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Despite etiologic and severity heterogeneity in neutropenic sepsis, management is often uniform. Understanding host response clinical subphenotypes might inform treatment strategies for neutropenic sepsis.This retrospective two-hospital study analyzed whether temperature trajectory modeling could identify distinct, clinically relevant subphenotypes among neutropenic oncology patients with suspected infection.Among adult oncologic admissions with neutropenia and blood cultures within 24 hours, a previously validated model classified patients' initial 72-hour temperature trajectories into one of four subphenotypes. We analyzed subphenotypes' independent relationships with hospital mortality and bloodstream infection using multivariable models.Patients (primary cohort n=1145, validation cohort n=6564) fit into one of four temperature subphenotypes. "Hyperthermic slow resolvers" (pooled n=1140 [14.8%], mortality n=104 [9.1%]) and "hypothermic" encounters (n=1612 [20.9%], mortality n=138 [8.6%]) had higher mortality than "hyperthermic fast resolvers" (n=1314 [17.0%], mortality n=47 [3.6%]) and "normothermic" (n=3643 [47.3%], mortality n=196 [5.4%]) encounters (p0.001). Bloodstream infections were more common among hyperthermic slow resolvers (n=248 [21.8%]) and hyperthermic fast resolvers (n=240 [18.3%]) than among hypothermic (n=188 [11.7%]) or normothermic encounters (n=418 [11.5%]), p0.001). Adjusted for confounders, hyperthermic slow resolvers had increased adjusted odds for mortality (primary cohort odds ratio 1.91 [p=0.03]; validation cohort odds ratio 2.19 [p0.001]) and bloodstream infection (primary odds ratio 1.54 [p=0.04]; validation cohort odds ratio 2.15 [p0.001]).Temperature trajectory subphenotypes were independently associated with important outcomes among hospitalized neutropenic patients in two independent cohorts.

Purpose Evaluate the frequency of benign versus malignant masses within the prestyloid parapharyngeal space (PPS) and determine if tumor margins on preoperative cross-sectional imaging can predict malignancy status. Materials and Methods The electronic health record at UC Davis Medical Center was searched for PPS masses surgically resected between 2015 and 2021. Cases located centrally within the prestyloid PPS with confirmed histologic diagnosis were included and separated into either benign or malignant groups. Margins of the tumors were categorized as “well defined” or “infiltrative” on preoperative cross-sectional imaging. Statistical analysis was performed to evaluate relationships between malignancy status and tumor margins. Results A total of 31 cases met the inclusion criteria. Fourteen separate histologic diagnoses were observed. Benign cases comprised 77% (24/31) and the remaining 23% (7/31) were malignant. Pleomorphic adenoma was the most common overall diagnosis at 48% (15/31). Adenoid cystic carcinoma 6% (2/31) was the most common malignant diagnosis. Well-defined tumor margins were seen in 81% (25/31) of cases. A benign diagnosis was found in 96% (24/25) of the cases with well-defined margins. Infiltrative tumor margins were displayed in 19% (6/31) of cases, all were malignant. The sensitivity and specificity of infiltrative tumor margins for malignancy were 85.7% and 100%, respectively. The negative predictive value of infiltrative margins for malignancy was 96%. Conclusion Infiltrative tumor margins on preoperative imaging demonstrate high specificity and negative predictive value for malignant histology in prestyloid PPS masses. Margins should therefore be considered when determining clinical management for newly diagnosed PPS tumors.

Remote sensing survey in southern Jordan has identified at least three Roman temporary camps that indicate a probable undocumented military campaign into what is today Saudi Arabia, and which we conjecture is linked to the Roman annexation of the Nabataean kingdom in AD 106.

