Coronary Artery Outcomes in Kawasaki Disease by Treatment Day Within 10 Days of Fever Onset.

Background: Kawasaki disease (KD) is an acute febrile illness of childhood that can lead to coronary artery aneurysms (CAAs) and myocardial infarction. Intravenous immunoglobulin reduces the prevalence of CAA when given to patients with KD within 10 days of fever onset. Children with KD may undergo evaluation for other diagnoses before treatment, particularly those with incomplete KD criteria. If KD outcomes are improved with early treatment, a delay in treatment while evaluating for other causes might place these patients at risk. Methods: We performed a retrospective cohort study of children treated for KD within the first 10 days of illness at our KD center from 2014 to 2021 to determine the prevalence of CAA by day of treatment. Results: A total of 290 patients met the study criteria. No statistically significant difference was found in the odds of developing a maximum z score ≥2.5 for each day of delayed treatment within 10 days of fever onset (adjusted odds ratio, 0.87; 95% CI, .72-1.05; P = .13). Subgroup analyses by age, sex, and year of treatment did not reveal a significant association between treatment day and maximum z score ≥2.5, although the number of patients <6 months of age was small. Conclusions: Our study supports current recommendations. We found similar odds of developing adverse coronary outcomes regardless of treatment day within 10 days from fever onset.

Group A Streptococcus pharyngitis in Children: New Perspectives on Rapid Diagnostic Testing and Antimicrobial Stewardship.

The most common cause of bacterial pharyngitis is Group A Streptococcus (GAS). Accurate diagnosis of GAS pharyngitis is crucial to identify children who would benefit from antibiotic treatment. Rapid diagnosis has the potential to reduce antibiotic overuse. Current national guidelines differ in their recommendations for GAS testing. While rapid antigen detection tests (RADTs) are widely used, their sensitivity is considered too low for stand-alone testing by several expert bodies. Newer molecular tests using nucleic acid amplification show higher accuracy and fast results, but their cost, complexity, and very high sensitivity may limit widespread adoption. This review provides up-to-date evidence regarding rapid diagnostic testing and antimicrobial stewardship in children with sore throat. We discuss discrepancies across GAS testing guidelines at the international level, patient selection for testing for GAS, rapid test accuracy, and the potential role of rapid GAS tests to promote antibiotic stewardship, with emphasis on emerging rapid molecular tests.

Place of Death From Cancer in US States With vs Without Palliative Care Laws.

Importance: In the US, improving end-of-life care has become increasingly urgent. Some states have enacted legislation intended to facilitate palliative care delivery for seriously ill patients, but it is unknown whether these laws have any measurable consequences for patient outcomes. Objective: To determine whether US state palliative care legislation is associated with place of death from cancer. Design, Setting, and Participants: This cohort study with a difference-in-differences analysis used information about state legislation combined with death certificate data for 50 US states (from January 1, 2005, to December 31, 2017) for all decedents who had any type of cancer listed as the underlying cause of death. Data analysis for this study occurred between September 1, 2021, and August 31, 2022. Exposures: Presence of a nonprescriptive (relating to palliative and end-of-life care without prescribing particular clinician actions) or prescriptive (requiring clinicians to offer patients information about care options) palliative care law in the state-year where death occurred. Main Outcomes and Measures: Multilevel relative risk regression with state modeled as a random effect was used to estimate the likelihood of dying at home or hospice for decedents dying in state-years with a palliative care law compared with decedents dying in state-years without such laws. Results: This study included 7 547 907 individuals with cancer as the underlying cause of death. Their mean (SD) age was 71 (14) years, and 3 609 146 were women (47.8%). In terms of race and ethnicity, the majority of decedents were White (85.6%) and non-Hispanic (94.1%). During the study period, 553 state-years (85.1%) had no palliative care law, 60 state-years (9.2%) had a nonprescriptive palliative care law, and 37 state-years (5.7%) had a prescriptive palliative care law. A total of 3 780 918 individuals (50.1%) died at home or in hospice. Most decedents (70.8%) died in state-years without a palliative care law, while 15.7% died in state-years with a nonprescriptive law and 13.5% died in state-years with a prescriptive law. Compared with state-years without a palliative care law, the likelihood of dying at home or in hospice was 12% higher for decedents in state-years with a nonprescriptive palliative care law (relative risk, 1.12 [95% CI 1.08-1.16]) and 18% higher for decedents in state-years with a prescriptive palliative care law (relative risk, 1.18 [95% CI, 1.11-1.26]). Conclusions and Relevance: In this cohort study of decedents from cancer, state palliative care laws were associated with an increased likelihood of dying at home or in hospice. Passage of state palliative care legislation may be an effective policy intervention to increase the number of seriously ill patients who experience their death in such locations.

