Longitudinal Quantitative Ultrawidefield Angiographic Features in Diabetic Retinopathy Treated with Aflibercept from the Intravitreal Aflibercept as Indicated by Real-Time Objective Imaging to Achieve Diabetic Retinopathy Improvement Trial.

OBJECTIVE: To report longitudinal trends of quantitative ultrawidefield fluorescein angiography (qUWFA) biomarkers in the Intravitreal Aflibercept as Indicated by Real-Time Objective Imaging to Achieve Diabetic Retinopathy Improvement (PRIME) diabetic retinopathy (DR) clinical trial. DESIGN: Post hoc analysis of the PRIME prospective randomized DR clinical trial comparing intravitreal aflibercept treatment based on the DR severity score (DRSS) or quantitative leakage index for DR improvement (ClinicalTrials.gov identifier: NCT03531294). PARTICIPANTS: Patients were enrolled with a DRSS level of 47A to 71A and best-corrected visual acuity of 20/800 or better. Key exclusion criteria were previous intravitreal injection, panretinal photocoagulation, vitrectomy, central-involving macular edema, or vitreous hemorrhage. METHODS: A previously validated, machine learning-based qUWFA analysis platform was used for panretinal leakage index assessment and differentiation of generalized and perivascular leakage phenotypes. Additionally, microaneurysm count and ischemic index were quantified in panretinal and macular regions. The trends in these biomarkers and therapeutic response were studied over 1 year. MAIN OUTCOME MEASURES: Longitudinal trends of qUWFA biomarkers. The impact of these qUWFA metrics on treatment response was assessed by studying their associations with time to 2-step DRSS improvement and number of treatment-free days. RESULTS: Forty eyes from 40 subjects with DR were enrolled. Lower baseline generalized leakage was noted in eyes that attained the 2-step DRSS improvement in < 16 weeks (1.9% vs. 2.8%; P = 0.026). Baseline macular perivascular-generalized leakage ratio had a significant correlation with the number of treatment-free days (r = 0.4; P = 0.012). At the end of 1 year, therapy significantly reduced the mean panretinal (3.9% vs. 5.8%; P = 0.002) and macular (6.2% vs. 12.2%; P = 0.008) generalized leakage indices compared with baseline, as well as the mean panretinal perivascular leakage index (1.5% vs. 2.3%; P = 0.002). The mean panretinal ischemic index demonstrated a small but likely clinically insignificant decrease from 12.5% at baseline to 11.6% at year 1 (P = 0.016). CONCLUSIONS: Down-trending leakage indices and microaneurysm counts were demonstrated over 1 year of anti-VEGF therapy. At baseline, DR eyes with lower generalized leakage responded to therapy more rapidly. Eyes with greater perivascular leakage relative to generalized leakage showed a longer-lasting anti-VEGF treatment response. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Ecotoxicology Evaluation of a Fenton-Type Process Catalyzed with Lamellar Structures Impregnated with Fe or Cu for the Removal of Amoxicillin and Glyphosate.

Antibiotics and pesticides, as well as various emerging contaminants that are present in surface waters, raise significant environmental concerns. Advanced oxidation processes, which are employed to eliminate these substances, have demonstrated remarkable effectiveness. However, during the degradation process, by-products that are not completely mineralized are generated, posing a substantial risk to aquatic ecosystem organisms; therefore, it is crucial to assess effluent ecotoxicity following treatment. This study aimed to assess the toxicity of effluents produced during the removal of amoxicillin and glyphosate with a Fenton-type process using a laminar structure catalyzed with iron (Fe) and copper (Cu). The evaluation included the use of Daphnia magna, Selenastrum capricornutum, and Lactuca sativa, and mutagenicity testing was performed using strains TA98 and TA100 of Salmonella typhimurium. Both treated and untreated effluents exhibited inhibitory effects on root growth in L. sativa, even at low concentrations ranging from 1% to 10% v/v. Similarly, negative impacts on the growth of algal cells of S. capricornutum were observed at concentrations as low as 0.025% v/v, particularly in cases involving amoxicillin-copper (Cu) and glyphosate with copper (Cu) and iron (Fe). Notably, in the case of D. magna, mortality was noticeable even at concentrations of 10% v/v. Additionally, the treatment of amoxicillin with double-layer hydroxides of Fe and Cu resulted in mutagenicity (IM ≥ 2.0), highlighting the necessity to treat the effluent further from the advanced oxidation process to reduce ecological risks.

