Validity evidence for a novel multiple-choice question bank in the field of child abuse pediatrics.

BACKGROUND: Though child abuse pediatrics has been a board-certified subspecialty for 15 years, there are few formalized board preparation resources available. OBJECTIVE: The purpose of this project was to establish a multiple-choice question bank with sufficient validity evidence for use in preparation for the child abuse pediatrics board examination. PARTICIPANTS AND SETTING: The question bank was distributed via an electronic child abuse pediatrics mailing list. Participants completing the entire question bank included 27 board-certified child abuse pediatricians (CAPs), 19 board-eligible CAPs, and 18 CAP fellows. METHODS: We used Messick's framework to conduct the validity investigation, which includes five components: content evidence, response process, internal structure, relation to other variables, and consequences. Item analyses included difficulty index, discrimination index, and distractor analysis. We used Cronbach's alpha to estimate internal consistency reliability. We conducted linear regressions of scores on the question bank compared to in-training exam scores and career stage. RESULTS: Eighty-four participants completed part of the question bank, and 64 completed the entire question bank. Of the original 117 questions ("items"), 94 met inclusion criteria. The mean score among board-certified CAPs was 80 %, and among participants reporting passing third-year ITE scores was 81 %. Correlation coefficient of scores on this question bank by career stage was r = 0.94, and by year of fellowship was r = 0.99. Cronbach's alpha for internal consistency reliability was 0.83. CONCLUSIONS: This multiple-choice question bank is the first question bank with a robust validity investigation for use by child abuse pediatrics trainees.

Reduced insulin/IGF-1 signalling upregulates two anti-viral immune pathways, decreases viral load and increases survival under viral infection in C. elegans.

Reduced insulin/IGF-1 signalling (rIIS) improves survival across diverse taxa and there is a growing interest in its role in regulating immune function. Whilst rIIS can improve anti-bacterial resistance, the consequences for anti-viral immunity are yet to be systematically examined. Here, we show that rIIS in adult Caenorhabditis elegans increases the expression of key genes in two different anti-viral immunity pathways, whilst reducing viral load in old age, increasing survival and reducing rate-of-senescence under infection by naturally occurring positive-sense single-stranded RNA Orsay virus. We found that both drh-1 in the anti-viral RNA interference (RNAi) pathway and cde-1 in the terminal uridylation-based degradation of viral RNA pathway were upregulated in early adulthood under rIIS and increased anti-viral resistance was not associated with reproductive costs. Remarkably, rIIS increased anti-viral gene expression only in infected worms, potentially to curb the costs of constitutively upregulated immunity. RNA viruses are found across taxa from plants to mammals and we demonstrate a novel role for rIIS in regulating resistance to viral infection. We therefore highlight this evolutionarily conserved signalling pathway as a promising therapeutic target to improve anti-viral immunity.

Desert diversity: genome sequence of Gordonia rubripertincta cluster DJ phage Mossy and cluster DV phage Erutan.

Lytic bacteriophages Mossy and Erutan were directly isolated from desert soil on Gordonia rubripertincta and characterized by their morphologies and genomes. Mossy, part of the DJ cluster of Actinobacteriophage, has a genome of 61,183 bp. The genome of Erutan, part of the DV cluster, is 66,957 bp.

Determination of sensed and paced atrial-ventricular delay in cardiac resynchronization therapy.

BACKGROUND: Optimization of atrial-ventricular delay (AVD) during atrial sensing (SAVD) and pacing (PAVD) provides the most effective cardiac resynchronization therapy (CRT). We demonstrate a novel electrocardiographic methodology for quantifying electrical synchrony and optimizing SAVD/PAVD. METHODS: We studied 40 CRT patients with LV activation delay. Atrial-sensed to RV-sensed (As-RVs) and atrial-paced to RV-sensed (Ap-RVs) intervals were measured from intracardiac electrograms (IEGM). LV-only pacing was performed over a range of SAVD/PAVD settings. Electrical dyssynchrony (cardiac resynchronization index; CRI) was measured at each setting using a multilead ECG system placed over the anterior and posterior torso. Biventricular pacing, which included multiple interventricular delays, was also conducted in a subset of 10 patients. RESULTS: When paced LV-only, peak CRI was similar (93 ± 5% vs. 92 ± 5%) during atrial sensing or pacing but optimal PAVD was 61 ± 31 ms greater than optimal SAVD. The difference between As-RVs and Ap-RVs intervals on IEGMs (62 ± 31 ms) was nearly identical. The slope of the correlation line (0.98) and the correlation coefficient r (0.99) comparing the 2 methods of assessing SAVD-PAVD offset were nearly 1 and the y-intercept (0.63 ms) was near 0. During simultaneous biventricular (BiV) pacing at short AVD, SAVD and PAVD programming did not affect CRI, but CRI was significantly (p < .05) lower during atrial sensing at long AVD. CONCLUSIONS: A novel methodology for measuring electrical dyssynchrony was used to determine electrically optimal SAVD/PAVD during LV-only pacing. When BiV pacing, shorter AVDs produce better electrical synchrony.

