426 participants, 3 studies), episiotomy (RR 0.91, 95% CI 0.71 to 1.15; 427 participants, 3 studies), first and second degree perineal lacerations (RR 1.02, 95% CI 0.87 to 1.18; 341 participants, 3 studies), third and fourth degree perineal lacerations (RR 0.46, 95% CI 0.11 to 2.05; 426 participants, 3 studies), and perineal oedema one hour after vaginal delivery (RR 0.99, 95% CI 0.78 to 1.25; 303 participants, 2 studies). Moreover, perineal HAase injection during the second stage of labour likely resulted in a reduction in incidence of perineal oedema 24 hours after vaginal delivery compared with placebo injection (RR 0.42, 95% CI 0.26 to 0.70; 303 participants, 2 studies; moderate-certainty evidence). There may be no difference between groups in Apgar scores less than 7 at five minutes (RR 5.00, 95% CI 0.24 to 105.95; 148 participants, 1 study; low-certainty evidence). Perineal HAase injection versus no intervention Data from three trials involving 373 women suggested that perineal HAase injection during the second stage of labour may result in a lower incidence of perineal trauma (tears or episiotomy, or both) (RR 0.61, 95% CI 0.42 to 0.88; 373 participants, 3 studies; low-certainty evidence) compared with no intervention. The evidence is very uncertain for episiotomy (RR 0.79, 95% CI 0.44 to 1.42; 373 participants, 3 studies), first and second degree perineal lacerations (RR 0.59, 95% CI 0.30 to 1.18; 373 participants, 3 studies) and perineal oedema one hour after vaginal delivery (RR 0.32, 95% CI 0.01 to 7.71; 139 participants, 1 study), all very low certainty evidence. No third and fourth degree perineal lacerations, perineal oedema 24 hours after vaginal delivery or Apgar scores less than 7 at five minutes were reported in these three trials. No side effects were reported in the included trials. Perineal HAase injection during the second stage of labour may result in a lower incidence of perineal trauma (tears or episiotomy, or both) compared with no intervention, but not compared with placebo injection, in women having a vaginal delivery. Meanwhile, perineal HAase injection likely reduces the incidence of perineal oedema 24 hours after vaginal delivery compared with placebo injection. The potential use of perineal HAase injection as a method to reduce perineal trauma and perineal oedema remains to be determined as the number of high-quality trials and outcomes reported was too limited to draw conclusions on its effectiveness and safety. Further rigorous randomised controlled trials are required to evaluate the role of perineal HAase injection in vaginal deliveries, including evaluating whether there is any differential effect based on the dose, frequency and positioning of HAase injection.

Preclinical delayed toxicity studies of BCMA CAR T-cell injection in B-NDG mice with multiple myeloma

PurposeBased on the efficacy data from the previous study of B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell injection, we further examined the delayed toxicity for 8 weeks after a single dose of BCMA CAR T-cell injection to observe possible toxic reactions.MethodsB-NDG mice transplanted with multiple myeloma (MM) cells were given a single dose of BCMA CAR T-cell injection at two dosages or human normal T cells and then subjected to examinations including clinical signs, weight and food intake measurements, haematology, blood biochemical analysis, cytokine assay, T-lymphocyte subpopulation quantification and histopathology on days 28 and 56 after dosing. In addition, quantitative polymerase chain reaction (qPCR) was used to quantify DNA fragments in different tissues to assess the tissue distribution of CAR and provide a basis for its preclinical safety evaluation and clinical dosing.ResultsIn the delayed toxicity study, no mortality or significant toxic effects such as reductions in food intake, body weight, relevant biochemical parameters and target organ weights were observed in the BCMA CAR T-cell-treated groups. Compared to the model group, restorative changes in clinical signs and clinicopathology indicating therapeutic effects were seen in the BCMA CAR T-cell-treated groups. Human-derived cytokines interleukin-2 (IL-2), IL-4, IL-6, IL-12, IL-10, tumor necrosis factor α (TNF-α), and interferon-γ (IFN-γ) could be detected in all cancer cell–bearing mice by cytokine level measurement. IFN-γ levels showed a geometric increase due to the graft versus host disease (GVHD) response induced in the mice, while the levels of the other cytokines did not show significant changes. Histopathological examination indicated that the BCMA CAR T-cell treatment groups showed mixed cellular infiltration of human-derived T cells, cancer cells, and inflammatory cells in several target organs including the liver, spleen, lung, and kidney, and some of them showed mild tissue damage, but the number of the animals and the severity of damage were significantly less than those of the T-cell control group as well as the model group. The results of the tissue distribution study showed that BCMA CAR T cells were mainly concentrated in the kidney, lung, bone marrow and the related immune organs/tissues, and the distribution of BCMA CAR T cells was highly consistent with that of MM cells, suggesting that BCMA CAR T cells could follow the cancer cells during metastatic targeting of the tissues.ConclusionsThe present study demonstrated a low toxicity of BCMA CAR T-cell injection, with manageable side effects and good anticancer activity and without observable adverse effects. This study provides data to support future clinical studies of BCMA CAR T-cell injection for MM.