Evaluation of the change in efficacy of erenumab when used long-term for migraine prevention after initial established benefit in a veteran population.

INTRODUCTION: With the increased use of erenumab and other calcitonin gene-related peptide antagonists for migraine prevention, increased evidence on long-term efficacy and real-world effectiveness is needed. Some reports of a wearing-off effect or waning efficacy over time have been observed with erenumab use. OBJECTIVE: This study evaluated the change in efficacy of erenumab after initial established benefits for migraine prevention in a veteran population. METHODS: This retrospective chart review evaluated patients who were prescribed erenumab for migraine prevention at a Veterans Affairs neurology clinic between June 1, 2018, and May 31, 2021. Patients with an initial 50% or greater reduction in mean monthly headache days (MHDs) by 12 weeks after erenumab 70 mg initiation were then followed forward to determine the change in MHDs until erenumab dose was increased, changed to galcanezumab, or by November 30, 2021, to ensure a minimum 6-month follow-up for all patients. RESULTS: Ninety-three patients were included for analysis. A significant reduction in mean MHDs from 16.1 to 5.7 days was found by 12 weeks after erenumab 70 mg initiation (p < 0.0001). Following this initial response to erenumab, 69% of patients experienced a significant increase in MHDs over an average time of 7.8 months and required a subsequent dose increase to erenumab 140 mg or change to galcanezumab. The remaining 31% of patients continued erenumab 70 mg monthly with a further nonstatistically significant decline in MHDs. CONCLUSIONS: A decrease in efficacy with the long-term use of erenumab was observed for the majority of patients evaluated in this analysis. This suggests that patients with initial benefits on lower dose erenumab should be monitored for change to effectiveness.

Clinical, humanistic and economic outcomes, including experiencing of patient safety events, associated with admitting patients to single rooms compared with shared accommodation for acute hospital admissions: a systematic review and narrative synthesis.

OBJECTIVES: Assess the impact of single rooms versus multioccupancy accommodation on inpatient healthcare outcomes and processes. DESIGN: Systematic review and narrative synthesis. DATA SOURCES: Medline, Embase, Google Scholar and the National Institute for Health and Care Excellence website up to 17 February 2022. ELIGIBILITY CRITERIA: Eligible papers assessed the effect on inpatients staying in hospital of being assigned to a either a single room or shared accommodation, except where that assignment was for a direct clinical reason like preventing infection spread. DATA EXTRACTION AND SYNTHESIS: Data were extracted and synthesised narratively, according to the methods of Campbell et al. RESULTS: Of 4861 citations initially identified, 145 were judged to be relevant to this review. Five main method types were reported. All studies had methodological issues that potentially biased the results by not adjusting for confounding factors that are likely to have contributed to the outcomes. Ninety-two papers compared clinical outcomes for patients in single rooms versus shared accommodation. No clearly consistent conclusions could be drawn about overall benefits of single rooms. Single rooms were most likely to be associated with a small overall clinical benefit for the most severely ill patients, especially neonates in intensive care. Patients who preferred single rooms tended to do so for privacy and for reduced disturbances. By contrast, some groups were more likely to prefer shared accommodation to avoid loneliness. Greater costs associated with building single rooms were small and likely to be recouped over time by other efficiencies. CONCLUSIONS: The lack of difference between inpatient accommodation types in a large number of studies suggests that there would be little effect on clinical outcomes, particularly in routine care. Patients in intensive care areas are most likely to benefit from single rooms. Most patients preferred single rooms for privacy and some preferred shared accommodation for avoiding loneliness. PROSPERO REGISTRATION NUMBER: CRD42022311689.

Minimally Invasive Treatments for Benign Prostatic Obstruction: A Systematic Review and Network Meta-analysis.