Patient and parent perspectives on paediatric cancer multidisciplinary team working and national advisory panels in the UK: a qualitative research study.

OBJECTIVE: The concept of patient-centred care is central to the role of cancer multidisciplinary teams (MDTs) and particularly pertinent with the recent rise in number of virtual national advisory panels (NAPs) for childhood cancer in the UK. We sought to explore patient and caregiver views regarding MDT working and NAPs. METHODS: Three focus groups were undertaken between March 2019 and January 2020. RESULTS: Sixteen participants attended. All regarded MDTs and NAPs highly, while highlighting patient involvement in decision-making should not be diluted by this process. The importance of personalised consultations was stressed, acknowledging that information-sharing preferences may change with circumstance and time. Most participants felt they had not been actively involved in decisions, including those made following MDT or NAP discussions. Group suggestions to improve patient-centred care included a clinician knowing them presenting their case, referral proformas to include family-related factors and an advocate attending meetings to represent the patient/family view. CONCLUSION: Several changes have been driven forward by this work, including the modification of NAP referral proformas to include additional information. Patient and parent perspectives are now embedded into a best practice model for the NAPs to promote personalised recommendations at national level.

Decision-support tools to build climate resilience against emerging infectious diseases in Europe and beyond.

Climate change is one of several drivers of recurrent outbreaks and geographical range expansion of infectious diseases in Europe. We propose a framework for the co-production of policy-relevant indicators and decision-support tools that track past, present, and future climate-induced disease risks across hazard, exposure, and vulnerability domains at the animal, human, and environmental interface. This entails the co-development of early warning and response systems and tools to assess the costs and benefits of climate change adaptation and mitigation measures across sectors, to increase health system resilience at regional and local levels and reveal novel policy entry points and opportunities. Our approach involves multi-level engagement, innovative methodologies, and novel data streams. We take advantage of intelligence generated locally and empirically to quantify effects in areas experiencing rapid urban transformation and heterogeneous climate-induced disease threats. Our goal is to reduce the knowledge-to-action gap by developing an integrated One Health-Climate Risk framework.

Investigation of CRISPR-Independent Phage Resistance Mechanisms Reveals a Role for FtsH in Phage Adsorption to Streptococcus thermophilus.

Prokaryotes are under constant pressure from phage infection and thus have evolved multiple means of defense or evasion. While CRISPR-Cas constitutes a robust immune system and appears to be the predominant means of survival for Streptococcus thermophilus when facing lytic phage infection, other forms of phage resistance coexist in this species. Here, we show that S. thermophilus strains with deleted CRISPR-Cas loci can still give rise to phage-resistant clones following lytic phage challenge. Notably, non-CRISPR phage-resistant survivors had multiple mutations which would truncate or recode a membrane-anchored host protease, FtsH. Phage adsorption was dramatically reduced in FtsH mutants, implicating this protein in phage attachment. Phages were isolated which could bypass FtsH-based resistance through mutations predicted to alter tape measure protein translation. Together, these results identify key components in phage propagation that are subject to mutation in the molecular arms race between phage and host cell. IMPORTANCE Streptococcus thermophilus is an important organism for production of cultured dairy foods, but it is susceptible to lytic phages which can lead to failed products. Consequently, mechanisms for phage resistance are an active area of research. One such mechanism is CRISPR-Cas, and S. thermophilus is a model organism for the study of this form of adaptive immunity. Here, we expand on known mechanisms with our finding that spontaneous mutations in ftsH, a gene encoding a membrane-anchored protease, protected against phage infection by disrupting phage adsorption. In turn, mutations in phage tail protein genes allowed phages to overcome ftsH-based resistance. Our results identified components in phage propagation that are subject to mutation in the molecular arms race between phage and host.

Communicating about the social determinants of health: development of a local brand.