Short-term efficacy and safety of endoscopic injection of low dose of sclerotherapy and cyanoacrylate injection for type GOV1 gastric varices combined with endoscopic variceal ligation for esophageal varices.

To explore the short-term efficacy and safety of endoscopic low dose injection of sclerotherapy and cyanoacrylate for gastric varices (GVs) combined with endoscopic variceal ligation (EVL) for esophageal varices (EVs) in cirrhosis with type GOV1 varices. A total of 521 patients with cirrhosis and GOV1 varices, who were divided into emergence endoscopy treatment layer and secondary prophylaxis for rebleeding layer, were selected. All patients underwent combined therapy or EVL alone (ligation therapy) for the treatment of type GOV1 varices. The baseline between the two groups with significant differences were used as covariates for 1:1 propensity score matching. The early rebleeding rate was compared and the risk factors for rebleeding were identified in each layer. After propensity score matching, a total of 122 patients were included in the emergence endoscopy treatment layer, and 234 patients were included in the secondary prophylaxis layer. The early rebleeding rates in the combined therapy group vs. ligation therapy group was 4.92% vs. 16.39% (P = 0.04) and 2.56% vs. 1.71% (P = 0.65) in the emergency endoscopy layer and in the secondary prophylaxis layer, respectively. The median length of hospital stay after endoscopy was 8days vs. 9days (P = 0.004) and 7days vs. 6days (P = 0.47), in each layer respectively. There was no significant difference in the adverse reactions of endoscopic treatment. EVL treatment (OR: 3.84; 95% CI: 1.05-13.96; P = 0.04) and discontinuation of NSBB (non-selective beta-blocker) use after discharge (OR: 3.58; 95% CI: 1.20-10.67; P = 0.02) were independent risk factors for early rebleeding after endoscopy in the emergency endoscopy layer. Combined therapy is comparable with ligation therapy in the short-term efficacy and safety of in cirrhosis patients with secondary prophylaxis for rebleeding while it is superior to EVL alone in cirrhosis in the emergency endoscopy treatment as it could reduce the early rebleeding rate and shorten the length of hospital stay.

Effect of Intravitreal Bevacizumab (Anti VEGF) Injection on Renal Function

Background: Vascular endothelial growth factor (VEGF) plays an important role in the development of both Proliferative Diabetic Retinopathy (PDR) &amp; Diabetic Macular Odema (DMO). An intravitreal anti-VEGF agent is an effective new modality of treatment. Some studies have dealt with systemic effects of intravitreal injection of anti-VEGF. However, decreasing renal function has been reported recently. Aims: To investigate the effect of intravitreal bevacizumab (anti VEGF) injection on renal function. Methods: This quasi-experimental study was carried out in the Department of ophthalmology, Bangabandhu Sheikh Mujib Medical University, Dhaka, during March 2019 to August 2021. A total of 40 patients with retinopathy treated with intravitreal injection bevacizumab were included in this study, out of which 20 patients having diabetic kidney disease (DKD) and rest 20 patients without diabetic kidney disease (No DKD). The patients having Diabetic Kidney Disease (DKD) whose Urinary Albumin Creatinine Ratio (UACR) &gt; 30 mg/g or Effective Glomerular Filtration Rate (eGFR) &lt; 60mL/min/1.73m2, No Diabetic Kidney Disease (No DKD) whose UACR &lt; 30 mg/g or eGFR &gt; 60mL/min/1.73m2. Patients of both sexes and age above 18 years were enrolled in this study. Pre- injection and 1 month after 3rd dose of intravitreal injection of bevacizumab, UACR, Serum Creatinine and eGFR were measured and compared. Results: It was observed that half (50.0%) of the patients in DKD and more than half (65.0%) in No DKD belonged to age group 50-59 years. Male was predominant in both the groups. The mean pre-injection of serum creatinine was 1.23±0.53 mg/dl in DKD and 0.87±0.22 mg/dl in No DKD. The mean post-injection of serum creatinine was 1.19±0.45 mg/dl in DKD and 0.87±0.16 mg/dl in No DKD. The mean pre-injection of UACR was 1294.9±968.26 mg/g in DKD and 13.8±5.99 mg/g in No DKD. The mean post-injection of UACR was 1142.11±1024.06 mg/g in DKD and 13.01±6.87 mg/g in No DKD. The mean difference of serum creatinine, eGFR and UACR were not significant (p&gt;0.05) between pre-injection and post-injection in both groups. Conclusion: Serum creatinine, eGFR and UACR were almost similar between pre-injection and post-injection in patients with diabetic kidney disease (DKD) and patients without diabetic kidney disease (No DKD).

