Epidemiology and Management of Pediatric Group A Streptococcal Pneumonia With Parapneumonic Effusion: An Observational Study.

BACKGROUND: During autumn/winter 2022, UK pediatricians reported an unseasonal increase in invasive group A streptococcal infections; a striking proportion presenting with pneumonia with parapneumonic effusion. METHODS: Clinicians across the United Kingdom were requested to submit pseudonymized clinical data using a standardized report form for children (<16 years) admitted between September 30, 2022 and February 17, 2023, with microbiologically confirmed group A streptococcal pneumonia with parapneumonic effusion. RESULTS: From 185 cases submitted, the median patient age was 4.4 years, and 163 (88.1%) were previously healthy. Respiratory viral coinfection was detected on admission for 101/153 (66.0%) children using extended respiratory pathogen polymerase chain reaction panel. Molecular testing was the primary method of detecting group A streptococcus on pleural fluid (86/171; 50.3% samples). Primary surgical management was undertaken in 171 (92.4%) children; 153/171 (89.4%) had pleural drain inserted (96 with fibrinolytic agent), 14/171 (8.2%) had video-assisted thoracoscopic surgery. Fever duration after admission was prolonged (median, 12 days; interquartile range, 9-16). Intravenous antibiotic courses varied in length (median, 14 days; interquartile range, 12-21), with many children receiving multiple broad-spectrum antibiotics, although evidence for additional bacterial infection was limited. CONCLUSIONS: Most cases occurred with viral coinfection, a previously well-recognized risk with influenza and varicella zoster, highlighting the need to ensure routine vaccination coverage and progress on vaccines for other common viruses (eg, respiratory syncytial virus, human metapneumovirus) and for group A streptococcus. Molecular testing is valuable to detect viral coinfection and confirm invasive group A streptococcal diagnosis, expediting the incorporation of cases into national reporting systems. Range and duration of intravenous antibiotics administered demonstrated the need for research on the optimal duration of antimicrobials and improved stewardship.

Enhancing current guidance for psoriatic arthritis and its comorbidities: recommendations from an expert consensus panel.

OBJECTIVES: Existing guidelines for psoriatic arthritis (PsA) cover many aspects of management. Some gaps remain relating to routine practice application. An expert group aimed to enhance current guidance and develop recommendations for clinical practice that are complementary to existing guidelines. METHODS: A steering committee comprising experienced, research-active clinicians in rheumatology, dermatology and primary care agreed on themes and relevant questions. A targeted literature review of PubMed and Embase following a PICO framework was conducted. At a second meeting, recommendations were drafted and subsequently an extended faculty comprising rheumatologists, dermatologists, primary care clinicians, specialist nurses, allied health professionals, non-clinical academic participants and members of the Brit-PACT patient group, was recruited. Consensus was achieved via an online voting platform when 75% of respondents agreed in the range of 7-9 on a 9-point scale. RESULTS: The guidance comprised 34 statements covering four PsA themes. Diagnosis focused on strategies to identify PsA early and refer appropriately, assessment of diagnostic indicators, use of screening tools and use of imaging. Disease assessment centred on holistic consideration of disease activity, physical functioning and impact from a patient perspective, and on how to implement shared decision-making. For comorbidities, recommendations included specific guidance for high-impact conditions such as depression and obesity. Management statements (which excluded extant guidance on pharmacological therapies) covered multidisciplinary team working, implementation of lifestyle modifications and treat-to-target strategies. Minimising corticosteroid use was recommended where feasible. CONCLUSION: The consensus group have made evidence-based best practice recommendations for the management of PsA to enhance the existing guidelines.

Receipt of high-frequency ventilation is associated with acute kidney injury in very preterm neonates.