BACKGROUND: Successful comprehensive population-based approaches to chronic disease prevention leverage mass media to amplify messages and support a culture of health. We report on a community-engaged formative evaluation to segment audiences and identify major themes to guide campaign message development for a transformative health communication campaign. METHODS: Four key phases of campaign development: (I) Formative evaluation to identify priorities, guiding themes, and audience segments (interviews/focus groups with residents, N = 85; representatives of community-based partner organizations, N = 10); (II) Brand development (focus groups and closed-ended surveys; N = 56); (III) Message testing approaches to verbal and visual appeals (N = 50 resident intercept interviews); (IV) Workshop (N = 26 participants representing 15 organizations). RESULTS: Residents were engaged throughout campaign development and the resulting campaign materials, including the campaign name and visual aesthetic (logo, color schemes, overall look and feel) reflect the diversity of the community and were accepted and valued by diverse groups in the community. Campaign materials featuring photos of county residents were created in English, Spanish, and Hmong. Plain language messages on social determinants of health resonate with residents. The county was described as a sort of idyllic environment burdened by inequality and structural challenges. Residents demonstrated enthusiasm for the campaign and provided specific suggestions for content (education about disease risks, prevention, management; information about accessing resources; testimonials from similar people) and tone. CONCLUSIONS: Communication to support a policy, systems, and environmental change approach to chronic disease prevention must carefully match messages with appropriate audiences. We discuss challenges in such messaging and effectiveness across multiple, diverse audiences.

Person-first language in diabetes and obesity scientific publications.

AIMS: We aimed to quantify the use of person-first language (PFL) among scholarly articles focusing on diabetes or obesity. METHODS: PFL and condition-first language (CFL) terms for diabetes and obesity (e.g. diabetic, obese) were identified from existing guidelines and a review of the literature. Exact phrase literature searches were conducted between 2011 and 2020 and results were categorised as PFL, CFL or both. RESULTS: Among diabetes articles, 43% used PFL, 40% used CFL and 17% contained both. Among obesity articles, 0.5% used PFL, 99% used CFL and 0.2% used both. The use of PFL increased by 3% per year for diabetes articles, compared to 117% for obesity articles. The rate of adoption of PFL in diabetes articles was unchanged in 2018-2020 compared to the 3 years prior. CONCLUSIONS: While the use of person-first language in diabetes articles had increased over the review period, its rate of adoption has started to slow. Conversely, the use of PFL in obesity articles is nascent and increasing.

Accidental and Abusive Mandible Fractures in Infants and Toddlers.

OBJECTIVE: Mandible fractures are uncommon injuries in infants and young children and may raise concern for nonaccidental trauma. Our study describes several children with mandible fractures to identify features that might differentiate abuse from accident. METHODS: Records and imaging were reviewed for children aged 24 months and younger who were diagnosed with mandible fractures at 2 tertiary pediatric care centers. Twenty-one cases were included, 8 of whom had formal child abuse consultations. Cases were reviewed for mechanisms of injury, physical examination findings, and occult injuries identified, as well as the final abuse determination. RESULTS: Among children with child abuse consultations, 5 injuries (62.5%) were determined to be accidental, 1 (12.5%) was abusive, and 2 were indeterminate for abuse or accident (25%). In each accidentally injured child, the reported mechanism of injury was a short fall with evidence of facial impact. No accidentally injured child had unexpected occult injuries or noncraniofacial cutaneous injuries. CONCLUSIONS: Infants and young children can sometimes sustain mandible fractures accidentally after well-described short falls with evidence of facial impact. Abuse remains in the differential diagnosis, and children should be evaluated accordingly. We propose that accidental injury be considered when a well-evaluated child with an isolated mandible fracture has a history of a short fall.

Traboulsi syndrome caused by mutations in ASPH: An autosomal recessive disorder with overlapping features of Marfan syndrome.

Traboulsi syndrome, otherwise known as facial dysmorphism, lens dislocation, anterior-segment abnormalities and spontaneous filtering blebs, is an autosomal recessive condition associated with characteristic ocular features including dislocated crystalline lenses, anterior segment abnormalities and in some individuals, non-traumatic conjunctival cysts. There is a distinctive facial appearance which includes flattened malar region with convex nasal ridge. Alterations in the aspartate beta-hydroxylase (ASPH) gene are known to be the cause of the condition. We report seven further individuals from six unrelated families with characteristic ocular and facial features. Five individuals had aortic root dilatation, with childhood onset in some, and one undergoing aortic root repair aged 47 years for severe aortic regurgitation and aortic root dilatation. Interestingly, inguinal hernias were commonly reported. Although some skeletal features were seen, these were not consistent. One of the patients had mild deficiency of factor VII on clotting studies. The ASPH protein hydroxylates specific asparagine- and aspartate-residues in epidermal growth factor (EGF)-domain containing proteins including coagulation factors and associated genes including FBN1. We propose this as an explanation for the overlap in clinical features with Marfan syndrome and conclude that Traboulsi syndrome is an important differential diagnosis. We strongly recommend echocardiography surveillance for patients with Traboulsi syndrome.

