Asthma medication adherence and exacerbations and lung function in children managed in Leicester primary care.

Poor adherence to asthma preventer medication is associated with life-threatening asthma attacks. The quality and outcomes framework mandated primary care annual asthma review does not include adherence monitoring and the effect of poor adherence on lung function in paediatric primary care patients is unknown. The aim was to investigate the link between inhaled corticosteroid (ICS) adherence and spirometry, fraction of exhaled nitric oxide (FeNO) and asthma control in asthmatic school-age children in this cross-sectional observational study involving three Leicestershire general practices. Children 5-16 years on the practice's asthma registers, were invited for a routine annual asthma review between August 2018 and August 2019. Prescription and clinical data were extracted from practice databases. Spirometry, bronchodilator reversibility (BDR) and FeNO testing were performed as part of the review. 130 of 205 eligible children (63.4%) attended their review. Mean adherence to ICS was 36.2% (SEM 2.1%) and only 14.6% of children had good adherence (≥75% prescriptions issued). We found no differences in asthma exacerbations in the preceding 12 months between the adherence quartiles. 28.6% of children in the lowest and 5.6% in the highest adherence quartile had BDR ≥ 12% but this was not statistically significant (p = 0.55). A single high FeNO value did not predict adherence to ICS. Adherence to ICS in children with asthma in primary care is poor. The link between adherence to ICS and asthma exacerbations, spirometry and FeNO is complex but knowledge of adherence to ICS is critical in the management of children with asthma.

Serial Genotyping of the Human Papillomavirus in Cervical Cancer: An Insight Into Virome Dynamics During Chemoradiation Therapy.

PURPOSE: Human papillomavirus (HPV) is the primary driver of cervical cancer. Although studies in other malignancies correlated peripheral blood DNA clearance with favorable outcomes, research on the prognostic value of HPV clearance in gynecologic cancers using intratumoral HPV is scarce. We aimed to quantify the intratumoral HPV virome in patients undergoing chemoradiation therapy (CRT) and associate this with clinical characteristics and outcomes. METHODS AND MATERIALS: This prospective study enrolled 79 patients with stage IB-IVB cervical cancer undergoing definitive CRT. Cervical tumor swabs collected at baseline and week 5 (end of intensity modulated radiation therapy) were sent for shotgun metagenome sequencing and processed via VirMAP, a viral genome sequencing and identification tool for all known HPV types. The data were categorized into HPV groups (16, 18, high risk [HR], and low risk [LR]). We used independent t tests and Wilcoxon signed-rank to compare continuous variables and χ2 and Fisher exact tests to compare categorical variables. Kaplan-Meier survival modeling was performed with log-rank testing. HPV genotyping was verified using quantitative polymerase chain reaction to validate VirMAP results using receiver operating characteristic curve and Cohen's kappa. RESULTS: At baseline, 42%, 12%, 25%, and 16% of patients were positive for HPV 16, HPV 18, HPV HR, and HPV LR, respectively, and 8% were HPV negative. HPV type was associated with insurance status and CRT response. Patients with HPV 16+ and other HPV HR+ tumors were significantly more likely to have a complete response to CRT versus patients with HPV 18 and HPV LR/HPV-negative tumors. Overall HPV viral loads predominantly decreased throughout CRT, except for HPV LR viral load. CONCLUSIONS: Rarer, less well-studied HPV types in cervical tumors are clinically significant. HPV 18 and HPV LR/negative tumors are associated with poor CRT response. This feasibility study provides a framework for a larger study of intratumoral HPV profiling to predict outcomes in patients with cervical cancer.

Practical approaches to the diagnosis of asthma in school-age children.

INTRODUCTION: Asthma is a chronic airways disease characterized by episodes of wheeze, chest tightness, and evidence of reversible airflow obstruction. Symptoms are frequently triggered by exercise, exposure to aeroallergens, and respiratory viruses. It is the commonest non-communicable respiratory condition in children, affecting over 5.5 million children in the European Union alone. Both over- and under- diagnosis of asthma are common for several reasons. AREAS COVERED: The diagnosis is frequently based on parental or patient reported non-specific symptoms alone. All major asthma guidelines now recommend the use of objective tests, including spirometry, bronchodilator reversibility testing, fraction of exhaled nitric oxide measurements and challenge testing to confirm the diagnosis. Recently, the European Respiratory Society published the first evidence-based international guidelines for diagnosing asthma in school-age children using objective measures. Major barriers to implementation in primary care and less well-resourced healthcare settings are access to relevant objective tests for children and quality assurance to obtain reliable results. EXPERT OPINION: We highlight the importance of diagnosing asthma in school-age children using objective tests and outline a practical approach for the use of widely available tests. We also review challenges and barriers to implementation of objective testing in children managed outside specialist settings.

