Oculomics: A Crusade Against the Four Horsemen of Chronic Disease.

Chronic, non-communicable diseases present a major barrier to living a long and healthy life. In many cases, early diagnosis can facilitate prevention, monitoring, and treatment efforts, improving patient outcomes. There is therefore a critical need to make screening techniques as accessible, unintimidating, and cost-effective as possible. The association between ocular biomarkers and systemic health and disease (oculomics) presents an attractive opportunity for detection of systemic diseases, as ophthalmic techniques are often relatively low-cost, fast, and non-invasive. In this review, we highlight the key associations between structural biomarkers in the eye and the four globally leading causes of morbidity and mortality: cardiovascular disease, cancer, neurodegenerative disease, and metabolic disease. We observe that neurodegenerative disease is a particularly promising target for oculomics, with biomarkers detected in multiple ocular structures. Cardiovascular disease biomarkers are present in the choroid, retinal vasculature, and retinal nerve fiber layer, and metabolic disease biomarkers are present in the eyelid, tear fluid, lens, and retinal vasculature. In contrast, only the tear fluid emerged as a promising ocular target for the detection of cancer. The retina is a rich source of oculomics data, the analysis of which has been enhanced by artificial intelligence-based tools. Although not all biomarkers are disease-specific, limiting their current diagnostic utility, future oculomics research will likely benefit from combining data from various structures to improve specificity, as well as active design, development, and optimization of instruments that target specific disease signatures, thus facilitating differential diagnoses.

Long-term diseases can stop people living long and healthy lives. In many cases, early diagnosis can help to prevent, monitor, and treat disease, which can improve patients' health. In order to diagnose disease, we need tools that are easy for patients to access, painless, and low-cost. The eye may provide the solution. In this review, we discuss the link between changes in the eye and four types of long-term disease that, together, kill most of the population: (1) Cardiovascular disease (affecting the heart and/or blood). (2) Cancer (abnormal growth of cells). (3) Neurodegenerative disease (affecting the brain and/or nervous system). (4) Metabolic disease (problems storing, accessing, and using the body's fuel). We show that neurodegenerative disease leaves tell-tale signs in lots of different parts of the eye. Signs of cardiovascular and metabolic disease biomarkers are mostly found in the back of the eye, and signs of cancer can be found in the tear fluid. Although signs of disease can be seen in the eye, not all of them will tell us what the disease is. We believe that future research will help us to understand more about long-term disease and how to detect it if we combine information from different structures within the eye and develop new tools to target these specific structures.

Strategies for case-based training with virtual patients: An experimental study of the impact of integrating mental model articulation and self-reflection.

Resilient system performance in high-stakes settings, which includes the ability to monitor, respond, anticipate, and learn, can be enhanced for trainees through simulation of realistic scenarios enhanced by augmented reality. Active learning strategies can enhance simulation-based training, particularly the mental model articulation principle where students are prompted to anticipate what will happen next and the reflection principle where students self-assess their performance compared to a gold standard expert model. In this paper, we compared simulation-based training for trauma care with and without active learning strategies during pauses in the simulated action for progressively deteriorating patients. The training was conducted online and real-time without a facilitator, with 42 medical students viewing training materials and then immediately taking an online quiz for three types of trauma cases: hemorrhage, airway obstruction, and tension pneumothorax. Participants were randomly assigned to either the experimental or control condition in a between-subjects design. We compared performance in the control and experimental conditions based on: A) the proportion of cues correctly recognized, B) the proportion of accurate diagnoses, C) the proportion of appropriate treatment interventions, and D) verbal briefing quality on a 1-5 scale. We found that the training intervention increased recognition of subtle cues critical for accurate diagnosis and appropriate treatment interventions; the training did not improve the accuracy of diagnoses or the quality of the verbal briefing. We conclude that incorporating active learning strategies in simulation-based training improved foundational capabilities in detecting subtle cues and intervening to rescue deteriorating patients that can increase the readiness for trainees to contribute to resilient system performance in the high-stakes setting of emergency care in hospitals.

Acute stress influences the emotional foundations of executive control: Distinct effects on control-related affective and cognitive processes.

