The Relationship Between Visual Sensitivity and Eccentricity,Cone Density and Outer Segment Length in the Human Foveola

PurposeThe cellular topography of the human foveola, the central 1° diameter of the fovea, is strikingly non-uniform, with a steep increase of cone photoreceptor density and outer segment (OS) length toward its center. Here, we assessed to what extent the specific cellular organization of the foveola of an individual is reflected in visual sensitivity and if sensitivity peaks at the preferred retinal locus of fixation (PRL).MethodsIncrement sensitivity to small-spot, cone-targeted visual stimuli (1 × 1 arcmin, 543-nm light) was recorded psychophysically in four human participants at 17 locations concentric within a 0.2° diameter on and around the PRL with adaptive optics scanning laser ophthalmoscopy-based microstimulation. Sensitivity test spots were aligned with cell-resolved maps of cone density and cone OS length.ResultsPeak sensitivity was at neither the PRL nor the topographical center of the cone mosaic. Within the central 0.1° diameter, a plateau-like sensitivity profile was observed. Cone density and maximal OS length differed significantly across participants, correlating with their peak sensitivity. Based on these results, biophysical simulation allowed to develop a model of visual sensitivity in the foveola, with distance from the PRL (eccentricity), cone density, and OS length as parameters.ConclusionsSmall-spot sensitivity thresholds in healthy retinas will help to establish the range of normal foveolar function in cell-targeted vision testing. Because of the high reproducibility in replicate testing, threshold variability not explained by our model is assumed to be caused by individual cone and bipolar cell weighting at the specific target locations.     

A Blueprint of Pain Curriculum Across Prelicensure Health Sciences Programs: One NIH Pain Consortium Center of Excellence in Pain Education (CoEPE) Experience

To improve U.S. pain education and promote interinstitutional and interprofessional collaborations, the National Institutes of Health Pain Consortium has funded 12 sites to develop Centers of Excellence in Pain Education (CoEPEs). Each site was given the tasks of development, evaluation, integration, and promotion of pain management curriculum resources, including case studies that will be shared nationally. Collaborations among schools of medicine, dentistry, nursing, pharmacy, and others were encouraged. The John D. Loeser CoEPE is unique in that it represents extensive regionalization of health science education, in this case in the region covering the states of Washington, Wyoming, Alaska, Montana, and Idaho. This paper describes a blueprint of pain content and teaching methods across the University of Washington’s 6 health sciences schools and provides recommendations for improvement in pain education at the prelicensure level. The Schools of Dentistry and Physician Assistant provide the highest percentage of total required curriculum hours devoted to pain compared with the Schools of Medicine, Nursing, Pharmacy, and Social Work. The findings confirm the paucity of pain content in health sciences curricula, missing International Association for the Study of Pain curriculum topics, and limited use of innovative teaching methods such as problem-based and team-based learning.     

Comparative Responsiveness of Verbal and Numerical Rating Scales to Measure Pain Intensity in Patients With Chronic Pain

Verbal rating scale (VRS) and numerical rating scale (NRS) are regularly used to assess and monitor pain in chronic pain patients. Although the NRS has been generally preferred, limited comparative responsiveness evidence was reported. This study compared the responsiveness of VRS and NRS measuring current pain and investigated the influence of different references (ie, worst, least, average, and current pain or their composite) on the NRSs' responsiveness. Two hundred fifty-four chronic pain patients attended a 10-day pain self-management program and were assessed with two 6-point VRSs (assessing current pain) and four 11-point NRSs (assessing worst, least, average, and current pain) at pre- and posttreatment. A patient-reported rating of pain improvement was used as the criterion for standardized response mean and receiver operating characteristic curve analyses. Results showed that the VRSs and NRSs exhibited small responsiveness in all patients, but the magnitude of responsiveness became moderate to large in patients with improved pain. However, in patients with pain improvements, the NRS current pain item and composite score (made up of the 4 pain items) were found to have significantly larger responsiveness and greater discriminatory ability to detect the presence of improvement than other current pain VRSs and the NRSs assessing worst, least, and average pain. Potential implications for clinical practice are discussed.     

Face Naming and Retrieval Inhibition in Old and Very Old Age

Background/Study Context: Aging has traditionally been related to impairments in proper name retrieval. This study analyzed the possible role of the Inhibitory Deficit Hypothesis in explaining face naming impairments during aging. The dynamics of inhibition have been thoroughly studied by the retrieval-practice paradigm (Anderson, Bjork, & Bjork, 1994, Journal of Experimental Psychology: Learning, Memory, and Cognition, 20, 1063–1087) and its aftereffect, the retrieval-induced forgetting effect.

