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Abstract Introduction Despite advances in atopic dermatitis (AD) treatments, many patients face challenges obtaining medications. This study aimed to determine the frequency and causes of insurance coverage delays and denials for AD prescriptions and characterize the associated wait times and extent to which patients understand what to do when faced with a coverage issue. Methods This was a cross-sectional, observational study in which adult U.S. residents (aged 18+ years) with AD or caregivers of pediatric U.S. patients with AD (aged 0–17 years) completed an online survey (3 June–16 July 2021). Results Respondents (N = 978) were primarily adults with AD (81.8%), female (67.7%), and white (70.2%). There were 645 insurance delays or denials for AD prescriptions, with 48.1% (470/978) of respondents experiencing at least one delay/denial in the past year. Most delays/denials were for topical steroids (39.2%, 253/645), the most highly used prescription treatment class (83.9%, 821/978). However, the highest rate of delay/denials was for biologics, of which 43.6% (109/250) of all prescriptions faced a delay or denial. Denials were caused primarily by step therapy (27.6%) and delays by prior authorization (55.1%). Only 56.0% of respondents said they would know what to do if they faced an issue with AD prescription coverage. Conclusions Patients with AD frequently experience insurance-related barriers to obtaining recommended therapies, and many do not know how to respond when these barriers arise. Strategies to improve timely therapeutic access are needed.

Background and Purpose Infarcts in acute ischemic stroke (AIS) patients may continue to grow even after reperfusion, due to mechanisms such as microvascular obstruction and reperfusion injury. We investigated whether and how much infarcts grow in AIS patients after near-complete (expanded Thrombolysis in Cerebral Infarction [eTICI] 2c/3) reperfusion following endovascular treatment (EVT), and to assess the association of post-reperfusion infarct growth with clinical outcomes. Methods Data are from a single-center retrospective observational cohort study that included AIS patients undergoing EVT with near-complete reperfusion who received diffusion-weighted magnetic resonance imaging (MRI) within 2 hours post-EVT and 24 hours after EVT. Association of infarct growth between 2 and 24 hours post-EVT and 24-hour National Institutes of Health Stroke Scale (NIHSS) as well as 90-day modified Rankin Scale score was assessed using multivariable logistic regression. Results Ninety-four of 155 (60.6%) patients achieved eTICI 2c/3 and were included in the analysis. Eighty of these 94 (85.1%) patients showed infarct growth between 2 and 24 hours post-reperfusion. Infarct growth ≥5 mL was seen in 39/94 (41.5%) patients, and infarct growth ≥10 mL was seen in 20/94 (21.3%) patients. Median infarct growth between 2 and 24 hours post-reperfusion was 4.5 mL (interquartile range: 0.4–9.2 mL). Post-reperfusion infarct growth was associated with the 24-hour NIHSS in multivariable analysis (odds ratio: 1.16 [95% confidence interval 1.09–1.24], P

Background: Research has shown that eczema patients prefer some degree of shared control over treatment decisions, but little is known about factors perceived to be important to facilitate shared decision making (SDM). Objective: To determine factors eczema patients and caregivers consider to be important for SDM, and how often they experience them with their eczema healthcare provider (HCP). Methods: A cross-sectional survey study (64 questions) was conducted, which included factors related to SDM rated by respondents on a Likert scale for importance, and how often these factors were true with their current eczema HCP. Results: Respondents (840, response rate 62.4%) most frequently rated their health literacy and communication skills as important for SDM. Factors which indicated a strong provider-patient relationship, and HCPs who initiate treatment conversations were also deemed beneficial. Low importance was placed on concordant HCP race/ethnicity, however, of those who did rate it as important, 53/91 identified as Black (half of all Black respondents). Limitations: A high proportion of respondents were aware of the term SDM prior to the survey. Conclusions: SDM is more likely to be facilitated when patient education and empowerment are coupled with HCPs who initiate treatment discussions, maintain compassion resilience, and listen to patient perspectives.

