Impact of intravitreal ranibizumab, aflibercept and bevacizumab on retinal ganglion cell and nerve fibre layer thickness in Neovascular age-related macular degeneration

Purpose: To compare the effects of monotherapy with intravitreal ranibizumab, aflibercept and bevacizumab on retinal ganglion cell layer (RGCL) and retinal nerve fibre layer (RNFL) in patients with naïve neovascular age-related macular degeneration (nAMD). Methods: This is a retrospective cohort study with three-groups comparison. 83 patients and 97 eyes on continuous monotherapy with an intravitreal anti-vascular endothelial growth factor (anti-VEGF) were followed for 24months and divided into three groups according to anti-VEGF (aflibercept: 25 eyes, ranibizumab: 34 eyes, bevacizumab: 38 eyes). Main outcome measures included: RGCL and RNFL thickness, best corrected visual acuity (BCVA), central macular thickness (CMT), macular volume (MV) and the presence of intraretinal fluids (IRF), subretinal fluids (SRF) and retinal pigment epithelial atrophy (RPE-atrophy). All outcome measures were recorded at the time of the first injection, 1 and 2years after treatment and compared longitudinally and between groups. Results: The mean age was 79±7years. The RGCL thickness, MV, CMT and the presence of IRF and SRF decreased significantly within all three medication groups (p<0.05 for all) with no significant difference between groups over the 2-year follow-up period (p>0.10 for all). The decrease in RNFL thickness was not significant within or between the groups after a 2-year follow-up (p>0.055 for all). RPE-atrophy increased significantly after 2 years in all three groups (p<0.028 for all) with no significant difference between groups at all three time points (p>0.307 for all). BCVA was comparable between the three groups over the 2-year follow-up period (p>0.22 for all). Conclusions: Monotherapy with intravitreal aflibercept, bevacizumab and ranibizumab was associated with comparable significant decreases in RGCL thickness, CMT, MV, IRF and SRF in naïve nAMD patients during the first 2 years of treatment. Furthermore, no significant differences either in BCVA or RNFL thickness were observed between the three intravitreal anti-VEFGs during the first 2 years of treatment

Einseitige Papillenschwellung – nicht immer ist es nur eine AION

Eine 53-jährige Patientin stellte sich notfallmäßig wegen seit 2 Tagen plötzlicher Visusminderung mit Gesichtsfeldausfall am linken Auge in unserer Ambulanz vor. Die Patientin hatte vor 6 Monaten am betroffenen linken Auge eine perforierende Keratoplastik bei Keratokonus erhalten. Außerdem litt sie unter arterieller Hypertonie, Adipositas (BMI 37 kg/m2) und hatte im Jahr 2001 ein Zervixkarzinom

Side effects and treatment initiation barriers of sodium-glucose cotransporter 2 inhibitors in heart failure: a systematic review and meta-analysis

Aims Physicians are sometimes reluctant to initiate guideline-directed therapy in patients with heart failure and reduced ejection fraction (HFrEF) due to concerns of adverse events. We explored the risk of hypotension, volume depletion, and acute kidney injury (AKI) on sodium–glucose cotransporter 2 (SGLT2) inhibitors in HFrEF populations. Methods and results We determined summary risk ratios (RRs) by conducting a meta-analysis on reported aforementioned adverse events on SGLT2 inhibitors from randomized controlled trials. We explored robustness of meta-analyses by computing fragility and/or reverse fragility index (FI or RFI) and its corresponding fragility quotient (FQ or RFQ) for each outcome. A total of 10 050 patients with HFrEF entered the final meta-analysis. Hypotension was reported in 4.5% (219/4836) on SGLT2 inhibitors and in 4.1% (202/4846) on placebo (RR 1.09, 95% confidence interval [CI] 0.91–1.31, p = 0.36). An RFI of 21 and RFQ of 0.002 suggest robust findings for hypotension. Volume depletion occurred in 9.4% (473/5019) on SGLT2 inhibitors and in 8.7% (438/5031) on placebo (RR 1.07, 95% CI 0.95–1.21, p = 0.25), respectively. RFI of 19 and RFQ of 0.001 suggest moderately robust findings for volume depletion. AKI was reported in fewer patients (1.9% [95/4888]) on SGLT2 inhibitors than on placebo (2.8% [140/4899]) providing lower incidence of AKI (RR 0.69, 95% CI 0.51–0.93, p = 0.02). FI of 14 and RFQ of 0.001 suggest moderately robust findings for AKI. Conclusion Sodium–glucose cotransporter 2 inhibitor therapy is not associated with a clinically relevant risk of hypotension and volume depletion. Its use reduces the risk of AKI. This analysis supports current guideline recommendations on early use of SGLT2 inhibitors

Compartmentalization of Cells Bearing "Rheumatic” Cell Surface Antigens in Peripheral Blood and Tonsils in Rheumatic Heart Disease

