A case of accommodation-induced lens subluxation with iris displacement causing intermittent angle closure.

Purpose: To present an uncommon cause of intermittent angle closure in a young adult patient presenting with intermittent headache and blurry vision exacerbated by accommodation. Observations: A 37-year-old man reported experiencing intermittent blurry vision, headache, and pain in both eyes associated with prolonged periods of reading beginning at age 17. Serial intraocular pressure (IOP) measurements showed an increase in IOP from 14 to 32 mmHg in the right eye and from 9 to 37 mmHg in the left eye after 145 minutes of sustained accommodation while sitting up. IOP did not normalize after laser peripheral iridotomy but did normalize after clear lens extraction. Conclusions and importance: This case characterized a rare presentation of accommodation-induced IOP elevation in a young adult male that resolved only after clear lens extraction. The clinical takeaway was the importance of considering accommodation-associated angle closure in patients presenting with high intraocular pressures, eye strain, and/or headache with accommodative activities. Notable symptoms that should raise suspicion for this syndrome include halos, changes in visual acuity, and headache with accommodation. We suggested that patients presenting with these symptoms be followed closely, with a full glaucoma evaluation including gonioscopy and possible ultrasound biomicroscopy to assess for pediatric eversional angle closure with headache, plateau iris, angle closure glaucoma, and lens-induced angle closure.

Clinical and healthcare utilization outcomes during the 6 months following COVID infection in children.

BACKGROUND: We aimed to identify the impact of COVID infection in children in the US prior to vaccine availability on clinical and healthcare utilization outcomes within 6 months of infection. METHODS: Using claims data from a large national insurer, we identified 223,842 children with a COVID diagnosis in May 2020-March 2021 and matched them to 223,842 children with a COVID test and no diagnosis. We compared the two cohorts' outcomes during the 6 months after infection/test. RESULTS: Uncommon acute adverse events occurring in <0.5% of cases, including MIS-C (relative risk (RR) = 45.2), myocarditis (RR = 10.3), acute heart failure (RR = 2.14), sepsis (RR = 2.02), and viral pneumonia (RR = 2.43) were more frequent in the COVID cohort (all p < 0.001). Development of arrhythmias (RR = 1.24, p < 0.001) and atherosclerotic cardiovascular disease (RR = 1.41, p = 0.007) were more common in the COVID group, while behavioral health disorders were less common (RR = 0.94, p < 0.001). Lab testing and imaging were slightly higher in the COVID group (RR ranging 1.05-1.11 depending on the service and timeframe), though medical costs did not increase. CONCLUSION: Severe disease and diagnoses of new conditions are rare in children following COVID infection. We observed an increase in cardiac complications, though they may not last long term. IMPACT: Few studies have analyzed the association between COVID infection and medium-term outcomes in children. Our study of >447,000 geographically and socioeconomically diverse children in the US found that uncommon acute adverse events, including myocarditis, MIS-C, and acute heart failure, were more frequent in children with COVID than matched controls, and development of arrhythmias and cardiovascular disease were 1.2 and 1.4 times more common, respectively. Six-month healthcare utilization was similar between cohorts. We provide data on the risks of COVID in children, particularly with respect to cardiac complications, that decision makers may find useful when weighing the benefits and harms of preventive measures.

Glaucoma and Systemic Disease.

Glaucoma is the leading cause of irreversible blindness in the world. Due to its potential to cause permanent vision loss, it is important to understand how systemic conditions and their respective treatments can be associated with or increase the risk for developing glaucoma. In this review, we examined the literature for up-to-date discussions and provided commentary on glaucoma, its pathophysiology, and associated risk factors. We discuss systemic diseases and the impact, risk, and mechanism for developing glaucoma, including pharmacologically induced glaucoma; inflammatory and auto-immune conditions; infectious, dermatologic, cardiovascular, pulmonary, renal, urologic, neurologic, psychiatric and systemic malignancies: intraocular tumors; as well as pediatric, and genetic conditions. The goal of our discussion of systemic conditions including their commonality, mechanisms, treatments, and associations with developing glaucoma is to emphasize the importance of ocular examinations and follow-up with the multidisciplinary teams involved in the care of each patient to prevent unnecessary vision-loss.

