A Review of Antimicrobial Therapy for Infectious Uveitis of the Posterior Segment

Treatment of infectious posterior uveitis represents a therapeutic challenge for ophthalmologists. The eye is a privileged site, maintained by blood ocular barriers, which limits penetration of systemic antimicrobials into the posterior segment. In addition, topical and subconjunctival therapies are incapable of producing sufficient drug concentrations, intraocularly. Posterior infectious uveitis can be caused by bacteria, virus, fungi, or protozoa. Mode of treatment varies greatly based on the infectious etiology. Certain drugs have advantages over others in the treatment of infectious uveitis. Topical and systemic therapies are often employed in the treatment of ocular infection, yet the route of treatment can have limitations based on penetration, concentration, and duration. The introduction of intravitreal antimicrobial therapy has advanced the management of intraocular infections. Being able to bypass blood-ocular barriers allows high drug concentrations to be delivered directly to the posterior segment with minimal systemic absorption. However, because the difference between the therapeutic and the toxic doses of some antimicrobial drugs falls within a narrow concentration range, intravitreal therapy could be associated with ocular toxicity risks.  In many cases of infectious uveitis, combination of intravitreal and systemic therapies are necessary. In this comprehensive review, the authors aimed at reviewing clinically relevant data regarding intraocular and systemic antimicrobial therapy for posterior segment infectious uveitis. The review also discussed the evolving trends in intraocular treatment, and elaborated on antibiotic pharmacokinetics and pharmacodynamics, efficacy, and adverse effects

A Review of Antimicrobial Therapy for Infectious Uveitis of the Posterior Segment

Treatment of infectious posterior uveitis represents a therapeutic challenge for ophthalmologists. The eye is a privileged site, maintained by blood ocular barriers, which limits penetration of systemic antimicrobials into the posterior segment. In addition, topical and subconjunctival therapies are incapable of producing sufficient drug concentrations, intraocularly. Posterior infectious uveitis can be caused by bacteria, virus, fungi, or protozoa. Mode of treatment varies greatly based on the infectious etiology. Certain drugs have advantages over others in the treatment of infectious uveitis. Topical and systemic therapies are often employed in the treatment of ocular infection, yet the route of treatment can have limitations based on penetration, concentration, and duration. The introduction of intravitreal antimicrobial therapy has advanced the management of intraocular infections. Being able to bypass blood-ocular barriers allows high drug concentrations to be delivered directly to the posterior segment with minimal systemic absorption. However, because the difference between the therapeutic and the toxic doses of some antimicrobial drugs falls within a narrow concentration range, intravitreal therapy could be associated with ocular toxicity risks.  In many cases of infectious uveitis, combination of intravitreal and systemic therapies are necessary. In this comprehensive review, the authors aimed at reviewing clinically relevant data regarding intraocular and systemic antimicrobial therapy for posterior segment infectious uveitis. The review also discussed the evolving trends in intraocular treatment, and elaborated on antibiotic pharmacokinetics and pharmacodynamics, efficacy, and adverse effects

A Review of Antimicrobial Therapy for Infectious Uveitis of the Posterior Segment

Treatment of infectious posterior uveitis represents a therapeutic challenge for ophthalmologists. The eye is a privileged site, maintained by blood ocular barriers, which limits penetration of systemic antimicrobials into the posterior segment. In addition, topical and subconjunctival therapies are incapable of producing sufficient drug concentrations, intraocularly. Posterior infectious uveitis can be caused by bacteria, virus, fungi, or protozoa. Mode of treatment varies greatly based on the infectious etiology. Certain drugs have advantages over others in the treatment of infectious uveitis. Topical and systemic therapies are often employed in the treatment of ocular infection, yet the route of treatment can have limitations based on penetration, concentration, and duration. The introduction of intravitreal antimicrobial therapy has advanced the management of intraocular infections. Being able to bypass blood-ocular barriers allows high drug concentrations to be delivered directly to the posterior segment with minimal systemic absorption. However, because the difference between the therapeutic and the toxic doses of some antimicrobial drugs falls within a narrow concentration range, intravitreal therapy could be associated with ocular toxicity risks.  In many cases of infectious uveitis, combination of intravitreal and systemic therapies are necessary. In this comprehensive review, the authors aimed at reviewing clinically relevant data regarding intraocular and systemic antimicrobial therapy for posterior segment infectious uveitis. The review also discussed the evolving trends in intraocular treatment, and elaborated on antibiotic pharmacokinetics and pharmacodynamics, efficacy, and adverse effects

European Vitreoretinal Society Macular Hole Study, Prognostic Factors for Anatomical and Functional Success

