Preinjection Levels Research Articles

Lipid-lowering therapy with Inclisiran in the real-world setting: initial data from a national health care service

Abstract Introduction Inclisiran, a first-in-class siRNA enabling long-term inhibition of PCSK9 synthesis, demonstrates good safety and efficacy profile in randomized clinical trials. Challenges for real-life use of inclisiran include limited access to therapy, injections by medical staff, lack of cardiovascular outcome data, and concern from adverse effects considering the novel mechanism and long-term activity. Real-life data on the potential to attain lipid-goals and reduce treatment gaps is lacking. We investigated the implementation of inclisiran in real-world clinical setting in Israel. Methods Data from a nationwide healthcare organization on patients initiating inclisiran therapy during the period of 3/2022-11/2023. Patients’ characteristics, efficacy, use of combination lipid-lowering therapies, and attainment of low-density lipoprotein cholesterol (LDL-C) goals, were evaluated. Results Inclisiran was initiated by 503 patients (57% women; mean age 66±11 years). Atherosclerotic cardiovascular disease was present in 54%, and peak historical LDL-C levels >190 mg/dL documented in 64%. Prior exposure to PCSK9 monoclonal antibodies was evident in 28%. Follow-up lipid profile >2 months after filling first prescription, was available in 397 patients (347 with ≥2 injections). In patients treated by inclisiran only (n=254), median LDL-C reduction from peak historical levels was 57% (IQR, 48%-67%), and from pre-injection levels 40% (19%-54%). In those with concomitant oral lipid-lowering therapies (n=143), median LDL-C reduction from peak levels was 66% (IQR, 55%-73%), and from pre-injection levels 46% (23%-59%) (Figure). LDL-C <70 mg/dL was attained by 39% and LDL-C <55 mg/dL by 21.9%. Of those treated with concomitant statin therapy, 38% attained LDL-C <55 mg/dL. Overall, 6.5% did not persist with inclisiran therapy after initial injection. Conclusions In real-life practice, inclisiran showed good efficacy with positive short-term adherence. However, attainment rates of lipid-goals were suboptimal due to limited use of combination lipid-lowering therapy and high-rates of severe hypercholesterolemia in our patient population cohort.Waterfall Plot of LDL-C (%) Reduction

Duration of Vascular Endothelial Growth Factor Suppression After Intravitreal Injection of Brolucizumab and Aflibercept in Macaque Eyes.

Purpose: To compare the duration of vascular endothelial growth factor (VEGF) suppression in the aqueous humor of macaque eyes after intravitreal injection of brolucizumab and aflibercept. Methods: Clinical dose of intravitreal brolucizumab (IVBr; 6.0 mg/50 μL) or intravitreal aflibercept (IVA; 2 mg/50 μL) was injected into the right eye of each of 8 macaques. Aqueous humor samples (150 μL) from both eyes were obtained just before injection and on days 1, 3, 7, 14, 21, 28, 42, 56, 84, and 112 after IVBr injection or IVA injection. VEGF concentrations were measured using enzyme-linked immunosorbent assays. Results: In the injected eyes, the mean VEGF suppression durations (range) were 4.9 (3-8) weeks for IVBr injection and 6.8 (6-8) weeks for IVA injection (P = 0.04). The VEGF concentrations returned to the preinjection level in the aqueous humor at 12 weeks both after IVBr and IVA injection. In the noninjected fellow eyes, the aqueous VEGF concentrations had decreased least at 1 day after IVBr injection and at 3 days after IVA injection, but were still detectable. The VEGF concentrations in the fellow eyes returned to the preinjection level in the aqueous humor at 1 week after IVBr injection and at 2 weeks after IVA injection. Conclusions: The duration of VEGF suppression in the aqueous humor after IVBr injection may be shorter than that after IVA injection, which may be related with clinical usage.

