Importance
Intravitreal injections (IVI) are often painful.
Background
To evaluate the analgesic effect of diclofenac in patients undergoing IVI.
Design
Single‐centre, prospective, randomized, ...triple‐arm, placebo‐controlled, interventional study in the University Hospital of Patras.
Participants
Seventy‐four patients.
Methods
Group 1 (n = 25) received topical diclofenac 45 min before IVI, Group 2 (n = 25) received oral diclofenac 4 h before IVI and topical diclofenac while Group 3 (n = 24) received placebo before IVI. Using the short form of the McGill Pain Questionnaire (SF‐MPQ), pain intensity was assessed with the visual analogue scale (VAS), the main component of the SF‐MPQ and the Present Pain Intensity (PPI) scores immediately and 6 h post‐IVI.
Main Outcome Measures
The VAS pain score immediately post‐IVI.
Results
Immediately post‐IVI, patients in Group 2 reported significantly lower VAS pain scores compared to placebo while no statistically significant difference was found between patients that received topical diclofenac and placebo. Six hours post‐IVI, patients in both treatment groups reported significant lower VAS pain scores compared to placebo. The scores of the main component of the SF‐MPQ were significantly lower in patients of treatment groups compared to placebo at both time‐points. Finally, while no statistically significant difference was found between the 3 Groups in PPI scores immediately post‐IVI, 6 h later, patients of both treatment groups reported significantly lower PPI scores compared to placebo.
Conclusions and Relevance
The combination of topical and oral diclofenac demonstrated better analgesic effect than topical diclofenac administration in patients undergoing IVI immediately and up to 6 h post‐IVI.
Immutep Limited - listed on the Australian Stock Exchange (IMM) and Nasdaq (IMMP) - is capturing the attention of the international biotech market with its concentration on the LAG-3 (Lymphocyte ...Activation Gene-3) immune checkpoint and combination therapies; expansive intellectual property; and global partnerships. The company's clinical trials in Europe and Australia are among the most advanced for a prospective immunotherapy drug related to LAG-3.
Immutep Limited - listed on the Australian Stock Exchange (IMM) and Nasdaq (IMMP) - is capturing the attention of the international biotech market with its concentration on the LAG-3 (Lymphocyte ...Activation Gene-3) immune checkpoint and combination therapies; expansive intellectual property; and global partnerships. The company's clinical trials in Europe and Australia are among the most advanced for a prospective immunotherapy drug related to LAG-3.
To compare the efficacy of diclofenac versus bevacizumab following single intravitreal injection in eyes with persistent diabetic macular edema.
Fifty eyes with persistent DME were randomly allocated ...to intravitreal injection of 500 µg/0.1 ml of diclofenac (N = 20) or 1.25 mg/0.05 mL of bevacizumab (N = 20) or to non-treatment (10 eyes). Preoperative and postoperative visual acuity, central, paracentral macular thickness and intraocular pressure (IOP) were recorded and compared between the three groups up to 4 weeks.
Diclofenac and bevacizumab groups showed statistically significant reduction in central and paracentral macular thickness (diclofenac: p = 0.006, 0.02 and bevacizumab: p = 0.02, 0.01), without statistically significant difference between the two groups. The two groups showed no statistically significant difference in mean visual acuity or mean line improvement. Mean visual acuity improvement didn't reach statistical significance in either group. Diclofenac group showed statistically significant reduced IOP (P = 0.02). Control eyes did not show any change in mean visual acuity, macular thickness or IOP.
In persistent DME, diclofenac has a structural effect comparable to bevacizumab on central macular thickness. However, significant functional gain may not be accomplished by single injection. Unlike naïve DME, persistent cases may be confounded by systemic and local factors necessitating repeated injection of diclofenac.
Background
Transnasal esophagogastroduodenoscopy (TN-EGDS) is well tolerated by patients and the examination is perceived comfortable without the need of a sedative drug. Conversely, mainly in ...Western literature, some authors report limitations in illumination, image quality, and working channel as affecting TN-EGDS diffusion. To overcome these disadvantages, a new transnasal endoscope (TNE) was tested but, due to its larger diameter, we have no evidence of its clinical safety and tolerability. A new adapted nasal anesthesia could be useful to improve TNE tolerance. In an independent, not sponsored, pilot prospective study we enrolled, in a busy clinical hospital setting, 30 adult patients receiving nasal atomized Lidocaine and Xylometazoline (XAL) to undergo a diagnostic TN-EGDS with TNE to evaluate its tolerance, safety, and feasibility.
Methods
Three physicians enrolled inpatients and outpatients with indication to diagnostic EGDS during a 6-month period. Main outcome measures were cardio-pulmonary monitoring data and patients’ answers to an adapted questionnaire investigating pain, anxiety level, willingness to repeat the examination, operators’ scores about endoscopy quality, examination conduction and anesthesia-related complications.
Results
The examination was completed by the transnasal route in 100 % of the enrolled patients, endoscopy satisfaction and feasibility were scored to nearly the highest levels by the three different physicians. A total of 29/30 patients (96.6 %) declared the willingness to repeat the same examination if needed. The mean patients’ score for overall pain was 3.7 ± 1 SD (range 1–10 by Visual Analog Scale). Mean endoscopy duration was 11.1 ± 2.6 min (range 5.0–19.0). In a total of 17/30 TN-EGDS that lasted more than 11 min, higher heart frequency variations and worse tolerance scores were found (
p
< 0.05).