BACKGROUND: High-frequency ventilation (HFV) is frequently used in critically ill preterm neonates. We aimed to determine the incidence of acute kidney injury (AKI) in neonates less than 29 weeks gestation who received HFV in the first week of life and to determine if the rates of AKI differed in those who received other forms of respiratory support. METHODS: This retrospective cohort study of 24 international, level III/IV neonatal intensive care units (NICUs) included neonates less than 29 weeks gestation from the AWAKEN study database. Exclusion criteria included the following: no intravenous fluids ≥ 48 h, admission ≥ 14 days of life, congenital heart disease requiring surgical repair at < 7 days of life, lethal chromosomal anomaly, death within 48 h, severe congenital kidney abnormalities, inability to determine AKI status, insufficient data on ventilation, and when the diagnosis of early AKI was unable to be made. Subjects were grouped into three groups based on ventilation modes (CPAP/no ventilation, conventional ventilation, and HFV). RESULTS: The incidence of AKI was highest in the CPAP/no ventilation group, followed by HFV, followed by conventional ventilation (CPAP/no ventilation 48.5% vs. HFV 42.6% vs. conventional ventilation 28.4% (p = 0.009). An increased risk for AKI was found for those on HFV compared to CPAP/no ventilation (HR = 2.65; 95% CI:1.22-5.73). CONCLUSIONS: HFV is associated with AKI in the first week of life. Neonates on HFV should be screened for AKI. The reasons for this association are not clear. Further studies should evaluate the relationship between ventilator strategies and AKI in premature neonates. A higher resolution version of the Graphical abstract is available as Supplementary information.

Prevalence & Risk Factors for Perinatal Stroke: A Population-Based Study.

Objectives: The study objective was to calculate the birth prevalence of perinatal stroke and examine risk factors in term infants. Some risk factors are present in healthy infants, making it difficult to determine at-risk infants. Study Design: Prospective population-based perinatal stroke data were compared to the Australian general population data using chi-squared and Fisher's exact tests and multivariable logistic regression analysis. Results: Sixty perinatal stroke cases were reported between 2017 and 2019. Estimated stroke prevalence was 9.6/100,000 live births/year including 5.8 for neonatal arterial ischemic stroke and 2.9 for neonatal hemorrhagic stroke. Eighty seven percent had multiple risk factors. Significant risk factors were cesarean section (p = 0.04), 5-min Apgar score <7 (p < 0.01), neonatal resuscitation (p < 0.01) and nulliparity (p < 0.01). Conclusions: Statistically significant independent risk factors do not fully explain the cause of perinatal stroke, because they are not a direct causal pathway to stroke. These data now require validation in a case-control study.

Distinction and prognosis of early arthritis phenotypes: an analysis in three European cohorts.

OBJECTIVES: The objective of this study is to evaluate whether there are differences in the long-term prognosis across various phenotypes of early arthritis (EA). METHODS: Three EA cohorts (Reade, Etude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) and Early Arthritis Clinic (EAC)) were analysed. Clinical data were collected up to 24 years. Hands and feet radiographs were scored according to the Sharp van der Heijde (SvdH) method. Latent class analysis was applied to determine the EA phenotypes at baseline. Each class received a label reflecting its most prominent features. Prognostic outcomes included Health Assessment Questionnaire (HAQ), Short Form 36 (SF36) and SvdH score. The association between class membership and outcomes over time was tested in multivariable models. RESULTS: In total, 390 (Reade), 798 (ESPOIR) and 3991 (EAC) patients were analysed separately. Two classes with symmetrical polyarthritis emerged; one of these labelled as autoimmune inflammatory polyarthritis (AIPA), had high likelihood of acute phase reactants (APR) elevation and autoantibody positivity, while the other (mild-inflammatory polyarthritis; MIPA) had not. A third class had oligoarthritis of upper limbs (OAUL) and could be subdivided into autoimmune OAUL and mild-inflammatory OAUL. A fifth class had oligoarthritis of lower limbs. The SvdH scores were worse in patients with APR/autoantibodies (AIPA) than in those without (MIPA). No clinically meaningful differences across classes in HAQ or SF36 over time were found. CONCLUSION: Radiographic progression over time primarily occurs in EA patients with APR/autoantibodies. The absence of these markers, however, does not necessarily translate into better long-term function and quality of life. Clinicians should not only aim at preventing joint damage, but look beyond structural progression in order to further improve the lives of people with EA.

Using Serum Cystatin C to Predict Acute Kidney Injury Following Infant Cardiac Surgery.

