Adaptation of the 2015 American College of Rheumatology treatment guideline for rheumatoid arthritis for the Eastern Mediterranean Region: an exemplar of the GRADE Adolopment

BACKGROUND: It has been hypothesized that adaptation of health practice guidelines to the local setting is expected to improve their uptake and implementation while cutting on required resources. We recently adapted the published American College of Rheumatology (ACR) Rheumatoid Arthritis (RA) treatment guideline to the Eastern Mediterranean Region (EMR). The objective of this paper is to describe the process used for the adaptation of the 2015 ACR guideline on the treatment of RA for the EMR. METHODS: We used the GRADE-Adolopment methodology for the guideline adaptation process. We describe in detail how adolopment enhanced the efficiency of the following steps of the guideline adaptation process: (1) groups and roles, (2) selecting guideline topics, (3) identifying and training guideline panelists, (4) prioritizing questions and outcomes, (5) identifying, updating or conducting systematic reviews, (6) preparing GRADE evidence tables and EtD frameworks, (7) formulating and grading strength of recommendations, (8) using the GRADEpro-GDT software. RESULTS: The adolopment process took 6 months from January to June 2016 with a project coordinator dedicating 40% of her time, and the two co-chairs dedicating 5% and 10% of their times respectively. In addition, a research assistant worked 60% of her time over the last 3 months of the project. We held our face-to-face panel meeting in Qatar. Our literature update included five newly published trials. The certainty of the evidence of three of the eight recommendations changed: one from moderate to very low and two from low to very low. The factors that justified a very low certainty of the evidence in the three recommendations were: serious risk of bias and very serious imprecision. The strength of five of the recommendations changed from strong to conditional. The factors that justified the conditional strength of these 5 recommendations were: cost (n = 5 [100%]), impact on health equities (n = 4 [80%]), the balance of benefits and harms (n = 1 [20%]) and acceptability (n = 1 [20%]). CONCLUSION: This project confirmed the feasibility of GRADE-Adolopment. It also highlighted the value of collaboration with the organization that had originally developed the treatment guideline. We discuss the implications for both guideline adaptation and future research to advance the field.(AU)

Timing of dexamethasone treatment in experimental Staphylococcus aureus endophthalmitis.

PURPOSE: This study sought to determine whether intravitreal dexamethasone with vancomycin preserves retinal function in eyes with experimental Staphylococcus aureus endophthalmitis better than intravitreal vancomycin alone. METHODS: Twenty-four rabbits received intravitreal injections in both eyes with S. aureus. Right eyes were treated with intravitreal dexamethasone plus vancomycin and left eyes were treated with vancomycin alone at 24, 36, 48, or 72 hours after inoculation. Evaluation was performed by slit-lamp biomicroscopy, indirect ophthalmoscopy, and electroretinogram. Vitreous humor cultures and histopathologic examinations were performed on the eyes after the rabbits were killed. RESULTS: The combination of intravitreal dexamethasone and vancomycin resulted in significantly less inflammation than vancomycin alone at 24 and 36 hours after inoculation, but electroretinograms showed significantly better preservation only at 36 hours after bacterial inoculation. Viable bacteria were cultured from eyes treated 48 and 72 hours after inoculation. CONCLUSION: Intravitreal dexamethasone was found to be beneficial by electroretinography when administered 36 hours after infection. In the authors' model, a single intravitreal injection of vancomycin with or without the addition of dexamethasone was insufficient to sterilize eyes 48 and 72 hours after bacterial inoculation.

Follow-up of HIV western blot indeterminate results.

