"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.

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.

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.

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.

Genetic features of red and green junglefowls and relationship with Indonesian native chickens Sumatera and Kedu Hitam.

BACKGROUND: More than 2,500 breeds of chicken are reared throughout the world as a source of eggs or meat and as pets. The primary ancestor of the present domestic chicken is widely believed to be the red junglefowl, although genetic contributions from other junglefowls cannot be excluded entirely. The reference genome for chicken was obtained from a red junglefowl, the genetic purity of which has been debated. There is, at present, insufficient data to resolve these interesting issues. RESULTS: In this study, we performed whole-genome sequencing to compare various species and breeds of chicken, including wild red and green junglefowl, as well as the Indonesian native chickens Sumatera and Kedu Hitam and their respective descendants, the American Black Sumatra and Black Java. The data indicate that wild junglefowls have retained their genetic identity, but the Indonesian and American breeds have not. The Black Sumatra and Black Java are now closely related to each other, suggesting loss of genetic identity after export to the United States. In addition, the results indicate that the red junglefowl used as reference genome is more closely related to domestic chickens and apparently different from other wild red junglefowls. CONCLUSIONS: This study illuminates the genetic and phylogenetic relationships among these species. It provides a framework for genetic studies in wild junglefowls and native and domestic chicken breeds.

Outward bound: women translators and scientific travel writing, 1780-1800.

As the Enlightenment drew to a close, translation had gradually acquired an increasingly important role in the international circulation and transmission of scientific knowledge. Yet comparatively little attention has been paid to the translators responsible for making such accounts accessible in other languages, some of whom were women. In this article I explore how European women cast themselves as intellectually enquiring, knowledgeable and authoritative figures in their translations. Focusing specifically on the genre of scientific travel writing, I investigate the narrative strategies deployed by women translators to mark their involvement in the process of scientific knowledge-making. These strategies ranged from rhetorical near-invisibility, driven by women's modest marginalization of their own public engagement in science, to the active advertisement of themselves as intellectually curious consumers of scientific knowledge. A detailed study of Elizabeth Helme's translation of the French ornithologist François le Vaillant's Voyage dans l'intérieur de l'Afrique [Voyage into the Interior of Africa] (1790) allows me to explore how her reworking of the original text for an Anglophone reading public enabled her to engage cautiously - or sometimes more openly - with questions regarding how scientific knowledge was constructed, for whom and with which aims in mind.

Targeted inactivation of fh1 causes proliferative renal cyst development and activation of the hypoxia pathway.

Germline mutations in the fumarate hydratase (FH) tumor suppressor gene predispose to leiomyomatosis, renal cysts, and renal cell cancer (HLRCC). HLRCC tumors overexpress HIF1alpha and hypoxia pathway genes. We conditionally inactivated mouse Fh1 in the kidney. Fh1 mutants developed multiple clonal renal cysts that overexpressed Hif1alpha and Hif2alpha. Hif targets, such as Glut1 and Vegf, were upregulated. We found that Fh1-deficient murine embryonic stem cells and renal carcinomas from HLRCC showed similar overexpression of HIF and hypoxia pathway components to the mouse cysts. Our data have shown in vivo that pseudohypoxic drive, resulting from HIF1alpha (and HIF2alpha) overexpression, is a direct consequence of Fh1 inactivation. Our mouse may be useful for testing therapeutic interventions that target angiogenesis and HIF-prolyl hydroxylation.

Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer: a network meta-analysis.

BACKGROUND: Nintedanib plus docetaxel has proven an overall survival benefit over docetaxel monotherapy in second-line treatment of non-small-cell lung cancer of adenocarcinoma histology in the LUME-Lung 1 pivotal trial. No published trials have previously compared nintedanib plus docetaxel with agents ­ other than docetaxel ­ that are approved second-line treatments for non-small-cell lung cancer. METHODS: The relative efficacy of nintedanib plus docetaxel versus second-line agents was evaluated by conducting a network meta-analysis of progression-free survival and overall survival. RESULTS: Nine suitable studies were identified. The estimated probability of nintedanib plus docetaxel being the best treatment with regard to overall survival was 70% (versus 16% for pemetrexed, 10% for docetaxel and 3% for erlotinib). Results for progression-free survival were similar. CONCLUSION: In patients with advanced non-small-cell lung cancer of adenocarcinoma histology, results suggest that nintedanib plus docetaxel offers clinical benefit compared with docetaxel alone, when used as second-line treatment, and suggests that this combination may also add clinical benefit compared with erlotinib in this patient group.