Monoclonal antibodies that recognize "rheumatic” antigens of peripheral blood non-T cells were used to study the compartmentalization of such cells in peripheral blood and tonsils of individuals with rheumatic heart disease (RHD) and suitable control subjects. The peripheral blood of most (71%) of the 42 individuals with RHD contained cells reacting with monoclonal antibody 83S19.23 or 256S.10, whereas these cells were present in only 17% of the 41 control subjects (P < .02). However, none of 21 individuals with RHD had such cells in their tonsils, although they were present in the tonsils of 50% of the 40 control subjects (P < .03). These results may reflect a failure in RHD of organ-specific homing of cells with the epitopes recognized by the antibodies. The presence of these cells in tonsils may be important in the immune response to streptococcal pharyngeal infection, and their absence in RHD may be involved in the unusual immune responses characteristic of this diseas

Cover crops and interrow tillage for weed control in short season maize (Zea mays)

Abstract Weed competition can cause substantial maize (Zea mays L.) yield reductions. Interseeding maize with cover crops or a combination of interrow cultivation and interseeded cover crops are possible alternative methods of weed control. This study was conducted to examine the potential of interrow cultivation plus cover crops to reduce weed density in maize without reducing the grain yield. Field experiments were conducted in 1993 and 1994 at two sites in Québec to determine the effects of planting 12 cover crops with maize on weed control. Fall rye (Secale cereal L.), hairy vetch (Vicia villosa Roth), a mixture of red clover (Trifolium pratense L.) and ryegrass (Lolium multiflorum Lam), a mixture of white clover (Trifolium repens L.) and ryegrass, subterranean clover (Trifolium subterraneum L.), yellow sweet clover (Meliotus officinalis Lam), black medic (Medicago lupulina L.), Persian clover (Trifolium resupinatum L.), strawberry clover (Trifolium fragiferum L.), crimson clover (Trifolium incarnatum L.), alfalfa (Medicago sativa L.), and berseem clover (Trifolium alexandrinum L.) were seeded at two planting dates, 10 and 20 days after maize emergence. Interrow cultivation was carried out weekly until forage seeding, with a final cultivation being conducted just prior to cover crop seeding. Cover crop planting date did not affect maize yields or the ability of interrow tillage plus cover crops to suppress the development of weed populations. Maize yield was less affected by the interseeded cover crops under conditions of adequate rainfall. Corn planted in fields heavily infested with weeds resulted in substantial yield reductions even when rainfall was adequate. Except for 1993 at l&apos;Assomption interrow tillage plus cover crop treatments had consistently lower weed biomass when compared to the weedy control. Most of the weed control was due to the interrow cultivation performed prior to seeding of the cover crops. The lowest weed density occurred in the herbicide treated plots. The ability of interrow tillage plus cover crops to suppress the development of weeds was affected by the level of weed infestation, the growing conditions and location. The cover crops provide additional weed control but the interrrow tillage or some herbicide application may still be necessary

Side effects and treatment initiation barriers of sodium-glucose cotransporter 2 inhibitors in heart failure: a systematic review and meta-analysis.

AIMS: Physicians are sometimes reluctant to initiate guideline-directed therapy in patients with heart failure and reduced ejection fraction (HFrEF) due to concerns of adverse events. We explored the risk of hypotension, volume depletion, and acute kidney injury (AKI) on sodium-glucose cotransporter 2 (SGLT2) inhibitors in HFrEF populations. METHODS AND RESULTS: We determined summary risk ratios (RRs) by conducting a meta-analysis on reported aforementioned adverse events on SGLT2 inhibitors from randomized controlled trials. We explored robustness of meta-analyses by computing fragility and/or reverse fragility index (FI or RFI) and its corresponding fragility quotient (FQ or RFQ) for each outcome. A total of 10 050 patients with HFrEF entered the final meta-analysis. Hypotension was reported in 4.5% (219/4836) on SGLT2 inhibitors and in 4.1% (202/4846) on placebo (RR 1.09, 95% confidence interval [CI] 0.91-1.31, p = 0.36). An RFI of 21 and RFQ of 0.002 suggest robust findings for hypotension. Volume depletion occurred in 9.4% (473/5019) on SGLT2 inhibitors and in 8.7% (438/5031) on placebo (RR 1.07, 95% CI 0.95-1.21, p = 0.25), respectively. RFI of 19 and RFQ of 0.001 suggest moderately robust findings for volume depletion. AKI was reported in fewer patients (1.9% [95/4888]) on SGLT2 inhibitors than on placebo (2.8% [140/4899]) providing lower incidence of AKI (RR 0.69, 95% CI 0.51-0.93, p = 0.02). FI of 14 and RFQ of 0.001 suggest moderately robust findings for AKI. CONCLUSION: Sodium-glucose cotransporter 2 inhibitor therapy is not associated with a clinically relevant risk of hypotension and volume depletion. Its use reduces the risk of AKI. This analysis supports current guideline recommendations on early use of SGLT2 inhibitors

Host stage preference and parasitism behaviour of Aenasius bambawaleian an encyrtid parasitoid of Phenacoccus solenopsis

