Association Between Treatments and Short-Term Biochemical Improvements and Clinical Outcomes in Post-Severe Acute Respiratory Syndrome Coronavirus-2 Inflammatory Syndrome.

OBJECTIVES: To 1) analyze the short-term biochemical improvements and clinical outcomes following treatment of children with post-severe acute respiratory syndrome coronavirus-2 inflammatory syndrome (multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2) admitted to U.K. PICUs and 2) collate current treatment guidance from U.K. PICUs. DESIGN: Multicenter observational study. SETTING: Twenty-one U.K. PICUs. PATIENTS: Children (< 18 yr) admitted to U.K. PICUs between April 1, 2020, and May 10, 2020, fulfilling the U.K. case definition of pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Routinely collected, deidentified data were analyzed. Propensity score and linear mixed effects models were used to analyze the effect of steroids, IV immunoglobulin, and biologic agents on changes in C-reactive protein, platelet counts, and lymphocyte counts over the course of PICU stay. Treatment recommendations from U.K. clinical guidelines were analyzed. Over the 6-week study period, 59 of 78 children (76%) received IV immunoglobulin, 57 of 78 (73%) steroids, and 18 of 78 (24%) a biologic agent. We found no evidence of a difference in response in clinical markers of inflammation between patients with multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 who were treated with IV immunoglobulin, steroids, or biologics, compared with those who were not. By the end of the study period, most patients had received immunomodulation. The 12 patients who did not receive any immunomodulators had similar decrease in inflammatory markers as those treated. Of the 14 guidelines analyzed, the use of IV immunoglobulin, steroids, and biologics was universally recommended. CONCLUSIONS: We were unable to identify any short-term benefit from any of the treatments, or treatment combinations, administered. Despite a lack of evidence, treatment guidelines for multisystem inflammatory syndrome in children/pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus-2 have become very similar in advising step-wise treatments. Retaining clinical equipoise regarding treatment will allow clinicians to enroll children in robust clinical trials to determine the optimal treatment for this novel important condition.

Intensive care admissions of children with paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the UK: a multicentre observational study.

BACKGROUND: In April, 2020, clinicians in the UK observed a cluster of children with unexplained inflammation requiring admission to paediatric intensive care units (PICUs). We aimed to describe the clinical characteristics, course, management, and outcomes of patients admitted to PICUs with this condition, which is now known as paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS). METHODS: We did a multicentre observational study of children (aged <18 years), admitted to PICUs in the UK between April 1 and May 10, 2020, fulfilling the case definition of PIMS-TS published by the Royal College of Paediatrics and Child Health. We analysed routinely collected, de-identified data, including demographic details, presenting clinical features, underlying comorbidities, laboratory markers, echocardiographic findings, interventions, treatments, and outcomes; serology information was collected if available. PICU admission rates of PIMS-TS were compared with historical trends of PICU admissions for four similar inflammatory conditions (Kawasaki disease, toxic shock syndrome, haemophagocytic lymphohistiocytosis, and macrophage activation syndrome). FINDINGS: 78 cases of PIMS-TS were reported by 21 of 23 PICUs in the UK. Historical data for similar inflammatory conditions showed a mean of one (95% CI 0·85-1·22) admission per week, compared to an average of 14 admissions per week for PIMS-TS and a peak of 32 admissions per week during the study period. The median age of patients was 11 years (IQR 8-14). Male patients (52 [67%] of 78) and those from ethnic minority backgrounds (61 [78%] of 78) were over-represented. Fever (78 [100%] patients), shock (68 [87%]), abdominal pain (48 [62%]), vomiting (49 [63%]), and diarrhoea (50 [64%]) were common presenting features. Longitudinal data over the first 4 days of admission showed a serial reduction in C-reactive protein (from a median of 264 mg/L on day 1 to 96 mg/L on day 4), D-dimer (4030 µg/L to 1659 µg/L), and ferritin (1042 µg/L to 757 µg/L), whereas the lymphocyte count increased to more than 1·0 × 109 cells per L by day 3 and troponin increased over the 4 days (from a median of 157 ng/mL to 358 ng/mL). 36 (46%) of 78 patients were invasively ventilated and 65 (83%) needed vasoactive infusions; 57 (73%) received steroids, 59 (76%) received intravenous immunoglobulin, and 17 (22%) received biologic therapies. 28 (36%) had evidence of coronary artery abnormalities (18 aneurysms and ten echogenicity). Three children needed extracorporeal membrane oxygenation, and two children died. INTERPRETATION: During the study period, the rate of PICU admissions for PIMS-TS was at least 11-fold higher than historical trends for similar inflammatory conditions. Clinical presentations and treatments varied. Coronary artery aneurysms appear to be an important complication. Although immediate survival is high, the long-term outcomes of children with PIMS-TS are unknown. FUNDING: None.

