Do intravitreal Ranibizumab injections for wet age-related macular degeneration affect the vitreomacular interface?

Presentation Abstract - Purpose:Serial intravitreal ranibizumab injections are the main treatment for wet age- related macular degeneration (AMD), and patients are monitored by optical coherence tomography (OCT). Our objective in conducting this study is to determine whether serial intravitreal injections of ranibizumab in eyes with wet AMD alter the vitreo-macular interface (VMI) Methods - Using a Topcon Spectral Domain OCT, we performed a prospective, observational study of 87 eyes of 82 consecutive patients undergoing treatment with intravitreal ranibizumab for wet AMD, with each patient followed up for a minimum of 6 months. The mean number of intravitreal ranibizumab injections was 4.28, range 3-6. Using macular OCT scans, the area of VMI was closely examined, for vitreo-macular adhesion (VMA), defined as perifoveal posterior vitreous detachment (PVD) with posterior vitreous attached to fovea. Any OCT separation of posterior vitreous face was observed and measured, every month for 6 months. Results - There was no change in the OCT appearance or measurement of VM interface in 80 eyes (92%). VM adhesion, defined on OCT as when the posterior hyaloid line is attached to inner foveal surface and dettached perifoveally, was identified in 7 out of 87 treated eyes (8%) .Of these 7 eyes, 1 eye developed complete PVD following three injections, 1 eye developed partial PVD and the remaining 5 eyes had no significant change in VM adhesion. Conclusions - To our knowledge this is the first study that has examined the VM interface following serial ranibizumab injections for wet AMD. This small pilot study suggests that most cases undergoing ranibizumab therapy suffer no disturbance to VM interface.

Efficacy and safety of second-generation antipsychotic long-acting injections (SGA LAIs) in maintenance treatment of bipolar disorder:protocol for a systematic review and meta-analysis

INTRODUCTION: Bipolar disorder requires long-term treatment but non-adherence is a common problem. Antipsychotic long-acting injections (LAIs) have been suggested to improve adherence but none are licensed in the UK for bipolar. However, the use of second-generation antipsychotics (SGA) LAIs in bipolar is not uncommon albeit there is a lack of systematic review in this area. This study aims to systematically review safety and efficacy of SGA LAIs in the maintenance treatment of bipolar disorder. METHODS AND ANALYSIS: The protocol is based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and will include only randomised controlled trials comparing SGA LAIs in bipolar. PubMed, EMBASE, CINAHL, Cochrane Library (CENTRAL), PsychINFO, LiLACS, http://www.clinicaltrials.gov will be searched, with no language restriction, from 2000 to January 2016 as first SGA LAIs came to the market after 2000. Manufacturers of SGA LAIs will also be contacted. Primary efficacy outcome is relapse rate or delayed time to relapse or reduction in hospitalisation and primary safety outcomes are drop-out rates, all-cause discontinuation and discontinuation due to adverse events. Qualitative reporting of evidence will be based on 21 items listed on standards for reporting qualitative research (SRQR) focusing on study quality (assessed using the Jadad score, allocation concealment and data analysis), risk of bias and effect size. Publication bias will be assessed using funnel plots. If sufficient data are available meta-analysis will be performed with primary effect size as relative risk presented with 95% CI. Sensitivity analysis, conditional on number of studies and sample size, will be carried out on manic versus depressive symptoms and monotherapy versus adjunctive therapy.

Incidencia y factores de riesgo asociados a hemorragia intraventricular en recién nacidos prematuros atendidos en el servicio de neonatología del Hospital Nacional de Niños Benjamín Bloom de Enero 2012 a Diciembre 2013