Early circulating tumor DNA dynamics as a pan-tumor biomarker for long-term clinical outcome in patients treated with durvalumab and tremelimumab.

There is an urgent need to identify biomarkers of early response that can accurately predict the benefit of immune checkpoint inhibitors (ICI). Patients receiving durvalumab/tremelimumab had tumor samples sequenced before treatment (baseline) to identify variants for the design of a personalized circulating tumor (ctDNA) assay. ctDNA was assessed at baseline and at 4 and/or 8 weeks into treatment. Correlations between ctDNA changes to radiographic response and overall survival (OS) were made to assess potential clinical benefit. 35/40 patients (87.5%) had personalized ctDNA assays designed, and 29/35 (82.9%) had plasma available for baseline analysis, representing 16 unique solid tumor histologies. As early as 4 weeks after treatment, decline in ctDNA from baseline predicted improved OS (P = 0.0144; HR = 9.98) and ctDNA changes on treatment-supported and refined radiographic response calls. ctDNA clearance at any time through week 8 identified complete responders by a median lead time of 11.5 months ahead of radiographic imaging. ctDNA response monitoring is emerging as a dynamic, personalized biomarker method that may predict survival outcomes in patients with diverse solid tumor histologies, complementing and sometimes preceding standard-of-care imaging assessments.

Effect of a Biopsychosocial Intervention or Postural Therapy on Disability and Health Care Spending Among Patients With Acute and Subacute Spine Pain: The SPINE CARE Randomized Clinical Trial.

Importance: Low back and neck pain are often self-limited, but health care spending remains high. Objective: To evaluate the effects of 2 interventions that emphasize noninvasive care for spine pain. Design, Setting, and Participants: Pragmatic, cluster, randomized clinical trial conducted at 33 centers in the US that enrolled 2971 participants with neck or back pain of 3 months' duration or less (enrollment, June 2017 to March 2020; final follow-up, March 2021). Interventions: Participants were randomized at the clinic-level to (1) usual care (n = 992); (2) a risk-stratified, multidisciplinary intervention (the identify, coordinate, and enhance [ICE] care model that combines physical therapy, health coach counseling, and consultation from a specialist in pain medicine or rehabilitation) (n = 829); or (3) individualized postural therapy (IPT), a postural therapy approach that combines physical therapy with building self-efficacy and self-management (n = 1150). Main Outcomes and Measures: The primary outcomes were change in Oswestry Disability Index (ODI) score at 3 months (range, 0 [best] to 100 [worst]; minimal clinically important difference, 6) and spine-related health care spending at 1 year. A 2-sided significance threshold of .025 was used to define statistical significance. Results: Among 2971 participants randomized (mean age, 51.7 years; 1792 women [60.3%]), 2733 (92%) finished the trial. Between baseline and 3-month follow-up, mean ODI scores changed from 31.2 to 15.4 for ICE, from 29.3 to 15.4 for IPT, and from 28.9 to 19.5 for usual care. At 3-month follow-up, absolute differences compared with usual care were -5.8 (95% CI, -7.7 to -3.9; P < .001) for ICE and -4.3 (95% CI, -5.9 to -2.6; P < .001) for IPT. Mean 12-month spending was $1448, $2528, and $1587 in the ICE, IPT, and usual care groups, respectively. Differences in spending compared with usual care were -$139 (risk ratio, 0.93 [95% CI, 0.87 to 0.997]; P = .04) for ICE and $941 (risk ratio, 1.40 [95% CI, 1.35 to 1.45]; P < .001) for IPT. Conclusions and Relevance: Among patients with acute or subacute spine pain, a multidisciplinary biopsychosocial intervention or an individualized postural therapy intervention, each compared with usual care, resulted in small but statistically significant reductions in pain-related disability at 3 months. However, compared with usual care, the biopsychosocial intervention resulted in no significant difference in spine-related health care spending and the postural therapy intervention resulted in significantly greater spine-related health care spending at 1 year. Trial Registration: ClinicalTrials.gov Identifier: NCT03083886.

Improving adherence to guidelines for spine pain care: what tools could support primary care clinicians in conforming to guidelines?