The overlap of medical child abuse and central sensitization in adolescents: An exploratory qualitative study.

BACKGROUND: Both medical child abuse (MCA) and central sensitization (CS) may present in adolescents with chronic pain, disability, high healthcare utilization, and unremarkable medical evaluations. OBJECTIVE: This study aimed to identify themes in the clinical narratives of adolescents with chronic pain that may help differentiate MCA from CS. PARTICIPANTS AND SETTING: Participants were 28 adolescents (ages 13-18 years) with chronic pain referred to either the Child Abuse Pediatrics team or the Pediatric Pain Medicine team at a tertiary children's hospital between 2011 and 2019, and diagnosed with MCA or CS, respectively. METHODS: This was a qualitative, retrospective study. Qualitative themes were derived through a process of inductive content analysis utilizing open coding, grouping, and secondary review by an interdisciplinary panel of experts. The relative prevalence of each code, theme, and overarching category was examined between groups to identify areas of convergence and divergence. RESULTS: Several themes appeared to be more prevalent in the MCA group (n = 9) compared to the CS group (n = 19). These included sick identity, homeschooling, caregiver with mental health disorder, maternal catastrophizing, maternal misrepresentation, persistence in healthcare-seeking, mandated reports made, medical neglect, and unnecessary and harmful medical care. CONCLUSIONS: This exploratory work identified themes from the clinical narratives of adolescents with chronic pain that may help differentiate MCA from CS. A visual reference, two illness scripts, and management recommendations are presented to aid pediatric providers in facilitating appropriate referrals for adolescents with chronic pain and disability out of proportion to diagnostic workup.

Altered subgenomic RNA abundance provides unique insight into SARS-CoV-2 B.1.1.7/Alpha variant infections.

B.1.1.7 lineage SARS-CoV-2 is more transmissible, leads to greater clinical severity, and results in modest reductions in antibody neutralization. Subgenomic RNA (sgRNA) is produced by discontinuous transcription of the SARS-CoV-2 genome. Applying our tool (periscope) to ARTIC Network Oxford Nanopore Technologies genomic sequencing data from 4400 SARS-CoV-2 positive clinical samples, we show that normalised sgRNA is significantly increased in B.1.1.7 (alpha) infections (n = 879). This increase is seen over the previous dominant lineage in the UK, B.1.177 (n = 943), which is independent of genomic reads, E cycle threshold and days since symptom onset at sampling. A noncanonical sgRNA which could represent ORF9b is found in 98.4% of B.1.1.7 SARS-CoV-2 infections compared with only 13.8% of other lineages, with a 16-fold increase in median sgRNA abundance. We demonstrate that ORF9b protein levels are increased 6-fold in B.1.1.7 compared to a B lineage virus in vitro. We hypothesise that increased ORF9b in B.1.1.7 is a direct consequence of a triple nucleotide mutation in nucleocapsid (28280:GAT > CAT, D3L) creating a transcription regulatory-like sequence complementary to a region 3' of the genomic leader. These findings provide a unique insight into the biology of B.1.1.7 and support monitoring of sgRNA profiles to evaluate emerging potential variants of concern.

Clinical utility of vinblastine therapeutic drug monitoring for the treatment of infantile myofibroma patients: A case series.

Infantile myofibroma is a rare, benign tumour of infancy typically managed surgically. In a minority of cases, more aggressive disease is seen and chemotherapy with vinblastine and methotrexate may be used, although evidence for this is limited. Chemotherapy dosing in infants is challenging, and vinblastine disposition in infants is unknown. We describe the use of vinblastine therapeutic drug monitoring in four cases of infantile myofibroma. Marked inter- and intrapatient variability was observed, highlighting the poorly understood pharmacokinetics of vinblastine in children, the challenges inherent in treating neonates, and the role of adaptive dosing in optimising drug exposure in challenging situations.