La hemorragia intraventricular constituye una complicación que con mucha frecuencia se asocia a la prematuréz; a pesar de los avances en atención hospitalaria, que buscan disminuir el número de recién nacidos prematuros, éstos continúan presentándose y por lo tanto el desarrollo de hemorragia intraventricular se detecta cada vez con más frecuencia en este grupo de recién nacidos, es sabido además de la influencia de un número importante de factores de riesgo que contribuyen a la presencia de dicha patología. Objetivo: conocer la incidencia y los factores de riesgo que llevan al desarrollo de hemorragia intraventricular en recién nacidos prematuros atendidos en el servicio de neonatos y cuidados intensivos neonatales del Hospital de Niños Benjamín Bloom. Dicho hospital recibe continuamente recién nacidos prematuros, que en diferente grado presentan hemorragia intraventricular; por lo que resultó necesario determinar con qué frecuencia se desarrolló ésta entre los prematuros atendidos y además cuales fueron los factores de riesgo asociados. Método: se realizó un estudio analítico de casos y controles, de fuentes documentales a partir de los expedientes clínicos de los recién nacidos prematuros que fueron atendidos en el servicio de neonatos y cuidados intensivos neonatales del HNNBB de enero de 2012 a diciembre de 2013. Se llevó a cabo la revisión de 140 expedientes clínicos, uno de ellos se excluyó por presentar múltiples malformaciones congénitas, que constituía un criterio de exclusión, de éstos datos se utilizaron para el análisis 117 expedientes, ya que a 22 pacientes no se les realizó ultrasonografía transfontanelar, sin tener información de las razones por las que no se tomó dicho estudio. Resultados: el estudio demostró que la hemorragia intraventricular se presentó en 25 pacientes, con una frecuencia del 21.4%, similar a los datos encontrados en las referencias bibliográficas. Los factores de riesgo parto vaginal se presentó en 15 pacientes (60%), APGAR bajo al primer minuto (6.52±2.06), presencia de síndrome de dificultad respiratoria que se identificó en 21 pacientes (84%), la ventilación mecánica se necesitó en el 96% de los pacientes (24) y el uso de derivados sanguíneos con un promedio de 3.6±3.13 transfusiones, se relaciona al desarrollo de hemorragia intraventricular con mayor frecuencia, pero no se asociaron de forma significativa. Los factores que con mayor significancia se asociaron al desarrollo de esta patología en la población estudiada fueron: Edad gestacional ˂ 28 semanas (OR 4.9), peso menor de 1500 gramos (OR 5.48) y presencia de sepsis neonatal (OR3.77)

Constrained fuzzy power flow models with correlation between nodal injections

This paper extends the symmetric/constrained fuzzy powerflow models by including the potential correlations between nodal injections. Therefore, the extension of the model allows the specification of fuzzy generation and load values and of potential correlations between nodal injections. The enhanced version of the symmetric/constrained fuzzy powerflow model is applied to the 30-bus IEEE test system. The results prove the importance of the inclusion of data correlations in the analysis of transmission system adequacy.

Maternal administration of erythromycin fails to eradicate intrauterine ureaplasma infection in an ovine model

Erythromycin is the standard antibiotic used for treatment of Ureaplasma species during 3 pregnancy; however, maternally administered erythromycin may be ineffective at eliminating 4 intra-amniotic ureaplasma infections. We asked if erythromycin would eradicate intra-amniotic 5 ureaplasma infections in pregnant sheep. At 50 days of gestation (d, term=150d) pregnant ewes 6 received intra-amniotic injections of erythromycin-sensitive U. parvum serovar 3 (n=16) or 10B 7 medium (n=16). At 100d, amniocentesis was performed; five fetal losses (ureaplasma group: 8 n=4; 10B group: n=1) had occurred by this time. Remaining ewes were allocated into treatment 9 subgroups: medium only (M, n=7); medium and erythromycin (M/E, n=8); ureaplasma only (Up, 10 n=6) or ureaplasma and erythromycin (Up/E, n=6). Erythromycin was administered intra11 muscularly (500 mg), eight-hourly for four days (100d-104d). Amniotic fluid samples were 12 collected at 105d. At 125d preterm fetuses were surgically delivered and specimens were 13 collected for culture and histology. Erythromycin was quantified in amniotic fluid by liquid 14 chromatography-mass spectrometry. Ureaplasmas were isolated from the amniotic fluid, 15 chorioamnion and fetal lung of animals from the Up and Up/E groups, however, the numbers of 16 U. parvum recovered were not different between these groups. Inflammation in the 17 chorioamnion, cord and fetal lung was increased in ureaplasma-exposed animals compared to 18 controls, but was not different between the Up and Up/E groups. Erythromycin was detected in 19 amniotic fluid samples, although concentrations were low (<10-76 ng/mL). This study 20 demonstrates that maternally administered erythromycin does not eradicate chronic, intra- amniotic ureaplasma infections or improve fetal outcomes in an ovine model, potentially due to 22 the poor placental passage of erythromycin.

The role of the multiple banded antigen of ureaplasma parvum in intra-amniotic infection : major virulence factor or decoy?