Acute kidney injury (AKI) following cardiopulmonary bypass (CPB) is associated with increased morbidity and mortality. Serum Cystatin C (CysC) is a novel biomarker synthesized by all nucleated cells that may act as an early indicator of AKI following infant CPB. Prospective observational study of infants (< 1 year) requiring CPB during cardiac surgery. CysC was measured at baseline and 12, 24, 48, and 72 h following CPB initiation. Each post-op percent difference in CysC (e.g. %CysC12h) from baseline was calculated. Clinical variables along with urine output (UOP) and serum creatinine (SCr) were followed. Subjects were divided into two groups: AKI and non-AKI based upon the Kidney Disease Improving Global Outcomes (KDIGO) classification. AKI occurred in 41.9% (18) of the 43 infants enrolled. Patient demographics and baseline CysC levels were similar between groups. CysC levels were 0.97 ± 0.28 mg/L over the study period, and directly correlated with SCr (R = 0.71, p < 0.0001). Although absolute CysC levels were not significant between groups, the %CysC12h was significantly greater in the AKI group (AKI: - 16% ± 22% vs. Non-AKI - 28% ± 9% mg/L; p = 0.003). However, multivariate analysis demonstrated that a lower UOP (Odds Ratio:0.298; 95% CI 0.073, 0.850; p = 0.02) but not %CysC12h was independently associated with AKI. Despite a significant difference in the %CysC12h, only UOP was independently associated with AKI. Larger studies of a more homogenous population are needed to understand these results and to explore the variability in this biomarker seen across institutions.

Current approach and attitudes toward neonatal near-miss and perinatal audits: An exploratory international survey.

BACKGROUND: Combined with perinatal mortality review, neonatal near-miss (NNM) audit has the potential to inform strategies to better prevent adverse perinatal outcomes. Nonetheless, there is lack of standardised definitions of NNM and limited evidence of implementation of NNM audits. AIM: To describe definitions of NNM and assess current approaches and attitudes toward perinatal mortality and morbidity audit. MATERIALS AND METHODS: Online survey from December 2021 to February 2022, with a mix of Likert scales, polar, pool, multi-choice, and open-ended questions, disseminated through national and international organisations to perinatal healthcare workers from high-income countries. RESULTS: One hundred and twenty participants came from Australia (n = 86), New Zealand (n = 18), Canada (n = 7), USA (n = 4), Netherlands (n = 2), other countries (n = 3). Neonatologists (35%), midwives (21.7%), obstetricians (12.5%), neonatal nurse practitioners (11.7%) and others (23.3%) responded. Most respondents thought the main characteristics to define NNM were birth asphyxia needing therapeutic hypothermia (68.3%), unexpected resuscitation at birth (67.5%), need for intubation/chest compression/adrenaline (65.0%) and metabolic acidosis at birth (60.0%). There were 97.5% of participants who considered NNM important for identifying cases for perinatal morbidity audits. However, only 10.0% of their institutions used a NNM definition. Overall, 98.4% of participants considered perinatal mortality and morbidity audits important to prevent adverse outcomes. CONCLUSION: Neonatal near-miss audit is viewed as a valuable tool to reduce adverse neonatal outcomes. There was reasonable consensus that NNM encompassed evidence of birth asphyxia and/or advanced neonatal resuscitation. Data from this international survey identifies a starting point for a consensus definition of NNM, which can be used for perinatal audits to identify opportunities for improvement.

Normative values of renin and aldosterone in clinically stable preterm neonates.

BACKGROUND: There is a paucity of literature on the normative levels of plasma renin concentration (PRC) and serum aldosterone (SA) in premature neonates. This study aims to provide normative data on PRC and SA levels in preterm neonates in the first 2 weeks after birth and explore associations with maternal, perinatal, or postnatal factors. METHODS: Neonates born at 26- to 34-week gestation were recruited from two neonatal intensive care units in Canada and Australia. The direct renin assay PRC and SA were analyzed on day 1 and days 14-21 after birth to compare across categorical variables and to produce normative values. RESULTS: A total of 262 subjects were enrolled from the Canadian (29%) and Australian (71%) sites. The mean gestational age was 30 weeks, with a mean birth weight of 1457 g. The normative values of PRC and SA for neonates born between 26 + 0 and 29 + 6 weeks and 30 + 0 and 34 + 0 weeks of gestation were produced for day 1 and day 14-21 after birth. Both PRC and SA increased from day 1 to day 14-21. The more premature neonates reached a higher PRC on days 14-21 after birth but exhibited lower SA levels on day 1 after birth. When comparing gender, birth weight, and maternal risk factor categories, no statistical differences in PRC or SA were found. A small but significant decrease in PRC, but not SA, was noted for neonates with placental pathology. CONCLUSIONS: This study produced normative values of PRA and SA in clinically stable preterm neonates that can be referenced for use in clinical practice. A higher resolution version of the Graphical abstract is available as Supplementary information.