A Comparison of Ocular Complications after 0.7 mg Dexamethasone Implant versus 2 mg of Intravitreal Triamcinolone in Vitrectomized Eyes

To compare the rates of complications in eyes that received a dexamethasone (DEX) implant (0.7mg) or intravitreal triamcinolone (IVT) (2 mg) to treat postvitrectomy macular edema (ME). Retrospective, comparative, case series. A total of 148 eyes (147 patients); 75 eyes (75 patients) in the DEX group and 73 eyes (72 patients) in the IVT group. The medical records of patients who received an intravitreal DEX 0.7 mg (Ozurdex) or triamcinolone (2 mg) (Triesence) for postvitrectomy ME between July 2014 and December 2021 with a minimum follow-up of 3 months were reviewed. Ocular hypotony and ocular hypertension were defined as intraocular pressure of <6mmHg and > 24 mmHg, respectively. The rates of complications. The follow-up duration was 2.5 ± 1.6 years, with no significant difference between the groups (P=0.398). The rate of transient ocular hypotony per eye and per injection was significantly higher in the DEX group (10 eyes [13%], 30 of 443 injections [7%]) compared with the IVT group (2 eyes [3%], 2 of 262 injections [0.8%]) (P= 0.039 and < 0.001, respectively). Mean visual acuity significantly decreased at the time of ocular hypotony (P= 0.031), but returned to preinjection level after resolution of the hypotony after a median of 12 days. The incidence of ocular hypertension was higher in the DEX group (23 eyes [31%]) than the IVT group (16 eyes [22%]), but this was not statistically significant (P= 0.307). Ocular hypertension was controlled with observation or topical medication. There were no between-group differences in the incidence of vitreous hemorrhage (DEX, 3eyes [4%]; IVT, 1 eye [1%]; P= 0.632) or rhegmatogenous retinal detachment (DEX, 3 eyes [4%]; IVT, 0 eyes [0%]; P= 0.253). Four eyes (5%) experienced migration of the DEX implant into the anterior chamber. No eye developed endophthalmitis. The incidence of ocular hypotony, which causes transient visual impairment, was significantly higher in vitrectomized eyes treated with DEX compared with eyes treated with IVT. Injections other than the inferotemporal quadrant or rotating injection sites may be recommended. Proprietary or commercial disclosure may be found after the references.

COVID-19 pandemisi sürecinde ileri evre gonartrozu olan hastalarda eklem içi enjeksiyonlar ağrı yönetiminde etkili midir? Tek merkez deneyimi.

Background: Primary gonarthrosis is a progressive disease that increases with age and leads to limitations in activities of daily living. Until surgery is performed, nonsteroidal anti-inflammatory drugs, intraarticular injections, and physical therapy methods are used.&#x0D; Purpose: This study aims to compare the clinical outcomes of intra- articular corticosteroid (CCS) and hyaluro nic acid (HA) injections for pain relief in primary gonartrhosis in COVID -19 pandemic period.&#x0D; Study Design: Retrospective Cohort Study.&#x0D; Methods: In this study, 88 patients who underwent intra-articular CCS and HA injection between August 2020 and March 2021 due to Kellgren-Lawrence stage 2 and higher gonarthrosis were investigated. Patients were divided into two groups. Group I represents the patients who received HA injections, and group II represents the patients who received CCS injection. Western Ontario and McMaster Universities Arthritis Index (WOMAC) and Knee Society Score (KSS) scores were used for the preoperative and postoperative functional evaluations of the patients. &#x0D; Results: Group I included 40 patients and group II included 48 patients. The mean age was 59.4 ± 7.3 years, and the average follow-up period was 12 ± 2,6 months. The pre-intervention WOMAC scores were 13,5 in Group I and 13.6 in Group II, KSS scores were 26,5 in Group I and 25,2 in Group II. While there was a significant change in the control at month 1 in both groups, no difference was found between the groups. At the 6th month control, the improvement in group 1 continued at a significant level compared to the pre-injection period, while group 2 returned to the pre-injection level. (p

Assessment of clinical, biochemical, and radiological outcomes following intra-articular injection of Wharton jelly-derived mesenchymal stromal cells in patients with knee osteoarthritis: A prospective clinical study.