The multiple banded antigen (MBA) is a predicted virulence factor of Ureaplasma species. Antigenic variation of the MBA is a potential mechanism by which ureaplasmas avoid immune recognition and cause chronic infections of the upper genital tract of pregnant women. We tested whether the MBA is involved in the pathogenesis of intra-amniotic infection and chorioamnionitis by injecting virulent or avirulent-derived ureaplasma clones (expressing single MBA variants) into the amniotic fluid of pregnant sheep. At 55 days of gestation pregnant ewes (n = 20) received intra-amniotic injections of virulent-derived or avirulent-derived U. parvum serovar 6 strains (2×104 CFU), or 10B medium (n = 5). Amniotic fluid was collected every two weeks post-infection and fetal tissues were collected at the time of surgical delivery of the fetus (140 days of gestation). Whilst chronic colonisation was established in the amniotic fluid of animals infected with avirulent-derived and virulent-derived ureaplasmas, the severity of chorioamnionitis and fetal inflammation was not different between these groups (p>0.05). MBA size variants (32–170 kDa) were generated in vivo in amniotic fluid samples from both the avirulent and virulent groups, whereas in vitro antibody selection experiments led to the emergence of MBA-negative escape variants in both strains. Anti-ureaplasma IgG antibodies were detected in the maternal serum of animals from the avirulent (40%) and virulent (55%) groups, and these antibodies correlated with increased IL-1β, IL-6 and IL-8 expression in chorioamnion tissue (p<0.05). We demonstrate that ureaplasmas are capable of MBA phase variation in vitro; however, ureaplasmas undergo MBA size variation in vivo, to potentially prevent eradication by the immune response. Size variation of the MBA did not correlate with the severity of chorioamnionitis. Nonetheless, the correlation between a maternal humoral response and the expression of chorioamnion cytokines is a novel finding. This host response may be important in the pathogenesis of inflammation-mediated adverse pregnancy outcomes.

Estimation on the mortality and disease burden attributed to selected risk factors in Shandong province [山东省主要危险因素的归因死亡和疾病负担分析]

Objective: To determine the major health related risk factors and provide evidence for policy-making,using health burden analysis on selected factors among general population from Shandong province. Methods: Based on data derived from the Third Death of Cause Sampling Survey in Shandong. Years of life lcrat(YLLs),yearS Iived with disability(YLDs)and disability-adjusted life years(DALYs) were calculated according to the GBD ethodology.Deaths and DALYs attributed to the selected risk factors were than estimated together with the PAF data from GBD 2001 study.The indirect method was employed to estimate the YLDs. Results: 51.09%of the total dearlls and 31.83%of the total DALYs from the Shandong population were resulted from the 19 selected risk factors.High blood pre.ure,smoking,low fruit and vegetable intake,aleohol consumption,indoor smoke from solid fuels,high cholesterol,urban air pollution, physical inactivity,overweight and obesity and unsafe injections in health care settings were identified as the top 10 risk faetors for mortality which together caused 50.21%of the total deaths.Alcohol use,smoking,high blood pressure,Low fruit and vegetable intake, indoor smoke from solid fuels, overweight and obesity,high cholesterol, physical inactivity,urban air pollution and iron-deficiency anemia were proved as the top 10 risk factors related to disease burden and were responsible for 29.04%of the total DALYs. Conclusion: Alcohol use.smoking and high blood pressure were determined as the major risk factors which influencing the health of residents in Shandong. The mortality and burden of disease could be reduced significantly if these major factors were effectively under control.

Zoledronic acid preserves bone structure and increases survival but does not limit tumour incidence in a prostate cancer bone metastasis model

Background The bisphosphonate, zoledronic acid (ZOL), can inhibit osteoclasts leading to decreased osteoclastogenesis and osteoclast activity in bone. Here, we used a mixed osteolytic/osteoblastic murine model of bone-metastatic prostate cancer, RM1(BM), to determine how inhibiting osteolysis with ZOL affects the ability of these cells to establish metastases in bone, the integrity of the tumour-bearing bones and the survival of the tumour-bearing mice. Methods The model involves intracardiac injection for arterial dissemination of the RM1(BM) cells in C57BL/6 mice. ZOL treatment was given via subcutaneous injections on days 0, 4, 8 and 12, at 20 and 100 µg/kg doses. Bone integrity was assessed by micro-computed tomography and histology with comparison to untreated mice. The osteoclast and osteoblast activity was determined by measuring serum tartrate-resistant acid phosphatase 5b (TRAP 5b) and osteocalcin, respectively. Mice were euthanased according to predetermined criteria and survival was assessed using Kaplan Meier plots. Findings Micro-CT and histological analysis showed that treatment of mice with ZOL from the day of intracardiac injection of RM1(BM) cells inhibited tumour-induced bone lysis, maintained bone volume and reduced the calcification of tumour-induced endochondral osteoid material. ZOL treatment also led to a decreased serum osteocalcin and TRAP 5b levels. Additionally, treated mice showed increased survival compared to vehicle treated controls. However, ZOL treatment did not inhibit the cells ability to metastasise to bone as the number of bone-metastases was similar in both treated and untreated mice. Conclusions ZOL treatment provided significant benefits for maintaining the integrity of tumour-bearing bones and increased the survival of tumour bearing mice, though it did not prevent establishment of bone-metastases in this model. From the mechanistic view, these observations confirm that tumour-induced bone lysis is not a requirement for establishment of these bone tumours.