Neonatal hypoxic ischemic encephalopathy increases acute kidney injury urinary biomarkers in a rat model.

Hypoxic ischemic encephalopathy (HIE) is associated with acute kidney injury (AKI) in neonates with birth asphyxia. This study aimed to utilize urinary biomarkers to characterize AKI in an established neonatal rat model of HIE. Day 7 Sprague-Dawley rat pups underwent HIE using the Rice-Vannucci model (unilateral carotid ligation followed by 120 mins of 8% oxygen). Controls included no surgery and sham surgery. Weights and urine for biomarkers (NGAL, osteopontin, KIM-1, albumin) were collected the day prior, daily for 3 days post-intervention, and at sacrifice day 14. Kidneys and brains were processed for histology. HIE pups displayed histological evidence of kidney injury including damage to the proximal tubules, consistent with resolving acute tubular necrosis, and had significantly elevated urinary levels of NGAL and albumin compared to sham or controls 1-day post-insult that elevated for 3 days. KIM-1 significantly increased for 2 days post-HIE. HIE did not significantly alter osteopontin levels. Seven days post-start of experiment, controls were 81.2% above starting weight compared to 52.1% in HIE pups. NGAL and albumin levels inversely correlated with body weight following HIE injury. The AKI produced by the Rice-Vannucci HIE model is detectable by urinary biomarkers, which can be used for future studies of treatments to reduce kidney injury.

Humidification Practices of Extremely Preterm Neonates: A Clinical Survey.

Extremely preterm neonates are at risk of morbidity and mortality related to their underdeveloped skin barrier. Humidified incubators are typically used in their care, but there is a paucity of literature to inform the standardization of specific evidence-based humidification practices in the NICU. A brief, voluntary, anonymous survey was distributed to our home institution and numerous national and international external institutions. Survey questions pertained to institutional humidification guidelines and were qualitatively analyzed. We received 89 responses from the home institution and 42 responses from the external institutions. Within the home institution, despite the presence of a guideline, individual practitioners reported varying practices in the starting levels of humidity and length of time spent in humidity. The results also demonstrated significant variability in individual humidification practices between the external institutions. There is no standard humidification guideline for extremely preterm neonates being cared for in the NICU. Further research is required to provide appropriate evidence on which to base clinical guidelines for the management of extremely preterm neonates to prevent morbidity and mortality in this population.

Fluid Homeostasis and Diuretic Therapy in the Neonate.

Understanding physiologic water balance and homeostasis mechanisms in the neonate is critical for clinicians in the NICU as pathologic fluid accumulation increases the risk for morbidity and mortality. In addition, once this process occurs, treatment is limited. In this review, we will cover fluid homeostasis in the neonate, explain the implications of prematurity on this process, discuss the complexity of fluid accumulation and the development of fluid overload, identify mitigation strategies, and review treatment options.

Maternal Hypertension Disorders and Neonatal Acute Kidney Injury: Results from the AWAKEN Study.

OBJECTIVE: This study aimed to examine the association between maternal hypertension (HTN) exposure and neonatal acute kidney injury (AKI). STUDY DESIGN: Retrospective cohort study of 2,162 neonates admitted to 24 neonatal intensive care units (NICUs). Neonates were classified into the following exposure groups: any maternal HTN, chronic maternal HTN, preeclampsia/eclampsia, both, or neither. Demographics, clinical characteristics, and AKI status were compared using Chi-square and analysis of variance. General estimating logistic regression was used to estimate adjusted odds ratios and included a stratified analysis for site of delivery. RESULT: Neonates exposed to any maternal HTN disorder had a tendency toward less overall and early AKI. When stratified by inborn versus outborn, exposure to both maternal HTN disorders was associated with a significantly reduced odds of early AKI only in the inborn neonates. CONCLUSION: Exposure to maternal HTN, especially preeclampsia/eclampsia superimposed on chronic HTN, was associated with less likelihood of early AKI in the inborn group. KEY POINTS: · Maternal HTN is associated with less neonatal AKI.. · Maternal HTN category is variably associated with AKI.. · Inborn status is an important contributor to this association..