Rationale: Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent airway inflammation and disordered macrophage function. The extent to which alterations in macrophage bioenergetics contribute to impaired antioxidant responses and disease pathogenesis has yet to be fully delineated. Objectives: Through the study of COPD alveolar macrophages (AMs) and peripheral monocyte-derived macrophages (MDMs), we sought to establish if intrinsic defects in core metabolic processes drive macrophage dysfunction and redox imbalance. Methods: AMs and MDMs from donors with COPD and healthy donors underwent functional, metabolic, and transcriptional profiling. Measurements and Main Results: We observed that AMs and MDMs from donors with COPD display a critical depletion in glycolytic- and mitochondrial respiration-derived energy reserves and an overreliance on glycolysis as a source for ATP, resulting in reduced energy status. Defects in oxidative metabolism extend to an impaired redox balance associated with defective expression of the NADPH-generating enzyme, ME1 (malic enzyme 1), a known target of the antioxidant transcription factor NRF2 (nuclear factor erythroid 2-related factor 2). Consequently, selective activation of NRF2 resets the COPD transcriptome, resulting in increased generation of TCA cycle intermediaries, improved energetic status, favorable redox balance, and recovery of macrophage function. Conclusions: In COPD, an inherent loss of metabolic plasticity leads to metabolic exhaustion and reduced redox capacity, which can be rescued by activation of the NRF2 pathway. Targeting these defects, via NRF2 augmentation, may therefore present an attractive therapeutic strategy for the treatment of the aberrant airway inflammation described in COPD. ispartof: AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE vol:207 issue:8 pages:998-1011 ispartof: location:United States status: published

Decreased preoperative physical fitness and low physical activity have been associated with preoperative functional reserve and surgical complications. We sought to evaluate daily step count as a measure of physical activity and its relationship with post-pancreatectomy outcomes.Patients undergoing pancreatectomy were given a remote telemonitoring device to measure their preoperative levels of physical activity. Patient activity, demographics, and perioperative outcomes were collected and compared in univariate and multivariate logistic regression analysis.73 patients were included. 45 (61.6%) patients developed complications, with 17 (23.3%) of those patients developing severe complications. These patients walked 3437.8 (SD 1976.7) average daily steps, compared to 5918.8 (SD 2851.1) in patients without severe complications (p 0.001). In logistic regression analysis, patients who walked less than 4274.5 steps had significantly higher odds of severe complications (OR = 7.5 (CI 2.1, 26.8), p = 0.002).Average daily steps below 4274.5 before surgery are associated with severe complications after pancreatectomy. Preoperative physical activity levels may represent a modifiable target for prehabilitation protocols.

VAR2CSA, a multidomain Plasmodium falciparum protein, mediates the adherence of parasite-infected red blood cells to chondroitin 4-sulfate (C4S) in the placenta, contributing to placental malaria. Therefore, detailed understanding of VAR2CSA structure likely help developing strategies to treat placental malaria. The VAR2CSA ectodomain consists of an N-terminal segment (NTS), six Duffy binding-like (DBL) domains, and three interdomains (IDs) present in sequence NTS-DBL1x-ID1-DBL2x-ID2-DBL3x-DBL4ε-ID3-DBL5ε-DBL6ε. Recent electron microscopy studies showed that VAR2CSA is compactly organized into a globular structure containing C4S-binding channel, and that DBL5ε-DBL6ε arm is attached to the NTS-ID3 core structure. However, the structural elements involved in inter-domain interactions that stabilize the VAR2CSA structure remain largely not understood. Here, limited proteolysis and peptide mapping by mass spectrometry showed that VAR2CSA contains several inter-domain disulfide bonds that stabilize its compact structure. Chemical crosslinking-mass spectrometry showed that all IDs interact with DBL4ε; additionally, IDs interact with other DBL domains, demonstrating that IDs are the key structural scaffolds that shape the functional NTS-ID3 core. Ligand binding analysis suggested that NTS considerably restricts the C4S binding. Overall, our study revealed that inter-domain disulfide bonds and interactions between IDs and DBL domains contribute to the stability of VAR2CSA structural architecture and formation of C4S-binding channel.