Therapeutic drug monitoring of posaconazole delayed-release tablets and injections in pediatric patients.

This study aimed to investigate the dose and trough concentration (Cmin) of posaconazole delayed-release tablets and injections, and their correlation with efficacy and safety in pediatric patients. Patients younger than 18 years old received posaconazole delayed-release tablets or injections for prophylaxis or treatment of invasive fungal disease (IFD). Blood samples were collected to determine the plasma Cmins, and dose regimen adjustments were made if necessary. Clinical data were collected. A total of 210 Cmins of 113 pediatric patients were detected. The median Cmins were 1.0 and 1.3 mg/L for tablets and injections, respectively (P < 0.05). The median doses required to achieve the target Cmin were about 6.0 mg/kg of body weight/day, and no statistical difference was observed between different age groups, formulations, or indications (P > 0.05). Concomitant treatment of tacrolimus and diarrhea were found to affect Cmins of tablets, while age, gender, and BMI were found to be correlated with Cmins of injections. IFD breakthrough occurred in 9.2% of patients with a median Cmins of 0.74 mg/L for prophylaxis, and infection progression occurred in 43.2% of patients with a median Cmins of 0.97 mg/L for treatment, respectively. Transaminitis was the most common adverse event. Posaconazole delayed-release tablets and injections are safe for prophylaxis and treatment of IFD in pediatric patients. An empirical initial dose of 6.0 mg/kg of body weight/day is appropriate for prophylaxis, while a higher dose should be required for the treatment of IFD. It is necessary to adjust the dose regimen according to the results of therapeutic drug monitoring.This study is registered with chictr.gov.cn under identifier ChiCTR2300070008.

Life-threatening antibodies: The discovery of anaphylaxis.

It was at the turn of the 20th century, that immune serum was found both to save children dying from toxins of deadly pathogens, and to kill a dog within minutes following an injection of harmless doses of sea anemone toxins. This means that, before being formally identified in immune serum, antibodies were already known to be both protective and pathogenic. For this provocative finding, Charles Richet was awarded the 1913 Nobel Prize in Physiology or Medicine. Because, as its name said, anaphylaxis was understood as "the contrary of protection," unique mechanisms were found to explain it. Because, as its name did not initially say but finally said, allergy was understood as a reaction "other" than immunity, its symptoms were explained by mechanisms similar to those that explained anaphylaxis. We examined here the intricate relationships between anaphylaxis, allergy and immunity. Progressively anaphylaxis became one among other pathological effects of an immune response, and allergy an inflammatory disease among others. Looking at antibodies back in the past enables us not only to learn where they come from, but also to follow trends that contributed to shape immunology, some of which may persist in today's immunological thinking and say something about the future.