Background: Erectile dysfunction (ED) is common after prostate cancer treatment. It has been studied for conventional radiotherapy, but associations in the hypofractionated radiotherapy context are less clear. This study aimed to determine which factors are predicted for worsening ED after highly conformal, modestly hypofractionated radiotherapy to the prostate. Methods: Two hundred and twelve patients treated with 6000 cGy in twenty fractions across four centers were included in this study. Demographic, clinical, and dosimetry factors were then evaluated for post-treatment declines in erectile function using logistic regression and an explainable machine learning-based neural network. Results: 212 patients with a median follow-up of 3.6 years were evaluated. A total of 104 (49%) patients received androgen deprivation therapy. Prior to treatment, 52 (25%) patients were on ED medication. Mean doses to the penile bulb, penile crus, and penile shaft were 2490 (IQR: 1529–3656) cGy, 2095 (1306–3036) cGy, and 444 (313–650) cGy, respectively. Fifty-nine (28%) patients had a worsening of ED after treatment. On multivariable analysis, only the mean dose to the penile shaft [OR >345 vs. ≤345: 4.47 (1.43–13.99); p = 0.010] and pretreatment use of ED medication [OR yes vs. no: 12.5 (5.7–27.5; p < 0.001)] predicted for worsening ED. The neural network confirmed that the penile shaft mean dose and pre-treatment ED medication use are the most important factors in predicting ED. Conclusions: Pre-treatment ED and penile shaft dosimetry are important predictors for ED after hypofractionated radiotherapy for prostate cancer.

Objective Patients with atopic dermatitis (AD) have low treatment satisfaction. In this study, we evaluated the humanistic burden, treatment satisfaction, and treatment expectations in patients with AD in the United States. Methods Adults with AD recruited through the National Eczema Association and clinical sites completed a web-based survey comprising the Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD), Dermatology Life Quality Index; Work Productivity and Activity Impairment Questionnaire-Atopic Dermatitis; Treatment Satisfaction Questionnaire for Medication (TSQM); and answered questions on healthcare provider (HCP) visits, treatment history, and treatment goals. Descriptive analyses were performed to compare participants by severity. Results Among 186 participants (mean [standard deviation] age 39.7 [15.3] years, 79.6% female), 26.9%, 44.6%, and 26.3% of the participants had mild, moderate, or severe AD, respectively, based on PO-SCORAD. Greater disease severity was associated with a greater impact on work and daily life, decreased TSQM scores, and increased HCP visits. Corticosteroid topical cream or ointment (53.8%) and oral antihistamines (31.2%) were most commonly used for the treatment of AD. Participants reported declining/stopping/changing AD treatment due to the potential for side effects or lack of efficacy. ‘Leading normal lives’ (28.0%) and ‘being itch-free’ (33.9%) were important treatment goals. Conclusions Individuals with AD, especially severe disease, face a considerable humanistic burden even while using treatment.

Introduction Cough as a symptom of renal cell carcinoma (RCC) was first described by Creevy in 1935, and despite one (unpublished) study suggesting it may affect 31% of these patients, as well as cough being discussed in forums for patients with kidney cancer, few clinicians are aware of this association. The cough has been described as unusual in nature, resolving rapidly after treatment with nephrectomy/embolisation but returning if the tumour recurs.Methods and analysis A prospective study using a questionnaire will identify the prevalence of cough in patients with suspected or confirmed RCC attending the Specialist Centre for Kidney Cancer (London, UK). A longitudinal study in a representative sample of these patients, using EQ-5D-5L and Leicester Cough Questionnaires, together with the use of semi-structured interviews with patients, will identify the impact of cough in addition to having a diagnosis of suspected or confirmed RCC on quality of life. To investigate cough mechanisms, a pilot study using cough hypersensitivity testing will be performed on patients with RCC, with and without a cough. Clinical samples (urine, blood, phlegm and breath condensate) from patients with RCC, with and without a cough, will be collected and analysed for the presence of substances known to trigger or enhance cough and compared with the results obtained from healthy volunteers.Ethics and dissemination Ethical approval has been granted (UK HR REC 22/PR/0791 dated 25/08/2022). Study outputs will be presented and published nationally and internationally at relevant conferences. This study will establish the prevalence of cough in patients with suspected or confirmed kidney cancer and support the education of clinicians to consider this diagnosis in patients with chronic cough (eg, recommending protocols to include both kidneys when investigating respiratory symptoms with chest CT scans). If substances known to trigger or enhance cough are identified and elevated in clinical samples, this research could offer potential targets for treatment for this distressing symptom.Trial registration number NIHR CRN portfolio CPMS ID:53 372.