Precision Medicine for Paediatric Severe Asthma: Current Status and Future Direction.

Asthma is a heterogeneous disease, characterised by different phenotypes and endotypes. Precision medicine in asthma refers to the implementation of a targeted therapy for each individual child, based on the identification of treatable traits, including environmental, immunological and genetic factors. Severe asthma in children is associated with increased hospitalisation rates, a lower quality of life, increased healthcare costs and an increased mortality. In the era of new molecular biologics treatments, it is essential to improve deep phenotyping of children with severe asthma in order to deliver the most effective treatment to each individual child. In this review, we discuss the personalised approach to the assessment and management of severe asthma. We explore the indications and use of the currently licensed biologics, as well as the potential of other emerging treatments.

European Respiratory Society clinical practice guidelines for the diagnosis of asthma in children aged 5-16†years.

BACKGROUND: Diagnosing asthma in children represents an important clinical challenge. There is no single gold-standard test to confirm the diagnosis. Consequently, over- and under-diagnosis of asthma is frequent in children. METHODS: A task force supported by the European Respiratory Society has developed these evidence-based clinical practice guidelines for the diagnosis of asthma in children aged 5-16 years using nine Population, Intervention, Comparator and Outcome (PICO) questions. The task force conducted systematic literature searches for all PICO questions and screened the outputs from these, including relevant full-text articles. All task force members approved the final decision for inclusion of research papers. The task force assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: The task force then developed a diagnostic algorithm based on the critical appraisal of the PICO questions, preferences expressed by lay members and test availability. Proposed cut-offs were determined based on the best available evidence. The task force formulated recommendations using the GRADE Evidence to Decision framework. CONCLUSION: Based on the critical appraisal of the evidence and the Evidence to Decision framework, the task force recommends spirometry, bronchodilator reversibility testing and exhaled nitric oxide fraction as first-line diagnostic tests in children under investigation for asthma. The task force recommends against diagnosing asthma in children based on clinical history alone or following a single abnormal objective test. Finally, this guideline also proposes a set of research priorities to improve asthma diagnosis in children in the future.

The role of objective tests to support a diagnosis of asthma in children.

In many healthcare settings asthma in children is a clinical diagnosis based on parental reported symptoms. These include intermittent episodes of wheezing, breathlessness and periodic nocturnal dry cough. Increased symptoms often coincide with colds. Confirming a diagnosis of asthma in children can be difficult and recent reports highlight that misdiagnosis, including over- and under-diagnosis of asthma are common. Recent UK National Institute of Health and Care Excellence guidelines recommend diagnostic algorithms for children from five years and adults to support a clinical suspicion of asthma. Spirometry, bronchodilator reversibility and fractional exhaled nitric oxide testing are the first line tests to diagnose asthma in children. The introduction of these tests across all healthcare settings has the potential to reduce misdiagnosis, improve asthma management and reduce healthcare spending for asthma.

Prospective observational cohort study of symptom control prediction in paediatric asthma by using the Royal College of Physicians three questions.

The Royal College of Physicians three questions (RCP3Q) is widely used for assessing asthma control within primary care in the UK, despite limited evidence in children. This study compared the RCP3Q as a tool for assessing asthma control in children (5-16 years) against the validated Asthma Control Test (ACT), Childhood Asthma Control Test (C-ACT), and Mini-Paediatric Quality of Life Questionnaire (MiniPAQLQ). We conducted a prospective observational cohort study involving children from eight primary care practices in Leicestershire. Children with doctor diagnosed asthma, or receiving regular asthma medication, were invited to participate. A total of 319 participants completed the MiniPAQLQ and the C-ACT/ACT questionnaires, before RCP3Q responses were collected as part of their routine asthma review conducted immediately afterwards. RCP3Q sensitivity for detecting uncontrolled asthma ranged from 43-60% and specificity from 80-82%. Using an RCP3Q score ≥2 to predict uncontrolled asthma and an RCP3Q score of zero to predict well-controlled asthma resulted in 10% of participants misclassified as uncontrolled and 8% as well-controlled, respectively. Using an RCP3Q threshold score of ≥1 resulted in 25% of participants being misclassified as uncontrolled. Our data suggests limited utility of the RCP3Q to assess asthma control in children. Alternative indicators of asthma control, such as the validated Asthma Control Test and the Children's Asthma Control Test should be considered instead.