Characterising within-hospitalSARS-CoV-2 transmission events using epidemiological and viral genomic data across two pandemic waves.

Hospital outbreaks of COVID19 result in considerable mortality and disruption to healthcare services and yet little is known about transmission within this setting. We characterise within hospital transmission by combining viral genomic and epidemiological data using Bayesian modelling amongst 2181 patients and healthcare workers from a large UK NHS Trust. Transmission events were compared between Wave 1 (1st March to 25th J'uly 2020) and Wave 2 (30th November 2020 to 24th January 2021). We show that staff-to-staff transmissions reduced from 31.6% to 12.9% of all infections. Patient-to-patient transmissions increased from 27.1% to 52.1%. 40%-50% of hospital-onset patient cases resulted in onward transmission compared to 4% of community-acquired cases. Control measures introduced during the pandemic likely reduced transmissions between healthcare workers but were insufficient to prevent increasing numbers of patient-to-patient transmissions. As hospital-acquired cases drive most onward transmission, earlier identification of nosocomial cases will be required to break hospital transmission chains.

Child Abuse Pediatricians Assess a Low Likelihood of Abuse in Half of 2890 Physical Abuse Consults.

The aim of this study was to examine the frequency with which child abuse pediatricians (CAPs) assess consultations as low versus high likelihood of abuse. In this retrospective secondary analysis of data from the Examining Siblings to Recognize Abuse (ExSTRA) study, the likelihood of abuse score for 2890 consultations at 20 medical centers was collected. Descriptive statistics were used to examine the percentage of cases representing low versus high likelihood of abuse (i.e., score of 1-4 vs. 5-7 on a 7-point scale). Linear and logistic regression analyses were used to examine score variability between medical centers. Overall, fifty-three percent of cases were assessed as low likelihood of abuse, suggesting that CAPs were equally as likely to assess a high versus low likelihood of abuse. The percentage of cases representing low likelihood of abuse differed significantly (P < .001) between medical centers after controlling for patient age, sex, race/ethnicity, twin/triplet status, injury types, and injury severity. The variability between CAP assessments at different medical centers is discussed, along with potential contributors to this variability and directions for future work.

Parental neurotic excoriation injury of children: A case series of hidden physical abuse.

BACKGROUND: Recognizable skin findings of child physical abuse include bruises, abrasions, lacerations, bite marks, burns, and oral injuries. Self-induced skin picking, or neurotic excoriation, can correspond to emotional stress, underlying psychiatric illness, or substance abuse. Parental neurotic excoriation injury of children has not been reported previously as a form of physical abuse. METHODS: We present a case series of five children abused via parental excoriation. All affected children were three years of age or younger and otherwise healthy. Each child presented with wounds determined to be consistent with chronic picking. Patient age, injury location, and in some cases, witness accounts confirmed the lesions were not self-inflicted. RESULTS: In three cases, caregivers reported methamphetamine use. In these cases, caregivers repeatedly picked or wiped the infants' skin. In two cases, the caregiver demonstrated personal neurotic excoriation behavior, which was imposed upon her children resulting in similar lesions. One affected child died at 14 days of age from abusive head trauma, while the other four children were placed in foster care by Child Protective Services. CONCLUSION: Excoriation injury places children at risk for significant scarring and other long-term effects. We report examples demonstrating that repetitive skin injury by caregivers is a diagnostic consideration for abuse in young children.

Palm Bruising in Infants: A Recognizable Pattern of Abuse.

BACKGROUND: Bruising in an infant is an important sentinel injury that should raise concern for child physical abuse, and should prompt a medical evaluation for occult injury. Hyperflexion during forceful squeezing of an infant's hand results in a distinct pattern of bruising along the palmar and interdigital creases, as well as the palmar eminences. Self-inflicted injury by the infant or injury resulting from benign handling should not be accepted as plausible explanations for this injury. The presence of concurrent occult injuries is common, and further supports concerns for abuse. However, when this distinct pattern of palm bruising is identified in an infant, the absence of occult injuries should not prevent the recognition of child physical abuse. CASE REPORT: We report 11 cases depicting this distinct pattern of palm bruising in infants. Additionally, we include a perpetrator's documented confession. To the best of our knowledge, this pattern of bruising has not been previously described in the medical literature. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Emergency physicians play a crucial role in recognizing and addressing child physical abuse. Prompt recognition of this finding can aid in the identification of child physical abuse, even in the absence of underlying occult injury. This, in turn, can potentially prevent further injury, and even death, of an infant.