Abstract Background Emerging digital measures and clinical outcome assessments (COAs) leveraging digital health technologies (DHTs) could address the need for objective, quantitative measures of symptoms of atopic dermatitis (AD), such as nocturnal scratching. Development of such measures needs to be supported by evidence reflecting meaningfulness to patients. Objectives To assess nocturnal scratching as a concept of interest associated with meaningful aspects of health of patients with AD (adults and children); and to explore patient‐centred considerations for novel COAs measuring nocturnal scratch using DHTs. Methods Phase 1 evaluated disease impacts on everyday life and the lived experience with nocturnal scratching through qualitative interviews of AD patients and caregivers. Phase 2 deployed a quantitative survey to a sample of AD patients as well as caregivers. Results Four cohorts with various AD severity levels participated in Phase 1: (1) adults with AD (n = 15), (2) their caregivers/spouses/partners (n = 6), (3) children with AD (n = 14), and (4) their adult caregivers (n = 14). Findings were used to develop a conceptual model for nocturnal scratching as a potential concept of interest. The Phase 2 survey was completed by 1349 of 27640 invited adults with AD and caregivers of children with AD. The most burdensome aspects of AD reported were itchy skin and scratching. Overall, ∼65% of participants reported nocturnal scratching ≥1 day/week, resulting in ∼1–1.4 h of sleep lost per night. In all, 85%–91% of respondents considered it at least somewhat valuable that a treatment reduces night‐time scratching. About 50% reported willingness to use technology to this end and ∼25% were unsure. Conclusion Our results represented by the conceptual model confirm that nocturnal scratch is a concept of interest related to meaningful aspects of health for patients with AD and therefore is worth being captured as a distinct outcome for clinical and research purposes. DHTs are suitable tools presenting an important measurement opportunity to assess and evaluate occurrence, frequency, and other parameters of nocturnal scratching as a disease biomarker or COA of treatment efficacy.

Despite the need for improved eczema therapies and a rapid increase in available eczema clinical trials, participation remains low. The aim of this study was to identify factors associated with clinical trial awareness, interest, and barriers to enrolment and participation. An online survey, administered 1 May to 6 June 2020 to adults (≥ 18 years) with eczema in the USA, was analysed. Among 800 patients included, mean age was 49.4 years, most respondents were female (78.1%), White (75.4%), non-Hispanic (91.4%), and geographically living in an urban/suburban area (Rural-Urban Continuum Codes (RUCC) 1–3, 90.8%). Only 9.7% of respondents reported previous participation in clinical trials, while 57.1% had considered participation and 33.2% never considered participation. Higher satisfaction with current eczema therapy, clinical trial literacy, and confidence in finding eczema trial information were all associated with clinical trial awareness, interest, and successful participation. Younger age and having atopic dermatitis were associated with increased awareness, while female gender was a barrier to interest and successful participation.

