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Vision changes can precipitate falls in the elderly resulting in significant morbidity and mortality. We hypothesized that pseudophakic monovision and ensuing anisometropia and aniseikonia impact elderly fall risk. This study assessed fall risk in patients with pseudophakic monovision, pseudophakic single vision distance (classic cataract surgery), and cataracts with no surgery.Retrospective single-institution cohort study PARTICIPANTS: Patients with bilateral cataracts diagnosed at 60 years of age or older who underwent bilateral cataract surgery (monovision or single vision distance) or did not undergo any cataract surgery (n = 13 385). Patients with unilateral surgery or a fall prior to cataract diagnosis were excluded.Data were obtained from the Stanford Research Repository. Time-to-fall analysis was performed across all 3 groups. Primary outcome was hazard ratio (HR) for fall after second eye cataract surgery or after bilateral cataract diagnosis.Of 13 385 patients (241 pseudophakic monovision, 2809 pseudophakic single vision, 10 335 no surgery), 850 fell after cataract diagnosis. Pseudophakic monovision was not associated with fall risk after controlling for age, sex, and myopia. Pseudophakic single-vision patients had a decreased time to fall compared with no-surgery patients (log rank, p0.001). Older age at cataract diagnosis (HR =1.05, 95% confidence interval [CI] 1.04-1.06, p0.001) or at time of surgery (HR = 1.05, 95% CI 1.03-1.07, p0.001) increased fall risk, as did female sex (HR = 1.29, 95% CI 1.10-1.51, p = 0.002) and preexisting myopia (HR = 1.31, 95% CI 1.01-1.71, p = 0.046) among nonsurgical patients.Pseudophakic monovision did not impact fall risk, but pseudophakic single vision may increase falls compared with patients without cataract surgery.

HIV pre-exposure prophylaxis (PrEP) is a safe and highly effective method to prevent HIV acquisition that is underutilized, particularly in marginalized populations. This article describes current and emerging modalities to prevent HIV with PrEP. Safe prescribing and monitoring of PrEP is presented to enable the nurse practitioner to incorporate HIV prevention into their routine clinical practice and minimize barriers to this valuable strategy.

The incidence of transfusion in contemporary revision total hip arthroplasty (THA) remains high despite recent advances in blood management, including the use of tranexamic acid. The purpose of this prospective investigation was to determine independent risk factors for transfusion in revision THA.Six centers prospectively collected data on 175 revision THAs. A multivariable logistic analysis was performed to determine independent risk factors for transfusion. Revisions were categorized into subgroups for analysis, including femur-only, acetabulum-only, both-component, explantation with spacer, and second-stage reimplantation. Patients undergoing an isolated modular exchange were excluded.Twenty-nine patients required at least one unit of blood (16.6%). In the logistic model, significant risk factors for transfusion were lower preoperative hemoglobin, higher preoperative international normalized ratio (INR), and longer operative time (P.01, P = .04, P = .05, respectively). For each preoperative 1g/dL decrease in hemoglobin, the chance of transfusion increased by 79%. For each 0.1-unit increase in the preoperative INR, transfusion chance increased by 158%. For each additional operative hour, the chance of transfusion increased by 74%. There were no differences in transfusion rates among categories of revision hip surgery (P = .23). No differences in demographic or surgical variables were found between revision types.Despite the use of tranexamic acid, transfusions are commonly required in revision THA. Preoperative hemoglobin and INR optimization are recommended when medically feasible. Efforts should also be made to decrease operative time when technically possible.

BACKGROUND Epidural hematoma (EDH) can result in a catastrophic outcome of traumatic brain injury. Current management guidelines do not consider the source of hemorrhage in decision making. The purpose of this study was to examine the relationship between EDH location and the source of hemorrhage. METHODS We report retrospectively reviewed, prospectively obtained surgical data of patients with acute traumatic cranial EDH treated between 2007 and 2018. Computed tomography (CT) scans were used to categorize EDH location as lateral or medial. The source of hemorrhage was identified intraoperatively by a single surgeon. RESULTS Overall, of 92 evacuated EDHs (in 87 patients), 71 (77.2%) were in the lateral location. Arterial bleeding was the cause of EDH in 63.4% of the lateral EDHs and 9.2% of the medial EDHs (P < 0.0001). In the cases where surgery was done primarily to treat EDH, 65.3% had an arterial bleed source (P < 0.0001). In those treated for primary reasons other than EDH evacuation, 75% had a venous bleed source (P = 0.002). CONCLUSIONS The location of EDH correlates with the source of hemorrhage. The decision to operate on EDH may be influenced by this factor.

Observational studies in critical care medicine offer a popular and practical approach to questions of treatment effectiveness. Although observational research is widely understood to be susceptible to design and interpretation challenges, one well-described source of bias-immortal time bias (ITB)-is frequently present yet often overlooked. ITB may be introduced by study design oversights or mishandled during data analysis. When present, ITB can create inappropriate estimates of the benefit or harm of an exposure or intervention. Studies examining treatments in critically ill patients may be particularly susceptible to ITB, with consequences for clinical adoption and design and initiation of randomized trials. In this Critical Care Perspective, we illustrate the persistent problem of ITB in observational research using recent studies of hydrocortisone, ascorbic acid, and thiamine therapy in patients with sepsis and septic shock. Of the eight studies examined, none contained enough design or reporting elements to rule out the presence of ITB. To mitigate the influence of ITB in future observational studies, we present a novel checklist to help readers assess the features of study design, analysis, and reporting that introduce ITB or obscure its presence. We recommend that commonly used tools designed to evaluate observational research studies should include an ITB assessment.

To assess the value of preoperative joint aspiration in detecting periprosthetic joint infection (PJI) in patients undergoing revision hip arthroplasty and to compare these with the clinical findings, serum markers, and intraoperative findings. Fluoroscopically guided hip aspirations in patients with pain after hip arthroplasty were retrospectively reviewed from January 2014 to December 2018. All hips underwent subsequent revision hip arthroplasty. Antibiotics were discontinued at least 2 weeks before the aspiration. The 2018 Musculoskeletal Infection Society (MSIS) criteria served as a standard of reference for PJI. Clinical, serum, synovial, and intraoperative parameters were recorded in all patients. Correlations between all parameters with PJI diagnosis were analyzed using linear and logistic regression models with ROC analysis. In 202 hips that included 91 septic hips, hip aspiration (AUC = 0.78) and intraoperative (0.80) parameters performed better than serum-based tests (0.64) and clinical parameters (0.68) in detecting PJI. Using MSIS criteria as a standard of reference, hip aspiration had a sensitivity of 64.0% and an accuracy of 78.5% for cultures and a sensitivity of 74.2% and an accuracy of 82.1% for synovial polymorphonuclear neutrophils% (PMN%). Results substantially improved sensitivity after excluding patients that were treated with antibiotics, particularly culture results. Preoperative hip aspiration showed good diagnostic performance in diagnosing PJI compared with MSIS criteria as a standard of reference. But a negative result from aspirate could not rule out PJI. Based on our findings, hip aspiration is an essential test for treatment planning in patients with pain after hip arthroplasty.

INTRODUCTION: Flight-related neck pain (FRNP) is a frequently reported musculoskeletal complaint among military helicopter aircrew. However, despite its prevalence and suspected causes, little is known of the underpinning pain mechanisms or the impact of neck pain on aircrews in-flight task performance. The biopsychosocial (BPS) approach to health, combined with the contemporary conceptualization of musculoskeletal pain, in which injury and pain are not necessarily synonymous, provides a relatively new holistic framework within which to consider the problem of FRNP in military helicopter aircrew. Combining these concepts, a new conceptual model is proposed to illustrate how biopsychosocial factors may influence pain perception, potentially affecting aircrews capacity to process information and, therefore, threatening in-flight task performance. Recommendations are made for considering the underlying pain mechanisms of FRNP to aid prognoses and guide the development of holistic evidence-based countermeasures for FRNP in military helicopter aircrew. Development of instruments able to measure psychosocial factors, such as self-efficacy and functional ability, validated in the military helicopter aircrew population, would assist this task.Vail RE, Harridge SDR, Hodkinson PD, Green NDC, Pavlou M. A novel biopsychosocial approach to neck pain in military helicopter aircrew. Aerosp Med Hum Perform. 2021; 92(5):333341.

Social needs, which are social risk factors including lack of access to stable housing, healthy food, or reliable transportation, are recognized as integral to health. Free clinics tend to serve patients with social needs, yet, few are screened or receive assistance. Lack of personnel, resources, and procedures to identify and assist patients are reasons few free clinics consider social needs. To address this service gap, a midwestern free clinic and neighboring Masters of Social Work (MSW) program established a partnership. A social needs screen was developed and integrated into health care practice. An MSW intern was also embedded as a member of the health care team to provide social needs assistance. A 6-month pilot study was conducted to assess the value of the screen and use of MSW assistance services. Of the 223 patients screened, 66.4% (n = 146) scored positive for social needs. Only four percent (n = 6) of the patients used MSW services. Chi-square analyses reveal significant differences in social needs by age, gender, race, education, and primary language. The findings suggest that the screening and MSW intern services are valuable; however, they further suggest that screening alone may be insufficient to encourage utilization of MSW services.