Methods: A version of the retrieval-practice paradigm was employed: younger-old (YO; mean age = 66.40, SD = 3.94) and older-old (OO; mean age = 80.94, SD = 4.53) adults were asked to repeatedly name faces of categorically related famous people.

Results: Retrieval-induced forgetting for names was observed in the YO group but not in the OO group.

Conclusion: These findings indicate that whereas the YO adults had enough resources to inhibit intrusive names, OO adults were not able to suppress competing names, supporting the proposal of the Inhibitory Deficit Hypothesis at older ages.     

Adding Once-Daily Lixisenatide for Type 2 Diabetes Inadequately Controlled by Established Basal Insulin: A 24-week,randomized, placebo-controlled comparison (GetGoal-L)

OBJECTIVE

To examine the efficacy and safety of adding the once-daily glucagon-like peptide-1 receptor agonist (GLP-1RA) lixisenatide to established basal insulin therapy alone or together with metformin, in people with type 2 diabetes and elevated glycated hemoglobin (HbA_1c).

RESEARCH DESIGN AND METHODS

We conducted a double-blind, parallel-group, placebo-controlled trial. Patients (n = 495) with established basal insulin therapy but inadequate glycemic control were randomized to add lixisenatide 20 μg or placebo for 24 weeks. Basal insulin dosage was unchanged except to limit hypoglycemia. HbA_1c reduction from baseline was the primary end point.

RESULTS

Mean duration of diabetes was 12.5 years, duration of insulin use was 3.1 years, insulin dosage was 55 units/day, and baseline HbA_1c was 8.4%. With lixisenatide, the placebo-corrected change of HbA_1c from baseline was –0.4% (95% CI –0.6 to –0.2; P = 0.0002), and mean HbA_1c at end point was 7.8%. HbA_1c <7.0% (53 mmol/mol) was attained by more lixisenatide (28%) than placebo (12%; P < 0.0001) participants. Lixisenatide reduced plasma glucose levels after a standardized breakfast (placebo-corrected reduction, –3.8 mmol/L; P < 0.0001); seven-point glucose profiles showed a reduction persisting through the day. Reductions in body weight (placebo corrected, –1.3 kg; P < 0.0001) and insulin dosage (–3.7 units/day; P = 0.012) were greater with lixisenatide. Main adverse events (AEs) with lixisenatide were gastrointestinal. Symptomatic hypoglycemia was 28% for lixisenatide and 22% for placebo; 4 of 328 subjects (1.2%) had severe hypoglycemia with lixisenatide vs. 0 of 167 with placebo.

CONCLUSIONS

By improving HbA_1c and postprandial hyperglycemia without weight gain in type 2 diabetes with inadequate glycemic control despite stable basal insulin, lixisenatide may provide an alternative to rapid-acting insulin or other treatment options.In type 2 diabetes, additional therapies are needed over time to maintain acceptable glycemic control (1–3). When lifestyle measures and oral antihyperglycemic agents are no longer sufficient, the addition of basal insulin optimized by systematic titration of dosage can restore glycated hemoglobin (HbA_1c) to 7.0% for 50–60% of people with type 2 diabetes (2,4,5). However, some people do not initially achieve this glycemic target with basal insulin plus oral therapy, and others experience later deterioration of control (6–9). Further therapy, especially for postprandial hyperglycemia, is then needed. A traditional option has been to add one or more injections of prandial insulin (10), but adding a glucagon-like peptide-1 receptor agonist (GLP-1RA) is a recently proposed alternative that may improve glycemic control without additional weight gain and, perhaps, with less hypoglycemia. Drugs of this class have effects that complement those of basal insulin; they potentiate endogenous insulin responses to hyperglycemia, suppress inappropriately elevated glucagon secretion, and favor weight loss by promoting satiety (11,12). In addition, GLP-1RAs can slow gastric emptying, further blunting postprandial hyperglycemia. However, slowing of gastric emptying appears to be greater with short-acting than with long-acting GLP-1RAs (13), possibly related to the observation that, with time, continuous exposure of GLP-1 leads to a reduction in its effect on gastric emptying (14).Lixisenatide is a novel GLP-1RA that, like other drugs of its class, has demonstrated significant improvements in glycemic control, low rates of hypoglycemia, and a beneficial effect on weight (15–17). Lixisenatide taken once daily (15) improves HbA_1c levels by reducing fasting plasma glucose (FPG) and has robust postprandial glucose (PPG) effects (18,19). Lixisenatide was granted marketing authorization by the European Medicines Agency in February 2013 (20). The objective of this study was to examine the efficacy and safety of adding once-daily lixisenatide to established basal insulin therapy (dosage maintained except for the avoidance of hypoglycemia), alone or together with metformin, in people with long-duration type 2 diabetes and inadequate glycemic control.