Background: Eczema can be difficult to treat due to its chronic, heterogeneous nature. Effective long-term treatments for adults and children are needed. Little is known about what considerations influence eczema patient and caregiver decision-making regarding clinical trial participation (CTP). This study identifies factors that adult patients and caregivers consider important for CTP and determines if differences exist between these groups. Methods: A 46-question survey was administered May 1-June 6, 2020, to adults and caregivers of children with eczema. Respondents were asked to rate the importance of a series of factors when considering CTP; adults and caregivers were compared. Results: Out of 31 total factors queried, eleven factors differed significantly in importance ratings between adults (n = 470) and caregivers (n = 134). The route of therapy (p = 0.030), side effects (p = 0.014), washout period (p = 0.028), receiving a placebo (p = 0.027), rescue therapy option (p = 0.033), access to test drug after trial (p = 0.027), sticking with the clinical trial regimen (p = 0.025), fit with work/school (p = 0.005), impact on overall health (p = 0.008), and satisfaction with current treatment (p = 0.033) were all more likely to be rated as important by caregivers than by adult patients. Only altruism was rated more highly by adult patients than caregivers (p = 0.027). Conclusions: Caregivers are more likely than adults to attribute high importance to factors that may affect their child's eczema or well-being when considering CTP. Patient-centered CTP education materials and decision aids may support patients and caregivers in CTP decision-making.

Abstract Background Atopic dermatitis (AD) is associated with elevated financial costs, including out‐of‐pocket (OOP) expenses. Yet, the full burden of OOP expenses in children with AD is poorly understood. Objectives We sought to characterise categories, impact, and associations of caregiver‐reported OOP AD healthcare expenses for US children. Methods An online survey was administered to National Eczema Association members (N = 113 502). Inclusion criteria (US resident; respondent age ≥18; self or caregiver report of AD diagnosis) was met by 77.3% (1118/1447) of those who completed the questionnaire. Results Caregivers of children (

Background The term 'flare' is used across multiple diseases, including atopic dermatitis (AD), to describe increased disease activity. While several definitions of an AD flare have been proposed, no single definition of AD flare is widely accepted and it is unclear what the term 'AD flare' means from the patient perspective. Objectives To understand AD flares from the adult patient perspective and to explore how adults with AD define an AD flare. Methods Participants were adults with AD recruited from the National Eczema Association Ambassadors programme, a volunteer patient-engagement programme. They participated in online focus groups to discuss how they describe AD flares from their perspective, how they define its start and stop, and how they relate to existing definitions of flare. Using a grounded theory approach, transcripts were analysed and coded using an iterative process to identify concepts to support a patient-centred conceptual framework of 'flare'. Results Six 90-min focus groups of 3–8 participants each were conducted with 29 US adults (≥ 18 years of age) with AD who had at least one self-reported AD flare in the past year. When participants were presented with examples of previously published definitions of AD flare, participants found them problematic and unrelatable. Specifically, they felt that flare is hard to quantify or put on a numerical scale, definitions cannot solely be about skin symptoms and clinical verbiage does not resonate with patients' lived experiences. Concepts identified by patients as important to a definition of flare were changes from patient's baseline/patient's normal, mental/emotional/social consequences, physical changes in skin, attention needed/all-consuming focus, itch–scratch–burn cycle and control/loss of control/quality of life. Figuring out the trigger that initiated a flare was an underlying concept of the experience of flare but was not considered a contributor to the definition. Conclusions The results highlight the complexity and diversity of AD flare experiences from the adult patient perspective. Previously published definitions of AD flares did not resonate with patients, suggesting a need for a patient-centred flare definition to support care conversations and AD management. [ABSTRACT FROM AUTHOR]

Cutaneous squamous cell carcinoma (cSCC) is the second most common form of human cancer and has an increasing annual incidence. Although most cSCC is cured with office-based therapy, advanced cSCC poses a significant risk for morbidity, impact on quality of life, and death. This document provides evidence-based recommendations for the management of patients with cSCC. Topics addressed include biopsy techniques and histopathologic assessment, tumor staging, surgical and nonsurgical management, follow-up and prevention of recurrence, and management of advanced disease. The primary focus of these recommendations is on evaluation and management of primary cSCC and localized disease, but where relevant, applicability to recurrent cSCC is noted, as is general information on the management of patients with metastatic disease.

