Sensitivity and Specificity of a Neuropathic Screening Tool (Self-Report Leeds Assessment of Neuropathic Symptoms and Signs, S-LANSS) in Adolescents With Moderate-Severe Chronic Pain.

Neuropathic screening tools improve recognition of neuropathic pain in adults. Although utilized in pediatric populations, the sensitivity, specificity and methodology of screening tool delivery have not been compared in children. We evaluated the Self-Report Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) in adolescents (10-18 years) referred to a tertiary pediatric pain clinic. History and examination by specialist clinicians and multidisciplinary assessment informed classification of the primary pain type. In a prospective cohort, scores were obtained at interview (S-LANSS interview; n = 161, 70% female), and following substitution of self-reported signs with examination findings in the primary pain region (Leeds Assessment of Neuropathic Symptoms and Signs, LANSS examination). Secondly, we retrospectively retrieved questionnaires self-completed by adolescents at their initial clinic appointment (S-LANSS self-completed; n = 456, 73% female). Thirdly, we explored relationships between patient-reported outcomes and S-LANSS scores. S-LANSS interview scores varied with pain classification, and S-LANSS self-completed scores were similarly highest with neuropathic pain (median [interquartile range]: 18 [11, 21]) and complex regional pain syndrome (21 [14, 24]), variable with musculoskeletal pain (13 [7, 19]) and lowest with visceral pain (6.5 [2, 11.5]) and headache (8.5 [4, 14]). As in adults, the cutpoint score of 12/24 was optimal. Sensitivity was highest with inclusion of examination findings and lowest with self-completion (LANSS examination vs S-LANSS interview vs S-LANSS self-completed: 86.3% vs 80.8% vs 74.7%), but specificity was relatively low (37.8% vs 36.7% vs 48%). High S-LANSS scores in non-neuropathic groups were associated with female sex and high pain catastrophizing. The S-LANSS is a sensitive screening tool for pain with neuropathic features in adolescents, but needs to be interpreted in the context of clinical evaluation (clinicaltrials.gov NCT03312881). PERSPECTIVE: This article reports high sensitivity of the S-LANSS screening tool for identifying pain with neuropathic features in adolescents with moderate-severe chronic pain. However, as sensitivity is lower than in adult populations, further interdisciplinary evaluation is necessary to inform diagnosis and management.

Effects of two treatments on interpersonal, affective, and lifestyle features of psychopathy and emotion dysregulation.

This study investigated the relative efficacy of Mentalization-based therapy (MBT) and United Protocol (UP) in reducing symptoms of psychopathy and emotion dysregulation in a sample of Iranian community residents with concurrent diagnoses of antisocial and borderline personality disorders (PDs). Interpersonal, affective, and lifestyle features of psychopathy were measured post-treatment and at 6-, 12-, 18-, 24-, and 36-months follow-up using the 13-item version of the Psychopathy Revised-Checklist (PCL-R), which excluded, by design, criminal history features. Emotion dysregulation was measured using the Deficits in Emotion Regulation Scale (DERS) developed by Gratz and Roemer (2004). After treatment, both UP- and MBT-treated individuals showed significantly fewer features of psychopathy and significantly less emotion dysregulation. Compared with those treated with MBT, UP-treated individuals showed significantly less emotion dysregulation in all DERS subscales and a greater reduction in psychopathy features, particularly affective features. It is suggested that this likely reflected the particular emphasis placed by UP on improving emotional self-regulation and facilitating the therapeutic alliance. These results suggest that, despite the traditional pessimism that surrounds psychopathic individuals' treatability, they can be successfully treated.

A mixed methods study to uncover impediments to accurate diagnosis of nonradiographic axial spondyloarthritis in the USA.

