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Aim: We investigated the effect of 52‐week treatment with liraglutide, a glucagon‐like peptide 1 receptor agonist, on glucose tolerance and incretin effect in women with previous gestational diabetes mellitus (pGDM). Materials and Methods: Women with overweight/obesity and pGDM were randomized to once daily subcutaneous liraglutide 1.8 mg or placebo for 52 weeks. Participants underwent oral glucose tolerance test (OGTT) and isoglycaemic intravenous glucose infusion at baseline and at 52 weeks, and an additional OGTT after the drug wash‐out. Results: In total, 104 women [age: mean ± SD, 38 ± 5 years; fasting plasma glucose (FPG): 5.5 ± 0.4 mmol/L; glycated haemoglobin (HbA1c): 33 ± 4 mmol/mol, bodyweight: 88.2 ± 14.8 kg, body mass index: 31.1 ± 4.3 kg/m2] were assigned to liraglutide (n = 49) or placebo (n = 55). Estimated treatment difference (ETD) for area under curve during OGTT was −173 (95% confidence interval −250 to −97) mmol/L × min, p <.0001, but after wash‐out the difference disappeared [ETD 58 (−30 to 146) mmol/L × min, p =.536]. Liraglutide reduced FPG [ETD −0.2 (−0.4 to −0.1) mmol/L, p =.018], HbA1c [−2.2 (−3.5 to −0.8) mmol/mol, p =.018] and bodyweight [−3.9 (−6.2 to −1.6) kg, p =.012]. No change in the incretin effect was observed. The number of women with prediabetes was reduced from 64% to 10% with liraglutide vs. 50% with placebo [adjusted odds ratio 0.10 (0.03‐0.32), p =.002]. Conclusions: Treatment with liraglutide for 52 weeks improved glucose tolerance, FPG, HbA1c and bodyweight in women with overweight/obesity and pGDM. Progression to prediabetes while on drug was markedly reduced, but after a 1‐week drug wash‐out, the effect was lost. [ABSTRACT FROM AUTHOR]

Objectives: Cognitive impairment affects many patients with bipolar disorder (BD), and treatments with replicated pro‐cognitive effects are lacking. This study aimed to assess the effect of Action‐Based Cognitive Remediation (ABCR) vs control treatment on cognitive impairment in patients with BD. Methods: Patients with remitted BD with objective cognitive impairment were randomized to 10 weeks of ABCR vs control treatment, and assessed at baseline, after 2 weeks of treatment, at treatment completion and at 6 months follow‐up. The primary outcome was a cognitive composite score. Secondary outcomes were executive function and observer‐rated functional capacity. Tertiary measures included additional neuropsychological tests, performance‐based functional capacity and quality of life. Data were analysed with linear mixed effects models. Results: In total, 64 participants were randomized; given three dropouts before the baseline assessments, data were analysed for 61 participants (ABCR: n = 32, control: n = 29). There was no effect on ABCR vs control on the primary cognitive composite score (P‐values ≥.60). At treatment completion, there was a large effect of ABCR vs control on the secondary executive function measure (treatment effect= −0.16, 95% CI [−0.27, −0.05], P ≤.01, d = 0.65), and on subjective cognitive functioning (treatment effect = −5.38, 95% CI [−8.13, −2.67], P ≤.001, d = 0.80), which disappeared at follow‐up. There was no treatment‐effect on functioning, and no association between cognitive and functional change. Conclusions: There was no effect of ABCR on the cognitive composite score. However, there was an effect on executive function and subjective cognitive functioning suggesting that ABCR may be relevant for patients with executive dysfunction. Trial Registration: ClinicalTrials.gov identifier: NCT03295305. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether a combination of topical nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids were superior in controlling early postoperative inflammation after cataract surgery compared with topical NSAIDs alone and with dropless surgery where a sub-Tenon depot of steroid was placed during surgery. Setting: Department of Ophthalmology, Rigshospitalet-Glostrup, Denmark. Design: Prospective randomized controlled trial with masked statistical analyses. Methods: Patients undergoing phacoemulsification for age-related cataract were randomized to 1 of 5 regimens: ketorolac and prednisolone eyedrops combined (Pred+NSAID-Pre [control group] and Pred+NSAID-Post group) vs ketorolac monotherapy (NSAID-Pre and NSAID-Post groups) vs sub-Tenon depot of dexamethasone (dropless group). Drops were used until 3 weeks postoperatively, starting 3 days preoperatively in the Pre groups and on the day of surgery in the Post groups. Aqueous flare was measured at baseline and 3 days postoperatively. Results: Four hundred fifty-six participants, with a mean age of 72.1 (SD 7.0) years and 283 (62%) women, were included. Flare increased significantly more in the dropless group compared with the control group (Pred+NSAID-Pre), but none of the other groups differed significantly from the control group. Intraocular pressure decreased in all groups but significantly less in groups receiving prednisolone eyedrops (Pred+NSAID-Pre and Pred+NSAID-Post groups) compared with NSAID monotherapy and dropless groups. No differences in postoperative visual acuity were found compared with the control group. Conclusions: No differences were found between groups randomized to NSAID monotherapy or combination of NSAID and steroid in controlling early inflammation after cataract surgery, but sub-Tenon depot of dexamethasone was less efficient. Initiating prophylactic eyedrops prior to surgery did not influence early postoperative anterior chamber inflammation. [ABSTRACT FROM AUTHOR]