The updated VCOG‐CTCAE v2 guidelines contain several important updates and additions since the last update (v1.1) was released in 2011 and published within Veterinary and Comparative Oncology in 2016. As the Veterinary Cooperative Oncology Group (VCOG) is no longer an active entity, the original authors and contributors to the VCOG‐CTCAE v1.0 and v1.1 were consulted for input, and additional co‐authors sought for expansion and refinement of the adverse event (AE) categories. VCOG‐CTCAE v2 includes expanded neurology, cardiac and immunologic AE sections, and the addition of procedural‐specific AEs. It is our intent that, through inclusion of additional authors from ACVIM subspecialties and the American College of Veterinary Surgery, that we can more comprehensively capture AEs that are observed during clinical studies conducted across a variety of disease states, clinical scenarios, and body systems. It is also our intent that these updated veterinary CTCAE guidelines will offer improved application and ease of use within veterinary practice in general, as well as within clinical trials that assess new therapeutic strategies for animals with a variety of diseases. Throughout the revision process, we strived to ensure the grading structure for each AE category was reflective of the decision‐making process applied to determination of dose‐limiting events. As phase I trial decisions are based on these criteria and ultimately determine the maximally tolerated dose, there is impact on standard dosing recommendations for any new drug registration or application. This document should be updated regularly to reflect ongoing application to clinical studies carried out in veterinary patients.

Background/aimsTo determine whether timing of ophthalmic screening influences prevalence of neonatal fundus haemorrhages. We compared the prevalence of fundus haemorrhages in two populations: term newborns screened early (less than 72 hours) and preterm newborns screened late (4–11 weeks). Additionally, we reviewed the literature on timing and prevalence of newborn haemorrhages.MethodsRetrospective observational cohort study. Infants who underwent wide-angle ophthalmic digital imaging over one overlapping year in the Newborn Eye Screen Testing (NEST) or Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) programme were included. The PubMed database was filtered to include English-language articles dating back to 1950. Nine articles were selected for review based on inclusion of the prevalence of newborn fundus haemorrhages at multiple time points.ResultsA total of 202 patients received early imaging in the NEST cohort and 73 patients received late imaging in the SUNDROP cohort. In the NEST cohort, 20.2% of newborns had haemorrhages. In contrast, we found haemorrhages in only one case or 1.4% of the SUNDROP cohort. Using prevalence data from nine additional studies, we developed a predicted probabilities model of newborn haemorrhages. Per this model, the probability of seeing a haemorrhage if you screen an infant at 1 hour is 18.8%, at 2 weeks is 2.9% and at 1 month is 0.28%.ConclusionWe found a significant difference in the prevalence of fundus haemorrhages between the early-screened NEST cohort and the late-screened, preterm SUNDROP cohort. Likely, this difference is due to the transient nature of most newborn haemorrhages.

BACKGROUND AND OBJECTIVE: To provide an updated estimate of incidence and prevalence of the foremost retinal diseases in the U.S. PATIENTS AND METHODS: Retrospective study of the Vestrum Health Database evaluating eyes with diagnoses of wet or dry age-related macular degeneration (AMD), diabetic macular edema (DME), diabetic retinopathy (DR), branch or central retinal vein occlusion (BRVO; CRVO) from January 2014 to December 2019 across 58 retina practices. RESULTS: Of the 3,086,791 eyes examined, 490,881 (15.9%) had dry AMD, 294,041 (9.5%) wet AMD, 270,703 (8.8%) DME, 254,690 (8.3%) DR without DME, 73,617 (2.4%) BRVO, and 50,670 (1.6%) CRVO. Dry AMD had the highest incidence. These diseases comprised 61.0% of total prevalence and 54.3% of incidence among patients at the retina practices analyzed. CONCLUSIONS: Based on a diverse database, these diseases comprised the majority of U.S. retina practice cases, with increasing annual incidences. AMD is the most common diagnosis, then diabetic eye disease. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:29–36.]

Background: Alcohol and drug screens in trauma patients are endorsed by the American College of Surgeons Committee on Trauma. The objective was to determine the characteristics and frequency of alcohol and poly-drug combinations in patients triaged by Trauma Team Activation (TTA) codes. Methods: A retrospective study of a Level I hospital trauma registry was initiated with 14,972 patients of whom 7028 (47%) were Substance Users (SU). There were 10,369 TTA patients: 5396 (52%) were SU, and 4603 (31%) non-TTA patients, of whom 1632 (35.5%) were SU. Inclusion criteria were: age ≥14 years old, blood alcohol level and Urine Drug Screen (UDS) documentation, Injury Severity Score (ISS), TTA code, hospital charges and Length of Hospitalization (LOS). Statistical analyses were performed with one-way ANOVA, Maximum Likelihood chi squared, and Mann-Whitney U tests. Results: The median ISS was 5 for both groups. TTA patients were younger than non-TTA patients (median 33 years versus 41 years). Mortality was significantly higher for TTA (4.7%) than for non-TTA (0.7%) patients. From 2010-2013 to 2014-2018, all substance users had a significant decrease in alcohol only use (58.0% to 42.0%) with an increase in single drug (42.0% to 58.0%) and poly-drug use (36.9% to 63.1%), p < 0.0001. For all SU patients (TTA and non-TTA), the major single drugs used were opiates (19.9%), cannabinoids (THC) (15.2%), benzodiazepines (7.7%), amphetamines (6.6%), and cocaine (2.5%). The major poly-drugs were: opiates/THC (4.7%), opiates/benzodiazepines (4.6%), THC/amphetamines (3.1%), THC/benzodiazepines (2.2%). Conclusions: By trauma activation code designation, the TTA group had most of the positive alcohol and drug screens in this study. Since the change in mandated opioid prescription practices in 2014, this study showed increased poly-drug use (two to six-drug combinations) in urban trauma patients between 2014-2018. Opioids and cannabinoids continued to be the most frequently used drugs singly and in combinations.

In vitro fertilization (IVF) comprises a sequence of interventions concerned with the creation and culture of embryos which are then transferred to the patient's uterus. While the clinically important endpoint is birth, the responses to each stage of treatment contain additional information about the reasons for success or failure. As such, the ability to predict not only the overall outcome of the cycle, but also the stage-specific responses, can be useful. This could be done by developing separate models for each response variable, but recent work has suggested that it may be advantageous to use a multivariate approach to model all outcomes simultaneously. Here, joint analysis of the sequential responses is complicated by mixed outcome types defined at two levels (patient and embryo). A further consideration is whether and how to incorporate information about the response at each stage in models for subsequent stages. We develop a case study using routinely collected data from a large reproductive medicine unit in order to investigate the feasibility and potential utility of multivariate prediction in IVF. We consider two possible scenarios. In the first, stage-specific responses are to be predicted prior to treatment commencement. In the second, responses are predicted dynamically, using the outcomes of previous stages as predictors. In both scenarios, we fail to observe benefits of joint modelling approaches compared to fitting separate regression models for each response variable., Comment: 28 pages, 2 figures, Stan and R code at osf.io/pmrn3/

Rationale: In December 2016, a single-center study describing significant improvements in mortality among a small group of patients with severe sepsis and septic shock treated with hydrocortisone, ...

To investigate the associations between clinical, procedural, and radiographic factors and outcomes of steroid hip injections, including long-term and immediate pain reduction, time to arthroplasty, time to reinjection, and the total number of injections. All intra-articular anesthetic and steroid injections of the hip under fluoroscopic guidance between January 2014 and March 2016 were retrospectively reviewed. Hip radiographs were scored using the Kellgren–Lawrence (KL) and Osteoarthritis Research Society International (OARSI) scores. Immediate pain relief and response were evaluated using a change in visual analog scale and OMERACT-OARSI criteria respectively. Long-term pain relief was evaluated at 2‑7 months after injection by reviewing the medical records. Correlation between patient characteristics, procedural variations, and radiographic factors with injection outcomes was analyzed by using linear and logistic regression models. Of 361 injections, 79.8% showed an immediate pain response and 32.7% had subjective long-term pain relief (> 2 months). There was no significant correlation between immediate pain relief and response with long-term pain relief and other outcomes. Older age and higher KL score, OARSI-central joint space narrowing (JSN), and inferior acetabular osteophyte were correlated with long-term pain relief (p = 0.01‑0.03). Higher KL and OARSI grades, particularly JSN, were significantly correlated with increased immediate pain relief and total number of injections but decreased time to arthroplasty. Baseline pain positively correlated with immediate pain response (p

Objective: To create a classification system based on stroke-related impairments. Data source: All adults with stroke admitted for at least 72 hours in England, Wales and Northern Ireland from July 2013 to July 2015 extracted from the Sentinel Stroke National Audit Programme Analysis: Impairments were defined using the National Institute of Health Stroke Scale scores at admission. Common combinations of impairments were identified based on geometric coding and expert knowledge. Validity of the classification was assessed using standard descriptive statistics to report and compare patients’ characteristics, therapy received and outcomes in each group. Results: Data from 94,905 patients were extracted. The items of the National Institute of Health Stroke Scale (on admission) were initially grouped into four body systems: Cognitive, Motor, Sensory and Consciousness. Seven common combinations of these impairments were identified (in order of stroke severity); Patients with Loss of Consciousness ( n = 6034, 6.4%); those with Motor + Cognitive + Sensory impairments ( n = 28,226, 29.7%); Motor + Cognitive impairments ( n = 16,967, 17.9%); Motor + Sensory impairments ( n = 9882, 10.4%); Motor Only impairments ( n = 20,471, 21.6%); Any Non-Motor impairments ( n = 7498, 7.9%); and No Impairments ( n = 5827, 6.1%). There was a gradation of age, premorbid disability, mortality and disability on discharge. People with the most and least severe categories were least likely to receive therapy, and received least therapy (−20 minutes/day of stay) compared to −35 minutes/day of stay for the moderately severe categories. Conclusions: A classification system of seven Stroke Impairment Categories has been presented.