Indeterminate results obtained with the Western blot (WB) confirmatory test on HIV enzyme immunoassay (EIA)-positive samples, constituted 15.6% (444/2849) over a 2.5-year period at the referral laboratory for the Western region at the King Fahd General Hospital, Jeddah. Two hundred and fourteen WB-indeterminate samples were followed up by repeat WB testing of subsequent samples from the same patients over a 3-12 month period. One hundred and forty-two samples (66.4%) gave negative results. Sixty-five samples (30%) remained indeterminate. Only seven samples (3.3%) not initially meeting WHO criteria for positivity turned clear-cut positive, with high EIA readings on follow-up. It was discovered initally that a significant proportion of indeterminates was due to low-grade cross-contamination between samples as a result of aerosol backflow during aspiration in the washing procedure. This was eliminated by rinsing the lines between samples, separating samples with high EIA from those with low EIA, and rerunning indeterminate samples. A reduction of indeterminates from 21% to 8.5% subsequently followed. After this improvement, most of the samples that remained indeterminate had low EIA readings, and few bands of mainly anti-gag (p55, p24 or p18) or anti-pol (p51) antibodies, while the few turning positive all had anti-gp160, in addition to anti-p24 or p55. Interestingly, over the last year and a half of the study, 1.4% of the total samples (21/1506) had repeatedly high EIA readings but were negative by WB. In addition, 16 samples (1.1%) were positive for HIV-2. A separate computer-based system for the storage of data was very helpful in ascertaining proper follow-up of indeterminate WB results.

Strain-related differences in the ability of T lymphocytes to recognize proteins encoded by the golli-myelin basic protein gene.

Protein products of the golli-MBP gene complex, expressed in the nervous and lymphoid systems, contain sequences in common with sequences in 'classic' MBP, expressed exclusively in the nervous system. In this report, it was determined whether T cell lines (TCLs) specific for encephalitogenic epitopes of 'classic' MBP were able to recognize sequences within golli-MBP. TCLs derived from SJL mice specific for the immunodominant 83-102 sequence and the subdominant 19-27 sequence of 'classic' MBP recognized golli-MBP J37 and BG21, respectively. In contrast, TCLs derived from PL and B10.PL mice specific for the immunodominant 1-9 sequence of 'classic' MBP did not recognize this sequence within either J37 or BG21. These strain-related differences in the ability of golli-MBP proteins to stimulate 'classic' MBP-specific TCLs are discussed with respect to a possible influence on whether the course of EAE is relapsing (SJL) or monophasic (PL and B10.PL).

The effect of Staphylococcus aureus phage lysate vaccine on a rabbit model of staphylococcal blepharitis, phlyctenulosis, and catarrhal infiltrates.

PURPOSE: To evaluate the effect of Staphylococcus aureus phage lysate (SPL) vaccination on the development of blepharitis, corneal phlyctenules, and catarrhal infiltrates and on the development of antibodies and the delayed-type hypersensitivity response to S. aureus. METHODS: Eighty rabbits received an intradermal immunization of cell wall-complete Freund's adjuvant followed by a booster immunization. Rabbits were given topical applications of viable S. aureus in both eyes and 40 rabbits received subcutaneous SPL vaccinations. Clinical observations were made weekly. An enzyme-linked immunosorbent assay was used to measure IgG, IgA, and IgM antibody levels to ribitol teichoic acid in sera, corneas, and tears. The delayed-type hypersensitivity response was evaluated by skin testing after subcutaneous injection of staphylococcal antigens. RESULTS: In the SPL-vaccinated group, phlyctenules developed in eight of 40 rabbits while blepharitis developed in 13 of 40. In the nonvaccinated group, phlyctenules developed in three of 40 rabbits and blepharitis developed in five of 40. The number of rabbits with blepharitis was significantly higher in the SPL-vaccinated group than in the nonvaccinated group. In general, the antibody response to ribitol teichoic acid was enhanced, while the delayed-type hypersensitivity response to S. aureus was depressed. CONCLUSIONS: Vaccination with SPL was not found to have a beneficial effect on the development of blepharitis, phlyctenules, and catarrhal infiltrates in our rabbit model.

Gender differences in autoimmune demyelination in the mouse: implications for multiple sclerosis.

Gender-related differences in experimental allergic encephalomyelitis (EAE) were examined in the SJL mouse with the purpose of characterizing an animal model ideal for the study of gender-related differences in multiple sclerosis (MS). For the model to allow for study of the induction and the effector phase of disease, the adoptive EAE model was characterized. First, the SJL strain was shown to be nonresponsive with regard to the development of antisyngeneic HY-specific responses in females, thereby permitting intergender adoptive transfers of T lymphocytes during EAE induction. Then, when myelin basic protein (MBP)-specific T cells derived from females were adoptively transferred into female and male recipients, female recipients demonstrated a more rapid onset of disease (p = 0.01), greater maximal acute-phase clinical scores (p < 0.0001) and greater mean clinical scores (p < 0.0001) compared with male recipients. When MBP-specific T cells derived from males were adoptively transferred, female recipients again tended to be more severely affected. Histopathologic analysis revealed quantitative differences between genders that paralleled clinical expression. These results document a clear gender-related difference in adoptive EAE in the SJL, with clinical and histopathologic disease greater in females compared with males. This model will be a useful tool for addressing autoimmune mechanisms underlying gender-related differences in MS.