Conclusion
Our pilot study demonstrates that TN-EGDS with TNE and NA is safe, well tolerated, and feasible. The best clinical tolerance is reached when TN-EGDS lasts <11 min.
A bibliometric analysis provided by Hernandez-Vasquez et al. listed the institutions that have published most extensively in the field of biosimilars. Sandoz and Novartis International were ...considered as separate entities, but are both are divisions of the same parent company. When considered as a single entity for purposes of tracking publications, Sandoz-Novartis is among the leaders in the number of articles published about biosimilars.
Summary
Background and Aim
Hepatocellular carcinoma (HCC) recurrence after orthotopic liver transplantation (OLT) continues to confound transplant surgeons and physicians. There are no effective ...methods to predict the patients at risk for recurrence so far although many studies have sought meaningful biomarkers. The ImmuKnow (IMK) assay is an immune cell function assay that detects cell‐mediated immunity in an immunosuppressed population, mainly measuring peripheral blood CD4+ adenosine triphosphate (ATP) release. The aim of this study was to assess the relationship between cellular immune function measured by the ImmuKnow assay and HCC recurrence post‐OLT.
Methods
A total of 76 HCC cases underwent Donation after Cardiac Death (DCD) liver transplant, which confirmed hepatocellular carcinoma by histology postoperatively. The ImmuKnow assay was prospectively performed in these cases at a range of 6–36 months post‐OLT. Every test was repeated 1 week later, obtaining the average value for every patient. In addition, every case had liver imaging findings at approximately the exam time.
Results
Fifteen cases with liver imaging findings showed HCC recurrence (19.7%) post‐OLT, and the average ImmuKnow assay in these patients was 190 ± 48 ng/ml, which was less (p < 0.05) than in patients without HCC recurrence, whose average ATP level was 313 ± 90 ng/ml. ATP levels post‐OLT were found to be significantly associated with the risk of tumour recurrence. The ratio of T reg cells and the levels of TGFβ and IL‐10 were higher in recurrence patients than in recurrence‐free patients.
Conclusion
Greater suppression of cellular immunity, as measured by the ImmuKnow assay, was associated with progression of HCC recurrence post‐OLT. ImmuKnow assay was helpful in determining the risk of early recurrence of HCC postliver transplant. A pathway consisting of T reg cells, TGFβ and IL‐10 might be the HCC recurrence‐predominant pathway.
Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) are disorders of the airways largely related to the presence of persistent inflammation. The approval of ...inhaled corticosteroids in the early 1970s pioneered a new age of therapy in treating chronic inflammatory airway diseases. This was the first time that an anti-inflammatory product was available to reduce the characteristic lung inflammation in airways and the associated obstruction, inflammation and hyper-responsiveness. Fast forward 40 years: corticosteroids are still an important therapeutic intervention; however, they exhibit limited use in moderate to severe asthma and COPD. Oligonucleotide therapies are an emerging class which include the antisense, the RNAi (siRNA and miRNA), the immunomodulatory, the aptamer and the decoy approaches. As these approaches are rather recent in the respiratory field, most are still early in development. Nevertheless, with limitations of current small molecule therapies and the hurdles faced with biologics, the use of oligonucleotides is relevant and the door is open to the development of this category of therapeutics. This review focuses on the major classes of oligonucleotides that are currently in late stage preclinical or clinical development for the treatment of asthma and COPD, and discusses the implications for their use as therapies for respiratory diseases.
Osteonecrosis (ON) of the femoral head in childhood can lead to loss of femoral head architecture and subsequent deformity. When femoral head ON was surgically induced in 24 rats, zoledronic acid ...treatment and prophylaxis improved sphericity and maintenance of architecture at 6 weeks. This preliminary experiment supports the use of bisphosphonates in childhood ON.
Introduction: We hypothesized that the bisphosphonate zoledronic acid could preserve femoral head structure while allowing bone repair.
Materials and Methods: Osteonecrosis (ON) was surgically induced in the right femoral head of 24 female Wistar rats. The rats were randomized into three treatment groups and dosed subcutaneously with saline, zoledronic acid (0.1 mg/kg) at 1 and 4 weeks postoperation (ZA post), or zoledronic acid (0.1 mg/kg) given 2 weeks preoperation and at 1 and 4 weeks postoperation (ZA pre‐post). After death at 6 weeks postoperation, undecalcified specimens were analyzed by DXA and standardized histomorphometric analysis.
Results: Seventy‐one percent of saline‐operated femoral heads were aspherical (Mose score > 1), whereas only 13% and 0% of operated heads in the ZA‐treated groups were aspherical (p < 0.05). DXA‐measured bone mineral density in saline‐treated femoral heads was reduced by 34% and 43% compared with the ZA‐treated groups (p < 0.01). Histomorphometry showed decreases of 12% and 17% in bone volume (BV/TV) in saline groups compared with ZA post and ZA pre‐post (p < 0.05), and a decrease in trabecular number (Tb.N) of 18% and 14% (p < 0.05), respectively. Bone formation rate (BFR) was increased by 56% in saline‐treated operated heads over ZA post and was 4.8 times increased over the ZA pre‐post group (p < 0.05). The differences in BV/TV and Tb.N in treated groups must therefore be caused by a reduction in bone turnover. Observational histology confirmed the retention of necrotic architecture in treated groups.
Conclusions: Zoledronic acid treatment and prophylaxis preserved femoral head architecture after traumatic ON in this rat model at 6 weeks. These data indicate that, by conserving femoral head architecture, bone repair may occur in conjunction with improved femoral head shape.
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