CONTEXT: Minimally invasive surgical therapies for male lower urinary tract symptoms secondary to benign prostatic obstruction were developed to be safer and more tolerable than standard ablative techniques. These treatments have not been compared with each other in a randomised fashion, and for some treatments, there are no trials against a reference technique. OBJECTIVE: To compare the efficacy, safety, and tolerability of water vapour thermal therapy (WVTT), prostatic urethral lift (PUL), prostatic arterial embolisation (PAE), temporary implantable nitinol device (iTIND), transurethral microwave thermotherapy (TUMT), and transurethral resection of the prostate (TURP). EVIDENCE ACQUISITION: A systematic search of MEDLINE/PubMed, Embase, Cochrane Library, and grey literature for randomised controlled trials was performed. Trials meeting the selection criteria were assessed for the risk of bias using the Cochrane RoB2 tool. Treatments were compared, using a network meta-analysis, in terms of outcomes including symptom score, quality of life, maximum urinary flow rate, postvoid residual urine, International Index of Erectile Function (IIEF-5), and scales from the Male Sexual Health Questionnaire. EVIDENCE SYNTHESIS: The search identified 63 trials. Symptoms and quality of life for PAE, PUL, and WVTT appeared similar to those for TURP, whereas TURP was found to have the most clinically significant improvement in flow rate. TUMT was less efficacious than TURP but provided similar results on quality of life. Comparisons of ejaculatory function favoured WVTT and PUL compared with TURP. The relative efficacy of iTIND was less clear because of the risk of bias in the respective trial. CONCLUSIONS: PAE, PUL, and WVTT appear favourable from a risk-benefit perspective despite probably having less efficacy than TURP for objective outcomes. These findings warrant confirmation through long-term randomised controlled trials. PATIENT SUMMARY: This paper has summarised the evidence from 63 clinical trials on minimally invasive surgical therapies for men with symptoms of an enlarged prostate, including water vapour thermal therapy (WVTT), prostatic urethral lift (PUL), prostatic arterial embolisation (PAE), temporary implantable nitinol device, and transurethral microwave thermotherapy (TUMT). Improvement in symptoms for each of PAE, PUL, TUMT, and WVTT in short-term follow-up was similar to that for the standard surgical treatment, although standard surgery appeared to provide the greatest increase in urine flow. Men who had WVTT or PUL were less likely to have problems with sexual function than those who had standard surgery.

Longitudinal Quantitative Ultrawide-field Fluorescein Angiography Dynamics in the RUBY Diabetic Macular Edema Study.

OBJECTIVE: The purpose of this study was to evaluate the longitudinal change in quantitative ultrawide-field angiographic (UWFA) parameters and correlate them with functional outcomes and spectral domain-OCT metrics. DESIGN: This study is a post hoc analysis of the phase II RUBY study: a prospective, randomized trial of patients with diabetic macular edema (DME) treated with either intravitreal aflibercept injection (IAI) or combined IAI/nesvacumab (antiangiopoietin 2 mAb). SUBJECTS: Subjects with DME that underwent UWFA across all treatment groups (n = 44). METHODS: A machine learning-enabled feature extraction system generated panretinal quantitative UWFA metrics, including leakage, ischemia, and microaneurysm (MA) burden. Zonal assessments were performed corresponding to the macula, midperiphery, and far periphery. MAIN OUTCOME MEASURES: Changes in ischemic area and index (proportion of nonperfusion in analyzable retina), leakage area and index (proportion of leakage in analyzable retina), and MA count at baseline, week 12, week 24, and week 36 were analyzed. Spectral-domain-OCT quantitative metrics, such as central subfield thickness, ellipsoid zone (EZ) integrity parameters, intraretinal fluid (IRF) volume, and subretinal fluid (SRF) volume were extracted via a machine learning-enhanced OCT feature extraction platform and analyzed. Additionally, the effect of these changes on best-corrected visual acuity (BCVA) was evaluated. RESULTS: Mean panretinal leakage index, zonal leakage area, and panretinal MA count improved significantly between baseline and week 36. Panretinal ischemic index decreased between baseline and week 36, with some aspects showing significant improvement. Mean BCVA significantly improved from baseline to week 36. There was a significant inverse correlation between change in BCVA and change in macular leakage area. A direct correlation was observed between both baseline macular leakage area and panretinal leakage index with IRF volume, SRF volume, and EZ disruption on OCT. CONCLUSIONS: Assessment of UWFA parameters demonstrates a significant improvement in panretinal leakage index, leakage area, and MA burden in eyes treated with IAI with or without nesvacumab. A numeric reduction in panretinal ischemic index and area was noted. The analysis also shows the critical association of leakage with visual and OCT features. This highlights the potential role of UWFA in disease burden assessment, with leakage parameters serving as a primary end point. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