The aim of the present study was to perform clinical, biochemical, and radiological evaluation of the efficacy of mesenchymal stem cells derived from Wharton jelly (WJ) present within the human umbilical cord in the treatment of knee osteoarthritis. Between 2018 and 2019, 10 patients with knee osteoarthritis for whom the conservative treatment was not beneficial were included in the study. Patients were clinically, radiologically, and biochemically evaluated before treatment initiation. Thereafter, the patients were intra-articularly injected using a solution containing 1 × 108 WJ-derived MSCs. Evaluations were performed on day 21 (V1) and 42 (V2) and month 3 (V3), 6 (V4), and 12 (V5) after the procedure. At 1-year post-injection, visual analogue scale, Western Ontario and McMaster Universities Osteoarthritis Index, and Lequesne scores of patients were lower than those observed during the initial evaluation, whereas the mean 36-Item Short Form Health Survey score was higher. Cartilage thicknesses were found to be increased in all regions except in the medial femur, medial posterior femur, lateral posterior femur, and lateral posterior tibia regions in magnetic resonance imaging. A significant increase was observed in tumor necrosis factor-alpha, interleukin-1β, adiponectin, resistin, and interleukin-6 levels compared with pre-injection values. The leptin levels at 6-month and 1-year controls were lower than the pre-injection levels, and the decrease observed at 6 months was significant. In patients with knee osteoarthritis, intra-articular WJ-derived MSC injection causes significant pain reduction, satisfactory functional improvement, and increased patient satisfaction following a 1-year follow-up. These clinical improvements were supported by magnetic resonance images, along with changes in adiponectin and leptin levels in synovial fluid.Level of evidence: IV.

Bi-specific T1 positive-contrast-enhanced magnetic resonance imaging molecular probe for hepatocellular carcinoma in an orthotopic mouse model

BACKGROUNDHepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality. HCC-targeted magnetic resonance imaging (MRI) is an effective noninvasive diagnostic method that involves targeting clinically-related HCC biomarkers, such as alpha-fetoprotein (AFP) or glypican-3 (GPC3), with iron oxide nanoparticles. However, in vivo studies of HCC-targeted MRI utilize single-target iron oxide nanoprobes as negative (T2) contrast agents, which might weaken their future clinical applications due to tumor heterogeneity and negative MRI contrast. Ultra-small superparamagnetic iron oxide (USPIO) nanoparticles (approximately 5 nm) are potential optimal positive (T1) contrast agents. We previously verified the efficiency of AFP/GPC3-double-antibody-labeled iron oxide MR molecular probe in vitro. AIMTo validate the effectiveness of a bi-specific probe in vivo for enhancing T1-weighted positive contrast to diagnose the early-stage HCC.METHODSThe single- and double-antibody-conjugated 5-nm USPIO probes, including anti-AFP-USPIO (UA), anti-GPC3-USPIO (UG), and anti-AFP-USPIO-anti-GPC3 (UAG), were synthesized. T1- and T2-weighted MRI were performed on day 10 after establishment of the orthotopic HCC mouse model. Following intravenous injection of U, UA, UG, and UAG probes, T1- and T2-weighted images were obtained at 12, 12, and 32 h post-injection. At the end of scanning, mice were euthanized, and a histologic analysis was performed on tumor samples. RESULTST1- and T2-weighted MRI showed that absolute tumor-to-background ratios in UAG-treated HCC mice peaked at 24 h post-injection, with the T1- and T2-weighted signals increasing by 46.7% and decreasing by 11.1%, respectively, relative to pre-injection levels. Additionally, T1-weighted contrast in the UAG-treated group at 24 h post-injection was enhanced 1.52-, 2.64-, and 4.38-fold compared to those observed for single-targeted anti-GPC3-USPIO, anti-AFP-USPIO, and non-targeted USPIO probes, respectively. Comparison of U-, UA-, UG-, and UAG-treated tumor sections revealed that UAG-treated mice exhibited increased stained regions compared to those observed in UG- or UA-treated mice. CONCLUSIONThe bi-specific T1-positive contrast-enhanced MRI probe (UAG) for HCC demonstrated increased specificity and sensitivity to diagnose early-stage HCC irrespective of tumor size and/or heterogeneity.