Immunopathologic features of Staphylococcus aureus endophthalmitis in the rat.

PURPOSE: To study the clinical, histopathologic, and immunologic responses to Staphylococcus aureus endophthalmitis in rats. METHODS: Experimental Lewis rats received an intravitreal injection of viable S. aureus (65 organisms), and control rats received sterile saline. The clinical scores, cellular infiltrate, delayed hypersensitivity reaction in skin tests, and serum and vitreous enzyme-linked immunosorbent assay titers of immunoglobulin (Ig) M, IgG, and IgA to ribitol teichoic acid (RTA), the major antigenic determinant of S. aureus cell wall, were measured and compared on days 3, 7, 10, 14, 21, and 30. The differences were statistically assessed using Mann-Whitney nonparametric t-tests and analysis of variance. RESULTS: The red reflex was abolished in the majority of rats between days 3 and 21. Ocular inflammation resolved by day 30. The vitreous of eyes injected with S. aureus showed bacterial growth on days 3 and 7, followed by a decrease in numbers on days 10 and 14 and disappearance on days 21 and 30. In the vitreous, a peak neutrophil count was observed at day 3 that rapidly declined by day 7. The number of lymphocytes and plasma cells peaked on day 3 but declined more slowly. Plasma cells and Mott cells were seen on days 10 and 14, suggesting intraocular antibody production. IgM titers to RTA increased progressively in serum and vitreous, reached a peak on day 21, and declined on day 30. A weak IgG but absent IgA response to RTA was observed in serum and vitreous. S. aureus endophthalmitis was not associated with delayed hypersensitivity to the bacteria in skin tests. CONCLUSIONS: S. aureus endophthalmitis is associated with the infiltration of neutrophils, lymphocytes, monocytes, and plasma cells in vitreous. Neutrophils, the predominant infiltrating cells, may be involved in bactericidal activity and opsonophagocytosis. In rat staphylococcal endophthalmitis, IgM rather than IgG may be the protective antibody.

[Esophageal carcinosarcoma: morphologic and cytometric study]. / Carcinosarcoma esofágico: estudio morfológico y citométrico.

Carcinosarcoma of the esophagus is a rare malignant neoplasm composed by both carcinomatous (epithelial) and sarcomatous (mesodermal) elements. We report a case, diagnosed by biopsy an endoscopic brushing. Cytometric analysis was also performed.

Complement system and host defense against staphylococcal endophthalmitis.

PURPOSE: The authors studied the role of the complement system in host defense against Staphylococcus epidermidis and S. aureus endophthalmitis. METHODS: Guinea pigs in the S. epidermidis model received an intravitreal injection of 7000 viable organisms, and guinea pigs in the S. aureus model received 50 viable organisms. The experimental animals in each model were decomplemented with intraperitoneal (IP) injections of cobra venom factor, whereas the control animals received IP injections of normal saline. Mean log bacterial counts in the vitreous and mean serum complement titers were compared in the experimental and control animals in each model on days 1, 2, 3, and 7. RESULTS: In the S. epidermidis model, mean log bacterial counts in the vitreous were significantly higher in the experimental group than the control group on days 1 and 2 (P < 0.01) and on day 3 (P < 0.05). Mean serum complement titers were significantly lower in the experimental group at all days (P < 0.01). In the S. aureus model, mean log bacterial counts in the vitreous were significantly higher in the experimental group than the control group on day 2 (P < 0.05) and day 3 (P < 0.01). Mean serum complement titers were significantly lower in the experimental group on days 1, 2, and 3 (P < 0.01), but not on day 7. CONCLUSION: These results suggest that decomplemented guinea pigs show impaired host defense to S. epidermidis and S. aureus endophthalmitis and that this defense is restored as complement levels approach normal.

Collagen shields impregnated with gentamicin-dexamethasone as a potential drug delivery device.