A systematic literature review of the clinical signs and symptoms of veno-occlusive disease/sinusoidal obstruction syndrome after haematopoietic cell transplantation in adults and children.

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a rare, serious complication following haematopoietic cell transplantation (HCT). This systematic literature review evaluated differences in clinical manifestations of VOD/SOS post-HCT in adults and children. Medline and Embase were searched up to 4 March 2021 for reports of VOD/SOS post-HCT; VOD/SOS diagnostic guidelines were included. Publications were evaluated based on inclusion of five cardinal clinical features of VOD/SOS (ascites, hepatomegaly, hyperbilirubinaemia, right upper quadrant [RUQ] pain and weight gain ≥5%). Overall, 204 publications were included. At diagnosis, hyperbilirubinaemia was more common in adults (93%) versus children (82%), weight gain ≥5% and hepatomegaly were more common in children (86%, 89%) versus adults (73%, 76%) and ascites and RUQ pain were similar between age groups. While 40% of cases had all five cardinal features, age was not a substantial determinant of the likelihood of missing any single specific feature. The proportion of cases, where hyperbilirubinaemia was the first recorded feature, was higher in children versus adults; weight gain and RUQ pain appeared first in a greater proportion of adults versus children. VOD/SOS diagnosis can be challenging; features may not present in a distinct sequence. This necessitates continuous vigilance by those involved in patient monitoring post-HCT.

Health Equity for Children and Youth With Special Health Care Needs: A Vision for the Future.

Health equity is a key pillar in supporting a future in which CYSHCN enjoy a full life and thrive, as envisioned by experts and community partners who gathered in 2019 and 2020 to develop the Blueprint for Change: Guiding Principles for a System of Services for Children and Youth With Special Health Care Needs and Their Families. However, a variety of contextual factors impact health outcomes across the life course and intergenerationally and must be addressed to achieve this goal. For example, poverty and discrimination, including by some health care professionals and systems, are important, modifiable root causes of poor health outcomes. There are numerous barriers to achieving health equity, including political will, lack of resources, insufficient training, and limited cross-sector collaborations. Political, cultural, societal, and environmental interventions are necessary to eliminate health disparities and achieve health equity. The entities that serve CYSHCN should be equitably designed and implemented to improve health outcomes and address health disparities. Many entities that serve CYSHCN are taking positive steps through workforce development, policy changes, community engagement, and other means. The purpose of this article is to frame health equity for CYSHCN, detail their health disparities, review barriers to health equity, provide examples of strategies to advance health equity for them, and describe a path toward the future in which all CYSHCN have a fair and just opportunity to be as healthy as possible.

The Efficacy and Safety of Laser and Electrosurgical Transurethral Procedures for the Treatment of BPO in High-Risk Patients: A Systematic Review.