Acute stress is known to influence performance on various task outcomes indicative of executive functioning (i.e., the top-down, goal-directed control of cognition and behavior). The most common interpretation of these effects is that stress influences control processes themselves. Another possibility, though, is that stress does not impair control per se, but instead alters the affective dynamics underlying the recruitment of control (e.g., reducing the extent to which making an error is aversive), resulting in less recruitment of control and thus poor performance. To date, however, no work has examined whether stress effects on executive function outcomes are driven by affective dynamics related to the recruitment of control. In the current study, we found that acute stress influenced-and cortisol responses related to-both executive control-related performance outcomes (e.g., post-error slowing) and control-related affective dynamics (e.g., negative affect following recruitment of control) in a modified Stroop task, but that these effects appeared to be independent of each other: The effects of stress on, and associations of cortisol with, control-related cognitive outcomes were not statistically mediated by task- or control-related affective dynamics. These results thus suggest that although stress influences affective dynamics underlying executive function, the effects of stress on executive function outcomes appear to be at least partially dependent on nonaffective processes, such as control processes themselves.

Hemoglobin on Admission for Childbirth and Postpartum Acute Care Use in a Southeastern Health Care System.

OBJECTIVE: Our objective was to evaluate whether hemoglobin on admission for childbirth is associated with postpartum acute care use (ACU). STUDY DESIGN: We conducted a retrospective cohort study of patients giving birth at a southeastern quaternary care hospital from January 2018 through June 2021 using electronic health records. Predelivery hemoglobin was categorized as <9, 9- < 10, 10- < 11, 11- < 12, and ≥12 g/dL. Acute care was defined as a visit to obstetric triage, the emergency department, or inpatient admission within 90 days postpartum. Generalized estimating equations quantified the crude and multivariable-adjusted association between predelivery hemoglobin and ACU. RESULTS: Among 8,677 pregnancies, 1,467 (17%) used acute care in the system within 90 days postpartum. In unadjusted models, those with predelivery hemoglobin <9 had twice the risk of postpartum ACU compared to those with hemoglobin ≥12 (95% confidence interval [CI]: 1.59-2.69), with a decrease in risk for each increase in hemoglobin category (9- < 10 g/dL: risk ratio [RR]: 1.47, CI: 1.21-1.79; 10- < 11 g/dL: RR: 1.44, CI: 1.26-1.64; 11- < 12 g/dL: RR: 1.20, CI: 1.07-1.34). The adjusted model showed a similar trend with smaller effect estimates (<9 g/dL: RR: 1.50, CI: 1.14-1.98; 9- < 10 g/dL: RR: 1.22, CI: 1.00-1.48; 10- < 11 g/dL: RR: 1.22, CI: 1.07-1.40; 11- < 12 g/dL: RR: 1.09, CI: 0.98-1.22). CONCLUSION: Low hemoglobin at childbirth admission was associated with increased postpartum ACU. Low hemoglobin on admission could signal to providers that additional follow-up, resources, and ongoing support are warranted to identify and address underlying health needs. Because hemoglobin is routinely assessed during the childbirth hospitalization, this indicator may be especially valuable for risk assessment among patients with limited prior engagement in health care. KEY POINTS: · Low hemoglobin on admission for birth is associated with postpartum acute care use.. · Hemoglobin on admission may aid in risk-stratification during childbirth hospitalization.. · Point-of-care metrics may help identify high-risk patients with limited preventive health care..

Mitogenome sequences of domestic cats demonstrate lineage expansions and dynamic mutation processes in a mitochondrial minisatellite.

BACKGROUND: As a population genetic tool, mitochondrial DNA is commonly divided into the ~ 1-kb control region (CR), in which single nucleotide variant (SNV) diversity is relatively high, and the coding region, in which selective constraint is greater and diversity lower, but which provides an informative phylogeny. In some species, the CR contains variable tandemly repeated sequences that are understudied due to heteroplasmy. Domestic cats (Felis catus) have a recent origin and therefore traditional CR-based analysis of populations yields only a small number of haplotypes. RESULTS: To increase resolution we used Nanopore sequencing to analyse 119 cat mitogenomes via a long-amplicon approach. This greatly improves discrimination (from 15 to 87 distinct haplotypes in our dataset) and defines a phylogeny showing similar starlike topologies within all major clades (haplogroups), likely reflecting post-domestication expansion. We sequenced RS2, a CR tandem array of 80-bp repeat units, placing RS2 array structures within the phylogeny and increasing overall haplotype diversity. Repeat number varies between 3 and 12 (median: 4) with over 30 different repeat unit types differing largely by SNVs. Five SNVs show evidence of independent recurrence within the phylogeny, and seven are involved in at least 11 instances of rapid spread along repeat arrays within haplogroups. CONCLUSIONS: In defining mitogenome variation our study provides key information for the forensic genetic analysis of cat hair evidence, and for the first time a phylogenetically informed picture of tandem repeat variation that reveals remarkably dynamic mutation processes at work in the mitochondrion.