Effect of perioperative single dose intravenous vitamin C on pain after total hip arthroplasty

IntroductionVitamin c can relieve the pain after other diseases, but there are no studies on whether vitamin C can relieve the pain after hip replacement. The purpose of this paper is to study whether vitamin C can relieve the pain after total hip replacement.PurposeIn this prospective, double-blind, placebo-controlled, randomized trial, 100 patients receiving THA at our hospital were randomly assigned to vitamin c or control groups. During the operation, the vitamin C group will receive intravenous injection of 3 g vitamin C, and the control group will receive 3 g placebo. If the patient has postoperative pain, 10 ml subcutaneous injection of morphine will be required as a rescue analgesic. The primary outcome was the amount of postoperative injection of morphine as a rescue analgesic and expression of inflammatory factors, and the secondary outcome was postoperative pain and hip recovery as assessed by visual analog scale (VAS).ResultsThe dosage of subcutaneous injection of morphine was significantly reduced in vitamin C group. VAS pain scores at rest and exercise were lower in the vitamin C group 24 h after surgery, and hip motion was better 24 h after surgery, but there was no significant difference between the two groups 24 h after surgery.Nonetheless, the overall changes in morphine usage and VAS scores did not surpass the established minimal clinically important differences (10 mg for morphine consumption; 1.5 at rest and 1.8 during movement for VAS scores).ConclusionAdding intravenous vitamin c to multimodal analgesia significantly improved morphine consumption, VAS pain score, and functional recovery. However, it is recommended that single intravenous administration of vitamin C during the perioperative period may achieve better pain relief for patients after THA.

Single intra-articular injection of human synovial membrane MSC from grade IV knee osteoarthritis patient improve cartilage repair in OA rat model

AimThis study aims to assess the effectiveness of therapy of human synovial membrane-derived MSCs (SM-MSC) from OA grade IV patients in treating knee OA.MethodsSM-MSC were isolated from patients undergoing total knee replacement surgery, cultured to the fourth passage, and characterized using flow cytometry. Differentiation potential was assessed through lineage-specific staining. Osteoarthritis was induced in 24 Wistar rats via monosodium iodoacetate (MIA). The rats were divided into three groups: negative control, OA control, and OA treated with SM-MSC. Radiological, histopathological, and molecular analyses were conducted to evaluate cartilage repair and gene expression.ResultsFlow cytometry confirmed the MSC phenotype of SM-MSC, and successful differentiation was observed. Radiological and histopathological analyses showed significant improvement in the SM-MSC treated group, with reduced cartilage damage and higher Safranin O staining compared to the OA control group. Gene expression analysis indicated increased type-2 collagen (COL-2) expression in the SM-MSC treated group, although MMP-13 levels remained unchanged across all groups.ConclusionHuman SM-MSCs from OA grade IV patients significantly improved cartilage repair in an OA rat model, demonstrating their potential as a therapeutic option for OA. To enhance long-term efficacy and anti-inflammatory effects, further studies are needed to optimize treatment protocols, including injection frequency and dosage.

Signature of diabetic cardiomyopathy progression using high-fat diet and streptozotocin mouse model: from subclinical to clinical with three-hit mouse model

Abstract Background Diabetic cardiomyopathy (DbCM) is a pre-heart failure (pre-HF) condition that usually exhibits early diastolic dysfunction and evolving systolic dysfunction, along with left ventricular (LV) remodelling. Although DbCM shows distinct pathophysiology, the transition from the subclinical to the symptomatic stage is not straightforward and usually involves multifaceted processes which are not fully understood. Purpose To define the signature of DbCM progression in a novel mouse model using longitudinal echocardiography and multi-omics approaches. Methods Male mice (C57BL/6) were fed with high-fat diet (HFD) or control diet (CD) for 24 weeks, with single dose of streptozotocin (STZ) or vehicle injection at 8 weeks (n=10 each). Serial functional and metabolic parameters were measured prior to endpoint single nuclei RNA sequencing (snRNA-seq) and mass spectrometry-based proteomics analysis with comparison to cardiac remodelling to define detailed mechanisms underlying DbCM progression. Results HFD/STZ mice developed type 2 diabetes mellitus (T2DM) based on higher fasting blood glucose and HbA1C levels, insulin resistance and decreased beta-cell function (HOMA-IR and HOMA-beta, respectively) compared to controls. Progressive diastolic dysfunction was evident in HFD/STZ mice compared to CD mice based on enlarged LVPW;d from 12 weeks (P&amp;lt;0.05), reduced MV E/A ratio (P&amp;lt;0.01) and IVRT (P&amp;lt;0.05) from 16 weeks, and increased cardiac filling pressure (Left atrial (LA) area and LA volume) at 24 weeks, with preserved systolic function. This was paralleled by elevated collagen deposition (Picrosirius red), myocyte cross-sectional area and Col1a1 expression in HFD/STZ versus CD mice (all P&amp;lt;0.05). snRNA-seq analysis indicated preferential monocyte migration into diabetic hearts (P&amp;lt;0.01) whilst inflammatory pathways were activated across all cardiac cell types. Proteomics analysis revealed elevated expression of the established inflammation marker, plasma C-reactive protein (CRP), in HFD/STZ versus CD mice (P&amp;lt;0.05), which was correlated with worsening diastolic function (MV E/A ratio: r=-0.839, P&amp;lt;0.01) and LV hypertrophy (LVPW;d: r=0.861, P&amp;lt;0.01). Conclusion Our HFD/STZ mouse model offers a ‘three-hit’ approach which effectively captures key stages of clinical DbCM progression: 1) T2DM with insulin resistance, 2) progressive diastolic dysfunction with elevated chronic filling pressure and cardiac remodelling, and 3) systemic inflammation. This improved HFD/STZ mouse model is therefore appropriate to support a detailed study of mechanisms underlying DbCM progression and subsequent translation.

