New oral anticoagulants: appropriateness of prescribing in real-world setting.

BACKGROUND: The new oral anticoagulants (NOAC) have been extensively studied in the clinical trial setting; however, concerns remain about the safety of prescribing in the elderly and patients with renal impairment. AIM: The aim of this study was to assess the appropriateness of NOAC prescribing in a real-world setting in terms of patient selection and to compare patient demographics to those included in pivotal clinical trials. METHODS: One hundred and seventy-six patients from three tertiary university teaching hospitals were identified over 3 months in 2014. RESULTS: Median age of the cohort was 74 years (interquartile range: 61-81 years), with a range of 23-96 years. Overall, 34% of the study population were prescribed a NOAC inappropriately. Of these, treatment was contraindicated in 40%, predominantly due to severe renal impairment, 22% were prescribed an excessively high dose, while 38% were under dosed. Although community-initiated patients had poorer renal function (glomerular filtration rate 91.7 ± 55.7 vs 69.3 ± 38.9, P = 0.024), appropriateness of prescription was no different compared to hospital-initiated patients (78% during admission cf. 61% prior, P = 0.061). Appropriate prescribing was better in patients with venous thromboembolism compared to AF (85% appropriate cf. 60%, P = 0.021). CONCLUSION: Our findings imply that there remains considerable uncertainty about appropriate prescribing and dosing of NOAC, particularly in patients with impaired renal function. We recommend judicious prescribing and regular monitoring of renal function in patients at high risk of complications from NOAC therapy.

A medication review and deprescribing method for hospitalised older patients receiving multiple medications.

BACKGROUND: Prescribing of multiple medications in older patients poses risk of adverse drug events. AIM: To determine whether a structured approach to deprescribing - identifying and discontinuing unnecessary medications - in the inpatient setting is feasible and reduces medication burden. METHODS: Prospective pilot study of a convenience sample of patients aged ≥65 years admitted acutely to general medicine units in a tertiary hospital and receiving eight or more regular medications on presentation. The intervention comprised an education programme and a paper-based or computerised proforma listing clinical and medication data linked with a five-step decision support tool for selecting drugs eligible for discontinuation, which were then ceased or were being weaned by the time of discharge. RESULTS: Among 50 patients of median age 82.5 years and six co-morbidities, 186 of 542 (34.3%) regular medications were discontinued, representing a significant decrease in the median (interquartile range) number of medications per patient at discharge compared with presentation (7 (5-9) vs 10 (9-12), P < 0.001). Medication lists were reduced by at least two medications in 84% of patients, and by four or more in 50%. Statins, gastric acid suppressive agents, angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists and inhaled bronchodilators were the most frequently ceased medications. Of 39 patients in whom follow-up status at a median of 78 days was ascertained, only 5 of 413 (1.2%) ceased medications were recommenced among three patients because of symptom relapse. CONCLUSION: A standardised method of medication review and deprescribing may significantly reduce medication burden in a cohort of older hospitalised patients.

Adherence to guideline-based antibiotic treatment for acute exacerbations of chronic obstructive pulmonary disease in an Australian tertiary hospital.

BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are an important cause of acute hospital admissions and incur significant costs, which include antibiotic costs. AIMS: This study aimed to (i) define antibiotic prescribing practice in patients admitted to a tertiary hospital with AECOPD and compare this with current locally and nationally recognised antibiotic prescribing guidelines and (ii) correlate variations in guideline-concordant antibiotic prescribing with mean length of stay (LOS) and rates of unplanned readmission to hospital. METHODS: Retrospective case series of 84 consecutive patients with uncomplicated AECOPD who met pre-specified selection criteria. RESULTS: Seventy-two of 84 participants (85.7%) received guideline-discordant antibiotics, of whom the majority (76%) received intravenous antibiotics. Mean LOS was significantly lower among patients receiving guideline-concordant therapy compared with those receiving guideline-discordant therapy (mean 1.6 days vs 3.7 days; P = 0.002). There was no significant difference between groups in rates of readmission. Estimated excess costs per patient associated with guideline-discordant therapy equalled $2642 which, if eliminated, would save approximately $300 000 per annum. CONCLUSION: In a tertiary hospital, Australian guidelines for treating patients with an AECOPD were rarely followed. The use of guideline-discordant therapy resulted in longer hospital stays and incurred greater costs. Studies are required to determine the reasons behind such discordant practice and to develop initiatives to improve antibiotic prescribing.

Prospective parallel randomized trial of the MultiCyte™ ThinPrep(®) imaging system: the Scottish experience.