Background: Health-related quality of life (HRQoL) assessment in patients with acne is recommended by several national guidelines. There are several acne-specific HRQoL instruments. Objectives: Participants of the European Academy of Dermatology and Venereology (EADV) Task Forces (TFs) on QoL and Patient Oriented Outcomes (PO) and Acne, Rosacea, and Hidradenitis Suppurativa (ARHS) agreed to scrutinize aspects of existing acne-specific HRQoL instruments for their relevance in international study. Methods: Consensus agreement on items related to QoL was reached after an independent assessment by seven experts from the EADV TFs on QoL and PO, and a list of 97 items was prepared and proposed to a group of acne patients. In order to have data from patients to check if any important topics were overseen, another group of acne patients from participating countries was asked to list how acne influenced different aspects of their lives. Results: Based on results obtained from 601 acne patients from nine countries, most of the items and topics showed low relevance for acne patients especially during the previous month or shorter time periods. Based on percentage of relevance and factor analysis, short (6 items) and long (45 items) lists of the most relevant topics were formed. Conclusion: Most of the items and topics from the initial list showed low relevance for acne patients. None of the identified acne-specific HRQoL instruments contain all the items that were deemed most relevant to acne patients. For this reason, participating members of the EADV TFs on QoL and PO, and ARHs are in the process of developing a new acne-specific HRQoL instrument.

Members of the European Academy of Dermatology and Venereology (EADV) Task Force on Quality of Life (QoL) and Patient Oriented Outcomes reviewed the instruments available for health-related (HR) QoL assessment in vitiligo and together with external vitiligo experts (including representatives of the EADV Vitiligo Task Force) have made practical recommendations concerning the assessment of QoL in vitiligo patients. The Dermatology Life Quality Index (DLQI) was the most frequently used HRQoL instrument, making comparison of results between different countries possible. Several vitiligo-specific instruments were identified. The vitiligo Impact Scale (VIS) is an extensively validated vitiligo-specific HRQoL instrument with proposed minimal important change and clinical interpretation for VIS-22 scores. VIS-22 was developed for use in India, where there are some specific cultural beliefs concerning vitiligo. The EADV Task Force on QoL and Patient Oriented Outcomes recommends use of the DLQI and the Children's Dermatology Life Quality Index (CDLQI) as dermatology-specific instruments in vitiligo. There is a strong need for a valid (including cross-cultural validation) vitiligo-specific instrument that can be either a new instrument or the improvement of existing instruments. This validation must include the proof of responsiveness.

The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the management of delusional infestation (DI) in adults. Linked Comment: I. Coulson. Br J Dermatol 2022; 187:457.

To undertake a comparison of Cal/BDP cream versus foam for the treatment of plaque psoriasis, with cross-trial population differences accounted for.An anchored matching-adjusted indirect comparison was undertaken, using individual patient data for Cal/BDP cream and published aggregated data for Cal/BDP foam. Altogether, 11 outcomes were analyzed, including PGA success, mPASI75, DLQI-related outcomes and treatment satisfaction across numerous domains. For each outcome an odds ratio or mean difference was calculated to represent the relative efficacy of Cal/BDP cream versus foam. Methods were guided by NICE Decision Support Unit recommendations.After adjustment, baseline characteristics were balanced across treatment arms in each analysis. There were no statistically significant differences in PGA success, mPASI75 or DLQI outcomes between Cal/BDP cream and foam when they were compared after their recommended treatment durations (8 weeks for cream and 4 weeks for foam). For treatment satisfaction after 1 week of treatment, Cal/BDP cream was significantly superior to the Cal/BDP foam in all but one domain of the questionnaire.Cal/BDP cream and Cal/BDP foam have equivalent efficacy and HRQoL (measured in DLQI) outcomes when used for the topical treatment of plaque psoriasis at their recommended treatment durations. A comparison of treatment satisfaction assessments after 1 week of treatment demonstrated that patients find Cal/BDP cream to be more convenient than foam.

Prurigo nodularis (PN), or chronic prurigo, is a distinct disease characterized by the presence of chronic pruritus and multiple localized or generalized pruriginous lesions. While there are few epidemiologic studies describing the prevalence of PN, it is thought to be relatively rare, but is likely underdiagnosed and underrecognized. Management of PN is challenging, and there are no approved drugs that can relieve the distress as well as signs and symptoms caused by PN and its pruritus. Improved understanding of the neuroimmune pathways involved in management of PN have led to discovery and trial of emerging treatments for PN. This publication provides an overview of PN and discusses several of the most promising treatments that are undergoing evaluation.

