Phototherapy for atopic dermatitis: A survey of European practice.

BACKGROUND: Phototherapy is used to treat atopic dermatitis (AD). Evidence for its efficacy, impact on quality of life, cost-effectiveness and short- and long-term safety with real-life usage is weak. OBJECTIVES: We established a taskforce to examine how phototherapy is currently being used as a treatment for AD across the United Kingdom and Europe to inform our understanding and guide future research into management of patients with AD using UV-based phototherapies. METHODS: An anonymous electronic multiple-response survey exploring phototherapy prescribing practices and experience of phototherapy modalities was developed by the study authors and sent to members of phototherapy networks from the United Kingdom and Europe. Responses were received between February and July 2021. RESULTS: About 144 respondents from 27 European countries completed the survey. NBUVB was the most widely used [n = 138 (96%)]. Home-based NBUVB was available in 8/27 countries (25/144 respondents, 17%). Oral psoralen-UVA (PUVA) was more widely available than bath PUVA (n = 106, 74% vs. n = 60, 42%) and used mainly in adult patients. 49/144 (34%) of respondents had access to UVA1. Phototherapy would be considered instead of systemic treatment in 96% of adults and 82% of children for NBUVB, versus 40% of adults and 3% of children for PUVA. Starting doses, standard dosing increments, length of treatment courses, lifetime limits for treatments and thresholds for performing annual skin assessments varied between responders. CONCLUSIONS: NBUVB was the most widely used phototherapy for AD in adult and paediatric patients, while PUVA and UVA1 were less used. Prescribing practices varied considerably, highlighting the lack of consensus practice in many different aspects of phototherapy for the treatment of AD in children and adults. This indicates that further studies are required to determine optimal phototherapeutic regimens for AD and informs our understanding of parameters that should be included in future high-quality randomized controlled trials (RCT) of phototherapy.

The correlation between occupation type and fibromyalgia severity.

BACKGROUND: Fibromyalgia (FM) is a chronic pain disorder associated with financial burden, decreased work productivity and absenteeism. Occupational stressors and specific employment factors may contribute to the severity of FM. AIMS: To determine if occupation type or employment status correlates with FM diagnostic and severity parameters, as assessed via validated instruments including tender points (TP), Widespread Pain Index (WPI), Symptom Severity (SS) and pain regions. METHODS: We performed a cross-sectional study of 200 adult patients diagnosed with FM at a single-centre FM clinic. Demographic and clinical data were extracted from the electronic medical records. Occupations were manually grouped in an iterative modified-Delphi approach and participants were grouped by employment status (Working, Not Working/Disabled or Retired) for analysis. RESULTS: In our cohort, 61% were employed and 24% were not working/disabled, while the remainder were students, homemakers or retired. SS score was significantly higher (P < 0.001) in not working/disabled patients compared to those employed. Business owners had the lowest TP count (median = 14) and the lowest median SS score (median = 7). WPI was highest for Others (Arts/Entertainment, Driver/Delivery and Housekeeper/Custodian workers; median=16) and the lowest for Retail/Sales/Wait Staff (median = 11). CONCLUSIONS: Work-related factors, occupation type and employment status correlate with diagnostic and severity parameters of FM. Employed participants had significantly lower SS scores suggesting that work loss correlates with SS. Participants employed in entry-level jobs or jobs with higher physical or financial stressors may experience greater FM symptoms. Further studies are required to explore work-related factors and their impact on the diagnostic and severity parameters of FM.

Cefazolin susceptibility of coagulase-negative staphylococci (CoNS) causing late-onset neonatal bacteraemia.

