Neuraxial administration of morphine combined with lidocaine induces regional antinociception in inland bearded dragons (Pogona vitticeps)

OBJECTIVE To assess the antinociceptive efficacy and safety of neuraxial morphine in inland bearded dragons (Pogona vitticeps). ANIMALS 10 healthy adult bearded dragons. PROCEDURES Animals were sedated with alfaxalone (15 mg/kg) SC prior to neuraxial injections. In a randomized, blinded, placebo-controlled, crossover design, animals received preservative-free morphine (0.5 mg/kg) combined with lidocaine (2 mg/kg) or lidocaine (2 mg/kg) only (control treatment). For both treatments, saline (0.9% NaCl) solution was used for dilution to a total volume of 0.3 mL/kg. If the initial injection did not result in motor block of the pelvic limbs or cloaca relaxation within 10 minutes, a second injection was performed. Measurements consisted of bilateral mechanical stimulation of the limbs and at 25%, 50%, and 75% of the trunk’s length as well as cloacal tone to assess spread and duration of motor block. Pelvic limb withdrawal latencies in response to a thermal noxious stimulus were measured over a 48-hour period to assess antinociception. RESULTS Success rate following the first injection was 90% (18/20 injections) and increased to 100% following a second injection. Motor block occurred within 5 minutes with both treatments. Pelvic limb withdrawal latencies were significantly prolonged following neuraxial morphine versus control treatment for at least 12 hours after injection. By 24 hours, no effect of morphine on pelvic limb latencies was detectable. CLINICAL RELEVANCE These results demonstrated that neuraxial administration of morphine results in regional antinociceptive effects for at least 12 hours and has no clinically relevant adverse effects in healthy bearded dragons. This technique has potential for providing regional analgesia in this species.

Intralesional Tetracycline Injection, Pinch Technique, and Canthopexy for the Treatment of Severe Festoons: Preliminary Results

Background Many techniques have been presented for the treatment of lower eyelid festoons, but no singular technique has become dominant. Objectives The authors describe the safety and efficacy of intralesional tetracycline injection, the pinch technique, and canthopexy for the treatment of severe festoons. Methods Institutional board review approval was obtained, and a retrospective chart review was performed on 15 consecutive patients who had received 2% tetracycline injections to treat lower eyelid large festoons between February 2017 and February 2020. Three months after the last injection, a series of patients underwent the surgical procedure: pinch technique and canthopexy bilaterally. Results Clinical and photographic records were reviewed, and 12 patients were included in the analysis. Three patients did not return for follow-up after the injection series. Of the 12 patients, there were 3 male patients and 9 female patients, with an average age of 66.6 years. The mean volume injected in each festoon was 0.43 mL, and the mean follow-up was 313 days. A series of injections with a 3-month time interval were performed for patients with a partial response to the initial injection. There was no evidence of complications at the site of the injection. Three months after the last injection, these 12 patients underwent complementary surgical treatment, which included pinch resection and canthopexy. Conclusions These preliminary results suggest that intralesional injections of tetracycline 2% may offer a safe option to treat lower eyelid festoons. This noninvasive procedure represents adjunct benefits to complementary surgical therapy. Level of Evidence: 4

The Preferred Premedication Order to Prevent Infusion Reactions in Patients with Breast Cancer Receiving Pertuzumab Plus Trastuzumab and Docetaxel