Objective: To compare efficacy and safety outcomes of GreenLight, Holmium and Thulium laser  techniques with standard monopolar and bipolar transurethral resection of the prostate (TURP) in high-risk patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO). Methods: We conducted a systematic literature review of studies in patients undergoing BPO surgeries who may be considered high-risk for standard TURP, with higher risk defined as follows: large prostates (≥80 mL) and/or taking antithrombotic agents and/or urinary retention and/or age >80 years and/or significant comorbidity.  Outcomes summarised included bleeding complications, re-intervention rates, hospital length of stay, and standard measures of disease and symptom severity for all available timepoints. Results: A total of 276 studies of 32,722 patients reported relevant data. Studies were heterogeneous in methodology, population and outcomes reported. IPSS reduction, Qmax improvement and PVR were similar across all interventions. Mean values at baseline and after 12 months across interventions were 13.2-29 falling to 2.3-10.8 for IPSS, 0-19 mL/s increasing to 7.5-34.1 mL/s for Qmax and 41.4-954 mL falling to 5.1-138.3 mL for PVR. Laser treatments show some advantages compared with monopolar and bipolar TURP for some adverse events and safety parameters such as bleeding complications. Duration of hospital stay, reinterventions and recatheterisations were lower with GreenLight, HoLEP, Thulium lasers, and bipolar enucleation than TURP. Conclusions: Laser therapies are effective and well-tolerated treatment options in high-risk patients with BPO compared with monopolar or bipolar TURP. The advantageous safety profile of laser treatments means that patients with a higher bleeding risk should be offered laser surgery preferentially to mTURP or bTURP.

Corneal epithelial defects following vitreoretinal surgery: incidence and outcomes from the DISCOVER study.

AIM: To investigate the incidence, risk factors, clinical course, and outcomes of corneal epithelial defects (CED) following vitreoretinal surgery in a prospective study setting. METHODS: This was a post-hoc analysis of all participants in DISCOVER intraoperative optical coherence tomography study. Subjects with CED 1d after surgery without intraoperative corneal debridement was defined as the postoperative CED group. Subjects who underwent intraoperative debridement were defined as intraoperative debridement group. Eyes were matched 2:1 with controls (eyes without postoperative CED) for comparative assessment. The primary outcomes were the incidence of CED on postoperative day one and the incidence of required intraoperative debridement. Secondary outcomes included time to defect closure, delayed healing (>2wk), visual acuity (VA) and presence of scarring at one year and cornea consult. RESULTS: This study included 856 eyes that underwent vitreoretinal surgery. Intraoperative corneal debridement was performed to 61 (7.1%) subjects and postoperative CED developed spontaneously in 94 (11.0%) subjects. Significant factors associated with postoperative CED included prolonged surgical duration (P=0.003), diabetes mellitus (P=0.04), postoperative ocular hypotension (P<0.001). Prolonged surgical duration was associated with intraoperative debridement. Delayed defect closure time (>2wk) was associated with corneal scar formation at the end of the 1y in all epithelial defect subjects (P<0.001). The overall rate of corneal scarring for all eyes undergoing vitrectomy was 1.8%. CONCLUSION: Prolonged duration of surgery is the strongest factor associated with both intraoperative debridement and spontaneous postoperative CED. Delayed defect closure is associated with a greater risk of corneal scarring at one year. The overall rate of corneal scarring following vitrectomy is low at <2%.

Longitudinal assessment of quantitative ultra-widefield ischaemic and vascular parameters in sickle cell retinopathy.

PURPOSE: To evaluate longitudinal quantitative ischaemic and vasculature parameters, including ischaemic index, vessel area, length and geodesic distance in sickle cell retinopathy (SCR) on ultra-widefield fluorescein angiography (UWFA). METHODS: Optimal UWFA images from two longitudinal timepoints of 74 eyes from 45 patients with SCR were aligned and a common region of interest was determined. A deep-learning augmented ischaemia and vascular segmentation platform was used for feature extraction. Geodesic distance maps demonstrating the shortest distance within the vascular masks from the centre of the optic disc were created. Ischaemic index, vessel area, vessel length and geodesic distance were measured. Paired t-test and linear mixed effect model analysis were performed. RESULTS: Overall, 25 (44 eyes) patients with HbSS, 14 (19 eyes) with HbSC, 6 (11 eyes) with HbSthal and other genotypes were included. Mean age was 40.1±11.0 years. Mean time interval between two UWFA studies was 23.0±15.1 months (range: 3-71.3). Mean panretinal ischaemic index increased from 10.0±7.2% to 10.9±7.3% (p<0.005). Mean rate of change in ischaemic index was 0.5±0.7% per year. Mean vessel area (p=0.020) and geodesic distance (p=0.048) decreased significantly. Multivariate analysis demonstrated baseline ischaemic index and Goldberg stage are correlated with progression. CONCLUSION: Longitudinal ischaemic index and retinal vascular parameter measurements demonstrate statistically significant progression in SCR. The clinical significance of these relatively small magnitude changes remains unclear but may provide insights into the progression of retinal ischaemia in SCR.

