A New Approach to Staging Diabetic Eye Disease: Staging of Diabetic Retinal Neurodegeneration and Diabetic Macular Edema.

Topic: The goal of this review was to summarize the current level of evidence on biomarkers to quantify diabetic retinal neurodegeneration (DRN) and diabetic macular edema (DME). Clinical relevance: With advances in retinal diagnostics, we have more data on patients with diabetes than ever before. However, the staging system for diabetic retinal disease is still based only on color fundus photographs and we do not have clear guidelines on how to incorporate data from the relatively newer modalities into clinical practice. Methods: In this review, we use a Delphi process with experts to identify the most promising modalities to identify DRN and DME. These included microperimetry, full-field flash electroretinogram, spectral-domain OCT, adaptive optics, and OCT angiography. We then used a previously published method of determining the evidence level to complete detailed evidence grids for each modality. Results: Our results showed that among the modalities evaluated, the level of evidence to quantify DRN and DME was highest for OCT (level 1) and lowest for adaptive optics (level 4). Conclusion: For most of the modalities evaluated, prospective studies are needed to elucidate their role in the management and outcomes of diabetic retinal diseases. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Phage Therapy in Korea: A Prescribers' Survey of Attitudes Amongst Korean Infectious Diseases Specialists Towards Phage Therapy.

BACKGROUND: Concerns about the rise in antimicrobial resistance have led to renewed interest in phage therapy worldwide, but perceptions among relevant medical professionals in Korea remain largely unknown. MATERIALS AND METHODS: We conducted a semi-quantitative online survey to evaluate the Korean infectious disease specialists' perception of phage therapy. RESULTS: We sent out the link to the questionnaire to 380 subjects and received 91 replies, with 90/91 respondents identifying as Korean infectious diseases specialists or trainees. Ten out of 91 (11.0%) respondents scored themselves as well-informed about phage therapy. The majority (93.4%) of respondents would consider using phage therapy if the safety of the phage formulation is guaranteed, and 80% of respondents would consider participating in clinical trials with phage therapy given adequate support. The biggest concern was uncertainty about safety (73.6%) and efficacy (65.9%). Acinetobacter baumannii was ranked as a high priority for phage therapy research, as were bone and joint infections. CONCLUSION: Korean infectious diseases specialists are receptive to phage therapy, but a better understanding of safety, efficacy and clinical trials are warranted to progress phage therapy within the Korean healthcare system.

Therapeutic Phage Monitoring: A Review.

With the global rise in antimicrobial resistance, there has been a renewed interest in the application of therapeutic phages to treat bacterial infections. Therapeutic phage monitoring (TPM) is proposed as an essential element of phage therapy (PT) protocols to generate data and fill knowledge gaps regarding the in vivo efficacy of therapeutic phages, patients' immune responses to PT, and the wider ecological effects of PT. By monitoring phage concentrations in blood and tissues, together with immune responses and possible ecological changes during PT, TPM may enable the optimization of dosing and the implementation of precision medicine approaches. Furthermore, TPM can validate diagnostic surrogates of efficacy, direct research efforts, and establish quality assurance indicators for therapeutic phage products. Thus, TPM holds great potential for enhancing our understanding of the multidirectional phage-bacteria-host interactions and advancing "best practice" PT, ultimately improving patient care.

Refractory Pseudomonas aeruginosa infections treated with phage PASA16: A compassionate use case series.

BACKGROUND: A growing number of compassionate phage therapy cases were reported in the last decade, with a limited number of clinical trials conducted and few unsuccessful clinical trials reported. There is only a little evidence on the role of phages in refractory infections. Our objective here was to present the largest compassionate-use single-organism/phage case series in 16 patients with non-resolving Pseudomonas aeruginosa infections. METHODS: We summarized clinical phage microbiology susceptibility data, administration protocol, clinical data, and outcomes of all cases treated with PASA16 phage. In all intravenous phage administrations, PASA16 phage was manufactured and provided pro bono by Adaptive Phage Therapeutics. PASA16 was administered intravenously, locally to infection site, or by topical use to 16 patients, with data available for 15 patients, mainly with osteoarticular and foreign-device-associated infections. FINDINGS: A few minor side effects were noted, including elevated liver function enzymes and a transient reduction in white blood cell count. Good clinical outcome was documented in 13 out of 15 patients (86.6%). Two clinical failures were reported. The minimum therapy duration was 8 days with a once- to twice-daily regimen. CONCLUSIONS: PASA16 with antibiotics was found to be relatively successful in patients for whom traditional treatment approaches have failed previously. Such pre-phase-1 cohorts can outline potential clinical protocols and facilitate the design of future trials. FUNDING: The study was funded in part by The Israeli Science Foundation IPMP (ISF_1349/20), Rosetrees Trust (A2232), United States-Israel Binational Science Foundation (2017123), and the Milgrom Family Support Program.

