Abigail Moore

Multi-Cellular Rosettes in the Mouse Visceral Endoderm Facilitate the Ordered Migration of Anterior Visceral Endoderm Cells

Modeling and experimental results suggest a role for Planar Cell Polarity-dependent multi-cellular rosette structures in ensuring correct epithelial cell migration in the mouse visceral endoderm.

Recognising Kawasaki disease in UK primary care: a descriptive study using the Clinical Practice Research Datalink

BACKGROUND Kawasaki disease is a rare childhood illness that can present non-specifically, making it a diagnostic challenge. The clinical presentation of Kawasaki disease has not been previously described in primary care. AIM To describe how children with an eventual diagnosis of Kawasaki disease initially present to primary care in the UK. DESIGN AND SETTING The Clinical Practice Research Datalink was used to find cases coded as Kawasaki disease. Hospital Episode Statistics, hospital admissions, and hospital outpatient attendances were used to identify the children with a convincing diagnosis of Kawasaki disease. METHOD Questionnaires and a request for copies of relevant hospital summaries, discharge letters, and reports were sent to GPs of the 104 children with a diagnosis of Kawasaki disease between 2007 and 2011. RESULTS Most children presented with few clinical features typical of Kawasaki disease. Of those with just one feature, a fever or a polymorphous rash were the most common. By the time that most children were admitted to hospital they had a more recognisable syndrome, with three or more clinical features diagnostic of Kawasaki disease. Most GPs did not consider Kawasaki disease among their differential diagnoses, but some GPs did suspect that the childs illness was unusual. CONCLUSION The study highlighted the difficulty of early diagnosis, with most children having a non-specific presentation to primary care. GPs are encouraged to implement good safety netting, and to keep Kawasaki disease in mind when children present with fever and rashes.

Cough Due to TB and Other Chronic Infections: CHEST Guideline and Expert Panel Report

Background Cough is common in pulmonary TB and other chronic respiratory infections. Identifying features that predict whether pulmonary TB is the cause would help target appropriate individuals for rapid and cost‐effective screening, potentially limiting disease progression and preventing transmission to others. Methods A systematic literature search for individual studies to answer eight key questions (KQs) was conducted according to established Chest Organization methods by using the following databases: MEDLINE via PubMed, Embase, Scopus, and the Cochrane Database of Systematic Reviews from January 1, 1984, to April 2014. Searches for KQ 1 and KQ 3 were updated in February 2016. An updated KQ 2 search was undertaken in March 2017. Results Even where TB prevalence is greatest, most individuals with cough do not have pulmonary TB. There was no evidence that 1, 3, or 4 weeks’ duration were better predictors than cough lasting ≥ 2 weeks to screen for pulmonary TB. In people living with HIV (PLWHIV), screening for fever, night sweats, hemoptysis, and/or weight loss in addition to cough (any World Health Organization [WHO]‐endorsed symptom) increases the diagnostic sensitivity for TB. Although the diagnostic accuracy of symptom‐based screening remains low, the negative predictive value of the WHO‐endorsed symptom screen in PLWHIV may help to risk‐stratify individuals who are not close TB contacts and who do not require further testing for pulmonary TB in resource‐limited settings. However, pregnant PLWHIV are more likely to be asymptomatic, and the WHO‐endorsed symptom screen is not sensitive enough to be reliable. Combined with passive case finding (PCF), active case finding (ACF) identifies pulmonary TB cases earlier and possibly when less advanced. Whether outcomes are improved or transmission is reduced is unclear. Screening asymptomatic patients is cost‐effective only in populations with a very high TB prevalence. The Xpert MTB/RIF assay on sputum is more cost‐effective than clinical diagnosis. To our knowledge, no published comparative studies addressed whether the rate of cough resolution is a reliable determinant of the response to treatment or whether the rate of cough resolution was faster in the absence of cavitary lung disease. All studies on cough prevalence in Mycobacterium avium complex (MAC) lung disease, other nontuberculous mycobacterial infections, fungal lung disease, and paragonimiasis were of poor quality and were excluded from the evidence review. Conclusions On the basis of relatively few studies of fair to good quality, we conclude that most individuals at high risk and household contacts with cough ≥ 2 weeks do not have pulmonary TB, but we suggest screening them regardless of cough duration. In PLWHIV, the addition of the other WHO‐endorsed symptoms increases the diagnostic sensitivity of cough. Earlier screening of patients with cough will help diagnose pulmonary TB sooner but will increase the cost of screening. The addition of ACF to PCF will increase the number of pulmonary TB cases identified. Screening asymptomatic individuals is cost‐effective only in groups with a very high TB prevalence. Data are insufficient to determine whether cough resolution is delayed in individuals with cavitary lung disease or in those for whom treatment fails because of drug resistance, poor adherence, and/or drug malabsorption compared with results in other individuals with pulmonary TB. Cough is common in patients with lung infections due to MAC, other nontuberculous mycobacteria, fungal diseases, and paragonimiasis.