Defining cat mitogenome variation and accounting for numts via multiplex amplification and Nanopore sequencing.

Hair shed by domestic cats is a potentially useful source of forensic evidence. Analysable hair DNA is predominantly mitochondrial, but the recent domestication history of cats means that mtDNA diversity is low. A 402-bp control region segment is usually sequenced, defining only a small number of distinct haplotypes in populations. Previously, we used a long-amplicon approach to sequence whole mitogenomes in a sample of blood DNAs from 119 UK cats, greatly increasing observed diversity and reducing random match probabilities. To exploit this variation for forensic analysis, we here describe a multiplex system that amplifies the cat mitogenome in 60 overlapping amplicons of mean length 360 bp, followed by Nanopore sequencing. Variants detected in multiplex sequence data from unrooted hair completely mirror those from long-amplicon data from blood from the same individuals. However, applying the multiplex to matched blood DNA reveals additional sequence variants which derive from the major feline nuclear mitochondrial insertion sequence (numt), which covers 7.9 kb of the 17-kb mitogenome and exists in multiple tandem copies. We use long-amplicon Nanopore sequencing to investigate numt variation in a set of cats, together with an analysis of published genome sequences, and show that numt arrays are variable in both structure and sequence, thus providing a potential source of uncertainty when nuclear DNA predominates in a sample. Forensic application of the multiplex was demonstrated by matching hairs from a cat with skeletal remains from its putative mother, both of which shared a globally common haplotype at the control region. The random match probability in this case with the CR 402-bp segment was 0.21 and this decreased to 0.03 when considering the whole mitogenome. The developed multiplex and sequencing approach, when applied to cat hair where nuclear DNA is scarce, can provide a reliable and highly discriminating source of forensic genetic evidence from a single hair. The confounding effect of numt co-amplification in degraded samples where mixed sequences are observed can be mitigated by variant phasing, and by comparison with numt sequence diversity data, such as those presented here.

Extracting spacing-derived estimates of rod density in healthy retinae.

Quantification of the rod photoreceptor mosaic using adaptive optics scanning light ophthalmoscopy (AOSLO) remains challenging. Here we demonstrate a method for deriving estimates of rod density and rod:cone ratio based on measures of rod spacing, cone numerosity, and cone inner segment area. Twenty-two AOSLO images with complete rod visualization were used to validate this spacing-derived method for estimating density. The method was then used to estimate rod metrics in an additional 105 images without complete rod visualization. The spacing-derived rod mosaic metrics were comparable to published data from histology. This method could be leveraged to develop large normative databases of rod mosaic metrics, though limitations persist with intergrader variability in assessing cone area and numerosity.

Perceptually Discriminating the Highest Priority Alarms Reduces Response Time: A Retrospective Pre-Post Study at Four Hospitals.

OBJECTIVE: Reduce nurse response time for emergency and high-priority alarms by increasing discriminability between emergency and all other alarms and suppressing redundant and likely false high-priority alarms in a secondary alarm notification system (SANS). BACKGROUND: Emergency alarms are the most urgent, requiring immediate action to address a dangerous situation. They are clinician-triggered and have higher positive predictive value (PPV). High-priority alarms are automatically triggered and have lower PPV. METHOD: We performed a retrospective pre-post study, analyzing data 15 months before and 25 months after a SANS redesign was implemented in four hospitals. For emergency alarms, we incorporated digitized human speech to distinguish them from automatically triggered alarms, leaving their onset and escalation pathways unchanged. For automatically triggered alarms, we suppressed some by delaying initial onset and escalation by 20 s. We used linear mixed models to assess the change in response time, Fisher's exact test for the proportion of response times longer than 120 s, and control charts for process stability. RESULTS: Response time for emergency alarms decreased at all hospitals (main, from 26.91 s to 22.32 s, p < .001; cardiac, from 127.10 s to 52.43 s, p < .001; cancer, from 18.03 s to 15.39 s, p < .001). Improvements were sustained. Automatically triggered alarms decreased 25.0%. Response time for the three automatically triggered cardiac alarms increased at the four hospitals. CONCLUSION: Auditory sound disambiguation was associated with a sustained reduced nurse response time for emergency alarms, but suppressing some high-priority automatically triggered alarms was not. APPLICATION: Distinguishing and escalating urgent, actionable alarms with higher PPV improves response time.