Mathematical Modeling Unveils Optimization Strategies for Targeted Radionuclide Therapy of Blood Cancers.

Targeted radionuclide therapy is based on injections of cancer-specific molecules conjugated with radioactive nuclides. Despite the specificity of this treatment, it is not devoid of side-effects limiting its use and is especially harmful for rapidly proliferating organs well perfused by blood, like bone marrow. Optimization of radioconjugates administration accounting for toxicity constraints can increase treatment efficacy. Based on our experiments on disseminated multiple myeloma mouse model treated by 225Ac-DOTA-daratumumab, we developed a mathematical model which investigation highlighted the following principles for optimization of targeted radionuclide therapy. 1) Nuclide to antibody ratio importance. The density of radioconjugates on cancer cells determines the density of radiation energy deposited in them. Low labeling ratio as well as accumulation of unlabeled antibodies and antibodies attached to decay products in the bloodstream can mitigate cancer radiation damage due to excessive occupation of specific receptors by antibodies devoid of radioactive nuclides. 2) Cancer binding capacity-based dosing. The total number of specific receptors on cancer cells is a critical factor for treatment optimization, which estimation may allow increasing treatment efficacy close to its theoretical limit. Injection of doses significantly exceeding cancer binding capacity should be avoided since radioconjugates remaining in the bloodstream have negligible efficacy to toxicity ratio. 3) Particle range-guided multi-dosing. The use of short-range particle emitters and high-affinity antibodies can allow for robust treatment optimization via initial saturation of cancer binding capacity, enabling redistribution of further injected radioconjugates and deposited dose towards still viable cells that continue expressing specific receptors.

Silicon-Enriched Meat Ameliorates Diabetic Dyslipidemia by Improving Cholesterol, Bile Acid Metabolism and Ileal Barrier Integrity in Rats with Late-Stage Type 2 Diabetes.

Silicon as a functional ingredient of restructured meat (RM) shows antidiabetic and hypocholesterolemic effects in a type 2 diabetes mellitus (T2DM) rat model. The present paper investigated the mechanisms involved in this cholesterol-lowering effect by studying the impact of silicon-RM consumption on bile acid (BA) and cholesterol metabolism. In addition, the main effects of cecal BA and short-chain fatty acids derived from the microbiota on intestinal barrier integrity were also tested. Rats were fed an RM high-saturated-fat, high-cholesterol diet (HSFHCD) combined with a low dose of streptozotocin plus nicotinamide injection (LD group) and for an 8 wk. period. Silicon-RM was included in the HSFHCD as a functional food (LD-Si group). An early-stage T2DM group fed a high-saturated-fat diet (ED group) was used as a reference. Silicon decreased the BA pool with a higher hydrophilic BA profile and a lower ability to digest fat and decreased the damaging effects, increasing the occludin levels and the integrity of the intestinal barrier. The ileal BA uptake and hepatic BA synthesis through CYP7A1 were reduced by FXR/FGF15 signaling activation. The silicon up-regulated the hepatic and ileal FXR and LXRα/β, improving transintestinal cholesterol (TICE), biliary BA and cholesterol effluxes. The inclusion of silicon in meat products could be used as a new therapeutic nutritional tool in the treatment of diabetic dyslipidemia.