Clinical characteristics of pertussis-associated cough in adults and children: a diagnostic systematic review and meta-analysis

Background Pertussis (whooping cough) is a highly infective cause of cough that causes significant morbidity and mortality. Existing case definitions include paroxysmal cough, whooping, and posttussive vomiting, but diagnosis can be difficult. We determined the diagnostic accuracy of clinical characteristics of pertussis‐associated cough. Methods We systematically searched CINAHL, Embase, Medline, and SCI‐EXPANDED/CPCI‐S up to June 2016. Eligible studies compared clinical characteristics in those positive and negative for Bordetella pertussis infection, confirmed by laboratory investigations. Two authors independently completed screening, data extraction, and quality and bias assessments. For each characteristic, RevMan was used to produce descriptive forest plots. The bivariate meta‐analysis method was used to generate pooled estimates of sensitivity and specificity. Results Of 1,969 identified papers, 53 were included. Forty‐one clinical characteristics were assessed for diagnostic accuracy. In adult patients, paroxysmal cough and absence of fever have a high sensitivity (93.2% [CI, 83.2‐97.4] and 81.8% [CI, 72.2‐88.7], respectively) and low specificity (20.6% [CI, 14.7‐28.1] and 18.8% [CI, 8.1‐37.9]), whereas posttussive vomiting and whooping have low sensitivity (32.5% [CI, 24.5‐41.6] and 29.8% [CI, 8.0‐45.2]) and high specificity (77.7% [CI, 73.1‐81.7] and 79.5% [CI, 69.4‐86.9]). Posttussive vomiting in children is moderately sensitive (60.0% [CI, 40.3‐77.0]) and specific (66.0% [CI, 52.5‐77.3]). Conclusions In adult patients, the presence of whooping or posttussive vomiting should rule in a possible diagnosis of pertussis, whereas the lack of a paroxysmal cough or the presence of fever should rule it out. In children, posttussive vomiting is much less helpful as a clinical diagnostic test.

Treatment of Interstitial Lung Disease Associated Cough: CHEST Guideline and Expert Panel Report

Background Chronic cough in interstitial lung disease (ILD) causes significant impairment in quality of life. Effective treatment approaches are needed for cough associated with ILD. Methods This systematic review asked: Is there evidence of clinically relevant treatment effects for therapies for cough in ILD? Studies of adults aged > 18 years with a chronic cough ≥ 8 weeks’ duration were included and assessed for relevance and quality. Based on the systematic review, guideline suggestions were developed and voted on by using CHEST guideline methodology. Results Eight randomized controlled trials and two case series (≥ 10 patients) were included that reported data on patients with idiopathic pulmonary fibrosis, sarcoidosis, and scleroderma‐related ILD who received a variety of interventions. Study quality was high in all eight randomized controlled trials. Inhaled corticosteroids were not supported for cough associated with sarcoidosis. Cyclophosphamide and mycophenolate were not supported for solely treating cough associated with scleroderma‐associated ILD. A recommendation for thalidomide to treat cough associated with idiopathic pulmonary fibrosis did not pass the panel vote. In view of the paucity of antitussive treatment options for refractory cough in ILD, the guideline panel suggested that the CHEST unexplained chronic cough guideline be followed by considering options such as the neuromodulator gabapentin and speech pathology management. Opiates were also suggested for patients with cough refractory to alternative therapies. Conclusions The evidence supporting the management of chronic cough in ILD is limited. This guideline presents suggestions for managing and treating cough on the best available evidence, but future research is clearly needed.

Chronic Cough Related to Acute Viral Bronchiolitis in Children.

Background Acute bronchiolitis is common in young children, and some children develop chronic cough after their bronchiolitis. We thus undertook systematic reviews based on key questions (KQs) using the PICO (Population, Intervention, Comparison, Outcome) format. The KQs were: Among children with chronic cough (> 4 weeks) after acute viral bronchiolitis, how effective are the following interventions in improving the resolution of cough?: (1) Antibiotics. If so what type and for how long? (2) Asthma medications (inhaled steroids, beta2 agonist, montelukast); and (3) Inhaled osmotic agents like hypertonic saline? Methods We used the CHEST expert cough panel’s protocol and the American College of Chest Physicians (CHEST) methodological guidelines and GRADE framework. Data from the systematic reviews in conjunction with patients’ values and preferences and the clinical context were used to form these suggestions. Delphi methodology was used to obtain consensus. Results Several studies and systematic reviews on the efficacy of the three types of interventions listed in the introduction were found but no data were relevant to our KQs. Thus, no recommendations on using the interventions above could be formulated. Conclusions The panel made several consensus‐based suggestions and identified directions for future studies to advance the field of managing chronic cough post‐acute bronchiolitis in children.