We investigated the ability of collagen shields impregnated with gentamicin sulfate and dexamethasone to deliver medication into rabbit eyes. We compared the aqueous humor gentamicin and dexamethasone levels delivered by collagen shield and subconjunctival injection therapy at five time points over a ten-hour period, by using a fluorescence polarization immunoassay and high-pressure liquid chromatography. Our in vitro studies showed that impregnated collagen shields released most of the gentamicin within the first 30 minutes of elution, whereas dexamethasone was released gradually over a ten-hour period. The collagen shields impregnated with gentamicin and dexamethasone produced aqueous gentamicin levels that were significantly lower (P = .014) than those produced by subconjunctival injection therapy at 30 minutes and that were comparable to subconjunctival injection therapy at the other time points. Minimum inhibitory concentrations of gentamicin (approximately 4 micrograms) were observed in aqueous humor within 30 minutes in rabbits that received subconjunctival injections and at one hour in rabbits treated with impregnated collagen shields. The impregnated collagen shields produced aqueous dexamethasone levels that were significantly lower (P = .004) than those produced by subconjunctival injection therapy at one hour, significantly higher (P = .028) than subconjunctival injection therapy at six hours, and comparable to subconjunctival injection therapy at the other time points. Collagen shield delivery of gentamicin-dexamethasone may be comparable to subconjunctival injections and provide an alternative therapy after intraocular surgery.

Immune response to Staphylococcus epidermidis-induced endophthalmitis in a rabbit model.

Although Staphylococcus epidermidis is the most common cause of postoperative pseudophakic endophthalmitis, little is known about the immune response to S. epidermidis-induced endophthalmitis. Using a rabbit model, the immune response to an intravitreal injection of 7000 S. epidermidis (group 1) or 30,000 S. epidermidis (group 2) organisms was investigated. Clinical evaluations showed that rabbits in group 2 had a more severe inflammatory reaction in the conjunctiva, cornea, iris, and vitreous than those in group 1. The inflammatory reaction in group 1 largely resolved by day 30; group 2 continued to show a severe inflammatory response. Histopathologic findings correlated with clinical findings, with rabbits in group 2 showing a more severe inflammatory reaction in both the anterior and posterior segments of the globe. Positive vitreous cultures for S. epidermidis were present in rabbits in group 1 on days 3, 7, 10, 14, and 21 but not thereafter. However, group 2 had higher vitreous colony counts at days 3, 7, and 14 and negative vitreous cultures thereafter. Neither group showed delayed hypersensitivity to S. epidermidis antigens (evaluated by skin tests). Serum immunoglobulin (Ig) G antibody levels to phenol-inactivated S. epidermidis and glycerol teichoic acid (GTA) increased progressively, reached a peak at days 10-14, and then declined in both groups. Serum IgA antibody levels to these antigens were not detected. Group 2 had a more prolonged IgG antibody response in vitreous and aqueous than group 1. Tear fluid showed the weakest IgG and IgA antibody response to S. epidermidis and GTA. S. epidermidis-induced endophthalmitis was associated with a humoral but not a delayed hypersensitivity response to this organism.

Antibody studies in a rabbit model of corneal phlyctenulosis and catarrhal infiltrates related to Staphylococcus aureus.

Hypersensitivity to ribitol teichoic acid (RTA), the major antigenic determinant of Staphylococcus aureus, may be important in a rabbit model of corneal phlyctenules and catarrhal infiltrates. Over a 5-month period, an enzyme-linked immunosorbent assay was used to measure immunoglobulin (Ig) G and IgA antibody levels to RTA in sera, tears, and corneas from rabbits immunized using the following routes: Group 1, intradermal injections of S. aureus cell wall (CW) mixed with complete Freund's adjuvant (CFA); Group 2, subconjunctival injections of CW-CFA; Group 3, prolonged topical application of viable S. aureus to the eye; Group 4, intradermal injections of CW-CFA plus prolonged topical application of viable S. aureus; and Group 5, subconjunctival injections of CW-CFA plus prolonged topical application of viable S. aureus. Over the 5-month period, the IgG and IgA antibody levels were correlated to RTA with the development of corneal phlyctenules and catarrhal infiltrates. The IgG titers to RTA were higher than IgA titers in serum, tears, and cornea. The highest antibody titers were IgG titers in cornea. Only rabbits immunized by intradermal or subconjunctival injections of CW-CFA followed by prolonged topical application of viable S. aureus (Groups 4 and 5) developed moderate to severe conjunctival hyperemia and edema with corneal phlyctenules and catarrhal infiltrates. When corneal lesions developed between 2-3 months, both groups had the highest corneal IgG and IgA antibody titers to RTA with IgG titers being more than 60 times higher than IgA titers. In the remaining 2 months of the study, the conjunctival response in both groups decreased from moderate-to-severe to mild, and no new corneal lesions developed, despite continued topical application of viable S. aureus and elevated antibody titers in cornea, serum, and tears. In this study, IgG and IgA antibody levels to RTA were measured in serum, tears, and cornea in a rabbit model of corneal phlyctenules and catarrhal infiltrates, and the antibody response was correlated with the development of these hypersensitivity lesions.