Predictive factors for Submacular Hemorrhage in Age-related Macular Degeneration: A Retrospective Study.

Little is known about the major risk factors for submacular hemorrhage (SMH). This study aimed to evaluate the factors associated with SMH in patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) receiving three consecutive loading doses of intravitreal aflibercept or ranibizumab injections. This retrospective cross-sectional study included 48 patients diagnosed with wAMD and PCV who completed three loading doses under a treat-and-extend regimen. Patients were divided into the SMH group (n=24) and the non-SMH group (age- and sex-matched without SMH). Intravitreal injections, agents, and optical coherence tomography (OCT) features were compared. In the SMH group, SMH occurred approximately 3.29 years after post-nAMD diagnosis. The non-SMH group received more intravitreal injections of aflibercept and brolucizumab during the follow-up period after the initial loading phase. The SMH group exhibited a higher prevalence of serous/hemorrhagic pigment epithelial detachments (PEDs) at the last visit before SMH occurrence compared to the non-SMH group. Patients with a PED increase in the past two visits showed a higher tendency in the SMH group. No other OCT features significantly correlated with SMH development. The presence of serous/hemorrhagic PEDs may indicate a higher risk of SMH, and eyes with these features should be closely monitored to prevent sudden and devastating visual loss caused by SMH.

Effects of exogenous progesterone on the ovine serum progesterone profile during the non-breeding season

Exogenous progesterone (PRG) sources are used to induce ovine estrus during the non-breeding season. Intramuscular injection (IM) of PRG is an uncommon route for this purpose. This study investigated serum progesterone (P4) levels after IM administration of 50 mg of two different PRG products. Ten ewes were selected and received two consecutive PGF2α injections at 24-h intervals. Serum samples were collected (Time 0), followed by the injection of single doses of Fertigest® or Vetagesterone®. Serum P4 levels were assayed at times (T) 0, 30 min, 3,6,12,24,48,72,96, and 120 h after injection. A large variation in the serum P4 levels at T0 was detected. The serum P4 level at T0 was 4.3 ng/mL, which is considerable for anestrus ewes, following PGF2α administration. The mean time to reach maximum serum P4 concentration was 5.8 h, with a mean concentration of 22.5 ng/mL. Serum P4 levels returned to basal values (T0) after 48 h. An increased P4 production rate (PR) was detected following PRG administration, which continued for 24 h. A single injection of PRG reduced the variety of serum P4 levels from 24 h onward. The two different PRG generated different serum P4 concentrations. This study indicates an unusual change in serum P4 levels in anestrus ewes following PGF2α administration. 48 h after 50 mg PRG injection, the plasma levels of P4 reached basal levels in anestrus ewes.

Deflazacort-induced Steven-Johnson syndrome: a case report and literature review

Objective: To summarize the clinical features and outcomes of deflazacort-induced Steven Johnson syndrome (SJS)-toxic epidermal necrolysis (TEN) to raise awareness among patients with Duchenne muscular dystrophy (DMD), neurologists as well as other deflazacort users. Methods: The clinical data of a boy with DMD who had SJS induced by deflazacort treated at the Department of Rheumatology & Clinical Immunology of Tianjin Children's Hospital in July 2024 was analyzed retrospectively. Taking "deflazacort" "Steven-Johnson syndrome" "toxic epidermal necrolysis" in Chinese or English as the keywords, literature was searched at CNKI, Wanfang, China Biomedical Literature Database and PubMed up to July 2024. The clinical characteristics, treatment and outcomes of deflazacort-induced SJS-TEN were summarized. Results: A 12-year-old boy was admitted with a 3-day history of rash. He was diagnosed with DMD at the age of 3 and had been treated with prednisolone since the age of 8. Forty-four days before admission, the patient started deflazacort to replace prednisolone. Three days before admission, progressively worsening erythematous maculopapular rashes, blisters and skin peeling (8% body surface area), oral mucosal erosion, and exudative conjunctivitis occurred, thus deflazacort was discontinued. Complete remission of SJS was achieved after treatment with intravenous immunoglobulin (IVIG, total 1.4 g/kg), 2 doses of etanercept (0.9 mg/kg, once), subcutaneous injection and intravenous methylprednisolone (0.7 mg/(kg·d)). Based on the literature, there were 5 reports in English while none in Chinese, altogether 7 cases were reported. All the patients were male, aged 3-45 years. Duration of deflazacort exposure was 2-8 weeks. Dermatology diagnosis of our case was SJS, and 5 cases were TEN. One patient was diagnosed with exudative erythema multiforme, and subsequent deflazacort oral challenge test was positive. Treatment included methylprednisolone or dexamethasone in 5 cases, IVIG in 6 cases, etanercept in 3 cases and cyclosporine in 1 case. All patients recovered completely. Conclusion: The synthetic corticosteroid deflazacort can cause rare but severe adverse reactions such as SJS-TEN, which needs close monitoring and prompt recognition and management.