BACKGROUND: Spine pain is one of the most common conditions seen in primary care and is often treated with ineffective, aggressive interventions, such as prescription pain medications, imagery and referrals to surgery. Aggressive treatments are associated with negative side effects and high costs while conservative care has lower risks and costs and equivalent or better outcomes. Despite multiple well-publicised treatment guidelines and educational efforts recommending conservative care, primary care clinicians (PCCs) widely continue to prescribe aggressive, low-value care for spine pain. METHODS: In this qualitative study semistructured interviews were conducted with PCCs treating spine pain patients to learn what prevents clinicians from following guidelines and what tools or support could promote conservative care. Interviews were conducted by telephone, transcribed and coded for thematic analysis. RESULTS: Forty PCCs in academic and private practice were interviewed. Key reflections included that while familiar with guidelines recommending conservative treatment, they did not find guidelines useful or relevant to care decisions for individual patients. They believed that there is an insufficient body of real-world evidence supporting positive outcomes for conservative care and guidance recommendations. They indicated that spine pain patients frequently request aggressive care. These requests, combined with the PCCs' commitment to reaching shared treatment decisions with patients, formed a key reason for pursuing aggressive care. PCCs reported not being familiar with risk-screening tools for spine patients but indicated that such screens might increase their confidence to recommend conservative care to low-risk patients. CONCLUSIONS: PCCs may be more willing to give conservative, guideline-consistent care for spine pain if they had tools to assist in making patient-specific evaluations and in countering requests for unneeded aggressive care. Such tools would include both patient risk screens and shared decision-making aids that include elements for resolving patient demands for inappropriate care.

Design of the Spine Pain Intervention to Enhance Care Quality And Reduce Expenditure Trial (SPINE CARE) study: Methods and lessons from a multi-site pragmatic cluster randomized controlled trial.

BACKGROUND: Low back and neck pain (together, spine pain) are among the leading causes of medical visits, lost productivity, and disability. For most people, episodes of spine pain are self-limited; nevertheless, healthcare spending for this condition is extremely high. Focusing care on individuals at high-risk of progressing from acute to chronic pain may improve efficiency. Alternatively, postural therapies, which are frequently used by patients, may prevent the overuse of high-cost interventions while delivering equivalent outcomes. METHODS: The SPINE CARE (Spine Pain Intervention to Enhance Care Quality And Reduce Expenditure) trial is a cluster-randomized multi-center pragmatic clinical trial designed to evaluate the clinical effectiveness and healthcare utilization of two interventions for primary care patients with acute and subacute spine pain. The study was conducted at 33 primary care clinics in geographically distinct regions of the United States. Individuals ≥18 years presenting to primary care with neck and/or back pain of ≤3 months' duration were randomized at the clinic-level to 1) usual care, 2) a risk-stratified, multidisciplinary approach called the Identify, Coordinate, and Enhance (ICE) care model, or 3) Individualized Postural Therapy (IPT), a standardized postural therapy method of care. The trial's two primary outcomes are change in function at 3 months and spine-related spending at one year. 2971 individuals were enrolled between June 2017 and March 2020. Follow-up was completed on March 31, 2021. DISCUSSION: The SPINE CARE trial will determine the impact on clinical outcomes and healthcare costs of two interventions for patients with spine pain presenting to primary care. TRIAL REGISTRATION NUMBER: NCT03083886.

Alzheimer-related altered white matter microstructural integrity in Down syndrome: A model for sporadic AD?

INTRODUCTION: Virtually all adults with Down syndrome (DS) develop Alzheimer's disease (AD)-associated neuropathology by the age of 40, with risk for dementia increasing from the early 50s. White matter (WM) pathology has been reported in sporadic AD, including early demyelination, microglial activation, loss of oligodendrocytes and reactive astrocytes but has not been extensively studied in the at-risk DS population. METHODS: Fifty-six adults with DS (35 cognitively stable adults, 11 with mild cognitive impairment, 10 with dementia) underwent diffusion-weighted magnetic resonance imaging (MRI), amyloid imaging, and had assessments of cognition and functional abilities using tasks appropriate for persons with intellectual disability. RESULTS: Early changes in late-myelinating and relative sparing of early-myelinating pathways, consistent with the retrogenesis model proposed for sporadic AD, were associated with AD-related cognitive deficits and with regional amyloid deposition. DISCUSSION: Our findings suggest that quantification of WM changes in DS could provide a promising and clinically relevant biomarker for AD clinical onset and progression.