BackgroundThis study evaluated whether fluorescence lifetime imaging (FLIm), coupled with standard diagnostic workups, could enhance primary lesion detection in patients with p16+ head and neck squamous cell carcinoma of the unknown primary (HNSCCUP).MethodsFLIm was integrated into transoral robotic surgery to acquire optical data on six HNSCCUP patients' oropharyngeal tissues. An additional 55-patient FLIm dataset, comprising conventional primary tumors, trained a machine learning classifier; the output predicted the presence and location of HNSCCUP for the six patients. Validation was performed using histopathology.ResultsAmong the six HNSCCUP patients, p16+ occult primary was surgically identified in three patients, whereas three patients ultimately had no identifiable primary site in the oropharynx. FLIm correctly detected HNSCCUP in all three patients (ROC-AUC: 0.90 ± 0.06), and correctly predicted benign oropharyngeal tissue for the remaining three patients. The mean sensitivity was 95% ± 3.5%, and specificity 89% ± 12.7%.ConclusionsFLIm may be a useful diagnostic adjunct for detecting HNSCCUP.

Background Topical steroid withdrawal (TSW) is a newly described disease characterised by erythema and burning following discontinuation of prolonged use of mid- to high-potency topical corticosteroids. No consensus diagnostic criterion exists. TSW is frequently interpreted as flaring of the underlying disorder or contact allergy to topical treatment. Objectives To better characterise TSW symptomatology, detail our experience with management, and assess the proportion of patients who pursue nonconventional management. Methods A retrospective review of case notes collected from our multidisciplinary service between January 2019 and June 2021 was carried out to identify patients presenting with TSW. Results Nineteen cases of TSW were identified, 15 females and four males. The majority were under 35 years old. Eighteen had atopic dermatitis. The most frequently reported features were redness, skin pain (typically ‘burning’), skin sensitivity, excessive skin flaking, insomnia, and severe itching. There was a high burden of anxiety and depression, with three patients expressing suicidal thoughts. Nonconventional treatments were pursued by approximately half the cohort, some of whom sought private consultation with international dermatologists. Improvements were noted in the context of open psychodermatology consultations with an earlier introduction of conventional management options. Conclusion Many patients report dismissal by dermatology healthcare professionals, often driving them to seek help from unregulated online sources, heightening the burden of mental, social and physical morbidity. Dermatology healthcare professionals need to be aware of TSW, and offer support with shared decision-making when considering treatments.

Background Tumour necrosis factor-alpha inhibitors (TNFi) have revolutionized the treatment of moderate-to-severe psoriasis. Following patent expiry of the originator biologics, TNFi biosimilars became available, presenting the opportunity for significant reductions in drug costs. Objectives To describe the uptake of TNFi biosimilars for psoriasis treatment in the UK and Ireland. Methods This observational cohort study utilizes data from the British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR), a national pharmacovigilance study register for patients with psoriasis on systemic treatments. We analysed biosimilar uptake trends over time in nine geographical regions of England along with Wales, Scotland, Northern Ireland and the Republic of Ireland. We assessed the incidence of switching to biosimilars in an originator-user cohort (switchers). Patients on originators infliximab, etanercept and adalimumab at the time originator patents expired, entered the cohort on 1 February 2015, August 2015 and October 2018, respectively, and were followed up until 31 October 2021. Trends in biosimilar initiations were assessed in an adalimumab-naïve cohort who started adalimumab between 1 October 2018 and 31 July 2019 (starters). We assessed the associations between patient factors and originator-to-biosimilar switching and biosimilar initiation using a multivariable Cox regression model and a multivariable logistic regression model, respectively. Results Included in the originator-user cohort were 4202 patients (209 on infliximab, 742 on etanercept and 3251 on adalimumab). For infliximab, etanercept and adalimumab, respectively, the cumulative incidence of originator-to-biosimilar switching increased with time to 14.8%, 23.6% and 66.6% after 3 years. Across geographical regions, 3-year switching rates varied from 0% to 43.7% for infliximab; from 0% to 40.4% for etanercept; and from 12.5% to 84.3% for adalimumab. Out of the 528 patients included in the adalimumab-naïve cohort, 67.8% started on biosimilars. Originator-to-biosimilar switching and biosimilar initiation were more common in men and in patients who had lower Psoriasis Area and Severity Index at cohort entry. Conclusions The uptake of biosimilars increased over time and varied considerably across the UK and Ireland; adalimumab had the highest biosimilar uptake rate compared with that of other TNFi drugs.

