Clinical Outcomes Following Implementation of a Formalized "Flashes and Floaters" Emergency Department Triage Protocol.

PURPOSE: To report outcomes of patients presenting to the emergency department (ED) with new-onset visual flashes and/or floaters following implementation of a formalized triage protocol allowing eligible patients to be discharged for prompt outpatient ophthalmic examination. DESIGN: Retrospective consecutive case series. METHODS: Patient characteristics, protocol eligibility, and clinical outcomes were recorded for adult patients triaged within a formal "flashes and floaters" protocol at a single academic ED. RESULTS: A total of 457 patients presented for 471 unique ED encounters with a chief complaint of visual flashes and/or floaters between October 2014 and May 2018. In all, 61% of patient encounters (287/471) met protocol criteria for prompt outpatient ophthalmic examination, of whom 94% (269/287) were examined within 48 hours. Final diagnoses of protocol-eligible patients were posterior vitreous detachment only (73%, 197/269), retinal break(s) (10%, 26/269), migraine (5%, 14/269), and no cause or new cause found (10%, 27/269). No protocol-eligible patients had retinal detachment or diagnoses requiring emergent diagnostic or therapeutic care (0%, 95% CI = 0%-1.1%). Final diagnoses following 175 encounters not meeting criteria for deferred examination included posterior vitreous detachment only (25%, 43/175), retinal break(s) (19%, 33/175), macula-involving retinal detachment (13%, 22/175), macula-sparing retinal detachment (11%, 19/175), retinal arterial occlusion (2%, 3/175), and stroke (0.6%, 1/175). The Cohen kappa for agreement on protocol eligibility between the ED physician and ophthalmologist was 0.85. CONCLUSIONS: A formalized ED "flashes and floaters" triage protocol may help identify patients for whom prompt outpatient ophthalmic examination may be more safely considered.

Transactivation of Herpes Simplex Virus 1 (HSV-1) Infected Cell Protein 4 Enhancer by Glucocorticoid Receptor and Stress-Induced Transcription Factors Requires Overlapping Krüppel-Like Transcription Factor 4/Sp1 Binding Sites.

Following acute infection, herpes simplex virus 1 (HSV-1) lytic cycle viral gene expression is silenced; consequently, lifelong latency in neurons is established. Certain external stimuli that trigger reactivation from latency also activate the glucocorticoid receptor (GR). The synthetic corticosteroid dexamethasone, but not a GR-specific antagonist, increases the frequency of explant-induced reactivation from latency and stimulates productive infection. Furthermore, dexamethasone increases expression of cellular transcription factors in trigeminal ganglionic neurons: for example, SLUG and three Krüppel-like transcription factor (KLF) family members, KLF4, KLF15, and promyelocytic leukemia zinc finger protein (PLZF). Consequently, we hypothesized that stress-induced transcription factors stimulate expression of ICP4, a viral transcriptional regulator required for productive infection. New studies demonstrated that GR and KLF4, PLZF, or SLUG cooperatively transactivate the ICP4 enhancer upstream of a minimal promoter in monkey kidney cells (Vero) and mouse neuroblastoma cells (Neuro-2A). Strikingly, mutagenesis of two KLF4/Sp1 binding sites reduced GR- plus KLF4-, PLZF-, or SLUG-mediated transactivation to basal levels. A consensus enhancer (E)-Box adjacent to a KLF4/Sp1 binding site was also required for GR- and SLUG-, but not KLF family member-, mediated transactivation of the ICP4 promoter. Chromatin immunoprecipitation studies (ChIP) revealed GR and stress-induced transcription factors occupy ICP4 enhancer sequences. Conversely, specific binding was generally reduced in the KLF4/Sp1 mutant. Furthermore, GR and SLUG occupancy of ICP4 enhancer sequences was reduced in the E-Box mutant. Based on these studies, we suggest stressful stimuli can trigger productive infection because GR and specific stress-induced transcription factors activate ICP4 expression.IMPORTANCE Certain stressful stimuli activate the glucocorticoid receptor (GR) and increase the incidence of herpes simplex virus 1 (HSV-1) reactivation from latency. For example, a corticosteroid antagonist impairs productive infection and virus shedding following explant of trigeminal ganglia from latently infected mice. Infected cell protein 4 (ICP4) is the only immediate early viral transcriptional regulator required for productive infection, suggesting stressful stimuli stimulate ICP4 expression. New studies revealed GR and stress-induced transcription factors identified during reactivation from latency, SLUG and three Krüppel-like transcription factor family members (KLF4, KLF15, and promyelocytic leukemia zinc finger protein), cooperatively transactivate the ICP4 enhancer. Two KLF4 consensus binding sites were crucial for cooperative transactivation of the ICP4 enhancer. A consensus enhancer-box also mediated cooperative transactivation of the ICP4 enhancer by GR and SLUG. The ability of GR and stress-induced transcription factors to transactivate ICP4 enhancer activity is predicted to trigger productive infection following stressful stimuli.

A Portable, Inexpensive, Nonmydriatic Fundus Camera Based on the Raspberry Pi® Computer.