Basal cell carcinoma (BCC) is the most common form of human cancer, with a continually increasing annual incidence in the United States. When diagnosed early, the majority of BCCs are readily treated with office-based therapy, which is highly curative. In these evidence-based guidelines of care, we provide recommendations for the management of patients with BCC, as well as an in-depth review of the best available literature in support of these recommendations. We discuss biopsy techniques for a clinically suspicious lesion and offer recommendations for the histopathologic interpretation of BCC. In the absence of a formal staging system, the best available stratification based on risk for recurrence is reviewed. With regard to treatment, we provide recommendations on treatment modalities along a broad therapeutic spectrum, ranging from topical agents and superficially destructive modalities to surgical techniques and systemic therapy. Finally, we review the available literature and provide recommendations on prevention and the most appropriate follow-up for patients in whom BCC has been diagnosed.

BackgroundAtopic dermatitis is a pruritic chronic condition associated with significant sleep disturbance, inattention, and sometimes behavioral problems. Enhancing resiliency in children with atopic dermatitis may promote coping strategies to improve quality of life. Positive psychology is one strategy that can be used to strengthen resiliency. ObjectiveOur objective was to identify positive psychology concepts mentioned by children with atopic dermatitis and their parent to inform strategies to strengthen resiliency in children with atopic dermatitis. MethodsA total of 20 patient-parent dyads were interviewed to share their experience with atopic dermatitis to help develop a novel psychologic intervention for atopic dermatitis. Patients were 8 to 17 years old and diagnosed with atopic dermatitis. Trained coders analyzed transcripts using a coding dictionary developed based on Seligman’s PERMA (positive emotion, engagement, relationships, meaning, and accomplishment) model of positive psychology. The frequency of unprompted mentions of PERMA themes and relevant quotations was captured. Transcripts were also separately coded for resiliency, which is the ultimate goal of PERMA. ResultsPositive psychology concepts were mentioned by 100% (20/20) of children and 95% (19/20) of parents. Engagement and relationships, both negative and positive aspects, were the most common unprompted PERMA themes mentioned by children (14/20, 70%) and parents (13/20, 65%). Emotion elicited the most negative comments from children (19/20, 95%) and parents (17/20, 85%). When analyzed for resiliency, 8 participants were identified with at least one resiliency code. On average, participants with a resiliency code mentioned PERMA concepts 9.1 (SD 4.7) times compared to those who mentioned none (mean 5.9, SD 4.6) (P=.14). When participants were stratified by disease severity, on average, more positive psychology concepts were mentioned by patients with mild atopic dermatitis (mean 13, SD 3.0) than those with moderate symptoms (mean 6.2, SD 4.9) or severe symptoms (mean 6.1, SD 4.0) (P=.03). ConclusionsAmong PERMA themes, engagement and relationships are the two most commonly mentioned categories for children with atopic dermatitis. Strategies targeting PERMA such as affirmations and positive reframing may improve psychosocial well-being and resiliency in pediatric atopic dermatitis. Future directions will look at incorporating “positive medicine” into atopic dermatitis treatment to not only relieve symptoms but also strengthen positive aspects of life.

Understanding patient experience is essential to providing high quality, person-centered care. A real-time baseline cross-sectional study was completed to identify gaps in patient experience that can be targeted for quality improvement (QI). This study is part of PROSE (Person-centered Radiation Oncology Service Enhancement), a QI initiative developed to improve patient experience at a tertiary cancer centre Radiation Oncology (RO) Department. Data was collected using the Your Voice Matters (YVM) questionnaire. The YVM captures information on the patient’s last visit, and questions are organized based on dimensions of person-centered care. Recruitment occurred between May and August 2019 in the radiation department. Consecutive patients during the study period were approached to complete the YVM either in reference to their initial consultation or previous treatment appointment. Percent positive scores were calculated for quantitative data and a content analysis was completed for open-text data. Of 512 patients approached, a total of 400 patients participated across tumors groups. Overall, patients highly endorsed positive experiences with feeling respected by their healthcare provider. Contacting the clinic, emotional support and wait times were rated as the least positive components of experience across appointment types and tumors groups. The Lung tumour group demonstrated worse experiences across all domains during treatments compared to all other tumour groups. Gaps and differences in patient experience were demonstrated across appointment types and tumour groups. This study provides direction to effectively develop and implement QI work aimed at improving patient experience. Experience Framework This article is associated with the Policy & Measurement lens of The Beryl Institute Experience Framework. (https://www.theberylinstitute.org/ExperienceFramework). Access other PXJ articles related to this lens. Access other resources related to this lens.

