Head home: implementation during COVID-19 pandemic.

BACKGROUND: Recent research suggests that between 20% and 50% of paediatric head injuries attending our emergency department (ED) could be safely discharged soon after triage, without the need for medical review, using a 'Head Injury Discharge At Triage' tool (HIDAT). We sought to implement this into clinical practice. METHODS: Paediatric ED triage staff underwent competency-based assessments for HIDAT with all head injury presentations 1 May to 31 October 2020 included in analysis. We determined which patients were discharged using the tool, which underwent CT of the brain and whether there was a clinically important traumatic brain injury or representation to the ED. RESULTS: Of the 1429 patients screened; 610 (43%) screened negative with 250 (18%) discharged by nursing staff. Of the entire cohort, 32 CTs were performed for head injury concerns (6 abnormal) with 1 CT performed in the HIDAT negative group (normal). Of those discharged using HIDAT, four reattended, two with vomiting (no imaging or admission) and two with minor scalp wound infections. Two patients who screened negative declined discharge under the policy with later medical discharge (no imaging or admission). Paediatric ED attendances were 29% lower than in 2018. CONCLUSION: We have successfully implemented HIDAT into local clinical practice. The number discharged (18%) is lower than originally described; this is likely multifactorial. The relationship between COVID-19 and paediatric ED attendances is unclear but decreased attendances suggest those for whom the tool was originally designed are not attending ED and may be accessing other medical/non-medical resources.

Head home: a prospective cohort study of a nurse-led paediatric head injury clinical decision tool at a district general hospital.

OBJECTIVES: To assess if a nurse-led application of a paediatric head injury clinical decision tool would be safe compared with current practice. METHODS: All paediatric (<17 years) patients with head injuries presenting to Frimley Park Emergency Department (ED), England from 1 May to 31 October 2018 were prospectively screened by a nurse using a mandated electronic 'Head Injury Discharge At Triage' questionnaire (HIDATq). We determined which patients underwent CT of brain and whether there was a clinically important intracranial injury or re-presentation to the ED. The negative predictive value of the screening tool was assessed. We determined what proportion of patients could have been sent home from triage using this tool. RESULTS: Of the 1739 patients screened, 61 had CTs performed due to head injury (six abnormal) with a CT rate of 3.5% and 2% re-presentations. Of the entire cohort, 1052 screened negative. 1 CT occurred in this group showing no abnormalities. Of those screened negative, 349 (33%)/1052 had 'no other injuries' and 543 (52%)/1052 had 'abrasions or lacerations'. HIDATq's negative predictive value for CT was 99.9% (95% CI 99.4% to 99.9%) and 100% (95% CI 99.0% to 100%) for intracranial injury. The positive predictive value of the tool was low. Five patients screened negative and re-presented within 72 hours but did not require CT imaging. CONCLUSION: A negative HIDATq appears safe in our ED. Potentially 20% (349/1739) of all patients with head injuries presenting to our department could be discharged by nurses at triage with adequate safety netting advice. This increases to 50% (543/1739), if patients with lacerations or abrasions were given advice and discharged at triage. A large multicentre study is required to validate the tool.

Process utilities for topical treatment in atopic dermatitis.

PURPOSE: Management of atopic dermatitis (AD) typically requires application of topical treatments, often multiple times a day. The cosmetic properties and burdensome application of these treatments can be detrimental to quality of life (QoL). Patients who achieve good disease control through use of systemic therapies may reduce the frequency and amount of topical applications, improving QoL. This study aimed to quantify the utility and disutility for topical AD treatment processes. METHODS: Seven vignettes describing different skincare regimens for people with moderate-to-severe AD were developed with input from healthcare professionals. 484 respondents from the general population completed time trade-off items for each vignette. Utility values for each regimen, and disutilities associated with the impact of changes to skincare regimens, were calculated. Analysis of variance assessed differences between skincare regimens. RESULTS: As skincare regimens increased in intensity (0.7968 for the most intense; 0.9999 for the least), utility values decreased. There were no statistically significant differences between skincare regimens followed by patients with good disease control (0.9862 to 0.9999); however, when compared to those involving topical corticosteroids and emollient combinations (0.7968 to 0.8835), significant differences were observed (p < 0.001). The largest disutilities (0.1521 to 0.1705) were between skincare regimens describing the use of topical corticosteroids plus emollient and those followed by patients with good disease control. CONCLUSIONS: The application of topical treatments has a detrimental effect on QoL, which increases with the duration and frequency of applications. Further research is needed to investigate how health and process utilities interact and both can be integrated into medical decision-making.