Beyond exercise. Can application of manual therapy before exercise benefit a low functioning person with limb loss? A case study.

BACKGROUND: Most people with lower-limb loss (PLL) have musculoskeletal conditions and range-of-motion and muscle performance impairments. Such impairments limit potential for functional movement but can be reduced with manual therapy. Manual therapy, however, is rarely used for PLL. This case demonstrated how integrating manual therapy, exercise, and functional training led to lasting benefits for one low functioning PLL. CASE DESCRIPTION: A 54-year-old woman more than 1 year after transtibial amputation due to peripheral artery disease presented with multiple comorbidities and yellow flags. Her function remained limited to the Medicare K-1 household walking level with slow gait speed <0.25 m/s. Treatment included four weekly sessions each beginning with manual therapy, followed by exercise and functional training. OUTCOMES: After 1 month, performance-based strength, balance, walking speed, and physical activity increased. She advanced to the K-2 limited community walking level and maintained her functional level without further treatment after 3 months. DISCUSSION: Improvements maintained without treatment expanded upon research that lacked follow-up and excluded K-1 level walkers. Marked improvement after only four sessions was noteworthy since exercise protocols require ≥4 sessions. CONCLUSION: Manual therapy followed by exercise and functional training may optimize movement potential and contribute to improving strength, balance, gait, and physical activity among PLL.

Analysis of Plasmablasts From Children With Kawasaki Disease Reveals Evidence of a Convergent Antibody Response to a Specific Protein Epitope.

BACKGROUND: Kawasaki disease (KD) is a febrile illness of young childhood that can result in coronary artery aneurysms and death. Coronavirus disease 2019 (COVID-19) mitigation strategies resulted in a marked decrease in KD cases worldwide, supporting a transmissible respiratory agent as the cause. We previously reported a peptide epitope recognized by monoclonal antibodies (MAbs) derived from clonally expanded peripheral blood plasmablasts from 3 of 11 KD children, suggesting a common disease trigger in a subset of patients with KD. METHODS: We performed amino acid substitution scans to develop modified peptides with improved recognition by KD MAbs. We prepared additional MAbs from KD peripheral blood plasmablasts and assessed MAb characteristics that were associated with binding to the modified peptides. RESULTS: We report a modified peptide epitope that is recognized by 20 MAbs from 11 of 12 KD patients. These MAbs predominantly use heavy chain VH3-74; two-thirds of VH3-74 plasmablasts from these patients recognize the epitope. The MAbs were nonidentical between patients but share a common complementarity-determining region 3 (CDR3) motif. CONCLUSIONS: These results demonstrate a convergent VH3-74 plasmablast response to a specific protein antigen in children with KD, supporting one predominant causative agent in the etiopathogenesis of the illness.

Monkeypox Emergence and the Eradication of Smallpox: An Historical Review.

BACKGROUND: Human monkeypox infection was first identified in 1970 in African. Small rodents were the natural reservoir of this orthopoxvirus, with humans and primates as incidental hosts. Smallpox vaccination induces cross protection against monkeypox. In Africa monkeypox overlapped with the Global Smallpox Eradication Program (GSEP) six decades ago. The 2022 human monkeypox epidemic prompted literature review re potential impact of monkeypox upon GSEP efforts. METHODS: Literature review from 1960 to present related to GSEP launched in 1969 with particular focus on monkeypox epidemiology during planning of GSEP in the 1960's through 1989 including surveillance years later. RESULTS: Establishing the lack of a non-human reservoir of smallpox was essential to assessing the GSEP because of the similarity of the two orthopoxviruses. It was found that a non-human smallpox reservoir was highly remote. Human monkeypox did not occur in smallpox-vaccinated humans and was limited to non-vaccinees. Surveillance in Democratic Republic of the Congo (DRC) until 1989 found monkeypox was very unlikely to persist in humans and unlikely to become a major public health problem. From 2005-2007, decades after cessation of smallpox vaccination, monkeypox surveillance in DRC revealed 20-fold higher incidence of human monkeypox correlated with much lower rates of prior smallpox vaccination. CONCLUSIONS: Human monkeypox rates in DRC were 20-fold higher decades after cessation of smallpox vaccination compared to when smallpox vaccination was still used. The resultant decreased cross-protection against monkeypox contributed to the 2022 multinational outbreak of human monkeypox.