Aims:Pertuzumab plus trastuzumab and docetaxel is a standard regimen for human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the metastatic, adjuvant, and neoadjuvant settings. Infusion reaction represents one of the common side effects of anti-HER2 agents. There is no standard premedication to prevent infusion reactions, although antihistamines, acetaminophen, and/or corticosteroids are often used for this purpose. This study evaluated the ability of premedication to prevent induction reactions in patients receiving pertuzumab, trastuzumab, and docetaxel. Methods: This retrospective, single-institute study assessed infusion reactions in 72 women with HER2-positive early breast cancer who received pertuzumab, trastuzumab, and docetaxel between November 2018 and April 2021. Thirty-six patients received premedication consisting of oral acetaminophen prior to pertuzumab and trastuzumab administration and dexamethasone and D-chlorpheniramine maleate intravenously prior to docetaxel administration (previous regimen). Thirty-six patients received premedication consisting of acetaminophen, dexamethasone, and D-chlorpheniramine maleate sequentially prior to pertuzumab, trastuzumab, and docetaxel administration (current regimen). Results: The rates of infusion reaction after the initial injection were 55.6 and 16.7% in the previous and current regiment groups, respectively (p = 0.001). Trastuzumab more frequently caused infusion reactions than pertuzumab and docetaxel. Chills, vomiting, and nausea were the major symptoms of infusion reactions. Conclusion: Premedication featuring the upfront use of dexamethasone and D-chlorpheniramine maleate prior to the administration of anti-HER2 targeted agents significantly prevented infusion reactions.

The effect of sample medication use on subsequent anti-VEGF agent selection for neovascular age-related macular degeneration

Purpose: To examine the effect of medication sample use (ranibizumab or aflibercept) on future anti-vascular endothelial growth factor (VEGF) agent selection in neovascular age-related macular degeneration (nvAMD). Design: Retrospective cohort study. Methods: nvAMD patients who underwent an initial anti-VEGF injection with a sample medication were compared to nvAMD control patients who never received a medication sample. Charts from 2017 through 2020 were reviewed for data regarding demographics, anti-VEGF agent selection, and visual acuity outcomes for both groups. Anti-VEGF agent selection for the first four injections and at one year were examined in both the sample and control groups. Results: Adherence to the initial agent was high between first and subsequent injections (2nd, 3rd, 4th injection, and 1 year) in both sample (96.2%, 95.9%, 91.9%, 93.4%, respectively) and control groups (98.1%, 94.2%, 94.9%, 87.8%, respectively). Bevacizumab usage was significantly lower among eyes receiving samples relative to controls at the second (1.9% vs. 38.7%, p<0.001), third (3.1% vs. 41.3%, p<0.001), fourth injections (4.7% vs. 40.4%, p<0.001), and at 1 year (0% vs. 33.8%, p<0.001). Aflibercept usage was significantly higher in sample eyes relative to controls at the second (78.3% vs. 43.4%, p<0.001), third (76.3% vs. 41.5%, p<0.001), and fourth injections (76.7% vs. 43.4%, p<0.001), and at 1 year (77.0% vs. 52.7%, p<0.001). Conclusions: Eyes receiving a sample anti-VEGF agent (ranibizumab or aflibercept) for their initial injection were less likely to receive bevacizumab at future visits relative to eyes that did not receive an anti-VEGF sample, even after one year of treatment.

Appropriate Dose of Ranibizumab for ROP: A Retrospective

Objective: To compare the recurrence rate of retinopathy of prematurity (ROP) after treatment with 0.3 mg vs. 0.25 mg ranibizumab. Subjects: All patients with ROP who underwent intravitreal injection of ranibizumab in Hainan General Hospital between January 2014 and May 2020 were included in this study. Methods: 82 cases (146 eyes) who received intravitreal injection of 0.25 mg ranibizumab were included in the conventional-dose group, and 59 cases (108 eyes) who received intravitreal injection of 0.3 mg ranibizumab were included in the high-dose group. The two groups were further divided into the 25-28-week, 29-31-week, 32-34-week, and 35-36-week GA subgroups. The differences between the conventional-dose group and the high-dose group in gestational age (GA), birth weight(BW), age at initial injection(weeks), incidence of systemic diseases, the recurrence rate of ROP, and age at retinal vascularization completed(weeks) were analyzed. Results: GA, BW, age at initial injection, and the incidence of systemic diseases were not significantly different between the conventional-dose group and the high-dose group (p>0.05). The recurrence rates of ROP were significantly lower in the 25-28-week, 29-31-week, and 32-34-week subgroups of the high-dose group than in the same subgroups of the conventional-dose group (p<0.05). Within the conventional-dose group, the recurrence rate of ROP was significantly lower in the 32-34-week and 35-36-week subgroups than in the 25-28-week and 29-31-week subgroups (p<0.05). Within the high-dose group, the recurrence rate of ROP was not significantly different between the four subgroups (p>0.05). Retinal vascularization was completed at a later age in the 32-34-week subgroup of the high-dose group than in the 32-34-week subgroup of the conventional-dose group (p<0.05) but was not significantly different between the two groups at any other GA range (p>0.05). No severe ocular or systemic complications occurred in any patient. Conclusion: Treatment with 0.3 mg ranibizumab can reduce the recurrence rate of ROP without prolonging retinal vascularization or causing serious systemic complications. Therefore, this dose may be an appropriate therapeutic dose for ROP.