Impact of Drug Interactions on Major Bleed Rates in Patients Taking Direct Oral Anticoagulants.

Background: While direct oral anticoagulants (DOACs) have less stringent monitoring, favorable pharmacokinetics, and fewer drug interactions compared to warfarin, there is still a potential for drug-drug interactions. There is limited evidence showing total impact of DOAC drug interactions on major bleeding events. Methods: This was an IRB-approved retrospective, case control, single center study. Patients were included if they had received a DOAC from January 2012 to September 2019 and were identified for major bleeding events and matched to a control group. The primary objective was to compare the presence of major drug interactions between patients on DOACs who did and did not have a major bleeding event. The secondary objectives were to compare the impact of specific interacting drug classes and their additive effects on major bleeding events. Results: There were 122 patients included in the study. While the number of patients on at least one interacting medication within duration of DOAC use was numerically higher in the bleed group (85% vs 72%), this was not significant (P = .077). There were significantly more patients on at least three interacting medications within the last 3 months of the study period in the bleed group (n = 9 vs 1), with significantly higher use of aspirin (n = 38 vs 17) and rate control agents (n = 24 vs 11). Conclusion: There may be a cumulative effect on risk of bleeding if patients are on three or more interacting medications concomitantly with a DOAC. This risk of bleeding may be higher with aspirin and rate control agents.

Foveal Cone Structure in Patients With Blue Cone Monochromacy.

Purpose: Blue cone monochromacy (BCM) is a rare inherited cone disorder in which both long- (L-) and middle- (M-) wavelength sensitive cone classes are either impaired or nonfunctional. Assessing genotype-phenotype relationships in BCM can improve our understanding of retinal development in the absence of functional L- and M-cones. Here we examined foveal cone structure in patients with genetically-confirmed BCM, using adaptive optics scanning light ophthalmoscopy (AOSLO). Methods: Twenty-three male patients (aged 6-75 years) with genetically-confirmed BCM were recruited for high-resolution imaging. Eight patients had a deletion of the locus control region (LCR), and 15 had a missense mutation-Cys203Arg-affecting the first two genes in the opsin gene array. Foveal cone structure was assessed using confocal and non-confocal split-detection AOSLO across a 300 × 300 µm area, centered on the location of peak cell density. Results: Only one of eight patients with LCR deletions and 10 of 15 patients with Cys203Arg mutations had analyzable images. Mean total cone density for Cys203Arg patients was 16,664 ± 11,513 cones/mm2 (n = 10), which is, on average, around 40% of normal. Waveguiding cone density was 2073 ± 963 cones/mm2 (n = 9), which was consistent with published histological estimates of S-cone density in the normal eye. The one patient with an LCR deletion had a total cone density of 10,246 cones/mm2 and waveguiding density of 1535 cones/mm2. Conclusions: Our results show that BCM patients with LCR deletions and Cys203Arg mutations have a population of non-waveguiding photoreceptors, although the spectral identity and level of function remain unknown.

Applying Human Factors Engineering to Address the Telemetry Alarm Problem in a Large Medical Center.

OBJECTIVE: Address the alarm problem by redesigning, reorganizing, and reprioritizing to better discriminate alarm sounds and displays in a hospital. BACKGROUND: Alarms in hospitals are frequently misunderstood, disregarded, and overridden. METHOD: Discovery-oriented, intervention, and translational studies were conducted. Study objectives and measures varied, but had the shared goals of increasing positive predictive value (PPV) of critical alarms by reducing low-PPV alarms in the background, prioritizing alarms, redesigning alarm sounds to increase information content, and transparently conveying who initiated alarms. An alarm ontology was iteratively generated and refined until consensus was achieved. RESULTS: The ontology distinguishes five levels of urgency that incorporate likely PPV, three categories for who initiates the alarm (hospital staff, patient, or machine), whether it is clinical or technical, and clinical functions. CONCLUSION: This unique collaboration allowed us to make progress on the alarm problem by making unintuitive leaps, avoiding common missteps, and refuting conventional healthcare approaches. APPLICATION: Hospitals can consistently redesign, reorganize, reprioritize, and better discriminate alarms by priority, PPV, and content to reduce nurse response times.