Performance of a Molecular Test for Group A Streptococcus Pharyngitis.

We performed a prospective study to determine if the pretest probability of a positive loop-mediated isothermal amplification test is greater when there are more signs and symptoms of GAS pharyngitis. Patients were enrolled if a clinician obtained a GAS RADT. The McIsaac score was calculated. The prevalence of positive LAMP and RADT results increased as the McIsaac score increased. The calculated sensitivity of LAMP was superior to RADT.

Walking asymmetry and its relation to patient-reported and performance-based outcome measures in individuals with unilateral lower limb loss.

Gait asymmetry persists for most people after lower limb amputation and is associated with slower walking speeds. However, the relationship between gait asymmetry and patient-reported function remains unclear because they are not commonly assessed together. The purpose of this study was to determine relationships between gait asymmetries in people with lower limb loss and (1) patient-reported outcomes and (2) performance-based prosthetic functional measures. This cross-sectional analysis included nine people with unilateral limb loss aged 48.2 ± 13.1 years of mixed amputation etiology. Patient-reported outcomes included the Prosthetic Evaluation Questionnaire mobility subscale and Activities-specific Balance Confidence scale. Performance outcomes included the Berg Balance Scale and the 30-second sit-to-stand test. Walking performance measures included the 2-Minute Walk Test, during which APDM Opal sensors recorded spatiotemporal gait parameters, and daily step-counts from StepWatch4 activity monitors. The study found that the most asymmetric gait symmetry ratios (prosthetic-limb divided by intact-limb) could be attributed to prosthetic foot dorsiflexion-plantarflexion and rotation motion limitations: prosthetic-limb trailing double support (0.789 ± 0.052), toe-off (0.760 ± 0.068) and toe-out angle (0.653 ± 0.256). Single limb stance, and stance and swing phase durations were most strongly associated with balance and walking performance measures. Notably, no symmetry ratio was significantly associated with patient-reported prosthetic function (unadjusted Pearson correlation coefficients r < 0.50, P > 0.05). More gait symmetry was associated with better balance and walking performance but had no significant relationship with patient-reported function. Although achieving gait symmetry after lower limb loss is a common walking goal, symmetry was unrelated to the perception of functional mobility for people with lower limb loss.

Preliminary analysis of reliability and validity of the Life Space Questionnaire as a real-world mobility measure for people with lower limb loss: A technical note.

People with lower-limb loss (PLL) often have reduced mobility that translates into limited community access. The Life Space Questionnaire (LSQ) measures a person's real-world mobility within their home environment and community but has not been used among PLL. This study assessed preliminary LSQ test-retest reliability and discriminant validity from subjective and objective balance and walking measures in PLL. In addition, LSQ was hypothesized to have an inverse association with overall health status. Nine subjects were analyzed with mean age 48.2 ± 13.1 years and 4.8 ± 3.9 years' time since amputation. Six had transtibial and three had transfemoral amputations due to diabetes (4), vascular disease (3), and trauma (2). The primary outcome was the LSQ, a 9-level scale quantifying the extent to which people accessed their life space including home, yard, and community. Test-retest reliability for the LSQ was moderate (intraclass coefficient = 0.61 with 90% confidence interval: 0.19-0.87). Discriminant validity from balance and walking function was demonstrated by lack of correlation between LSQ score and the Activities-specific Balance Confidence and Berg Balance Scale and the Prosthetic Evaluation Questionnaire mobility subscale and walking speed (r < 0.50, P > .05). LSQ correlated with health status assessed with the Charlson Comorbidity Index (r = -0.84, P = .005). In this sample of PLL, the LSQ demonstrated moderate test-retest reliability as a measure of real-world mobility distinct as a construct from subjective and objective balance or walking measures. People may access their communities using various levels of assistance and methods of transportation. For this sample of PLL, health status was most strongly associated with LSQ score.

Standardization of Epidemiological Surveillance of Group A Streptococcal Pharyngitis.

