Search

Because of the broad clinical spectrum, heritable autoinflammatory diseases present a management and therapeutic challenge. The most common genetic interferonopathy, Aicardi Goutières Syndrome (AGS), is associated with early onset neurologic disability and systemic inflammation. The chronic inflammation of AGS is the result of dysregulation of interferon (IFN) expression by one of nine genes within converging pathways. While each AGS subtype shares common features, distinct patterns of severity and potential for systemic complications amongst the genotypes are emerging. Multilineage cytopenias are a potentially serious, but poorly understood, complication of AGS. As immunomodulatory treatment options are developed, it is important to characterize the role of the disease versus treatment in hematologic abnormalities. This will allow for better understanding and management of cytopenia.In total, 142 individuals with molecularly-confirmed AGS were included. Information on genotype, demographics, and all available hematologic laboratory values were collected from existing medical records. As part of a clinical trial, a subset of this cohort (n = 52) were treated with a janus kinase inhibitor (baricitinib), and both pre- and post-treatment values were included. Abnormal values were graded based on Common Terminology Criteria for Adverse Events (CTCAE v5.0), supplemented with grading definitions for thrombocytosis, and were compared across genotypes and baricitinib exposure.In total, 11,184 laboratory values were collected over a median of 2.54 years per subject (range 0-22.68 years). To reduce bias from repeated sampling within a limited timeframe, laboratory results were restricted to the most abnormal value within a month (n = 8485). The most common abnormalities were anemia (noted in 24% of subjects prior to baricitinib exposure), thrombocytopenia (9%), and neutropenia (30%). Neutropenia was most common in the SAMHD1 cohort and increased with baricitinib exposure (38/69 measurements on baricitinib versus 14/121 while not on baricitinib). Having an abnormality prior to treatment was associated with having an abnormality on treatment for neutropenia and thrombocytopenia.By collecting available laboratory data throughout the lifespan, we were able to identify novel patterns of hematologic abnormalities in AGS. We found that AGS results in multilineage cytopenias not limited to the neonatal period. Neutropenia, anemia, and thrombocytopenia were common. Moderate-severe graded events of neutropenia, anemia, and leukopenia were more common on baricitinib, but rarely of clinical consequence. Based on these results, we would recommend careful monitoring of hematologic parameters of children affected by AGS throughout the lifespan, especially while on therapy, and consideration of AGS as a potential differential diagnosis in children with neurologic impairment of unclear etiology with hematologic abnormalities. Trial registration ClinicalTrials.gov Identifier: NCT01724580 ClinicalTrials.gov Identifier: NCT03921554.

To assess the postoperative timeline for the return to activities of daily living (ADLs) in pediatric patients after arthroscopic drilling of a stable osteochondritis dissecans (OCD) lesion of the knee and to determine the rate of and risk factors for complications after the procedure.In a retrospective chart review, data from all patients aged 18 years or younger who underwent arthroscopic drilling for a stable OCD lesion of either femoral condyle from May 2009 through July 2017 were collected. Demographic data, lesion characteristics, operative data, postoperative course, radiographic outcomes, and complications were recorded. Statistical analysis was performed to determine the risk factors for reoperations.A total of 139 knees in 131 patients were evaluated, with a mean age of 12.7 years, of which 102 (73%) were male knees. The average follow-up period was 17.8 ± 13.2 months after surgery. All patients regained full extension and flexion within 5° of the contralateral knee at a mean of 12.9 ± 3.2 weeks postoperatively, with 95% having returned fully to ADLs by the 3-month postoperative visit. No cases of infection, stiffness, arthrofibrosis, or other procedure-related complications were recorded. A total of 133 knees (95.7%) showed healing on radiographs, whereas 6 knees (4.3%) underwent additional surgical procedures, all of which were performed for treatment failure related to nonhealing lesions (including loose body removal, chondroplasty, and repeated drilling). Lesion size was the only significant risk factor for reoperation (Our findings suggest that arthroscopic drilling for stable, intact OCD lesions in the pediatric knee is a safe procedure with reliable outcomes and return to ADLs and a minimal risk of complications. Most patients return to their preoperative daily activity level with a full range of motion of the knee by 3 months after surgery. Complications, including reoperations, are related to the progression of the OCD lesion rather than to the surgical procedure. Each 1-cmLevel IV, therapeutic case series.

Neuropsychiatric manifestations of Huntington's disease (HD) can present years before motor symptoms. Nurses with specialized training provide superior care for HD patients, but HD exposure in nursing education is limited. Here we aimed to describe the historical neuropsychiatric burden in 50 HD patients and discuss implications for psychiatric nurses. Fifty patients with HD were assessed by a board-certified psychiatrist and completed surveys about symptoms, social history, medication use, and quality of life outcomes. Descriptive statistics were used to summarize patient characteristics, and correlation analyses assessed the relationships between neuropsychiatric symptoms and quality of life outcomes. Most patients (72%) reported a history of neuropsychiatric symptoms prior to their HD diagnosis. Prodromal anger/irritability was most common (52%), though few patients received treatment for this. Anxiety was the most common current symptom (78%), yet 40% of patients had never been prescribed an SSRI. Anxiety was associated with poorer patient-reported quality of life outcomes (p < .01). HD patients in this sample experienced frequent, early-onset neuropsychiatric symptoms. In coming years, psychiatric nurses in community settings will be more likely to encounter gene-positive HD patients before they develop motor symptoms. Psychiatric nurses can address identified gaps through enhanced screening and encouraging early intervention in those at risk.