Oxygen saturation and haemodynamic changes prior to circulatory arrest: Implications for transplantation and resuscitation.

AIMS: To describe the progression of oxygen saturations and blood pressure observations prior to death. INTRODUCTION: The progression of physiological changes around death is unknown. This has important implications in organ donation and resuscitation. Donated organs have a maximal warm ischaemic threshold. In hypoxic cardiac arrest, an understanding of pre-cardiac arrest physiology is important in prognosticating and will allow earlier identification of terminal states. METHODS: Data were examined for all regional patients over a two-year period offering organ donation after circulatory death. Frequent observations were taken contemporaneously by the organ donation nurse at the time of and after withdrawal of intensive care. RESULTS: In all, 82 case notes were examined of patients aged 0 to 76 (median 52, 4 < 18 years). From withdrawal of intensive care to death took a mean of 28.5 min (range 4 to 185). A terminal deterioration in saturations (from an already low baseline) commenced 14 min prior to circulatory arrest, followed by a blood pressure fall commencing 8 min prior to circulatory arrest, and finally a rapid fall in heart rate commencing 4 min prior to circulatory arrest. Two patients had a warm ischaemic time of greater than 30 min; 15 patients had a warm ischaemia time of 10 min or greater; and 53 patients had a warm ischaemia time of 5 min or less. It was observed that 0/82 patients had saturations of less than 40% for more than 3 min prior to cardiac arrest and 74/82 for more than 2 min. CONCLUSIONS: There is a perimortem sequence of hypoxia, then hypotension, and then bradycardia. The heart is extremely resistant to hypoxia. A warm ischaemic time of over 30 min is rare.

Physico-chemical stability of Plasma-Lyte 148® and Plasma-Lyte 148® + 5% Glucose with eight common intravenous medications.

BACKGROUND: Plasma-Lyte 148® is a balanced, crystalloid intravenous (IV) fluid which is both calcium-free and isotonic. It prevents the hyperchloremic metabolic acidosis and iatrogenic hyponatremia seen with use of 0.9% sodium chloride and hypotonic solutions, respectively. However, data on compatibility with commonly used drugs are lacking. AIMS: To investigate the stability of Plasma-Lyte 148® and Plasma-Lyte 148® + 5% Glucose with eight commonly used therapeutic agents when compared with 5% glucose and 0.9% sodium chloride as diluents. We aimed to provide vital data which may facilitate the introduction of what appears to be a safer and more economic fluid. METHODS: Plasma-Lyte 148® and Plasma-Lyte 148® + 5% Glucose were mixed with morphine, midazolam, fentanyl, ketamine, clonidine, aminophylline, salbutamol, and furosemide at set concentrations. Comparisons were made to 0.9% sodium chloride and 5% glucose fluid controls. Six repeats of each IV fluid and drug admixture were analyzed through high-performance liquid chromatography at three time points: 0, 2, and 24 hours. A concentration change of <5% was defined as chemically stable. Physical stability was assessed by observation of precipitate formation or color change. pH changes were measured using a Fisherbrand Hydrus 300 pH meter. RESULTS: Relative to starting concentration, all drugs except midazolam were stable to ±3%. All examined therapeutic agents were chemically stable at 2 and 24 hours relative to control solutions. No precipitate formed in any of the samples. All Plasma-Lyte 148® and Plasma-Lyte 148® + 5% Glucose drug admixtures remained in a safe, peripheral administration pH range of 5-9 and were closer to the pH of blood than standard fluid-drug admixtures. CONCLUSION: Morphine, fentanyl, ketamine, salbutamol, aminophylline, and clonidine are stable for 24 hours when mixed with Plasma-Lyte 148® and Plasma-Lyte 148®+5% Glucose for administration at concentrations equivalent to those found at a typical Y-site with maintenance fluid. Furosemide is stable at lower concentrations than those seen at a Y-site, but midazolam displayed instability.