BACKGROUND: Computer-assisted screening of cervical liquid-based cytology (LBC) preparations using the ThinPrep® Imaging System (TIS) has shown improved qualitative and quantitative gains. The use of Multicyte™ has not been described in a well-established national screening programme with a low incidence of high-grade dyskaryosis. OBJECTIVES: To assess the impact of computer-assisted screening within the Scottish Cervical Screening Programme (SCSP). METHODS: Two groups of three laboratories, each sharing a ThinPrep® Imager, screened 79 366 slides randomized to test and 90 551 to control arms by laboratory accession. Screeners were not blinded. Standard laboratory reporting profiles of the SCSP, sensitivity, specificity and false-negative rates of all grades of LBC abnormalities with respect to final cytology reports, predictive value for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) on histology; and screening rates were compared for both arms. RESULTS: Inadequate and negative reporting rates were significantly lower and low-grade reporting rates significantly higher in the imager arm. Imager-assisted screening showed significantly better specificity than manual screening with respect to the final cytology result. There was no evidence of a significant difference in the detection of CIN2+ or CIN3 +. Positive, abnormal and total predictive values (high-grade, low-grade and all abnormal cytology found to be CIN2+, respectively) were similar in both arms. Productivity was significantly higher in the imager arm. CONCLUSION: Computer-assisted screening in a well established screening programme showed significantly improved productivity without loss of quality. These findings should inform future policy for cervical screening programmes.

Diagnosis of bladder cancer by immunocytochemical detection of minichromosome maintenance protein-2 in cells retrieved from urine.

BACKGROUND: We tested the accuracy of immunocytochemistry (ICC) for minichromosome maintenance protein-2 (MCM-2) in diagnosing bladder cancer, using cells retrieved from urine. METHODS: Adequate samples were obtained from 497 patients, the majority presenting with gross haematuria (GH) or undergoing cystoscopic surveillance (CS) following previous bladder cancer. We performed an initial study of 313 patients, followed by a validation study of 184 patients. In all cases, presence/absence of bladder cancer was established by cystoscopy/biopsy. RESULTS: In the initial study, receiver operator characteristic analysis showed an area under the curve of 0.820 (P<0.0005) for the GH group and 0.821 (P<0.01) for the CS group. Optimal sensitivity/specificity were provided by threshold values of 50+ MCM-2-positive cells in GH samples and 200+ cells in CS samples, based on a minimum total cell number of 5000. Applying these thresholds to the validation data set gave 81.3% sensitivity, 76.0% specificity and 92.7% negative predictive value (NPV) in GH and 63.2% sensitivity, 89.9% specificity and 89.9% NPV in CS. Minichromosome maintenance protein-2 ICC provided clinically relevant improvements over urine cytology, with greater sensitivity in GH and greater specificity in CS (P=0.05). CONCLUSIONS: Minichromosome maintenance protein-2 ICC is a reproducible and accurate test that is suitable for both GH and CS patient groups.

Endobronchial ultrasound-transbronchial needle aspiration and its practical application.

Endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) has emerged over the past decade as one of the most exciting and innovative developments in the field of respiratory medicine. This procedure allows sampling of mediastinal lymph nodes and masses in both malignant and benign disease and overcomes some of the disadvantages associated with mediastinoscopy and blind transbronchial needle aspiration. We describe the clinical use, indications for and limitations of EBUS-TBNA along with several illustrated clinical examples.

Inflammatory myofibroblastic tumours of the respiratory tract: paediatric case series with varying clinical presentations.

OBJECTIVES: To highlight the clinical importance of inflammatory myofibroblastic tumours of the respiratory tract in children, and to present a case series of three children which illustrates this tumour's variable clinical presentation. CASE HISTORY: The series includes: a nine-year-old girl with a diagnosis of juvenile idiopathic arthritis, who presented with finger clubbing and was found to have an inflammatory myofibroblastic tumour in her right upper lobe; a 15-year-old adolescent with a left main stem bronchial inflammatory myofibroblastic tumour, who presented with breathlessness and chest pain; and a 12-year-old girl with a tracheal inflammatory myofibroblastic tumour who presented with stridor. In each case, the tumour was resected surgically. CONCLUSION: Inflammatory myofibroblastic tumour are a rare but clinically important and pathologically distinct lesion of the respiratory tract in children. The cases in this series highlight some of the varied clinical presentations of inflammatory myofibroblastic tumours, and illustrate some of this tumour's different anatomical locations within the paediatric respiratory tract.

Raised interleukin-17 is immunolocalised to neutrophils in cystic fibrosis lung disease.

