A case of reed syndrome with an unusually extensive cutaneous burden treated with fully ablative Erbium:YAG laser resurfacing therapy.

Reed Syndrome, or hereditary leiomyomatosis and renal cell carcinoma syndrome, is a rare, autosomal dominant genetic condition that predisposes individuals to a triad of cutaneous leiomyomas, uterine leiomyomas and renal cell carcinoma. Cutaneous leiomyomas are often the first manifestation of the syndrome, occurring in 76% of patients and average 26 in number. We present a case of a 47 year old female with Reed Syndrome with an unusually extensive cutaneous burden, with a total of 361 cutaneous lesions, far above the average reported number of 26. Due to the extent of her cutaneous burden, painful nature of the lesions and failure to respond to standard therapies, she was referred for fully ablative Erbium:Yag laser resurfacing therapy. The use of fully ablative Erbium:YAG laser resurfacing therapy for treatment of cutaneous leiomyomas has not been reported in the literature to date. One year following laser therapy, the treatment area not only began to repigment, but there was also no evidence of cutaneous leiomyomas recurrence or associated pain. Given the effectiveness of this unique therapy, fully ablative Erbium:YAG laser resurfacing should be kept in mind as a treatment option for both cosmetic and symptomatic cutaneous leiomyomas.

Optimal strategies to improve uptake of and adherence to HIV prevention among young people at risk for HIV acquisition in the USA (ATN 149): a randomised, controlled, factorial trial.

BACKGROUND: Pre-exposure prophylaxis (PrEP), condom use, post-exposure prophylaxis (PEP), and sexual partner reduction help to prevent HIV acquisition but have low uptake among young people. We aimed to assess the efficacy of automated text messaging and monitoring, online peer support, and strengths-based telehealth coaching to improve uptake of and adherence to PrEP, condom use, and PEP among adolescents aged 12-24 years at risk of HIV acquisition in Los Angeles, CA, USA, and New Orleans, LA, USA. METHODS: We conducted a four-arm randomised controlled factorial trial, assessing interventions designed to support uptake and adherence of HIV prevention options (ie, PrEP, PEP, condom use, and sexual partner reduction). We recruited young people aged 12-24 years who were at risk of HIV acquisition from 13 community-based organisations, adolescent medicine clinics, and organisations serving people who are unstably housed, people who were previously incarcerated, and other vulnerable young people, and through dating apps, peer referrals, and social venues and events in Los Angeles, CA, USA, and New Orleans, LA, USA. Young people who tested seronegative and reported being gay, bisexual, or other men who have sex with men, transgender men or women, or gender diverse (eg. non-binary or genderqueer) were eligible for inclusion. Participants were randomly assigned to one of four intervention groups in a factorial design: automated text messaging and monitoring (AMMI) only, AMMI plus peer support via private social media, AMMI plus strengths-based telehealth coaching by near-peer paraprofessionals, or AMMI plus peer support and coaching. Assignment was further stratified by race or ethnicity and sexual orientation within each interviewer's group of participants. Participants were masked to intervention assignment until after baseline interviews when offered their randomly assigned intervention, and interviewers were masked throughout the study. Interventions were available throughout the 24-month follow-up period, and participants completed baseline and follow-up assessments, including rapid diagnostic tests for sexually transmitted infections, HIV, and substance use, at 4-month intervals over 24 months. The primary outcomes were uptake and adherence to HIV prevention options over 24 months, measured by self-reported PrEP use and adherence, consistent condom use with all partners, PEP prescription and adherence, and number of sexual partners in participants with at least one follow-up. We used Bayesian generalised linear modelling to assess changes in outcomes over time comparing the four study groups. This study is registered with ClinicalTrials.gov (NCT03134833) and is completed. FINDINGS: We screened 2314 adolescents beginning May 1, 2017, to enrol 1037 participants (45%) aged 16-24 years between May 6, 2017, and Aug 30, 2019, of whom 895 (86%) had follow-up assessments and were included in the analytical sample (313 assigned to AMMI only, 205 assigned to AMMI plus peer support, 196 assigned to AMMI plus coaching, and 181 assigned to AMMI plus peer support and coaching). Follow-up was completed on Nov 8, 2021. Participants were diverse in race and ethnicity (362 [40%] Black or African American, 257 [29%] Latinx or Hispanic, 184 [21%] White, and 53 [6%] Asian or Pacific Islander) and other sociodemographic factors. At baseline, 591 (66%) participants reported anal sex without a condom in the past 12 months. PrEP use matched that in young people nationally, with 101 (11%) participants reporting current PrEP use at baseline, increasing at 4 months to 132 (15%) and continuing to increase in the AMMI plus peer support and coaching group (odds ratio 2·31, 95% CI 1·28-4·14 vs AMMI control). There was no evidence for intervention effect on condom use, PEP use (ie, prescription or adherence), PrEP adherence, or sexual partner numbers. No unanticipated or study-related adverse events occurred. INTERPRETATION: Results are consistent with hypothesised synergistic intervention effects of evidence-based functions of informational, motivational, and reminder messaging; peer support for HIV prevention; and strengths-based, goal-focused, and problem-solving telehealth coaching delivered by near-peer paraprofessionals. These core functions could be flexibly scaled via combinations of technology platforms and front-line or telehealth HIV prevention workers. FUNDING: Adolescent Medicine Trials Network for HIV/AIDS Interventions, US National Institutes of Health.