INTRODUCTION/OBJECTIVES: Delayed diagnosis of axial spondyloarthritis (axSpA) is well documented; little is known about the diagnostic journey and impediments for US patients with nonradiographic axSpA (nr-axSpA). It is hypothesized that impediments are varied and exist at both the healthcare provider (HCP) and patient levels. This study aims to understand patient experiences and contributors to delayed nr-axSpA diagnosis in the USA. METHOD: Interviews of adults with rheumatologist-diagnosed nr-axSpA, recruited through Spondylitis Association of America outreach and patient panels, and of rheumatologists, explored the diagnostic journey and diagnostic barriers. Emerging themes were further explored in an online patient survey. A multiple logistic regression analysis evaluated the main outcome variable, factors affecting time to nr-axSpA diagnosis. RESULTS: Interviews were conducted with 25 patients and 16 rheumatologists. Survey responses from 186 eligible patients revealed median time from symptom onset to diagnosis of nr-axSpA was 3.25 years. Delayed diagnosis was significantly more likely for women and people in rural areas. Most patients consulted ≥4 different types of HCPs before a rheumatologist and ≥2 rheumatologists before diagnosis. Impediments to timely diagnosis included insidious chronic pain; episodic symptom patterns attributed to activity; symptoms other than chronic lumbosacral back pain requiring medical consultation; and unfamiliarity with and misperceptions about nr-axSpA among HCPs, radiologists, and rheumatologists. CONCLUSIONS: Delayed nr-axSpA diagnosis is common and reflects HCP knowledge gaps and frequent patient presentation with dominant nonaxial symptoms. Targeted HCP education, research into early disease patterns, and interventions sensitive to the broader spectrum of nr-axSpA manifestations are needed to improve timely diagnosis. Key Points • Patients with nr-axSpA often see multiple types of HCPs, and multiple rheumatologists, before receiving a diagnosis. • Both patients and HCPs are unfamiliar with nr-axSpA and its symptoms, lacking understanding that nr-axSpA can occur in young people, females, and those presenting with normal x-rays. • Disease recognition by nonrheumatology HCPs is key for early referral. • Education on cardinal features, epidemiology, burden, and benefits of timely nr-axSpA diagnosis is warranted for HCPs who commonly manage back pain.

Development of the generation III (ATR generation I) Plutonium-238 production target design.

A domestic supply chain to produce 238Pu fuel for radioisotope thermoelectric generators is critical for enabling future space exploration. A multi-laboratory effort has worked to establish a common target design to efficiently produce 238Pu in two research reactors. This approach ensures that the annual production goals set forth by NASA are met, while also establishing redundant production capabilities. This paper describes the effort to develop the common target design as well as considerations for future applications for the irradiation platform.

The International Map of Axial Spondyloarthritis Survey: A US Patient Perspective on Diagnosis and Burden of Disease.

OBJECTIVE: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that causes inflammation in the axial skeleton, resulting in structural damage and disability. We aimed to understand the effect of axSpA on work activity, day-to-day function, mental health, relationships, and quality of life and to examine barriers to early diagnosis. METHODS: A 30-minute quantitative US version of the International Map of Axial Spondyloarthritis survey was administered online to US patients aged 18 years and older with a diagnosis of axSpA who were under the care of a health care provider from July 22 to November 10, 2021. This analysis describes demographics, clinical characteristics, journey to axSpA diagnosis, and disease burden. RESULTS: We surveyed 228 US patients with axSpA. Patients had a mean diagnostic delay of 8.8 years, with a greater delay in women versus men (11.2 vs. 5.2 years), and 64.5% reported being misdiagnosed before receiving an axSpA diagnosis. Most patients (78.9%) had active disease (Bath Ankylosing Spondylitis Disease Activity Index score ≥4), reported psychological distress (57.0%; General Health Questionnaire 12 score ≥3), and experienced a high degree of impairment (81.6%; Assessment of Spondyloarthritis International Society Health Index score ≥6). Overall, 47% of patients had a medium or high limitation in activities of daily living, and 46% were not employed at survey completion. CONCLUSION: The majority of US patients with axSpA had active disease, reported psychological distress, and reported impaired function. US patients experienced a substantial delay in time to diagnosis of axSpA that was twice as long in women versus men.

"Self" and "other": A conceptual bridge linking normal with pathological personality.

The goal of this paper is to try and close the gap between the ways in which pathological and normal personality, including their development, are conceptualized. To this end, attention is drawn to parallels that exist between the ways self-function is conceptualized in contemporary personality psychology and in recent iterations of the major psychiatric nosologies, particularly ICD-11. Conceptualizations in both normal and abnormal personality see a fundamental dichotomy between self as identity and self as socially interdependent (vs autonomous). Evidence is reviewed supporting a basic dichotomy between two categories of personality pathology that can be subsumed under the labels "Acting Out" and "Anxious-Inhibited." It is suggested that fundamental to the personality pathology subsumed under "Acting Out" is a deficient interdependent self, while a defective self-identity is proposed to underlie the personality pathology subsumed under "Anxious-Inhibited."

Was There a Cambrian Explosion on Land? The Case of Arthropod Terrestrialization.

