Secukinumab for treating moderate to severe plaque psoriasis in children and young people – NICE Guidance

Recommendations

1.1Secukinumab is recommended as an option for treating plaque psoriasis in children and young people aged 6 to 17 years, only if:

• the disease is severe, as defined by a total Psoriasis Area and Severity Index (PASI) of 10 or more and
• the disease has not responded to other systemic treatments, including ciclosporin, methotrexate and phototherapy, or these options are contraindicated or not tolerated and
• the company provides the drug according to the commercial arrangement.

1.2Stop secukinumab treatment at 12 weeks if the psoriasis has not responded adequately. An adequate response is defined as a 75% reduction in the PASI score (PASI 75) from when treatment started.

1.3Choose the least expensive treatment if patients (or their parents or carers) and their clinicians consider secukinumab to be one of a range of suitable treatments. Take into account availability of biosimilar products, administration costs, dosage, price per dose and commercial arrangements.

1.4Take into account how skin colour could affect the PASI score and make any appropriate clinical adjustments.

1.5These recommendations are not intended to affect treatment with secukinumab that was started in the NHS before this guidance was published. People having treatment outside these recommendations may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop. This decision should be made jointly by the clinician, the child or young person and their parents or carers.

Why the committee made these recommendations

Secukinumab is a possible alternative to other biological treatments (adalimumab, etanercept and ustekinumab) already recommended by NICE for treating severe plaque psoriasis in children and young people.

Evidence from clinical trials shows that secukinumab is more effective than etanercept. Evidence from an indirect comparison suggests that it is similarly effective to ustekinumab. How its effectiveness compares with that of adalimumab is uncertain because of a lack of evidence, but adalimumab is thought to be similarly effective to ustekinumab.

Comparing the costs of secukinumab with those of adalimumab, etanercept and ustekinumab is appropriate because they work in a similar way and are all options for plaque psoriasis. The costs of secukinumab are similar to or lower than those of adalimumab, etanercept and ustekinumab. Therefore, secukinumab is recommended.

Link to full guidance here

Crizanlizumab for preventing sickle cell crises in sickle cell disease – NICE Guidance

Recommendations

1.1 Crizanlizumab is recommended as an option for preventing recurrent sickle cell crises (vaso-occlusive crises) in people aged 16 or over with sickle cell disease only if the conditions in the managed access agreement are followed.

1.2 This recommendation is not intended to affect treatment with crizanlizumab that was started in the NHS before this guidance was published. People having treatment outside this recommendation may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop.

Why the committee made these recommendations

Treatments to prevent sickle cell crises include hydroxycarbamide (also known as hydroxyurea), which is taken as a tablet, or regular blood transfusions. Crizanlizumab is a treatment injected into the vein (intravenous, or IV) that people aged 16 or over can take on its own or alongside hydroxycarbamide.

The clinical evidence suggests that people taking crizanlizumab have fewer sickle cell crises in a year than if they have best supportive care with or without hydroxycarbamide. However, because the trial was short and included only a small number of people on the licensed dose of the drug, the long-term benefits are uncertain.

There is also uncertainty about the cost-effectiveness estimates because some of the inputs used in the model do not reflect the clinical evidence. The most likely cost-effectiveness estimate is above what NICE normally considers a cost-effective use of NHS resources. Therefore, the committee could not recommend crizanlizumab for routine use in the NHS.

However, there is an unmet need for effective treatments for people with sickle cell disease. They also face health inequalities because the condition is not well understood, results in disability, and is more common in people of African or African-Caribbean family origin, who tend to have poorer health outcomes than other ethnicities. Access to crizanlizumab may help address these inequalities. Because of this, crizanlizumab is recommended for people with sickle cell disease and recurrent vaso-occlusive crises if more data is collected using a managed access agreement, to address the uncertainties in the evidence. This recommendation will be reviewed based on the data collected.

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Effect of Screen Time on Recovery From ConcussionA Randomized Clinical Trial

JAMA Pediatr. 2021;175(11):1124-1131.

