A qualitative investigation of paediatric intensive care staff attitudes towards the diagnosis of lower respiratory tract infection in the molecular diagnostics era.

Background: In the past decade, molecular diagnostic syndromic arrays incorporating a range of bacterial and viral pathogens have been described. It is unclear how paediatric intensive care unit (PICU) staff diagnose lower respiratory tract infection (LRTI) and integrate diagnostic array results into antimicrobial decision-making. Methods: An online survey with eleven questions was distributed throughout paediatric intensive care societies in the UK, continental Europe and Australasia with a total of 755 members. Participants were asked to rate the clinical factors and investigations they used when prescribing for LRTI. Semi-structured interviews were undertaken with staff who participated in a single-centre observational study of a 52-pathogen diagnostic array. Results: Seventy-two survey responses were received; most responses were from senior doctors. Whilst diagnostic arrays were used less frequently than routine investigations (i.e. microbiological culture), they were of comparable perceived utility when making antimicrobial decisions. Prescribers reported that for arrays to be clinically impactful, they would need to deliver results within 6 h for stable patients and within 1 h for unstable patients to inform their immediate decision to prescribe antimicrobials. From 16 staff interviews, we identified that arrays were helpful for the diagnosis and screening of bacterial LRTI. Staff reported it could be challenging to interpret results in some cases due to the high sensitivity of the test. Therefore, results were considered within the context of the patient and discussed within the multidisciplinary team. Conclusions: Diagnostic arrays were considered of comparable value to microbiological investigations by PICU prescribers. Our findings support the need for further clinical and economic evaluation of diagnostic arrays in a randomised control trial. Trial registration: Clinicaltrials.gov, NCT04233268. Registered on 18 January 2020. Supplementary Information: The online version contains supplementary material available at 10.1007/s44253-023-00008-z.

The rapid detection of respiratory pathogens in critically ill children.

PURPOSE: Respiratory infections are the most common reason for admission to paediatric intensive care units (PICU). Most patients with lower respiratory tract infection (LRTI) receive broad-spectrum antimicrobials, despite low rates of bacterial culture confirmation. Here, we evaluated a molecular diagnostic test for LRTI to inform the better use of antimicrobials. METHODS: The Rapid Assay for Sick Children with Acute Lung infection Study was a single-centre, prospective, observational cohort study of mechanically ventilated children (> 37/40 weeks corrected gestation to 18 years) with suspected community acquired or ventilator-associated LRTI. We evaluated the use of a 52-pathogen custom TaqMan Array Card (TAC) to identify pathogens in non-bronchoscopic bronchoalveolar lavage (mini-BAL) samples. TAC results were compared to routine microbiology testing. Primary study outcomes were sensitivity and specificity of TAC, and time to result. RESULTS: We enrolled 100 patients, all of whom were tested with TAC and 91 of whom had matching culture samples. TAC had a sensitivity of 89.5% (95% confidence interval (CI95) 66.9-98.7) and specificity of 97.9% (CI95 97.2-98.5) compared to routine bacterial and fungal culture. TAC took a median 25.8 h (IQR 9.1-29.8 h) from sample collection to result. Culture was significantly slower: median 110.4 h (IQR 85.2-141.6 h) for a positive result and median 69.4 h (IQR 52.8-78.6) for a negative result. CONCLUSIONS: TAC is a reliable and rapid adjunct diagnostic approach for LRTI in critically ill children, with the potential to aid early rationalisation of antimicrobial therapy.

Fifteen-minute consultation: Intubation of the critically ill child presenting to the emergency department.

Intubation of critically ill children presenting to the emergency department is a high-risk procedure. Our article aims to offer a step-by-step guide as to how to plan and execute a rapid, successful intubation in a way that minimises risk of adverse events and patient harm. We address considerations such as the need for adequate resuscitation before intubation and selection of equipment and personnel. We also discuss drug choice for induction and peri-intubation instability, difficult airway considerations as well as postintubation care. Focus is also given on the value of preintubation checklists, both in terms of equipment selection and in the context of staff role designation and intubation plan clarity. Finally, in cases of failed intubation, we recommend the application of the Vortex approach, highlighting, thus, the importance of avoiding task fixation and maintaining our focus on what matters most: adequate oxygenation.