Arthropods, the most diverse form of macroscopic life in the history of the Earth, originated in the sea. Since the early Cambrian, at least ~518 million years ago, these animals have dominated the oceans of the world. By the Silurian-Devonian, the fossil record attests to arthropods becoming the first animals to colonize land, However, a growing body of molecular dating and palaeontological evidence suggests that the three major terrestrial arthropod groups (myriapods, hexapods, and arachnids), as well as vascular plants, may have invaded land as early as the Cambrian-Ordovician. These dates precede the oldest fossil evidence of those groups and suggest an unrecorded continental "Cambrian explosion" a hundred million years prior to the formation of early complex terrestrial ecosystems in the Silurian-Devonian. We review the palaeontological, phylogenomic, and molecular clock evidence pertaining to the proposed Cambrian terrestrialization of the arthropods. We argue that despite the challenges posed by incomplete preservation and the scarcity of early Palaeozoic terrestrial deposits, the discrepancy between molecular clock estimates and the fossil record is narrower than is often claimed. We discuss strategies for closing the gap between molecular clock estimates and fossil data in the evolution of early ecosystems on land.

Prolonged COVID-19 symptom duration in people with systemic autoimmune rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey.

OBJECTIVE: We investigated prolonged COVID-19 symptom duration, defined as lasting 28 days or longer, among people with systemic autoimmune rheumatic diseases (SARDs). METHODS: We analysed data from the COVID-19 Global Rheumatology Alliance Vaccine Survey (2 April 2021-15 October 2021) to identify people with SARDs reporting test-confirmed COVID-19. Participants reported COVID-19 severity and symptom duration, sociodemographics and clinical characteristics. We reported the proportion experiencing prolonged symptom duration and investigated associations with baseline characteristics using logistic regression. RESULTS: We identified 441 respondents with SARDs and COVID-19 (mean age 48.2 years, 83.7% female, 39.5% rheumatoid arthritis). The median COVID-19 symptom duration was 15 days (IQR 7, 25). Overall, 107 (24.2%) respondents had prolonged symptom duration (≥28 days); 42/429 (9.8%) reported symptoms lasting ≥90 days. Factors associated with higher odds of prolonged symptom duration included: hospitalisation for COVID-19 vs not hospitalised and mild acute symptoms (age-adjusted OR (aOR) 6.49, 95% CI 3.03 to 14.1), comorbidity count (aOR 1.11 per comorbidity, 95% CI 1.02 to 1.21) and osteoarthritis (aOR 2.11, 95% CI 1.01 to 4.27). COVID-19 onset in 2021 vs June 2020 or earlier was associated with lower odds of prolonged symptom duration (aOR 0.42, 95% CI 0.21 to 0.81). CONCLUSION: Most people with SARDs had complete symptom resolution by day 15 after COVID-19 onset. However, about 1 in 4 experienced COVID-19 symptom duration 28 days or longer; 1 in 10 experienced symptoms 90 days or longer. Future studies are needed to investigate the possible relationships between immunomodulating medications, SARD type/flare, vaccine doses and novel viral variants with prolonged COVID-19 symptoms and other postacute sequelae of COVID-19 among people with SARDs.

Carer preferences of route of administration of transmucosal diamorphine and willingness to take part in a randomised controlled trial: an interview study (DIPPER).

BACKGROUND: Children and young people are usually given liquid morphine by mouth for breakthrough pain, which can take thirty minutes to work. A faster-acting, quickly absorbed, needle-free pain medicine, that is easy to administer is needed such as transmucosal (sublingual, buccal, intranasal) diamorphine. Research evidence relating to the administration of medication for breakthrough pain in children and young people is limited. This study aims to describe the experiences and preferences of parents and/or children and young people regarding the route of administration of diamorphine, barriers and facilitators comparative to oral morphine, and participation in a randomised controlled trial. METHODS: In-depth, semi-structured interviews with parents and/or children and young people at home or hospital/hospice. RESULTS: Thirteen interviews with: nine mothers, one father, and three sets of parents jointly. No interviews took place with a child/young person. Most families had experience of the buccal route which was effective in ease of administration and time to control pain. The intranasal route was preferred by parents irrespective of experience. Parents' willingness for their child to take part in a trial depended on the time commitment, their child's pain trajectory and the stability of analgesic requirements. CONCLUSION: A randomised controlled trial of oral morphine versus transmucosal diamorphine would need to consider trial logistics, especially time commitment. Parents felt that the trial should be introduced initially by the clinical team, with written information from the research team, and sufficient time to ask questions. Patients who had discontinued oral morphine because of side effects, or those with gastrointestinal failure, should be excluded. Maintaining stability in pain management was essential to families, so the timing of the trial is a potential issue.

Diamorphine pharmacokinetics and conversion factor estimates for intranasal diamorphine in paediatric breakthrough pain:systematic review.