Interleukin (IL)-17 is pivotal in orchestrating the activity of neutrophils. Neutrophilic inflammation is the dominant pathology in cystic fibrosis (CF) lung disease. We investigated IL-17 protein expression in the lower airway in CF, its cellular immunolocalisation and the effects of IL-17 on CF primary bronchial epithelial cells. Immunohistochemistry was performed on explanted CF lungs and compared with the non-suppurative condition pulmonary hypertension (PH). Airway lavages and epithelial cultures were generated from explanted CF lungs. Immunoreactivity for IL-17 was significantly increased in the lower airway epithelium in CF (median 14.1%) compared with PH (2.95%, p=0.0001). The number of cells staining positive for IL-17 in the lower airway mucosa was also increased (64 cells·mm(-1) compared with 9 cells·mm(-1) basement membrane, p=0.0005) and included both neutrophils in addition to mononuclear cells. IL-17 was detectable in airway lavages from explanted CF lungs. Treatment of epithelial cultures with IL-17 increased production of IL-8, IL-6 and granulocyte macrophage colony-stimulating factor. In conclusion, immunoreactive IL-17 is raised in the lower airway of people with CF and localises to both neutrophils and mononuclear cells. IL-17 increases production of pro-neutrophilic mediators by CF epithelial cells, suggesting potential for a positive feedback element in airway inflammation.

An investigation of adequate volume for the diagnosis of malignancy in pleural fluids.

OBJECTIVE: The cytological examination of pleural effusions is an important investigation in the diagnosis of malignancy. Maximizing the chances of identifying malignant effusions is therefore desirable. Recent Royal College of Pathologists guidelines, based on the British Society for Clinical Cytology codes of practice, have suggested that a minimum of 20 ml of pleural fluid is required for diagnostic purposes. METHODS & RESULTS: We examined 2155 pleural fluids received over a 6-year period in order to define a minimum required volume for adequacy. By examining the plateau phase of a graph of threshold volumes for initial samples received for each patient (n =1584) we determine that a minimum fluid volume of 25 ml is required and that more than 50 ml does not improve sensitivity. CONCLUSION: Between 25 and 50 ml of fluid are required for the adequate assessment of pleural effusions for malignancy.

The outcome of expectant management of congenital cystic adenomatoid malformations (CCAM) of the lung.

INTRODUCTION: The appropriate management of asymptomatic congenital cystic adenomatoid malformations of the lung (CCAM) remains controversial. The aim of this study is to determine the outcome of expectant management of these lesions and the sensitivity of antenatal ultrasound diagnosis. MATERIAL AND METHODS: A retrospective review was undertaken of all cases identified from prospectively collected databases with an antenatal or postnatal diagnosis of CCAM in the Northern region of England between 1985 and 2006 where such lesions underwent resection only when symptomatic. RESULTS: Thirty-seven cases of confirmed CCAM were identified antenatally or postnatally. Twenty-six (70%) were identified by antenatal ultrasound scans (during a period of near-universal antenatal scanning), of whom 21 (81%) were liveborn. In total, 16 of 29 (55%) liveborn infants with CCAM were symptomatic, and either died within the first postnatal week or underwent resection. Thirteen (45% of livebirths) were managed expectantly and remained asymptomatic. The sensitivity of antenatal ultrasound screening for CCAM increased over the period to 90% in the latter half of the study (p=0.035), although the positive predictive value (66%) did not improve. CONCLUSIONS: Expectant management was a reasonable option for almost half of the babies, but over one third required surgery for CCAM, most becoming symptomatic in infancy. In view of the uncertainty that surrounds decisions regarding expectant or pre-emptive resection in asymptomatic infants, the authors advocate having an open and honest discussion when counselling parents (particularly antenatally) regarding surveillance or expectant management as a reasonable strategy.

Paediatric respiratory nursing posts in secondary care reduce asthma morbidity, but provision is variable.

British guidelines on asthma recommend nurse delivered structured discharges for all children with asthma. This study carried out a postal and telephone survey to investigate the provision of this service. Twenty out of 34 (59%) hospitals in the Northern and Yorkshire regions do not have a recognised paediatric respiratory nurse post to facilitate this aspect of care.

Nedocromil sodium for chronic asthma in children.