A theoretically based STEM talent development program that bridges excellence gaps.

The pipeline of highly trained STEM (science, technology, engineering, and mathematics) professionals has narrowed in recent decades, forcing society to re-examine how schools are discovering and developing STEM talent. Of particular concern is the finding that rural students attend post-secondary schools at lower rates than their urban counterparts, and when they do attend, they are less likely to graduate from STEM programs. One reason may be that they are not prepared for advanced STEM coursework because they lack access to essential STEM talent-development programs in middle or high school. This creates excellence gaps, which exacerbate the narrowing STEM pipeline to the workforce. To address this, we formed a university-school partnership to develop an outside-of-school STEM talent development program, called STEM Excellence, for rural middle-school students who attend under-resourced schools. The aim of STEM Excellence was to increase students' achievement and aspirations while empowering their teachers to develop local STEM programs grounded in developmental psychology theories. STEM Excellence integrated the Talent Development Megamodel Principles of ability, domains of talent, opportunity, and psychosocial variables. STEM Excellence also recognized the interplay of multiple person-environment systems as presented in the Bioecological Systems Model.

Outcomes of shared institutional review board compared with multiple individual site institutional review board models in a multisite clinical trial.

BACKGROUND: Institutional review boards play a crucial role in initiating clinical trials. Although many multicenter clinical trials use an individual institutional review board model, where each institution uses their local institutional review board, it is unknown if a shared (single institutional review board) model would reduce the time required to approve a standard institutional review board protocol. OBJECTIVE: This study aimed to compare processing times and other processing characteristics between sites using a single institutional review board model and those using their individual site institutional review board model in a multicenter clinical trial. STUDY DESIGN: This was a retrospective study of sites in an open-label, multicenter randomized control trial from 2014 to 2021. Participating sites in the multicenter Chronic Hypertension and Pregnancy trial were asked to complete a survey collecting data describing their institutional review board approval process. RESULTS: A total of 45 sites participated in the survey (7 used a shared institutional review board model and 38 used their individual institutional review board model). Most sites (86%) using the shared institutional review board model did not require a full-board institutional review board meeting before protocol approval, compared with 1 site (3%) using the individual institutional review board model (P<.001). Median total approval times (41 vs 56 days; P=.42), numbers of submission rounds (1 vs 2; P=.09), and numbers of institutional review board stipulations (1 vs 4; P=.12) were lower for the group using the shared institutional review board model than those using the individual site institutional review board model; however, these differences were not statistically significant. CONCLUSION: The findings supported the hypothesis that the shared institutional review board model for multicenter studies may be more efficient in terms of cumulative time and effort required to obtain approval of an institutional review board protocol than the individual institutional review board model. Given that these data have important implications for multicenter clinical trials, future research should evaluate these findings using larger or multiple multicenter trials.

Risk Factors for Retinal Detachment in Acute Retinal Necrosis.