Purpose. Nonmydriatic fundus cameras allow retinal photography without pharmacologic dilation of the pupil. However, currently available nonmydriatic fundus cameras are bulky, not portable, and expensive. Taking advantage of recent advances in mobile technology, we sought to create a nonmydriatic fundus camera that was affordable and could be carried in a white coat pocket. Methods. We built a point-and-shoot prototype camera using a Raspberry Pi computer, an infrared-sensitive camera board, a dual infrared and white light light-emitting diode, a battery, a 5-inch touchscreen liquid crystal display, and a disposable 20-diopter condensing lens. Our prototype camera was based on indirect ophthalmoscopy with both infrared and white lights. Results. The prototype camera measured 133mm × 91mm × 45mm and weighed 386 grams. The total cost of the components, including the disposable lens, was $185.20. The camera was able to obtain good-quality fundus images without pharmacologic dilation of the pupils. Conclusion. A fully functional, inexpensive, handheld, nonmydriatic fundus camera can be easily assembled from a relatively small number of components. With modest improvements, such a camera could be useful for a variety of healthcare professionals, particularly those who work in settings where a traditional table-mounted nonmydriatic fundus camera would be inconvenient.

Health-related quality of life improves during one year of medical and surgical treatment in a European population-based inception cohort of patients with inflammatory bowel disease--an ECCO-EpiCom study.

BACKGROUND & AIMS: Health-related quality of life (HRQoL) is impaired in patients with Inflammatory Bowel Disease (IBD). The aim was prospectively to assess and validate the pattern of HRQoL in an unselected, population-based inception cohort of IBD patients from Eastern and Western Europe. METHODS: The EpiCom inception cohort consists of 1560 IBD patients from 31 European centres covering a background population of approximately 10.1 million. Patients answered the disease specific Short Inflammatory Bowel Disease Questionnaire (SIBDQ) and generic Short Form 12 (SF-12) questionnaire at diagnosis and after one year of follow-up. RESULTS: In total, 1079 patients were included in this study. Crohn's disease (CD) patients mean SIBDQ scores improved from 45.3 to 55.3 in Eastern Europe and from 44.9 to 53.6 in Western Europe. SIBDQ scores for ulcerative colitis (UC) patients improved from 44.9 to 57.4 and from 48.8 to 55.7, respectively. UC patients needing surgery or biologicals had lower SIBDQ scores before and after compared to the rest, while biological therapy improved SIBDQ scores in CD. CD and UC patients in both regions improved all SF-12 scores. Only Eastern European UC patients achieved SF-12 summary scores equal to or above the normal population. CONCLUSION: Medical and surgical treatment improved HRQoL during the first year of disease. The majority of IBD patients in both Eastern and Western Europe reported a positive perception of disease-specific but not generic HRQoL. Biological therapy improved HRQoL in CD patients, while UC patients in need of surgery or biological therapy experienced lower perceptions of HRQoL than the rest.

Health care and patients' education in a European inflammatory bowel disease inception cohort: an ECCO-EpiCom study.

BACKGROUND AND AIMS: The EpiCom study and inception cohort was initiated in 2010 in 31 centers from 14 Western and 8 Eastern European countries, covering a 10.1million person background population. Our aim was to investigate whether there is a difference between Eastern and Western Europe in health care and education of patients with inflammatory bowel disease (IBD). METHODS: A quality of care (QoC) questionnaire was developed in the EpiCom group consisting of 16 questions covering 5 items: time interval between the onset of symptoms and diagnosis, information, education, empathy and access to health care providers. RESULTS: Of 1,515 patients, 947 (217 east/730 west) answered the QoC questionnaire. Only 23% of all patients had knowledge about IBD before diagnosis. In Eastern Europe, significantly more patients searched out information about IBD themselves (77% vs. 68%, p<0.05), the main source was the Internet (92% vs. 88% p=0.23). In Western Europe, significantly more patients were educated by nurses (19% vs. 1%, p<0.05), while in Eastern Europe, gastroenterologists were easier to contact (80% vs. 68%, p<0.05). CONCLUSION: Health care differed significantly between Eastern and Western Europe in all items, but satisfaction rates were high in both geographic regions. Because of the low awareness and the rising incidence of IBD, general information should be the focus of patient organizations and medical societies. In Western Europe IBD nurses play a very important role in reducing the burden of patient management.

East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort.

OBJECTIVE: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East-West gradient in the incidence of IBD in Europe exists. DESIGN: A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience. RESULTS: 1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohn's disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100,000 in 2010 for CD were 6.5 (range 0-10.7) in Western European centres and 3.1 (range 0.4-11.5) in Eastern European centres, for UC 10.8 (range 2.9-31.5) and 4.1 (range 2.4-10.3), respectively, and for IBDU 1.9 (range 0-39.4) and 0 (range 0-1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy. CONCLUSIONS: An East-West gradient in IBD incidence exists in Europe. Among this inception cohort--including indolent and aggressive cases--international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.

Environmental factors in a population-based inception cohort of inflammatory bowel disease patients in Europe--an ECCO-EpiCom study.