BACKGROUND: Currently inhaled corticosteroids are the main stay in the maintenance treatment of chronic asthma in children. Although inhaled corticosteroids play a crucial role in the management of childhood asthma, the long-term side effects of inhaled corticosteroids used in the management of chronic asthma in children are not clearly known. OBJECTIVES: The objective of this review is to compare the safety and efficacy of inhaled nedocromil sodium with placebo in the treatment of chronic asthma in children. SEARCH STRATEGY: We searched the Cochrane airway group trials register, Cochrane controlled trials register, Current contents, review articles, reference lists of articles. We also contacted the drug manufacturer and primary authors for additional citations. We also searched abstracts of major respiratory society meetings. The last search was carried out in October 2004 SELECTION CRITERIA: Randomised placebo controlled trials comparing nedocromil sodium to placebo in the treatment of chronic asthma in children (0 to 18 years). DATA COLLECTION AND ANALYSIS: Both authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: Fifteen trials (twelve parallel group studies; three crossover trials recruiting 1422 children (837 males and 585 females)) were included. The studies were generally of good methodological quality. Two large long term studies used nedocromil for six months and four to six years and showed conflicting results in symptom free days. Short term studies (duration between 4 weeks to 12 weeks) showed that nedocromil sodium produced some improvement in a number of efficacy measures compared to placebo including FEV(1), FVC, FEV(1) % predicted, PC20 FEV(1), evening PEF and symptom scores. The parent's assessment of efficacy was in favour of nedocromil (odds ratio (OR) 0.5 (95% CI 0.3 to 0.8). Nedocromil sodium has a good safety profile. The only significant side effect observed was unpleasant taste. There was little evidence for a clinically dose response effect and only a few studies recruited participants with severe asthma. AUTHORS' CONCLUSIONS: A limited number of small studies have shown that nedocromil is of benefit in improving lung function and some measures of symptoms, but the evidence with regard to the primary outcome of the review was conflicting. Two long-term trials did not show consistent effects on lung function outcomes, whereas several small short-term trials have shown benefit in these outcomes. Differing severities at baseline may explain this difference with milder participants experiencing less benefit, although the discrepancy between study findings may also reflect publication bias. Nedocromil sodium is associated with a very good safety profile with no significant short term or long- term adverse side effects. Although nedocromil may have advantages over inhaled corticosteroids in terms of side effects, there is a need for head to head trials of nedocromil and inhaled corticosteroids to establish whether asthma control is similar, especially in mild asthma. It is not yet clear where nedocromil should sit in relation to other therapies in the treatment of asthma in children.

Interdigitating dendritic cell sarcoma of the parotid gland.

Interdigitating dendritic cell sarcomas (IDCSs) are extremely uncommon tumours that arise predominantly in lymphoid tissue. We report a case of an IDCS arising in the parotid gland of a 73-year-old man. Clinically, a primary salivary gland tumour was suspected but fine needle aspiration cytology suggested a soft tissue tumour. A diagnosis of IDCS was made on histopathological examination of the resection specimen, with subsequent confirmation by electron microscopy. Given the extreme rarity of this tumour at this site, it is unlikely to be a common diagnostic problem, but the importance of multiple diagnostic modalities is emphasized. The findings of cytology, histology, immunohistochemistry and electron microscopy have not previously been described together in a single case report of this tumour.

Inhaled corticosteroids for non-specific chronic cough in children.

BACKGROUND: Cough in isolation of other clinical features is known as non-specific cough, which has been defined as non-productive cough in the absence of identifiable respiratory disease or any known aetiology. In children with non-specific cough the possibility of asthma being the underlying disorder is often raised (so called cough variant asthma). The proponents of cough variant asthma suggest a therapeutic trial of medications usually used to treat asthma. OBJECTIVES: To determine the efficacy of inhaled corticosteroids in non-specific cough in children over the age of two years. SEARCH STRATEGY: Searches were conducted on Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Searches were current as of March 2004. SELECTION CRITERIA: All randomised (randomised and quasi-randomised) controlled clinical trials in which an inhaled corticosteroid (beclomethasone (BDP), fluticasone (FP), triamcinalone (TAA) or any other corticosteroid) were given for cough in children over two years of age were included. Two review authors independently assessed articles for inclusion and methodological quality. DATA COLLECTION AND ANALYSIS: Data from trials was extracted by both review authors and entered into the Cochrane Collaboration software program RevMan Analyses 1.0.2. MAIN RESULTS: Two trials met the inclusion criteria (123 participants). One compared inhaled beclomethasone dipropionate (400 micrograms per day) with placebo and the other compared fluticasone propionate (2 mg per day for 3 days followed by 1 mg per day for 11 days) with placebo. Both studies used metered dose inhalers via a spacer. With the lower dose of inhaled corticosteroid there was no significant difference between the beclomethasone and placebo groups. With the higher dose there was a significant improvement in nocturnal cough frequency after two weeks in children presenting with persistent nocturnal cough. However, a significant but smaller improvement was also seen with placebo. AUTHORS' CONCLUSIONS: In one study beclomethasone dipropionate (400 micrograms per day) was no different from placebo in reducing the frequency of cough measured objectively or scored subjectively. There might be a small improvement with very high-dose inhaled corticosteroid but the clinical impact of this is unlikely to beneficial.