Retinal alterations in patients with Lafora disease.

PURPOSE: Lafora disease is a genetic neurodegenerative metabolic disorder caused by insoluble polyglucosan aggregate accumulation throughout the central nervous system and body. The retina is an accessible neural tissue, which may offer alternative methods to assess neurological diseases quickly and noninvasively. In this way, noninvasive imaging may provide a means to characterize neurodegenerative disease, which enables earlier identification and diagnosis of disease and the ability to monitor disease progression. In this study, we sought to characterize the retina of individuals with Lafora disease using non-invasive retinal imaging. METHODS: One eye of three individuals with genetically confirmed Lafora disease were imaged with optical coherence tomography (OCT) and adaptive optics scanning light ophthalmoscopy (AOSLO). When possible, OCT volume and line scans were acquired to assess total retinal thickness, ganglion cell-inner plexiform layer thickness, and outer nuclear layer + Henle fiber layer thickness. OCT angiography (OCTA) scans were acquired in one subject at the macula and optic nerve head (ONH). AOSLO was used to characterize the photoreceptor mosaic and examine the retinal nerve fiber layer (RNFL). RESULTS: Two subjects with previous seizure activity demonstrated reduced retinal thickness, while one subject with no apparent symptoms had normal retinal thickness. All other clinical measures, as well as parafoveal cone density, were within normal range. Nummular reflectivity at the level of the RNFL was observed using AOSLO in the macula and near the ONH in all three subjects. CONCLUSIONS: This multimodal retinal imaging approach allowed us to observe a number of retinal structural features in all three individuals. Most notably, AOSLO revealed nummular reflectivity within the inner retina of each subject. This phenotype has not been reported previously and may represent a characteristic change produced by the neurodegenerative process.

Lessons from the Glass Cockpit: Innovation in Alarm Systems to Support Cognitive Work.

Nurses working in the hospital setting increasingly have become overburdened by managing alarms that, in many cases, provide low information value regarding patient health. The current trend, aided by disposable, wearable technologies, is to promote patient monitoring that does not require entering a patient's room. The development of telemetry alarms and middleware escalation devices adds to the continued growth of auditory, visual, and haptic alarms to the hospital environment but can fail to provide a more complete understanding of patient health. As we begin to innovate to both address alarm overload and improve patient management, perhaps using fundamentally different integration architectures, lessons from the aviation flight deck are worth considering. Commercial jet transport systems and their alarms have evolved slowly over many decades and have developed integration methods that account for operational context, provide multiple response protocol levels, and present a more integrated view of the airplane system state. We articulate three alarm system objectives: (1) supporting hazard management, (2) establishing context, and (3) supporting alarm prioritization. More generally, we present the case that alarm design in aviation can spur directions for innovation for telemetry monitoring systems in hospitals.

Patients Are Knowledge Workers in the Clinical Information Space.

BACKGROUND: Limited research exists on patient knowledge/cognition or "getting inside patients' heads." Because patients possess unique and privileged knowledge, clinicians need this information to make patient-centered and coordinated treatment planning decisions. To achieve patient-centered care, we characterize patient knowledge and contributions to the clinical information space. METHODS AND OBJECTIVES: In a theoretical overview, we explore the relevance of patient knowledge to care provision, apply historical perspectives of knowledge acquisition to patient knowledge, propose a representation of patient knowledge types across the continuum of care, and include illustrative vignettes about Mr. Jones. We highlight how the field of human factors (a core competency of health informatics) provides a perspective and methods for eliciting and characterizing patient knowledge. CONCLUSION: Patients play a vital role in the clinical information space by possessing and sharing unique knowledge relevant to the clinical picture. Without a patient's contributions, the clinical picture of the patient is incomplete. A human factors perspective informs patient-centered care and health information technology solutions to support clinical information sharing.

Hemolytic disease and reticulocytopenia of the newborn attributable to maternal immunoglobulin G anti-M reacting optimally at cold temperatures.