Clinically Diagnosing Pertussis-Associated Cough in Adults and Children: Chest Guideline and Expert Panel Report

BACKGROUND: The decision to treat a suspected case of pertussis with antibiotics is usually based on a clinical diagnosis rather than waiting for laboratory confirmation. The current guideline focuses on making the clinical diagnosis of pertussis‐associated cough in adults and children. METHODS: The American College of Chest Physicians (CHEST) methodologic guidelines and the Grading of Recommendations, Assessment, Development, and Evaluation framework were used. The Expert Cough Panel based their recommendations on findings from a systematic review that was recently published on the topic; final grading was reached by consensus according to Delphi methodology. The systematic review was carried out to answer the Key Clinical Question: In patients presenting with cough, how can we most accurately diagnose from clinical features alone those who have pertussis‐associated cough as opposed to other causes of cough? RESULTS: In adults, after pre‐specified meta‐analysis exclusions, pooled estimates of sensitivity and specificity were generated for only 4 clinical features: paroxysmal cough, post‐tussive vomiting, inspiratory whooping, and absence of fever. Both paroxysmal cough and absence of fever had high sensitivity (93.2% [95% CI, 83.2‐97.4] and 81.8% [95% CI, 72.2‐88.7], respectively) and low specificity (20.6% [95% CI, 14.7‐28.1] and 18.8% [95% CI, 8.1‐37.9]). Inspiratory whooping and posttussive vomiting had a low sensitivity (32.5% [95% CI, 24.5‐41.6] and 29.8% [95% CI, 18.0‐45.2]) but high specificity (77.7% [95% CI, 73.1‐81.7] and 79.5% [95% CI, 69.4‐86.9]). In children, after pre‐specified meta‐analysis exclusions, pooled estimates of sensitivity and specificity were generated for only 1 clinical feature in children (0‐18 years): posttussive vomiting. Posttussive vomiting in children was only moderately sensitive (60.0% [95% CI, 40.3‐77.0]) and specific (66.0% [95% CI, 52.5‐77.3]). CONCLUSIONS: In adults with acute (< 3 weeks) or subacute (3‐8 weeks) cough, the presence of whooping or posttussive vomiting should rule in a possible diagnosis of pertussis, whereas the lack of a paroxysmal cough or the presence of fever should rule it out. In children with acute (< 4 weeks) cough, posttussive vomiting is suggestive of pertussis but is much less helpful as a clinical diagnostic test. Guideline suggestions are made based upon these findings and conclusions.

Cough Due to TB and Other Chronic Infections

Background Cough is common in pulmonary TB and other chronic respiratory infections. Identifying features that predict whether pulmonary TB is the cause would help target appropriate individuals for rapid and cost‐effective screening, potentially limiting disease progression and preventing transmission to others. Methods A systematic literature search for individual studies to answer eight key questions (KQs) was conducted according to established Chest Organization methods by using the following databases: MEDLINE via PubMed, Embase, Scopus, and the Cochrane Database of Systematic Reviews from January 1, 1984, to April 2014. Searches for KQ 1 and KQ 3 were updated in February 2016. An updated KQ 2 search was undertaken in March 2017. Results Even where TB prevalence is greatest, most individuals with cough do not have pulmonary TB. There was no evidence that 1, 3, or 4 weeks’ duration were better predictors than cough lasting ≥ 2 weeks to screen for pulmonary TB. In people living with HIV (PLWHIV), screening for fever, night sweats, hemoptysis, and/or weight loss in addition to cough (any World Health Organization [WHO]‐endorsed symptom) increases the diagnostic sensitivity for TB. Although the diagnostic accuracy of symptom‐based screening remains low, the negative predictive value of the WHO‐endorsed symptom screen in PLWHIV may help to risk‐stratify individuals who are not close TB contacts and who do not require further testing for pulmonary TB in resource‐limited settings. However, pregnant PLWHIV are more likely to be asymptomatic, and the WHO‐endorsed symptom screen is not sensitive enough to be reliable. Combined with passive case finding (PCF), active case finding (ACF) identifies pulmonary TB cases earlier and possibly when less advanced. Whether outcomes are improved or transmission is reduced is unclear. Screening asymptomatic patients is cost‐effective only in populations with a very high TB prevalence. The Xpert MTB/RIF assay on sputum is more cost‐effective than clinical diagnosis. To our knowledge, no published comparative studies addressed whether the rate of cough resolution is a reliable determinant of the response to treatment or whether the rate of cough resolution was faster in the absence of cavitary lung disease. All studies on cough prevalence in Mycobacterium avium complex (MAC) lung disease, other nontuberculous mycobacterial infections, fungal lung disease, and paragonimiasis were of poor quality and were excluded from the evidence review. Conclusions On the basis of relatively few studies of fair to good quality, we conclude that most individuals at high risk and household contacts with cough ≥ 2 weeks do not have pulmonary TB, but we suggest screening them regardless of cough duration. In PLWHIV, the addition of the other WHO‐endorsed symptoms increases the diagnostic sensitivity of cough. Earlier screening of patients with cough will help diagnose pulmonary TB sooner but will increase the cost of screening. The addition of ACF to PCF will increase the number of pulmonary TB cases identified. Screening asymptomatic individuals is cost‐effective only in groups with a very high TB prevalence. Data are insufficient to determine whether cough resolution is delayed in individuals with cavitary lung disease or in those for whom treatment fails because of drug resistance, poor adherence, and/or drug malabsorption compared with results in other individuals with pulmonary TB. Cough is common in patients with lung infections due to MAC, other nontuberculous mycobacteria, fungal diseases, and paragonimiasis.