Interventions for the eradication of meticillin-resistant Staphylococcus aureus (MRSA) in people with cystic fibrosis.

BACKGROUND: Cystic fibrosis is an inherited recessive disorder of chloride transport that is characterised by recurrent and persistent pulmonary infections from resistant organisms that result in lung function deterioration and early mortality in sufferers.Meticillin-resistant Staphylococcus aureus (MRSA) has emerged as, not only an important infection in long-term hospitalised patients, but also as a potentially harmful pathogen in cystic fibrosis, and has been increasing steadily in prevalence internationally. Chronic pulmonary infection with MRSA is thought to confer cystic fibrosis patients with a worse overall clinical outcome and, in particular, result in an increased rate of decline in lung function. Clear guidance for the eradication of MRSA in cystic fibrosis, supported by robust evidence from good quality trials, is urgently needed. OBJECTIVES: To evaluate the effectiveness of treatment regimens designed to eradicate MRSA and to determine whether the eradication of MRSA confers better clinical and microbiological outcomes for people with cystic fibrosis. SEARCH METHODS: Randomised and quasi-randomised controlled trials were identified by searching the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register, PUBMED, MEDLINE, Embase, handsearching article reference lists and through contact with local and international experts in the field.Date of the last search of the Group's Cystic Fibrosis Trials Register: 04 September 2014. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing any combinations of topical, inhaled, oral or intravenous antimicrobials with the primary aim of eradicating MRSA compared with placebo, standard treatment or no treatment. DATA COLLECTION AND ANALYSIS: The authors independently assessed all search results for eligibility. No eligible trials were identified for inclusion. MAIN RESULTS: No current published eligible trials were identified, although three ongoing clinical trials are likely to be eligible for inclusion in future updates of this review. AUTHORS' CONCLUSIONS: We did not identify any randomised trials which would allow us to make any evidence-based recommendations. Although the results of several non-randomised studies would suggest that, once isolated, the eradication of MRSA is possible; whether this has a significant impact on clinical outcome is still unclear. Further research is required to guide clinical decision making in the management of MRSA infection in cystic fibrosis.

Interventions for the eradication of methicillin-resistant Staphylococcus aureus (MRSA) in people with cystic fibrosis.

BACKGROUND: Cystic fibrosis is an inherited recessive disorder of chloride transport that is characterised by recurrent and persistent pulmonary infections from resistant organisms that result in lung function deterioration and early mortality in sufferers.Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as, not only an important infection in long-term hospitalised patients, but also as a potentially harmful pathogen in cystic fibrosis, and has been increasing steadily in prevalence internationally. Chronic pulmonary infection with MRSA is thought to confer cystic fibrosis patients with a worse overall clinical outcome and, in particular, result in an increased rate of decline in lung function. Clear guidance for the eradication of MRSA in cystic fibrosis, supported by robust evidence from good quality trials, is urgently needed. OBJECTIVES: To evaluate the effectiveness of treatment regimens designed to eradicate MRSA and to determine whether the eradication of MRSA confers better clinical and microbiological outcomes for people with cystic fibrosis. SEARCH METHODS: Randomised and quasi-randomised controlled trials were identified by searching the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register, MEDLINE, EMBASE, handsearching article reference lists and through contact with local and international experts in the field.Date of the last search of the Group's Cystic Fibrosis Trials Register: 24 January 2013. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing any combinations of topical, inhaled, oral or intravenous antimicrobials with the primary aim of eradicating MRSA compared with placebo, standard treatment or no treatment. DATA COLLECTION AND ANALYSIS: The authors independently assessed all search results for eligibility. No eligible trials were identified. MAIN RESULTS: No current published eligible trials were identified, although two ongoing clinical trials are likely to be eligible for inclusion in future updates of this review. AUTHORS' CONCLUSIONS: We did not identify any randomised trials which would allow us to make any evidence-based recommendations. Although the results of several non-randomised studies would suggest that, once isolated, the eradication of MRSA is possible; whether this has a significant impact on clinical outcome is still unclear. Further research is required to guide clinical decision making in the management of MRSA infection in cystic fibrosis.