To determine the incidence of central serous chorioretinopathy (CSC) stratified by age, sex, and diagnosis with obstructive sleep apnea (OSA), and to determine whether some patients with newly diagnosed CSC may be candidates for OSA evaluation.Retrospective cohort study.We used the IBM MarketScan database to select 59,016,145 commercially insured patients in the United States between 2007 and 2016. We identified patients' first diagnosis with CSC, and defined patients as having OSA if they had a diagnosis following a sleep study. We specified Cox proportional hazard models with interactions between age, sex, and OSA status to determine patients' risk of developing CSC. We estimated the positive predictive value (PPV) that a new diagnosis of CSC would have in predicting a subsequent diagnosis of OSA.Risk of CSC increased with age in years (hazard ratio [HR] = 1.030, P.001) and OSA diagnosis (HR = 1.081, P.033), and was lower in women (HR = 0.284, P.001). We estimated the annual incidence of CSC was 9.6 and 23.4 per 100,000 women and men, respectively. Incidence was higher in women and men with OSA (17.2 and 40.8 per 100,000). The PPV of CSC diagnosis as a predictor of OSA was highest in the fifth decade of life.The incidence of CSC in our patient sample is higher than previously reported. Risk of CSC is higher in men than in women, and OSA increases risk of CSC in both men and women. Some patients, particularly older male patients, may be good candidates for OSA evaluation following a CSC diagnosis.

Background Atlanto-occipital transarticular screw fixation (AOTSF) has rarely been reported for fixation of the craniovertebral junction (CVJ). Methods A retrospective chart review of all pediatric patients (less than 18 years of age) with an attempt of AOTSF for fixation of traumatic CVJ instability was conducted. Results A total of 4 patients (2 boys and 2 girls; ages 2, 3, 5, and 8 years) who suffered from acute traumatic CVJ instability managed during 2007–2018 underwent an attempted AOTSF. In 2 patients, this method was technically successful. In the other 2 instances, we were not able to engage the screw into the occipital condyle. These were converted to standard occipital plate, rod, and screw fixation. All were placed in a halo subsequently for a minimum of 3 months. Three patients were fused at last follow-up (range, 17–48 months). One patient after successful AOTSF did not fuse. There were no surgical complications or revision procedures. Conclusions AOTSF was feasible in half of pediatric patients suffering from traumatic CVJ instability. Therefore, intraoperative salvage options and strategies should be on hand readily. In the pediatric population, where bony anatomy may pose challenges to fixation, this technique may offer a viable first-line option in selected cases, despite the overall modest success rate.

Spatial neglect has profound implications for quality of life after stroke, yet we lack consensus for screening/diagnosing this heterogeneous syndrome. Our first step in a multi-stage research programme aimed to determine which neglect tests are used (within four categories: cognitive, functional, neurological and neuroimaging/neuromodulation), by which stroke clinicians, in which countries, and whether choice is by professional autonomy or institutional policy. 454 clinicians responded to an online survey: 12 professions (e.g., 39% were occupational therapists) from 33 countries (e.g., 38% from the UK). Multifactorial logistic regression suggested inter-professional differences but fewer differences between countries (Italy was an outlier). Cognitive tests were used by 82% (particularly by psychologists, cancellation and drawing were most popular); 80% used functional assessments (physiotherapists were most likely). 20% (mainly physicians, from Italy) used neuroimaging/ neuromodulation. Professionals largely reported clinical autonomy in their choices. Respondents agreed on the need for a combined approach to screening and further training. This study raises awareness of the translation gap between theory and practice. These findings lay an important foundation to subsequent collaborative action between clinicians, researchers and stroke survivors to reach consensus on screening and diagnostic measures. The immediate next step is a review of the measures' psychometric properties. Published online: 21 Jul 2020

Objectives: To understand why most stroke patients receive little therapy. We investigated the factors associated with the amount of stroke therapy delivered. Methods: Data regarding adults admitted to hospital with stroke for at least 72 hours (July 2013–July 2015) were extracted from the UK’s Sentinel Stroke National Audit Programme. Descriptive statistics and multilevel mixed effects regression models explored the factors that influenced the amount of therapy received while adjusting for confounding. Results: Of the 94,905 patients in the study cohort (mean age: 76 (SD: 13.2) years, 78% had a mild or moderate severity stroke. In all, 92% required physiotherapy, 87% required occupational therapy, 57% required speech therapy but only 5% were considered to need psychology. The average amount of therapy ranged from 2 minutes (psychology) to 14 minutes (physiotherapy) per day of inpatient stay. Unmodifiable characteristics (such as stroke severity) dominated the variation in the amount of therapy. However important, modifiable organizational factors were the day and time of admission, type of stroke team, timely therapy assessments, therapy and nursing staffing levels (qualified and support staff), and presence of weekend or early supported discharge services. Conclusion: The amount of stroke therapy is associated with unmodifiable patient-related characteristics and modifiable organizational factors in that more therapy was associated with higher therapy and nurse staffing levels, specialist stroke rehabilitation services, timely therapy assessments, and the presence of weekend and early discharge services.

BACKGROUND AND OBJECTIVE: To investigate whether surgical management of newly diagnosed rhegmatogenous retinal detachment (RRD) varies if patients are diagnosed during a major national ophthalmology conference. PATIENTS AND METHODS: This retrospective cohort study included 34,759 patients with incident RRD, of whom, 1,246 (3.6%) were diagnosed during dates of three national ophthalmology conferences, and 1,170 (3.4%) underwent surgery during conference dates. The authors identified patients with primary repair with cryotherapy, laser, scleral buckle, pneumatic retinopexy, or pars plana vitrectomy. Multinomial logistic regression models were used to determine patients' likelihood of receiving each type of repair within 30 days of their diagnosis depending on whether they were diagnosed during a national ophthalmology conference. Linear regression models were used to determine the relationship between the date patients were diagnosed and how long they waited to receive a repair. Main outcome measures included days between diagnosis with RRD and RRD repair, receiving repair on the same day of diagnosis, and reoperation rate within 30 days of the primary repair. RESULTS: Mean time from diagnosis to repair was 1.5 days (standard deviation: ± 2.4 days), and 71% of patients underwent repair within a day of diagnosis. Repairs were followed by a second surgery within 30 days in 11.1% of patients. Patients diagnosed during conferences waited 0.23 days longer between diagnosis and repair compared with patients diagnosed outside of conference dates ( P = .001). Patients diagnosed with RRD during conferences were less likely to receive surgical repair within a day of diagnosis compared to patients diagnosed during non-conference dates ( P = .037). Patients who were diagnosed with RRD during a conference date and also received surgery during a conference date were more likely to undergo a second surgery within 30 days of the primary procedure ( P = .006) CONCLUSIONS: Patients diagnosed with RRD during national ophthalmology conference dates waited slightly longer for surgery, were slightly less likely to receive surgery within a day, and were more likely to undergo a second surgery within 30 days of the primary procedure. The “national meeting effect” phenomenon is present in ophthalmology, albeit to a lesser degree that is likely not visually significant. [ Ophthalmic Surg Lasers Imaging Retina . 2020;51:328–337. ]

Background: Stroke causes communication impairments but we lack the real-world population-level data needed to inform inpatient and community services. Objectives: To establish prevalence of aphasia and dysarthria within inpatient stroke survivors, describe those affected, the amount of therapy they receive and their outcomes. Methods: Secondary analysis of data from the Sentinel Stroke National Audit Programme including inpatient stroke survivors after 72 hours, with completed National Institute of Health Stroke Scale data (communication items), excluding those already discharged, not conscious or with incomplete data. Results: 64% of the 88,974 stroke survivors meeting our criteria were communication impaired: 28% had both aphasia and dysarthria, 24% had dysarthria only and 12% had aphasia only. Those in the older age range and with more severe stroke were more likely to have a communication impairment and had a worse outcome than those without communication impairment. Subgroups with communication impairment received an average of 10 minutes of speech and language therapy for communication and/or dysphagia per day of stay. Conclusions: Communication impairment is common during the inpatient phase of stroke care yet average therapy provision is below the recommended levels and is likely to include dysphagia assessment and intervention. Dysarthria is reported as more prevalent than aphasia at this early stage, although this is not necessarily diagnosed by a speech and language therapist. The most common presentation is to have a combination of aphasia and dysarthria for which there is limited clinical guidance.