Pertussis has low prevalence in adults with acute cough and is difficult to distinguish clinically from other causes

Commentary on: Teepe J, Broekhuizen BD, Ieven M, et al. Prevalence, diagnosis, and disease course of pertussis in adults with acute cough: a prospective, observational study in primary care. Br J Gen Pract 2015;65:e662–7.[OpenUrl][1][Abstract/FREE Full Text][2] Pertussis (whooping cough) is an important cause of persistent cough, even in fully vaccinated individuals, where risk of pertussis increases with time since vaccination.1 ,2 In adults, symptoms may be milder and without the classical paroxysms, whoop and vomiting traditionally associated with pertussis, but nonetheless can be associated with considerable morbidity.1 Several previous studies have investigated incidence and clinical characteristics of pertussis in adults with persistent cough, including a recent study in New Zealand (2 weeks cough duration or greater, n=156 adults) in which 7% adults had laboratory-confirmed pertussis.3 The present study aimed to investigate the prevalence and clinical features of pertussis in adults presenting … [1]: {openurl}?query=rft.jtitle%253DBritish%2BJournal%2Bof%2BGeneral%2BPractise%26rft.stitle%253Dbjgp%26rft.aulast%253DTeepe%26rft.auinit1%253DJ.%26rft.volume%253D65%26rft.issue%253D639%26rft.spage%253De662%26rft.epage%253De667%26rft.atitle%253DPrevalence%252C%2Bdiagnosis%252C%2Band%2Bdisease%2Bcourse%2Bof%2Bpertussis%2Bin%2Badults%2Bwith%2Bacute%2Bcough%253A%2Ba%2Bprospective%252C%2Bobservational%2Bstudy%2Bin%2Bprimary%2Bcare%26rft_id%253Dinfo%253Adoi%252F10.3399%252Fbjgp15X686917%26rft_id%253Dinfo%253Apmid%252F26412843%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=bjgp&resid=65/639/e662&atom=%2Febmed%2F21%2F3%2F116.atom

Supporting and enhancing peer review in the BJGP

The BJGP has for many years operated on an open peer review system, in which a minimum of two peer reviewers report on each original research article considered for publication and where the identities of the authors and reviewers are known to each other. Although peer review remains the ‘gatekeeper’ to research publication, its efficacy and reliability are still a topic of controversy. There is concern about the variation in the quality of peer review, both within and between journals.1,2 Editorial decisions such as the choice of reviewers, the interpretation of their comments, and the need to navigate between reviews offering divergent advice add to the difficulties. Formal training for reviewers is rare. Recently the ability of the system to identify fraud and plagiarism has been questioned. A 2007 Cochrane review has highlighted the urgent need for high-quality research into the outcomes of peer review.3 One place to focus efforts at improvement is at the level of the individual reviewer. Until now BJGP reviewers have not routinely received feedback on their performance, although they do receive a copy of the other review(s) and the editor’s comments sent to the manuscript authors. While the quality of reviews carried out for the BJGP is almost uniformly good, we are now committed to implementing a more formal feedback system to help new reviewers, support existing reviewers, and further improve the quality of future reviews and publications. We examined the literature to identify existing tools used to assess the quality of peer reviews. These tools have often been devised to provide a quantitative measure of quality for comparison purposes in research studies. Most comprise a numerical scoring system to rate reviews ranging from 4-point to 100-point scales, some providing a single global score and others with multiple scores for subcategories. …