BACKGROUND AND AIMS: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe possibly due to changes in environmental factors towards a more "westernised" standard of living. The aim of this study was to investigate differences in exposure to environmental factors prior to diagnosis in Eastern and Western European IBD patients. METHODS: The EpiCom cohort is a population-based, prospective inception cohort of 1560 unselected IBD patients from 31 European countries covering a background population of 10.1 million. At the time of diagnosis patients were asked to complete an 87-item questionnaire concerning environmental factors. RESULTS: A total of 1182 patients (76%) answered the questionnaire, 444 (38%) had Crohn's disease (CD), 627 (53%) ulcerative colitis (UC), and 111 (9%) IBD unclassified. No geographic differences regarding smoking status, caffeine intake, use of oral contraceptives, or number of first-degree relatives with IBD were found. Sugar intake was higher in CD and UC patients from Eastern Europe than in Western Europe while fibre intake was lower (p<0.01). Daily consumption of fast food as well as appendectomy before the age of 20 was more frequent in Eastern European than in Western European UC patients (p<0.01). Eastern European CD and UC patients had received more vaccinations and experienced fewer childhood infections than Western European patients (p<0.01). CONCLUSIONS: In this European population-based inception cohort of unselected IBD patients, Eastern and Western European patients differed in environmental factors prior to diagnosis. Eastern European patients exhibited higher occurrences of suspected risk factors for IBD included in the Western lifestyle.

Early treatment response of fluocinolone (retisert) implantation in patients with uveitic macular edema: an optical coherence tomography study.

PURPOSE: To analyze the early spectral domain optical coherence tomography changes after fluocinolone implantation in eyes with baseline uveitic macular edema. METHODS: Patients with uveitic macular edema and who received fluocinolone implantations by 2 surgeons (R.P.S. and J.E.S.) at the Cole Eye Institute (Cleveland Clinic, Cleveland, OH) from September 2009 to July 2010 were eligible for this study. Best-corrected visual acuity, intraocular pressure, central subfield thickness, cube volume, cube average thickness, and cystoid macular edema grade were recorded before implantation and in the early postoperative period (median: 3 months postimplantation). Changes in these variables were analyzed using the Wilcoxon signed-rank test for paired comparisons of clustered data. P values were 2 sided, and alpha was set at 0.05. RESULTS: Twelve eyes of seven patients were included in the study. The median best-corrected visual acuity improved in the early postoperative period after implantation (20/80 before implantation and 20/50 after implantation), but this improvement was not found to be significant (P = 0.12). However, the spectral domain optical coherence tomography measurements-central subfield thickness, cube volume, cube average thickness, and cystoid macular edema grade-were all significantly reduced (median changes: -234 µm [P = 0.02], -1 mm [P = 0.04], -39 µm [P = 0.04], and -3 [P = 0.03], respectively). CONCLUSION: Fluocinolone implantation is associated with a significant reduction in macular edema as measured by spectral domain optical coherence tomography in the early postoperative period, a result that is consistent with the proposed mechanism of the drug.

Activation of guanylate cyclase in the guinea-pig trachea reduces contractile responses of the smooth muscle.

Guinea-pig tracheal strips were used to investigate whether activation of guanylate cyclase in the trachea can reduce the contractile responses of the smooth muscle. Guanylate cyclase was activated by glyceryl trinitrate and a combination of sodium nitrite and ascorbic acid. These activators inhibited tracheal smooth muscle contractions produced by acetylcholine, histamine and electrical field stimulation. However, in the presence of methylene blue, a guanylate cyclase inhibitor, tracheal smooth muscle contractions were not inhibited by the activators. But, in the presence of propranolol, which blocked inhibition mediated by beta-adrenoceptor, both glyceryl trinitrate and the sodium nitrite/ascorbic acid combination were still capable of inhibiting tracheal smooth muscle contractions. Additionally, methylene blue inhibited tracheal smooth muscle relaxation that was electrically induced. These results suggest that the inhibitory action mediated by activated guanylate cyclase may be a mechanism for regulating tracheal smooth muscle contractile responses.

Activation of guanylate cyclase in the guinea-pig trachea reduces contractile responses of the smooth muscle

Guinea-pig tracheal strips were used to investigate whether activation of guanylate cyclase in the trachea can reduce the contractile response of the smooth muscle. Guanylate cyclase was activated by glyceryl trinitrate and a combination of sodium nitrite and ascorbic acid. These activators inhibited tracheal smooth muscle contractions produced by acetylcholine histamine and electrical field stimulation. However, in the presence of methylene blue, a guanylate cyclase inhibitor, tracheal smooth muscle contractions were not inhibited by the activators. But, in the presence of propranolol, which blocked inhibition mediated by beta-adrenoceptor, both glyceryl trinitrate and the sodium nitrite/ascorbic acid combination were still capable of inhibiting tracheal smooth muscle contractions. Additionally, methylene blue inhibited tracheal smooth muscle relaxation that was electrically induced. These results suggest that the inhibitory action mediated by activated guanylate cyclase may be a mechanism for regulating tracheal smooth muscle contractile reponses