Factors affecting compliance to intravitreal anti-vascular endothelial growth factor therapy in Indian patients with retinal vein occlusion,age-related macular degeneration,and diabetic macular edema

Purpose:To evaluate the rate of compliance and the reasons for loss to follow-up in Indian patients with diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO) being treated with anti-vascular endothelial growth factor (VEGF) therapy.Methods:This was a retrospective single-center study. Patients with DME, AMD, or RVO were eligible if they initiated anti-VEGF therapy between January 2013 and December 2017. Patients'' data were obtained from hospital electronic records, including the number of injections received, visits, details of follow-up, missed appointments, and reasons for loss to follow-up (>365 days).Results:A total of 648 patients were eligible for the study, of which 334 (51.54%) patients were lost to follow-up. Overall, 343 (64.96%) were males and the overall mean (SD) age was 66.40 (7.44) years. A total of 376 (58.0%) patients had a history of diabetes and 364 (56.2%) patients had a history of hypertension. Further, 127 (38.0), 112 (33.5), and 95 (28.4) had DME, AMD, and RVO, respectively and were lost to follow-up. The most commonly reported reason for loss to follow-up was “non-affordability” (n = 120; 41.1%) followed by “no improvement in vision” (n = 83; 28.4%). “No improvement in vision” (42.2%) and “non-affordability” (37.5%) were higher among patients with DME. No association was found in gender- and treatment-wise distribution of reasons for loss to follow-up.Conclusion:The results showed that around half of the patients with DME, AMD, and RVO were lost to follow-up to intravitreal anti-VEGF therapy, and the most common factors were “non-affordability” and “no improvement in vision.”     

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia (COVID STEROID) trial—Protocol and statistical analysis plan

Introduction

Severe acute respiratory syndrome coronavirus-2 has caused a pandemic of coronavirus disease (COVID-19) with many patients developing hypoxic respiratory failure. Corticosteroids reduce the time on mechanical ventilation, length of stay in the intensive care unit and potentially also mortality in similar patient populations. However, corticosteroids have undesirable effects, including longer time to viral clearance. Clinical equipoise on the use of corticosteroids for COVID-19 exists.

Methods

The COVID STEROID trial is an international, randomised, stratified, blinded clinical trial. We will allocate 1000 adult patients with COVID-19 receiving ≥10 L/min of oxygen or on mechanical ventilation to intravenous hydrocortisone 200 mg daily vs placebo (0.9% saline) for 7 days. The primary outcome is days alive without life support (ie mechanical ventilation, circulatory support, and renal replacement therapy) at day 28. Secondary outcomes are serious adverse reactions at day 14; days alive without life support at day 90; days alive and out of hospital at day 90; all-cause mortality at day 28, day 90, and 1 year; and health-related quality of life at 1 year. We will conduct the statistical analyses according to this protocol, including interim analyses for every 250 patients followed for 28 days. The primary outcome will be compared using the Kryger Jensen and Lange test in the intention to treat population and reported as differences in means and medians with 95% confidence intervals.

Discussion

The COVID STEROID trial will provide important evidence to guide the use of corticosteroids in COVID-19 and severe hypoxia.

     

Sarcomas of head and neck — A 10 yrs experience

38 cases of sarcoma of head and neck region were analysed in a retrospective way in relation to age, anatomic location, histological, clinical profile, and surgical approaches. Compared to other types of head and neck neoplasms, such as squamous cell carcinoma, soft tissue sarcomas have low rates of regional metastases. However the biological behaviour of soft tissue sarcoma is more aggressive specially in paediatric age group. In the present series, CT scan was considered as the primary modality of investigation. Surgery generally has been recommended as the primary method of treatment for achieving local control, except in those high-grade tumours arising in sites not amenable to resection. 3-year and 5-year survival rates in this present series 50% and 31.6% respectively.     