Background Aboriginal women experience disproportionately higher rates of cervical cancer mortality yet are less likely to participate in screening for early detection. This study sought to determine whether a community-based HPV self-sampling service model can effectively recruit never-screened and under-screened Aboriginal women to participate in cervical cancer screening; assess the clinical outcomes; and explore the acceptability of the model from the perspective of the participants. Methods Aboriginal women aged 25–69 years of age were recruited from eight rural and remote communities in New South Wales, Australia to participate in HPV self-sampling via a community-based service model. Outcome measures were: number of women screened by HPV self-sampling, their prior cervical screening status (under-screened or never-screened), clinical outcomes and participation in follow-up pathways of care, and satisfaction with the service model. Results In total, 215 women conducted a HPV self-sampling test and 200 evaluation surveys were completed. One-fifth of participants (n = 46) were never-screened and one-third (n = 69) were under-screened. Many were unsure of their screening status. Nine women were HPV 16/18 positive and eight had completed all follow up by the conclusion of the study. A further 30 women tested positive for a high risk type other than HPV 16/18 (HPV other), of which 14 had completed follow up at the conclusion of the study. Satisfaction with the HPV self-sampling kit, the process of self-sampling and the service model was high (> 92% satisfied on all items). Many women had difficulty understanding their official HPV results and placed high importance on the nurse explaining it to them. Conclusions A community-based service model that respects Aboriginal Women’s Business can effectively recruit under-screened and never-screened Aboriginal women to complete cervical cancer screening. Furthermore, this service model supports them to complete recommended follow-up care and engage with their local existing health services.

Purpose To determine the association and cumulative dose–response pattern between pentosan polysulfate sodium (PPS) use for interstitial cystitis (IC) and maculopathy. Design Large, multicenter, retrospective cohort study of commercially insured patients in the MarketScan database (Truven Health Analytics, San Jose, CA). Participants Two hundred twenty-seven thousand three hundred twenty-five patients with IC who were enrolled continuously in the MarketScan database. Methods Cox proportional hazards models (controlling for patient gender, age at index diagnosis of IC, and diagnosis with diabetes mellitus) followed up patients from index diagnosis of IC for 5 years, or until patients discontinued insurance coverage, or until patients’ first diagnosis with a maculopathy. As a sensitivity analysis, we re-estimate all models after excluding all patients with diabetes. To assess for dose response, we calculated the total days of PPS prescriptions filled and created a categorical variable indicating total exposure. Main Outcome Measures The primary outcome measure was association between binary PPS exposure and any maculopathy. Secondary outcome measures included exposure between binary and categorical, time-dependent, exposure to PPS and to drusen, nonexudative age-related macular degeneration (AMD), exudative AMD, hereditary maculopathy, and toxic maculopathy. Results The most common diagnoses of maculopathy in patients with IC were exudative AMD (1.5%), drusen (0.8%), nonexudative AMD (0.3%), toxic maculopathy (0.1%), and hereditary dystrophy (0.04%). In unadjusted analyses, the percentage of patients who filled a PPS prescription and were diagnosed later with a maculopathy (2.37%) was very similar to the percentage of patients who did not fill a prescription (2.77%). Survival models using a binary variable indicating PPS exposure showed no significant associations between PPS exposure and diagnosis of drusen, nonexudative AMD, exudative AMD, toxic maculopathy, hereditary dystrophy, or an aggregate variable of any maculopathy. Similarly, there was no dose-dependent relationship between PPS exposure and diagnosis of any maculopathy. These findings remained stable in sensitivity analysis models that excluded patients with diabetes mellitus. Conclusions In this large, commercial claims database analysis, no association was found between PPS exposure and subsequent diagnosis of maculopathy.

Objective: To map and describe how patients pass through stroke services. Methods: Data from 94,905 stroke patients (July 2013–July 2015) who were still inpatients 72 hours after hospital admission were extracted from a national stroke register and were used to identify the routes patients took through hospital and community stroke services. We sought to categorize these routes through iterative consultations with clinical experts and to describe patient characteristics, therapy provision, outcomes and costs within each category. Results: We identified 874 routes defined by the type of admitting stroke team and subsequent transfer history. We consolidated these into nine distinct routes and further summarized these into three overlapping ‘pathways’ that accounted for 99% of the patients. These were direct discharge (44%), community rehabilitation (47%) and inpatient transfer (19%) with 12% of the patients receiving both inpatient transfer and community rehabilitation. Patients with the mildest and most severe strokes were more likely to follow the direct discharge pathway. Those perceived to need most therapy were more likely to follow the inpatient transfer pathway. Costs were lowest and mortality was highest for patients on the direct discharge pathway. Outcomes were best for patients on the community rehabilitation pathway and costs were highest where patients underwent inpatient transfers. Conclusion: Three overarching stroke care pathways were identified which differ according to patient characteristics, therapy needs and outcomes. This pathway mapping provides a benchmark to develop and plan clinical services, and for future research.

Background: Optic disc pits frequently lead to visual deterioration due to macular retinoschisis or serous retinal detachment. Here, we report a case of optic disc pit–associated macular retinoschisis due to intraretinal fluid accumulation that resolved with improvement in visual acuity after treatment with topical dorzolamide. Case description: A 56-year-old otherwise healthy female with no ocular history presented with 2 weeks of slowly worsening blurry vision in her right eye. Visual acuity was 20/30 in the right eye. Posterior segment examination revealed posterior vitreous detachment, an optic disc pit at 9 o’clock, macular edema and foveoschisis with fluid extending from the optic nerve, and a normal peripheral retina. Optical coherence tomography imaging of the macula showed central subfield thickness of 526 µm. The patient preferred no surgical intervention, so topical dorzolamide 2% three times daily was initiated. Over the next 2 years, the central subfield thickness steadily declined from 526 to 262 µm, and her vision improved to 20/20 with improvement in the macular retinoschisis. Conclusion: Our report presents a case of resolution of optic disc pit–associated macular retinoschisis due to intraretinal fluid accumulation with possible role for dorzolamide as a potential treatment option.

BACKGROUND AND OBJECTIVE: To describe a case series of three patients in one family with Von Hippel-Lindau (VHL) disease who presented with vitreoretinal neovascularization and resulting tractional retinal detachments (TRDs). This vitreoretinal phenotype of VHL may benefit from early surgical intervention. PATIENTS AND METHODS: Descriptive case series of three patients in one family with VHL disease. A review of the literature regarding surgical intervention for VHL was performed. RESULTS: All three patients developed prominent intravitreal neovascularization with fibrovascular growth within the vitreous secondary to a retinal capillary hemangioma. Two subjects with intravitreal neovascularization were treated with laser and cryotherapy but eventually developed a TRD. The final vision in these two patients was light perception and 20/300. The eye that was preemptively treated with vitrectomy to remove the vitreous sustaining the neovascularization had visual acuity of 20/50 after surgery. CONCLUSION: Intravitreal neovascularization with fibrovascular proliferation may be an indication for vitrectomy prior to the development of retinal detachment. [ Ophthalmic Surg Lasers Imaging Retina . 2020;51:109–115.]

Background Rabacfosadine (RAB), a novel antineoplastic agent conditionally licensed for the treatment of lymphoma in dogs, is efficacious in both naive and previously treated dogs. Its use in combination with L-asparaginase (L-ASP) has not been studied. Hypothesis/objectives To evaluate the safety and efficacy of L-ASP given concurrently with RAB in dogs with relapsed multicentric lymphoma. Animals Fifty-two dogs with relapse of lymphoma after treatment with at least 1 doxorubicin-based chemotherapy protocol. Methods Open-label, multicenter, prospective single-arm clinical trial. Dogs were treated with RAB at 1.0 mg/kg IV every 21 days for up to a total of 5 doses. L-asparaginase was administered at 400 IU/kg SQ concurrently with the first 2 treatments of RAB. Results The overall response rate (ORR) for all dogs was 67%, with 19 dogs (41%) achieving a complete response (CR). The median progression-free survival time (MPFS) was 63 days (range 5-428 days). Dogs experiencing a CR as their best response had an MPFS of 144 days (range 44-428 days). Adverse events were similar to previous studies evaluating single agent RAB. Failure to achieve a CR and having previously received L-ASP were negative prognostic factors on multivariate analysis. Conclusions and clinical importance Concurrent RAB/L-ASP appears to be both efficacious and safe for treating relapsed multicentric lymphoma in dogs. Adverse events were most often mild and no unexpected toxicoses were observed.

