How to quickly critically appraise a randomized control trial

Being able to critically appraise scientific papers is an important skill. A thorough and methodical approach is necessary, particularly for peer-review purposes. However, it is also important to be able to do this quickly and efficiently. In some circumstances, students and trainees may be asked to perform a review on an unseen paper as part of an assessment. With apologies to my erstwhile teacher, David Sackett, this brief article offers a framework which will allow a fairly complete review of a randomized controlled trial in 15–20 min. This framework requires a reviewer to assess the Validity, Importance, Applicability, GReatness of benefit and Acceptability of any study and is encompassed by the acronym VIAGRA

Single-centre survey of parents regarding the hidden burden of paediatric flexible bronchoscopy.

Although paediatric flexible bronchoscopy is safe with relatively few side effects, parents frequently report an associated burden. To assess this, we undertook 25 semi-structured interviews with the parents of children who had recently undergone this procedure. Despite reporting the procedure was well explained, parental worry about procedure was common. The procedure resulted in children missing a median of 2 days from nursery/school and the parents having to take a median of 2 days carers leave. There was an additional financial burden related to sibling childcare, travel costs and car parking. Clinicians should address these issues in pre-procedure counselling

Interventions for treating distal intestinal obstruction syndrome (DIOS) in cystic fibrosis.

BACKGROUND: Cystic fibrosis is the most common life-limiting autosomal recessive genetic disorder in white populations. Distal intestinal obstruction syndrome (DIOS) is an important morbidity in cystic fibrosis. It is the result of the accumulation of viscid faecal material within the bowel which combines with thick, sticky mucus produced in the intestines of people with cystic fibrosis. The intestine may be completely blocked (complete DIOS) or only partially blocked (incomplete DIOS). Once a diagnosis of DIOS has been made, the goal of therapy is to relieve the acute complete or incomplete faecal obstruction and ultimately prevent the need for surgical intervention. OBJECTIVES: This review aimed to evaluate the effectiveness and safety of different treatment regimens for the treatment of DIOS (complete and incomplete) in children and adults with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of search: 09 September 2021. We also searched online trial registries. Date of last search: 12 October 2021. SELECTION CRITERIA: Randomised controlled trials, quasi-randomised controlled trials (including cross-over trials (to be judged on an individual basis)) comparing the use of laxative agents or surgery for treating DIOS in children, young people and adults with cystic fibrosis to each other, placebo or no intervention. DATA COLLECTION AND ANALYSIS: Two authors independently screened papers, extracted trial details and assessed for risk of bias. The authors assessed the quality of evidence using GRADE. MAIN RESULTS: There was one trial with 20 participants (16 females) included in the review. The mean age of participants was 13.1 years. The trial was a double-blinded, randomised cross-over trial which had a duration of 12 months in total and compared high-dose and low-dose pancreatic enzyme therapy. As only the abstract of the trial was available, the overall risk of bias was judged to be unclear. The trial did not address either of our primary outcomes (time until resolution of DIOS and treatment failure rate), but reported episodes of acute DIOS, presence of abdominal mass and abdominal pain. There were no numerical data available for these outcomes, but the authors stated that there was no difference between treatment with high-dose or low-dose pancreatic enzymes. The overall certainty of the evidence was found to be very low. AUTHORS' CONCLUSIONS: There is a clear lack of evidence for the treatment of DIOS in people with cystic fibrosis. The included abstract did not address our primary outcome measures and did not provide numerical data for the two secondary outcomes it did address. Therefore, we cannot justify the use of high-dose pancreatic enzymes for treating DIOS, nor can we comment on the efficacy and safety of other laxative agents. From our findings, it is clear that more randomised controlled trials need to be conducted in this area

Less sun, more cough: Annual hours of sunshine are inversely associated with hospital admissions for children with lower respiratory tract infection

Background: Vitamin D deficiency affects immune function increasing susceptibility to respiratory tract infections (RTI). Randomised controlled trials show vitamin D supplementation protects against acute RTIs. Most vitamin D (>90%) is acquired from sun exposure. Objective: To determine whether there is an association between hours of sunshine, deprivation status and severe lower respiratory tract infection rates (LRTI) in English children. Methods: The annualised age-gender corrected severe LRTI (agc-LRTI) rate for children <15 years was determined using Hospital Episodes Statistics data for April 2002-2011. Hours of sunshine (HoS) were calculated for matched regions using Met Office data. Regional deprivation index scores (IDACI) were taken from DoH statistics. Multivariate regression was used to explore the relationship between HoS, agc-LRTI rate & IDACI. Results: During the study period 314,226 children were admitted to English hospitals with LRTI. The child population varied between 9,654,027 and 9,853,580. The mean agc-LRTI rate was 357/100,000. The annual HoS in each region varied between 1287 hours (NW 2008-9) and 1815 hours (SE & Central 2006-7). There was a strong inverse association between HoS and agc-LRTI admission rates in English regions (p<0.001). In the model regional deprivation showed no statistical association with severe LRTI rate (p=0.54). Conclusion: Long-term weather patterns are associated with admissions to hospital for children with LRTI. Sunnier regions and sunnier years have lower LRTI admission rates when correcting for age, gender and deprivation. It is biologically plausible that this effect is mediated by vitamin D

Developing a core outcome set for children with protracted bacterial bronchitis.