Fifteen-minute consultation: Emergency management of children presenting with hyperkalaemia.

Hyperkalaemia can lead to life-threatening cardiac arrhythmias. A good understanding of the physiological basis of management can help us rationalise treatment and reduce plasma potassium levels efficiently and effectively. Management focuses on avoidance of arrythmias, rapid intracellular movement of potassium and finally reduction of total body potassium. Fluid management in hyperkalaemia should be carefully considered, with balanced solutions providing theoretical benefits compared to 0.9% saline in certain situations.

How to interpret the paediatric 12-lead ECG.

ECG interpretation is a core skill for any healthcare practitioner that looks after children. The article aims to educate the reader in basic interpretation of paediatric ECG in a succinct, interactive, organised manner in a way that it can be easily referenced and applied in everyday clinical practice. We include clinical examples as well as age and sex-related reference ranges for QT intervals, P-wave duration, Q-wave amplitude, QRS complex duration, R-wave and S-wave amplitude, R/S ratio and PR intervals.

Foetal surgery and using in utero therapies to reduce the degree of disability after birth. Could it be morally defensible or even morally required?

In 2008 the Human Fertilisation and Embryology Act amendments made deliberately choosing to bring disability into the world, using assisted reproduction, a criminal offence. This paper considers whether the legal prohibition above, should influence other policy areas concerning the welfare of future children such as new possibilities presented by foetal surgery and in utero gene therapy. If we have legal duties to avoid disability in one context should this influence our avoidance of disability in this other context? This paper investigates whether the State might have a stake in wider promotion of practices to reduce the degree of disability in foetuses that will come to exist (as opposed to those that will be aborted). Not selecting for disability does not affect the welfare of any future individual, whereas treating in utero abnormalities can optimize the eventual child's welfare; antenatal interventions stand to improve clinical outcomes and welfare should that specific child be born. I explore why the State may want to intervene in the antenatal setting and to what extent, if at all; the State should implement these technologies. I argue that if the State is justified in intervening to outlaw the choosing to create disabled lives using assisted reproductive techniques, it is also justified in putting pressure on prospective parents to accept therapies in utero to help their child be born less disabled. However, I qualify this with the argument that the State is not justified in using force or the criminal law in this situation during pregnancy.

Endocrine complications in patients with Thalassaemia Major.

Patients with multi-transfused thalassaemia major may develop severe endocrine complications due to iron overload. The anterior pituitary is particularly sensitive to iron overload which disrupts hormonal secretion resulting in hypogonadism, short stature , acquired hypothyroidism and hypoparathyroidism. Glucose intolerance and diabetes mellitus are also common in thalassaemic patients. The severity of the clinical manifestation and laboratory findings in thalassaemia largely depends on the genotype; thus homozygotes or compound heterozygotes for the mutations beta0 or beta+ depend for life on frequent transfusions. A multicenter study in Cyprus including 435 patients showed hypogonadotrophic hypogonadism in 32.5%, short stature in 35%, acquired hypothyroidism in 5.9%, hypoparathyroidism in 1.2% and diabetes mellitus in 9.4%. A slowing down of growth velocity and a reduced or absent pubertal growth spurt is observed in early adolescence leading to short adult height. Delayed or absent puberty and hypogonadism may result in fertility problems which affect enormously the life of thalassemics. Glucose intolerance in adolescence and diabetes mellitus later in life are also frequent complications mainly due to iron overload, chronic liver disease and genetic predisposition. Primary hypothyroidism and hypoparathyroidsm usually appear in the second decade of life; are related to iron overload and may be reversible at an early stage by intensive chelation. Osteopenia and osteoporosis due to a complicated pathogenesis represent prominent causes of morbidity in young adults of both genders with thalassaemia. Early recognition and prevention of the endocrine complications, by early and regular chelation therapy, is mandatory for the improvement of the quality of life and psychological outcome of these patients.