PDF file, 1027K, Mesenchymal-like cells in PDXs of SCCs with infiltrative invasion.

PDF file, 69K, Clinical and pathologic features of 10 human head and neck SCCs grouped by pattern of invasion.

PDF file, 82K, Erlotinib resistance in mesenchymal-like SCC cells.

In January 1979, Robert Edwards and Patrick Steptoe delivered a lecture detailing the ten-year clinical and scientific research programme that led to the birth of Louise Brown, the first baby born utilising IVF. This thoroughly-researched book provides both a full annotated transcript of the lecture as well as recorded reminiscences from those who attended, detailing the contemporary understandings of the event. An essay on the lecture's historical context adds fresh insight into the biographies of Edwards and Steptoe and highlights sources from print and broadcast media that have received scant attention in earlier publications. Current and future implications of the advances in IVF since the first procedure are also explored, examining future medical and scientific possibilities as well as ethical issues that may arise. A foreword by Louise Brown herself places this remarkable leap of science in a personal context, one that so many families have since experienced themselves.

The objective of this study was to develop and externally validate a model to predict adjunctive vasopressin response in patients with septic shock being treated with norepinephrine for bedside use in the intensive care unit.This was a retrospective analysis of two adult tertiary intensive care unit septic shock populations.Barnes-Jewish Hospital (BJH) from 2010 to 2017 and Beth Israel Deaconess Medical Center (BIDMC) from 2001 to 2012.Two septic shock populations (548 BJH patients and 464 BIDMC patients) that received vasopressin as second-line vasopressor.Patients who were vasopressin responsive were compared with those who were nonresponsive. Vasopressin response was defined as survival with at least a 20% decrease in maximum daily norepinephrine requirements by one calendar day after vasopressin initiation, without a third-line vasopressor.Two supervised machine learning models (gradient-boosting machine [XGBoost] and elastic net penalized logistic regression [EN]) were trained in 1000 bootstrap replications of the BJH data and externally validated in the BIDMC data to predict vasopressin responsiveness.Vasopressin responsiveness was similar among each cohort (BJH 45% and BIDMC 39%). Mortality was lower for vasopressin responders compared with nonresponders in the BJH (51% vs. 73%) and BIDMC (45% vs. 83%) cohorts, respectively. Both models demonstrated modest discrimination in the training (XGBoost area under receiver operator curve [AUROC] 0.61 [95% confidence interval (CI) 0.61-0.61], EN 0.59 [95% CI 0.58-0.59]) and external validation (XGBoost 0.68 [95% CI 0.63-0.73], EN 0.64 [95% CI 0.59-0.69]) datasets.Vasopressin nonresponsiveness is common and associated with increased mortality. The models' modest performances highlight the complexity of septic shock and indicate that more research will be required before clinical decision support tools can aid in anticipating patient-specific responsiveness to vasopressin.

Hypothermia or Normothermia after Cardiac ArrestThis trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes.BackgroundTargeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty.MethodsIn an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, >= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device.ResultsA total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score >= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, PConclusionsIn patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)