Blood Culture Ordering After Sepsis Alerts and Subsequent Patient Outcomes: An Electronic Health Record-Based Study.

Sepsis is a global health priority associated with high mortality. Clinical decision support systems have been developed to support clinicians with sepsis management. Ordering blood cultures (BCs) for suspected sepsis patients are strongly recommended by clinical guidelines. However, limited evidence exists investigating BC ordering following sepsis alerts and subsequent patient outcomes. This study aimed to investigate this issue using electronic health record data from an acute care hospital in Australia. Of 4,092 patients, only 16.6% had a BC ordered following a sepsis alert. The median time from the first sepsis alert to a BC order was 15.3 hours. Patients had 5.89 times higher odds of being diagnosed with sepsis if a BC was ordered following a sepsis alert than those without BC ordered (p<0.0001). Further investigation is needed to understand reasons behind the delay or failure to order a BC despite receiving electronic sepsis alerts and how decision support can be optimized to improve patient outcomes.

Implementing Germ Defence digital behaviour change intervention via all primary care practices in England to reduce respiratory infections during the COVID-19 pandemic: an efficient cluster randomised controlled trial using the OpenSAFELY platform.

BACKGROUND: Germ Defence ( www.germdefence.org ) is an evidence-based interactive website that promotes behaviour change for infection control within households. To maximise the potential of Germ Defence to effectively reduce the spread of COVID-19, the intervention needed to be implemented at scale rapidly. METHODS: With NHS England approval, we conducted an efficient two-arm (1:1 ratio) cluster randomised controlled trial (RCT) to examine the effectiveness of randomising implementation of Germ Defence via general practitioner (GP) practices across England, UK, compared with usual care to disseminate Germ Defence to patients. GP practices randomised to the intervention arm (n = 3292) were emailed and asked to disseminate Germ Defence to all adult patients via mobile phone text, email or social media. Usual care arm GP practices (n = 3287) maintained standard management for the 4-month trial period and then asked to share Germ Defence with their adult patients. The primary outcome was the rate of GP presentations for respiratory tract infections (RTI) per patient. Secondary outcomes comprised rates of acute RTIs, confirmed COVID-19 diagnoses and suspected COVID-19 diagnoses, COVID-19 symptoms, gastrointestinal infection diagnoses, antibiotic usage and hospital admissions. The impact of the intervention on outcome rates was assessed using negative binomial regression modelling within the OpenSAFELY platform. The uptake of the intervention by GP practice and by patients was measured via website analytics. RESULTS: Germ Defence was used 310,731 times. The average website satisfaction score was 7.52 (0-10 not at all to very satisfied, N = 9933). There was no evidence of a difference in the rate of RTIs between intervention and control practices (rate ratio (RR) 1.01, 95% CI 0.96, 1.06, p = 0.70). This was similar to all other eight health outcomes. Patient engagement within intervention arm practices ranged from 0 to 48% of a practice list. CONCLUSIONS: While the RCT did not demonstrate a difference in health outcomes, we demonstrated that rapid large-scale implementation of a digital behavioural intervention is possible and can be evaluated with a novel efficient prospective RCT methodology analysing routinely collected patient data entirely within a trusted research environment. TRIAL REGISTRATION: This trial was registered in the ISRCTN registry (14602359) on 12 August 2020.