Organ and tissue donation in a regional paediatric intensive care unit: evaluation of practice.

Approximately 2% of those on the organ transplant list in the UK are children. Early identification of donors and referral to organ donation teams (ODT) has proven to increase both the success rate of gaining consent and the number of organs actually retrieved. To evaluate the practice relating to organ donation for children receiving end-of-life care on a paediatric intensive care unit (PICU) measured against the National Guidelines. All children 0-18 who received their end-of-life care and died on the PICU. A retrospective cohort study of organ donation patterns including referral, approach, consent and donation. This involved a review of case notes on PICU between the years 2009 and 2014. One hundred five deaths were identified and 100 notes were examined and data analysed to ascertain if religion, age and length of stay on PICU impacted on practice. Eighty-six children met the early identification criteria for potential donors, 40 (46.5%) children were referred to the ODT and 33 (38.3%) families were approached regarding donation. Twenty-one (24.4%) families consented to donation. Seventeen donations took place with a total of 41 sets of organs/tissues retrieved. Despite the majority of children meeting early identification for potential donors, many were not being referred. CONCLUSIONS: All children on end-of-life care should be referred for potential organ donation. Organ donation needs to be seen as a priority for hospitals as a part of routine end-of-life care to help increase referral rates and give families the opportunity to donate. Many paediatric deaths are not referred for consideration of organ donation, despite guidelines stating that this process should be standard of care. Further optimization of referral rates may aid in increasing the number of organs available for donation. What is Known: • Shortage of organs continues to be a national problem. • NICE guidelines state that all patients who are on end-of-life care should have the option of organ donation explored. • Required referral both increases the number of donors and organs donated. What is New: • The process of identifying and referring children for paediatric organ donation. • Identifies that children are still not being referred for organ donation. • Organ donation is still not a priority for hospitals.

TPMT, COMT and ACYP2 genetic variants in paediatric cancer patients with cisplatin-induced ototoxicity.

OBJECTIVES: Cisplatin ototoxicity affects 42-88% of treated children. Catechol-O-methyltransferase (COMT), thiopurine methyltransferase (TPMT) and AYCP2 genetic variants have been associated with ototoxicity, but the findings have been contradictory. The aims of the study were as follows: (a) to investigate these associations in a carefully phenotyped cohort of UK children and (b) to perform a systematic review and meta-analysis. METHODS: We recruited 149 children from seven UK centres using a retrospective cohort study design. All participants were clinically phenotyped carefully. Genotyping was performed for one ACYP2 (rs1872328), three TPMT (rs12201199, rs1142345 and rs1800460) and two COMT (rs4646316 and rs9332377) variants. RESULTS: For CTCAE grading, hearing loss was present in 91/120 (75.8%; worst ear) and 79/120 (65.8%; better ear). Using Chang grading, hearing loss was diagnosed in 85/119 (71.4%; worst ear) versus 75/119 (63.0%; better ear). No TPMT or COMT single-nucleotide polymorphisms (SNPs) were associated with ototoxicity. ACYP2 SNP rs1872328 was associated with ototoxicity (P=0.027; worst ear). Meta-analysis of our data with that reported in previous studies showed the pooled odds ratio (OR) to be statistically significant for both the COMT SNP rs4646316 (OR: 1.50; 95% confidence interval: 1.15-1.95) and the ACYP2 SNP rs1872328 (OR: 5.91; 95% confidence interval: 1.51-23.16). CONCLUSION: We showed an association between the ACYP2 polymorphism and cisplatin-induced ototoxicity, but not with the TPMT and COMT. A meta-analysis was statistically significant for both the COMT rs4646316 and the ACYP2 rs1872328 SNPs. Grading the hearing of children with asymmetric hearing loss requires additional clarification.