Injected Anhydrous Ammonia Is More Effective Than Broadcast Urea as a Source of Nitrogen for Drill Seeded Rice

Anhydrous ammonia is a cheaper source of nitrogen (N) fertiliser than granular urea for rice production, but it is not widely used in developing countries. It can only be applied pre-crop with any in-crop applications being applied in the form of urea. This 2-year study conducted in the Nile delta region of Egypt compared pre-crop anhydrous ammonia injected to a depth of 20 cm with broadcast urea as N sources for rice, along with 4 combinations of pre-crop ammonia and in-crop urea. Each treatment supplied a total of 165 kg N/ha. The rice crop was direct seeded rather than transplanted. The highest yields were achieved in the full anhydrous ammonia treatment, which yielded 53% more grain than the nil-N control, while the full urea treatment yielded 22% more than the control; most combination treatments were intermediate. The higher grain yield of the anhydrous ammonia treatment was through a higher panicle density per unit area and more filled grains per panicle. An economic analysis found that the anhydrous ammonia treatment had a net return 70–94% higher than supplying the same quantity of N as urea. Counts of bacteria, fungi and actinomycetes showed a decline by day 2 after injection of anhydrous ammonia, followed by an increase to numbers similar to or above pre-injection levels by day 5. The findings indicated that pre-crop anhydrous ammonia in rice is both economically promising and not deleterious to soil microbes.

Vascular endothelial growth factor-A level in human breast milk after intravitreal injection of ranibizumab: a case report

BackgroundRanibizumab is one of intravitreal anti-vascular endothelial growth factor agents. It is applied in the treatments of choroidal neovascularization, age-related macular degeneration, diabetic macular edema, and macular edema secondary to retinal vein occlusion. Preliminary evidence suggests that intravitreal ranibizumab may enter the plasma and human breast milk in very low-level concentration. As a precaution, breastfeeding is not recommended during the treatment of intravitreal injection of ranibizumab. There are limited data regarding the change of anti-vascular endothelial growth factor concentration in human breast milk after intravitreal injection of ranibizumab, especially in the first 24 h after injection. The purpose of this report is to analyse the concentration change of vascular endothelial growth factor-A in human breast milk with time, in the short term after intravitreal injection of ranibizumab.Case presentationIn June 2018, a 30-year-old patient breastfeeding a six-month-old baby was diagnosed with choroidal neovascularization of left eye in Eye Hospital of Wenzhou Medical University. She received four administrations of 0.5 mg intravitreal injection of ranibizumab of the left eye, and breast milk was collected just before the injection, and 1–3, 6, 12, 24, 48, and 72 h after intravitreal injection, and assessed for vascular endothelial growth factor-A concentration. The change in vascular endothelial growth factor-A concentration in human breast milk showed the same trend after each injection, decreasing significantly within 6–12 h (about 20–30% lower), and increasing to pre-injection level by 24 h after injection.ConclusionsThe concentration of vascular endothelial growth factor-A in human breast milk of a mother who continues lactating dropped initially and rose to pre-injection level about 24 h after intravitreal injection of ranibizumab. The data may offer more information to evaluate the impact of anti-vascular endothelial growth factor agent intravitreal injection of lactating mothers and their breastfed infants.

In Situ Enhancement and Isotopic Labeling of Biogenic Coalbed Methane.

Subsurface microbial (biogenic) methane production is an important part of the global carbon cycle that has resulted in natural gas accumulations in many coal beds worldwide. Laboratory studies suggest that complex carbon-containing nutrients (e.g., yeast or algae extract) can stimulate methane production, yet the effectiveness of these nutrients within coal beds is unknown. Here, we use downhole monitoring methods in combination with deuterated water (D2O) and a 200-liter injection of 0.1% yeast extract (YE) to stimulate and isotopically label newly generated methane. A total dissolved gas pressure sensor enabled real-time gas measurements (641 days preinjection and for 478 days postinjection). Downhole samples, collected with subsurface environmental samplers, indicate that methane increased 132% above preinjection levels based on isotopic labeling from D2O, 108% based on pressure readings, and 183% based on methane measurements 266 days postinjection. Demonstrating that YE enhances biogenic coalbed methane production in situ using multiple novel measurement methods has immediate implications for other field-scale biogenic methane investigations, including in situ methods to detect and track microbial activities related to the methanogenic turnover of recalcitrant carbon in the subsurface.

Comprehensive Assessment of the Time Course of Biomechanical, Electrophysiological and Neuro-Motor Effects after Botulinum Toxin Injections in Elbow Flexors of Chronic Stroke Survivors with Spastic Hemiplegia: A Cross Sectional Observation Study.