Exploring the angiographic-biologic phenotype in the IMAGINE study: quantitative UWFA and cytokine expression.

BACKGROUND: This study investigates the association of intraocular cytokine expression and ultrawide-field fluorescein angiography (UWFA) quantitative imaging biomarkers and their association with angiographical feature response after antivascular endothelial growth factor (VEGF) therapy in diabetic macular oedema (DME). METHODS: The IMAGINE DME study is a post hoc imaging biomarker and intraocular cytokine assessment from the DAVE study, a prospective DME clinical trial that included aqueous humour sampling and UWFA imaging. Fifty-four cytokines associated with inflammation and angiogenesis were evaluated through multiplex arrays. UWFA parameters were assessed using an automated feature analysis platform to determine ischaemic and leakage indices and microaneurysm (MA) count. Eyes were classified into UWFA responder or non-responder groups based on longitudinal quantitative UWFA parameter improvement. Cytokine expression was correlated with UWFA metrics and evaluated in the context of therapeutic response. RESULTS: Twenty-one eyes were included with a mean age of 55±10 years. Increased panretinal leakage index correlated with VEGF (r=0.70, p=0.0005), angiopoietin-like 4 (r=0.77, p=4.6E-5) and interleukin (IL)-6 (r=0.64, p=0.002). Panretinal ischaemic index was associated with tissue inhibitor of metalloproteinases 1 (TIMP-1, r=0.49, p=0.03) and peripheral ischaemia correlated with VEGF (r=0.45, p=0.05). MA count correlated with increased monocyte chemotactic protein-4 (MCP-4, r=0.60, p=0.004) and platelet and endothelial cell adhesion molecule 1 (PECAM-1, r=0.58, p=0.005). Longitudinal MA reduction was associated with decreased baseline VEGF and urokinase receptor (uPAR) (p<0.05). High baseline VEGF and IL-6 were associated with dramatic reduction in macular leakage (p<0.05). CONCLUSIONS: Baseline and longitudinal quantitative UWFA imaging parameters correlated with multiple aqueous humour cytokine concentrations, including VEGF and IL-6. Further research is needed to assess the possible implications of using these findings for evaluating treatment response.

"All circuits ended": Family experiences of transitioning from pediatric to adult healthcare for young adults with medical complexity in Oregon.

BACKGROUND: Transition to adult health care for young adults with medical complexity (YAMC) is challenging and much work needs to be done in this area. The Oregon Center for Children and Youth with Special Health Needs participates in a federally-funded Collaborative Improvement and Innovation Network (CoIIN) to improve the quality of care for children with medical complexity. AIMS: This study aimed to explore the experiences of Oregon families of YAMC who had recently transitioned to adult health care providers, and obtain recommendations for transition from family members, to inform the development of the CoIIN quality improvement project. METHODS: We recruited caregivers of YAMC, ages 18 through 22 years, using a purposive sampling approach and conducted semi-structured interviews with 12 parents and grandparents. We analyzed the interview data to generate themes and sub-themes. RESULTS: Families described having little to no notice about transitioning out of pediatric care and reported that their providers did not communicate with them about the steps needed to ensure a continuation of care into adulthood. Poor transition processes contributed to gaps in needed care, decline in health status of the young adults and psychological burden on the family. Families had to take on the responsibility of meeting the transition needs of YAMC and faced challenges in finding adult providers. CONCLUSIONS: The results of this study suggest that YAMC and their families cared for by Oregon health care settings are not adequately prepared for, or supported in, the transition from pediatric to adult health care.

Smooth Triaxial Weaving with Naturally Curved Ribbons.