Background: Extubation failure, defined as reintubation within 48 hours is associated with increased intensive care unit (ICU) length of stay and higher mortality risk. One cause of extubation failure is secretion retention, resulting from an inability to cough effectively. Mechanical Insufflation-Exsufflation (MI-E) simulates a cough aiding secretion clearance. However, MI-E is not routinely used in the ICU setting for invasively ventilated patients. This study aims to determine the feasibility and acceptability of a randomised controlled trial (RCT) examining MI-E use to promote extubation success in intubated, ventilated adults. Methods: Single centre, feasibility RCT with semi-structured interviews, economic scoping, and an exploratory physiology study. The feasibility RCT (n=50) will compare standard care to a MI-E protocol including a minimum of two MI-E sessions via the endotracheal tube prior to extubation. Post-extubation, MI-E will be delivered via facemask or mouthpiece up to two times/day for 48 hours. MI-E settings will be individualised based on patient tolerance, chest expansion and secretion clearance. All patients will receive standard care in relation to mechanical ventilation, weaning, rehabilitation, physiotherapy techniques such as positioning, manual airway clearance techniques, manual/ventilator hyperinflation, endotracheal suctioning and nebulisation. Clinical data collection will occur before, on completion and 5 minutes after all physiotherapy sessions (intervention and control arms). Resource use will be calculated for each 24 hour period. Analyses will be descriptive and address feasibility outcomes. We will conduct semi-structured online interviews informed by the Theoretical Framework of Acceptability (TFA) with patients, clinicians and family members, exploring the acceptability of the MI-E intervention and study processes. Interview data will be analysed using reflexive thematic analysis based on TFA domains through first level coding. The embedded physiology study will use Electrical Impedance Tomography and Lung Ultrasound to explore lung recruitment and de-recruitment during MI-E in a subset of 5-10 patients. Discussion: This study will examine the feasibility and acceptability of a RCT protocol of MI-E to promote extubation success. Study findings will inform further design modification and conduct of a future adequately powered trial. Furthermore, the study will contribute and advance the understanding of MI-E use in critically ill intubated adults. Trial Registration: ISRCTN 24603037; IRAS 303674.

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with itch, eczematous lesions and impaired quality of life (QoL). Although the frequency of skin pain in AD is often underestimated, it is associated with a substantial health burden, similar to itch and is known to contribute to sleep disruption and mood disturbance. Abrocitinib is an oral, once-daily, selective Janus kinase-1 inhibitor approved for the treatment of moderate-to-severe AD. In phase 3 clinical trials JADE MONO-1 (NCT03349060) and JADE MONO-2 (NCT03575871), abrocitinib demonstrated rapid relief from itch and skin pain, as well as meaningful improvements in QoL compared with placebo. The interrelationships between abrocitinib treatment and improvements in itch, skin pain and QoL have not yet been investigated. This mediation analysis aimed to characterize the effect of abrocitinib treatment via itch and skin pain on dermatology-specific QoL in patients with AD. Data from JADE MONO-1 and JADE MONO-2 were pooled in this analysis. Adult patients with moderate-to-severe AD received abrocitinib (200 or 100 mg) as monotherapy or placebo for 12 weeks. Three separate models were evaluated whereby QoL was assessed using the Dermatology Life Quality Index (DLQI) score, and itch and skin pain were assessed via the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) items #1 (How itchy was your skin over the past 24 h?) and #2 (How painful was your skin over the past 24 h?), respectively. The cross-sectional mediation model (CSMM) was run separately at weeks 2, 4, 8 and 12 using all available data at each timepoint. The longitudinal mediation model (LMM), which does not assume independence among measurements of itch, skin pain and DLQI at each timepoint, estimated relationships using all available data from all weeks simultaneously. Based on the results of the CSMM and LMM, a pseudo-steady-state model, in which the relationship among variables was assumed to be the same across timepoints, was applied. Effects with P < 0.05 were considered statistically significant. In the CSMM, the indirect effect of abrocitinib on DLQI mediated via itch was considered approximately stable (24–30%) for the first 8 weeks before increasing at week 12 (42%), while the indirect effect mediated via skin pain was considered approximately stable from week 2 to week 12 (33–41%). In the LMM, the indirect effect of abrocitinib treatment on DLQI mediated via both itch and skin pain was considered approximately stable from week 2 to week 12 (17–26% and 42–48%, respectively). The cross-sectional and longitudinal models were generally consistent and indicated a pseudo-steady-state period between weeks 2 and 12. Using the pseudo-steady-state model, the direct effect of abrocitinib on DLQI was estimated to be 34.8% (P < 0.0001), and the indirect effects mediated via itch and skin pain were estimated to be 19.5% and 45.8%, respectively (P ≤ 0.0001 for both). Improvements in dermatology-specific QoL with abrocitinib are mostly mediated indirectly via a reduction in skin pain and less so by relief of itch. These findings warrant further research to examine to what extent patients consider itch and skin pain as separate concepts in terms of their impact on dermatology-specific QoL.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by intense itch, skin pain and impaired quality of life. Skin pain is a common and bothersome symptom of AD and increases in prevalence and intensity with worsening disease severity. Abrocitinib is an oral, once-daily, selective Janus kinase-1 inhibitor approved for the treatment of moderate-to-severe AD. Abrocitinib treatment resulted in improvements in skin clearance as well as rapid itch reduction in patients with moderate-to-severe AD across multiple phase 3 studies. Work productivity loss and activity impairment were assessed in the phase 3 JADE MONO-2 (NCT03575871) trial, with greater improvements being associated with abrocitinib treatment compared with placebo. The mechanism(s) through which abrocitinib reduces work productivity loss and activity impairment are unclear. To describe the interrelationships among abrocitinib treatment, itch, skin pain, and work productivity and activity impairment using a mediation modelling analysis in patients with AD. Data from adult patients treated with abrocitinib monotherapy (200 or 100 mg) or placebo in JADE MONO-2 were included in this analysis. As separate outcomes, work productivity loss and activity impairment (outcome variables) were measured by the Work Productivity and Activity Impairment Questionnaire: Atopic Dermatitis version 2.0 (WPAI-AD 2.0). Itch and skin pain (mediator variables) were evaluated using the Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) item #1 (How itchy was your skin over the past 24 h?) and item #2 (How painful was your skin over the past 24 h?), respectively. Mediation modelling was conducted independently for work productivity loss and activity impairment. All available data at week 12 were used in the modelling. Effects with P < 0.05 were considered statistically significant. The direct effects of abrocitinib were estimated to be 7.3% (P = 0.779) and 17.5% (P = 0.258) on work productivity loss and activity impairment, respectively. The indirect effects of abrocitinib treatment on work productivity loss and, separately, on activity impairment mediated via itch were estimated to be 50.6% (P = 0.017) and 20.9% (P = 0.062), respectively, and via skin, pain were estimated to be 42.1% and 61.5%, respectively, (P < 0.05 for both). The indirect effect of abrocitinib treatment on work productivity loss is mediated approximately equally through the reduction in itch severity and skin pain. The effect of abrocitinib treatment on activity impairment is mostly mediated indirectly through the reduction of skin pain, along with a smaller indirect contribution from the reduction in itch. These findings support further research into the extent that patients consider itch and skin pain as separate concepts in terms of their impact on work productivity.