Carcinoid crisis is a life-threatening manifestation of carcinoid syndrome characterized by profound autonomic instability in the setting of catecholamine release from stress, tumor manipulation, or anesthesia. Here, we present an unusual case of carcinoid crisis leading to acute systolic heart failure requiring mechanical circulatory support. (Level of Difficulty: Intermediate.)

Abstract The traditional view of innate immunity in insects is that every exposure to a pathogen triggers an identical and appropriate immune response and that prior exposures to pathogens do not confer any protective (i.e., adaptive) effect against subsequent exposure to the same pathogen. This view has been challenged by experiments demonstrating that encounters with sublethal doses of a pathogen can prime the insect's immune system and, thus, have protective effects against future lethal doses. Immune priming has been reported across several insect species, including the red flour beetle, the honeycomb moth, the bumblebee, and the European honeybee, among others. Immune priming can also be transgenerational where the parent's pathogenic history influences the immune response of its offspring. Phenotypic evidence of transgenerational immune priming (TGIP) exists in the tobacco moth Manduca sexta where first‐instar progeny of mothers injected with the bacterium Serratia marcescens exhibited a significant increase of in vivo bacterial clearance. To identify the gene expression changes underlying TGIP in M. sexta, we performed transcriptome‐wide, transgenerational differential gene expression analysis on mothers and their offspring after mothers were exposed to S. marcescens. We are the first to perform transcriptome‐wide analysis of the gene expression changes associated with TGIP in this ecologically relevant model organism. We show that maternal exposure to both heat‐killed and live S. marcescens has strong and significant transgenerational impacts on gene expression patterns in their offspring, including upregulation of peptidoglycan recognition protein, toll‐like receptor 9, and the antimicrobial peptide cecropin.

PurposeTo identify which patient-reported outcomes (PROs) may be most improved through adaptive radiation therapy (ART) with the goal of reducing toxicity incidence among head and neck cancer patients.MethodsOne hundred fifty-five head and neck cancer patients receiving radical VMAT (chemo)radiotherapy (66-70 Gy in 30-35 fractions) completed the MD Anderson Symptom Inventory, MD Anderson Dysphagia Inventory (MDADI), and Xerostomia Questionnaire while attending routine follow-up clinics between June-October 2019. Hierarchical clustering characterized symptom endorsement. Conventional statistical approaches indicated associations between dose and commonly reported symptoms. These associations, and the potential benefit of interfractional dose corrections, were further explored via logistic regression.ResultsRadiotherapy-related symptoms were commonly reported (dry mouth, difficulty swallowing/chewing). Clustering identified three patient subgroups reporting: none/mild symptoms for most items (60.6% of patients); moderate/severe symptoms affecting some aspects of general well-being (32.9%); and moderate/severe symptom reporting for most items (6.5%). Clusters of PRO items broadly consisted of acute toxicities, general well-being, and head and neck-specific symptoms (xerostomia, dysphagia). Dose-PRO relationships were strongest between delivered pharyngeal constrictor Dmean and patient-reported dysphagia, with MDADI composite scores (mean ± SD) of 25.7 ± 18.9 for patients with Dmean