PURPOSE: Retinal detachment (RD) is associated with poor visual outcomes in patients with acute retinal necrosis (ARN). This research was undertaken to assess the risk factors for RD in ARN. DESIGN: Retrospective cohort study. SUBJECTS: Patients diagnosed with ARN at a tertiary referral center from 2010 to 2020. METHODS: A chart review was performed for all clinical and surgical encounters. Univariate and multivariate logistic analyses of demographic and clinical variables associated with RD were performed. Survival analyses with Kaplan-Meier estimates were performed to compare the time to RD in herpes simplex virus (HSV)- and varicella zoster virus (VZV)-associated ARN. MAIN OUTCOME MEASURES: Demographic information, clinical information (including visual acuity [VA]), intraocular pressure (IOP), intraocular inflammation level, the extent of retinitis, incidence and timing of retinal detachment, date of diagnosis, and treatments performed (including intravitreal injections of antiviral medications). RESULTS: Fifty-four eyes of 47 patients who were diagnosed with ARN were included, with equal proportions of eyes (n = 27; 50%) with VZV-ARN and HSV-ARN. Patients with VZV-ARN were, on average, older, more likely to be men, and more likely to be immunosuppressed compared with patients with HSV-ARN. The clinical characteristics, including the initial VA, initial IOP, anterior segment inflammation, clock hours, and posterior extent of retinitis, were similar between eyes with VZV- and HSV-ARN. In the univariate analysis of clinical and demographic variables associated with the development of RD, initial VA (P = 0.0083) and greater clock hours of retinitis (P = 0.009) were significantly associated with RD. These 2 variables remained significant in the multivariate logistic regression; worse VA at presentation had an odds ratio of 2.34 (95% confidence interval [CI], 1.01-5.44; P = 0.042), and greater clock hours of retinitis had an odds ratio of 1.23 (95% CI, 1.02-1.47; P = 0.025). A Kaplan-Meier survival analysis demonstrated no statistical difference in RD-free survival between HSV- and VZV-ARN. CONCLUSIONS: Patients with VZV-ARN were more likely to be older, male, and immunosuppressed compared with those with HSV-ARN, although no clear difference was observed in RD by viral etiology. Poor initial VA and clock hours of retinitis were significantly associated with RD development and may be relevant for patient counseling and prognosis.

Phage-Encoded Endolysins.

Due to the global emergence of antibiotic resistance, there has been an increase in research surrounding endolysins as an alternative therapeutic. Endolysins are phage-encoded enzymes, utilized by mature phage virions to hydrolyze the cell wall from within. There is significant evidence that proves the ability of endolysins to degrade the peptidoglycan externally without the assistance of phage. Thus, their incorporation in therapeutic strategies has opened new options for therapeutic application against bacterial infections in the human and veterinary sectors, as well as within the agricultural and biotechnology sectors. While endolysins show promising results within the laboratory, it is important to document their resistance, safety, and immunogenicity for in-vivo application. This review aims to provide new insights into the synergy between endolysins and antibiotics, as well as the formulation of endolysins. Thus, it provides crucial information for clinical trials involving endolysins.

The Complex Diseases of Staphylococcus pseudintermedius in Canines: Where to Next?

Staphylococcus pseudintermedius is a pathogenic bacterium of concern within the veterinary sector and is involved in numerous infections in canines, including topical infections such as canine pyoderma and otitis externa, as well as systemic infections within the urinary, respiratory and reproductive tract. The high prevalence of methicillin-resistant Staphylococcus pseudintermedius (MRSP) within such infections is a growing concern. Therefore, it is crucial to understand the involvement of S. pseudintermedius in canine disease pathology to gain better insight into novel treatment avenues. Here, we review the literature focused on S. pseudintermedius infection in multiple anatomic locations in dogs and the role of MRSP in treatment outcomes at these niches. Multiple novel treatment avenues for MRSP have been pioneered in recent years and these are discussed with a specific focus on vaccines and phage therapy as potential therapeutic options. Whilst both undertakings are in their infancy, phage therapy is versatile and has shown high success in both animal and human medical use. It is clear that further research is required to combat the growing problems associated with MRSP in canines.

Educating Nurses on the Use of the Clinical Opiate Withdrawal Scale to Improve Care of Adult Patients Undergoing Buprenorphine Induction.

INTRODUCTION: Opioid addiction disease has become a global health and social problem complicated by drug misuse and abuse (Pearlman, 2016; Rettig & Yarmolinsky, 1995; Watkins, 2016). Buprenorphine, a partial opioid agonist, is an effective treatment for opioid addiction disease (Loreck et al., 2016). Its induction can trigger severe precipitated withdrawal in opioid-dependent patients whose mu receptors are occupied opioids (American Society of Addiction Medicine, 2015). Knowledge of assessing a patient's level of withdrawal using a validated tool is key to successful transition from other opioids to buprenorphine. AIM: The aim of this study was to evaluate the effectiveness of training nurses on the use of the Clinical Opioid Withdrawal Scale (COWS) screening instrument by assessing their confidence in assessing and satisfaction with communicating withdrawal information crucial for patient safety. METHOD: Ten registered nurses and three nurse practitioners working at a mental health community service center completed two surveys at three time points (Pre, Post, and Post-90 days). The first survey measured nurses' confidence in assessing, whereas the second survey measured their satisfaction with communicating withdrawal symptoms. RESULTS: The means' (M) magnitude for both assessment and satisfaction scores increased with time (across Pre, Post, and Post-90). Standard deviations tended to become smaller. Improvements were noted in nurses' confidence in the assessment of and satisfaction in communicating withdrawal symptoms after the intervention. CONCLUSION: Participants expressed increased knowledge, confidence, and satisfaction with the COWS screening instrument. Ultimately, the patients benefited from the participants having more experience, education, skills, and confidence in monitoring withdrawal symptoms depicted by aggregate data of COWS screenings postintervention.