Botulinum neurotoxin (BoNT) is commonly used to manage focal spasticity in stroke survivors. This study aimed to a perform comprehensive assessment of the effects of BoNT injection. Twelve stroke subjects with spastic hemiplegia (age: 52.0 ± 10.1 year; 5 females) received 100 units of BoNT to the spastic biceps brachii muscles. Clinical, biomechanical, electrophysiological, and neuro-motor assessments were performed one week (wk) before (pre-injection), 3 weeks (wks) after, and 3 months (mons) after BoNT injection. BoNT injection significantly reduced spasticity, muscle strength, reflex torque, and compound muscle action potential (CMAP) amplitude of spastic elbow flexors (all p < 0.05) during the 3-wks visit, and these values return to the pre-injection level during the 3-mons visit. Furthermore, the degree of reflex torque change was negatively correlated to the amount of non-reflex component of elbow flexor resistance torque. However, voluntary force control and non-reflex resistance torque remained unchanged throughout. Our results revealed parallel changes in clinical, neurophysiological and biomechanical assessment after BoNT injection; BoNT injection would be more effective if hypertonia was mainly mediated by underlying neural mechanisms. BoNT did not affect voluntary force control of spastic muscles.

Intraocular complications after caudal epidural steroid injection for discogenic lumbar pain with radiculopathy

Background: Epidural steroid injection is a common intervention for symptomatic lumbar disc herniation. It is safe, but not absolutely free from complications. Visual complications and adverse intraocular events are sparse in the literature. This study is done to determine any intraocular complication after caudal epidural steroid injection for discogenic low back pain and radiculopathy. Materials and Methods: It was a prospective study, conducted from April 2018 to December 2019 by the orthopedics and ophthalmology departments of our institute. A total of 31 patients were recruited based on inclusion/exclusion criteria. All the patients presented to this institute with complaints of low back pain and sciatica were investigated. After proper diagnosis, the decision was made for caudal epidural steroid injection as per the standard principles of orthopedic surgery. Eye evaluations (intraocular pressure [IOP], visual acuity, and ocular examination) were done 1 day before, and 2–4 h, 1 week, and 2 weeks after epidural injection. The differences in eye evaluation values between time points were determined and discussed. Results: A total of 31 patients were recruited for this study, out of which the majority of the patients (27 patients) were between 41 and 60 years of age, and males (22 patients) outnumbered females (nine patients). Most of the patients (17 patients) had prolapsed IV disc of L5-S1. IOP was found to be raised after the intervention of epidural steroid injection which gradually came down to a preinjection level within 2 weeks. There was no change in visual acuity and no other intraocular complications, like hemorrhages. Conclusion: Epidural steroid injection for discogenic low backache (LBA) with radiculopathy did not adversely affect IOP, and neither had any ocular complication (in an ophthalmologically normal set of patients). A prudent approach should always be implemented.

Changes of plasma nitric oxide, endothelin-1, and blood coagulation following intravitreal conbercept

Intravitreal anti-VEGF (anti-vascular endothelial growth factor) biologics have revolutionized the pharmacological management of chorioretinal diseases. However, the systemic adverse events such as stroke or bleeding are the concerns for many patients and physicians. The mechanism to develop these side effects are poorly understood. Consecutive 95 patients with retinal diseases were studied for their blood activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR), and concentration of fibrinogen before and after intravitreal conbercept. Additionally, plasma nitric oxide (NO) and endothelin-1 (ET-1) were investigated on 38 of the 95 patients. Compared with the pre-injection, 4-week post-injection values of APTT and PT were increased by 0.582 s (p = 0.038, paired t test) and by 0.086 s (p = 0.080, paired t test; p = 0.0475, Sign test), respectively. At the same time, fibrinogen decreased by 0.048 g/L. Plasma levels of NO or ET-1 or VEGF did not significantly change from pre-injection levels. Our findings advanced the understanding of mechanism for systemic side effects associated with intravitreal anti-VEGF and emphasized paying more attention to higher risk of possible bleedings for patients following intravitreal conbercept.