Stress and Anxiety basic overview

This shows day-to-day experiences of children on long term ventilation

Partnership working

This presentation looks at the needs of children with physical disabilities in relation to keeping them safe

Tissue Viability basic facts and example of a pressure sore

This presentation looks at the needs of children with physical disabilities in relation to keeping them safe

Resilience how does this happen

BACKGROUND: Health-related quality of life (HRQoL) assessment in patients with acne is recommended by several national guidelines. There are several acne-specific HRQoL instruments. OBJECTIVES: Participants of the European Academy of Dermatology and Venereology (EADV) Task Forces (TFs) on QoL and Patient Oriented Outcomes (PO) and Acne, Rosacea, and Hidradenitis Suppurativa (ARHS) agreed to scrutinize aspects of existing acne-specific HRQoL instruments for their relevance in international study. METHODS: Consensus agreement on items related to QoL was reached after an independent assessment by seven experts from the EADV TFs on QoL and PO, and a list of 97 items was prepared and proposed to a group of acne patients. In order to have data from patients to check if any important topics were overseen, another group of acne patients from participating countries was asked to list how acne influenced different aspects of their lives. RESULTS: Based on results obtained from 601 acne patients from nine countries, most of the items and topics showed low relevance for acne patients especially during the previous month or shorter time periods. Based on percentage of relevance and factor analysis, short (6 items) and long (45 items) lists of the most relevant topics were formed. CONCLUSION: Most of the items and topics from the initial list showed low relevance for acne patients. None of the identified acne-specific HRQoL instruments contain all the items that were deemed most relevant to acne patients. For this reason, participating members of the EADV TFs on QoL and PO, and ARHs are in the process of developing a new acne-specific HRQoL instrument.