Tourette syndrome (TS) is a neurodevelopmental disorder defined by tics, but most patients also experience bothersome sensory phenomena, in the form of premonitory urges and/or sensory hypersensitivity. Whereas premonitory urges are temporally paired with tics, sensory hypersensitivity is a constant, heightened awareness of external and/or internal stimuli. The intensity of sensory hypersensitivity does not strongly correlate with the severity of tics or premonitory urges, suggesting it is a dissociable clinical phenomenon. At least 80% of TS patients report subjectively enhanced perception of various sensory stimuli. These same patients demonstrate normal static detection thresholds. However, individuals with TS habituate abnormally to repetitive stimuli, indicating incapacity to appropriately filter redundant sensory input, i.e. impaired sensory gating. Physiologic support for this hypothesis is provided by abnormal pre-pulse inhibition (PPI) and event-related potential (ERP) investigations. Preclinical data implicates parvalbumin-positive (PV+) interneuron dysfunction in altered sensory gating in TS and other neurodevelopment disorders. Studies probing TS sensory hypersensitivity must methodically account for comorbid psychiatric conditions, namely obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD), as these entities appear to involve pathophysiologic processes shared with TS. The presence of psychiatric comorbidities in TS is associated with even more profound sensory processing dysfunction. A deepened understanding of TS sensory hypersensitivity will afford novel insights into disease mechanisms, clinical phenotype, and therapeutic management.

Summary Background Very low birthweight or preterm infants are at increased risk of adverse outcomes including sepsis, necrotising enterocolitis, and death. We assessed whether supplementing the enteral diet of very low-birthweight infants with lactoferrin, an antimicrobial protein, reduces all-cause mortality or major morbidity. Methods We did a multicentre, double-blind, pragmatic, randomised superiority trial in 14 Australian and two New Zealand neonatal intensive care units. Infants born weighing less than 1500 g and aged less than 8 days, were eligible and randomly assigned (1:1) using minimising web-based randomisation to receive once daily 200 mg/kg pasteurised bovine lactoferrin supplements or no lactoferrin supplement added to breast or formula milk until 34 weeks' post-menstrual age (or for 2 weeks, if longer), or until discharge from the study hospital if that occurred first. Designated nurses preparing the daily feeds were not masked to group assignment, but other nurses, doctors, parents, caregivers, and investigators were unaware. The primary outcome was survival to hospital discharge or major morbidity (defined as brain injury, necrotising enterocolitis, late-onset sepsis at 36 weeks' post-menstrual age, or retinopathy treated before discharge) assessed in the intention-to-treat population. Safety analyses were by treatment received. We also did a prespecified, PRISMA-compliant meta-analysis, which included this study and other relevant randomised controlled trials, to estimate more precisely the effects of lactoferrin supplementation on late-onset sepsis, necrotising enterocolitis, and survival. This trial is registered with the Australian and New Zealand Clinical Trials Registry, ACTRN12611000247976. Findings Between June 27, 2014, and Sept 1, 2017, we recruited 1542 infants; 771 were assigned to the intervention group and 771 to the control group. One infant who had consent withdrawn before beginning lactoferrin treatment was excluded from analysis. In-hospital death or major morbidity occurred in 162 (21%) of 770 infants in the intervention group and in 170 (22%) of 771 infants in the control group (relative risk [RR] 0·95, 95% CI 0·79–1·14; p=0·60). Three suspected unexpected serious adverse reactions occurred; two in the lactoferrin group, namely unexplained late jaundice and inspissated milk syndrome, but were not attributed to the intervention and one in the control group had fatal inspissated milk syndrome. Our meta-analysis identified 13 trials completed before Feb 18, 2020, including this Article, in 5609 preterm infants. Lactoferrin supplements significantly reduced late-onset sepsis (RR 0·79, 95% CI 0·71–0·88; p Interpretation Lactoferrin supplementation did not improve death or major morbidity in this trial, but might reduce late-onset sepsis, as found in our meta-analysis of over 5000 infants. Future collaborative studies should use products with demonstrated biological activity, be large enough to detect moderate and clinically important effects reliably, and assess greater doses of lactoferrin in infants at increased risk, such as those not exclusively receiving breastmilk or infants of extremely low birthweight. Funding Australian National Health and Medical Research Council.