Temporal Pattern of Pain and Disability Following the Administration of a Selective Nerve Root Block in Lumbar Disc Herniation With Radiculopathy

Lumbar disc herniation with radiculopathy has a favorable natural history, and a selective nerve root block (SNRB) is an accepted treatment modality. This study aims to ascertain the temporal pattern of pain and disability following the administration of an SNRB in the management of lumbar disc herniation with radiculopathy because there is limited evidence regarding this issue in the published literature. This prospective study included 50 patients who underwent an SNRB and were followed for 3 months. Numerical Rating Scale (NRS) for back and leg pain and Oswestry Disability Index (ODI) and Depression Anxiety Stress Scales-21 (DASS-21) scores were collected. At the final follow-up at 3 months, the number of patients who underwent surgery was ascertained. Forty-two of 50 (84%) patients avoided the surgery with a reduction in mean preinjection NRS for back and leg pain from 7.5 (SD 1.33) and 7.7 (SD 1.35) to 3.1 (SD 1.69) and 2.3 (SD 1.14) (P < 0.001), respectively, within the 30 minutes after injection. The pain relief was sustained until the last follow-up. The ODI score also decreased from a mean preinjection level of 59.4 (SD 14.69) to 26.3 (SD 9.43) (P < 0.001) at 3 months. The mean preinjection depression score was higher in patients who had recurrence of pain and eventually underwent surgery. Early administration of an SNRB in the course of lumbar radiculopathy is recommended as it provides instantaneous and sustained relief of back and leg pain and disability in a majority of patients. SNRB should be administered early in the course of management of lumbar radiculopathy and should not be delayed until after other non-surgical modalities have failed. 2.

Preemptive Midazolam Can Reduce the Glycemic Stress Response to Surgery for Type-2 Diabetics Undergoing Simple Eye Surgery

Abstract Background: Estimation of percentage of change of blood glucose concentration (BGC) at 30- and 60-min after single dose of intravenous midazolam injection and at end of surgery in relation to pre-injection concentration. Aim of Study: Estimation of percentage of changes of blood glucose concentration (BGC) at 30- and 60-min after intravenous injection of single dose of midazolam and at end of surgery in relation to pre-injection BGC. Patients and Methods: 100 type-2 diabetic patients with fasting BGC of ³200mg/dl, ASA grade II or III and assigned for cataract surgery were evaluated clinically and received midazolam injection in a dose of 0. 0 1-0. 1 mg/kg, up to a total dose of 2.5mg, over two minutes or until patient was sedated and achieved Ramsy score 2 or 3. BGC was estimated before midazolam injection and at 30-min, 60-min after injection and at end of surgery. Then, patients received peribulbar and subtenon local anesthetic infiltration was performed. Results: All surgeries were conducted uneventfully within a mean operative time of 62.6±8.8 min. BGC showed progres-sive increases during surgery reaching a maximum at 60-min after injection and declined at end of surgery, but with non-significant differences between the three estimations and the pre-injection levels. Median value of percentage of increase of BGC at 60-min was significantly higher in comparison to median values of other estimations, with significantly higher percentage of increase at end of surgery than at 30-min after injection. Conclusion: Preemptive administration of midazolam for diabetic patients could control the surgery-induced hypergly-cemic effect and thus could protect patients against postoper-ative hyperglycemic complications.

Changes in cortical, cardiac, and respiratory activities in relation to spontaneous rhythmic jaw movements in ketamine-anesthetized guinea pigs.

It has been reported that rhythmic jaw movements (RJMs) spontaneously occur in ketamine-anesthetized animals. The present study investigated the physiological processes that occur during the cortical, cardiac, and respiratory events which contribute to the genesis of RJMs in animals after supplemental ketamine injections. Fourteen guinea pigs were prepared to allow electroencephalographic, electrocardiographic, and electromyographic activities to be recorded from the digastric muscle, measurement of jaw movements, and nasal expiratory airflow under ketamine-xylazine anesthesia. Rhythmic jaw movements spontaneously occurred with rhythmic digastric muscle contractions, 23-29minutes after injection of supplemental ketamine (12.5 and 25.0mgkg-1 , intravenously). The cycle length of RJMs did not differ significantly between the two doses of ketamine (mean±SD: 12.5mgkg-1 , 326.5±60.0ms; 25mgkg-1 , 278.5±45.1ms). Following injection of ketamine, digastric muscle activity, heart and respiratory rates, and cortical beta power significantly decreased, while cortical delta and theta power significantly increased. These changes were significantly larger in animals given 25.0mgkg-1 of ketamine than in those given 12.5mgkg-1 . With the onset of RJMs, the levels of these variables returned to pre-injection levels, regardless of the dose of ketamine administered. These results suggest that, following supplemental ketamine injections, spontaneous RJMs occur during a specific period when the pharmacological effects of ketamine wear off, and that these RJMs are characterized by stereotypical changes in cardiac, respiratory, and cortical activities.