Charting Cognitive Growth of Nursing Students Using Linguistic Software.

BACKGROUND: Students' word choice when writing in a reflective journal may reveal their emotional development, sense of belonging, cognitive processing, and ability to appraise their own growth and understanding. New linguistic analysis software can scan and categorize these journals for the use of pronouns, positive and negative emotions, and cognitive keywords. METHODS: A retrospective study design evaluated student journaling from a psychiatric clinical course. Journal entries from weeks 1 and 12 were compared by z-score analysis. FINDINGS: Significant increases were found in the use of "we" (P = .001), positive emotions (P < .001), inclusion words (P < .001), and insight words (P = .004), whereas the use of cause and self-discrepancy words were not significantly different. CONCLUSION: Identification of learning as expressed in words could have an impact on how student assignments are designed by including the use of the Linguistic Inquiry and Word Count software to assess changes in student cognition.

Validation of a Weight Threshold-Based Vancomycin Dosing Protocol for Patients Undergoing Intermittent Hemodialysis.

BACKGROUND: Patients receiving intermittent hemodialysis (IHD) are at high risk of acquiring gram-positive infections, which are often treated with IV vancomycin. Despite frequent use of vancomycin in the IHD setting, there is variability in dosing and monitoring practices among clinicians at the study institution. There is also a paucity of evidence regarding optimal vancomycin dosing to achieve target pre-IHD serum concentration. OBJECTIVES: The primary objective was to compare the percentage of treatment courses with a serum vancomycin concentration between 15 and 20 mg/L, measured before the third IHD session, before and after implementation of a weight threshold-based dosing protocol. The secondary objectives were to compare the percentage of treatment courses with a pre-third IHD vancomycin concentration between 10 and 22 mg/L and the number of vancomycin measurements per treatment day, before and after protocol implementation. METHODS: This quasi-experimental, single-centre study included inpatients and outpatients who underwent IHD and received at least 2 IV doses of vancomycin, with vancomycin being measured in an appropriately drawn sample before the third IHD session. Before protocol implementation, vancomycin dosing was at the clinician's discretion (usual care). After protocol implementation, each patient received a loading dose of 1000, 1500, or 2000 mg and a maintenance dose of 500, 750, or 1000 mg, depending on body weight. RESULTS: The percentage of treatment courses with a pre-third IHD vancomycin concentration between 15 and 20 mg/L was greater after implementation of the protocol than with usual care, but the difference was nonsignificant (44% [8/18] versus 20% [3/15], p = 0.27). However, the percentage of treatment courses with a pre-third IHD vancomycin concentration between 10 and 22 mg/L was significantly higher after protocol implementation (94% [17/18] versus 53% [8/15], p = 0.012). There was no difference in the median number of vancomycin measurements per treatment day before and after protocol implementation (0.133 versus 0.125, p = 0.99). CONCLUSIONS: At the study institution, the likelihood of achieving recommended vancomycin concentration increased (relative to previous practice) after implementation of a simplified vancomycin dosing protocol for patients undergoing IHD.