BACKGROUND: CoNS bacteraemia causes significant neonatal morbidity. Previous work has suggested that ß-lactam antibiotics vary in their binding affinity to PBP2a (produced by the mecA gene) present in most CoNS. OBJECTIVES: We evaluated cefazolin MICs for CoNS isolated in an Australian neonatal ICU (NICU) and correlated them with isolate genotype and phenotype. METHODS: Significant blood isolates from 2009 to 2017 were speciated and underwent broth microdilution testing for cefazolin, cefoxitin, oxacillin and flucloxacillin. Correlation with mecA presence and PBP2a expression was evaluated. A selection of Staphylococcus capitis isolates underwent WGS. RESULTS: The CoNS (n = 99) isolates were confirmed as S. capitis (n = 57), Staphylococcus epidermidis (n = 32), Staphylococcus haemolyticus (n = 2) and Staphylococcus warneri (n = 8). The MIC of cefazolin was ≤2 mg/L for 30% of isolates and 75% had an MIC of ≤8 mg/L (MIC90 = 16 mg/L). This contrasted with MIC90s of cefoxitin, oxacillin and flucloxacillin, which were all ≥32 mg/L. WGS found a number of S. capitis isolates closely related to the globally established NRCS-A clone. CONCLUSIONS: CoNS displayed distinctly lower MIC values of cefazolin than of other agents tested. MIC variation may be related to binding affinity of PBP2a or regulation of expression of mecA by mecR1-mecI functional genes. Further, NRCS-A S. capitis strains were present in this Australian NICU before and after the unit underwent physical relocation, which raised questions about a common environmental source. It is considered justified to conduct a randomized clinical trial that assesses cefazolin versus vancomycin for management of late-onset neonatal sepsis.

Outcomes of normothermic machine perfusion of liver grafts in repeat liver transplantation (NAPLES initiative).

BACKGROUND: Retransplantation candidates are disadvantaged owing to lack of good-quality liver grafts. Strategies that can facilitate transplantation of suboptimal grafts into retransplant candidates require investigation. The aim was to determine whether late liver retransplantation can be performed safely with suboptimal grafts, following normothermic machine perfusion. METHODS: A prospectively enrolled group of patients who required liver retransplantation received a suboptimal graft preserved via normothermic machine perfusion. This group was compared with both historical and contemporaneous cohorts of patient who received grafts preserved by cold storage. The primary outcome was 6-month graft and patient survival. RESULTS: The normothermic machine perfusion group comprised 26 patients. The historical (cold storage 1) and contemporaneous (cold storage 2) groups comprised 31 and 25 patients respectively. The 6-month graft survival rate did not differ between groups (cold storage 1, 27 of 31, cold storage 2, 22 of 25; normothermic machine perfusion, 22 of 26; P = 0.934). This was despite the normothermic machine perfusion group having significantly more steatotic grafts (8 of 31, 7 of 25, and 14 of 26 respectively; P = 0.006) and grafts previously declined by at least one other transplant centre (5 of 31, 9 of 25, and 21 of 26; P < 0.001). CONCLUSION: In liver retransplantation, normothermic machine perfusion can safely expand graft options without compromising short-term outcomes.

Liver transplantation is a life-saving procedure for many different diseases. In the UK, one in 10 patients awaiting transplant have had a previous liver transplant. These retransplant operations are complex, and the general belief is that a good-quality donor liver graft is required for best outcomes. However, there is a significant shortage of good-quality organs for liver transplantation, so many patients awaiting retransplantation spend longer on the waiting list. This study investigated whether a new technology, called normothermic machine perfusion, could be used to preserve lower-quality donor livers and have successful outcomes for patients undergoing retransplantation. Traditionally, good-quality livers are preserved in an ice box and the study compared the outcomes of these two different approaches. The aim was to prove that normothermic machine perfusion improves access to transplantation for this group of patients, without compromising outcomes. A group of patients who underwent retransplantation and received a lesser-quality liver preserved with normothermic machine perfusion was compared with two groups of patients who had received a transplant with traditional ice-box preservation. The complications, graft, and patient survival of the former group was compared with those in the latter two groups who underwent liver retransplantation with better-quality liver grafts. The rate of survival and adverse surgical outcomes were comparable between the groups of patients who received a liver preserved via traditional ice-box preservation, and those who received a lesser-quality liver preserved via normothermic machine perfusion. Normothermic machine perfusion can potentially expand the number of suitable donor livers available for retransplant candidates.

NCCN Guidelines® Insights: Lung Cancer Screening, Version 1.2022.

The NCCN Guidelines for Lung Cancer Screening recommend criteria for selecting individuals for screening and provide recommendations for evaluation and follow-up of lung nodules found during initial and subsequent screening. These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Lung Cancer Screening.

Reference Protocol to Assess Analytical Performance of Higher Order Structural Analysis Measurements: Results from an Interlaboratory Comparison.