Fever in a child with cerebrospinal fluid access device or shunt: a pragmatic approach to management.

Children with shunts commonly present with fever, and often the focus of infection will be unrelated to their shunt. However, as shunt infections may present with few or even no specific symptoms, evaluation of a child with a shunt presenting with fever should be careful and comprehensive to ensure shunt infections are not missed. Treatment of an infected shunt involves removal of the shunt followed by a long course of antibiotics; missing or partially treating shunt infections can result in significant morbidity and potentially even mortality. Our experience of managing children with shunts presenting with fever is that many non-specialist clinicians have little experience in this area so initial management may not always be appropriate. Those children who are most at risk of shunt infection are those who within the preceding 8 weeks have had insertion, revision or access of their shunt or chemotherapy device, or have had abdominal surgery in the presence of a ventriculoperitoneal shunt. We have chosen 8 weeks as a pragmatic time point, as in our experience the vast majority of children who have had shunt infections have presented within this period. The caveat is that this should not be used as an absolute cut-off where there is strong suspicion of shunt infection or no clear focus at a later time point.

North-South divide: distribution and outcome of respiratory viral infections in paediatric intensive care units in Cape Town (South Africa) and Nottingham (United Kingdom).

AIM: This study aims to describe and compare the spectrum, course, seasonality and outcome of children with virus-associated respiratory symptoms (VARS) admitted to two paediatric intensive care units (PICUs) in the United Kingdom (UK) and South Africa (SA). METHODS: Cross-sectional study of routinely collected data on subjects admitted to PICU with respiratory symptoms and positive respiratory viral polymerase chain reaction between July 2009 and July 2011. RESULTS: Six hundred forty-six samples yielding 765 viral isolates (74% from SA) from 599 patients (53% male; median (interquartile range) age 6.0 (2.3-16.5) months) were included. Rhinovirus, respiratory syncytial virus and adenovirus were most commonly isolated. Adenovirus was more prevalent in SA (24.3% vs. 16.8%, P = 0.03). Possible or likely nosocomial viral acquisition occurred in 78% of isolates in SA versus 48% in the UK (P < 0.0001).Total mortality was 13.5%; 17% in SA versus 4% in the UK (P < 0.0001). Mortality for community acquired VARS was 8.4% versus 16.1% in those with possible nosocomial viral acquisition (P = 0.009). Factors independently associated with mortality were: SA study site (adjusted odds ratio (OR) 3.4, 95% confidence interval (CI) 1.4-8.5; P = 0.008); age (months) (OR 1.0, 95% CI 1.0-1.02; P = 0.001); Paediatric Index of Mortality 2 score (%) (OR 1.0, 95% CI 1.01-1.03; P = 0.0002) and isolation of adenovirus (OR 3.0, 95% CI 1.8-5.0; P < 0.0001). CONCLUSIONS: The outcome of children with VARS was worse in SA compared with the UK PICU. Nosocomial VARS was highlighted as an important concern and requires further investigation.

Does hypernatremia cause subdural hematoma in children?: two case reports and a meta-analysis of the literature.