CONTEXTE: Les patients recevant une hémodialyse intermittente (HDI) présentent un risque élevé de contracter des infections à Gram positif, souvent traitées à l'aide de vancomycine par intraveineuse (IV). Malgré l'utilisation fréquente de la vancomycine dans les environnements d'HDI, les pratiques portant sur le dosage et le suivi varient entre les cliniciens de l'institution où l'étude s'est déroulée. Il existe également peu de données probantes sur la dose optimale de vancomycine permettant d'atteindre la concentration sérique cible avant l'HDI. OBJECTIFS: L'objectif principal visait à comparer le pourcentage de traitements à la vancomycine, dont la concentration sérique se situait entre 15 et 20 mg/L, lors de la mesure prise avant la troisième séance de HDI, avant et après la mise en place d'un protocole de dosage basé sur le poids. Les objectifs secondaires visaient à comparer le pourcentage de traitements, dont la concentration de vancomycine mesurée avant la troisième séance d'HDI était comprise entre 10 et 22 mg/L, et le nombre de mesures de vancomycine par jour de traitement, avant et après la mise en place du protocole. MÉTHODES: Cette étude quasi expérimentale, menée dans un seul centre, comprenait des patients hospitalisés et ambulatoires ayant subi une HDI et reçu au moins deux doses de vancomycine par IV et dont un échantillon prélevé de manière appropriée avant la troisième séance d'HDI a permis de mesurer la vancomycine. Avant la mise en place du protocole, le dosage de vancomycine était laissé à la discrétion du clinicien (soins habituels). Après sa mise en place, chaque patient recevait une dose de charge de 1000, 1500 ou 2000 mg et une dose de maintenance de 500, 750 ou 1000 mg selon sa masse corporelle. RÉSULTATS: Le pourcentage de traitements dont la concentration de vancomycine mesurée avant la troisième séance d'HDI était comprise entre 15 et 20 mg/L était plus élevé après la mise en place du protocole qu'après les soins habituels, mais la différence n'était pas significative (44 % [8/18] contre 20 % [3/15], p = 0,27). Cependant, le pourcentage de traitements dont la concentration de vancomycine mesurée avant la troisième séance d'HDI était comprise entre 10 et 22 mg/L était significativement plus élevé après la mise en place du protocole (94 % [17/18] contre 53 % [8/15], p = 0,012). Le nombre moyen de mesures de vancomycine par traitement n'avait pas varié entre le jour précédant et le jour suivant la mise en place du protocole (0,133 contre 0,125, p = 0,99). CONCLUSIONS: Dans l'institution où l'étude s'est déroulée, la probabilité d'atteindre la concentration de vancomycine recommandée avait augmenté après la mise en place d'un protocole simplifié de dosage de vancomycine pour les patients recevant une HDI comparativement à une pratique antérieure.

Intravitreal Fluocinolone Acetonide May Decelerate Diabetic Retinal Neurodegeneration.

Purpose: There is no prevention or treatment for diabetic retinal neurodegeneration (DRN), which is a complication of diabetes that can occur independently of diabetic retinopathy (DR). We hypothesized that an intravitreal fluocinolone acetonide (FAc) implant may affect the rate of DRN when used in patients with diabetic macular edema (DME). Methods: In this retrospective analysis, optical coherence tomography with neuroretinal analysis was obtained at 3-month intervals from 130 patients in the USER study both before (mean duration 903 days, range 35-4005 days) and after administration of FAc (mean 408 days, range 7 to 756 days). The rate of DRN was defined as the change over time on inner neuroretinal thickness using logistic regression. A DRN rate was calculated independently for two areas: region 1 located within 1.5 mm of the fovea, and region 2 from 1.5 mm to 3.0 mm from the fovea. Results: In regions of the macula more than 1.5 mm from the central fovea, there was a statistically significant decrease in the rate of DRN in the post-FAc period. The pre-FAc neuroretinal loss in this area occurred at 4.0 µm/y, compared with a post-FAc loss rate of 1.1 µm/y (P = 0.001). Conclusions: This retrospective study suggests that FAc may decelerate the rate of inner retinal thinning in patients with persistent DME. Further prospective studies are necessary to determine the effects of FAc on the rate of DRN in patients with DME.

Converging Cultures: Partnering in Affirmative and Inclusive Health Care for Members of the Lesbian, Gay, Bisexual, and Transgender Community.

BACKGROUND: Members of the lesbian, gay, bisexual, and transgender (LGBT) community suffer from disproportionate rates of physical and mental illness. This population experiences enhanced vulnerability to illness as a result of societal marginalization, known as minority stress, which is compounded by insufficient LGBT education for health care professionals and stigmatizing experiences within medical institutions. AIMS: The aims of this study were to review the literature on LGBT cultural competence interventions; evaluate the effect of a 4-hour pilot workshop, "Converging Cultures," on the development of cultural competence; and make recommendations for best practices in developing LGBT cultural competence among health care providers. METHOD: The study used a repeated-measures pre-/posttest design among a sample of 130 hospital employees and undergraduate nursing students. The GAP (Gay Affirmative Practice scale) scale, a measure of LGBT-affirmative practice beliefs, and an objective Knowledge Quiz were administered before and directly following the training. The posttest included three open-ended questions to elicit self-reflection and capture the development of cultural competence according to Campinha-Bacote's theory, the process of cultural competence in the delivery of healthcare services. RESULTS: Paired sample t tests revealed significant improvement on the GAP and Knowledge Quiz. Open-ended responses reflected the five constructs of Campinha-Bacote's theory. CONCLUSIONS: Self-reflection is an essential component of LGBT cultural competence education to uncover personal biases that affect clinical behavior. Future educational efforts for sexual and gender minorities should strive to avoid inadvertent marginalization of LGBT people through integration of concepts with existing curricula and workplace training.