Evaluation of the auxological and metabolic status in prepubertal children born small for gestational age.

BACKGROUND: Low birth weight (BW) (<2,500 g) is associated with a high risk of impaired postnatal growth and late metabolic consequences. The aim of this study is to describe the postnatal growth pattern and the metabolic status of children born small for gestational age (SGA) and compare them with premature children born with low (1,500-2,500 g) and very low (<1,500 g) BW. CHILDREN AND METHODS: 104 prepubertal children (47 males and 57 females) aged 3.0 to 8.9 years were divided into four groups according to their birth weight adjusted for gestational age (GA): SGA-premature (SGApr): BW < -2 SD, GA <37 wk (n = 17); SGA-full-term (SGAt): BW < -2 SD, GA >37 wk (n = 29); low birth weight (LBW): BW = 1,500-2,500 g, GA <37 wk (n = 35); very low birth weight (VLBW): BW <1,500 g, GA <37 wk (n = 23). The control group consisted of 27 full-term appropriate for gestational age, prepubertal children matched for age. All children had anthropometric and laboratory measurements. The HOMA model was used to estimate insulin resistance (IR). RESULTS: Weight, height and body mass index (BMI) were significantly lower in the SGA groups -- both term and premature -- (p <0.05) and particularly lower in the VLBW children (p <0.01). At the age of 36 months, 99.6% of SGAt and a smaller percentage of SGApr (88.2%) children achieved catch-up growth. IGF-I and IGFBP-3 levels were lower in the children born SGA, both term and premature, compared to the controls (p <0.05) and especially in those who had catch-up after the age of 6 months (p <0.002). VLBW children aged 6-8.9 years had significantly higher HOMA compared to controls of the same age group (p = 0.005), whereas no evidence of IR was found in the SGA children. None of the children had developed premature adrenarche by the day of examination. CONCLUSIONS: Prepubertal children born SGA and VLBW are thinner and shorter than their age-matched controls. A larger percentage of SGA full-term children achieve catch-up growth than SGA premature children by 3 years of age. SGA children and especially those with late catch-up growth have lower IGF-I levels. Children with VLBW show evidence of IR at age 6-8.9 years. None of the girls showed precocious sexual development by the day of examination.

The impact of iron overload and genotype on gonadal function in women with thalassaemia major.

OBJECTIVE: The purpose of this study is to evaluate the impact of chronic iron overload and genotype on gonadal function in women with thalassaemia major. PATIENTS AND METHODS: The study population consists of 101 women aged 15-48 years who were treated between 1981 and 1999. These women were divided into two groups according to their genotype: [A=no modifying genetic factor and B=presence of modifying factors], and into four groups according to their menstrual history: NM (normal menstruation), OLM (oligomenorrhea), PA (primary amenorrhea), and SA (secondary amenorrhea). RESULTS: Women with NM maintained eumenorrhoea for 14.62 years, whereas those with SA did so for 6.94 years. The serial values of both FSH and LH after stimulation with GnRH were lower in women with SA and PA (p<0.05) compared to women with OLM and NM. The average value of the minimum, mean and maximum ferritin levels over a period of 20 years displayed an increasing trend from women with NM to those with SA and PA. The lower levels of ferritin in women in Group A did not protect them from developing SA. In addition women with SA, who belong to Group A, had a shorter duration of eumenorrhoea compared to the ones with SA who belong to Group B. CONCLUSIONS: Although the pathogenesis of gonadal dysfunction in thalassaemia is known to be the consequence of iron overload, this study demonstrates that genotype acts as an independent variable, contributing to the development of SA in thalassaemic women.