Triaxial weaving is a handicraft technique that has long been used to create curved structures using initially straight and flat ribbons. Weavers typically introduce discrete topological defects to produce nonzero Gaussian curvature, albeit with faceted surfaces. We demonstrate that, by tuning the in-plane curvature of the ribbons, the integrated Gaussian curvature of the weave can be varied continuously, which is not feasible using traditional techniques. Further, we reveal that the shape of the physical unit cells is dictated solely by the in-plane geometry of the ribbons, not elasticity. Finally, we leverage the geometry-driven nature of triaxial weaving to design a set of ribbon profiles to weave smooth spherical, ellipsoidal, and toroidal structures.

Reasons for discontinuing oral anticoagulation therapy for atrial fibrillation: a systematic review.

INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia and can lead to significant comorbidities and mortality. Persistence with oral anticoagulation (OAC) is crucial to prevent stroke but rates of discontinuation are high. This systematic review explored underlying reasons for OAC discontinuation. METHODS: A systematic review was undertaken to identify studies that reported factors influencing discontinuation of OAC in AF, in 11 databases, grey literature and backwards citations from eligible studies published between 2000 and 2019. Two reviewers independently screened titles, abstracts and papers against inclusion criteria and extracted data. Study quality was appraised using Gough's weight of evidence framework. Data were synthesised narratively. RESULTS: Of 6,619 sources identified, 10 full studies and 2 abstracts met the inclusion criteria. Overall, these provided moderate appropriateness to answer the review question. Four reported clinical registry data, six were retrospective reviews of patients' medical records and two studies reported interviews and surveys. Nine studies evaluated outcomes relating to dabigatran and/or warfarin and three included rivaroxaban (n = 3), apixaban (n = 3) and edoxaban (n = 1). Bleeding complications and gastrointestinal events were the most common factors associated with discontinuation, followed by frailty and risk of falling. Patients' perspectives were seldom specifically assessed. Influence of family carers in decisions regarding OAC discontinuation was not examined. CONCLUSION: The available evidence is derived from heterogeneous studies with few relevant data for the newer direct oral anticoagulants. Reasons underpinning decision-making to discontinue OAC from the perspective of patients, family carers and clinicians is poorly understood.

Plasma Neurofilament Light as a Biomarker of Neurological Involvement in Wilson's Disease.

BACKGROUND: Outcomes are unpredictable for neurological presentations of Wilson's disease (WD). Dosing regimens for chelation therapy vary and monitoring depends on copper indices, which do not reflect end-organ damage. OBJECTIVE: To identify a biomarker for neurological involvement in WD. METHODS: Neuronal and glial-specific proteins were measured in plasma samples from 40 patients and 38 age-matched controls. Patients were divided into neurological or hepatic presentations and those with recent neurological presentations or deterioration associated with non-adherence were subcategorized as having active neurological disease. Unified WD Rating Scale scores and copper indices were recorded. RESULTS: Unlike copper indices, neurofilament light (NfL) concentrations were higher in neurological than hepatic presentations. They were also higher in those with active neurological disease when controlling for severity and correlated with neurological examination subscores in stable patients. CONCLUSION: NfL is a biomarker of neurological involvement with potential use in guiding chelation therapy and clinical trials for novel treatments. © 2020 University College London. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Adoption of recommended hand hygiene practices to limit zoonotic disease transmission at agricultural fairs.

Rapid transmission and spread of infectious pathogens are enhanced by the agricultural fair environment, where large numbers of livestock and people from numerous backgrounds congregate for several days. The transmission of influenza A virus and zoonotic enteric pathogens to fairgoers is a considerable risk and has occurred several times over the past decade. In an effort to mitigate zoonotic disease transmission in these settings, public health guidelines and recommendations including hand sanitation stations have been implemented. While hand hygiene recommendations to prevent the spread of zoonotic disease are well communicated, it is hypothesized that the adoption of these recommendations by agricultural fairs and fairgoers is low. To test this hypothesis, hand hygiene data collected from 658 agricultural fairs between 2012 and 2019 was analyzed to determine frequency and function of hand sanitation stations at the fairs, as well as utilization of educational signage. In addition, an observational study was performed to calculate the proportion of fairgoers who use hand sanitation stations at the fair. Lastly, samples were taken from working hand sanitation stations present at the exits of livestock barns and tested for the presence of influenza A virus and antimicrobial resistant coliform bacteria. Hand sanitation stations were present at most fairs (77.4 %) as recommended, but only 142 out of 2021 (7.0 %) visitors were observed using the stations. Health risk signage was displayed at more than half of fairs while the proper wash procedure was displayed at less than half. No influenza A virus was detected on any of the hand sanitation stations, however antimicrobial resistant coliform bacteria were recovered from 75.5 % of the sampled hand sanitation stations. Fairs should employ educational material along with functional hand sanitation stations in order to promote hand hygiene at fairs. Stations should be maintained and cleaned often to ensure effectiveness, as hand hygiene continues to be recommended to fairgoers when exiting animal barns to reduce zoonotic disease transmission.