BACKGROUND: Hemolytic disease of the fetus and newborn (HDFN) attributable to anti-M is rare, although case reports implicate anti-M in varying severities of HDFN, including fetal hydrops and intrauterine death. CASE DESCRIPTION: We describe the case of a newborn with HDFN associated with an atypical immunoglobulin (Ig) G anti-M that reacted best at cold temperatures. The maternal antibody detected in pregnancy was not reactive at 37°C, and a direct antiglobulin test (DAT) on red blood cells (RBCs) from the newborn was negative, suggesting an anti-M that should not have been clinically relevant. However, the infant developed hyperbilirubinemia (bilirubin level, 17.6 mg/dL), hemolytic anemia (hemoglobin nadir, 5.5 g/dL), and reticulocytopenia. Laboratory testing demonstrated the presence of an IgG anti-M in maternal and neonatal samples reacting best at 4°C. This passively acquired IgG anti-M provoked hemolytic anemia in the infant and likely suppressed erythropoiesis, resulting in reticulocytopenia with prolonged anemia. He was treated for IgG anti-M HDFN with 10 intravenous Ig infusions and 10 days of oral prednisone followed by a taper. He required seven transfusions with M- RBCs. His hemoglobin level normalized at 3 months of age. Follow-up at 2 years revealed no hematologic or neuro-developmental concerns. CONCLUSION: To our knowledge, this is the second report of HDFN attributable to an IgG anti-M reacting preferentially at cold temperature with no 37°C reactivity. Clinically relevant IgG anti-M may elude standard testing. Early recognition and testing for cold-reacting IgG anti-M should be considered for newborns with hemolysis, a negative DAT, and prolonged anemia.

Optical Coherence Tomography Artifacts Are Associated With Adaptive Optics Scanning Light Ophthalmoscopy Success in Achromatopsia.

Purpose: To determine whether artifacts in optical coherence tomography (OCT) images are associated with the success or failure of adaptive optics scanning light ophthalmoscopy (AOSLO) imaging in subjects with achromatopsia (ACHM). Methods: Previously acquired OCT and non-confocal, split-detector AOSLO images from one eye of 66 subjects with genetically confirmed achromatopsia (15 CNGA3 and 51 CNGB3) were reviewed along with best-corrected visual acuity (BCVA) and axial length. OCT artifacts in interpolated vertical volumes from CIRRUS macular cubes were divided into four categories: (1) none or minimal, (2) clear and low frequency, (3) low amplitude and high frequency, and (4) high amplitude and high frequency. Each vertical volume was assessed once by two observers. AOSLO success was defined as sufficient image quality in split-detector images at the fovea to assess cone quantity. Results: There was excellent agreement between the two observers for assessing OCT artifact severity category (weighted kappa = 0.88). Overall, AOSLO success was 47%. For subjects with OCT artifact severity category 1, AOSLO success was 65%; for category 2, 47%; for category 3, 11%; and for category 4, 0%. There was a significant association between OCT artifact severity category and AOSLO success (P = 0.0002). Neither BCVA nor axial length was associated with AOSLO success (P = 0.07 and P = 0.75, respectively). Conclusions: Artifacts in OCT volumes are associated with AOSLO success in ACHM. Subjects with less severe OCT artifacts are more likely to be good candidates for AOSLO imaging, whereas AOSLO was successful in only 7% of subjects with category 3 or 4 OCT artifacts. These results may be useful in guiding patient selection for AOSLO imaging. Translational Relevance: Using OCT to prescreen patients could be a valuable tool for clinical trials that utilize AOSLO to reduce costs and decrease patient testing burden.

Comparing Retinal Structure in Patients with Achromatopsia and Blue Cone Monochromacy Using OCT.

Purpose: To compare foveal hypoplasia and the appearance of the ellipsoid zone (EZ) at the fovea in patients with genetically confirmed achromatopsia (ACHM) and blue cone monochromacy (BCM). Design: Retrospective, multi-center observational study. Subjects: Molecularly confirmed patients with ACHM (n = 89) and BCM (n = 33). Methods: We analyzed high-resolution spectral domain optical coherence tomography (SD-OCT) images of the macula from aforementioned patients with BCM. Three observers independently graded SD-OCT images for foveal hypoplasia (i.e. retention of one or more inner retinal layers at the fovea) and four observers judged the integrity of the EZ at the fovea, based on an established grading scheme. These measures were compared with previously published data from the ACHM patients. Main Outcome Measures: Presence of foveal hypoplasia and EZ grade. Results: Foveal hypoplasia was significantly more prevalent in ACHM than in BCM (p<0.001). In addition, we observed a significant difference in the distribution of EZ grades between ACHM and BCM, with grade II EZ being by far the most common phenotype in BCM (61% of patients). In contrast, ACHM patients had a relatively equal prevalence of EZ grades I, II, and IV. Interestingly, grade IV EZ was 2.6 times more prevalent in ACHM compared to BCM, while grade V EZ (macular atrophy) was present in 3% of both the ACHM and BCM cohorts. Conclusions: The higher incidence of foveal hypoplasia in ACHM than BCM supports a role for cone activity in foveal development. Although there are differences in EZ grades between these conditions, the degree of overlap suggests EZ grade is not sufficient for definitive diagnosis, in contrast to previous reports. Analysis of additional OCT features in similar cohorts may reveal differences with greater diagnostic value. Finally, the extent to which foveal hypoplasia or EZ grade is prognostic for therapeutic potential in either group remains to be seen, but motivates further study.

