The Royal College of Paediatrics and Child Health Retinopathy of Prematurity Screening Guidelines (2022): a series of treated infants falling outside the updated criteria.

BACKGROUND/OBJECTIVES: Screening for retinopathy of prematurity (ROP) is a core healthcare intervention in premature babies to avoid preventable sight loss. A variety of screening criteria are in place globally for this purpose. The Royal College of Paediatrics and Child Health recently updated the United Kingdom ROP screening guidelines (March 2022). A key change was the reduction in the gestational age (GA) to warrant retinal screening (from 32 to 31 weeks). SUBJECTS/METHODS: In the course of informal national surveillance during guideline development (2017-2022) and soon after, babies under our care falling outside the updated screening criteria who underwent treatment for ROP were identified. A retrospective case review was carried out. RESULTS: Six babies were identified as having undergone screening and treatment, prior to implementation of the new guidance. Screening and treatment would have been forfeited as per the March 2022 guidelines. All six had numerous systemic risk factors for developing ROP. Specifically, all had documented poor postnatal weight gain. CONCLUSIONS: We present this case series to bring forth an urgent discussion amongst key stakeholders as to whether the new guidance, as it stands, is safe and fit for purpose.

A Case of Morning Glory Disc Associated With Unilateral Retinopathy of Prematurity.

Morning glory disc anomaly is associated with serous retinal detachments, high refractive errors, amblyopia, and strabismus. There have been limited reports of an association between morning glory disc and peripheral retinal non-perfusion. The authors report a case of unilateral morning glory disc anomaly associated with markedly asymmetric retinopathy of prematurity. [J Pediatr Ophthalmol Strabismus. 2022;59(5):e55-e57.].

Postoperative diplopia test-repeatability and prediction of surgical outcomes.

BACKGROUND: The postoperative diplopia test (PODT) is used to assess the risk of postoperative diplopia in older children and adults prior to strabismus surgery for nonfunctional reasons. The purpose of this study was to evaluate the test-retest and interobserver reliability of the PODT and its predictive value in assessing diplopia risk. METHODS: In the first phase of this study, the repeatability of the PODT method was prospectively assessed with two groups of patients (group 1, test-retest; group 2, interobserver). In the second phase, notes were reviewed retrospectively to evaluate the predictive value of the PODT. RESULTS: For phase 1, 39 participants were recruited. In group 1, 12 participants showed agreement in the area of suppression for both near and distance fixation; 8 showed variability. In group 2, 10 showed agreement for near, and 9 showed variability; 9 showed agreement for distance, and 10 showed variability. Group 1 differences ranged from 0 to 9 points (median, 0.5; IQR, 0-3); group 2, from 0 to 36 points (median, 1; IQR, 0-4.5). In phase 2, outcomes of 39 strabismus surgeries were reviewed: none of the patients without diplopia on PODT and 2 of 14 patients with diplopia on PODT had persistent diplopia 3 months after surgery. CONCLUSIONS: Many patients develop diplopia postoperatively, but this generally resolves spontaneously. Current testing procedures have excessive test-retest and interobserver variability and insufficient predictive value to be useful in predicting postoperative diplopia.

Insights from the evaluations of the NIH Centers for Accelerated Innovation and Research Evaluation and Commercialization Hubs programs.

BACKGROUND: The National Institutes of Health launched the NIH Centers for Accelerated Innovation and the Research Evaluation and Commercialization Hubs programs to develop approaches and strategies to promote academic entrepreneurship and translate research discoveries into products and tools to help patients. The two programs collectively funded 11 sites at individual research institutions or consortia of institutions around the United States. Sites provided funding, project management, and coaching to funded investigators and commercialization education programs open to their research communities. METHODS: We implemented an evaluation program that included longitudinal tracking of funded technology development projects and commercialization outcomes; interviews with site teams, funded investigators, and relevant institutional and innovation ecosystem stakeholders and analysis and review of administrative data. RESULTS: As of May 2021, interim results for 366 funded projects show that technologies have received nearly $1.7 billion in follow-on funding to-date. There were 88 start-ups formed, a 40% Small Business Innovation Research/Small Business Technology Transfer application success rate, and 17 licenses with small and large businesses. Twelve technologies are currently in clinical testing and three are on the market. CONCLUSIONS: Best practices used by the sites included leadership teams using milestone-based project management, external advisory boards that evaluated funding applications for commercial merit as well as scientific, sustained engagement with the academic community about commercialization in an effort to shift attitudes about commercialization, application processes synced with education programs, and the provision of project managers with private-sector product development expertise to coach funded investigators.