Use of Prize Competitions to Develop Advanced Military Medical Capabilities.

Research and development of military-required innovations are usually funded through the issuance of grants and contracts. The limitations of these funding methods are the a priori specifications and objectives that limit creativity and often do not produce capabilities beyond the desired outcomes or leverage the best ideas and solutions available. This limited engagement of commercial industry to develop military-required innovations usually relies solely on government funding and receipt of proposals from companies whose business model is built on receiving government grants and contracts, with the government owning most of the risks. Because the produced capabilities or products are designed to be military-unique, there is a limited or no commercial market available, usually driving the price per unit extremely high to the point that the military cannot afford to procure products in quantities sufficient to enable businesses to keep production lines open, however, for military-required or desired capabilities or products that have a commercial market, there are other funding pathways available to develop products by partnering with industry, academia, and other non-government organizations and leveraging their ideas and funding. One such way of engaging the commercial industry is through the use of prize competitions. This often under-utilized pathway has several notable strengths such as (1) reduced risks and costs for the military to develop novel capabilities and products; (2) new and novel creative solutions to solve military problems; (3) utilizing a results-oriented approach that funds the successful achievement of acceptance criteria versus funding of potential to achieve; (4) enticing investors by increased competition for a successful product or capability; and (5) delivery of a commercially available, affordable, field-tested, and viable capabilities and products. Prize competitions may be used by any/all federal agencies as authorized by Congressional Public Laws and Federal regulations. The specifics of this pathway for funding pathway and applications for use by medical researchers, developers, and project/program managers are spelled out in the article, along with the regulatory guidance and resources for finding out more about current and past prize competitions.

Efficacy, Safety, and Durability of Brolucizumab: An 8-Month Post-Marketing Surveillance Analysis.

Importance: Brolucizumab (Beovu®) is an anti-vascular endothelial growth factor (anti-VEGF) agent approved for the treatment of neovascular age-related macular degeneration (nvAMD). Brolucizumab was marketed for its noninferiority to aflibercept and its potential for greater durability. However, post-marketing utilization has been tempered by safety concerns. Objective: We evaluate the visual and anatomic efficacy of brolucizumab, examine changes in treatment intervals after switching to brolucizumab, and estimate the incidence of drug-related adverse events in the real world. Design Setting and Participants: This was a retrospective consecutive case series of 626 eyes (543 patients) with nvAMD treated with 1438 brolucizumab injections at a single retina practice between 10/1/2019 and 5/15/2020. Main Outcomes and Measures: Changes in visual acuity (VA); anatomic outcomes assessed by optical coherence tomography (OCT) including central subfield thickness (CST), macular volume (MV), presence of intraretinal fluid (IRF), subretinal fluid (SRF), and serous pigment epithelial detachment (sPED) on foveal line scans; treatment intervals before and after receiving brolucizumab; and the incidence of brolucizumab-related adverse events. Results: The majority of eyes (N = 531, 89.7%) had received prior anti-VEGF therapy with aflibercept, ranibizumab, and/or bevacizumab. VA improved in treatment-naïve eyes (+3.7 letters, p = 0.04), and was maintained in previously treated eyes. There were significant improvements in all anatomic outcomes in both groups (p < 0.001). We observed a 4.8% incidence of intraocular inflammation (IOI) and a 0.6% incidence of retinal vasculitis. The average treatment interval increased from 6.3 to 6.8 weeks (p = 0.001). Conclusions and Relevance: Brolucizumab treatment was associated with VA improvement in naïve eyes and maintenance of VA in previously treated eyes. Switching to brolucizumab was associated with improved anatomic outcomes and extended treatment intervals in most eyes. We observed a similar incidence of IOI and a lower incidence of retinal vasculitis compared to the Safety Review Committee's analysis of HAWK and HARRIER.

Impact of rapid near-patient STI testing on service delivery outcomes in an integrated sexual health service in the United Kingdom: a controlled interrupted time series study.