Development of a refined tenocyte differentiation culture technique for tendon tissue engineering.

We have established that human tenocytes can differentiate in the absence of exogenous fetal bovine serum (FBS) but in the presence of insulin-like growth factor-1 (IGF-1) and transforming growth factor-ß3 (TGF-ß3). The extent of tenocyte differentiation was assessed by examining cell survival, collagen synthesis, cell morphology and expression of tenocyte differentiation markers such as scleraxis (Scx), tenomodulin (Tnmd), collagen type I (Col-I) and decorin (Dcn). Our results indicate that 50 ng/ml IGF-1 and 10 ng/ml TGF-ß3 (in the absence of FBS) were capable of maintaining in vitro human tenocyte survival in 14-day cultures. The extent of collagen synthesis and messenger ribonucleic acid expression of Scx, Tnmd, Col-I and Dcn were significantly upregulated in response to IGF-1 and TGF-ß3. These findings have shown for the first time that human tenocytes can be maintained in long-term culture, in serum-free conditions, making this approach a suitable one for the purpose of tendon tissue engineering.

Observing expert opinion of medical affairs pharmaceutical physicians on the value of their clinical experience to the pharmaceutical industry using the Jandhyala method.

BACKGROUND: The pharmaceutical industry requires a highly qualified workforce with diverse skillsets. Medical affairs pharmaceutical physicians (MAPPs) have unique qualifications among pharmaceutical company employees, but the exact contribution of their education and training is unknown. This study aimed to identify the medical education and training competencies MAPPs use in the pharmaceutical industry in relation to the four external stakeholders, regulators, payors, prescribers, and patients. METHOD: Ten MAPPs were recruited using convenience sampling via professional networks. A systematic literature review and the Jandhyala method, a two-stage qualitative online consensus method, identified which of MAPPs' medical education and training competencies they used in their work with each external stakeholder. Statistical analyses determined heterogeneity in the relevance of competencies and competency categories to each stakeholder. RESULTS: Nine MAPPs completed the study. Of the 59 competencies identified, 54 were relevant to all external stakeholders. Relevance of competencies varied significantly between external stakeholders (p = .0434). Binary competency scores varied significantly for three pairs of stakeholders, "patient vs. payor" (p = .025), "prescriber vs. regulator" (p = .013) and "prescriber vs. payor" (p = .008). Between-stakeholder overall frequency count varied significantly for two of the nine competency categories. CONCLUSION: MAPPs develop a highly specialized set of competencies during medical education and training from which they use distinct subsets to meet the needs of external stakeholders in the pharmaceutical industry. Undergraduate and postgraduate competency-based medical education appears to prepare MAPPs for cognitive and technical work. Further exploration may aid understanding of how they develop soft skills.

Medical affairs pharmaceutical physicians (MAPPs) are of key importance in promoting patient centricity in the pharmaceutical industry. Their competency-based medical education and clinical experience give them a unique skillset among pharmaceutical company employees. MAPPs utilize their training to benefit pharmaceutical companies as well as the four external stakeholders in medicine adoption: regulators, payors, prescribers and patients. Previous work has suggested that their education and training may account for their ability to benefit all external stakeholders; however, this has not been explored in detail. The aim of this study was to identify competencies MAPPs develop during medical education, training and clinical experience and which of these they use in their work with each of the four external stakeholders.To do this, first, we reviewed the literature and asked MAPPs to self-report the competencies they developed during medical education and training, and which were relevant to their work with each of the four stakeholders. We found that 54 of the 59 identified competencies were relevant to work with all external stakeholders. However, the relevance of individual competencies varied between external stakeholders, with further analysis showing that the difference appeared to be accounted for by differences between three main pairs of stakeholders. These were "patient vs. payor", "prescriber vs. regulator" and "prescriber vs. payor. In other words, MAPPs were likely to use different competencies in their work with each stakeholder. With our analysis of competency categories, we concluded that MAPPs use a highly specialized combination of competencies adapted to each external stakeholder.

Real-World Cost of Nasal Polyps Surgery and Risk of Major Complications in the United States: A Descriptive Retrospective Database Analysis.

