NIMO-CKD-UK: a real-world, observational study of iron isomaltoside in patients with iron deficiency anaemia and chronic kidney disease.

BACKGROUND: Intravenous iron is often used to treat iron deficiency anaemia in non-dialysis chronic kidney disease (ND-CKD), but the optimal dosing regimen remains unclear. We evaluated the impact of high- versus low-dose intravenous iron isomaltoside on the probability of retreatment with intravenous iron in iron-deficient ND-CKD patients. METHODS: This real-world, prospective, observational study collected data from 256 ND-CKD patients treated for anaemia in the UK. Following an initial course of iron isomaltoside, patients were followed for ≥12 months. Iron dose and the need for retreatment were determined at the investigators' discretion. The primary study outcome was the need for retreatment at 52 weeks compared between patients who received >1000 mg of iron during Course 1 and those who received ≤1000 mg. Safety was evaluated through adverse drug reactions. RESULTS: The probability of retreatment at Week 52 was significantly lower in the >1000 mg iron group (n = 58) versus the ≤1000 mg group (n = 198); hazard ratio (95% confidence interval [CI]): 0.46 (0.20, 0.91); p = 0.012. Mean (95% CI) haemoglobin increased by 6.58 (4.94, 8.21) g/L in the ≤1000 mg group and by 10.59 (7.52, 13.66) g/L in the >1000 mg group (p = 0.024). Changes in other blood and iron parameters were not significantly different between the two groups. Administering >1000 mg of iron isomaltoside saved 8.6 appointments per 100 patients compared to ≤1000 mg. No serious adverse drug reactions were reported. Of the patients who received ≤1000 mg of iron in this study, 82.3% were eligible for a dose >1000 mg. CONCLUSIONS: The >1000 mg iron isomaltoside regimen reduced the probability of retreatment, achieved a greater haemoglobin response irrespective of erythropoiesis-stimulating agent treatment, and reduced the total number of appointments required, compared to the ≤1000 mg regimen. Many of the patients who received ≤1000 mg of iron were eligible for >1000 mg, indicating that there was considerable underdosing in this study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02546154 , 10 September 2015.

The use of daily disposable lenses in problematic reusable contact lens wearers.

PURPOSE: Replacing soft contact lenses (CLs) on a daily basis brings a number of advantages, most notably, reduced exposure to deposits, disinfectants, allergens, and other contaminants. This retrospective study estimated the prevalence of problems in current wearers of reusable soft CLs and tested the effect of refitting "problem" patients with daily disposable (DD) hydrogel lenses. METHODS: Prevalence was estimated from 398 current reusable CL wearers for: frequent/constant discomfort or dryness, ≥2 h of uncomfortable wear, ≥grade 2 conjunctival hyperaemia (0-4), or ≥grade 3 corneal staining (0-15). In the second part of the study, 217 reusable CL wearers classified as problem patients were randomly refitted with DD lenses manufactured from one of two materials: etafilcon A (n=96) or nelfilcon A (n=121) and reassessed 1 week later. RESULTS: Thirty-nine percent (154/398) had some qualifying criterion: reduced comfortable wearing time (CWT), 20%; dryness, 20%; irritation, 5%; corneal staining, 8%; and hyperaemia, 7%. After refitting with DDs, the prevalence of reduced CWT was decreased from 65% to 51% (P=0.0039), dryness from 60% to 41% (P < 0.0001) and corneal staining from 28% to 21% (P=0.04). There was no significant change in the prevalence of irritation, or hyperaemia. Some differences were noted between the two lens materials. CONCLUSIONS: A high proportion of reusable soft lens wearers encounter clinically relevant signs or symptoms with their current CLs. This study provides evidence that refitting with DD lenses is a useful strategy for alleviating some of the common problems of CL wear.

Eye sensitivity in soft contact lens wearers.

PURPOSE: To estimate the prevalence of self-reported "sensitive eyes" (SEs) in soft contact lens (CL) wearers, evaluate the clinical characteristics of patients with SEs, and examine the effect of refitting them with silicone hydrogel lenses. METHODS: After self-assessment, 2154 CL wearers were separated into SE and non-SE patients. Demographics, biometric data, wearing time, symptoms, and signs were compared between the two populations. Sixty-three SE patients were randomized into senofilcon A (senA) lenses and 65 into a non-senA arm (lotrafilcon B, omafilcon A, and balafilcon A lenses). The performance of senA lenses was compared against habitual and non-senA lenses 2 weeks later. RESULTS: A total of 12.2% of CL wearers reported SEs with their habitual CLs. No significant differences were noticed between SE and non-SE patients in sex, age, or refraction. The prevalence of dryness (43 vs 19%, p < 0.0001), irritation (25 vs 11%, p < 0.0001), redness (20 vs 6%, p < 0.0001), and stinging (6 vs 1%, p < 0.0001) was higher in SE patients. Average wearing time (13.0 vs 14.1 hours, p < 0.0001) was lower in this group. Limbal/bulbar hyperemia and corneal/conjunctival staining were not significantly different between the two populations. Senofilcon A increased the number of patients reporting no dryness (habitual vs senA, 20 vs 44%, p < 0.0003), irritation (22 vs 37%, p = 0.015), redness (52 vs 76%, p =0.009) and stinging (58 vs 77%, p = 0.012) but did not significantly affect clinical signs. Senofilcon A was significantly more efficient than non-senA lenses in improving dryness (scale of 0 to 3: senA vs non-senA, 0.64 vs 1.02, p = 0.0056), irritation (0.72 vs 1.16, p = 0.0015), and stinging (0.18 vs 0.53, p = 0.0049). CONCLUSIONS: A substantial proportion of CL wearers report SEs with their habitual lenses. These patients are characterized by a high prevalence of additional symptoms, which are not reflected in clinical signs. Senofilcon A, or lenses with similar properties, may help reduce these symptoms in SE patients.

LXR as a novel antithrombotic target.

Liver X receptors (LXRs) are transcription factors involved in the regulation of cholesterol homeostasis. LXR ligands have athero-protective properties independent of their effects on cholesterol metabolism. Platelets are involved in the initiation of atherosclerosis and despite being anucleate express nuclear receptors. We hypothesized that the athero-protective effects of LXR ligands could be in part mediated through platelets and therefore explored the potential role of LXR in platelets. Our results show that LXR-ß is present in human platelets and the LXR ligands, GW3965 and T0901317, modulated nongenomically platelet aggregation stimulated by a range of agonists. GW3965 caused LXR to associate with signaling components proximal to the collagen receptor, GPVI, suggesting a potential mechanism of LXR action in platelets that leads to diminished platelet responses. Activation of platelets at sites of atherosclerotic lesions results in thrombosis preceding myocardial infarction and stroke. Using an in vivo model of thrombosis in mice, we show that GW3965 has antithrombotic effects, reducing the size and the stability of thrombi. The athero-protective effects of GW3965, together with its novel antiplatelet/thrombotic effects, indicate LXR as a potential target for prevention of athero-thrombotic disease.