Ophthalmol Ther

There is little understanding of long-term treatment persistence in patients receiving anti-vascular endothelial growth factor (anti-VEGF) injections for diabetic macular edema (DME), particularly relating to treatment intervals. The aim of this study was to investigate the association between treatment interval and discontinuation rate after 24 months of unilateral anti-VEGF treatment in patients with DME under routine clinical care in the USA. This was a non-interventional, retrospective cohort study to review the health insurance claims of adults with DME linked with the IBM MarketScan Commercial and Medicare Supplemental databases, who were continuously enrolled in a health plan for at least 6 months prior to their first anti-VEGF treatment and for a duration of at least 24 months between July 2011 and June 2017. Patients were grouped on the basis of the injection interval they achieved at 24 months of treatment. Discontinuation rate beyond 24 months and its association with treatment intervals at 24 months was estimated using the Kaplan-Meier method and Cox proportional hazards models. The overall discontinuation rate among the 1702 eligible patients from 24 to 60 months after treatment initiation was 30%. At 60 months, patients were more likely to remain on treatment in shorter (75.3% [4-week interval group]) versus longer treatment interval groups (62.1% [> 12-week interval group], difference = 13.2%, [95% confidence interval (CI) 1.06, 2.06], p = 0.01). Patients on a > 12-week interval were twice as likely to discontinue treatment compared with those on an 8-week interval (hazard ratio = 2.01 [95% CI 1.43, 2.82], p < 0.001). Patients with DME on longer anti-VEGF treatment intervals at 24 months consistently had higher discontinuation rates in the following years than those on shorter treatment intervals

Attendance in a national screening program for diabetic retinopathy:a population-based study of 205,970 patients

AIMS: A nationwide diabetic retinopathy (DR) screening program has been established in Denmark since 2013. We aimed to perform an evaluation of adherence to DR screenings and to examine whether non-adherence was correlated to DR progression. METHODS: The population consisted of a register-based cohort, who participated in the screening program from 2013 to 2018. We analyzed age, gender, marital status, DR level (International Clinical DR severity scale, none, mild-, moderate-, severe non-proliferative DR (NPDR) and proliferative DR (PDR)), comorbidities and socioeconomic factors. The attendance pattern of patients was grouped as either timely (no delays > 33%), delayed (delays > 33%) or one-time attendance (unexplained). RESULTS: We included 205,970 patients with 591,136 screenings. Rates of timely, delayed and one-time attendance were 53.0%, 35.5% and 11.5%, respectively. DR level at baseline was associated with delays (mild-, moderate-, severe NPDR and PDR) and one-time attendance (moderate-, severe NPDR and PDR) with relative risk ratios (RRR) of 1.68, 2.27, 3.14, 2.44 and 1.18, 2.07, 1.26, respectively (P < 0.05). Delays at previous screenings were associated with progression to severe NPDR or PDR (hazard ratio (HR) 2.27, 6.25 and 12.84 for 1, 2 and 3+ delays, respectively). Any given delay doubled the risk of progression (HR 2.28). CONCLUSIONS: In a national cohort of 205,970 patients, almost half of the patients attended DR screening later than scheduled or dropped out after first screening episode. This was, in particular, true for patients with any levels of DR at baseline. DR progression in patients with delayed attendance, increased with the number of missed appointments

Cerebrospinal fluid biomarkers for predicting development of multiple sclerosis in acute optic neuritis: a population-based prospective cohort study

Background: Long-term outcome in multiple sclerosis (MS) depends on early treatment. In patients with acute optic neuritis (ON), an early inflammatory event, we investigated markers in cerebrospinal fluid (CSF), which may predict a diagnosis of MS. Methods: Forty patients with acute ON were recruited in a prospective population-based cohort with median 29 months (range 19–41) of follow-up. Paired CSF and serum samples were taken within 14 days (range 2–38), prior to treatment. Prospectively, 16/40 patients were by a uniform algorithm diagnosed with MS (MS-ON) and 24 patients continued to manifest isolated ON (ION) during follow-up. Levels of cytokines and neurofilament light chain (NF-L) were measured at the onset of acute ON and compared to healthy controls (HC). Significance levels were corrected for multiple comparisons (“q”). The predictive value of biomarkers was determined with multivariable prediction models using nomograms. Results: CSF TNF-α, IL-10, and CXCL13 levels were increased in MS-ON compared to those in ION patients (q = 0.021, 0.004, and 0.0006, respectively). MS-ON patients had increased CSF pleocytosis, IgG indices, and oligoclonal bands (OCBs) compared to ION (q = 0.0007, q = 0.0058, and q = 0.0021, respectively). CSF levels of IL-10, TNF-a, IL-17A, and CXCL13 in MS-ON patients correlated with leukocyte counts (r &gt; 0.69 and p &lt; 0.002) and IgG index (r &gt; 0.55, p &lt; 0.037). CSF NF-L levels were increased in ON patients compared to those in HC (q = 0.0077). In MS-ON, a progressive increase in NF-L levels was observed at 7 to 14 days after disease onset (r = 0.73, p &lt; 0.0065). Receiver-operating characteristic (ROC) curves for two multivariable prediction models were generated, with IL-10, CXCL13, and NF-L in one (“candidate”) and IgG index, OCB, and leukocytes in another (“routine”). Area under the curve was 0.89 [95% CI 0.77–1] and 0.86 [0.74–0.98], respectively. Predictions of the risk of MS diagnosis were illustrated by two nomograms. Conclusions: CSF TNF-α, IL-10, CXCL13, and NF-L levels were associated with the development of MS, suggesting that the inflammatory and neurodegenerative processes occurred early. Based on subsequent diagnosis, we observed a high predictive value of routine and candidate biomarkers in CSF for the development of MS in acute ON. The nomogram predictions may be useful in the diagnostic work-up of MS

Physiological and molecular characterization of yeast cultures pre&#8208;adapted for fermentation of lignocellulosic hydrolysate.

Economically feasible bioethanol process from lignocellulose requires efficient fermentation by yeast of all sugars present in the hydrolysate. However, when exposed to lignocellulosic hydrolysate, Saccharomyces cerevisiae is challenged with a variety of inhibitors that reduce yeast viability, growth, and fermentation rate, and in addition damage cellular structures. In order to evaluate the capability of S. cerevisiae to adapt and respond to lignocellulosic hydrolysates, the physiological effect of cultivating yeast in the spruce hydrolysate was comprehensively studied by assessment of yeast performance in simultaneous saccharification and fermentation (SSF), measurement of furaldehyde reduction activity, assessment of conversion of phenolic compounds and genome&#8208;wide transcription analysis. The yeast cultivated in spruce hydrolysate developed a rapid adaptive response to lignocellulosic hydrolysate, which significantly improved its fermentation performance in subsequent SSF experiments. The adaptation was shown to involve the induction of NADPHdependent aldehyde reductases and conversion of phenolic compounds during the fed&#8208;batch cultivation. These properties were correlated to the expression of several genes encoding oxidoreductases, notably AAD4, ADH6, OYE2/3, and YML131w. The other most significant transcriptional changes involved genes involved in transport mechanisms, such as YHK8, FLR1, or ATR1. A large set of genes were found to be associated with transcription factors (TFs) involved in stress response (Msn2p, Msn4p, Yap1p) but also cell growth and division (Gcr4p, Ste12p, Sok2p), and these TFs were most likely controlling the response at the post&#8208;transcriptional level