Background: Protracted bacterial bronchitis (PBB) is a chronic endobrochial infection and a leading cause of chronic wet cough in children. There is an urgent need for a randomised controlled trial to investigate the optimal treatment but there is no core outcome set (COS) to inform choice of outcomes. A COS is a standardised set of outcomes representing the minimum that should be measured and reported in clinical trials of a specific condition. We have developed a COS for PBB. Methods: Potential core outcomes were collated from a systematic review, interviews with parents and a clinician survey. A two-round Delphi survey of healthcare professionals identified which outcomes had consensus for inclusion. The final COS was agreed at a consensus meeting of parent representatives and clinicians. Results: 20 outcomes were identified for the Delphi survey. After two rounds, 10 reached consensus. These were combined and edited at the consensus meeting into the final six: 1) Resolution of cough assessed using a cough score/diary recorded daily by parent(s) during treatment; 2) relapse of chronic wet cough and/or cumulative antibiotic treatment during ≥12 months follow-up; 3) change in child's quality of life (parent-proxy reporting for young children); 4) emergence of antibiotic resistance; 5) development of bronchiectasis diagnosed on clinically indicated computed tomography scans; and 6) microbiological clearance of identified respiratory pathogen if samples readily available. Conclusions: We have developed a COS for PBB which will reduce the outcome heterogeneity and bias of future clinical trials, as well as promoting comparison between studies

Healthcare utilisation in children with SMA type 1 treated with nusinersen: a single centre retrospective review.

Background: Nusinersen has been used to treat spinal muscular atrophy type 1 (SMA1) in the UK since 2017. While initial trials showed neuromuscular benefit from treating SMA1, there is little information on the respiratory effects of nusinersen. We aimed to look at the respiratory care, hospital utilisation and associated costs in newly treated SMA1. Methods: We reviewed the medical records of all children within the West Midlands with SMA1 treated with nusinersen at Royal Stoke University Hospital. Baseline demographics and hospital admission data were collected including: the reason for admission, total hospital days, days of critical care, days intubated, discharge diagnosis, doses of nusinersen and treatment complications. Results: 11 children (six girls) received nusinersen between May 2017 and April 2019. Their median (range) age was 29 (7-97) months. The median (range) number of nusinersen doses per child was 6 (4-8). All children were receiving long-term ventilatory support; this was mask ventilation in nine and tracheostomy ventilation in two. The total number of hospital days since diagnosis was 1101 with a median (range) of 118 (7-235) days per child. This included general paediatric ward days 0 (0-63), High Dependency Unit 79 (7-173) days and Paediatric Intensive Care Unit 13 (0-109) days per child. This equated to a median (range) of 20 (2-72) % of their life in hospital. The estimated cost of this care was £2.2M. Conclusion: Patients with SMA1 treated with nusinersen initially spend a considerable proportion of their early life in hospital. Parents should be counselled accordingly. These data suggest that for every 10 children started on nusinersen an extra HDU bed is required. This has a significant cost implication

Radiation dose from common radiological investigations and cumulative exposure in children with cystic fibrosis: an observational study from a single UK centre.

OBJECTIVES: Cumulative radiation exposure is associated with increased risk of malignancy. This is important in cystic fibrosis (CF) as frequent imaging is required to monitor disease progression and diagnose complications. Previous estimates of cumulative radiation are outdated as the imaging was performed on older equipment likely to deliver higher radiation. Our objectives were to determine the radiation dose delivered to children during common radiological investigations using modern equipment and to identify the number of such investigations performed in a cohort of children with CF to calculate their cumulative radiation exposure. DESIGN, SETTING AND PARTICIPANTS: Data including age at investigation and radiation exposure measured as estimated effective dose (EED) were collected on 2827 radiological studies performed on children at one UK paediatric centre. These were combined with the details of all radiological investigations performed on 65 children with CF attending the same centre to enable calculation of each child's cumulative radiation exposure. RESULTS: The mean EED for the common radiological investigations varied according to age. The range was 0.01-0.02 mSv for chest X-rays, 0.03-0.11 mSv for abdominal X-rays, 0.57-1.69 mSv for CT chest, 2.9-3.9 mSv for abdominal and pelvic CT, 0.20-0.21 mSv for sinus CT and 0.15-0.52 mSv for fluoroscopy-guided procedures. The mean EED was three to five times higher for helical compared with axial chest CT scans. The mean annual cumulative EED for our cohort of children with CF was 0.15 mSv/year with an estimated cumulative paediatric lifetime EED (0-18 years) of 3.5 mSv. CONCLUSIONS: This study provides up-to-date estimations of the radiation exposure when using common radiological investigations. These doses and the estimates of cumulative radiation exposure in children with CF are lower than previously reported. This reflects the reduced EED associated with modern equipment and the use of age-specific scanning protocols