10-year trends in English primary care glaucoma prescribing.

BACKGROUND: In 2018 NHS prescriptions in England cost £8.83 billion. Within ophthalmic prescribing, glaucoma is the most costly indication. The 2017 glaucoma NICE guideline shows there is little evidence for clinical preference of particular molecules within a therapeutic class, yet the cost of these products varies greatly. We aim to describe trends in glaucoma prescribing and its relation to recent NICE Guidance. METHODS: Prescription cost analyses for England from 2009 to 2018 were reviewed and data concerning items for the treatment of glaucoma were extracted. Costs and prescription frequencies were normalised for inflation and population. RESULTS: The 2018 cost of glaucoma prescribing was £114.2 million. This cost is 18.1% lower than in 2009 but the annual number of items prescribed per 10,000 people has increased from 1382 to 1668 (20.7%). This is despite an increased prescription of combination drops from 265 to 478 per 10,000 (80.4%). Preservative free item prescriptions rose from 1.7% of total spend in 2009, at £3.4 million in 2009, to 13.9%, in 2018, at £22.5 million. Generic items represented 11.7% of prescriptions in 2009 and 55.2% in 2018. Around half of glaucoma spending is accounted for by the use of preservative free or branded items in the place of the cheapest item in each therapeutic class. CONCLUSIONS: Glaucoma prescribing costs the NHS a great deal. There is a broad trend to generic prescribing as per recent NICE guidance, but significant further costs could be saved with no robustly evidenced clinical consequence.

Folding and Assembly of Short α, ß, γ-Hybrid Peptides: Minor Variations in Sequence and Drastic Differences in Higher-Level Structures.

Multilevel protein structures typically involve polypeptides of sufficient lengths. Here we report the folding and assembly of seven short tetrapeptides sharing the same types of α-, ß-, and aromatic γ-amino acid residues. These are two sets of hybrid peptides, with three members in one set and four in the other, having complementary hydrogen-bonding sequences that were hypothesized to pair into linear H-bonded duplexes. However, instead of undergoing the anticipated pairing, the initially examined three oligomers, 1 and 2a or 2b, differing only in their central αß hybrid dipeptide sequence, do not associate with each other and exhibit distinctly different folding behavior. Experiments based on NMR and mass spectrometry, along with computational studies and systematic inference, reveal that oligomer 1 folds into an expanded ß-turn containing an unusual hybrid α/ß-amino acid sequence composed of glycine and ß-alanine, two α- and ß-amino acid residues that are conformationally most flexible, and peptides 2a and 2b adopt a noncanonical, extended helical conformation and dimerize into double helices undergoing rapid conformational exchange or helix inversion. The different central dipeptide sequences, αß vs ßα, result in drastically different intramolecular H-bonding patterns that are responsible for the observed folding behavior of 1 and 2. The revealed turn and double helix have few natural or synthetic counterparts, and provide novel and unique folding prototypes based on which chiral α- and ß-amino acids are incorporated. The resultant derivatives 1a, 1b, 2c, and 2d follow the same folding and assembling behavior and demonstrate the generality of this system with the formation of expanded ß-turns and double helices with enhanced folding stabilities, hampered helix inversion, as well as defined and dominant helical sense. This work has demonstrated the unique capability of synthetic foldamers in generating structures with fascinating folding and assembling behavior. The revealed systems offer ample opportunity for further structural optimization and applications.

Effects of Oligomer Length, Solvents, and Temperature on the Self-Association of Aromatic Oligoamide Foldamers.

The effects of oligomer length, solvent, and temperature on the self-association of stably folded short aromatic oligoamide are probed. With large flat surfaces, these aromatic oligoamides undergo stacking interaction with strength that increases nonlinearly with oligomer lengths. Opposite to typical aromatic stacking, the stacking of these molecules is enhanced in solvents of low polarity, but it is greatly weakened in polar solvents, especially those with hydrogen bond donors, and it is very sensitive to changes in temperature.