In Pakistan, the cotton mealybug, Phenacoccus solenopsis Tinsley (Sternorrhyncha (Homoptera): Pseudococcidae), is a serious pest of many cultivated plants. A parasitoid, Aenasius bambawalei Hayat (Hymenoptera: Encyrtidae), is associated with P. solenopsis. In order to mass rear A. bambawalei for a biological control program, it is important to investigate the parasitoid’s host stage preference and its parasitism behavior for P. solenopsis in order to optimize production. The present tudy showed that under both choice and no choice conditions, the parasitoid preferred 3rd instar and pre-reproductive host stage mealybugs for parasitism. Parasitoid larva developing inside the host exhibited a greater longevity, shorter developmental period and longer body size in these preferred host stages. Our study also confirmed that A. bambawalei showed no attraction to male mealybugs and no host feeding on any host stage was recorded. The ability of the parasitoid to effectively discriminate between suitable and non-suitable stages means that it is feasible to rear it on a mixed population

Measuring the impact and costs of a universal group based parenting programme : protocol and implementation of a trial

Background Sub-optimal parenting is a common risk factor for a wide range of negative health, social and educational outcomes. Most parenting programmes have been developed in the USA in the context of delinquency prevention for targeted or indicated groups and the main theoretical underpinning for these programmes is behaviour management. The Family Links Nurturing Programme (FLNP) focuses on family relationships as well as behaviour management and is offered on a universal basis. As a result it may be better placed to improve health and educational outcomes. Developed in the UK voluntary sector, FLNP is popular with practitioners, has impressed policy makers throughout the UK, has been found to be effective in before/after and qualitative studies, but lacks a randomised controlled trial (RCT) evidence base. Methods/Design A multi-centre, investigator blind, randomised controlled trial of the FLNP with a target sample of 288 south Wales families who have a child aged 2-4 yrs living in or near to Flying Start/Sure Start areas. Changes in parenting, parent child relations and parent and child wellbeing are assessed with validated measures immediately and at 6 months post intervention. Economic components include cost consequences and cost utility analyses based on parental ranking of states of quality of life. Attendance and completion rates and fidelity to the FLNP course delivery are assessed. A nested qualitative study will assess reasons for participation and non-participation and the perceived value of the programme to families. By the end of May 2010, 287 families have been recruited into the trial across four areas of south Wales. Recruitment has not met the planned timescales with barriers including professional anxiety about families entering the control arm of the trial, family concern about video and audio recording, programme facilitator concern about the recording of FLNP sessions for fidelity purposes and delays due to the new UK research governance procedures. Discussion Whilst there are strong theoretical arguments to support universal provision of parenting programmes, few universal programmes have been subjected to randomised controlled trials. In this paper we describe a RCT protocol with quantitative and qualitative outcome measures and an economic evaluation designed to provide clear evidence with regard to effectiveness and costs. We describe challenges implementing the protocol and how we are addressing these

Less loop diuretic use in patients on sacubitril/valsartan undergoing remote pulmonary artery pressure monitoring

Aims Control of pulmonary pressures monitored remotely reduced heart failure hospitalizations mainly by lowering filling pressures through the use of loop diuretics. Sacubitril/valsartan improves heart failure outcomes and increases the kidney sensitivity for diuretics. We explored whether sacubitril/valsartan is associated with less utilization of loop diuretics in patients guided with haemodynamic monitoring in the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF). Methods and results The MEMS-HF population (n = 239) was separated by the use of sacubitril/valsartan (n = 68) or no use of it (n = 164). Utilization of diuretics and their doses was prespecified in the protocol and was monitored in both groups. Multivariable regression, ANCOVA, and a generalized linear model were used to fit baseline covariates with furosemide equivalents and changes for 12 months. MEMS-HF participants (n = 239) were grouped in sacubitril/valsartan users [n = 68, 64 ± 11 years, left ventricular ejection fraction (LVEF) 25 ± 9%, cardiac index (CI) 1.89 ± 0.4 L/min/m2] vs. non-users (n = 164, 70 ± 10 years, LVEF 36 ± 16%, CI 2.11 ± 0.58 L/min/m2, P = 0.0002, P < 0.0001, and P = 0.0015, respectively). In contrast, mean pulmonary artery pressure (PAP) values were comparable between groups (29 ± 11 vs. 31 ± 11 mmHg, P = 0.127). Utilization of loop diuretics was lower in patients taking sacubitril/valsartan compared with those without (P = 0.01). Significant predictor of loop diuretic use was a history of renal failure (P = 0.005) but not age (P = 0.091). After subjects were stratified by sacubitril/valsartan or other diuretic use, PAP was nominally, but not significantly lower in sacubitril/valsartan-treated patients (baseline: P = 0.52; 6 months: P = 0.07; 12 months: P = 0.53), while there was no difference in outcome or PAP changes. This difference was observed despite lower CI (P = 0.0015). Comparable changes were not observed for other non-loop diuretics (P = 0.21). Conclusions In patients whose treatment was guided by remote PAP monitoring, concomitant use of sacubitril/valsartan was associated with reduced utilization of loop diuretics, which could potentially be relevant for outcomes