Question  What is the effect of screen time in the first 48 hours after concussion on the duration of concussive symptoms?

Findings  In this randomized clinical trial including 125 patients with concussion aged 12 to 25 years, those who abstained from screen time during the first 48 hours of recovery had a statistically significant shorter duration of symptoms (3.5 days) than those who were permitted screen time (8 days).

Meaning  This study provides preliminary evidence supporting clinical recommendations to limit screen time in the acute period after concussion.Abstract

Importance  There are limited data to guide screen time recommendations after concussion.

ABSTRACT:

Objective  To determine whether screen time in the first 48 hours after concussion has an effect on the duration of concussive symptoms.

Design, Setting, and Participants  This randomized clinical trial was conducted in the pediatric and adult emergency departments of a tertiary medical center between June 2018 and February 2020. Participants included a convenience sample of patients aged 12 to 25 years presenting to the emergency department within 24 hours of sustaining a concussion. A total of 162 patients were approached, 22 patients met exclusion criteria, and 15 patients declined participation; 125 participants were enrolled and randomized.

Interventions  Patients were either permitted to engage in screen time (screen time permitted group) or asked to abstain from screen time (screen time abstinent group) for 48 hours after injury.

Main Outcomes and Measures  The primary outcome was days to resolution of symptoms, defined as a total Post-Concussive Symptom Scale (PCSS) score of 3 points or lower. Patients completed the PCSS, a 22-symptom scale that grades each symptom from 0 (not present) to 6 (severe), each day for 10 days. Kaplan-Meier curves and Cox regression modeling were used to compare the 2 groups. A Wilcoxon rank sum test was also performed among participants who completed the PCSS each day through recovery or conclusion of the study period.

Results  Among 125 patients with concussion, the mean (SD) age was 17.0 (3.4) years; 64 participants (51.2%) were male. A total of 66 patients were randomized to the screen time permitted group, and 59 patients were randomized to the screen time abstinent group. The Cox regression model including the intervention group and the patient’s self-identified sex demonstrated a significant effect of screen time (hazard ratio [HR], 0.51; 95% CI, 0.29-0.90), indicating that participants who engaged in screen time were less likely to recover during the study period. In total, 91 patients were included in the Wilcoxon rank sum test (47 patients from the screen time permitted group, and 44 patients from the screen time abstinent group). The screen time permitted group had a significantly longer median recovery time of 8.0 days (interquartile range [IQR], 3.0 to >10.0 days) compared with 3.5 days (IQR, 2.0 to >10.0 days; P = .03) in the screen time abstinent group. The screen time permitted group reported a median screen time of 630 minutes (IQR, 415-995 minutes) during the intervention period compared with 130 minutes (IQR, 61-275 minutes) in the screen time abstinent group.

Conclusions and Relevance  The findings of this study indicated that avoiding screen time during acute concussion recovery may shorten the duration of symptoms. A multicenter study would help to further assess the effect of screen time exposure.

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Clinical relevance of neutrophil-to-lymphocyte ratio and mean platelet volume in pediatric Henoch-Schonlein Purpura: a meta-analysis

Bioengineered. 2021 Dec;12(1):286-295.

Abstract

The association of neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume (MPV) with the severe gastrointestinal (GI) involvement in pediatric Henoch-Schonlein Purpura (HSP) has been reported in many studies. However, the conclusions from the previous studies were controversial. Therefore, for the first time, we performed a meta-analysis to systematically evaluate the relationship of NLR and MPV to the severe GI involvements. We retrieved PubMed, EMBASE, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) (up to October 2020) thoroughly to acquire eligible studies. The pooled standard mean difference (SMD) with 95% confidence interval (CI) was used to describe the correlation of NLR and MPV with the severe GI involvement. A total of 1² studies comprising 2168 patients with HSP were included in this meta-analysis. Our combined analysis showed that NLR in HSP patients with the severe GI involvement was significantly higher than that in those without the severe GI involvement (SMD = 1.37; 95% CI: 0.70-2.05; p < 0.01). In addition, a lower MPV was observed in children with severe GI involvement (SMD = -0.29; 95% CI: -0.56 – -0.01, p = 0.042). Our sensitivity analysis and publication bias evaluation indicated that our combined results were reliable.