EULAR points to consider for the management of difficult-to-treat rheumatoid arthritis.

OBJECTIVE: To develop evidence-based European Alliance of Associations for Rheumatology (EULAR) points to consider (PtCs) for the management of difficult-to-treat rheumatoid arthritis (D2T RA). METHODS: An EULAR Task Force was established comprising 34 individuals: 26 rheumatologists, patient partners and rheumatology experienced health professionals. Two systematic literature reviews addressed clinical questions around diagnostic challenges, and pharmacological and non-pharmacological therapeutic strategies in D2T RA. PtCs were formulated based on the identified evidence and expert opinion. Strength of recommendations (SoR, scale A-D: A typically consistent level 1 studies and D level 5 evidence or inconsistent studies) and level of agreement (LoA, scale 0-10: 0 completely disagree and 10 completely agree) of the PtCs were determined by the Task Force members. RESULTS: Two overarching principles and 11 PtCs were defined concerning diagnostic confirmation of RA, evaluation of inflammatory disease activity, pharmacological and non-pharmacological interventions, treatment adherence, functional disability, pain, fatigue, goal setting and self-efficacy and the impact of comorbidities. The SoR varied from level C to level D. The mean LoA with the overarching principles and PtCs was generally high (8.4-9.6). CONCLUSIONS: These PtCs for D2T RA can serve as a clinical roadmap to support healthcare professionals and patients to deliver holistic management and more personalised pharmacological and non-pharmacological therapeutic strategies. High-quality evidence was scarce. A research agenda was created to guide future research.

Impact of introducing a lactation consultant into a neonatal unit.

AIM: Benefits of mothers' own milk (MOM) for premature and sick neonates are well documented. To increase access, many neonatal units have a lactation consultant (LC) on staff. This study aimed to assess the impact of a permanent LC on (i) maternal access to LC support; (ii) staff confidence in providing Breast Feeding (BF) education and (iii) provision of MOM. METHODS: Study included a staff survey and chart audit. Questions provided feedback on access to lactation support and meeting maternal needs. Audit data included: gestational age, birthweight, intention to breastfeed, documentation of LC appointment, provision of MOM at 12 hours, days 3, 7, 28 and discharge. Student's t-tests were used for numerical data and chi-squared tests for categorical variables. RESULTS: Ninety-one staff surveys were returned, (pre 35/75 (47%), post 56/85 (66%) with staff reporting organising an LC appointment was significantly easier (P < 0.0001). Staff perceived maternal lactation needs and confidence to breastfeed post-discharge had significantly improved post-LC. The chart audit showed a significant increase in maternal access to LC appointments (15% vs. 80%; P < 0.01), breast pump education by day 3 (65% vs. 81%; P < 0.01), and an increase in MOM provision by 12 h (46% vs. 61%; P < 0.01) post-LC but not at days 7, 28 or discharge. CONCLUSION: A dedicated LC increases staff and maternal access to lactation education and support, improving provision of early MOM. Further research is required to assess the effect of LCs in improving breastfeeding rates in neonatal units.

EULAR points to consider for the use of imaging to guide interventional procedures in patients with rheumatic and musculoskeletal diseases (RMDs).