OBJECTIVES: To evaluate the impact of a new clinic-based rapid sexually transmitted infection testing, diagnosis and treatment service on healthcare delivery and resource needs in an integrated sexual health service. DESIGN: Controlled interrupted time series study. SETTING: Two integrated sexual health services (SHS) in UK: Unity Sexual Health in Bristol, UK (intervention site) and Croydon Sexual Health in London (control site). PARTICIPANTS: Electronic patient records for all 58 418 attendances during the period 1 year before and 1 year after the intervention. INTERVENTION: Introduction of an in-clinic rapid testing system for gonorrhoea and chlamydia in combination with revised treatment pathways. OUTCOME MEASURES: Time-to-test notification, staff capacity, cost per episode of care and overall service costs. We also assessed rates of gonorrhoea culture swabs, follow-up attendances and examinations. RESULTS: Time-to-notification and the rate of gonorrhoea swabs significantly decreased following implementation of the new system. There was no evidence of change in follow-up visits or examination rates for patients seen in clinic related to the new system. Staff capacity in clinics appeared to be maintained across the study period. Overall, the number of episodes per week was unchanged in the intervention site, and the mean cost per episode decreased by 7.5% (95% CI 5.7% to 9.3%). CONCLUSIONS: The clear improvement in time-to-notification, while maintaining activity at a lower overall cost, suggests that the implementation of clinic-based testing had the intended impact, which bolsters the case for more widespread rollout in sexual health services.

A long-snouted and long-necked polycotylid plesiosaur from the Late Cretaceous of North America.

Plesiosaurs are a group of Mesozoic marine diapsids. Most derived plesiosaurs fall into one of two typical body forms: those with proportionately small heads, short snouts, and elongated necks, and those with large heads, elongated snouts, and short necks. Serpentisuchops pfisterae is a polycotylid plesiosaur from the Upper Cretaceous Pierre Shale that presents the trait combination of both an elongate snout and elongate neck (consisting of 32 vertebrae). Phylogenetic analysis places Serpentisuchops within the Polycotylinae, indicating that its long snout is an ancestral trait, while its long neck is secondarily derived and convergent with that of ancestral plesiosaurs, contemporaneous elasmosaurids, and some more basal members of the Polycotylidae. The conical, recurved, and narrow teeth are consistent with a piscivorous diet. The tall and anteroposteriorly broad cervical neural spines indicate large epaxial muscles, suggesting that Serpentisuchops used both its neck and snout in fast lateral strikes aimed at proportionately small prey.

Autoimmune retinopathy with associated anti-retinal antibodies as a potential immune-related adverse event associated with immunotherapy in patients with advanced cutaneous melanoma: case series and systematic review.

OBJECTIVE: To demonstrate the spectrum of autoimmune retinopathy (AIR) associated with immunotherapy for advanced cutaneous melanoma. METHODS AND ANALYSIS: Retrospective chart review on patients with advanced cutaneous melanoma who developed AIR after initiating immunotherapy. Complete ophthalmic examination and relevant ancillary testing were performed on each patient. The presence of AIR-associated anti-retinal antibodies was confirmed by western blot and/or immunohistochemical staining. Ophthalmic and systemic outcomes after treatment for AIR were followed over time. A systematic review of AIR associated with immunotherapy for cutaneous or non-ocular mucosal melanoma was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Case 1 developed photopsia and nyctalopia with electroretinographic findings characteristic for melanoma-associated retinopathy 1 week after initiating ipilimumab/nivolumab immunotherapy. Case 2 experienced new severe bilateral visual field loss associated with anti-retinal and anti-optic nerve antibodies while on maintenance nivolumab immunotherapy. Case 3 developed decreased visual acuity due to acute exudative polymorphous vitelliform maculopathy within 2 weeks of initiating ipilimumab/nivolumab immunotherapy. All patients had concurrent extraocular immune-related adverse events in addition to the presence of anti-retinal antibodies on serological testing. 14 published cases of AIR associated with immunotherapy for cutaneous or non-ocular mucosal melanoma were identified and reviewed. CONCLUSIONS: Immune checkpoint inhibition can trigger the development of AIR with varied clinical manifestations in patients with advanced cutaneous melanoma. This study highlights the need for close monitoring in cutaneous melanoma patients receiving immunotherapy who develop new visual symptoms with or without funduscopic changes, as well as the potential role for screening of patients prior to initiating immunotherapy.

Emergency department physicians' distribution of time in the fast paced-workflow-a novel time-motion study of drug-related activities.