Taken together, our study suggested NLR and MPV may be used as biomarkers for predicting or diagnosing the severe GI involvement in children with HSP. Nevertheless, more homogeneous studies with a larger sample size are required to validate these findings.

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Evidence-Based Practices for Children, Youth, and Young Adults with Autism: Third Generation Review

Image: Pixabay

J Autism Dev Disord. 2021 Nov;51(11):4013-4032. 

Abstract

This systematic review describes a set of practices that have evidence of positive effects with autistic children and youth. This is the third iteration of a review of the intervention literature (Odom et al. in J Autism Dev Disorders 40(4):425-436, 2010a; Prevent School Fail 54(4):275-282, 2010b; Wong et al. in https://autismpdc.fpg.unc.edu/sites/autismpdc.fpg.unc.edu/files/imce/documents/2014-EBP-Report.pdf ; J Autism Dev Disorders 45(7):1951-1966, 2015), extending coverage to articles published between 1990 and 2017. A search initially yielded 31,779 articles, and the subsequent screening and evaluation process found 567 studies to include.

Combined with the previous review, 972 articles were synthesized, from which the authors found 28 focused intervention practices that met the criteria for evidence-based practice (EBP). Former EBPs were recategorized and some manualized interventions were distinguished as meeting EBP criteria. The authors discuss implications for current practices and future research.

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Predictors of failed enema reduction in children with intussusception: a systematic review and meta-analysis

Eur Radiol. 2021 Nov;31(11):8081-8097.

Abstract

Objective: To identify predictors of failed enema reduction in children with intussusception.

Methods: PubMed and EMBASE were searched for all studies published over a 20-year time frame, prior to March 25, 2020. Original articles that reported predictors of failed enema reduction were included. The pooled odds ratio (OR) for successful enema reduction according to various features was calculated. The combined estimates were meta-analytically pooled by random-effects modeling. The risk of bias was assessed using the National Institute of Health Quality Assessment Tool. This review was registered to the PROSPERO (CRD42020190178).

Results: A total of 38 studies, comprising 40,133 cases, were included. The shorter duration of symptoms (< 24 h; combined OR, 3.812; 95% CI, 2.150-6.759) and abdominal pain (combined OR, 2.098; 95% CI, 1.405-3.133) were associated with the success (all p < 0.001). Age < 1 year (combined OR, 0.385; 95% CI, 0.166-0.893; p = 0.026), fever (combined OR, 0.519; 95% CI, 0.371-0.725; p < 0.001), rectal bleeding (combined OR, 0.252; 95% CI, 0.165-0.387; p < 0.001), and vomiting (combined OR, 0.497; 95% CI, 0.372-0.664; p < 0.001) were associated with the failed reduction. The ascites (combined OR, 0.127; 95% CI, 0.044-0.368; p = 0.001), left-sided intussusception (combined OR, 0.121; 95% CI, 0.058-0.252; p < 0.001), and trapped fluid (combined OR, 0.179; 95% CI, 0.061-0.525; p = 0.017) on US were associated with the failed reduction.

Conclusions: Successful predictors for intussusception reduction have been summarized. This evidence can help identify patients who are more likely to fail non-operative reduction and could be potential surgical candidates.

Key points: • A shorter duration of symptoms and presence of abdominal pain were associated with increased probability of success. • Age (less than 1 year), presence of fever, rectal bleeding, vomiting, and presence of ascites, left-sided intussusception, or trapped fluid on ultrasonography were associated with decreased probability of success. • This study suggests that various clinical and ultrasonography predictors would help identify patients who are more likely to fail nonoperative reduction and identify potential preoperative candidates.

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Multisystem inflammatory syndrome in children (MISC): A systematic review

Int J Clin Pract. 2021 Nov;75(11):e14450.