Measurements of protein higher order structure (HOS) provide important information on stability, potency, efficacy, immunogenicity, and biosimilarity of biopharmaceuticals, with a significant number of techniques and methods available to perform these measurements. The comparison of the analytical performance of HOS methods and the standardization of the results is, however, not a trivial task, due to the lack of reference protocols and reference measurement procedures. Here, we developed a protocol to structurally alter and compare samples of somatropin, a recombinant biotherapeutic, and describe the results obtained by using a number of techniques, methods and in different laboratories. This, with the final aim to provide tools and generate a pool of data to compare and benchmark analytical platforms and define method sensitivity to structural changes. Changes in somatropin HOS, induced by the presence of zinc at increasing concentrations, were observed, both globally and at more localized resolution, across many of the methods utilized in this study and with different sensitivities, suggesting the suitability of the protocol to improve understanding of inter- and cross-platform measurement comparability and assess analytical performance as appropriate.

Photodiagnostic services in the UK and Republic of Ireland: a British Photodermatology Group Workshop Report.

BACKGROUND: Photodiagnostic investigations are essential for the accurate diagnosis of abnormal cutaneous photosensitivity and provide important information for the management of patients with photodermatoses (cutaneous photosensitivity disorders). Although photodiagnosis has been undertaken since the early 1970s, specialist services in the United Kingdom (UK) and Republic of Ireland are limited and there is no formal guidance on diagnostic approach. Indeed, there is a limited literature in this area of methodology and diagnostic practice. OBJECTIVES: The primary objective was to undertake a British Photodermatology Group Workshop to review the role and activities of specialist centres in the UK and Republic of Ireland in order to ascertain whether there were consensus practices. Secondary objectives were to identify key priorities for service, training and research. METHODS: An initial detailed survey review of current activities was undertaken prior to the Workshop and data from this survey were used to inform discussion at the Workshop, which was attended by key photodermatology experts from the UK and Republic of Ireland. RESULTS/CONCLUSIONS: We have undertaken a detailed review of current Photodiagnostic Services in the UK and Republic of Ireland and report on our findings from the 12 centres and we have identified key areas of consensus practice. This is an important step in the process of standardising and optimising procedures and protocols and defining minimum clinical standards for photodiagnostic investigations, which are of such diagnostic importance in Dermatology.

The protocol-guided rapid evaluation of veterans experiencing new transient neurological symptoms (PREVENT) quality improvement program: rationale and methods.

BACKGROUND: Transient ischemic attack (TIA) patients are at high risk of recurrent vascular events; timely management can reduce that risk by 70%. The Protocol-guided Rapid Evaluation of Veterans Experiencing New Transient Neurological Symptoms (PREVENT) developed, implemented, and evaluated a TIA quality improvement (QI) intervention aligned with Learning Healthcare System principles. METHODS: This stepped-wedge trial developed, implemented and evaluated a provider-facing, multi-component intervention to improve TIA care at six facilities. The unit of analysis was the medical center. The intervention was developed based on benchmarking data, staff interviews, literature, and electronic quality measures and included: performance data, clinical protocols, professional education, electronic health record tools, and QI support. The effectiveness outcome was the without-fail rate: the proportion of patients who receive all processes of care for which they are eligible among seven processes. The implementation outcomes were the number of implementation activities completed and final team organization level. The intervention effects on the without-fail rate were analyzed using generalized mixed-effects models with multilevel hierarchical random effects. Mixed methods were used to assess implementation, user satisfaction, and sustainability. DISCUSSION: PREVENT advanced three aspects of a Learning Healthcare System. Learning from Data: teams examined and interacted with their performance data to explore hypotheses, plan QI activities, and evaluate change over time. Learning from Each Other: Teams participated in monthly virtual collaborative calls. Sharing Best Practices: Teams shared tools and best practices. The approach used to design and implement PREVENT may be generalizable to other clinical conditions where time-sensitive care spans clinical settings and medical disciplines. TRIAL REGISTRATION: clinicaltrials.gov: NCT02769338 [May 11, 2016].

Retention of cricothyrotomy skills by paramedics using a wire guided technique.