Background: To identify prognostic preoperative and intraoperative factors for anatomical and visual success of idiopathic macular hole (MH) surgery. Methods: We conducted a non-randomized, collaborative multicenter study using data of 4207 MH surgery from 140 surgeons. Main study outcomes were anatomical closure and best corrected visual acuity (BCVA) improvement postoperative at 6-12 months. Results: Information on anatomical success was available for 4138 eyes of 4207 operations. Anatomical closure of MH was achieved in 85.7% (3546 eyes). Closure was higher in smaller MH (stages 1-2 versus stage 3: OR=0.35; stage 2 versus stage 4: OR=0.16, and in MH with shorter duration before the operation (OR=0.94). Macular Holes were more likely to close when dyes were used to facilitate internal limiting membrane (ILM) peeling (odds ratio=1.73 to 3.58). The most important predictors of postoperative BCVA were the preoperative BCVA (estimate=0.39, p<0.001) and closure of the macular hole (estimate=0.34, p<0.001). We observed Larger improvement in BCVA in combined vitrectomy and phacoemulsification (estimate = 0.10) and post cataract surgery in phakic eyes (estimate=0.05). Retinal tears occurred in 5.1% of eyes, and were less with use of trocars (OR= -1.246) and in combined vitrectomy/ phacoemulsification surgery (OR= -0.688). Conclusion: This international survey confirmed that staining with dyes improves anatomical results but not visual outcomes. After surgery, visual acuity improved during the first year, and final visual acuity was better in both pseudophakic eyes and eyes that underwent cataract surgery during the first year following MH repair

Ocular Complications from Retained Intraocular Ointment Discovered 33 Months after Cataract Surgery

Topical antibiotic and steroid ointments are sometimes used topically at the conclusion of intraocular surgery, and inadvertent entry into the eye has been reported. Dispersed ointment droplets or consolidated globules in the anterior chamber (AC) can sometimes be visualized on exam. Occasionally, intraocular ointment is found incidentally without apparent toxic effect, but retained ointment usually presents with early or delayed intraocular inflammation, pressure rise, macular edema, or corneal edema. The usual treatment for toxicity from retained ointment is removal of the ointment. While the complication of ointment-induced cystoid macular edema has been reported, there is paucity of literature on the anatomical response and eventual visual outcome of patients who have been treated for long-standing edema from retained ointment. We present a case of a patient who presented with history of poor vision since the time of cataract surgery 33 months prior, who had cystoid macular edema, reduced endothelial cell count, and apparent Maxitrol ointment (neomycin, polymyxin B sulfate, and dexamethasone in paraffin vehicle; Novartis Pharmaceuticals UK) floating in the AC. The patient was treated with AC washout and sub-Tenon injection of triamcinolone. His vision, retinal architecture by optical coherence tomography, endothelial cell count, and pachymetry has been followed for 9 months following this treatment

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Genetic architecture of common bunt resistance in winter wheat using genome-wide association study

Background: Common bunt (caused by Tilletia caries and T. foetida) has been considered as a major disease in wheat (Triticum aestivum) following rust (Puccinia spp.) in the Near East and is economically important in the Great Plains, USA. Despite the fact that it can be easily controlled using seed treatment with fungicides, fungicides often cannot or may not be used in organic and low-input fields. Planting common bunt resistant genotypes is an alternative. Results: To identify resistance genes for Nebraska common bunt race, the global set of differential lines were inoculated. Nine differential lines carrying nine different genes had 0% infected heads and seemed to be resistant to Nebraska race. To understand the genetic basis of the resistance in Nebraska winter wheat, a set of 330 genotypes were inoculated and evaluated under field conditions in two locations. Out of the 330 genotypes, 62 genotypes had different degrees of resistance. Moreover, plant height, chlorophyll content and days to heading were scored in both locations. Using genome-wide association study, 123 SNPs located on fourteen chromosomes were identified to be associated with the resistance. Different degrees of linkage disequilibrium was found among the significant SNPs and they explained 1.00 to 9.00% of the phenotypic variance, indicating the presence of many minor QTLs controlling the resistance. Conclusion: Based on the chromosomal location of some of the known genes, some SNPs may be associated with Bt1, Bt6, Bt11 and Bt12 resistance loci. The remaining significant SNPs may be novel alleles that were not reported previously. Common bunt resistance seems to be an independent trait as no correlation was found between a number of infected heads and chlorophyll content, days to heading or plant height

The effect of type of femoral component fixation on mortality and morbidity after hip hemiarthroplasty:A systematic review and meta-analysis

Background: Hip hemiarthroplasty is a well-established treatment of displaced femoral neck fracture, although debate exists over whether cemented or uncemented fixation is superior. Uncemented prostheses have typically been used in younger, healthier patients and cemented prostheses in older patients with less-stable bone. Also, earlier research has suggested that bone cement has cytotoxic effects and may trigger cardiovascular and respiratory adverse events. Questions/Purposes: The aim of this systematic review and meta-analysis was to compare morbidity and mortality rates after cemented and uncemented hemiarthroplasty for the treatment of displaced femoral neck fractures in elderly patients. Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched seven medical databases for randomized clinical trials and observational studies. We compared cemented and uncemented hemiarthroplasty using the Harris Hip Score (HHS), as well as measures of postoperative pain, mortality, and complications. Data were extracted and pooled as risk ratios or standardized mean difference with their corresponding 95% confidence intervals in a meta-analysis model. Results: The meta-analysis included 34 studies (12 randomized trials and 22 observational studies), with a total of 42,411 patients. In the pooled estimate, cemented hemiarthroplasty was associated with less risk of postoperative pain than uncemented hemiarthroplasty. There were no significant differences between groups regarding HHS or rates of postoperative mortality, pulmonary embolism, cardiac arrest, myocardial infarction, acute cardiac arrhythmia, or deep venous thrombosis. Conclusions: While we found that cemented hemiarthroplasty results in less postoperative pain than uncemented hemiarthroplasty in older patients with femoral neck fracture, the lack of significant differences in functional hip scores, mortality, and complications was surprising. Further high-level research is needed

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially