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Highlights from this issue

2017-11-15T08:40:51-08:00

Sweet Thursday

In his novel ‘Sweet Thursday’ John Steinbeck chronicles the lives of the poor residents of Monterey, California. The novel contains the remark: ‘I guess a man is the only kind of varmint sets his own trap, baits it, and then steps in it.’ This month’s Editors’ Choice, Qiu and colleagues describe some of the ‘traps’, which are set within the human body – ‘neutrophil extracellular traps’ or ‘NETs’ (see page 1084). These NETs comprise a mesh of DNA, containing antimicrobial proteins and enzymes which allow extracellular killing of microbes. Qiu et al studied circulating neutrophils from mice exposed to cigarette smoke extract. They showed that, in these conditions, neutrophils release NETs more readily and that they provide an important link between the innate and adaptive immune systems. Whether these findings are true ‘...of mice and men...’ remains to be seen.

The grapes of...



Lessons from the lower airway microbiome in early CF

2017-11-15T08:40:51-08:00

Lung disease in cystic fibrosis (CF) is characterised by chronic airway infection and inflammation.1 Advances in sequencing technology have expanded our understanding of airway infection in CF, with complex polymicrobial bacterial communities frequently detected along with typical CF bacterial pathogens such as Pseudomonas aeruginosa.2 Investigations of CF airway microbiota rely on interrogation of airway samples, most commonly expectorated sputum. Young children with CF rarely expectorate sputum spontaneously, leaving clinicians with the option of oropharyngeal swabs which may not reflect lower airway bacteriology or bronchoalveolar lavage fluid (BALF) collection which requires an invasive procedure with anaesthesia.3

Microbial diversity, a measure that takes into account the number of different bacterial taxa and the relative amount of each taxa detected within a community, has been associated with disease status in CF with lower diversity associated with lower lung function, the presence of pathogenic bacteria and increased...




Pneumothorax management: time to improve the evidence base

2017-11-15T08:40:51-08:00

Background

Pneumothorax remains a common reason for medical admission to hospital with a UK annual incidence of 16.7 cases per 100 000 for men and 5.8 cases per 100 000 for women.1 This equates to around 8000 admissions a year for pneumothorax accounting for 50 000 bed days given an average length of stay of just under 1 week.2 Despite its frequency and the existence of established guidelines,3 4 there is still wide variation in pneumothorax management, which is likely to be driven by the paucity of good quality evidence in this field.

Pneumothorax has traditionally been divided into primary spontaneous pneumothorax (PSP), with no known underlying lung disease and secondary spontaneous pneumothorax (SSP), with existing lung disease. This is likely to be too simplistic an approach. Smoking cessation has been shown to significantly reduce the risk of recurrence in PSP and this...




Prediction of long-term outcome subtypes in ARDS: first steps towards personalised medicine in critical care

2017-11-15T08:40:51-08:00

In Thorax, Samuel Brown and colleagues present their result on early identification of physical, cognitive and mental health outcome subtypes in patients who survived acute respiratory distress syndrome (ARDS).1 Using data from the ARDSNet Long-Term Outcomes Study, the authors identified a group of 645 patients who had been studied with a comprehensive battery of validated health outcome instruments, which included measures of physical, cognitive and mental health (anxiety, depression and post-traumatic stress disorder), as well as quality of life status, obtained at 6-month follow-up. After splitting the data into derivation and validation datasets, the authors used a data mining approach, weighted network analysis, to identify and validate four outcome subphenotypes. They identified four subtypes: (1) mildly impaired physical and mental health status; (2) moderately impaired physical and mental health status; (3) severely impaired physical and moderately impaired mental health status; and (4) severely impaired physical and mental health...




Hydropersulfides, the new kids in the COPD inflammatory town

2017-11-15T08:40:51-08:00

Hydrogen sulfide (H2S) is one of several small molecules, formerly known primarily as toxic gases (such as nitric oxide (NO) and carbon monoxide) that over the past 20 years have been shown to be endogenously generated small, signalling molecules.1 2 H2S has accompanied life since its origin. Its toxicological potential, related to the inhibition of cellular respiration, has been known for centuries.3 Indeed, the Permian-Triassic mass extinction event has been linked to this toxicity. H2S has been the cause of mining, industrial and sewage accidents, as well as deaths by the inhalation of gases emanating from volcanic and sulfur-rich water wells.

In spite of this felonious record, as it happens with other primeval redox processes, ancient H2S pathways have evolved to play physiological roles in eukaryotic cells.

The rush of discovery for H2S and its derivative compounds started in the late 1980s by...




Pulmonary arteriovenous malformations emerge from the shadows

2017-11-15T08:40:51-08:00

For many years, pulmonary arteriovenous malformations (PAVMs) have been an underdiagnosed and poorly understood aspect of respiratory medicine. Recent increases in the published literature have improved our understanding of their diagnosis and management. The British Thoracic Society Clinical Statement on PAVMs published in Thorax aims to drive an improvement in the care provided to this often-neglected patient group.1 The Statement is the first example of a new method of summarising data and providing an expert view of best practice in a given clinical area. 

Three major issues are associated with poor health outcomes in patients with PAVMs: lack of clinician awareness and education, an absence of standardised approaches to patient management and an urgent need for service development for a condition estimated to affect more than 10 000 people in the UK.2

Clinician awareness and education

PAVMs are under-represented in medical school syllabuses and, more importantly,...




Production of reactive persulfide species in chronic obstructive pulmonary disease

2017-11-15T08:40:51-08:00

Background

Oxidative stress is a major aetiological factor driving chronic obstructive pulmonary disease (COPD). Recently recognised as potent antioxidants, reactive persulfide and polysulfide species are biosynthesised by cystathionine β-synthase and cystathionine -lyase. The production of reactive persulfide and polysulfide species in the lungs of patients with COPD remain unknown.

Objectives

The aim of this study was to examine the production of reactive persulfides and polysulfides, such as glutathione persulfide (GSSH), cysteine persulfide (CysSSH) and glutathione trisulfide (GSSSH), in lung-resident cells and epithelial lining fluid (ELF) obtained from patients with mild to moderate COPD.

Methods

Lung tissues, primary lung cells, ELF and sputum were obtained. The amounts of reactive persulfides and polysulfides in the cells and ELF were measured by liquid chromatography–tandem mass spectrometry with β-(4-hydroxyphenyl) ethyl iodoacetamide as a trapping agent for hydroper/polysulfides. The amounts of synthases in the lung tissues, sputum and primary cells were quantified.

Results

The amounts of GSSH, CysSSH and GSSSH were decreased in the lung cells and ELF from patients with COPD. The amounts of reactive persulfides and polysulfides in the lung cells had a positive correlation with the degree of airflow limitation. By contrast, the amounts of the synthases were increased in the lung tissues and sputum cells of patients with COPD.

Conclusions

We have identified a decrease in reactive persulfide and polysulfide species in the lungs of patients with COPD. These data suggest that the newly detected antioxidants reactive persulfides and polysulfides could be associated with the redox balance in the lungs of patients with COPD.




Neutrophil extracellular traps induced by cigarette smoke activate plasmacytoid dendritic cells

2017-11-15T08:40:51-08:00

Background

Neutrophil extracellular traps (NETs) represent a distinct strategy by which neutrophils trap, confine and eliminate invading microorganisms. Emerging evidence suggests that NETs exert a deleterious effect to the host in the absence of microbial stimuli. However, the role of NETs in smoking-related lung diseases remains to be elucidated.

Objectives

To evaluate the formation of NETs in the context of chronic inflammation induced by cigarette smoking and explore its potential role in an experimental mouse model of emphysema.

Methods

The formation and degradation of NETs in cigarette smoke exposed mice was assessed with a fluorescence microscope. The potential influences of NETs on plasmacytoiddendritic cells were also investigated.

Results

NETs were more prone to formation by polymorphonuclearneutrophils but defective in degradation in cigarette smoke exposed mice. Cigarette smoke extract (CSE) served as an important facilitator that triggered neutrophils to undergo NETosis in vitro. Furthermore, CSE-induced NETs were capable of driving plasmacytoiddendritic cell maturation and activation, thereby initiating a T-cell-mediated immune response.

Conclusions

NETs may represent a critical connection between innate and adaptive immune responses under conditions of chronic inflammation induced by cigarette smoke exposure.




Understanding patient outcomes after acute respiratory distress syndrome: identifying subtypes of physical, cognitive and mental health outcomes

2017-11-15T08:40:51-08:00

Purpose

With improving short-term mortality in acute respiratory distress syndrome (ARDS), understanding survivors’ posthospitalisation outcomes is increasingly important. However, little is known regarding associations among physical, cognitive and mental health outcomes. Identification of outcome subtypes may advance understanding of post-ARDS morbidities.

Methods

We analysed baseline variables and 6-month health status for participants in the ARDS Network Long-Term Outcomes Study. After division into derivation and validation datasets, we used weighted network analysis to identify subtypes from predictors and outcomes in the derivation dataset. We then used recursive partitioning to develop a subtype classification rule and assessed adequacy of the classification rule using a kappa statistic with the validation dataset.

Results

Among 645 ARDS survivors, 430 were in the derivation and 215 in the validation datasets. Physical and mental health status, but not cognitive status, were closely associated. Four distinct subtypes were apparent (percentages in the derivation cohort): (1) mildly impaired physical and mental health (22% of patients), (2) moderately impaired physical and mental health (39%), (3) severely impaired physical health with moderately impaired mental health (15%) and (4) severely impaired physical and mental health (24%). The classification rule had high agreement (kappa=0.89 in validation dataset). Female Latino smokers had the poorest status, while male, non-Latino non-smokers had the best status.

Conclusions

We identified four post-ARDS outcome subtypes that were predicted by sex, ethnicity, pre-ARDS smoking status and other baseline factors. These subtypes may help develop tailored rehabilitation strategies, including investigation of combined physical and mental health interventions, and distinct interventions to improve cognitive outcomes.




The lower airway microbiota in early cystic fibrosis lung disease: a longitudinal analysis

2017-11-15T08:40:51-08:00

Rationale

In infants and young children with cystic fibrosis, lower airway infection and inflammation are associated with adverse respiratory outcomes. However, the role of lower airway microbiota in the pathogenesis of early cystic fibrosis lung disease remains uncertain.

Objectives

To assess the development of the lower airway microbiota over time in infants and young children with cystic fibrosis, and to explore its association with airway inflammation and pulmonary function at age 6 years.

Methods

Serial, semi-annual bronchoscopies and bronchoalveolar lavage (BAL) procedures were performed in infants newly diagnosed with cystic fibrosis following newborn screening. Quantitative microbiological cultures and inflammatory marker (interleukin 8 and neutrophil elastase) measurements were undertaken contemporaneously. 16S ribosomal RNA gene sequencing was conducted on stored BAL samples. Spirometry results recorded at 6 years of age were extracted from medical records.

Measurements and main results

Ninety-five BAL samples provided 16S ribosomal RNA gene data. These were collected from 48 subjects aged 1.2–78.3 months, including longitudinal samples from 27 subjects and 13 before age 6 months. The lower airway microbiota varied, but diversity decreased with advancing age. Detection of recognised cystic fibrosis bacterial pathogens was associated with reduced microbial diversity and greater lower airway inflammation. There was no association between the lower airway microbiota and pulmonary function at age 6 years.

Conclusions

In infants with cystic fibrosis, the lower airway microbiota is dynamic. Dominance of the microbiota by recognised cystic fibrosis bacterial pathogens is associated with increased lower airway inflammation, however early microbial diversity is not associated with pulmonary function at 6 years of age.




Rapid decline in lung function is temporally associated with greater metabolically active adiposity in a longitudinal study of healthy adults

2017-11-15T08:40:51-08:00

Rationale

Adiposity is associated with low lung function, but the longitudinal relationship between lung function and adiposity is inadequately studied.

Objective

To examine the bidirectional longitudinal associations between rapid decline in lung function and adiposity phenotypes in healthy adults.

Methods

This secondary analysis used a 25-year longitudinal dataset from the Coronary Artery Risk Development in Young Adults (CARDIA) study that enrolled 5115 participants.

Measurements

In the first analysis, metabolic syndrome at or before CARDIA year (Y) 10 (Y10) was the predictor, and subsequent rapid decline in forced vital capacity (FVC) or forced expiratory volume in 1 s (FEV1) between Y10 and Y20 was the outcome. In the second analysis, rapid decline was the predictor, and incident metabolic syndrome at Y20 and/or Y25 was the outcome. In the third analysis, rapid decline was the predictor, and subsequent CT-assessed regional fat depots at Y25 were the outcome.

Results

Metabolic syndrome at or before Y10 is temporally associated with rapid decline in FVC between Y10 and Y20 (adjusted p=0.04), but this association was explained by body mass index (BMI) at Y10. Rapid decline in FVC or FEV1 is temporally associated with greater incident metabolic syndrome at Y20 and/or Y25 (adjusted OR 2.10 (1.69, 2.61); p<0.001, and 1.56 (1.26, 1.94); p<0.001, respectively) and greater CT-assessed intrathoracic visceral adiposity at Y25 (adjusted standardised β 0.09; p<0.001 for both analyses). These associations were not explained by BMI levels prior to the outcome measurement.

Conclusions

Healthy adults with rapid decline in lung function are at risk for developing metabolic syndrome and for disproportionate accumulation of intrathoracic visceral fat. Metabolic abnormalities may be an early extrapulmonary manifestation of lung impairment that may be preventable by improving lung health.




Effectiveness of chemical pleurodesis in spontaneous pneumothorax recurrence prevention: a systematic review

2017-11-15T08:40:51-08:00

Objectives

Spontaneous pneumothorax is a common pathology. International guidelines suggest pleurodesis for non-resolving air leak or recurrence prevention at second occurrence. This study comprehensively reviews the existing literature regarding chemical pleurodesis efficacy.

Design

We systematically reviewed the literature to identify relevant randomised controlled trials (RCTs), case–control studies and case series. We described the findings of these studies and tabulated relative recurrence rates or ORs (in studies with control groups). Meta-analysis was not performed due to substantial clinical heterogeneity.

Results

Of 560 abstracts identified by our search strategy, 50 were included in our systematic review following screening. Recurrence rates in patients with chest tube drainage only were between 26.1% and 50.1%. Thoracoscopic talc poudrage (four studies (n=249)) provided recurrence rates of between 2.5% and 10.2% with the only RCT suggesting an OR of 0.10 compared with drainage alone. In comparison, talc administration during video-assisted thoracic surgery (VATS) from eight studies (n=2324) recurrence was between 0.0% and 3.2%, but the RCT did not demonstrate a significant difference compared with bleb/bullectomy alone. Minocycline appears similarly effective post-VATS (recurrence rates 0.0–2.9%). Prolonged air leak and recurrence prevention using tetracycline via chest drain (n=726) is likely to provide recurrence rates between 13.0% and 33.3% and autologous blood patch pleurodesis (n=270) between 15.6% and 18.2%.

Conclusions

Chemical pleurodesis postsurgical treatment or via thoracoscopy appears to be most effective. Evidence for definitive success rates of each agent is limited by the small number of randomised trials or other comparative studies.




Educational video to improve CPAP use in patients with obstructive sleep apnoea at risk for poor adherence: a randomised controlled trial

2017-11-15T08:40:51-08:00

Background

Suboptimal adherence to CPAP limits its clinical effectiveness in patients with obstructive sleep apnoea (OSA). Although rigorous behavioural interventions improve CPAP adherence, their labour-intensive nature has limited widespread implementation. Moreover, these interventions have not been tested in patients at risk of poor CPAP adherence. Our objective was to determine whether an educational video will improve CPAP adherence in patients at risk of poor CPAP adherence.

Methods

Patients referred by clinicians without sleep medicine expertise to an urban sleep laboratory that serves predominantly minority population were randomised to view an educational video about OSA and CPAP therapy before the polysomnogram, or to usual care. The primary outcome was CPAP adherence during the first 30 days of therapy. Secondary outcomes were show rates to sleep clinic (attended appointment) and 30-day CPAP adherence after the sleep clinic visit date.

Results

A total of 212 patients met the eligibility criteria and were randomised to video education (n=99) or to usual care (n=113). There were no differences in CPAP adherence at 30 days (3.3, 95% CI 2.8 to 3.8 hours/day video education; vs 3.5, 95% CI 3.1 to 4.0 hours/day usual care; p=0.44) or during the 30 days after sleep clinic visit. Sleep clinic show rate was 54% in the video education group and 59% in the usual care group (p=0.41). CPAP adherence, however, significantly worsened in patients who did not show up to the sleep clinic.

Conclusions

In patients at risk for poor CPAP adherence, an educational video did not improve CPAP adherence or show rates to sleep clinic compared with usual care.

Trial registration number

ClinicalTrials.gov Identifier: NCT02553694.




Tumour-associated neutrophils and loss of epithelial PTEN can promote corticosteroid-insensitive MMP-9 expression in the chronically inflamed lung microenvironment

2017-11-15T08:40:51-08:00

Matrix metalloproteinase-9 (MMP-9) is increased in a number of pathological lung conditions, where the proteinase contributes to deleterious remodelling of the airways. While both lung cancer and COPD are associated with increased MMP-9 expression, the cellular and molecular drivers of MMP-9 remain unresolved. In this study, MMP-9 transcript measured within the tumour region from patients with non-small-cell lung cancer (NSCLC) and coexisting COPD was found to be uniformly increased relative to adjacent tumour-free tissue. MMP-9 gene expression and immunohistochemistry identified tumour-associated neutrophils, but not macrophages, as a predominant source of this proteinase. In addition, PTEN gene expression was significantly reduced in tumour and there was evidence of epithelial MMP-9 expression. To explore whether PTEN can regulate epithelial MMP-9 expression, a small interfering (si)RNA knockdown strategy was used in Beas-2B bronchial epithelial cells. PTEN knockdown by siRNA selectively increased MMP-9 expression in response to lipopolysaccharide in a corticosteroid-insensitive manner. In summary, tumour-associated neutrophils represent an important source of MMP-9 in NSCLC, and loss of epithelial PTEN may further augment steroid-insensitive expression.




The interaction between bronchoconstriction and cough in asthma

2017-11-15T08:40:51-08:00

Variable airflow obstruction is a pathophysiological hallmark of asthma; however, the interactions between acute bronchoconstriction and the cough reflex are poorly understood. We performed a randomised, single-blind, placebo-controlled, crossover study to investigate the interaction between bronchoconstriction and cough in asthma. Capsaicin was administered to evoke coughs and methacholine to induce bronchoconstriction. We demonstrated that acute bronchoconstriction increased capsaicin-evoked coughs, which improved as airway calibre spontaneously resolved. However, capsaicin-evoked coughing had no impact on methacholine-induced bronchoconstriction. This study provides evidence that bronchoconstriction increases the activation of capsaicin-responsive airway nerves, but the precise mechanisms and mediators involved require further evaluation.

Trial registration number

ISRCTN14900082.




The effect of different radiological models on diagnostic accuracy and lung cancer screening performance

2017-11-15T08:40:51-08:00

High false-positive (FP) scan rates associated with low-dose computed tomography (LDCT) lung cancer screening result in unnecessary follow-up tests and exposure to harm. The definition of a ‘positive’ scan can impact FP rates and screening performance. We explored the effect of Lung Imaging Reporting and Data System (Lung-RADS) criteria, PanCan Nodule Malignancy Probability Model and varying nodule size thresholds (≥4 mm, ≥6 mm, ≥8 mm) on diagnostic accuracy and screening performance compared with original trial definitions (National Lung Screening Trial (NLST) criteria) in a secondary analysis of a lung cancer screening cohort. We found Lung-RADS criteria and the PanCan Nodule Malignancy Probability Model could substantially improve screening performance and reduce FP scan rates compared with NLST definitions of positivity but that this needs to be balanced against possible risk of false-negative results.

Trial registration number

Australian New Zealand Clinical Trials Registry, ACTRN12610000007033.




Chronic breathlessness associated with poorer physical and mental health-related quality of life (SF-12) across all adult age groups

2017-11-15T08:40:51-08:00

Little is known about the impact of chronic breathlessness (modified Medical Research Council (mMRC) score ≥2 for most days, at least three of the last six months) on health-related quality of life (Short Form-12 (SF-12)). 3005 adults from randomly selected households were interviewed face-to-face in South Australia. mMRC ≥2 community prevalence was 2.9%. Adjusted analyses showed clinically meaningful and statistically significant decrements of physical and mental components of SF-12 (mean SF-12 summary scores in physical (–13.0 (–16.0 to –10.2)) and mental (–10.7 (–13.7 to –7.8)) components compared with people with mMRC=0) as chronic breathlessness severity increased, across five age groupings.




British Thoracic Society Clinical Statement on Pulmonary Arteriovenous Malformations

2017-11-15T08:40:51-08:00

Pulmonary arteriovenous malformations (PAVMs) are structurally abnormal vascular communications that provide a continuous right-to-left shunt between pulmonary arteries and veins. Their importance stems from the risks they pose (>1 in 4 patients will have a paradoxical embolic stroke, abscess or myocardial infarction while life-threatening haemorrhage affects 1 in 100 women in pregnancy), opportunities for risk prevention, surprisingly high prevalence and under-appreciation, thus representing a challenging condition for practising healthcare professionals. The driver for the current Clinical Statement was the plethora of new data since previous hereditary haemorrhagic telangiectasia (HHT) guidelines generated in 2006 and a systematic Cochrane Review for PAVM embolisation in 2011. The British Thoracic Society (BTS) identified key areas in which there is now evidence to drive a change in practice. Due to the paucity of data in children, this Statement focused on adults over 16 years. The Statement spans the management of PAVMs already known to be present (interventional and medical), screening and diagnosis (for PAVMs and HHT) and follow-up of patients following a first diagnosis, intervention or negative screen for PAVMs. The Good Practice Points (in bold) were generated for a target audience of general respiratory, medical and specialist clinicians and were approved by the BTS Standards of Care Committee, before formal peer review and public consultation. The Statement spans embolisation treatment, accessory medical management and issues related to the likelihood of underlying HHT.