Subcaudate Tractotomy White Matter Anatomy and Variability: A Diffusion Tensor Imaging Study.

BACKGROUND: Subcaudate tractotomy is a functional ablative procedure performed for treatment-resistant psychiatric disease, targeting the white matter tracts ventral to the head of the caudate nucleus. The white matter anatomy of this region has extensive interindividual variability, and this is thought to impact upon the treatment response to ablative and deep brain stimulation procedures. OBJECTIVE: We aim to assess in detail the white matter tract anatomy and topographic variability underlying subcaudate tractotomy. METHODS: 74 non-depressed adult volunteers underwent MRI including diffusion tensor imaging. Individualized regions of interest were formed in both hemispheres using native non-normalized data to simulate a subcaudate tractotomy. Tractography and analysis were performed and the exact tract locations measured including mean distances and standard deviations to assess variability. RESULTS: The cingulum bundle, uncinate fasciculus, corticostriatal fibres, and corticothalamic fibres were consistently demonstrated. The location of the cingulum bundle was consistent across subjects, but there was extensive interindividual variability in the topographic location of the other tracts. CONCLUSION: We have demonstrated a detailed analysis of the white matter tracts and their anatomical variability underlying subcaudate tractotomy. This has significant implications for neurosurgical targeting.

Reduced integrity of the uncinate fasciculus and cingulum in depression: A stem-by-stem analysis.

INTRODUCTION: The subgenual cingulate gyrus (Brodmann's Area 25: BA25) is hypermetabolic in depression and has been targeted successfully with deep brain stimulation. Two of the white matter tracts that play a role in treatment response are the uncinate fasciculus (UF) and the cingulum bundle. The UF has three prefrontal stems, the most medial of which extends from BA25 (which deals with mood regulation) and the most lateral of which extends from the dorso-lateral prefrontal cortex (concerned with executive function). The cingulum bundle has numerous fibers connecting the lobes of the cerebrum, with the longest fibers extending from BA25 to the amygdala. We hypothesize that there is reduced integrity in the UF, specific to the medial prefrontal stems, as well as in the subgenual and amygdaloid fibers of the cingulum bundle. Our secondary hypothesis is that these changes are present from the early stages of depression. OBJECTIVE: Compare the white matter integrity of stems of the UF and components of the cingulum bundle in first-onset depressed, recurrent/chronic depressed, and non-depressed control subjects. METHODS: Depressed patients (n = 103, first-onset = 57, chronic = 46) and non-depressed control subjects (n = 74) underwent MRI with 32-directional DTI sequences. The uncinate fasciculi and cingulum bundles were seeded, and the fractional anisotropy (FA) measured in each of the three prefrontal stems and the body of the UF, as well as the subgenual, body, and amygdaloid fiber components of the cingulum bundle. FA measurements were compared between groups using ANOVA testing with post-hoc Tukey analysis. RESULTS: There were significant reductions in FA in the subgenual and polar stems of the UF bilaterally, as well as the subgenual and amygdaloid fibers of the cingulum bundle, in depressed patients compared with controls (p < 0.001). There was no significant difference seen in the lateral UF stem or the main body of the cingulum. No significant difference was demonstrated in any of the tracts between first-onset and chronic depression patients. CONCLUSION: Depressed patients have reduced white matter integrity in the subgenual and polar stems of the uncinate fasciculi but not the lateral stems, as well as in the subgenual and amygdaloid cingulum fibers. These changes are present from the first-onset of the disease.

Magnetic Resonance Imaging Appearance of Schwannomas from Head to Toe: A Pictorial Review.

Schwannomas are benign soft-tissue tumors that arise from peripheral nerve sheaths throughout the body and are commonly encountered in patients with neurofibromatosis Type 2. The vast majority of schwannomas are benign, with rare cases of malignant transformation reported. In this pictorial review, we discuss the magnetic resonance imaging (MRI) appearance of schwannomas by demonstrating a collection of tumors from different parts of the body that exhibit similar MRI characteristics. We review strategies to distinguish schwannomas from malignant soft-tissue tumors while exploring the anatomic and histologic origins of these tumors to discuss how this correlates with their imaging findings. Familiarity with the MRI appearance of schwannomas can help aid in the differential diagnosis of soft-tissue masses, especially in unexpected locations.

