REDUCTION OF POSTINTRAVITREAL INJECTION PAIN USING ICE: An Open-Label Interventional Randomized Controlled Trial.

PURPOSE: Intravitreal injections of intraocular therapeutic agents are a common and effective treatment for various retinal pathologies. Patient discomfort related to injection is a potential barrier to treatment. Our aim in this study was to evaluate whether cooling the eye using topical ice compresses before intravitreal injection will reduce pain or bleeding. METHODS: This randomized controlled open-label study included 42 patients. All patients received a standard topical anesthesia protocol and then were randomly assigned to either receive a placement of ice packs (intervention group) or a room-temperature pack (control group) on the eyelid, 2 minutes before the intravitreal injection. Patients' discomfort, itching, burning and pain (using visual analog scale), and bleeding size (using photographs) were measured 1 and 10 minutes after the injection. Tolerability was calculated by averaging patients' discomfort, itching, burning, and pain scores. RESULTS: At 1 minute, pain (1.95 vs. 4.27, P = 0.01) and overall tolerability (1.66 vs. 2.98, P = 0.03) were significantly lower in patients receiving ice packs. At 10 minutes, pain (1.6 vs. 3.73, P = 0.02), burning (0.9 vs. 3.09, P = 0.007), discomfort (2.1 vs. 4.27, P = 0.008), and overall tolerability (1.23 vs. 2.87, P = 0.004) were all significantly lower in the ice group compared with the controls. Bleeding size (area or circumference) was not statistical different between groups. CONCLUSION: Topical ice patch administered before intravitreal injection significantly decreased pain and overall tolerability. This simple and inexpensive method may be used to ameliorated pain and improve tolerability.

Frequency, comprehension and attitudes of physicians towards abbreviations in the medical record.

AIMS: Abbreviations are common in the medical record. Their inappropriate use may ultimately lead to patient harm, yet little is known regarding the extent of their use and their comprehension. Our aim was to assess the extent of their use, their comprehension and physicians' attitudes towards them, using ophthalmology consults in a tertiary hospital as a model. METHODS: We first mapped the frequency with which English abbreviations were used in the departments' computerised databases. We then used the most frequently used abbreviations as part of a cross-sectional survey designed to assess the attitudes of non-ophthalmologist physicians towards the abbreviations and their comprehension of them. Finally, we tested whether an online lecture would improve comprehension. RESULTS: 4375 records were screened, and 235 physicians responded to the survey. Only 42.5% knew at least 10% of the abbreviations, and no one knew them all. Ninety-two per cent of respondents admitted to searching online for the meanings of abbreviations, and 59.1% believe abbreviations should be prohibited in medical records. A short online lecture improved the number of respondents answering correctly at least 50% of the time from 1.2% to 42% (P<0.001). CONCLUSIONS: Abbreviations are common in medical records and are frequently misinterpreted. Online teaching is a valuable tool for physician education. The majority of respondents believed that misinterpreting abbreviations could negatively impact patient care, and that the use of abbreviations should be prohibited in medical records. Due to low rates of comprehension and negative attitudes towards abbreviations in medical communications, we believe their use should be discouraged.

Tyrosine residues at the carboxyl terminus of Vav1 play an important role in regulation of its biological activity.

The guanine nucleotide exchange factor (GEF) Vav1 is an essential signal transducer protein in the hematopoietic system, where it is expressed physiologically. It is also involved in several human malignancies. Tyrosine phosphorylation at the Vav1 amino terminus plays a central role in regulating its activity; however, the role of carboxyl terminal tyrosine residues is unknown. We found that mutation of either Tyr-826 (Y826F) or Tyr-841 (Y841F) to phenylalanine led to loss of Vav1 GEF activity. When these Vav1 mutants were ectopically expressed in pancreatic cancer cells lacking Vav1, they failed to induce growth in agar, indicating loss of transforming potential. Furthermore, although Y841F had no effect on Vav1-stimulated nuclear factor of activated T cells (NFAT) activity, Y826F doubled NFAT activity when compared with Vav1, suggesting that Tyr-826 mediates an autoinhibitory effect on NFAT activity. SH2 profiling revealed that Shc, Csk, Abl, and Sap associate with Tyr-826, whereas SH2-B, Src, Brk, GTPase-activating protein, and phospholipase C-gamma associate with Tyr-841. Although the mutations in the Tyr-826 and Tyr-841 did not affect the binding of the carboxyl SH3 of Vav1 to other proteins, binding to several of the proteins identified by the SH2 profiling was lost. Of interest is Csk, which associates with wild-type Vav1 and Y841F, yet it fails to associate with Y826F, suggesting that loss of binding between Y826F and Csk might relieve an autoinhibitory effect, leading to increased NFAT. Our data indicate that GEF activity is critical for the function of Vav1 as a transforming protein but not for NFAT stimulation. The association of Vav1 with other proteins, detected by SH2 profiling, might affect other Vav1-dependent activities, such as NFAT stimulation.

The association of Sam68 with Vav1 contributes to tumorigenesis.

Vav1 functions in the hematopoietic system as a specific GDP/GTP nucleotide exchange factor regulated by tyrosine phosphorylation. An intact C-terminal SH3 domain of Vav1 (Vav1SH3C) was shown to be necessary for Vav1-induced transformation, yet the associating protein(s) necessary for this activity have not yet been identified. Using a proteomics approach, we identified Sam68 as a Vav1SH3C-associating protein. Sam68 (Src-associated in mitosis of 68 kD) belongs to the heteronuclear ribonucleoprotein particle K (hnRNP-K) homology (KH) domain family of RNA-binding proteins. The Vav1/Sam68 interaction was observed in vitro and in vivo. Mutants of Vav1SH3C previously shown to lose their transforming potential did not associate with Sam68. Co-expression of Vav1 and Sam68 in Jurkat T cells led to increased localization of Vav1 in the nucleus and changes in cell morphology. We then tested the contribution of Sam68 to known functions of Vav1, such as focus-forming in NIH3T3 fibroblasts and NFAT stimulation in T cells. Co-expression of oncogenic Vav1 with Sam68 in NIH3T3 fibroblasts resulted in a dose-dependent increase in foci, yet no further enhancement of NFAT activity was observed in Jurkat T cells, as compared to cells overexpressing only Vav1 or Sam68. Our results strongly suggest that Sam68 contributes to transformation by oncogenic Vav1.