Why are children with asthma bullied? A quantitative analysis of bullying risk factors in the Room to Breathe cohort

Background: Bullying and asthma are common challenges faced by children worldwide. It has been shown that children with chronic health conditions are at higher risk of being bullied, but this has not been explored in detail in asthma. Aims and Objectives: To determine what child/parent factors and attitudes are associated with increased asthma related bullying risks. Methods: The Room to Breathe1 survey parental and child responses (n=943) were analysed to examine the relationship between asthma control, activity restriction and parental concern and bullying. All analyses were undertaken using STATA statistical software (v14.0). Results: 1 in 10 children reported being “made fun of, or bullied because of their asthma” (n=93). Being a victim of asthma related bullying was associated with poorer asthma control (p=0.0001; 95% CI 1.44, 3.60), child perceived asthma control (p=0.0000; 95% CI 1.85, 4.84), activity restriction (p=0.0095; 95% CI 1.11, 2.77) and parental worry (p=0.0248; 95% CI 1.03, 2.57). Bullying was not statistically significantly associated with parent’s perceived asthma control, parental worry regarding use of steroids, or spacer use in public. Conclusion: Bullying in asthma is strongly associated with control, as perceived by the child and by validated control score, as well as activity restriction and parental worry. However, bullying is not associated with parental perception of control. Parent-reported data may be misrepresentative of bullying rates and asthma control. Asthma consultations must be child-focussed in order to gain a representative appreciation of asthma control and its impact on life

Factors affecting the growth of infants diagnosed with cystic fibrosis by newborn screening

Newborn screening (NBS) for cystic fibrosis (CF) improves nutritional outcomes. Despite early dietetic intervention some children fail to grow optimally. We report growth from birth to 2 years in a cohort of children diagnosed with CF by NBS and identify the variables that influence future growth. Methods One hundred forty-four children were diagnosed with CF by the West Midlands Regional NBS laboratory between November 2007 and October 2014. All anthropometric measurements and microbiology results from the first 2 years were collated as was demographic and CF screening data. Classification modelling was used to identify the key variables in determining future growth. Results Complete data were available on 129 children. 113 (88%) were pancreatic insufficient (PI) and 16 (12%) pancreatic sufficient (PS). Mean birth weight (z score) was 3.17 kg (− 0.32). There was no significant difference in birth weight (z score) between PI and PS babies: 3.15 kg (− 0.36) vs 3.28 kg (− 0.05); p = 0.33. By the first clinic visit the difference was significant: 3.42 kg (− 1.39) vs 4.60 kg (− 0.48); p < 0.0001. Weight and height remained lower in PI infants in the first year of life. In the first 2 years of life, 18 (14%) infants failed to regain their birth weight z score. The median time to achieve a weight z score of − 2, − 1 and 0 was 18, 33 and 65 weeks respectively. The median times to reach the same z scores for height were 30, 51 and 90 weeks. Birth weight z score, change in weight z score from birth to first clinic, faecal elastase, isolation of Pseudomonas aeruginosa, isolation of Staphylococcus aureus and sweat chloride were the variables identified by the classification models to predict weight and height in the first and second year of life. Conclusions Babies with CF have a lower birth weight than the healthy population. For those diagnosed with CF by NBS, the weight difference between PI and PS babies was not significantly different at birth but became so by the first clinic visit. The presence of certain factors, most already identifiable at the first clinic visit can be used to identify infant at increased risk of poor growth

Clinical indications and scanning protocols for chest CT in children with cystic fibrosis: a survey of UK tertiary centres.

Objectives: Chest CT is increasingly used to monitor disease progression in children with cystic fibrosis (CF) but there is no national guideline regarding its use. Our objective was to assess the indications for undertaking chest CT and the protocols used to obtain scans. Design Setting and participants: An electronic questionnaire was developed to assess clinicians views on chest CT in children with CF. It included general questions on perceived benefits and specific questions about its role in five clinical scenarios. It was sent to the clinical lead in 27 UK paediatric CF centres. A separate questionnaire was developed to collect the technical details of chest CT in children with CF. It was sent to the superintendent radiographer at each of the 27 centres. Results: Responses were obtained from 27 (100%) clinical leads and 22 (81%) superintendent radiographers. 93% clinicians reported chest CT useful in monitoring disease progression and 70% said it frequently altered management. Only 5 (19%) undertook routine scans. To aid diagnosis, 81% performed chest CT in non-tuberculous mycobacterial disease and 15% in allergic bronchopulmonary aspergillosis. There was wide variation in the perceived need for and/or timing of chest CT in children with reduced lung function with no benefit from intravenous antibiotics, new cystic changes on chest X-ray, and lobar collapse. The radiographers reported using a mixture of helical (volumetric) and axial scans depending on the clinical question, the age and the cooperation of the child. When indicated, 6 (27%) used sedation and 16 (73%) general anaesthetic. Only 1 (5%) used intravenous contrast routinely and 3 (14%) obtained expiratory images routinely. Conclusions: There is marked variation in the use of chest CT in children with CF and in the scan protocols. The lack of a national guideline is likely to be contributing to this lack of standardisation