Hypernatremia has been causally linked with subdural hematoma (SDH), but more recently this has been called into question. Conversely, there is a well-established link between SDH and injury. We wish to examine the evidence base that hypernatremia in infants and young children causes SDH.We present 2 cases of children with severe hypernatremia whose intracranial contents were assessed by imaging in the first case and postmortem examination in the second. Neither demonstrated SDH. The first case was important as the hypernatremia was iatrogenic occurring in a controlled hospital environment.We also searched the literature from 1950 to 2007, collecting data on all reported cases of hypernatremia in children younger than 7 years whose intracranial contents were examined by imaging, surgery, and/or postmortem examination. Of 124 cases reported in 31 articles, 112 cases developed hypernatremia in the community, and 12 in the hospital. Subdural hematoma was demonstrated in 7 cases, all of which had developed hypernatremia in the community under circumstances that would make it difficult to exclude nonaccidental injury. None of the 12 cases that developed hypernatremia in a controlled hospital environment had SDH.The evidence base supporting the hypothesis that hypernatremia causes SDH is poor, depending on isolated reports with uncertain histories.

Dexamethasone in children mechanically ventilated for lower respiratory tract infection caused by respiratory syncytial virus: a randomized controlled trial.

OBJECTIVE: To determine the efficacy of dexamethasone in the treatment of mechanically ventilated children with respiratory syncytial virus-severe lower respiratory tract infection. DESIGN: International, multicenter, randomized, double-blind, placebo-controlled trial. SETTING: Twelve pediatric intensive care units. SUBJECTS: Children (<2 yrs) mechanically ventilated for respiratory syncytial virus lower respiratory tract infection. Children were prestratified for severity of oxygen abnormalities on admission. INTERVENTION: Intravenous dexamethasone (0.6 mg/kg/day, 48 hrs) or placebo. MEASUREMENTS AND MAIN RESULTS: A superiority approach was used in the subgroup of patients with mild oxygen abnormalities (arterial partial pressure of oxygen/fractional inspired oxygen concentration [PaO(2)/FIO(2)] >200 mm Hg and/or mean arterial pressure ≤10 cm H(2)O) and a noninferiority approach in those with severe oxygen abnormalities (PaO(2)/FIO(2) ≤200 mm Hg and mean arterial pressure >10 cm H(2)O). Primary outcome was the duration of mechanical ventilation. In the subgroup with mild oxygenation abnormalities, 45 of the 89 included patients received dexamethasone and 44 placebo; in the subgroup with severe oxygenation abnormalities, 28 of the 56 included patients received dexamethasone and 28 placebo. Baseline characteristics in both treatment arms were similar for both subgroups. After the third interim analysis, the trial was stopped early for futility taking the slow enrollment into account. At that time, the median duration (interquartile range) of mechanical ventilation was 137 (91-195) hrs in the dexamethasone- and 139 (117-188) hrs in the placebo-treated patients in the subgroup with mild oxygenation abnormalities (p = .6). In the subgroup with severe oxygenation abnormalities, it was 171 (136-212) hrs in the dexamethasone- and 170 (125-201) hrs in the placebo-treated patients (p = .6). CONCLUSION: In this prematurely ended trial in children mechanically ventilated for severe respiratory syncytial virus-lower respiratory tract infection, we found no evidence of a beneficial effect of dexamethasone in children with mild oxygenation abnormalities. Neither was evidence found that dexamethasone may prolong mechanical ventilation in those with severe oxygenation abnormalities.

Characteristics of deaths in paediatric intensive care: a 10-year study.