Background: Endoscopic nasal polyp (NP) surgery is a treatment option for patients with chronic rhinosinusitis with nasal polyps (CRSwNP). Previous studies report NP surgery costs of $8000-13,000 and risk of major complications of NP surgery of ~0.1-1%. Limited contemporary data for costs and complications associated with NP surgery in US clinical practice are available. Methods: IQVIA PharMetrics Plus claims data were used to identify patients with NP surgery in 2019 with ≥3 years continuous baseline health-plan enrollment prior to index date (date of first eligible NP surgery) and ≥30 days continuous enrollment after index (follow-up). In this descriptive analysis, total costs of NP surgery were estimated as all medical costs on the index date (or during the entire hospital stay for patients who received surgery in the inpatient setting). Total medical costs (all-cause) were estimated for all medical services occurring from the index date to the index date +9 or +29 days (10-day and 30-day). Major complication was defined as cerebrospinal fluid (CSF) leak, orbital injury, or major hemorrhage within 30 days of index. Results: Of 6311 patients, median age was 46 years (interquartile range: 34-56); 59.7% were male; 88.2% had no NP surgery in the prior 3 years; 63.7% had allergic rhinitis, and 37.1% had asthma. Mean (SD) total medical cost of surgery was $14,697 (11,679) and mean (SD) 10-day total medical cost was $15,401 (11,968). Major complications occurred in 102 (1.7%) patients. Total medical costs and 10-day costs were higher in patients with major complications than those without ($23,605 [19,264] vs $15,251 [11,741]). Conclusion: In this descriptive analysis, NP surgery costs and rates of major surgical complications were updated using recent real-world data in the US. Results indicated that NP surgery complication rates were numerically higher than previously reported.

Treatment patterns in UK adult patients with atopic dermatitis treated with systemic immunosuppressants: data from The Health Improvement Network (THIN).

Background: There is limited understanding on patterns of systemic treatment in adults with moderate-to-severe atopic dermatitis (AD) in the UK.Objective: To characterize treatment patterns in adult AD patients prescribed immunosuppressants (IMMs) in the primary care setting.Results: Six hundred and fifty-six patients with AD (6.6%) were prescribed IMM in the analysis (mean age 52.1 years; 59.1% female; age-adjusted Charlson comorbidity index 1.4). Most prevalent (>5%) conditions at baseline were depression (10.8%), contact dermatitis (10.7%), rheumatological disease (7.9%), skin/subcutaneous tissue disorders (6.4%), upper respiratory disease (5.8%), and psoriasis (5.2%). At baseline, up to 50% of patients were prescribed ≥1 IMM. During follow-up, 42.7% of patients were prescribed oral corticosteroids (OCSs), increasing in line with IMM exposure. The most commonly prescribed IMM was methotrexate (43.3%). Ciclosporin, the only approved IMM for AD, was prescribed to 16.9% of patients.Conclusions: The prevalence of comorbidities and high rate of IMM prescriptions demonstrate the impact of AD on quality of life. The frequency of OCS prescribing in AD patients treated with IMMs suggests a lack of disease control with existing therapies, and an unmet need for safe and effective targeted agents for long-term disease control.

Three-dimensional reconstructed magnetic resonance scans: Accuracy in identifying and defining knee meniscal tears.

AIM: To determine whether three-dimensional (3D) reconstruction from conventional magnetic resonance imaging (MRI) is able to accurately detect a meniscal tear, and define the configuration. METHODS: Thirty-three patients' 3T MRI scan data were collected and sagittal uni-planar 3D reconstructions performed from the preoperative MRI. There were 24 meniscal tears in 24 patients, and nine controls. All patients had arthroscopic corroboration of MRI findings. Two independent observers prospectively reported on all 33 reconstructions. Meniscal tear presence or absence was noted, and tear configuration subsequently categorised as either radial, bucket-handle, parrot beak, horizontal or complex. RESULTS: Identification of control menisci or meniscal tear presence was excellent (Accuracy: observer 1 = 90.9%; observer 2 = 81.8%). Of the tear configurations, bucket handle tears were accurately identified (Accuracy observer 1 and 2 = 80%). The remaining tear configurations were not accurately discernable. CONCLUSION: Uni-planar 3D reconstruction from 3T MRI knee scan sequences are useful in identifying normal menisci and menisci with bucket-handle tears. Advances in MRI sequencing and reconstruction software are awaited for accurate identification of the remaining meniscal tear configurations.