Purpose To evaluate geographic variation and characterize the relative contributions of patient characteristics, physician practice, and geographic region on variation in primary rhegmatogenous retinal detachment (RRD) management. Design Retrospective claims-based analysis. Participants Commercially insured patients with incident RRD diagnosed between 2008 and 2016 (12 779 patients). Methods We determined whether patients underwent primary RRD repair within 60 days of diagnosis and identified repair type. We characterized physicians using physician identifier variables and characterized geography by Combined Statistical Areas or Core-Based Statistical Area. We used multilevel mixed effects logistic regression models to evaluate patient-, physician-, and geographic-level variation in whether patients underwent RRD repair and used multilevel mixed effects multinomial models to characterize variation in repair type. For each model, we evaluated patient fixed effects and physician random effects nested within geographic random effects. We estimated intraclass correlation coefficients and variance partition coefficients, respectively, to compare relative contributions of patient, physician, and geography to overall variation. Main Outcome Measures Odds ratios for RRD repair and variation estimates for patient, physician, and geography. Results Most incident RRD patients received treatment within 60 days post-diagnosis. Pars plana vitrectomy was most common (49%), followed by laser barricade (23%), scleral buckle and pneumatic retinopexy (both 11%), and cryotherapy (5%). Physician-level variation showed greater impact on receipt of any treatment than geographic-level variation (estimated variance coefficients of 1.09 and 0.32, respectively). Patient-level characteristics represented approximately 82% of overall variation in receipt of any repair, versus 16% from physician-level and 2% from geographic-level factors. Among RRD patients who underwent repair, estimated variance coefficients were 0.07 for geography and 3.37 for physician. Physician-level factors represented approximately 50% of total variation in repair type, followed by patient-level (49%), and geographic-level (1%) factors. Conclusions Rhegmatogenous retinal detachment repair decisions are influenced by patient-level and physician-level factors, less so by geographic variation. Patient characteristics account for most of the variation in receipt of repair, and physician practice accounts for most of the variation in choice of procedure. These findings indicate a need for additional studies to understand drivers behind differences in care and clinical outcomes and to identify barriers in access to care.

The optimal flap cover for managing open lower limb fractures is debated. Most studies have reported on surgical outcome but clinical outcome is not well recognised. We aimed to determine whether there are differences in patient-reported quality of life (QoL) outcome between local flap versus free flap. All patients admitted with lower limb open fractures were retrospectively reviewed. Patient notes were assessed for demographics, time to fracture union, wound healing and patient-reported QoL with EQ-5D-5L alongside a novel flap assessment tool. A total of 40 patients had flap reconstruction of their lower limb injury; 23 local flap (Group I) and 17 free flap (Group II). Average length of follow-up was 33.8 months. Group I - 10 revisions of flaps (43.5%) and 14 surgical complications (60.9%). Fracture union was 171 days and wound healing 130 days. EQ-5D index and EQ-VAS scores were 0.709 and 79.3, respectively. Group II – 8 revision of flaps (47.1%) and 12 surgical complications (70.6%). Fracture union was 273 days and wound healing 213 days. EQ-5D index and EQ-VAS scores were 0.525 and 57.2, respectively. Aesthetic appeal - 48% Group I vs. 66% Group II. Significant differences were found between the two flap groups with higher scores for daily living in Group I (p = 0.007) compared to higher overall flap ratings in Group II (p = 0.049). Both groups were comparable in terms of complications; while flap congestion and dehiscence were more common with free flaps statistical interrogation did not elicit significance (p > 0.05). Local flap and free flap techniques offer distinct advantages. Local flaps have better surgical outcome and patient-reported QoL in the first few years post soft tissue reconstruction. Differences between local and free reconstructive techniques in terms of patient health and function are ameliorated in the longer term.

Background and Purpose: Neuroprotective strategies for stroke remain inadequate. Nanoliposomes comprised of phosphatidylcholine, cholesterol, and monosialogangliosides (nanoliposomes) induced an antioxidant protective response in endothelial cells exposed to amyloid insults. We tested the hypotheses that nanoliposomes will preserve human neuroblastoma (SH-SY5Y) and human brain microvascular endothelial cells viability following oxygen-glucose deprivation (OGD)–reoxygenation and will reduce injury in mice following middle cerebral artery occlusion. Methods: SH-SY5Y and human brain microvascular endothelial cells were exposed to oxygen-glucose deprivation–reoxygenation (3 hours 0.5%–1% oxygen and glucose-free media followed by 20-hour ambient air/regular media) without or with nanoliposomes (300 µg/mL). Viability was measured (calcein-acetoxymethyl fluorescence) and protein expression of antioxidant proteins HO-1 (heme oxygenase-1), NQO1 (NAD[P]H quinone dehydrogenase 1), and SOD1 (superoxide dismutase 1) were measured by Western blot. C57BL/6J mice were treated with saline (n=8) or nanoliposomes (10 mg/mL lipid, 200 µL, n=7) while undergoing 60-minute middle cerebral artery occlusion followed by reperfusion. Day 2 postinjury neurological impairment score and infarction size were compared. Results: SH-SY5Y and human brain microvascular endothelial cells showed reduced viability post–oxygen-glucose deprivation–reoxygenation that was reversed by nanoliposomes. Nanoliposomes increased protein expressions of HO-1, NQO1 in both cell types and SOD1 in human brain microvascular endothelial cells. Nanoliposomes-treated mice showed reduced neurological impairment and brain infarct size (18.8±2% versus 27.3±2.3%, P =0.017) versus controls. Conclusions: Nanoliposomes reduced stroke injury in mice subjected to middle cerebral artery occlusion likely through induction of an antioxidant protective response. Nanoliposome is a candidate novel agent for stroke.

Background: \ud Few data exist on the comparative safety and immunogenicity of different COVID-19 vaccines given as a third (booster) dose. To generate data to optimise selection of booster vaccines, we investigated the reactogenicity and immunogenicity of seven different COVID-19 vaccines as a third dose after two doses of ChAdOx1 nCov-19 (Oxford–AstraZeneca; hereafter referred to as ChAd) or BNT162b2 (Pfizer–BioNtech, hearafter referred to as BNT).\ud \ud Methods: \ud COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of third dose booster vaccination against COVID-19. Participants were aged older than 30 years, and were at least 70 days post two doses of ChAd or at least 84 days post two doses of BNT primary COVID-19 immunisation course, with no history of laboratory-confirmed SARS-CoV-2 infection. 18 sites were split into three groups (A, B, and C). Within each site group (A, B, or C), participants were randomly assigned to an experimental vaccine or control. Group A received NVX-CoV2373 (Novavax; hereafter referred to as NVX), a half dose of NVX, ChAd, or quadrivalent meningococcal conjugate vaccine (MenACWY) control (1:1:1:1). Group B received BNT, VLA2001 (Valneva; hereafter referred to as VLA), a half dose of VLA, Ad26.COV2.S (Janssen; hereafter referred to as Ad26) or MenACWY (1:1:1:1:1). Group C received mRNA1273 (Moderna; hereafter referred to as m1273), CVnCov (CureVac; hereafter referred to as CVn), a half dose of BNT, or MenACWY (1:1:1:1). Participants and all investigatory staff were blinded to treatment allocation. Coprimary outcomes were safety and reactogenicity and immunogenicity of anti-spike IgG measured by ELISA. The primary analysis for immunogenicity was on a modified intention-to-treat basis; safety and reactogenicity were assessed in the intention-to-treat population. Secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ISRCTN, number 73765130.\ud \ud Findings: \ud Between June 1 and June 30, 2021, 3498 people were screened. 2878 participants met eligibility criteria and received COVID-19 vaccine or control. The median ages of ChAd/ChAd-primed participants were 53 years (IQR 44–61) in the younger age group and 76 years (73–78) in the older age group. In the BNT/BNT-primed participants, the median ages were 51 years (41–59) in the younger age group and 78 years (75–82) in the older age group. In the ChAd/ChAD-primed group, 676 (46·7%) participants were female and 1380 (95·4%) were White, and in the BNT/BNT-primed group 770 (53·6%) participants were female and 1321 (91·9%) were White. Three vaccines showed overall increased reactogenicity: m1273 after ChAd/ChAd or BNT/BNT; and ChAd and Ad26 after BNT/BNT. For ChAd/ChAd-primed individuals, spike IgG geometric mean ratios (GMRs) between study vaccines and controls ranged from 1·8 (99% CI 1·5–2·3) in the half VLA group to 32·3 (24·8–42·0) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·1 (95% CI 0·7–1·6) for ChAd to 3·6 (2·4–5·5) for m1273. For BNT/BNT-primed individuals, spike IgG GMRs ranged from 1·3 (99% CI 1·0–1·5) in the half VLA group to 11·5 (9·4–14·1) in the m1273 group. GMRs for wild-type cellular responses compared with controls ranged from 1·0 (95% CI 0·7–1·6) for half VLA to 4·7 (3·1–7·1) for m1273. The results were similar between those aged 30–69 years and those aged 70 years and older. Fatigue and pain were the most common solicited local and systemic adverse events, experienced more in people aged 30–69 years than those aged 70 years or older. Serious adverse events were uncommon, similar in active vaccine and control groups. In total, there were 24 serious adverse events: five in the control group (two in control group A, three in control group B, and zero in control group C), two in Ad26, five in VLA, one in VLA-half, one in BNT, two in BNT-half, two in ChAd, one in CVn, two in NVX, two in NVX-half, and one in m1273.\ud \ud Interpretation: \ud All study vaccines boosted antibody and neutralising responses after ChAd/ChAd initial course and all except one after BNT/BNT, with no safety concerns. Substantial differences in humoral and cellular responses, and vaccine availability will influence policy choices for booster vaccination.\ud \ud Funding: \ud UK Vaccine Taskforce and National Institute for Health Research.