Comparative study of labour analgesia onset with injection of loading dose through epidural needle versus catheter

Comparative study of labour analgesia onset with injection of loading dose through epidural needle versus catheter

Exposure-Efficacy Analysis and Dopamine D2 Receptor Occupancy in Adults with Schizophrenia after Treatment with the Monthly Intramuscular Injectable Risperidone ISM.

Dopamine D2 receptor occupancy (D2RO) significantly influences the clinical effectiveness and safety of many antipsychotic drugs. Maintaining a D2RO range of 65%-80% provides the best antipsychotic effects while minimizing adverse reactions. Data from a Phase III trial were used to establish an exposure-response relationship for monthly intramuscular Risperidone ISM (75 and 100 mg) or placebo administered to adults with schizophrenia. Pharmacodynamic analysis was based on an Emax model for Positive and Negative Syndrome Scale (PANSS) developed in NONMEM. Plasma concentrations of the active moiety were derived using a previously developed population pharmacokinetic model, which was used for D2RO simulations in conjunction with a published Emax model. The optimal D2RO range (65%-80%) was reached for the median within hours following the first injection of both Risperidone ISM doses. At steady state, median D2RO for both doses remained above 65% throughout the 28-day dosing period and demonstrated lower variability than oral risperidone. PANSS response did not differ significantly between dose groups, most likely because active moiety concentrations had already reached the plateau of the concentration-response relationship. The pharmacokinetic/pharmacodynamic analysis showed a profound placebo effect (-11.7%), and an additional maximal drug effect (-6.6%) resulting in a total PANSS improvement over time of -18.3%. Pharmacokinetic/pharmacodynamic modeling quantified a PANSS improvement over time after Risperidone ISM administration. The response was not significantly different in either dose group, likely because D2RO was already above the proposed efficacy threshold (65%) within 1 h after the first Risperidone ISM injection and remained above this level following repeated administrations.

Comparison between Effects of Intralesional Platelet Rich Plasma and Corticosteroid Injection on Pain and Functional Outcome in Patients with Lateral Epicondylitis of Elbow

Background: A debilitating and painful elbow problem is lateral epicondylitis. Objective: In this study, pain and functional outcomes were examined in relation to intralesional platelet-rich plasma (PRP) and corticosteroid injections patients with lateral epicondylitis. Methodology: This randomized experimental study was done in the Department of Physical Medicine and Rehabilitation, Bangabandhu Sheikh Mujib Medical University (BSMMU) from March 2017 to February 2018. Thirty patients with diagnosed lateral epicondylitis, aged between 21- 60 years and had been ill for more than a month were enrolled and randomly assigned into two groups. In Group A received two doses of intralesional PRP injection, and Group B received two doses of intralesional corticosteroid injection. Pain and functional outcomes were evaluated by using a visual analog scale (VAS) for pain and a patient-rated tennis elbow assessment (PRTEE) questionnaire, respectively. In the lateral epicondylar region, intralesional PRP or corticosteroids were administered during the first (week 1=W1) and fourth (week 7=W7) treatment visits. Results: The findings revealed a statistically significant decline in pain over time, as well as improvements of functional outcomes in both groups as evidenced by significantly lower VAS scores and lower PRTEE scores up to 11 weeks post-injection. There was no discernible difference in progress between the two groups up until W1 to W9 scores, however at the eleventh week, group A showed greater improvement than group B (p&lt;00.5). Conclusions: Intralesional PRP injection is a promising therapy option for lateral epicondylitis, offering sustained pain relief and improved functional outcomes over time compared to corticosteroid injection. Journal of Monno Medical College June, 2024; 10 (1):30-35

Adrenaline Auto-Injectors for Preventing Fatal Anaphylaxis.