OBJECTIVE: To describe the patient mortality over a 10-year period in a paediatric intensive care unit (PICU) including patient demographics, length of stay, cause and mode of death and to compare these findings with pre-existing literature from the western world. DESIGN: A retrospective chart review. SETTING: A UK tertiary PICU. PATIENTS: All children who died in the PICU over a 10-year period between 1 November 1997 and 31 October 2007 (n = 204). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data recorded for each patient included patient demographics, length of stay and cause of death according to the International Classification of Disease-10 classification, and mode of death. Mode of death was assigned for each patient by placement in one of four categories: (i) brain death (BD), (ii) managed withdrawal of life-sustaining medical therapy (MWLSMT), (iii) failed cardiopulmonary resuscitation (CPR) and (iv) limitation of treatment (LT). Over the study period, findings showed a median length of stay of 2 days (IQR 0-5 days), with a mortality rate of 5%. The most common mode of death was MWLSMT (n = 112, 54.9%) and this was consistent across the 10-year period. Linear regression analysis demonstrated no significant change in trend over the 10 years in each of the modes of death; BD (p = 0.84), MWLSMT (p = 0.88), CPR (p = 0.35) and LT (p = 0.67). CONCLUSION: End-of-life care is an important facet of paediatric intensive nursing/medicine. Ten years on from the Royal College of Paediatrics and Child Health publication 'Withholding or withdrawing life sustaining treatment in children: A framework for practice', this study found managed withdrawal of MWLSMT to be the most commonly practised mode of death in a tertiary PICU, and this was consistent over the study period.

An international assessment of a web-based diagnostic tool in critically ill children.

Improving diagnostic accuracy is essential. The extent of diagnostic uncertainty at patient admission is not well described in critically ill children. Therefore, we studied the extent that pediatric trainee diagnostic performance could be improved with the aid of a computerized diagnostic tool. Data regarding patient admissions to five Pediatric Intensive Care Units were collected. Information included patients' clinical details, admitting team's diagnostic workup and discharge diagnosis. An attending physician assessed each case independently and suggested additional diagnostic possibilities. Diagnostic accuracy was calculated using the discharge diagnosis as the gold standard. 206 out of 927 patients (22.2%) admitted to the PICUs did not have an established diagnosis at admission. The trainee teams considered a median of three diagnoses in their workup (IQR 3-5) and made an accurate diagnosis in 89.4% cases (95% CI 84.6%-94.2%). Diagnostic accuracy improved to 92.5% with use of the diagnostic tool alone, and to 95% with the addition of attending physicians' diagnostic suggestions. We conclude that a modest proportion of admissions to these PICUs were characterized by diagnostic uncertainty during initial assessment. Although there was a relatively high accuracy rate of initial assessment in our clinical setting, it was further improved by both the diagnostic tool and the physicians' diagnostic suggestions. It is plausible that the tool's utility would be even greater in clinical settings with less expertise in critical illness assessment, such as community hospitals, or emergency departments of non-training institutions. The role of diagnostic aids in the care of critically ill children merits further study.further study.

Comparison of oral amoxicillin and intravenous benzyl penicillin for community acquired pneumonia in children (PIVOT trial): a multicentre pragmatic randomised controlled equivalence trial.

OBJECTIVE: To ascertain whether therapeutic equivalence exists for the treatment of paediatric community acquired pneumonia by the oral and intravenous (IV) routes. METHODS: A multicentre pragmatic randomised controlled non-blinded equivalence trial was undertaken in eight paediatric centres in England (district general and tertiary hospitals). Equivalence was defined as no more than a 20% difference between treatments of the proportion meeting the primary outcome measure at any time. 246 children who required admission to hospital and had fever, respiratory symptoms or signs and radiologically confirmed pneumonia were included in the study. Exclusion criteria were wheeze, oxygen saturations <85% in air, shock requiring >20 ml/kg fluid resuscitation, immunodeficiency, pleural effusion at presentation requiring drainage, chronic lung condition (excluding asthma), penicillin allergy and age <6 months. The patients were randomised to receive oral amoxicillin for 7 days (n = 126) or IV benzyl penicillin (n = 120). Children in the IV group were changed to oral amoxicillin after a median of six IV doses and received 7 days of antibiotics in total. The predefined primary outcome measure was time for the temperature to be <38 degrees C for 24 continuous hours and oxygen requirement to cease. Secondary outcomes were time in hospital, complications, duration of oxygen requirement and time to resolution of illness. RESULTS: Oral amoxicillin and IV benzyl penicillin were shown to be equivalent. Median time for temperature to settle was 1.3 days in both groups (p<0.001 for equivalence). Three children in the oral group were changed to IV antibiotics and seven children in the IV group were changed to different IV antibiotics. Median time to complete resolution of symptoms was 9 days in both groups. CONCLUSION: Oral amoxicillin is effective for most children admitted to hospital with pneumonia (all but those with the most severe disease who were excluded from this study). Prior to this study, the British Thoracic Society guidelines on childhood pneumonia could not draw on evidence to address this issue. This will spare children and their families the trauma and pain of cannulation, and children will spend less time in hospital.