Adolescent Stress Treatment Study: A Cluster Randomized Trial.

High school students experience a variety of stressors. Mental health issues are critical to their health. The "Adolescent Stress Treatment (AST) Study: A Cluster Randomized Trial" compared the efficacy of two stress reduction devices, the EnergyPod™ and the SleepWing™. The EnergyPod™ is a device that provides a semiprivate acoustical and visual environment for rest, stress reduction, and sleep. The SleepWing™ is a smaller device offering similar benefits. High school students were offered the opportunity to participate in the AST study when they exhibited signs of agitation. The students completed the Profile of Mood States-Short Form (POMS-SF) pre- and postintervention. Total Mood Disturbance (TMD) was measured from the POMS-SF and significant improvement postintervention (p < .001), regardless of intervention used. POMS-SF subscales were all significantly improved no matter which device was used. All participants in the study dramatically improved their mood after being in either therapeutic device.

A Multicenter Investigation of Factors Influencing Women's Participation in Clinical Trials.

OBJECTIVE: To identify factors that influence women's participation in clinical research. METHODS: We administered a survey in outpatient and inpatient populations of Obstetrics and Gynecology facilities of six institutions located in four states. The survey included questions regarding any of the participant's past experiences in clinical research and the factors that would influence their participation in clinical research. Analyses included descriptive statistics and a Principal Component Analysis. RESULTS: The analysis included 3,773 respondents; 2,477 (68.1%) were pregnant. The majority of participants were Caucasian (1,453, 40.2%), followed by Hispanic (933, 25.8%), African American/black (744, 20.6%), other minorities (270, 7.5%), and multiracial (212, 5.9%). Ten potential motivating factors and 10 potential barriers were assessed. The greatest motivating factor was "how well research is explained" (mean = 2.87) while "risk of unknown side effects" was the greatest barrier (mean = 3.07) for women's participation in clinical trials. Among six helpful resources assessed, "material in my own language" was scored as the highest (mean = 2.8) in facilitating women's decision to participate. For "risk to the fetus/future fertility" as a barrier, pregnant women's score (mean = 3.25) was significantly higher than nonpregnant women's score (mean = 2.37). CONCLUSIONS: Overall, the risk of unknown side effects discourages women in general, and the risk to the fetus/future fertility discourages pregnant women the most from participating in clinical trials. However, explaining a study well and providing written material in the patients' own language may increase their willingness to participate.

How much atopy is attributable to common childhood environmental exposures? A population-based birth cohort study followed to adulthood.

Background: The rising prevalence of atopic diseases implies a strong influence of environmental determinants. Epidemiological studies have identified several early life exposures that appear to influence the risk of developing atopic sensitization, but the combined influence of these exposures is unknown. We sought to estimate the proportion of atopy that could be attributed to common childhood exposures associated with atopic sensitization in adolescence and young adulthood. Methods: Atopic sensitization was measured by skin-prick tests for common aeroallergens in a population-based New Zealand birth cohort at ages 13 and 32 years. The independent effects of previously identified risk and protective factors for atopic sensitization were assessed using multiple logistic regression. Population attributable fractions were calculated for atopic sensitization in childhood and adulthood. Results: Tobacco smoke exposure, dog and cat ownership, nail-biting and thumb-sucking, attending pre-school day care, and household crowding were associated with a lower risk of atopic sensitization whereas breastfeeding was associated with a higher risk. Population attributable fractions for combined effects of these environmental factors suggest that they may account for 58% of atopic sensitization at age 13 and 49% at age 32 years. Conclusions: A substantial proportion of atopic sensitization appears to be attributable to common childhood environmental and lifestyle factors, and the influence of these exposures persists into adulthood. The absolute risks attributable to these exposures will be different in other cohorts and we cannot assume that these associations are necessarily causal. Nevertheless, the findings suggest that identifiable childhood environmental factors contribute substantially to atopic sensitization.