Pulmonary hypertension with warm hands

2017-11-15T08:40:51-08:00

A 19-year-old woman of Moroccan descent presented with severe dyspnoea on exertion. She had difficulty walking stairs (New York Heart Association functional class 3) and accompanying symptoms included fatigue, palpitations and near collapse. She had no cough or wheezing, but mentioned severe and continuous menstrual bleeds since menarche without use of contraceptives. Her medical history included long-standing complaints of fainting, abdominal pains and chest pain, without a clear diagnosis. The family history included hypercholesterolaemia and venous thromboembolic disease (VTE). In fact, 1 year prior to this presentation, the patient was diagnosed with PE herself. Other than a temporary mild polycythaemia (haemoglobin concentration of 16 g/dL) no risk factors for VTE had been discovered at that time.

Physical examination showed a thin woman with a body mass index of 17 kg/m2 (height 161 cm and weight 44 kg). Her blood pressure was 82/51 mm Hg, while her extremities appeared warm. Her heart rate was 91 bpm, the...




Pulmonary artery aneurysms and thrombi

2017-11-15T08:40:51-08:00

A 19-year-old previously healthy boy was referred to our hospital with fever, progressive coughing, dyspnoea and haemoptysis for 2 weeks. He had lost weight (3 kg) and was experiencing night sweats.

In the past 6 months, he had experienced that his overall condition and training capacity in sports had decreased noticeably.

On examination, he was tachypnoeic and tachycardic with normal blood pressure. Oxygen saturation was 90% with 15 L of oxygen delivered by Venturi mask. There were diminished breathing sounds in the basal segments of the right lung and in the upper paravertebral region. No other abnormalities were identified.

The laboratory results included a mild microcytic anaemia, leucocytosis and elevation of C reactive protein.

CT and conventional studies showed a central mass in the right upper lobe (figure 1A, B).

Positron emission tomography-CT (PET-CT) and magnetic resonance angiography (figure 1C) demonstrated (pseudo-) aneurysms of the pulmonary arteries in both...




Let air out of the bowel to allow more air in the lungs: surgical treatment of weaning failure

2017-11-15T08:40:51-08:00

A 79-year-old man was electively admitted for a Whipple's procedure for a pancreatic cancer. Following surgery, he was extubated, but subsequently developed a hospital-acquired pneumonia with multiple organ failure requiring admission to the intensive care unit for organ support. After a protracted period of failed weaning from mechanical ventilation, he was transferred to a regional weaning centre 7 months after the initial operation. Since the surgery, the patient had complained of abdominal bloating and discomfort with distended bowel loops observed on the plain abdominal film. Because of frailty of the patient, a conservative management approach was taken, including high positive extrinsic pressure to enhance lung volume and the use of prokinetics, low-volume enteral feeding, regular aspiration of air from the nasogastric tube, sitting out and mobilisation, a bowel management regime, pancreatic enzyme replacement and high-dose cholinesterase inhibitor to promote peristalsis and reduce bowel distension. The patient complained of dyspnoea associated...




Whats hot that the other lot got

2017-11-15T08:40:51-08:00

Rapid diagnosis of second-line drug resistance in TB

Rapid diagnosis of the gene mutation associated with rifampicin resistance using GeneXpert MTB/RIF has improved the speed of diagnosis of multidrug-resistant TB; however, there are no established rapid techniques to assess for resistance to fluoroquinolones and injectable drugs. Xie et al (N Engl J Med 2017;377:1043–54)have conducted a multicentre, prospective, blinded study in Korea and China to determine the sensitivity and specificity of a GeneXpert compatible assay which detects genes associated with resistance to isoniazid, moxifloxacin, ofloxacin, amikacin and kanamycin. A total of 405 patients were enrolled from June 2014 to June 2015 with 304 suitable samples included in the final analysis. The sensitivity of the assay for detection of Mycobacterium tuberculosis was 98%, which equalled GeneXpert MTB/RIF. The WHO recommended performance for molecular tests of drug resistance is a sensitivity of 95% and specificity of 98%. Sensitivity for resistance gene detection compared...