Toxicity of legume seeds to rhizobia: Selective marker for strain identification and selection of toxin-free seeds

Seeds of legume species Argyrolobium flaccidum, Desmodium elegans, D. tortuosum, Indigofera gangetica, Lespedeza stenocarpa and Sesbania sesban have been evaluated for the toxicity to rhizobia for the first time. Legume species differ in quantity and quality of released seed toxins to which the symbiotic bacteria respond differentially. Therefore, seed toxicity may be used as a selectable taxonomic marker for the strainal identification of rhizobia. Seed toxins are located in seed coat and are thermolabile to some extent. The seed genotypes, within the species, differ in toxicity and such polymorphism can be used in the selection of toxin-free seeds. Seed surface-disinfection procedures involving subsequent soaking and washing with water are the most useful methods for reducing the seed toxins. The seed toxins from I. gangetica inhibited the growth of its homologous strain but did not affect nodulation and symbiotic parameters. Various seed-toxin-producing legume species did not affect nodulation and symbiotic efficiency and effectiveness.     

The use of a double-marker shuttle vector to study DNA double-strand break repair in wild-type and radiation-sensitive mutants of the yeast Saccharomyces cerevisiae

An episomal DNA vector (YpJA18), encoding two selectable recombinant yeast genes (TRP1, URA3), was constructed to assess the fidelity of DNA repair in haploid repair-competent (RAD) wild-type yeast and several radiation-sensitive mutants. Either a DNA double-strand break (DSB) or a double-strand gap of 169 bp (DSG) was introduced by restriction enzymes in-vitro within the coding sequence of the URA3 gene of this vector. To eliminate transfer artefacts, selection was first applied for the undamaged TRP1 gene followed by counter selection for URA3 gene activity, which indicated correct repair of the DSB and DSG. Correct repair of the damaged URA3 gene was found to be about 90% in RAD cells (normalized for the expression of undamaged URA3 in TRP ⁺ transformants). Plasmids isolated from the transformants (URA ⁺ TRP ⁺) carry both unique sites (ApaI and NcoI) within the URA3 gene indicating the precise restitution of the 169-bp gap. An excision-repair-defective rad4-4 mutant repaired these lesions as correctly as RAD cells, whereas the mutants rad50-1, rad51-1 and rad54-1, proven to be defective in DSB repair and mitotic recombination, showed less than 5% correct repair of such lesions. In contrast, a representative of the RAD6 epistasis group of genes, the rev2-1 mutant which is sensitive towards UV and ionizing radiation, had a significantly reduced ability (about 20%) for the correct repair of both DSBs and DSGs.     

Sleep-related neurons in the central nucleus of the amygdala of rats and their modulation by the dorsal raphe nucleus

The amygdala (AMY) plays an important role in initiating appropriate neurobehavioral responses to emotionally arousing events. Its major efferents from the central nucleus (Ace) to the basal forebrain, hypothalamus and brainstem permit it to influence sleep mechanisms. To characterize further the neuronal activity of AMY during sleep and wakefulness, we recorded single neuronal activity in Ace across behavioral states in freely moving, normally behaving rats. Of the 49 neurons recorded from Ace, 24 neurons had firing patterns related to sleep-wakefulness (S-W). Of these, 50% (n = 12) had a high firing frequency during wakefulness (W) or both W and REM sleep (REM), 12% (n = 3) were non-REM (NREM)-related, 17% (n = 4) had a high firing rate in REM (REM-ON), and 20% (n = 5) fired at a low rate during REM. Because serotonin introduced into AMY during REM induces short-latency changes of state, we also studied the effects of low frequency (1 Hz) electrical stimulation of the dorsal raphe nucleus (DRN) on Ace neurons. All REM-ON neurons recorded from Ace were inhibited by DRN stimulation, and other cell types were unaffected. Thus, we found that the majority of cells in Ace related to S-W fired slowly during NREM and increased their discharge during W and/or REM, and that the DRN has the potential for modulating the spontaneous activity of REM-ON cells in rats.