Background: Treatment development that targets cognitive impairment is hampered by a lack of biomarkers that can predict treatment efficacy. Erythropoietin (EPO) improves verbal learning and memory in mood disorders, and this scales with an increase in left hippocampal volume. This study investigated whether pretreatment left hippocampal volume, interhemisphere hippocampal asymmetry or both influenced EPO treatment response with respect to verbal learning. Methods: Data were available for 76 of 83 patients with mood disorders from our previous EPO trials (EPO = 37 patients; placebo = 39 patients). We performed cortical reconstruction and volumetric segmentation using FreeSurfer. We conducted multiple linear regression and logistic regression to assess the influence of left hippocampal volume and hippocampal asymmetry on EPO-related memory improvement, as reflected by change in Rey Auditory Verbal Learning Test total recall from baseline to post-treatment. We set up a corresponding exploratory general linear model in FreeSurfer to assess the influence of prefrontal cortex volume on verbal learning improvement, controlling for age, sex and total intracranial volume. Results: At baseline, more rightward (left < right) hippocampal asymmetry -- but not left hippocampal volume per se -- was associated with greater effects of EPO versus placebo on verbal learning (p ≤ 0.05). Exploratory analysis indicated that a larger left precentral gyrus surface area was also associated with improvement of verbal learning in the EPO group compared to the placebo group (p = 0.002). Limitations: This was a secondary analysis of our original EPO trials. Conclusion: Rightward hippocampal asymmetry may convey a positive effect of EPO treatment efficacy on verbal learning. [ABSTRACT FROM AUTHOR]

Abstract: We explored use of the suction‐blister wound model in the assessment of not only epidermal regeneration but also pain, the microvascular response and bacteriology. The effects of topical zinc sulfate were studied to articulate the methodologies in this double‐blind trial. One epidermal suction blister (10 mm) was induced on each buttock in 30 healthy volunteers (15 females:15 males) and deroofed on day 0. The wounds were randomized to daily treatment with 1.4% zinc sulfate shower gel (n = 20), placebo (n = 20) or control (n = 20). Digital photography coupled with planimetry, transepidermal water loss (TEWL) measurement and optical coherence tomography (OCT) was benchmarked to the gold standard of histology of 60 full‐thickness wound biopsies on day 4. Pain increased after application of the shower gels. Microvessel density, determined from OCT images, increased from day 0 to day 2 in the three groups but increased more with the placebo than with the zinc shower gel (p = 0.003) or the control treatment (p = 0.002) and correlated (rS = 0.313, p = 0.015) with the inflammatory response on day 4, as determined by histology. Coagulase‐negative staphylococci were more common in wounds compared with skin (p = 0.002) and was reduced (p = 0.030) with zinc sulfate treatment. Planimetric analysis of digital wound images was not biased (p = 0.234) compared with histology, and TEWL measurements showed no correlation (rS = 0.052, p = 0.691) with epithelialization. Neoepidermal formation, determined by histology, did not differ (p = 0.290) among the groups. Zinc sulfate reduced (p = 0.031) the release of lactate dehydrogenase from cultured gel‐treated keratinocytes isolated from the blister roofs. Therefore, combination of the standardized suction‐blister wound model with noninvasive planimetry and OCT is a useful tool for assessing wound therapies. Zinc sulfate transiently dampened inflammation and reduced bacterial growth. [ABSTRACT FROM AUTHOR]

To our knowledge, this is the first study reporting the effect of sodium-glucose cotransporter 2 inhibitors on insulin resistance in patients who have HFrEF primarily without diabetes. In total, 120 patients were enrolled,[4] including 108 (90%) patients without a history of T2D, of whom 19 (18%) had new-onset T2D and 35 (32%) had impaired glucose tolerance based on the oral glucose tolerance testing. Keywords: body composition; diabetes mellitus, type 2; empagliflozin; heart failure; insulin resistance; sodium-glucose transporter 2 inhibitors EN body composition diabetes mellitus, type 2 empagliflozin heart failure insulin resistance sodium-glucose transporter 2 inhibitors 2208 2210 3 06/02/21 20210601 NES 210601 The general notion has been that the mechanisms behind the clinical benefits of sodium-glucose cotransporter 2 inhibitors in patients with heart failure and reduced ejection fraction (HFrEF) are related to effects beyond improved glycemic control.[1] However, insulin resistance is a common metabolic characteristic of heart failure, and improved insulin resistance may better the long-term prognosis,[2] for example, by preventing type 2 diabetes (T2D) or by reverse cardiac remodeling. [Extracted from the article]