Background In the emergency department physicians are forced to distribute their time to ensure that all admitted patients receive appropriate emergency care. Previous studies have raised concerns about medication discrepancies in patient's drug lists at admission to the emergency department. Thus, it is important to study how emergency department physicians distribute their time, to highlight where workflow redesign can be needed.Aim to quantify how emergency department physicians distribute their time between various task categories, with particular focus on drug-related tasks.Method Direct observation, time-motion study of emergency department physicians at Diakonhjemmet Hospital, Oslo, Norway. Physicians' activities were categorized in discrete categories and data were collected with the validated method of Work Observation Method By Activity Timing between October 2018 to January 2019. Bootstrap analysis determined 95% confidence intervals for proportions and interruption rates.Results During the observation time of 91.4 h, 31 emergency department physicians were observed. In total, physicians spent majority of their time gathering information (36.5%), communicating (26.3%), and documenting (24.2%). Further, physicians spent 17.8% (95% CI 16.8%, 19.3%) of their time on drug-related tasks. On average, physicians spent 7.8 min (95% CI 7.2, 8.6) per hour to obtain and document patients' drug lists.Conclusion Emergency department physicians are required to conduct numerous essential tasks and distributes a minor proportion of their time on drug-related tasks. More efficient information flow regarding drugs should be facilitated at transitions of care. The presence of healthcare personnel dedicated to obtaining drug lists in the emergency department should be considered.

Time distribution for pharmacists conducting a randomized controlled trial-An observational time and motion study.

INTRODUCTION: An expected future increase in older adults will demand changes in health care delivery, making development, implementation and evaluation of new health care models essential. The rationale for political decision-making concerning the implementation and application of interventions in health care should include cost estimations, specifically those involving clinical interventions. To provide such data knowledge of time spent on the intervention is imperative. Time and motion methodology is suitable to quantify health care personnel's time distribution. AIM: To investigate the time distribution for pharmacists conducting a randomized controlled trial (RCT) implementing a clinical intervention. MATERIALS AND METHODS: The setting was an RCT with a 5-step pharmacist-intervention in collaboration with the interdisciplinary team in a geriatric ward. Two pharmacists were involved in the trial during the observation period. Pharmacist activities, classified as RCT-tasks (intervention or administrative), non-RCT tasks and social/breaks, were recorded applying the Work Observation Method By Activity Timing methodology, enabling recording of predefined work tasks as well as interruptions and multitasking. One observer collected data over eight weeks. RESULTS: In total, 109.1 hours were observed resulting in 110.2 hours total task time, including multitasking. RCT tasks comprised 85.4% of the total observed time, and nearly 60% of the RCT time was spent on intervention tasks. Medication reviews was the most time consuming task, accounting for 32% of the observed time. The clinical pharmacists spent 14% of the intervention time communicating verbally, mainly with patients and healthcare professionals. CONCLUSION: During the RCT, the clinical pharmacists spent about half their time performing the actual intervention. Consequently, costs for providing such a clinical pharmacist service should reflect actual time spent; otherwise, we may risk overestimating theoretical costs.

Pilot program for test-based SARS-CoV-2 screening and environmental monitoring in an urban public school district

ImportanceScalable programs for school-based SARS-CoV-2 testing and surveillance are needed to guide in-person learning practices and inform risk assessments in K-12 settings. ObjectivesTo characterize SARS-CoV-2 infections in staff and students in an urban public school setting and evaluate test-based strategies to support ongoing risk assessment and mitigation for K-12 in-person learning. Design, Setting, and ParticipantsThe pilot program engaged three schools for weekly saliva PCR testing of staff and students participating in in-person learning over a 5-week period. Wastewater, air, and surface samples were collected weekly and tested for SARS-CoV-2 RNA to determine surrogacy for case detection and interrogate transmission risk of in-building activities. Main Outcomes and MeasuresSARS-CoV-2 detection in saliva and environmental samples and risk factors for SARS-CoV-2 infection. Results2,885 supervised self-collected saliva samples were tested from 773 asymptomatic staff and students during November and December, 2020. 46 cases (22 students, 24 staff) were detected, representing a 5.8- and 2.5-fold increase in case detection rates among students and staff, respectively, compared to conventional reporting mechanisms. SARS-CoV-2 RNA was detected in wastewater samples from all pilot schools, as well as in air samples collected from two choir rooms. Sequencing of 21 viral genomes in saliva specimens demonstrated minimal clustering associated with one school. Geographic analysis of SARS-CoV-2 cases reported district-wide demonstrated higher community risk in zip codes proximal to the pilot schools. Conclusions and RelevanceWeekly screening of asymptomatic staff and students by saliva PCR testing dramatically increased SARS-CoV-2 case detection in an urban public-school setting, exceeding infection rates reported at the county level. Experiences differed among schools, and virus sequencing and geographic analyses suggest a dynamic interplay of school-based and community-derived transmission risk. Environmental testing for SARS-CoV-2 RNA in air and surface samples enabled real-time risk assessment of in-school activities and allowed for interventions in choir classes. Wastewater testing demonstrated the utility of school building-level SARS-CoV-2 surveillance. Collectively, these findings provide insight into the performance and community value of test-based SARS-CoV-2 screening and surveillance strategies in the K-12 educational setting. KEY POINTSO_ST_ABSQuestionC_ST_ABSDo test-based programs reduce SARS-CoV-2 risk in K-12 schools? FindingsWeekly school-based saliva PCR testing at three urban public schools doubled case detection among staff and students over symptom-based strategies, exceeding county-level case rates. SARS-CoV-2 was detected in school wastewater samples each week, as well as air and surface samples related to choir classrooms. MeaningRoutine SARS-CoV-2 testing removes infected staff and students from school who are not identified through conventional case detection. With rigorous infection control and environmental monitoring, this helps mitigate risk during school operations. Furthermore, screening in K-12 schools may provide insight into disease burdens of undertested communities.