Diffusion Tensor Imaging Investigation of Uncinate Fasciculus Anatomy in Healthy Controls: Description of a Subgenual Stem.

The uncinate fasciculus is the largest white matter association tract connecting the prefrontal cortex and the anteromedial temporal lobe. The traditional anatomical description outlines a temporal stem that hooks around the posterior insula, a subinsular body, and 2 prefrontal stems extending to the lateral orbital gyri and the frontopolar cortex. Recent imaging studies of the white matter tracts deep to the subgenual cingulate gyrus (Brodmann area 25: BA25) suggest the presence of white matter fibers extending from BA25 to the amygdala, via a route that would run in close proximity to the uncinate fasciculus, that are of functional importance in mood disorders. We hypothesized that these fibers represent a third, medial prefrontal stem of the uncinate fasciculus. Using diffusion tensor imaging in 74 healthy volunteer humans, we seeded the uncinate fasciculus using 2 regions of interest centered over the temporal stem and the caudal body of the uncinate fasciculus in the coronal plane at the level of the anterior commissure. A medial prefrontal stem extending to the subgenual cingulate gyrus was demonstrated in 65/74 left and 70/74 right cerebral hemispheres, and had a mean fractional anisotropy value of 0.43 (95% CI 0.40-0.47). The medial subgenual stem fibers were inseparable from the caudal body and temporal stem of the main uncinate fasciculus and followed the same hook-shaped morphology. A probable medial subgenual prefrontal stem of the uncinate fasciculus was demonstrated in a cohort of healthy volunteers and is of potential significance in our understanding of neuropsychiatry and mood disorders.

SPECT-CT/VQ versus CTPA for diagnosing pulmonary embolus and other lung pathology: Pre-existing lung disease should not be a contraindication.

INTRODUCTION: Single Photon Emission Computed Tomography-Ventilation-Perfusion (SPECT-VQ) with low-dose CT (SPECT-CT/VQ) has equivalent diagnostic accuracy to CTPA for diagnosing pulmonary embolus (PE) while using lower radiation doses, but is underutilized owing to perceived inaccuracy of scintigraphy in the setting of pre-existing lung disease. This study assesses the accuracy of SPECT-CT/VQ compared with CTPA for the diagnosis of PE, including in patients with pre-existing lung disease. METHODS: Retrospective non-inferiority cohort study of all patients who underwent SPECT-CT/VQ scanning at St Vincent's Hospital, NSW, from June 2012 to November 2013, who also had a CTPA within the same admission and <72 h apart (n = 102). RESULTS: SPECT-CT/VQ had 100% sensitivity and 94.4% specificity when compared with CTPA. Of the 102 patients, 14 were lung transplant patients, and 27 had other pre-existing lung disease (41/102, 40.2%), with SPECT-CT/VQ having a sensitivity of 100% and specificity of 97.2% in this patient group. Non-inferiority of SPECT-CT/VQ was demonstrated at a significance level of 0.005. CONCLUSION: SPECT-CT/VQ has high sensitivity and specificity for diagnosing PE compared with CTPA, even among patients with pre-existing lung disease, with lower radiation doses.

Anti-nerve growth factor in pain management: current evidence.

There continues to be an unmet need for safe and effective pain medications. Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) dominate the clinical landscape despite limited effectiveness and considerable side-effect profiles. Although significant advancements have identified myriad potential pain targets over the past several decades, the majority of new pain pharmacotherapies have failed to come to market. The discovery of nerve growth factor (NGF) and its interaction with tropomyosin receptor kinase A (trkA) have been well characterized as important mediators of pain initiation and maintenance, and pharmacotherapies targeting this pathway have the potential to be considered promising methods in the treatment of a variety of nociceptive and neuropathic pain conditions. Several methodologic approaches, including sequestration of free NGF, prevention of NGF binding and trkA activation, and inhibition of trkA function, have been investigated in the development of new pharmacotherapies. Among these, NGF-sequestering antibodies have exhibited the most promise in clinical trials. However, in 2010, reports of rapid joint destruction leading to joint replacement prompted the US Food and Drug Administration (FDA) to place a hold on all clinical trials involving anti-NGF antibodies. Although the FDA has since lifted this hold and a number of new trials are under way, the long-term efficacy and safety profile of anti-NGF antibodies are yet to be established.