Small doses of adrenaline contained in the local anaesthetic may result in prolonged increased cardiac function even after the vital signs return to normal

IntroductionThe effects of adrenaline contained in the local anaesthetic on vital signs have been reported under general anaesthesia or sedation. The ClearSight™ system measures cardiac parameters, including cardiac index, stroke volume, systemic vascular resistance index, continuous blood pressure, and heart rate, non-invasively and continuously. AimThis study aimed to assess the effect of adrenaline contained in the local anaesthetic on cardiac function in conscious participants. Materials and methodsEight healthy adults were recruited for the study. Local anaesthesia was administered to the maxillary gingiva using 3.6 mL of 2% lidocaine with 1/80,000 of adrenaline (group AD) or without adrenaline (group non-AD) on separate days. The above listed cardiac parameters were recorded with the ClearSight™ system. All data were continuously monitored until these values returned to normal levels. ResultsThe cardiac index and heart rate increased by 40% in group AD. Moreover, the cardiac index and systemic vascular resistance index in group AD required 50 min to recover to the pre-injection levels. Heart rate variations showed no intergroup differences, and variations in systolic continuous blood pressure persisted for only 30 min. ConclusionsThe effect of anaesthetic injection containing adrenaline on cardiac function may persist even after the vital signs return to normal.

FACTORS ASSOCIATED WITH REACTIVATION AFTER INTRAVITREAL BEVACIZUMAB OR RANIBIZUMAB THERAPY IN INFANTS WITH RETINOPATHY OF PREMATURITY.

To investigate the efficacy and risk factors of intravitreal antivascular endothelial growth factor injection (anti-VEGF therapy) for retinopathy of prematurity (ROP). We retrospectively reviewed 80 consecutive eyes of 43 patients with Type 1 ROP or worse who received anti-VEGF therapy during January 2012-February 2018. Patients were divided into those who were injected with 0.25 mg of bevacizumab (IVB group, 37 eyes) and 0.25 mg of ranibizumab (IVR group, 43 eyes). Serum VEGF concentrations of 18 patients were measured before and after IVR. Antivascular endothelial growth factor injection therapy reduced ROP activity in all eyes; however, 14 eyes (17.5%) exhibited reactivation. The reactivation rates of the IVB and IVR groups were 13.5% and 20.9%, respectively (P = 0.556). Multivariate logistic regression analysis showed that postmenstrual age ≤35 weeks at anti-VEGF therapy (P = 0.014) and aggressive posterior ROP (P = 0.044) was significantly associated with reactivation. Serum VEGF was significantly suppressed at Days 1 (P < 0.001) and 7 (P = 0.012) after IVR and returned to the preinjection level by Day 14 (P = 0.210). Both IVR and IVB seemed effective in reducing ROP activity. Reactivation after anti-VEGF therapy may be associated with younger postmenstrual age at anti-VEGF therapy and aggressive posterior ROP.

The effectiveness of ultrasonogram guided intervention in chronic shoulder pain cases attending pain clinic of a government hospital of East zone, India: a prospective observational study

Background: Ultrasonogram guided intervention in chronic shoulder pain is well known for relief of pain and improvement of range of movement (ROM) of affected shoulder joint. Ultrasonogram gives accuracy helps in localized corticosteroid delivery. Corticosteroids relieve the pain by its anti-inflammatory effect. There is conflicting evidence available regarding the effectiveness of the intervention in chronic shoulder pain, questioned in many studies. We planned this study to evaluate the efficacy of ultrasonogram guided intervention in chronic shoulder pain in a tertiary teaching hospital of rural Bengal.Methods: The prospective observational study was carried out in 100 patients with chronic shoulder pain attending pain clinic who fulfilled predetermined inclusion criteria. Patients were injected with 40 mg of depomethyl prednisolone and 10 ml of 1% preservative free lignocaine via standard posterior approach. Then half an hour of standard shoulder range of motion (ROM) exercise regimen was performed under supervision. Pre injection and post injection pain level were scored by visual analogue score (VAS) shoulder exercises were taught and home-based physiotherapy was carried out by patients themselves. Patient were followed at 4, 8, and 12 weeks.Results: The mean age of patients was 53.23±5.680 years with 63 % male study subjects, After the intervention, excellent result in VAS score and improvement of ROM observed in patients. There was statistically significant difference from baseline in both pain relief and shoulder movement.Conclusions: USG guided intervention is effective in pain relief and in improvement in ROM in chronic shoulder pain in long term.