Ultra-low-dose intravitreal bevacizumab for the treatment of retinopathy of prematurity: a case series.

BACKGROUND: Intravitreal bevacizumab (IVB) has emerged as an effective treatment modality for the management of retinopathy of prematurity (ROP) where the disease is severe and posterior. Despite evidence of systemic vascular endothelial growth factor suppression and concerns about how this might affect the developing neonate, the optimal dose is unknown to date. We report our experience of using ultra-low-dose (0.16 mg) IVB, one-quarter of the 'standard' dose that has widely been reported in the treatment of ROP. METHODS: A retrospective observational case series of consecutive infants who underwent ultra-low-dose IVB injection for the management of ROP at a regional neonatal intensive care unit in the North East of England, between November 2013 and August 2016. RESULTS: 29 eyes of 15 infants underwent IVB injection. We defined 'treatment success' as complete regression of retinopathy and vascularisation into (or laser ablation of) zone 3. Primary success (in response to IVB 0.16 mg alone) was observed in 23/29 eyes (79.3%). Secondary success (where additional treatment was required) was observed in 27/29 eyes (93.1%). One infant died of respiratory disease during follow-up. Retreatment occurred in 6/29 eyes (20.6%). Retreatments occurred at a mean of 9.8 weeks after initial IVB (range 6-15) and at a mean of 44 weeks postmenstrual age (range 40-50). CONCLUSION: 0.16 mg IVB is effective in the treatment of severe and posterior ROP, with no adverse ocular outcomes occurring in our series.

Mapping of Standards to Facilitate Immunization Information Exchange through Two-Dimensional Bar Coding of Vaccine Products.

Purpose: A two-dimensional barcode that includes both static information (vaccine identifier) and variable information (expiration date and lot number) can facilitate streamlined documentation and sharing of vaccine administration. We sought to identify how vaccine tracking information in the two-dimensional barcode is represented in systems that are used by pharmacies, providers, and public health agencies. Methods: We identified and reviewed relevant information technology standards that govern data storage and exchange for providers, pharmacy systems, billing systems, and manufacturers to identify how each system codes the vaccine identifier, expiration date, and lot number. We selected standards commonly used by manufacturers, providers, and pharmacies and mapped the critical vaccine data elements across them. We shared the mapping with stakeholders to identify areas of alignment across standards and discussed how to address misalignment going forward. Results: Data elements were not consistently formatted in each type of information system. The vaccine lot number and expiration date were consistent, which would facilitate sharing across information systems. However, the way to identify a given vaccine is not consistent in each standard and would require manual entry. This inconsistency is related to the segmentation of the National Drug Code into three components. Therefore, vaccine identification methods differ across the systems governed by different standards. Conclusion: Patient safety can be enhanced by automated verification of the vaccine ordered versus the vaccine administered. Immunizers' back-end systems would benefit from automated documentation and reporting.

Enforced Tubular Assembly of Electronically Different Hexakis(m-Phenylene Ethynylene) Macrocycles: Persistent Columnar Stacking Driven by Multiple Hydrogen-Bonding Interactions.

Hexakis(m-phenylene ethynylene) (m-PE) macrocycles 1-4, sharing the same hydrogen-bonding side chains but having backbones of different electronic properties, are designed to probe the effectiveness of multiple H-bonding interactions in enforcing columnar assemblies. 1H NMR, absorption, fluorescence, and circular dichroism (CD) spectroscopy indicate that, compared with analogous macrocycles that self-associate based on aromatic stacking which is highly sensitive to the electronic nature of the macrocyclic backbones, macrocycles 1-4 all exhibit strong aggregation down to the micromolar (µM) concentrations in nonpolar solvents. Increasing solvent polarity quickly weakens aggregation. In THF and DMF, the macrocycles exist as free molecules. The observed solvent effects, along with the behavior of 5-F6 that cannot self-associate via H-bonding, confirm that H-bonding plays the dominating role in driving the self-association of 1-4. The backbone electronic nature does not change the self-assembling pattern common to 1-4. Fluorescence and CD spectra confirm that macrocycles 1-4 assemble anisotropically, forming helical stacks in which adjacent molecules undergo relative rotation to place individual benzene residues in the favorable offset fashion. Columnar alignment of 1-4 is confirmed by atomic force microscopy (AFM), which resolves single tubes consisting of stacked macrocycles. In addition, macrocycles with backbones of different electronic properties are found to undergo heteroassociation, forming hybrid nanotubes. This study has demonstrated the generality of enforcing the alignment of shape-persistent macrocycles, which represents an invaluable addition to the small number of known tubular stacks capable of accommodating structurally varied molecular components and provides self-assembling nanotubes with inner pores allowing ready structural and functional modification.