Ranibizumab or Aflibercept for Neovascular Age-Related Macular Degeneration, Twelve-Month Outcomes of Therapeutic Program in Non-Tertiary Institution: A Comparative Study.

Purpose: This single center study aimed to compare the 12-month treatment outcomes of ranibizumab with that of aflibercept in routine clinical practice.Methods: Cohort of patients diagnosed with treatment-naïve neovascular AMD, treated using either ranibizumab (n = 33 eyes) or aflibercept (n = 44 eyes) monotherapy over a 12-month follow-up period was analyzed. Anonymous data were extracted from the electronic database dedicated to the drug program.Results: In the ranibizumab group, there were not statistically significant changes in BCVA (ETRDS letters) and CRT (µm), between baseline (67.9 ± 8.6 & 384.9 ± 97.9) and at 12 months (67.9 ± 12.1 & 398.9 ± 127.1; P = 0.372 & P = 0.884, respectively). In the aflibercept, there was an improvement in BCVA and reduction in CRT between baseline (64.2 ± 8.1 & 414.3 ± 97.8) and at 12 months (70.7 ± 7.4 & 342.3 ± 71.6; P <.001 & P <.001, respectively). There was no difference in BCVA between the two groups at either diagnosis (P= 0.101) or 12 months (P= 0.917). Mean number of injections in the ranibizumab group was significantly lower (4.9 ± 1.5) than in the aflibercept group (6.7 ± 1; P<.001).Conclusions: One initial injection of ranibizumab and then PRN regimen resulted in stabilization of disease progression. Drug selection and treatment scheme could influence twelve-months outcomes. In the aflibercept group, three initial monthly injections and then every two months provided both significant BCVA improvement and CRT reduction at 12 months of treatment.

Endoscopic Management of Complicated High-Grade Vesicoureteral Reflux in the First Year of Life

Purpose:The treatment of high-grade vesicoureteral reflux in infants is controversial. Subureteric injection has been tried recently with its advantage of easy application and less invasiveness. In this study, we aimed to assess the efficacy of endoscopic sub-ureteric injection to correct high-grade reflux in infants with documented indications for anti-reflux surgery.Materials and Methods:Hospital records of high-grade (grade 4-5) VUR patients who had undergone endoscopic sub-ureteric injection in the first year of life with documented breakthrough infections, between 2009-2016 were reviewed. Radiologic success was defined as complete resolution of reflux in VCUG obtained at least three months after the injection and clinical success was defined as the downgrading of reflux degree below three and absence of urinary infection.Results:A total of 23 patients with 34 high-grade refluxing units were included in the study. The mean age at first injection was 6.3±1.8 months (1-11 months). Radiologic success rate with initial injection was 61.7% and increased to 85.2% after repeated injections. The overall clinical success rate at first injection was 70.6% and 97.1% after repeated injections. Mean injected material volume was 0.34±0.27 (0.1-1) ml per ureter. Conclusion:Endoscopic treatment is a successful alternative in infants with high-grade vesicoureteral reflux suffering breakthrough infections.