Outcome after neonatal continuous negative-pressure ventilation: follow-up assessment.

BACKGROUND: A previous randomised trial of continuous negative extrathoracic pressure (CNEP) versus standard treatment for newborn infants with respiratory distress syndrome raised public concerns about mortality and neonatal morbidity. We studied the outcome in late childhood of children entered into the trial to establish whether there were long-term sequelae attributable to either mode of ventilation. METHODS: Outpatient assessment of neurological outcome, cognitive function, and disability was done by a paediatrician and a psychologist using standardised tests. 133 of 205 survivors from the original trial were assessed at 9-15 years of age. Of the original pairs randomly assigned to each ventilation mode, the results from 65 complete pairs were available. The primary outcome was death or severe disability. FINDINGS: Primary outcome was equally distributed between groups (odds ratio for the CNEP group 1.0; 95% CI 0.41-2.41). In unpaired analysis there was no significant difference between treatment modalities (1.05; 0.54-2.06). Full IQ did not differ significantly between the groups, but mean performance IQ was 6.8 points higher in the CNEP group than in the conventional-treatment group (95% CI 1.5-12.1). Results of neuropsychological testing were consistent with this finding, with scores on language production and visuospatial skills being significantly higher in the CNEP group. INTERPRETATION: We saw no evidence of poorer long-term outcome after neonatal CNEP whether analysis was by original pairing or by unpaired comparisons, despite small differences in adverse neonatal outcomes. The experience of our study indicates that future studies of neonatal interventions with the potential to influence later morbidity should be designed with longer-term outcomes in mind.

Hashimoto's encephalopathy: an unusual cause of seizures in the intensive care unit.

OBJECTIVE: To present a case study of Hashimoto's encephalopathy. DESIGN: Case report. SETTING: Paediatric Intensive Care Unit, Nottingham University Hospital, UK. PATIENTS: Two adolescent females presented with encephalopathy and raised venous lactate. Both had subtle signs of neurocognitive deterioration before initial presentation. Extensive investigation revealed elevated antithyroid antibody titer, suggesting Hashimoto's encephalopathy. INTERVENTIONS: Steroid administration. MEASUREMENTS AND MAIN RESULTS: Symptoms rapidly resolved in both cases after steroid treatment. CONCLUSION: Hashimoto's encephalopathy should be considered in cases of unexplained encephalopathy presenting to the intensive care unit. Teenage girls with an antecedent history suggestive of thyroid disease or progressive cognitive decline warrant special attention. Antithyroid antibody titers should be measured even if standard thyroid function tests are normal. Although the etiology is unknown, prompt steroid responsiveness suggests an inflammatory or autoimmune disorder, and patients should be treated accordingly.

Toxic shock syndrome and streptococcal myositis: three case reports.

UNLABELLED: Group A streptococcal (GAS) infection is the most common cause of bacterial pharyngitis and has an important role in the pathogenesis of post-infective phenomena including rheumatic fever and glomerulonephritis. Mortality from GAS is uncommon, particularly in the paediatric population. Toxic shock syndrome reflects the most severe form of GAS-related disease and is often associated with fasciitis or myositis. CONCLUSION: We present three cases of toxic shock syndrome secondary to (GAS) myositis demonstrating the importance of early recognition and provision of intensive care management.

Mydriasis due to self-administered inhaled ipratropium bromide.

Mydriasis due to ipratropium bromide has previously been described in children and adults. Children as young as 4 years of age may attempt to self-administer their inhalers. This possibility should be considered if an asthmatic child presents with abnormal neurological signs.