A Qualitative Analysis of Outpatient Medication Use in Community Settings: Observed Safety Vulnerabilities and Recommendations for Improved Patient Safety.

OBJECTIVE: The aim of the study was to analyze diverse patients' experiences throughout the medication use process to inform the development of overarching interventions that support safe medication use in community settings. METHODS: Using a qualitative observational approach, we conducted approximately 18 hours of direct observation of the medication use process across multiple settings for a sample of vulnerable, high-risk patients. Observers recorded detailed field notes during the observations. To enrich the observational findings, we also conducted six semistructured interviews with medication safety experts representing a diversity of perspectives. Barriers and facilitators to safe medication use were identified based on inductive coding of the data. RESULTS: A variety of safety vulnerabilities plague all stages of the medication use process and many of the well-established evidence-based interventions aimed at improving the safety of medication use at key stages of the process have not been widely implemented in community settings observed in this study. Key safety vulnerabilities identified include: limited English proficiency, low health literacy, lack of clinician continuity, incomplete medication reconciliation and counseling, unsafe medication storage and disposal habits, and conflicting healthcare agendas with caregivers. CONCLUSIONS: Our findings underscore a need for overarching, comprehensive interventions that span the entire process of medication use, including integrated communication systems between clinicians, pharmacies, and patients, and a "patient navigator" program that assists patients in navigating the entire medication-taking process. Collective ownership of the medication management system and mutual motivation for devising collaborative solutions is needed among key sectors.

Efficacy of a patient decision aid for improving person-centered decision-making by older adults with obstructive sleep apnea.

STUDY OBJECTIVES: Person-centered obstructive sleep apnea (OSA) care is a collaborative approach that is respectful of an individual's health priorities. Informed decision-making is essential to person-centered care, especially as patients age. In a feasibility study, we evaluated the effects of a new decision aid (Decide2Rest) on OSA treatment decision-making in older adults. METHODS: Patients (aged ≥ 60 years) with newly diagnosed OSA were recruited from two health care systems and randomized either to Decide2Rest or to a control program. Postintervention outcomes included 1) Decisional Conflict Scale (0-100, where 0 = low and 100 = high conflict), which measures perceptions of uncertainty, whether decisions reflect what matters most to patients, and whether patients feel supported in decision-making; 2) Preparation for Decision-Making scale (0-100, where 0 = least and 100 most prepared); and 3) OSA knowledge (0-100, where 0 = poor and 100 = outstanding). Multivariable linear regression models examined relationships between Decide2Rest and outcomes (Decisional Conflict Scale, Preparation for Decision-Making, OSA knowledge). RESULTS: Seventy-three patients were randomized to Decide2Rest (n = 36; mean age, 69 years; 72% male) vs control (n = 37; mean age, 69 years; 70% male). Results from the regressions, controlling for study site, indicate that the Decide2Rest program resulted in less decisional conflict (20.5 vs 32.7 on the Decisional Conflict Scale; P = .014), more preparedness for decision-making (87.8 vs 66.2 on the Preparation for Decision-Making scale; P < .001), and greater OSA knowledge (75.1 vs 65.3 OSA knowledge score; P = .04) scores than in the control group. CONCLUSIONS: The Decide2Rest program promotes person-centered OSA decision-making for older patients with newly diagnosed OSA. Future studies are needed to optimize implementation of the program. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov, Name: Improving Older Adults' Decision-Making for OSAT (eDecide2Rest); URL: https://clinicaltrials.gov/ct2/show/NCT03138993; Identifier: NCT03138993.