Estimating the effectiveness of the Pfizer COVID-19 BNT162b2 vaccine after a single dose. A reanalysis of a study of ‘real-world’ vaccination outcomes from Israel

A distinctive feature of the roll out of vaccination against SARS-CoV-2 virus in the UK was the decision to delay the timing of the second injection till 12 weeks after the first. The logic behind this is to protect more people sooner and so reduce the total number of severe infections, hospitalisations, and deaths. This decision caused criticism from some quarters due in part to a belief that a single injection may not give adequate immunity. A recent paper based on Israel’s experience of vaccination suggested that a single dose may not provide adequate protection. Here we extract the primary data from the Israeli paper and then estimate the incidence per day for each day after the first injection and also estimate vaccine effectiveness for each day from day 13 to day 24. We used a pooled estimate of the daily incidence rate during days 1 to 12 as the counterfactual estimate of incidence without disease and estimated confidence intervals using Monte Carlo modelling. After initial injection case numbers increased to day 8 before declining to low levels by day 21. Estimated vaccine effectiveness was pretty much 0 at day 14 but then rose to about 90% at day 21 before levelling off. The cause of the initial surge in infection risk is unknown but may be related to people being less cautious about maintaining protective behaviours as soon as they have the injection. What our analysis shows is that a single dose of vaccine is highly protective, although it can take up to 21 days to achieve this. The early results coming from Israel support the UK policy of extending the gap between doses by showing that a single dose can give a high level of protection.

Acute-Onset Achilles Tendon Pain and Swelling Treated with an Amniotic Fluid–Derived Allograft: A Case Study

Background Tendinopathies are common musculoskeletal disorders that often develop because of chronic loading and failed healing. Tendinopathy related to systemic inflammation has been less extensively examined. Furthermore, although the use of biological agents to treat tendinopathies continues to gain popularity, the use of amniotic fluid–derived allografts in outpatient settings to resolve tendinopathies requires further evaluation. Methods The focus of this case report is a 25-year-old man who presented for a second opinion, having been diagnosed with Haglund deformity and Achilles tendinopathy. At the time of presentation, he complained of 10 of 10 pain to the right Achilles tendon. He was treating the injury conservatively with intermittent use of a controlled ankle motion boot and working with physiotherapy for approximately 5 months before presentation. Diagnostic ultrasound along with magnetic resonance imaging indicated distal thickening of the Achilles tendon, substantial fluid and edema in the Kager fat pad, and retrocalcaneal erosions with bursitis. Conservative management did not resolve the symptoms. As an alternative to surgery, the patient elected to undergo an Achilles tendon injection of an amniotic fluid–derived allograft. Before and after the initial injection, a microdialysis catheter was inserted into the Achilles peritendinous space to sample local levels of extracellular matrix enzymes and growth factors important for tendon remodeling. The patient received considerable relief with the initial injection, but did not return to full strength. Over the subsequent 8 weeks, the patient was followed closely and was able to return to daily activities with minimal pain. He was not able to return to a more active lifestyle without further Achilles pain, so a second amniotic fluid–derived allograft injection was performed 8 weeks after the initial injection. Results Injection of the initial allograft resulted in significant improvement, but not complete resolution of pain and swelling. Microdialysis findings suggested a reduction in peritendinous levels of the cytokine interlukin-6 in addition to changes in extracellular matrix regulatory enzymes. After 8 weeks of additional conservative therapy and a second injection, no further improvement in pain was noted. Conclusions Based on the clinical improvement of symptoms in this individual and the changes seen with microdialysis methodology, the authors find the use of amniotic fluid–derived allograft injection for treatment of Achilles pain in this patient to be a viable treatment. Additional comorbidities of systemic inflammatory polyarthritis and possible seronegative disease were addressed after rheumatology consultation with a variety of medications that provided the patient additional relief of his symptoms. The patient ultimately moved and was lost to further follow-up.