Healthcare personnel (HCP) with unprotected exposures to aerosol-generating procedures (AGPs) on patients with coronavirus disease 2019 (COVID-19) are at risk of infection with severe acute respiratory coronavirus virus 2 (SARS-CoV-2). A retrospective review at an academic medical center demonstrated an infection rate of

There is a knowledge gap when treating comorbid chronic pain and posttraumatic stress disorder (PTSD) during the COVID-19 pandemic. Addressing this gap, 169 individuals (57.4% female), aged 39.8 years were recruited based on levels of pain-related disability and PTSD symptoms. Participants were assessed prior to, and during, the COVID-19 pandemic. Improvements in pain-related disability were marginally attenuated for the comorbid group, compared to the chronic pain group. Results show that some condition-specific symptoms may not have been affected by the COVID-19 pandemic. Cautious interpretation is warranted due to only two time points and the lack of a diverse sample.

Background Newly detected atrial fibrillation (NDAF) following an ischemic stroke or transient ischemic attack is often paroxysmal in nature. While challenging to detect, extended electrocardiographic (ECG) monitoring is often used to identify NDAF which has resource implications. Prognostic risk scores have been derived which may stratify the risk of NDAF and inform patient selection for ECG monitoring approaches after ischemic stroke/transient ischemic attack. Aim The overall aim was to identify risk scores that were derived and/or validated to predict NDAF after ischemic stroke/transient ischemic attack and evaluate their performance. Summary of review A systematic literature review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, with application of the Quality Assessment of Diagnostic Accuracy-2 tool. Published studies, which derived and validated clinical risk scores in patients with ischemic stroke/transient ischemic attack, or externally validated an existing score to predict NDAF after ischemic stroke/transient ischemic attack, were considered and independently screened by two reviewers. Twenty-one studies involving 23 separate cohorts were analyzed from which 17 integer-based risk scores were identified. The overall frequency of NDAF was 9.7% (95% confidence intervals 8%–11.5%; I2 = 98%). The performance of the scores varied widely among derivation and validation cohorts (area under the receiver operating characteristic curve (AUC) 0.54–0.94); scores derived from stroke cohorts (12 scores) appeared to perform better (AUC 0.7–0.94) than those derived from non-stroke cohorts (five scores; AUC 0.53–0.79). The scores also varied considerably in their complexity, ascertainment, component variables, participant characteristics, outcome definition, and ease of application limiting their generalizability and utility. Conclusion Overall, the risk scores identified performed variably in their discriminative ability and the utility of these scores to predict NDAF in clinical practice remains uncertain. Further studies are required using larger prospective cohorts and randomized control trials to evaluate the usefulness of such scores for clinical decision making and preventative intervention.

People with spatial neglect have difficulty attending to one side of space, which can affect their ability to carry out many everyday tasks and reduce independence. We examined the evidence for any type of nonpharmacological intervention.1MethodsWe searched for randomized controlled trials of any nonpharmacological intervention versus any control specifically aimed at spatial neglect, searching 6 databases including MEDLINE, Embase, CINAHL, and international trials registers in October 2020. Review authors independently assessed risk of bias of included trials and extracted data and assessed the quality of evidence for each outcome using the Grading of Recommendations, Assessment, Development and Evaluations approach. We categorized interventions into 8 broad types through iterative discussion. Our primary outcome was longer term functional ability in activities of daily living (ADL), that is, ≥1 month after the end of intervention.Main ResultsWe included 65 small randomized controlled trials (1951 participants); 43 provided data for meta-analyses. All included people with stroke, one included 3 participants with nonstroke brain injury, and only 7 included participants with left brain damage. All evidence is very low quality, with very low certainty. There were only 2 low risk of bias trials and no adequately powered definitive trials. None reported patient involvement in design or reporting. Outcome measurement focused on cognitive tests and short-term effects; 58 of 65 trials measured ADL using different methods and 16 measured it longer term. Other meaningful outcomes were rarely reported.Four intervention types measured our primary outcome:Visual interventions (training eye movements or scanning): 17 trials (n=398). No evidence of effect on ADL from visual interventions (2 trials, 55 participants; standardized mean difference, −0.04 [95% CI, −0.57 to 0.49]).Noninvasive brain stimulation: 17 trials (n=467). No evidence of effect on ADL from noninvasive brain stimulation (3 trials, 92 participants; standardized mean difference, 0.35 [95% CI, −0.08 to 0.77]).Body awareness (increasing awareness of affected side): 12 trials (n=447). Very low certainty evidence suggesting possible benefit on ADL from body awareness interventions (5 trials, 125 participants; standardized mean difference, 0.61 [95% CI, 0.24–0.97]).Prism adaptation training: 8 trials (n=257). No evidence of effect on ADL from prism adaptation (2 trials, 39 participants; standardized mean difference, −0.29 [95% CI, −0.93 to 0.35]).Four intervention types did not provide data on longer term ADL: electrical stimulation, 8 trials (n=270); mental function (increasing mental processing skills), 7 trials (n=170); movement (of the arm/body), 6 trials (n=220); and acupuncture, 2 trials (n=104).DiscussionDespite 65 trials (1951 participants), evidence of benefit/risk of nonpharmacological intervention to improve longer term functional ability remains very uncertain due to study quality. No rehabilitation approach can be supported or refuted over any other based on current evidence.Implications for Clinical Practice and Future ResearchNo strategy for neglect rehabilitation has been researched through fully powered randomized controlled trials. One way to improve the quality of research is by involving patients in trial design and management. Clinicians should continue to follow national clinical guidelines and are strongly encouraged to participate in trials.AcknowledgmentsThis article is based on a Cochrane Review published in The Cochrane Library 2021, Issue 7, doi: 10.1002/14651858.CD003586.pub4/full (see www.thecochranelibrary.com for information). Cochrane Reviews are regularly updated as new evidence emerges and in response to feedback, and The Cochrane Library should be consulted for the most recent version of the review. This review was supported by the Cochrane Stroke Review Group.Sources of FundingNational Institute for Health Research (NIHR) Development and Skills Enhancement Award, United Kingdom: funded Verity Longley; The Stroke Association, United Kingdom: part-funded Audrey Bowen and Christine Hazelton; NIHR NETSCC Incentive Award, United Kingdom: awarded to Audrey Bowen for the update.

In humans, advanced mast cell (MC) neoplasms are rare malignancies with a poor prognosis. Only a few preclinical models are available, and current treatment options are limited. In dogs, MC neoplasms are the most frequent malignant skin tumours. Unlike low-grade MC neoplasms, high-grade MC disorders usually have a poor prognosis with short survival. In both species, neoplastic MCs display activating KIT mutations, which are considered to contribute to disease evolution. Therefore, tyrosine kinase inhibitors against KIT have been developed. Unfortunately, clinical responses are unpredictable and often transient, which remains a clinical challenge in both species. Therefore, current efforts focus on the development of new improved treatment strategies. The field of comparative oncology may assist in these efforts and accelerate human and canine research regarding diagnosis, prognostication, and novel therapies. In this article, we review the current status of comparative oncology approaches and perspectives in the field of MC neoplasms.

Neuroprotective strategies for stroke remain inadequate. Nanoliposomes comprised of phos-phatidylcholine, cholesterol and monosialogangliosides (NL) induced an antioxidant protective response in endothelial cells exposed to amyloid insults. We tested the hypotheses that NL will preserve SH-SY5Y neuroblastoma cell viability following hypoxic injury and will reduce injury in mice following middle cerebral artery occlusion (MCAO). Neuroblastoma were exposed to 20-hour physoxic (5% oxygen) or hypoxic (1% oxygen) condition without or with NL (100 or 300 µg/mL). Viability was measured using calcein-AM fluorescence and SH-SY5Y gene expression of antioxidant proteins heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1) and superoxide dismutase 1 (SOD1) were measured by quantitative polymerase chain reaction. C57BL/6J mice were treated with saline (N=8) or NL (10000 ug/mL, N=7) while undergoing 60-minute MCAO followed by reperfusion. Day 2 post-injury neurologic impairment score and infarction size were compared. Neuroblastoma showed reduced viability following hypoxia that was reversed by NL. NL increased gene expression of HO-1, NQO1 and SOD1 versus controls. NL-treated mice showed reduced neurologic impairment and brain infarct size (18.8±2% versus 27.3±2.3%, p=0.017) versus controls. NL reduced stroke injury in mice subjected to MCAO likely through induction of an antioxidant stress response. NL is a candidate novel agent for stroke.