BACKGROUND: Intranasal diamorphine is a potential treatment for breakthrough pain but few paediatric data are available to assist dose estimation. AIM: To determine an intranasal diamorphine dose in children through an understanding of pharmacokinetics. DESIGN: A systematic review of the literature was undertaken to seek diamorphine pharmacokinetic parameters in neonates, children and adults. Parenteral and enteral diamorphine bioavailability were reviewed with respect to formation of the major metabolite, morphine. Clinical data quantifying equianalgesic effects of diamorphine and morphine were reviewed. REVIEW SOURCES: PubMed (1960-2020); EMBASE (1980-2020); IPA (1973-2020) and original human research studies that reported diacetylmorphine and metabolite after any dose or route of administration. RESULTS: The systematic review identified 19 studies: 16 in adults and 1 in children and 2 neonatal reports. Details of study participants were extracted. Age ranged from premature neonates to 67 years and weight 1.4-88 kg. Intranasal diamorphine bioavailability was predicted as 50%. The equianalgesic intravenous conversion ratio of morphine:diamorphine was 2:1. There was heterogeneity between pharmacokinetic parameter estimates attributed to routes of administration, lack of size standardisation, methodology and pharmacokinetic analysis. Estimates of the pharmacokinetic parameters clearance and volume of distribution were reduced in neonates. There were insufficient paediatric data to characterise clearance or volume maturation of either diamorphine or its metabolites. CONCLUSIONS: We estimate equianalgesic ratios of intravenous morphine:diamorphine 2:1, intravenous morphine:intranasal diamorphine 1:1 and oral morphine:intranasal diamorphine of 1:3. These ratios are based on adult literature, but are reasonable for deciding on an initial dose of 0.1 mg/kg in children 4-13 years.

Pain assessment tools in paediatric palliative care: A systematic review of psychometric properties and recommendations for clinical practice.

BACKGROUND: Assessing pain in infants, children and young people with life-limiting conditions remains a challenge due to diverse patient conditions, types of pain and often a reduced ability or inability of patients to communicate verbally. AIM: To systematically identify pain assessment tools that are currently used in paediatric palliative care and examine their psychometric properties and feasibility and make recommendations for clinical practice. DESIGN: A systematic literature review and evaluation of psychometric properties of pain assessment tools of original peer-reviewed research published from inception of data sources to April 2021. DATA SOURCES: PsycINFO via ProQuest, Web of Science Core, Medline via Ovid, EMBASE, BIOSIS and CINAHL were searched from inception to April 2021. Hand searches of reference lists of included studies and relevant reviews were performed. RESULTS: From 1168 articles identified, 201 papers were selected for full-text assessment. Thirty-four articles met the eligibility criteria and we examined the psychometric properties of 22 pain assessment tools. Overall, the Faces Pain Scale-Revised (FPS-R) had high cross-cultural validity, construct validity (hypothesis testing) and responsiveness; while the Faces, Legs, Activity, Cry and Consolability (FLACC) scale and Paediatric Pain Profile (PPP) had high internal consistency, criterion validity, reliability and responsiveness. The number of studies per psychometric property of each pain assessment tool was limited and the methodological quality of included studies was low. CONCLUSION: Balancing aspects of feasibility and psychometric properties, the FPS-R is recommended for self-assessment, and the FLACC scale/FLACC Revised and PPP are the recommended observational tools in their respective age groups.

A vegetative storage protein improves drought tolerance in maize.

Vegetative storage proteins (VSPs) are known to serve as nitrogen reserves in many dicot plants but remain undiscovered in grasses, most widely grown group of crops globally. We identified and characterized a VSP in maize and demonstrated that its overexpression improved drought tolerance. Nitrogen supplementation selectively induced a mesophyll lipoxygenase (ZmLOX6), which was targeted to chloroplasts by a novel N-terminal transit peptide of 62 amino acids. When ectopically expressed under the control of various tissue-specific promoters, it accumulated to a fivefold higher level upon expression in the mesophyll cells than the wild-type plants. Constitutive expression or targeted expression specifically to the bundle sheath cells increased its accumulation by less than twofold. The overexpressed ZmLOX6 was remobilized from the leaves like other major proteins during grain development. Evaluated in the field over locations and years, transgenic hybrids overexpressing ZmLOX6 in the mesophyll cells significantly outyielded nontransgenic sibs under managed drought stress imposed at flowering. Additional storage of nitrogen as a VSP in maize leaves ameliorated the effect of drought on grain yield.