Abstract Introduction Myringoplasty has often been viewed as a “basic” ENT procedure. This paper will discuss the factors that can make a myringoplasty more challenging and suggest some techniques to overcome these. Affecting Factors Patient factors The age of the patient, their habitus and co-existing co-morbidities are usually the factors affecting the choice and outcome of the procedure. The ear Anatomical variations, the nature of the pathology itself and the condition of the remnant tympanic membrane and the middle ear are important factors for consideration. Other factors Equipment availability, expertise of the surgical team and anaesthetic support can also influence the surgical procedure. Surgical Procedure The actual procedure can be done in a variety of ways including but not limited to different approaches, different techniques and using different equipment like microscopes, endoscopes, LASER, etc. Results and Complications The primary author reported a success rate of about 95% in her series. Complications of myringoplasty include myringitis, residual perforations, otitis externa and epithelial pearl formation.

PurposeTo determine which head and neck adaptive radiotherapy (ART) correction objectives are feasible and to derive efficient ART patient selection guidelines.MethodsWe considered various head and neck ART objectives including independent consideration of dose-sparing of the brainstem/spinal cord, parotid glands, and pharyngeal constrictor, as well as prediction of patient weight loss. Two-hundred head and neck cancer patients were used for model development and an additional 50 for model validation. Patient chart data, pre-treatment images, treatment plans, on-unit patient measurements, and combinations thereof were assessed as potential predictors of each objective. A stepwise approach identified combinations of predictors maximizing the Youden index of random forest (RF) models. A heuristic translated RF results into simple patient selection guidelines which were further refined to balance predictive capability and practical resource costs. Generalizability of the RF models and simplified guidelines to new data was tested using the validation set.ResultsTop performing RF models used various categories of predictors, however, final simplified patient selection guidelines only required pre-treatment information for ART predictions, indicating the potential for significant ART process streamlining. The simplified guidelines for each objective predicted which patients would experience increases in dose to: brainstem/spinal cord with sensitivity = 1.0, specificity = 0.66; parotid glands with sensitivity = 0.82, specificity = 0.70; and pharyngeal constrictor with sensitivity = 0.84, specificity = 0.68. Weight loss could be predicted with sensitivity = 0.60 and specificity = 0.55. Furthermore, depending on the ART objective, 28%-58% of patients required replan assessment, less than for previous studies, indicating a step towards more effective patient selection.ConclusionsThe above ART objectives appear to be practically achievable, with patients selected for ART according to simple clinical patient selection guidelines. Explicit ART guidelines are rare in the literature, and our guidelines may aid in balancing the potential clinical gains of ART with high associated resource costs, formalizing ART trials, and ensuring the reproducibility of clinical successes.

Summary: We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of receptor binding motif replacements such as N439K and Y453F, known to increase binding affinity to the ACE2 receptor and confer antibody escape. In vitro, we show that, although ΔH69/V70 itself is not an antibody evasion mechanism, it increases infectivity associated with enhanced incorporation of cleaved spike into virions. ΔH69/V70 is able to partially rescue infectivity of spike proteins that have acquired N439K and Y453F escape mutations by increased spike incorporation. In addition, replacement of the H69 and V70 residues in the Alpha variant B.1.1.7 spike (where ΔH69/V70 occurs naturally) impairs spike incorporation and entry efficiency of the B.1.1.7 spike pseudotyped virus. Alpha variant B.1.1.7 spike mediates faster kinetics of cell-cell fusion than wild-type Wuhan-1 D614G, dependent on ΔH69/V70. Therefore, as ΔH69/V70 compensates for immune escape mutations that impair infectivity, continued surveillance for deletions with functional effects is warranted.

Summary: Background: The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods: We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings: From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation: The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding: Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society.

Atopic dermatitis is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in atopic dermatitis management and care, providing recommendations based on the available evidence. In this third of 4 sections, treatment of atopic dermatitis with phototherapy and systemic immunomodulators, antimicrobials, and antihistamines is reviewed, including indications for use and the risk-benefit profile of each treatment option.