Structured Data Capture for Oncology.

Lack of interoperability is one of the greatest challenges facing healthcare informatics. Recent interoperability efforts have focused primarily on data transmission and generally ignore data capture standardization. Structured Data Capture (SDC) is an open-source technical framework that enables the capture and exchange of standardized and structured data in interoperable data entry forms (DEFs) at the point of care. Some of SDC's primary use cases concern complex oncology data such as anatomic pathology, biomarkers, and clinical oncology data collection and reporting. Its interoperability goals are the preservation of semantic, contextual, and structural integrity of the captured data throughout the data's lifespan. SDC documents are written in eXtensible Markup Language (XML) and are therefore computer readable, yet technology agnostic-SDC can be implemented by any EHR vendor or registry. Any SDC-capable system can render an SDC XML file into a DEF, receive and parse an SDC transmission, and regenerate the original SDC form as a DEF or synoptic report with the response data intact. SDC is therefore able to facilitate interoperable data capture and exchange for patient care, clinical trials, cancer surveillance and public health needs, clinical research, and computable care guidelines. The usability of SDC-captured oncology data is enhanced when the SDC data elements are mapped to standard terminologies. For example, an SDC map to Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) enables aggregation of SDC data with other related data sets and permits advanced queries and groupings on the basis of SNOMED CT concept attributes and description logic. SDC supports terminology maps using separate map files or as terminology codes embedded in an SDC document.

BILATERAL INTRAVITREAL 0.19-MG FLUOCINOLONE ACETONIDE IMPLANT FOR PERSISTENT NONDIABETIC CYSTOID MACULAR EDEMA AFTER VITRECTOMY.

BACKGROUND/PURPOSE: Iluvien (Alimera Science, Alpharetta, GA) is an injectable, nonbiodegradable, sustained-release 0.19-mg fluocinolone acetonide intravitreal implant. Although currently approved by the Food and Drug Administration only for diabetic macular edema previously treated with a course of corticosteroids without a clinically significant intraocular pressure response, the 0.19-mg fluocinolone acetonide implant could theoretically be used to treat other noninfectious inflammatory conditions including persistent cystoid macular edema because of nondiabetic etiologies. METHODS: Interventional case report. A 79-year-old man had persistent cystoid macular edema after pars plana vitrectomy in both eyes that was refractory to topical treatments and intravitreal anti-vascular endothelial growth factor. His cystoid macular edema was responsive to preservative-free intravitreal triamcinolone acetonide after which he developed noninfectious endophthalmitis or pseudoendophthalmitis in both eyes precluding further intravitreal triamcinolone acetonide injections. He was subsequently treated with bilateral intravitreal 0.19-mg fluocinolone acetonide implants. RESULTS: At the most recent post-treatment follow-up (11 months for the right eye and 13 months for the left eye), the patient demonstrated an improvement in visual acuity, 20/126 to 20/50 in the right eye and 20/80 to 20/40 in the left eye, and in central subfield thickness, 592 µm to 288 µm in the right eye and 565 µm to 287 µm in the left eye, without intraocular pressure elevation. CONCLUSION: The intravitreal 0.19-mg fluocinolone acetonide implant is an effective and potentially safe off-label therapeutic option for persistent nondiabetic cystoid macular edema after vitrectomy.