Randomised controlled trials in reproductive medicine are often subject to outcome truncation, where study outcomes are only defined in a subset of participants. Examples include birthweight (measurable only in the subgroup of participants who give birth) and miscarriage (which can only occur in participants who become pregnant). These are typically analysed by making a comparison between treatment arms within the subgroup (comparing birthweights in the subgroup who gave birth, or miscarriages in the subgroup who became pregnant). However, this approach does not represent a randomised comparison when treatment influences the probability of being observed (i.e. survival). The practical implications of this for reproductive trials are unclear. We developed a simulation platform to investigate the implications of outcome truncation for reproductive medicine trials. We used this to perform a simulation study, in which we considered the bias, Type 1 error, coverage, and precision of standard statistical analyses for truncated continuous and binary outcomes. Increasing treatment effect on the intermediate variable, strength of confounding between the intermediate and outcome variables, and interactions between treatment and confounder were found to adversely affect performance. However, within parameter ranges we would consider to be more realistic, the adverse effects were generally not drastic. For binary outcomes, the study highlighted that outcome truncation may lead to none of the participants in a study arm experiencing the outcome event. This was found to have severe consequences for inferences, and this may have implications for meta-analysis., Comment: 63 pages (including supplementary files). 49 Figures (7 in main document, 42 supplementary figures). Code available at, https://osf.io/gzqbr/

Rationale Murine syngeneic tumor models have revealed efficacious systemic antitumor responses following primary tumor in situ vaccination combined with targeted radionuclide therapy to secondary or metastatic tumors. Here we present studies on the safety and feasibility of this approach in a relevant translational companion dog model (n = 17 dogs) with advanced cancer. Methods The three component of the combination immuno-radiotherapy approach were employed either separately or in combination in companion dogs with advanced stage cancer. In situ vaccination was achieved through the administration of hypofractionated external beam radiotherapy and intratumoral hu14.18-IL2 fusion immunocytokine injections to the index tumor. In situ vaccination was subsequently combined with targeted radionuclide therapy using a theranostic pairing of IV 86Y-NM600 (for PET imaging and subject-specific dosimetry) and IV 90Y-NM600 (therapeutic radionuclide) prescribed to deliver an immunomodulatory 2 Gy dose to all metastatic sites in companion dogs with metastatic melanoma or osteosarcoma. In a subset of dogs, immunologic parameters preliminarily assessed. Results The components of the immuno-radiotherapy combination were well tolerated either alone or in combination, resulting in only transient low grade (1 or 2) adverse events with no dose-limiting events observed. In subject-specific dosimetry analyses, we observed 86Y-NM600 tumor:bone marrow absorbed-dose differential uptakes ≥2 in 4 of 5 dogs receiving the combination, which allowed subsequent safe delivery of at least 2 Gy 90Y-NM600 TRT to tumors. NanoString gene expression profiling and immunohistochemistry from pre- and post-treatment biopsy specimens provide evidence of tumor microenvironment immunomodulation by 90Y-NM600 TRT. Conclusions The combination of external beam radiotherapy, intratumoral immunocytokine, and targeted radionuclide immuno-radiotherapy known to have activity against syngeneic melanoma in murine models is feasible and well tolerated in companion dogs with advanced stage, spontaneously arising melanoma or osteosarcoma and has immunomodulatory potential. Further studies evaluating the dose-dependent immunomodulatory effects of this immuno-radiotherapy combination are currently ongoing.

Supplemental Digital Content is available in the text., IMPORTANCE: Even with its proclivity for older age, coronavirus disease 2019 has been shown to affect all age groups. However, there remains a lack of research focused primarily on the young adult population. OBJECTIVES: To describe the epidemiology and outcomes of coronavirus disease 2019 and identify the risk factors associated with critical illness and mortality in hospitalized young adults. DESIGN, SETTINGS, AND PARTICIPANTS: A retrospective cohort study of the Society of Critical Care Medicine’s Viral Infection and Respiratory Illness Universal Study registry. Patients 18–40 years old, hospitalized from coronavirus disease 2019 from March 2020 to April 2021, were included in the analysis. MAIN OUTCOMES AND MEASURES: Critical illness was defined as a composite of mortality and 21 predefined interventions and complications. Multivariable logistic regression was used to assess associations with critical illness and mortality. RESULTS: Data from 4,005 patients (152 centers, 19 countries, 18.6% non-U.S. patients) were analyzed. The median age was 32 years (interquartile range, 27–37 yr); 51% were female, 29.4% Hispanic, and 42.9% had obesity. Most patients (63.2%) had comorbidities, the most common being hypertension (14.5%) and diabetes (13.7%). Hospital and ICU mortality were 3.2% (129/4,005) and 8.3% (109/1,313), respectively. Critical illness occurred in 25% (n = 996), and 34.3% (n = 1,376) were admitted to the ICU. Older age (p = 0.03), male sex (adjusted odds ratio, 1.83 [95% CI, 1.2–2.6]), and obesity (adjusted odds ratio, 1.6 [95% CI, 1.1–2.4]) were associated with hospital mortality. In addition to the above factors, the presence of any comorbidity was associated with critical illness from coronavirus disease 2019. Multiple sensitivity analyses, including analysis with U.S. patients only and patients admitted to high-volume sites, showed similar risk factors. CONCLUSIONS: Among hospitalized young adults, obese males with comorbidities are at higher risk of developing critical illness or dying from coronavirus disease 2019.

BackgroundPeople with spatial neglect after stroke or other brain injury have difficulty attending to one side of space. Various rehabilitation interventions have been used, but evidence of their benefit is unclear.ObjectivesThe main objective was to determine the effects of non‐pharmacological interventions for people with spatial neglect after stroke and other adult‐acquired non‐progressive brain injury.Search methodsWe searched the Cochrane Stroke Group Trials Register (last searched October 2020), the Cochrane Central Register of Controlled Trials (CENTRAL; last searched October 2020), MEDLINE (1966 to October 2020), Embase (1980 to October 2020), the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1983 to October 2020), and PsycINFO (1974 to October 2020). We also searched ongoing trials registers and screened reference lists.Selection criteriaWe included randomised controlled trials (RCTs) of any non‐pharmacological intervention specifically aimed at spatial neglect. We excluded studies of general rehabilitation and studies with mixed participant groups, unless separate neglect data were available.Data collection and analysisWe used standard Cochrane methods. Review authors categorised the interventions into eight broad types deemed to be applicable to clinical practice through iterative discussion: visual interventions, prism adaptation, body awareness interventions, mental function interventions, movement interventions, non‐invasive brain stimulation, electrical stimulation, and acupuncture. We assessed the quality of evidence for each outcome using the GRADE approach.Main resultsWe included 65 RCTs with 1951 participants, all of which included people with spatial neglect following stroke. Most studies measured outcomes using standardised neglect assessments. Fifty‐one studies measured effects on ADL immediately after completion of the intervention period; only 16 reported persisting effects on ADL (our primary outcome). One study (30 participants) reported discharge destination, and one (24 participants) reported depression. No studies reported falls, balance, or quality of life. Only two studies were judged to be entirely at low risk of bias, and all were small, with fewer than 50 participants per group. We found no definitive (phase 3) clinical trials. None of the studies reported any patient or public involvement.Visual interventions versus any control: evidence is very uncertain about the effects of visual interventions for spatial neglect based on measures of persisting functional ability in ADL (2 studies, 55 participants) (standardised mean difference (SMD) ‐0.04, 95% confidence interval (CI) ‐0.57 to 0.49); measures of immediate functional ability in ADL; persisting standardised neglect assessments; and immediate neglect assessments.Prism adaptation versus any control: evidence is very uncertain about the effects of prism adaptation for spatial neglect based on measures of persisting functional ability in ADL (2 studies, 39 participants) (SMD ‐0.29, 95% CI ‐0.93 to 0.35); measures of immediate functional ability in ADL; persisting standardised neglect assessments; and immediate neglect assessments.Body awareness interventions versus any control: evidence is very uncertain about the effects of body awareness interventions for spatial neglect based on measures of persisting functional ability in ADL (5 studies, 125 participants) (SMD 0.61, 95% CI 0.24 to 0.97); measures of immediate functional ability in ADL; persisting standardised neglect assessments; immediate neglect assessments; and adverse events.Mental function interventions versus any control: we found no trials of mental function interventions for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of mental function interventions on spatial neglect based on measures of immediate functional ability in ADL and immediate neglect assessments.Movement interventions versus any control: we found no trials of movement interventions for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of body awareness interventions on spatial neglect based on measures of immediate functional ability in ADL and immediate neglect assessments.Non‐invasive brain stimulation (NIBS) versus any control: evidence is very uncertain about the effects of NIBS on spatial neglect based on measures of persisting functional ability in ADL (3 studies, 92 participants) (SMD 0.35, 95% CI ‐0.08 to 0.77); measures of immediate functional ability in ADL; persisting standardised neglect assessments; immediate neglect assessments; and adverse events.Electrical stimulation versus any control: we found no trials of electrical stimulation for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of electrical stimulation on spatial neglect based on immediate neglect assessments.Acupuncture versus any control: we found no trials of acupuncture for spatial neglect reporting on measures of persisting functional ability in ADL. Evidence is very uncertain about the effects of acupuncture on spatial neglect based on measures of immediate functional ability in ADL and immediate neglect assessments.Authors' conclusionsThe effectiveness of non‐pharmacological interventions for spatial neglect in improving functional ability in ADL and increasing independence remains unproven. Many strategies have been proposed to aid rehabilitation of spatial neglect, but none has yet been sufficiently researched through high‐quality fully powered randomised trials to establish potential or adverse effects. As a consequence, no rehabilitation approach can be supported or refuted based on current evidence from RCTs. As recommended by a number of national clinical guidelines, clinicians should continue to provide rehabilitation for neglect that enables people to meet their rehabilitation goals. Clinicians and stroke survivors should have the opportunity, and are strongly encouraged, to participate in research. Future studies need to have appropriate high‐quality methodological design, delivery, and reporting to enable appraisal and interpretation of results. Future studies also must evaluate outcomes of importance to patients, such as persisting functional ability in ADL. One way to improve the quality of research is to involve people with experience with the condition in designing and running trials.