A Profile of Care Coordination, Missed School Days, and Unmet Needs Among Oregon Children with Special Health Care Needs with Behavioral and Mental Health Conditions.

To inform Oregon's Title V needs assessment activities, we aimed to (1) characterize the state's subpopulation of children with special health care needs (CSHCN) with behavioral and mental health conditions (B/MHC) and (2) determine associations of care coordination with missed school days and unmet needs for this subpopulation. We analyzed 2009-2010 National Survey of Children with Special Health Care Needs data on 736 Oregon CSHCN < 18 years, including 418 CSHCN with B/MHC. Among Oregon CSHCN with B/MHC: 48.9% missed ≥ 4 school days, 25% had ≥ 1 unmet health services need, and 14.8% had ≥ 1 unmet family support services need. Care coordination was associated with lower adjusted odds of ≥ 1 unmet health services need but was not significantly associated with missed school days or unmet family support services need. The approach to identify Oregon CSHCN with B/MHC may be adopted by other states endeavoring to improve health for this vulnerable subpopulation.

Unusual Fungal Lesion Presenting as a Neoplastic Pediatric Tongue Mass.

Tongue lesions in the pediatric population are rare. The differential diagnosis of these lesions is broad, and rapid growth of the lesion is concerning for a neoplastic process. We present a rare case of a fungal lesion mimicking a neoplastic growth in a 22-month-old girl. She underwent complete excision successfully. Full evaluation for benign and malignant neoplasms was negative. Tissue culture demonstrated growth of a rare Candida species to be the cause of the lesion. Postoperatively, she continues to do well, without regrowth 6 months later. This case reinforces the role of tissue culture when histology fails to demonstrate a diagnosis and emphasizes the need for efficient communication between the pediatrician, otolaryngologist, and pathologist for timely excision.

Erythropoiesis-stimulating agents in elderly patients with anemia: response and cardiovascular outcomes.

A specific cause of anemia cannot be identified in many elderly patients. Erythropoiesis-stimulating agents (ESAs) may play a role in treating these patients with anemia of unknown etiology (AUE). This study examines hemoglobin and cardiovascular outcomes among elderly anemic patients treated with ESAs. We conducted a retrospective cohort study that included all anemic patients older than age 60 years who had erythropoietin (EPO) measured between 2005 and 2013 at a single center. Three independent reviewers used defined criteria to assign each patient's anemia to 1 of 4 groups: chronic kidney disease (CKD), myelodysplastic syndrome, AUE, or other etiology. Logistic regression was used to compare treatment response (defined per the International Working Group response criteria in myelodysplasia). Adjusted Cox regression analysis was used to calculate the cardiovascular event hazard ratios associated with ESA treatment. A total of 570 patients met the inclusion criteria, of whom 101 received ESAs. There was a nonstatistically significant but quantitatively better response in AUE (47%) and CKD (54%) compared with other etiologies (22%). The adjusted odds ratio for response in AUE compared with other etiologies was 3.3 (95% confidence interval, 0.838-13.0). A baseline EPO level <200 IU/L independently predicted treatment response. There was no statistically significant difference in cardiovascular events or cardiovascular event-free survival between the treated and untreated groups after adjusting for confounders. Our results suggest that ESAs may effectively treat AUE, and responses may be similar to those in CKD. We could not detect a statistically significant increase in cardiovascular events in the studied cohort.