Risk of geographic atrophy in the comparison of age-related macular degeneration treatments trials.

PURPOSE: To describe risk factors for geographic atrophy (GA) in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). DESIGN: Cohort within a randomized clinical trial. PARTICIPANTS: We analyzed 1024 CATT patients with no GA visible on color fundus photographs (CFPs) and/or fluorescein angiograms (FAs) at enrollment. METHODS: Eyes were assigned to ranibizumab (0.5 mg) or bevacizumab (1.25 mg) treatment and to a 2-year monthly or pro re nata (PRN) injection regimen, or monthly injections for 1 year and PRN for 1 year. Demographic, genetic, and baseline ocular characteristics and lesion features of CFP/FA and optical coherence tomography (OCT) were evaluated as risk factors for GA through 2 years of follow-up. Time-dependent Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs). MAIN OUTCOME MEASURES: Development of GA. RESULTS: By 2 years, GA developed in 187 of 1024 patients (18.3%). Baseline risk factors for GA development included baseline visual acuity (VA) ≤20/200 (aHR, 2.65; 95% confidence interval [CI], 1.43-4.93), retinal angiomatous proliferation (RAP; aHR, 1.69; 95% CI, 1.16-2.47), GA in the fellow eye (aHR, 2.07; 95% CI, 1.40-3.08), and intraretinal fluid at the foveal center (aHR, 2.10; 95% CI, 1.34-3.31). Baseline factors associated with lower risk for GA development included blocked fluorescence (aHR, 0.49; 95% CI, 0.29-0.82), OCT measurements of subretinal fluid thickness of >25 µ (aHR, 0.52; 95% CI, 0.35-0.78), subretinal tissue complex thickness of >275 compared with ≤75 µ (aHR, 0.31; 95% CI, 0.19-0.50), and vitreomacular attachment (aHR, 0.55; 95% CI, 0.31-0.97). Ranibizumab compared with bevacizumab had a higher risk (aHR, 1.43; 95% CI, 1.06-1.93), and monthly dosing had a higher risk (aHR, 1.59; 95% CI, 1.17-2.16) than PRN dosing. There were no strong associations between development of GA and the presence of risk alleles for CFH, ARMS 2, HTRA1, C3, or TLR3. CONCLUSIONS: Approximately one fifth of CATT patients developed GA within 2 years of treatment. Independent baseline risk factors included poor VA, RAP, foveal intraretinal fluid, monthly dosing, and treatment with ranibizumab. Anti-vascular endothelial growth factor therapy may have a role in the development of GA.

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.

Assessment of Baseline Ultra-Widefield Fluorescein Angiographic Quantitative Leakage Parameters with Ultra-widefield Fundus Features and Clinical Parameters in Diabetic Retinopathy in Protocol AA.