Anaphylaxis affects up to 5% of people during their lifetime. Although anaphylaxis usually resolves without long-term physical consequences, it can result in anxiety and quality of life impairment. Rarely and unpredictably, community anaphylaxis can cause rapid physiological decompensation and death. Adrenaline (epinephrine) is the cornerstone of anaphylaxis treatment, and provision of adrenaline autoinjectors (AAI) has become a standard of care for people at risk of anaphylaxis in the community. In this article, we explore the effectiveness of AAIs for preventing fatal outcomes in anaphylaxis, using information drawn from animal and human invivo studies and epidemiology. We find that data support the effectiveness of intravenous adrenaline infusions for reversing physiological features of anaphylaxis, typically at doses from 0.05 to 0.5 μg/kg/min for 1-2 h, or ~ 10 μg/kg total dose. Intramuscular injection of doses approximating 10 μg/kg in humans can result in similar peak plasma adrenaline levels to intravenous infusions, at 100-500 pg/mL. However, these levels are typically short-lived following intramuscular adrenaline, and pharmacokinetic and pharmacodynamic outcomes can be unpredictable. Epidemiological data do not support an association between increasing AAI prescriptions and reduced fatal anaphylaxis, although carriage and activation rates remain low. Taken together, these data suggest that current AAIs have little impact on rates of fatal anaphylaxis, perhaps due to a lack of sustained and sufficient plasma adrenaline concentration. Effects of AAI prescription on quality of life may be variable. There is a need to consider alternatives, which can safely deliver a sustained adrenaline infusion via an appropriate route.

Toxicity and safety profile evaluation of Shenfu injection in a murine sepsis model

AimThis study aimed to evaluate the preclinical safety of Shenfu injection for the treatment of sepsis. Tests were designed and conducted to determine the acute and long-term toxicity of Shenfu injection in rats, based on the recommended indications and dosage for human use. Materials and methodsRats were administered 22.5 g of raw drug/kg/day via tail vein injection. Toxicity symptoms were monitored for 14 days following the intravenous injection of Shenfu injection, and target organs affected by toxicity were analyzed. To assess long-term toxicity, rats were given 12, 9, or 6 g of raw drug/kg/day by intraperitoneal injection, equivalent to 12, 9, and 6 times the daily clinical dose for adult sepsis patients (3.3 mL of stock solution per 1 g of raw drug/kg/day), for 30 consecutive days. This was followed by a 28-day recovery period after withdrawal of the drug. During the administration and recovery periods, signs of toxicity were observed and compared with those in the control (stromal fluid) group. The aim was to predict potential clinical adverse reactions, including the nature and severity of these reactions, dose-response and time-response relationships, and the reversibility of the effects. Additionally, the study sought to identify the target organs or tissues potentially affected by repeated administration and suggest clinical indicators that should be monitored during the product's use. Furthermore, the safety of co-administration with commonly used chemical medications for the treatment of sepsis was investigated. ResultsIn the acute toxicity test, administration of the maximum dose of Shenfu injection (75 mL of stock solution/22.5 g of raw drug/kg/day) via tail vein injection resulted in transient symptoms, including piloerection (vertical hair response), weight loss, and reduced food intake. In the long-term toxicity experiments, rats received intraperitoneal injections of 0.3 g/mL (stock solution), 0.225 g/mL, and 0.15 g/mL Shenfu injection per day, which corresponded to 12, 9, and 6 times the daily clinical dose for adults with sepsis. The injections were administered twice daily for 30 days, followed by a 28-day drug withdrawal period for recovery. After 28 days, no significant toxicological changes were observed, apart from a hemodilution effect caused by the excessive volume of the drug and a slight increase in alkaline phosphatase and total bilirubin levels. The effects were reversible upon drug discontinuation. ConclusionsA single intravenous injection of 22.5 g of raw drug/kg/day and long-term intraperitoneal administration of up to 12 g of raw drug/kg/day are considered safe doses for rats.