P02 Osteoporosis management when denosumab therapy ends: an audit of current practice

Abstract Background In recent years denosumab therapy has been widely used in the treatment of osteoporosis. However, since its first introduction to clinical practice, evidence has demonstrated discontinuation leads to rebound bone loss and risk of vertebral fracture. In view of this, guidance has been updated recommending transition to an alternative osteoporosis therapy. Given that osteoporosis management is largely managed in primary care, we performed this audit to investigate whether this educational message was being effectively relayed to primary care clinicians. Methods In this study, we closed the audit loop of a previous study of the first 50 patients commenced on denosumab at University Hospital Southampton in 2013; we explored the percentage of patients remaining on denosumab 6 years later, using the hospital electronic system, which is linked to the general practice electronic system, to confirm prescriptions for osteoporosis therapy. In cases where it was unclear, letters were written, or telephone calls were made to general practices for clarification. Continuation of denosumab or use of an alternative agent was then recorded. Results Nineteen (38%) patients had died since the initial audit, reflecting the use of the agent in later life post hip fracture. Of 15 patients no longer on denosumab, 9 (60%) were found not to be on alternative bone protection without other information recorded, 1 (7%) had denosumab suspended by the GP (with the presumption it may be restarted at a later date), 1 (7%) had denosumab suspended due to recurrent cellulitis with the view to reassess in a year and 3 (20%) were on alternative therapy. One patient was recorded as being on a ‘drug holiday’. Of 16 patients remaining on denosumab, 13 (81%) had pre-injection calcium level checks, and 12 (75%) had a recorded pre-injection renal function check. Conclusion These data reflect inappropriate widespread discontinuation of denosumab without follow-on with an alternative osteoporosis therapy, suggesting that targeted education of primary care physicians is necessary. A high proportion of patients on denosumab are having the relevant blood tests in primary care as per clinical guidelines. Disclosures J. Zhang None. M.A. Clynes None. C. Cooper None. E.M. Dennison None.

Correlation between electromechanical parameters (NOGA XP) and changes of myocardial ischemia in patients with refractory angina.

IntroductionCell therapy has the potential to improve symptoms and clinical outcomes in refractory angina (RFA). Further analyses are needed to evaluate factors influencing its therapeutic effectiveness.AimAssessment of electromechanical (EM) parameters of the left ventricle (LV) and investigation of correlation between EM parameters of the myocardium and response to CD133+ cell therapy.Material and methodsThirty patients with RFA (16 active and 14 placebo individuals) enrolled in the REGENT-VSEL trial underwent EM evaluation of the LV with intracardiac mapping system. The following parameters were analyzed: unipolar voltage (UV), bipolar voltage (BV), local linear shortening (LLS). Myocardial ischemia was evaluated with single-photon emission computed tomography (SPECT). The median value of each EM parameter was used for intra-group comparisons.ResultsGlobal EM parameters (UV, BV, LLS) of LV in active and placebo groups were 11.28 mV, 3.58 mV, 11.12%, respectively; 13.00 mV, 3.81 mV, 11.32%, respectively. EM characteristics analyzed at global and segmental levels did not predict response to CD133+ cell therapy in patients with RFA (Global UV, BV and LLS at rest R = –0.06; R = 0.2; R = –0.1 and at stress: R = 0.07, R = 0.09, R = –0.1, respectively; Segmental UV, BV, LLS at rest R = –0.2, R = 0.03, R = –0.4 and at stress R = 0.02, R = 0.2, R = –0.2, respectively). Multiple linear regression of the treated segments showed that only pre-injection SPECT levels were significantly correlated with post-injection SPECT, either at rest or stress (p < 0.05).ConclusionsElectromechanical characteristics of the left ventricle do not predict changes of myocardial perfusion by SPECT after cell therapy. Baseline SPECT results are only predictors of changes of myocardial ischemia observed at 4-month follow-up.