Immune response to Staphylococcus aureus endophthalmitis in a rabbit model.

Staphylococcus aureus is an important cause of severe bacterial endophthalmitis. Both immunoglobulin (Ig) G and A antibody titers to ribitol teichoic acid (RTA), the major antigenic determinant of the S. aureus cell wall, were measured by an enzyme-linked immunosorbent assay in serum, tears, aqueous, and vitreous on days 3, 7, 10, 14, 21, and 30 after intravitreal injection of viable S. aureus in rabbits. Clinical examination showed vitreous opacification in all rabbits from days 7-30. Histopathologic examination showed acute inflammation on day 3 and chronic inflammation on days 7-30 in the conjunctiva, cornea, iris, ciliary body, and trabecular meshwork. The vitreous cavity contained neutrophils and necrotic cells on all days. Retinal necrosis was present on days 14-30. Lymphoid follicles with plasma cells were identified in the conjunctiva, ciliary body, and choroid. The vitreous of experimental eyes showed increasing numbers of bacteria from days 3-14, followed by a decrease in numbers on day 21 and absence of viable bacteria on day 30. Increases in IgG antibody levels to RTA were first detected in serum where they were higher than in tears, aqueous, and vitreous until day 14. Vitreous IgG antibody levels to RTA in experimental eyes exceeded all other samples on day 14 and progressively increased thereafter; the other samples declined. The IgA antibody levels were increased in tears on day 14 and in the vitreous of experimental eyes on days 14, 21, and 30. Vitreous IgG antibody levels to RTA were substantially higher than vitreous IgA antibody levels. An inverse correlation was found between vitreous IgG antibody levels and positive vitreous cultures, suggesting that the humoral immune response may be important in the spontaneous sterilization of the vitreous in this model.

[Esophagitis caused by Candida albicans]. / Esofagitis por Candida albicans.

The topic of esophagitis due to Candida (ED), the most frequent infection of the esophagus, is reviewed. In recent years we have seen increased interest in candida esophagitis, fundamentally due to its relation with AIDS, for which it constitutes a diagnostic criteria. Candida esophagitis, although it can appear in apparently healthy subjects, is usually associated with processes that impair the immune system, as well as with local lesions of the esophagus. The typical clinical presentation is as odynophagia, dysphagia and/or retrosternal pain, although asymptomatic forms are frequent, and its association with oropharyngeal candidiasis is variable. Oral endoscopy is the diagnostic technique of choice, since it permits samples to be taken for histologic and cytologic study and cultures; cytology is the most sensitive and specific technique. The differential diagnosis should be made fundamentally with other infectious esophagitis pictures, particularly herpes, and with reflux esophagitis. Treatment is based on antifungal drugs, most frequently nystatin, amphotericin B and ketoconazole.

[Groups at risk and early detection of cancer of the colon and rectum]. / Grupos de riesgo y detección precoz del cáncer de colon y recto.

Early detection of cancer of the colon and rectum is fundamental because survival is linked to the pathologic stage. The population groups at high risk are reviewed, as well as the different screening techniques: search for occult blood in stool (Hemoccult), rectal palpation, rigid rectosigmoidoscopy, flexible fiberoptic sigmoidoscopy, radiology and determination of carcinoembryonic antigen. It is concluded that the Hemoccult test is the most useful technique for early diagnosis and it should be performed in individuals over 40 years and in the high risk population. The other diagnostic tests should be carried out if this test is positive.