Abstract

Objective: The aim of this systematic review was to analyse current literature and reported cases of multisystem inflammatory syndrome in children (MISC), concerning its clinical spectrum, complications associated, therapeutic strategies and distinguishing features of other clinical syndromes.

Methods: Extensive literature research was performed in MEDLINE (through PubMed), Scopus and Web of Science from December 2019 to December 2020. First analysis included all article titles and abstracts screening to identify relevant studies, and second analysis included a full-text screening of previously selected studies. Eligibility was assessed independently by two authors, and disagreements were resolved by discussion and consensus. Data were extracted on MISC definition, demographic data, clinical features, diagnostic tests, laboratory analysis and imaging, therapeutical approach and outcomes.

Results: Common symptoms included gastrointestinal (70%), rash (57%) and cardiovascular (52% with shock). Notable differences with Kawasaki disease were identified including age, clinical presentation and cardiac involvement. Thirty per cent presented positive severe acute respiratory syndrome coronavirus-2 reverse transcription polymerase chain reaction and 51% positive serologies. Sixty-two per cent received intravenous immunoglobulin and 42% glucocorticoids. Sixty-two per cent required intensive care and 21 children died (<2%). Severe presentations were associated with neurological symptoms, hepatitis and acute kidney injury.

Conclusions: MISC raises concern on its severe cardiac involvement at presentation, with frequent intensive care and immunomodulatory therapy need. Short-term outcomes seem to be favourable, with cardiac dysfunction recovery and low mortality rates.

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Accuracy of PECARN decision rule in minor blunt head trauma in pediatric emergency department: A meta-analysis

Clin Pract. 2021 Nov;75(11):e14586.

Abstract

Background: Paediatric Emergency Care Applied Research Network (PECARN) is a useful Clinical Decision Support Tool (CDST) to identify traumatic brain injuries and reduce the use of head computed tomography (CT) scans among paediatric patients. The present Meta-analysis aims to evaluate the diagnostic accuracy of the PECARN rule from 2009 to 2020 in children with a very low risk of blunt head trauma.

Methods: A detailed search was conducted from the databases of Medline (via PubMed), Cinahl (via Ebsco), Scopus, Web of Sciences, from 2009 till the end of December 2020 using the keywords like decreased use of CT scan, blunt head trauma (BHT) combined with accuracy, PECARN OR CDST. Studies showing the diagnostic accuracy of the PECARN rule in children younger than 18 years of age with minor BHT were included.

Results: Thirteen studies were included in the present analysis. Pooled sensitivity of 0.08, (95% confidence interval of 0.074-0.087), pooled specificity of 0.20 (95% CI of 0.196-0.213) and diagnostic odds ratio of 0.004 (95% CI of 0.000-0.1666) was in <2 years of age. The overall sensitivity of 0.07, specificity of 0.66, and the diagnostic odds ratio of 0.54 (95% CI of 0.10-2.78) were seen in ≥2 years of age. Overall sensitivity of 0.13 (95% CI 0.12-0.14), specificity of 0.81 (95% CI 0.80-0.82) and diagnostic odds ratio of 0.79 (95% CI of 0.08-7.71) was in 0-18 years of age.

Conclusion: The present analysis indicates the PECARN decision tool as an accurate CDST in low-risk minor BHT cases in children below two years of age and can become a valuable tool in reducing Head CT scan overuse in paediatric emergency departments.

Abstract

Background: Paediatric Emergency Care Applied Research Network (PECARN) is a useful Clinical Decision Support Tool (CDST) to identify traumatic brain injuries and reduce the use of head computed tomography (CT) scans among paediatric patients. The present Meta-analysis aims to evaluate the diagnostic accuracy of the PECARN rule from 2009 to 2020 in children with a very low risk of blunt head trauma.

Methods: A detailed search was conducted from the databases of Medline (via PubMed), Cinahl (via Ebsco), Scopus, Web of Sciences, from 2009 till the end of December 2020 using the keywords like decreased use of CT scan, blunt head trauma (BHT) combined with accuracy, PECARN OR CDST. Studies showing the diagnostic accuracy of the PECARN rule in children younger than 18 years of age with minor BHT were included.