Expert opinion on emerging drugs: chronic low back pain.

INTRODUCTION: It is difficult to overestimate the personal and socioeconomic impact of chronic low back pain (CLBP). It is the leading cause of years lost to disability and poses the highest economic toll among chronic illnesses. Despite the strong need for extensive research efforts, few drugs have consistently demonstrated effectiveness for this condition. AREAS COVERED: In this review, the epidemiology, rationale for mechanism-based treatment, competitive environment and market trends, and the preclinical and clinical evidence supporting over 15 different classes of analgesic medications studied for CLBP or related pain conditions are discussed. Treatments are divided by drug category, type of CLBP they are likely to treat (e.g., neuropathic or mechanical), and whether they are new formulations of existing treatments, new indications for existing treatments or represent novel mechanisms of action. Databases searched included MEDLINE, Embase, Pharmaprojects and various clinical trial registries. EXPERT OPINION: Many barriers exist for the development of medications for CLBP including difficulties in identifying pathophysiological mechanisms, biologic resiliency secondary to multiple concurrent pain pathways and off-target and sometimes serious side effects. Nevertheless, the volume and diversity of novel molecular entities has continued to surge and includes possible disease-modifying therapies such as gene and stem cell therapy.

Orthopedic resident work-shift analysis: are we making the best use of resident work hours?

BACKGROUND: Surgery programs have been tasked to meet rising demands in patient surgical care while simultaneously providing adequate resident training in the midst of increasing resident work-hour restrictions. The purpose of this study was to quantify orthopedic surgery resident workflow and identify areas needing improved resident efficiency. We hypothesize that residents spend a disproportionate amount of time involved in activities that do not relate directly to patient care or maximize resident education. METHODS: We observed 4 orthopedic surgery residents on the orthopedic consult service at a major tertiary care center for 72 consecutive hours (6 consecutive shifts). We collected minute-by-minute data using predefined work-task criteria: direct new patient contact, direct existing patient contact, communications with other providers, documentation/administrative time, transit time, and basic human needs. A seventh category comprised remaining less-productive work was termed as standby. RESULTS: In a 720-minute shift, residents spent on an average: 191 minutes (26.5%) performing documentation/administrative duties, 167.0 minutes (23.2%) in direct contact with new patient consults, 129.6 minutes (17.1%) in communication with other providers regarding patients, 116.2 (16.1%) minutes in standby, 63.7 minutes (8.8%) in transit, 32.6 minutes (4.5%) with existing patients, and 20 minutes (2.7%) attending to basic human needs. Residents performed an additional 130 minutes of administrative work off duty. Secondary analysis revealed residents were more likely to perform administrative work rather than directly interact with existing patients (p = 0.006) or attend to basic human needs (p = 0.003). CONCLUSIONS: Orthopedic surgery residents spend a large proportion of their time performing documentation/administrative-type work and their workday can be operationally optimized to minimize nonvalue-adding tasks. Formal workflow analysis may aid program directors in systematic process improvements to better align resident skills with tasks. LEVEL OF EVIDENCE: III.

Doing well by doing good: assessing the cost savings of an intervention to reduce central line-associated bloodstream infections in a Hawaii hospital.

A complete understanding of the financial impact of patient safety interventions must consider the economic incentives of both payers and providers within the current fee-for-service payment model. This study evaluated the impact of a central line-associated bloodstream infection (CLABSI) initiative on costs, reimbursements, and margins for 1 Hawaii hospital and its payers. Intensive care unit patients (January 2009-December 2011) who developed a CLABSI were compared to matched controls. Mean hospital cost, reimbursement, and margin was $222 692 versus $80 144 (P = .01), $259 433 versus $72 543 (P < .01), and $54 906 versus $6506 (P < .01), respectively. Although hospitals and payers reduce costs by preventing CLABSIs, hospitals also would decrease their margins, which creates a perverse incentive to have more line infections. An optimal reimbursement system must reward hospitals and payers for preventing harm rather than treating illness. This study highlights the critical role that health care payers have as patient safety advocates, financial sponsors, and facilitators.