Pharyngitis, more commonly known as sore throat, is caused by viral and/or bacterial infections. Group A Streptococcus (Strep A) is the most common bacterial cause of pharyngitis. Strep A pharyngitis is an acute, self-limiting disease but if undertreated can lead to suppurative complications, nonsuppurative poststreptococcal immune-mediated diseases, and toxigenic presentations. We present a standardized surveillance protocol, including case definitions for pharyngitis and Strep A pharyngitis, as well as case classifications that can be used to differentiate between suspected, probable, and confirmed cases. We discuss the current tests used to detect Strep A among persons with pharyngitis, including throat culture and point-of-care tests. The type of surveillance methodology depends on the resources available and the objectives of surveillance. Active surveillance and laboratory confirmation is the preferred method for case detection. Participant eligibility, the surveillance population and additional considerations for surveillance of pharyngitis are addressed, including baseline sampling, community engagement, frequency of screening and season. Finally, we discuss the core elements of case report forms for pharyngitis and provide guidance for the recording of severity and pain associated with the course of an episode.

Utilisation of disease modifying treatment and diversity of treatment pathways in relapsing remitting multiple sclerosis.

BACKGROUND: There is minimal information on the utilisation of Disease Modifying Treatment (DMTs) for multiple sclerosis. The appropriate and safe use of medicines is informed by utilisation studies. Outcomes can inform health interventions to improve appropriate use of medicines and post marketing surveillance activities to improve safety. OBJECTIVE: To evaluate utilisation and treatment patterns of disease modifying treatments (DMTs) for relapsing remitting multiple sclerosis (RRMS). METHODS: A representative sample of the Australian pharmaceutical benefits scheme data were analysed (2006-2016). Demographics of incident users and trends in incident and prevalent users were determined. Individual patient treatment pathways were determined by sequential initiation of medicines in two different periods (2006-2013 and 2014-2019). RESULTS: There were 20,660 patients with at least one dispensing of a DMT for RRMS during the study period (median age 41 years, 75% female). Incident and prevalent use increased by 20% and 88%, respectively. The market was responsive to 13 new listings of DMTs over the study period. Sequential treatment was found for 66% of initiators in 2006-2013 and 28.5% of initiators in 2014-2019. Diverse treatment pathways were found, with 278 and 93 unique sequences in 2006-2013 and 2014-2019, respectively. CONCLUSION: The availability of new DMTs has influenced both initial treatment choice and prevalence of users. Individualised treatment patterns and exposure to multiple medicines over time will challenge traditional pharmacovigilance systems.

Congenital and Perinatal Tuberculosis.

This review discusses the recent literature (2006-2020) about the epidemiology, clinical presentation, diagnosis, and management of infants with congenital or perinatal tuberculosis (TB). While the incidence of childhood TB is declining in the United States and worldwide, many case reports describe how clinical suspicion for neonatal TB is raised only if an ill-appearing neonate does not improve with broad-spectrum antibiotics. Furthermore, the delay in initiating appropriate anti-TB therapy often results in the need for significant cardiopulmonary support and/or an increase in mortality. This review summarizes important clinical indications in the maternal and newborn history, the evaluation of an infant with possible TB exposure, and step-by-step recommendations for the treatment and follow-up of infants with TB.

Quantifying the risk of falls and injuries for amputees beyond annual fall rates-A longitudinal cohort analysis based on person-step exposure over time.

People with lower-limb loss (PLL) have high annual fall and injury rates. People with transtibial amputations have better walking function than those with transfemoral amputations but paradoxically incur more fall-related injuries. Risk exposure, however, has not been previously considered. This study examined whether all-cause fall and injury incidence per person-step exposure over time varied in PLL of different walking abilities. The prospective cohort design, conducted at a major medical center, included five assessments 1-month apart. Walking ability level was categorized by Houghton Scale scores: ≥9 indicating community walking and ≤ 8 indicating limited community-household walking. Accelerometer-measured daily step counts were collected via StepWatch4 monitors. The main outcome measures, self-reported all-cause falls and injuries were assessed using the standard National Health Injury Survey. Generalized estimating equations, using Poisson distributions and log of step count as an offset, determined fall and injury incidence rate ratio [IRR] according to walking ability level. Ten people, aged 33-63 years with amputations of different causes and levels, were assessed monthly over five months. The community walking group (n = 6) had six falls and seven injuries; the limited community walking group (n = 4) had four falls and three injuries. For PLL, limited community walking ability was associated with higher incidence of falls (IRR = 6.10, 95%CI = 1.12-33.33, p = 0.037) and injuries (IRR = 8.56, 95%CI = 1.73-42.40, p = 0.009) when accounting for person-steps. Considering per person-step exposure over time added precision to fall and injury risk assessment that clarified the risks: PLL with limited community walking ability have higher fall and injury risks.