INTRODUCTION: Cricothyrotomy may be necessary for airway management when a patient's airway cannot be maintained through standard techniques such as oral airway placement, blind insertion airway device, or endotracheal intubation. Wire-guided cricothyrotomy is one of many techniques used to perform a cricothyrotomy. Although there is some controversy over which cricothyrotomy technique is superior, there is no published data regarding long term retention rates. The purpose of this study is to determine whether ground based paramedics can be taught and are able to retain the skills necessary to successfully perform a wire-guided cricothyrotomy. METHODS: This retrospective study was performed in a suburban county with a population of 160,000 with 23,000 EMS calls per year. Participants were ground-based paramedics who were taught wire-guided cricothyrotomy as part of a standardized paramedic educational update program. After viewing an instructional video, the paramedics were shown each the steps of the procedure on a simulation model, using a low fidelity task trainer previously developed to train emergency medicine residents. Using a 16 step procedural checklist, participants were allowed open-ended practice using the task trainer. Critical steps in the checklist were marked in bold lettering indicating automatic failure. Each paramedic was then individually supervised performing a minimum of 5 successful simulations. Retention was assessed using the same 16 step checklist 6 to 12 weeks following the initial training. RESULTS: A total of 55 paramedics completed both the initial training and reassessment during the time period studied. During the initial training phase 100% (55 of 55) of the paramedics were successful in performing all 16 steps of the wire-guided cricothyrotomy. During the retention phase, 87.3% (48 of 55) of paramedics retained the skills necessary to successfully perform the wire-guided cricothyrotomy. On the 16 step checklist, most steps were performed successfully by all the paramedics or missed by only 1 of the 55 paramedics. The step involving removal of the needle prior to advancing the airway device over the guide wire was missed by 34.5% (19 of 55) of the participants. This was not an automatic failure since most participants immediately self-corrected and completed the procedure successfully. CONCLUSION: Paramedics can be taught and can retain the skills necessary to successfully perform a wire-guided cricothyrotomy on a simulator. Future research is necessary to determine if paramedics can successfully transfer these skills to real patients.

A Bronchial Genomic Classifier for the Diagnostic Evaluation of Lung Cancer.

BACKGROUND: Bronchoscopy is frequently nondiagnostic in patients with pulmonary lesions suspected to be lung cancer. This often results in additional invasive testing, although many lesions are benign. We sought to validate a bronchial-airway gene-expression classifier that could improve the diagnostic performance of bronchoscopy. METHODS: Current or former smokers undergoing bronchoscopy for suspected lung cancer were enrolled at 28 centers in two multicenter prospective studies (AEGIS-1 and AEGIS-2). A gene-expression classifier was measured in epithelial cells collected from the normal-appearing mainstem bronchus to assess the probability of lung cancer. RESULTS: A total of 639 patients in AEGIS-1 (298 patients) and AEGIS-2 (341 patients) met the criteria for inclusion. A total of 43% of bronchoscopic examinations were nondiagnostic for lung cancer, and invasive procedures were performed after bronchoscopy in 35% of patients with benign lesions. In AEGIS-1, the classifier had an area under the receiver-operating-characteristic curve (AUC) of 0.78 (95% confidence interval [CI], 0.73 to 0.83), a sensitivity of 88% (95% CI, 83 to 92), and a specificity of 47% (95% CI, 37 to 58). In AEGIS-2, the classifier had an AUC of 0.74 (95% CI, 0.68 to 0.80), a sensitivity of 89% (95% CI, 84 to 92), and a specificity of 47% (95% CI, 36 to 59). The combination of the classifier plus bronchoscopy had a sensitivity of 96% (95% CI, 93 to 98) in AEGIS-1 and 98% (95% CI, 96 to 99) in AEGIS-2, independent of lesion size and location. In 101 patients with an intermediate pretest probability of cancer, the negative predictive value of the classifier was 91% (95% CI, 75 to 98) among patients with a nondiagnostic bronchoscopic examination. CONCLUSIONS: The gene-expression classifier improved the diagnostic performance of bronchoscopy for the detection of lung cancer. In intermediate-risk patients with a nondiagnostic bronchoscopic examination, a negative classifier score provides support for a more conservative diagnostic approach. (Funded by Allegro Diagnostics and others; AEGIS-1 and AEGIS-2 ClinicalTrials.gov numbers, NCT01309087 and NCT00746759.).