PURPOSE: Evaluate quantitative leakage parameters on ultra-widefield fluorescein angiography (UWF-FA) images and explore their association with Diabetic Retinopathy Severity Scale (DRSS), predominantly peripheral lesions (PPLs), visual acuity, and clinical characteristics. DESIGN: A post-hoc analysis of baseline UWF-FA images in the DRCR Retina Network observational study Protocol AA. PARTICIPANTS: N = 575 eyes from 384 adults across 38 sites in the US and Canada with gradable UWF-FA. METHODS: A machine learning-enhanced feature extraction platform provided initial leakage segmentation of UWF-FA images sequentially reviewed and corrected by two certified readers for segmentation accuracy. UWF-FA leakage was measured in five retinal zones: panretinal (whole retina), central macular (3-disc diameter fovea-centered circle), posterior pole (6-disc diameter fovea-centered circle), peripheral (outside 6-disc diameter circle) and widefield far peripheral (outside 9-disc diameter circle); associations with clinical factors were evaluated with marginal beta regression models. MAIN OUTCOME MEASURES: UWF-FA leakage index, calculated as the area with leakage divided by the analyzable retinal area. RESULTS: The mean quantitative leakage index was 3.5% for panretinal, 6.6% for macular, 4.8% for posterior pole, 3.3% for peripheral and 2.8% for wide-field far peripheral retinal zones. Panretinal leakage was associated with DRSS (mean 2.2% for no to mild NPDR, 3.4% for moderate NPDR, 4.2% for moderately severe NPDR, 4.8% for severe NPDR and 5.1% for PDR; P<.001), HbA1c (3.2% for HbA1c <8% vs. 3.8% for HbA1c ≥8%; P=.01 for continuous HbA1c), visual acuity (3.3% for 20/25 or better vs. 4.7% for 20/32 or worse; continuous P<.001), and UWF-FA-PPL types of IRMA (4.3% vs. 3.3%; P=.005) or NVE (5.7% vs. 3.4%; P=.003). DRSS was also statistically significant for leakage within all retinal zones (P<.001); eyes with non-central DME versus no DME had higher mean leakage in the central macular (11.2% vs. 5.9%; P=0.005) and posterior pole regions (9.2% vs. 4.2%; P=.002). CONCLUSION: Quantitative UWF-FA leakage analysis identified associations between leakage and DRSS, visual acuity, and presence of DME. In the future, quantitative UWF-FA leakage parameters may be explored as potential biomarkers for disease progression risk.

Epinephrine in local anesthesia in finger and hand surgery: the case for wide-awake anesthesia.

Traditionally, surgeons were taught that local anesthesia containing epinephrine should not be injected into fingers. This idea has since been refuted in many basic and clinical scientific studies, and today, injection of lidocaine plus epinephrine is widely used for digital and hand anesthesia in Canada. The key advantages of the wide-awake technique include the creation of a bloodless field without the use of an arm tourniquet, which in turn reduces the need for conscious sedation. The use of local anesthesia permits active motion intraoperatively, which is particularly helpful in tenolysis, flexor tendon repairs, and setting the tension on tendon transfers. Additional benefits of wide-awake anesthesia include efficiencies and cost savings in outpatient surgical case flow due to the absence of conscious sedation.

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.

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.

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.

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.

Protection from clinical disease against three highly virulent strains of Newcastle disease virus after in ovo application of an antibody-antigen complex vaccine in maternal antibody-positive chickens.

Worldwide, Newcastle disease (ND) remains one of the most economically important diseases of poultry. Current vaccination strategies for commercial poultry include the use of inactivated and live ND vaccines that typically induce protection against virulent field viruses. Here, we tested the efficacy of an antigen-antibody complex (AAC) ND vaccine delivered in ovo. Commercial maternal antibody-positive broiler chickens (Gallus domesticus) were vaccinated in ovo with an AAC vaccine composed of live B1-LaSota Newcastle disease virus (NDV) complexed with NDV-specific antiserum, and then they were challenged at weekly intervals after hatch. Challenge viruses included three exotic ND disease (END) viruses: the neurotropic strain Texas GB NDV-92-01 (TxGB) and two viscerotropic isolates, one isolate from the 2002-2003 outbreak in California (California 2002 isolate S212676 [CA]) and the other isolate from a 1997 END outbreak in South Korea (South Korea 94-147 [SK]). Results demonstrate that maternal antibody was able to provide approximately 50% protection in either vaccinated or control chickens at 7 days of age after TxGB challenge. However, with challenge at > or = 14 days, most control birds died, whereas all AAC-vaccinated birds were protected. Challenge with the CA or SK viruses in chickens at 28 days of age resulted in 100% protection of vaccinated birds, whereas all control birds died. In addition, AAC-vaccinated birds displayed decreased incidence of viral shedding in oral and cloacal swabs than control birds. Antibody titers were significantly (P < 0.05) higher in vaccinated chickens, as determined by enzyme-linked immunosorbent assay and hemagglutinin-inhibition tests, than in nonvaccinated controls. Together, these results demonstrate the efficacy of AAC vaccines delivered in ovo to protect commercial poultry.