Aims While interdisciplinary protocols and expedited surgical treatment improve the management of hip fractures in the elderly, the impact of such interventions on patients specifically undergoing arthroplasty for a femoral neck fracture is not clear. We sought to evaluate the efficacy of an interdisciplinary protocol for the management of patients with a femoral neck fracture who are treated with an arthroplasty. Methods In 2017, our institution introduced a standardized interdisciplinary hip fracture protocol. We retrospectively reviewed adult patients who underwent hemiarthroplasty (HA) or total hip arthroplasty (THA) for femoral neck fracture between July 2012 and March 2020, and compared patient characteristics and outcomes between those treated before and after the introduction of the protocol. Results A total of 157 patients were treated before the introduction of the protocol (35 (22.3%) with a THA), and 114 patients were treated after its introduction (37 (32.5%) with a THA). The demographic details and medical comorbidities were similar in the two groups. Patients treated after the introduction of the protocol had a significantly reduced median time between admission and surgery (22.8 hours (interquartile range (IQR) 18.8 to 27.7) compared with 24.8 hours (IQR 18.4 to 43.3) (p = 0.042), and a trend towards a reduced mean time to surgery (24.1 hours (SD 10.7) compared with 46.5 hours (SD 165.0); p = 0.150), indicating reduction in outliers. Patients treated after the introduction of the protocol had a significantly decreased rate of major complications (4.4% vs 17.2%; p = 0.005), decreased median hospital length of stay in hospital (4.0 days vs 4.8 days; p = 0.008), increased rate of discharge home (26.3% vs 14.7%; p = 0.030), and decreased one-year mortality (14.7% vs 26.3%; p = 0.049). The 90-day readmission rate (18.2% vs 21.7%; p = 0.528) and 30-day mortality (3.7% vs 5.1%; p = 0.767) did not significantly differ. Patients who underwent HA were significantly older than those who underwent THA (82.1 years (SD 10.4) vs 71.1 years (SD 9.5); p < 0.001), more medically complex (mean Charlson Comorbidity Index 6.4 (SD 2.6) vs 4.1 (SD 2.2); p < 0.001), and more likely to develop delirium (8.5% vs 0%; p = 0.024). Conclusion The introduction of an interdisciplinary protocol for the management of elderly patients with a femoral neck fracture was associated with reduced time to surgery, length of stay, complications, and one-year mortality. Such interventions are critical in improving outcomes and reducing costs for an ageing population. Cite this article: Bone Joint J 2021;103-B(7 Supple B):3–8.

Purpose: The mTOR pathway has been identified as a key nutrient signaling hub that participates in metastatic progression of high-grade osteosarcoma. Inhibition of mTOR signaling is biologically achievable with sirolimus, and might slow the outgrowth of distant metastases. In this study, pet dogs with appendicular osteosarcoma were leveraged as high-value biologic models for pediatric osteosarcoma, to assess mTOR inhibition as a therapeutic strategy for attenuating metastatic disease progression. Patients and Methods: A total of 324 pet dogs diagnosed with treatment-naïve appendicular osteosarcoma were randomized into a two-arm, multicenter, parallel superiority trial whereby dogs received amputation of the affected limb, followed by adjuvant carboplatin chemotherapy ± oral sirolimus therapy. The primary outcome measure was disease-free interval (DFI), as assessed by serial physical and radiologic detection of emergent macroscopic metastases; secondary outcomes included overall 1- and 2-year survival rates, and sirolimus pharmacokinetic variables and their correlative relationship to adverse events and clinical outcomes. Results: There was no significant difference in the median DFI or overall survival between the two arms of this trial; the median DFI and survival for standard-of-care (SOC; defined as amputation and carboplatin therapy) dogs was 180 days [95% confidence interval (CI), 144–237] and 282 days (95% CI, 224–383) and for SOC + sirolimus dogs, it was 204 days (95% CI, 157–217) and 280 days (95% CI, 252–332), respectively. Conclusions: In a population of pet dogs nongenomically segmented for predicted mTOR inhibition response, sequentially administered adjuvant sirolimus, although well tolerated when added to a backbone of therapy, did not extend DFI or survival in dogs with appendicular osteosarcoma.

Objectives Accurate and timely diagnosis of pneumonia complicating stroke remains challenging and the diagnostic accuracy of chest X-ray (CXR) in the setting of stroke-associated pneumonia (SAP) is uncertain. The overall objective of this study was to evaluate the use of pulmonary computed tomography (CT) in diagnosis of suspected SAP. Materials and Methods Patients with acute ischemic stroke (IS) or intracerebral hemorrhage (ICH) were recruited within 24h of clinically suspected SAP and underwent non-contrast pulmonary CT within 48h of antibiotic initiation. CXR and pulmonary CT were reported by two radiologists. Pulmonary CT was used as the reference standard for final diagnosis of SAP. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and diagnostic odds ratio (OR) for CXR were calculated. Results 40 patients (36 IS, 4 ICH) with a median age of 78y (range 44y-90y) and a median National Institute of Health Stroke Scale score of 13 (range 3-31) were included. All patients had at least one CXR and 35/40 patients (88%) underwent pulmonary CT. Changes consistent with pneumonia were present in 15/40 CXRs (38%) and 12/35 pulmonary CTs (34%). 9/35 pulmonary CTs (26%) were reported normal. CXR had a sensitivity of 58.3%, specificity of 73.9%, PPV of 53.8 %, NPV of 77.2 %, diagnostic OR of 3.7 (95% CI 0.7 - 22) and an accuracy of 68.5% (95% CI 50.7% -83.1%). Discussion CXR has limited diagnostic accuracy in SAP. The majority of patients started on antibiotics had no evidence of pneumonia on pulmonary CT with potential implications for antibiotic stewardship. Conclusions Pulmonary CT could be applied as a reference standard for evaluation of clinical and biomarker diagnostic SAP algorithms in multi-center studies.

The conclusion of the Human Fertilisation and Embryology Authority that ‘add-on’ therapies in IVF are not supported by high-quality evidence has prompted new questions regarding the role of the randomized controlled trial (RCT) in evaluating infertility treatments. Critics argue that trials are cumbersome tools that provide irrelevant answers. Instead, they argue that greater emphasis should be placed on large observational databases, which can be analysed using powerful algorithms to determine which treatments work and for whom. Although the validity of these arguments rests upon the sciences of statistics and epidemiology, the discussion to date has largely been conducted without reference to these fields. We aim to remedy this omission, by evaluating the arguments against RCTs in IVF from a primarily methodological perspective. We suggest that, while criticism of the status quo is warranted, a retreat from RCTs is more likely to make things worse for patients and clinicians.

To evaluate the impact of lipid-lowering medications on diabetic retinopathy and diabetic complications requiring intervention in the US population.Retrospective cohort analysis.Administrative insurance claims were drawn from the Truven MarketScan Commercial Claims and Encounters databases. Population consisted of beneficiaries with type 2 diabetes mellitus (T2DM). Main outcome measurements were any signs of diabetic retinopathy, as measured by diagnosis codes for nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), or diabetic macular edema (DME) and procedure codes for retinopathy treatments (anti-VEGF injections, laser therapy, and vitrectomy).A population of 269,782 patients diagnosed with T2DM between 2008 and 2015 were analyzed. A total of 99,233 patients (37%) were undergoing treatment with lipid-lowering medications. Approximately 6% of patients taking lipid-lowering medications had a diagnosis code for NPDR, PDR, or DME or a procedural code for intravitreal injections, pars plana vitrectomy (PPV) or laser treatment in their record following diagnosis with diabetes compared to 6.5% of patients who did not take lipid-lowering medications (P0.01). In adjusted time-to-event analyses, patients who took lipid-lowering medications prior to diagnosis of T2DM were less likely to progress to any retinopathy diagnosis (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.55-0.65) and less likely to receive any treatment for retinopathy (HR, 0.81; 95% CI, 0.78-0.84). These findings were significant at the aggregate level, at the individual level of diagnosis (NPDR HR, 0.63; 95% CI, 0.57-0.69; PDR HR, 0.45; 95% CI, 0.37-0.54; and DME HR, 0.39; 95% CI, 0.33-0.45), and at the level of each treatment category (anti-VEGF injection HR, 0.81; 95% CI, 0.78-0.84; laser HR, 0.62; 95% CI, 0.47-0.81; and vitrectomy HR, 0.71; 95% CI, 0.59-0.85).This study found consistent evidence that patients taking lipid-lowering medications were less likely to develop NPDR, PDR, or DME and modest evidence that these patients are less likely to receive intravitreal injections of anti-VEGF medication, laser treatments, or vitrectomy. The study validates the findings of studies that have used claims databases in East Asia in relatively homogeneous populations to estimate an association between statin use and retinopathy, replicating them in a US context in a large commercial claims database.