Helical Folding of Meta-Connected Aromatic Oligoureas.

Aromatic oligoureas composed of meta-linked residues bearing phenolic ether side chains are synthesized. The basic N,N'-diarylurea units adopt a trans,trans intramolecularly H-bonded conformation that is further strengthened by additional intermolecular H-bonding. Such basic units, in combination with meta-linked benzene residues, result in stably folded helical oligoureas in the highly polar DMF with up to four turns and with a small cylindrical inner pore that would be difficult to acquire.

Two Hour Evaluation and Referral Model for Shorter Turnaround Times in the emergency department.

OBJECTIVE: The objective of this study was to assess the implementation of a novel ED model of care, which combines clinical streaming, team-based assessment and early senior consultation to reduce length of stay. METHODS: A pre-post-intervention study was used to compare ED performance following an extensive clinical redesign programme. Clinical teams and work sequences were reconfigured to promote the role of the staff specialist, with a focus on earlier decisions regarding disposition. Primary outcome measures were ED length of stay and National Emergency Access Target (NEAT) compliance. Secondary outcomes included referral and workup times, wait times by triage category, ambulance offload times, ward discharges and unit transfers within 24 h of admission, representation within 48 h, and Medical Emergency Response Team (MERT) calls within 24 h of admission. RESULTS: Two seasonally matched 26 week intervals were compared with adjustment for demographics, triage category and arrival by ambulance. Overall, there was an 18.4% rise in NEAT performance (95% confidence interval (CI): 17.7-19.1) while ED length of stay decreased by a total of 86.8 min (95% CI: 83.6-90.1). Time series analysis did not suggest any preexisting trends to explain these results. The average time to referral decreased by 74.7 min (95% CI: 69.8-79.6) and waiting times decreased across all triage categories. Rates of MERT activation and unplanned representation were unchanged. CONCLUSION: A facilitated team leader role for senior doctors can help to reduce length of stay by via early disposition, without significant risks to the patient.

Aromatic oligureas as hosts for anions and cations.

Aromatic oligoureas 3 and 4 have urea moieties engaging in weak intramolecular H-bonding that constrains their backbones. The shorter 3a and 3b are able to bind chloride and acetate but not their corresponding counterion. The longer 4 binds both an anion and its counterion with the same affinity.

Ultra-low dose of intravitreal bevacizumab in the treatment of retinopathy of prematurity.

Intravitreal bevacizumab is an increasingly common treatment choice for posterior retinopathy of prematurity. Despite concern about its systemic effects, there have been few studies on the lowest effective dose. The authors describe a case that was successfully treated with 0.16 mg of bevacizumab, the first time this dose has been reported.

Economic analysis of opportunities to accelerate Alzheimer's disease research and development.

The development of disease-modifying treatments for Alzheimer's disease (AD) faces a number of barriers. Among these are the lack of surrogate biomarkers, the exceptional size and duration of clinical trials, difficulties in identifying appropriate populations for clinical trials, and the limitations of monotherapies in addressing such a complex multifactorial disease. This study sets out to first estimate the consequent impact on the expected cost of developing disease-modifying treatments for AD and then to estimate the potential benefits of bringing together industry, academic, and government stakeholders to co-invest in, for example, developing better biomarkers and cognitive assessment tools, building out advanced registries and clinical trial-readiness cohorts, and establishing clinical trial platforms to investigate combinations of candidate drugs and biomarkers from the portfolios of multiple companies. Estimates based on interviews with experts on AD research and development suggest that the cost of one new drug is now $5.7 billion (95% confidence interval (CI) $3.7-9.5 billion) and could be reduced to $2.0 billion (95% CI $1.5-2.9 billion). The associated acceleration in the arrival of disease-modifying treatments could reduce the number of case years of dementia by 7.0 million (95% CI 4.4-9.4 million) in the United States from 2025 through 2040.