OBJECTIVES: To develop evidence-based Points to Consider (PtC) for the use of imaging modalities to guide interventional procedures in patients with rheumatic and musculoskeletal diseases (RMDs). METHODS: European Alliance of Associations for Rheumatology (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound (US), fluoroscopy, MRI, CT and fusion imaging to guide interventional procedures. Based on evidence and expert opinion, the task force (25 participants consisting of physicians, healthcare professionals and patients from 11 countries) developed PtC, with consensus obtained through voting. The final level of agreement was provided anonymously. RESULTS: A total of three overarching principles and six specific PtC were formulated. The task force recommends preference of imaging over palpation to guide targeted interventional procedures at peripheral joints, periarticular musculoskeletal structures, nerves and the spine. While US is the favoured imaging technique for peripheral joints and nerves, the choice of the imaging method for the spine and sacroiliac joints has to be individualised according to the target, procedure, expertise, availability and radiation exposure. All imaging guided interventions should be performed by a trained specialist using appropriate operational procedures, settings and assistance by technical personnel. CONCLUSION: These are the first EULAR PtC to provide guidance on the role of imaging to guide interventional procedures in patients with RMDs.

Advances in Neonatal Acute Kidney Injury.

In this state-of-the-art review, we highlight the major advances over the last 5 years in neonatal acute kidney injury (AKI). Large multicenter studies reveal that neonatal AKI is common and independently associated with increased morbidity and mortality. The natural course of neonatal AKI, along with the risk factors, mitigation strategies, and the role of AKI on short- and long-term outcomes, is becoming clearer. Specific progress has been made in identifying potential preventive strategies for AKI, such as the use of caffeine in premature neonates, theophylline in neonates with hypoxic-ischemic encephalopathy, and nephrotoxic medication monitoring programs. New evidence highlights the importance of the kidney in "crosstalk" between other organs and how AKI likely plays a critical role in other organ development and injury, such as intraventricular hemorrhage and lung disease. New technology has resulted in advancement in prevention and improvements in the current management in neonates with severe AKI. With specific continuous renal replacement therapy machines designed for neonates, this therapy is now available and is being used with increasing frequency in NICUs. Moving forward, biomarkers, such as urinary neutrophil gelatinase-associated lipocalin, and other new technologies, such as monitoring of renal tissue oxygenation and nephron counting, will likely play an increased role in identification of AKI and those most vulnerable for chronic kidney disease. Future research needs to be focused on determining the optimal follow-up strategy for neonates with a history of AKI to detect chronic kidney disease.

Neonatal Acute Kidney Injury: Understanding of the Impact on the Smallest Patients.

The study of neonatal acute kidney injury (AKI) has transitioned from small, single-center studies to the development of a large, multicenter cohort. The scope of research has expanded from assessment of incidence and mortality to analysis of more specific risk factors, novel urinary biomarkers, interplay between AKI and other organ systems, impact of fluid overload, and quality improvement efforts. The intensification has occurred through collaboration between the neonatology and nephrology communities. This review discusses 2 case scenarios to illustrate the clinical presentation of neonatal AKI, important risk factors, and approaches to minimize AKI events and adverse long-term outcomes.

EULAR definition of difficult-to-treat rheumatoid arthritis.

BACKGROUND: Despite treatment according to the current management recommendations, a significant proportion of patients with rheumatoid arthritis (RA) remain symptomatic. These patients can be considered to have 'difficult-to-treat RA'. However, uniform terminology and an appropriate definition are lacking. OBJECTIVE: The Task Force in charge of the "Development of EULAR recommendations for the comprehensive management of difficult-to-treat rheumatoid arthritis" aims to create recommendations for this underserved patient group. Herein, we present the definition of difficult-to-treat RA, as the first step. METHODS: The Steering Committee drafted a definition with suggested terminology based on an international survey among rheumatologists. This was discussed and amended by the Task Force, including rheumatologists, nurses, health professionals and patients, at a face-to-face meeting until sufficient agreement was reached (assessed through voting). RESULTS: The following three criteria were agreed by all Task Force members as mandatory elements of the definition of difficult-to-treat RA: (1) Treatment according to European League Against Rheumatism (EULAR) recommendation and failure of ≥2 biological disease-modifying antirheumatic drugs (DMARDs)/targeted synthetic DMARDs (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated); (2) presence of at least one of the following: at least moderate disease activity; signs and/or symptoms suggestive of active disease; inability to taper glucocorticoid treatment; rapid radiographic progression; RA symptoms that are causing a reduction in quality of life; and (3) the management of signs and/or symptoms is perceived as problematic by the rheumatologist and/or the patient. CONCLUSIONS: The proposed EULAR definition for difficult-to-treat RA can be used in clinical practice, clinical trials and can form a basis for future research.