Comparison of the quick Sepsis-related Organ Failure Assessment and adult sepsis pathway in predicting adverse outcomes among adult patients in general wards: a retrospective observational cohort study.

BACKGROUND: Quick Sepsis-related Organ Failure Assessment (qSOFA) is recommended for use by the most recent international sepsis definition taskforce to identify suspected sepsis in patients outside the intensive care unit (ICU) at risk of adverse outcomes. Evidence of its comparative effectiveness with existing sepsis recognition tools is important to guide decisions about its widespread implementation. AIM: To compare the performance of qSOFA with the adult sepsis pathway (ASP), a current sepsis recognition tool widely used in NSW hospitals and systemic inflammatory response syndrome criteria in predicting adverse outcomes in adult patients on general wards. METHODS: A retrospective observational cohort study was conducted which included all adults with suspected infections admitted to a Sydney teaching hospital between December 2014 and June 2016. The primary outcome was in-hospital mortality with two secondary composite outcomes. RESULTS: Among 2940 patients with suspected infection, 217 (7.38%) died in-hospital and 702 (23.88%) were subsequently admitted to ICU. The ASP showed the greatest ability to correctly discriminate in-hospital mortality and secondary outcomes. The area under the receiver-operating characteristic curve for mortality was 0.76 (95% confidence interval (CI): 0.74-0.78), compared to 0.64 for the qSOFA tool (95% CI: 0.61-0.67, P < 0.0001). Median time from the first ASP sepsis warning to death was 8.21 days (interquartile range (IQR): 2.29-16.75) while it was 0 days for qSOFA (IQR: 0-2.58). CONCLUSIONS: The ASP demonstrated both greater prognostic accuracy and earlier warning for in-hospital mortality for adults on hospital wards compared to qSOFA. Hospitals already using ASP may not benefit from switching to the qSOFA tool.

Understanding the work of case managers in Australian community aged care: a longitudinal time and motion study.

Objective The aim of this study was to quantify the work activities of community aged care case managers and assess changes following consumer-directed policy reforms. Methods A longitudinal, time and motion study was performed, with direct observation (n=339h) of case managers undertaking work in the office or in the community. We compared the distribution of proportions of time spent across seven broad work task categories during May-August 2014 (P1) and May-October 2016 (P2). Results Office time was primarily consumed by communication (43.7%) and documentation (33.3%) tasks. Documentation increased substantially from P1 to P2 (29.4% vs 37.0% respectively; P<0.001), with more time spent on the subtask of recording information (18.0% vs 24.5% respectively; P=0.039). Travel (45.9%) and communication (41.0%) accounted for most community time. Time in communication increased from P1 to P2 (37.3% vs 48.4% respectively; P=0.047), with more time allocated to client communication (14.6% vs 31.7%; P<0.001). Case managers spent 33.6% of community time in clients' homes (median 25.2min per client; 22.8 vs 30.1min in P1 and P2 respectively) and visited a median of two clients per day (3 vs 1 visits per day in P1 and P2 respectively). Conclusions This study provides the first quantification of task-time distribution among this workforce and how work patterns have changed during a time of significant policy reform and operational changes within the community aged care sector. What is known about the topic? Early qualitative studies gauging case managers' perceptions of the effect of consumer-directed care reforms on their work activities indicate an increase in time spent working directly with aged care clients. However, there is no existing quantitative evidence examining changes to case managers' work activities. What does this paper add? By capturing timed, multidimensional data, this study provides new quantitative evidence of how case managers distribute their time on work activities in office and community settings. Further, the results provide an indication of changes in work task-time distribution over a 2-year period when significant policy reforms and operational changes occurred. Amid a changing aged care landscape, how and with whom case managers spend their time was found to shift, with an increase in time spent recording information and communicating with clients identified. What are the implications for practitioners? This study demonstrates that direct observational studies provide important evidence of the ways in which policy and organisational changes affect community aged care case managers' work activities in practice. Triangulating this quantitative evidence with existing qualitative accounts of policy impact can further allow assessment of how complex reforms may affect everyday work. For policy makers and aged care organisations, such evidence can help discern whether policies and changes are having their desired effects, as well as providing insights as to why or why not.