Diabetic retinopathy is a neurodegenerative disorder.

Since 1875, controversy has ensued over whether ocular diabetic complications are primarily vasculopathic or neuropathic in nature. Here, we discuss the historical context by which diabetic retinopathy (DR) came to be considered a primary vasculopathy, in contrast to more recent data suggesting the importance of diabetic retinal neurodegeneration (DRN) as the primary manifestation of ocular diabetic damage. Unsurprisingly, DRN parallels other diabetic complications related to neuropathy. In general, there are three possible relationships between microvascular DR and DRN: i) microvasculopathy causes neurodegeneration; ii) neurodegeneration causes microvasculopathy or iii) they are mutually independent. The authors' group has recently produced experimental data showing that DRN precedes even the earliest manifestations of DR microvasculopathy. In combination with earlier studies showing that focal implicit time delays predicted future development of DR microvasculopathy in the same location, relationships i) and iii) are unlikely. As such, ii) is the most likely relationship: DRN is a cause of DR. Granted, additional studies are needed to confirm this hypothesis and elucidate the mechanism of diabetes-induced neurodegeneration. We conclude this review by proposing experimental approaches to test the hypothesis that DRN causes DR. If confirmed, this new paradigm may lead to earlier detection of ocular diabetic damage and earlier treatment of early DR, thereby preventing visual loss in people with diabetes.

Phosphate-Containing Prescription Medications Contribute to the Daily Phosphate Intake in a Third of Hemodialysis Patients.

OBJECTIVES: Hyperphosphatemia is associated with all-cause mortality in hemodialysis (HD) patients and is managed by restricting dietary phosphate. Many patients are unable to adhere to the recommended dietary phosphate limit. We sought to quantify the additional phosphate burden from prescription medication in a hemodialysis population. DESIGN: Cross-sectional study. SUBJECTS: Adult patients on hemodialysis at a single center. SETTING: The Health Canada Drug Product Database was used to identify formulations of medications prescribed in an HD program that contain phosphate salts. The manufacturers of formulations containing a phosphate salt were contacted to request the phosphate content per tablet, and amounts were confirmed in select medications by the malachite green method. MAIN OUTCOME MEASUREMENTS: Prescription bottles of 101 HD patients were evaluated. Reported phosphate contents were used to determine patients' daily phosphate load from prescribed medications. RESULTS: A total 1,744 drug formulations of 124 different medications were reviewed. A total of 185 (11%) contained a phosphate salt. Central nervous system (CNS) and cardiovascular (CVS) medications accounted for 65% and 24% of phosphate-containing medications, respectively. Of HD patients, 30% were taking at least one medication that contained phosphate. The median phosphate burden from prescribed medications was 111 (67-168) mg per day. CONCLUSIONS: Knowledge about the phosphate content of commonly prescribed drugs within different classes should influence prescribing patterns. Particular consideration of which formulation of CVS and CNS drugs contain phosphate should be applied when prescribing. Phosphate-containing medications can meaningfully contribute to the daily phosphate load in HD patients; however, this burden will differ based on local dispensing patterns.

Definitive chemoradiation alters the immunologic landscape and immune checkpoints in head and neck cancer.

BACKGROUND: Preclinical and clinical studies suggest potential synergy between high dose per fraction focal radiation and immunotherapy. However, conventionally fractionated radiation regimens in combination with concurrent chemotherapy are more commonly administered to patients as definitive treatment and may have both immune-stimulating and -suppressive effects. METHODS: We prospectively collected longitudinal samples from head and neck squamous cell carcinoma patients receiving definitive radiation therapy. We quantified changes in populations of circulating immune cells and chemokines CXCL9, 10, and 16. Analyses of humoral and cellular immune responses were conducted in select patients via proteomic analysis and T-cell receptor sequencing. RESULTS: Treatment not only increased circulating CD-8+ T-effector cells, but also myeloid-derived suppressor cells, regulatory T cells, and checkpoint receptor-expressing T cells, particularly PD-1+ T cells. Significant decreases in CXCL10 and increases in CXLC16 were noted. Treatment also increased the percentage of unique and dominant TCR clones, and increased humoral responses as measured by proteomic array. CONCLUSIONS: Our results suggest that fractionated chemoradiation leads to quantifiable effects in circulating immune mediators, including a balance of stimulatory and suppressive mechanisms. These results suggest future combinations with immune checkpoint blockade.