Results: Thirteen studies were included in the present analysis. Pooled sensitivity of 0.08, (95% confidence interval of 0.074-0.087), pooled specificity of 0.20 (95% CI of 0.196-0.213) and diagnostic odds ratio of 0.004 (95% CI of 0.000-0.1666) was in <2 years of age. The overall sensitivity of 0.07, specificity of 0.66, and the diagnostic odds ratio of 0.54 (95% CI of 0.10-2.78) were seen in ≥2 years of age. Overall sensitivity of 0.13 (95% CI 0.12-0.14), specificity of 0.81 (95% CI 0.80-0.82) and diagnostic odds ratio of 0.79 (95% CI of 0.08-7.71) was in 0-18 years of age.

Conclusion: The present analysis indicates the PECARN decision tool as an accurate CDST in low-risk minor BHT cases in children below two years of age and can become a valuable tool in reducing Head CT scan overuse in paediatric emergency departments.

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Systematic Review and Meta-Analysis of Diagnostic Biomarkers for Pediatric Pneumonia

J Pediatric Infect Dis Soc. 2021 Oct 27;10(9):891-900.

Abstract

Background: Pneumonia causes significant morbidity and mortality in children worldwide, especially in resource-poor settings. Accurate identification of bacterial etiology leads to timely antibiotic initiation, minimizing overuse, and development of resistance. Host biomarkers may improve diagnostic sensitivity and specificity. We assessed the ability of biomarkers to correctly identify bacterial pneumonia in children who present with respiratory distress.

Methods: A librarian-directed search was conducted of MEDLINE, EMBASE, CENTRAL, Global Health, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov to May 2020 with no language restriction. Included studies compared a diagnostic biomarker in children with bacterial pneumonia to those with nonbacterial respiratory distress.

Results: There were 31 observational studies of 23 different biomarkers. C-reactive protein (CRP), procalcitonin (PCT), white blood cell (WBC) count, and erythrocyte sedimentation rate (ESR) were the biomarkers with sufficient data for meta-analysis. Meta-analysis revealed that CRP and PCT best differentiated bacterial from viral pneumonia with CRP summary AUROC (area under the receiver operating characteristic curve) 0.71 (0.69-0.73), Youden index 53 mg/L, sensitivity 0.70 (0.68-0.78), and specificity 0.64 (0.58-0.68) and PCT summary AUROC 0.70 (0.67-0.74), Youden index 0.59 ng/mL, sensitivity 0.69 (0.65-0.77), and specificity 0.64 (0.60-0.68). WBC and ESR did not perform as well. Nineteen other inflammatory and immunologic biomarkers were identified including CRP/mean platelet value, neutrophil/leukocyte ratio, interleukin 6, and interferon-alpha, with sensitivities from 60% to 85% and specificities from 76% to 83%.

Conclusion: CRP and PCT performed better than WBC and ESR but had suboptimal sensitivity. Some less well-studied novel biomarkers appear to have promise particularly in combination.

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Tools available to screen for child feeding dysfunction: A systematic review

Appetite. 2021 Dec 1;167:105611.

Abstract

Introduction: The aim of this systematic review is to identify existing pediatric feeding screening tools that have been shown to be valid and reliable in identifying feeding dysfunction in children.

Method: A database search produced 5862 relevant articles to be screened based on pre-determined inclusion/exclusion criteria. After full text review of 183 articles, 64 articles were included in the review.

Results: Forty-four studies detailed development and validation of unique feeding screening tools for the pediatric population. The remaining twenty studies were validations studies of already developed screening tools.

Discussion: Multiple screening tools identified were effective in determining feeding dysfunction in children. Several tools employed excellent techniques to measure reliability and validity for diverse pediatric populations. Careful consideration of the tools listed in this review will help practitioners determine the best method for feeding screening in their facility.

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