Mutations in SREBF1, Encoding Sterol Regulatory Element Binding Transcription Factor 1, Cause Autosomal-Dominant IFAP Syndrome.

IFAP syndrome is a rare genetic disorder characterized by ichthyosis follicularis, atrichia, and photophobia. Previous research found that mutations in MBTPS2, encoding site-2-protease (S2P), underlie X-linked IFAP syndrome. The present report describes the identification via whole-exome sequencing of three heterozygous mutations in SREBF1 in 11 unrelated, ethnically diverse individuals with autosomal-dominant IFAP syndrome. SREBF1 encodes sterol regulatory element-binding protein 1 (SREBP1), which promotes the transcription of lipogenes involved in the biosynthesis of fatty acids and cholesterols. This process requires cleavage of SREBP1 by site-1-protease (S1P) and S2P and subsequent translocation into the nucleus where it binds to sterol regulatory elements (SRE). The three detected SREBF1 mutations caused substitution or deletion of residues 527, 528, and 530, which are crucial for S1P cleavage. In vitro investigation of SREBP1 variants demonstrated impaired S1P cleavage, which prohibited nuclear translocation of the transcriptionally active form of SREBP1. As a result, SREBP1 variants exhibited significantly lower transcriptional activity compared to the wild-type, as demonstrated via luciferase reporter assay. RNA sequencing of the scalp skin from IFAP-affected individuals revealed a dramatic reduction in transcript levels of low-density lipoprotein receptor (LDLR) and of keratin genes known to be expressed in the outer root sheath of hair follicles. An increased rate of in situ keratinocyte apoptosis, which might contribute to skin hyperkeratosis and hypotrichosis, was also detected in scalp samples from affected individuals. Together with previous research, the present findings suggest that SREBP signaling plays an essential role in epidermal differentiation, skin barrier formation, hair growth, and eye function.

Retinal Vasculitis and Intraocular Inflammation after Intravitreal Injection of Brolucizumab.

PURPOSE: To evaluate features and outcomes of eyes with retinal vasculitis and intraocular inflammation (IOI) after intravitreal injection (IVI) of brolucizumab 6 mg/0.05 ml for treatment of neovascular age-related macular degeneration. DESIGN: Retrospective case series. PARTICIPANTS: Fifteen eyes from 12 patients identified from 10 United States centers. METHODS: Review of patient demographics, ophthalmologic examination results, and retinal imaging findings. MAIN OUTCOME MEASURES: Baseline and follow-up visual acuity (VA), prior anti-vascular endothelial growth factor (VEGF) injections, clinical presentation, retinal findings, fluorescein angiography results, and treatment strategies. RESULTS: The number of previous anti-VEGF IVIs ranged between 2 and 80 in the affected eye before switching to brolucizumab. Retinal vasculitis and IOI were diagnosed at a mean of 30 days after brolucizumab IVI. Mean VA before brolucizumab IVI was 0.426 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/53) and VA at diagnosis of retinal vasculitis was 0.981 logMAR (Snellen equivalent, 20/191; range, 20/25-20/1600; P = 0.008). All affected eyes showed IOI with variable combinations of focal or elongated segmental sheathing and discontinuity of small and large retinal arteries, sclerotic arteries, regions of vascular nonperfusion, cotton-wool spots, Kyrieleis plaques, irregular venous caliber with dilated and sclerotic segments, perivenular hemorrhages, and foci of phlebitis. Fluorescein angiography revealed delayed retinal arterial filling, retinal vascular nonperfusion, and variable dye leakage from affected vessels and the optic nerve. Systemic evaluation for embolic causes was unrevealing in 2 patients, and 3 patients showed negative laboratory assessment for uveitis. Treatment consisted of various combinations of corticosteroids (systemic, intravitreal, and topical), and 2 eyes underwent vitrectomy without improvement in vision. After a mean follow-up of 25 days, mean VA was 0.833 logMAR (Snellen equivalent, 20/136), which was reduced compared with baseline (P = 0.033). CONCLUSIONS: Retinal vasculitis and IOI after brolucizumab IVI are characterized by variable occlusion of large or small retinal arteries, or both, and perivenular abnormalities. It may span from peripheral vasculitis to occlusion of large retinal arteries around the optic nerve or macula with severe vision loss. A high index of suspicion is required because vitreous cells may obscure visualization of retinal details.