The Interplay Between COVID-19 and Spondyloarthritis or Its Treatment.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has created multiple uncertainties regarding rheumatic diseases or their treatment, with regard to the susceptibility to or severity of the viral disease. We aimed to address these questions as they relate to spondyloarthritis (SpA). METHODS: We created a longitudinal survey from April 10, 2020, to April 26, 2021. There were 4723 subjects with SpA and 450 household contacts who participated worldwide. Of these, 3064 respondents were from the US and 70.4% of them provided longitudinal data. To control for the duration of potential risk of COVID-19, the rate of contracting the disease was normalized for person-months of exposure. RESULTS: In an analysis of US subjects who provided longitudinal data, the incident rate ratio for the 159 (out of 2157) subjects who tested positive for COVID-19 was 1.16 compared to the US population as adjusted for age and sex (range 0.997-1.361, P = 0.06). A paired evaluation using patients and household members did not show a statistically significant effect to indicate a predisposition for developing COVID-19 as a result of SpA or its treatment. Our data failed to show that any class of medication commonly used to treat SpA significantly affected the risk of developing COVID-19 or increasing the severity of COVID-19. CONCLUSION: These data do not exclude a small increased risk of developing COVID-19 as a result of SpA, but the risk, if it exists, is low and not consistently demonstrated. The data should provide reassurance to patients and to rheumatologists about the risk that COVID-19 poses to patients with SpA.

Oral morphine versus transmucosal diamorphine for breakthrough pain in children: methods and outcomes: UK (DIPPER study) consensus.

OBJECTIVES: No randomised controlled trials have been conducted for breakthrough pain in paediatric palliative care and there are currently no standardised outcome measures. The DIPPER study aims to establish the feasibility of conducting a prospective randomised controlled trial comparing oral and transmucosal administration of opioids for breakthrough pain. The aim of the current study was to achieve consensus on design aspects for a small-scale prospective study to inform a future randomised controlled trial of oral morphine, the current first-line treatment, versus transmucosal diamorphine. METHODS: The nominal group technique was used to achieve consensus on best practice for mode of administration, dose regimen and a range of suitable pain intensity outcome measures for transmucosal diamorphine in children and young people with breakthrough pain. An expert panel of ten clinicians in paediatric palliative care and three parent representatives participated. Consensus was achieved when agreement was reached and no further comments from participants were forthcoming. RESULTS: The panel favoured the buccal route of administration, with dosing according to the recommendations in the Association for Paediatric Palliative Medicine formulary (fifth Edition, 2020). The verbal Numerical Rating Scale was selected to measure pain in children 8 years old and older, the Faces Pain Scale-Revised for children between 4 and 8 years old, and Face, Legs, Activity, Cry and Consolability (FLACC)/FLACC-Revised as the observational tools. CONCLUSIONS: The nominal group technique allowed consensus to be reached for a small-scale, prospective, cohort study and provided information to inform the design of a randomised controlled trial.

Early experience of COVID-19 vaccination in adults with systemic rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey.

BACKGROUND: We describe the early experiences of adults with systemic rheumatic disease who received the COVID-19 vaccine. METHODS: From 2 April to 30 April 2021, we conducted an online, international survey of adults with systemic rheumatic disease who received COVID-19 vaccination. We collected patient-reported data on clinician communication, beliefs and intent about discontinuing disease-modifying antirheumatic drugs (DMARDs) around the time of vaccination, and patient-reported adverse events after vaccination. RESULTS: We analysed 2860 adults with systemic rheumatic diseases who received COVID-19 vaccination (mean age 55.3 years, 86.7% female, 86.3% white). Types of COVID-19 vaccines were Pfizer-BioNTech (53.2%), Oxford/AstraZeneca (22.6%), Moderna (21.3%), Janssen/Johnson & Johnson (1.7%) and others (1.2%). The most common rheumatic disease was rheumatoid arthritis (42.3%), and 81.2% of respondents were on a DMARD. The majority (81.9%) reported communicating with clinicians about vaccination. Most (66.9%) were willing to temporarily discontinue DMARDs to improve vaccine efficacy, although many (44.3%) were concerned about rheumatic disease flares. After vaccination, the most reported patient-reported adverse events were fatigue/somnolence (33.4%), headache (27.7%), muscle/joint pains (22.8%) and fever/chills (19.9%). Rheumatic disease flares that required medication changes occurred in 4.6%. CONCLUSION: Among adults with systemic rheumatic disease who received COVID-19 vaccination, patient-reported adverse events were typical of those reported in the general population. Most patients were willing to temporarily discontinue DMARDs to improve vaccine efficacy. The relatively low frequency of rheumatic disease flare requiring medications was reassuring.