Objectives: To document the health needs of refugee children accessing comprehensive refugee health services in New South Wales (NSW), to match needs with available services and establish gaps in services. Methods: We collated clinical data on all children aged under 14 years attending the three refugee specific clinics seeing children in NSW in 2005. We compared these data to the number of refugee children settling in NSW in 2005. Results: NSW received 1,557 refugee children (

Pneumonia is one of the most common global childhood illnesses. The diagnosis relies on a combination of clinical judgement and radiological and laboratory investigations. Streptococcus pneumoniae remains the most important cause of childhood community-acquired pneumonia. In addition, viruses (including respiratory syncytial virus) and atypical bacteria (Mycoplasma and Chlamydia) are likely pathogens in younger and older children in developed countries. In the minority of cases only, the actual organism is isolated to guide treatment. Antibiotics effective against the expected bacterial pathogens should be instituted where necessary. The route and duration of antibiotic therapy, the role of emerging pathogens and the impact of pneumococcal resistance and conjugate pneumococcal vaccines are also discussed.

Primary and recurrent herpes simplex virus (HSV) infections are a common clinical problem. HSV disease in the very young or the immunocompromised can be especially severe and rapidly progressive. Management recommendations vary depending on the child's age, immune state, and the site and severity of infection. In this review, guidelines for the management of the common clinical syndromes of HSV infection in childhood are provided using the best available evidence. However, there are few controlled clinical trials documenting the efficacy of treatment strategies for HSV disease in childhood beyond the neonatal period, and recommendations for treating mucocutaneous and genital HSV disease must be extrapolated from adult data. Future research is needed to define the role of antiviral therapy in many childhood HSV syndromes, and there is a strong need to develop oral suspensions of antiviral drugs that can be given to young children at practical dosing intervals.

Objective: Estimate the economic impact of introducing inactivated poliovir us vaccine (IPV) into the Australian childhood immunisation schedule to eliminate vaccine-associated paralytic poliomyelitis (VAPP). Methods: Cost-effectiveness of two different four-dose IPV schedules (monovalent vaccine and IPV-containing combination vaccine) compared with the current four-dose oral poliovirus vaccine (OPV) schedule for Australian children through age six years. Model used estimates of VAPP incidence, costs, and vaccine utilisation and price obtained from published and unpublished sources. Main outcome measures were total costs, outcomes prevented, and incremental cost-effectiveness, expressed as net cost per case of VAPP prevented. Results: Changing to an IPVbased schedule would prevent 0.395 VAPP cases annually. At $20 per dose for monovalent vaccine and $14 per dose for the IPV component in a combination vaccine, the change would incur incremental, annual costs of $19.5 million ($49.3 million per VAPP case prevented) and $6.7 million ($17.0 million per VAPP case prevented), respectively. Threshold analysis identified break-even prices per dose of $1 for monovalent and $7 for combination vaccines. Conclusions: Introducing IPV into the Australian childhood immunisation schedule is not likely to be cost-effective unless it comes in a combined vaccine with the IPV-component price below $10. Implications: More precise estimates of VAPP incidence in Australia and IPV price are needed. However, poor cost-effectiveness will make the decision about switching from OPV to IPV in the childhood schedule difficult.

Neonatal meningitis is a relatively rare but extremely important problem for the practising neonatologist. The mortality and morbidity remain high, and delay in diagnosis often worsens the prognosis. This review of the management of neonatal meningitis will deal with clinical features, diagnosis, including the role of lumbar puncture and interpretation of cerebrospinal fluid (CSF) findings, and then management including choice of antimicrobial agents and the role of adjunctive therapy. It will not include shunt infections.

This study compared Hib antibody responses to a single lot of PRP-OMPC vaccine given at 2, 4 and 12 months to 57 Aboriginal infants in rural areas of the Northern Territory and 56 Caucasian infants in Sydney, Australia. The Aboriginal infants had lower levels of antibody in cord blood (P>0.05), which were significantly lower (P

Nosocomial infections are an important cause of morbidity and prolonged hospital stay in newborn infants. Mortality is lower than that of vertically acquired infection. A variety of bacteria, viruses and fungi are responsible for infection. Low birth weight infants are particularly at risk and other possible risk factors are discussed. Routine surveillance cultures are of limited value in preventing nosocomial infection. Simple infection control measures, such as handwashing, may reduce the burden of nosocomial infection.

Summary Preterm infants are at increased risk of severe respiratory syncytial virus (RSV) infection. The monoclonal antibody palivizumab reduces the frequency of preterm infants being admitted to hospital with RSV infection. However, palivizumab is expensive, has to be given by intramuscular injection monthly for 5 months and has to be given prophylactically to 17 preterm children to prevent one hospital admission with RSV and to 59 children to prevent one intensive care admission. Cost-effectiveness analyses have not shown that palivizumab is cost-effective for any sub-group with sufficient certainty to recommend its public funding. Palivizumab will only be cost-effective if the price drops. Paying for palivizumab is an opportunity cost; the money could be spent better on other more cost-effective health care interventions. Palivizumab should not be prescribed for any preterm child unless it can be shown to be cost-effective in that situation.

This book is aimed primarily at the clinician and more at the infectious disease specialist than the general paediatrician. It is an excellent reference work, with the chapters each dealing with specific clinical contexts (e.g. the renal transplant patient, asplenia, burns patients). There are some surprising inclusions, such as premature infants, and some surprising omissions, most notably bone marrow transplant patients, whereas stem cell transplant patients merit a chapter; a real sign of the times.