The pattern of cartilage damage in antero-medial osteoarthritis of the knee and its relationship to the anterior cruciate ligament.

Within antero-medial gonarthrosis (AMG) of the knee, there is a spectrum of damage seen in the functionally intact anterior cruciate ligament (ACL). Our aim was to correlate the degree of ACL damage to the geographical extent and degree of cartilage loss on the tibial plateau. Ninety tibial plateaus resected during unicompartmental arthroplasty were photographed and digitally mapped. The ACL damage was graded (0: normal, 1: synovium loss, 2: longitudinal splits), and dimensions of full thickness cartilage loss and damage recorded. The percentage of full thickness loss in patients with a normal ACL was compared to those with a damaged, but functionally intact ligament. All specimens showed similar elliptical loss of cartilage in the antero-medial part of the tibial plateau. A total of 45(50%) patients had a macroscopically normal ACL, 21(23%) had synovial loss, and 24(27%) had longitudinal splits. An increase in the area of cartilage damage was seen with progressive ACL damage (p < 0.001). The area of macroscopically normal cartilage found posteriorly did not change. This study demonstrates that phenotypic distribution of cartilage damage in AMG is highly reproducible with a pattern of increasing cartilage erosion associated with increasing ACL damage.

Hyaluronidase treatment of synovial fluid to improve assay precision for biomarker research using multiplex immunoassay platforms.

Synovial fluid (SF) is a difficult biological matrix to analyse due to its complex non-Newtonian nature. This can result in poor assay repeatability and potentially inefficient use of precious samples. This study assessed the impact of SF treatment by hyaluronidase and/or dilution on intra-assay precision using the Luminex and Meso Scale Discovery (MSD) multiplex platforms. SF was obtained from patients with knee osteoarthritis at the time of joint replacement surgery. Aliquots derived from the same sample were left untreated (neat), 2-fold diluted, 4-fold diluted or treated with 2mg/ml testicular hyaluronidase (with 2-fold dilution). Preparation methods were compared in a polysterene-bead Luminex 10-plex (N=16), magnetic-bead Luminex singleplex (N=7) and MSD 4-plex (N=7). Each method was assessed for coefficient of variation (CV) of replicate measurements, number of bead events (for Luminex assays) and dilution-adjusted analyte concentration. Percentage recovery was calculated for dilutions and HAse treatment. Hyaluronidase treatment significantly increased the number of wells with satisfactory bead events/region (95%) compared to neat (48%, p<0.001) in the polystyrene-bead Luminex assay, but the magnetic-bead Luminex assay achieved ≥50 bead events irrespective of treatment method. Hyaluronidase treatment resulted in lower intra-assay CVs for detectable ligands (group average CV<10%) than neat, 2-fold and 4-fold dilution (CV~25% for all, p<0.05) in both polystyrene- and magnetic-bead Luminex assays. In addition, measured sample concentrations were higher and recovery was poor (elevated) after hyaluronidase treatment. In the MSD 4-plex, within-group comparison of the intra-assay CV or concentration was not conclusively influenced by SF preparation. However, only hyaluronidase treatment resulted in CV<25% for all samples for TNF-α. There was no effect on analyte concentrations or recovery. Hyaluronidase treatment can improve intra-assay precision and assay signal of SF analysis by multiplex immunoassays and should be recommended for SF biomarker research, particularly using the Luminex platform.

Coexistence of LMPP-like and GMP-like leukemia stem cells in acute myeloid leukemia.

The relationships between normal and leukemic stem/progenitor cells are unclear. We show that in ∼80% of primary human CD34+ acute myeloid leukemia (AML), two expanded populations with hemopoietic progenitor immunophenotype coexist in most patients. Both populations have leukemic stem cell (LSC) activity and are hierarchically ordered; one LSC population gives rise to the other. Global gene expression profiling shows the LSC populations are molecularly distinct and resemble normal progenitors but not stem cells. The more mature LSC population most closely mirrors normal granulocyte-macrophage progenitors (GMP) and the immature LSC population a previously uncharacterized progenitor functionally similar to lymphoid-primed multipotential progenitors (LMPPs). This suggests that in most cases primary CD34+ AML is a progenitor disease where LSCs acquire abnormal self-renewal potential.