An overview of the management of Congestive Heart Failure in Malta

Background: In July 2003 the National Institute of Clinical Excellence (NICE) issued guidelines on the management of congestive heart failure. We set out to assess the management of congestive heart failure in St. Luke's Hospital (SLH), Malta. Methods: The files of patients admitted to SLH during the month of January 2002 were retrieved. Eligible patients were those with a history of congestive heart failure. Patients who had passed away by the time of the audit or whose files were untraceable were excluded from the audit. Data from the file pertaining to that specific admission was entered in a preprepared data sheet. This includes demographic data about the patient, investigations performed to reach diagnosis and assess severity, pharmacological and non-pharmacological management of heart failure, and planned follow-up at time of discharge. Results: The management of 97 patients was assessed. All patients with a clinical diagnosis of congestive heart failure had an electrocardiogram, chest X-ray, urea, electrolytes and creatinine estimation and a full blood count. Regarding the other tests recommended by NICE, echocardiography was performed in 28% of patients, serum glucose was assayed in 87%, liver function tests in 36%, thyroid function tests in 24%, urinalysis in 13%, lipids in 8% and spirometry in none. Two per cent of patients had lifestyle modification advice documented in the file. Pharmacological treatment consisted of diuretics (98%), ACE inhibitors (71%), angiotensin II receptor blockers (4%), ß-blockers (9%), spironolactone (12%) and digoxin (25%). Conclusions: There is still scope for improvement in the management of congestive heart failure locally.peer-reviewe

Insights into a Multidrug Resistant Escherichia coli Pathogen of the Globally Disseminated ST131 Lineage: Genome Analysis and Virulence Mechanisms

Escherichia coli strains causing urinary tract infection (UTI) are increasingly recognized as belonging to specific clones. E. coli clone O25b:H4-ST131 has recently emerged globally as a leading multi-drug resistant pathogen causing urinary tract and bloodstream infections in hospitals and the community. While most molecular studies to date examine the mechanisms conferring multi-drug resistance in E. coli ST131, relatively little is known about their virulence potential. Here we examined E. coli ST131 clinical isolates from two geographically diverse collections, one representing the major pathogenic lineages causing UTI across the United Kingdom and a second representing UTI isolates from patients presenting at two large hospitals in Australia. We determined a draft genome sequence for one representative isolate, E. coli EC958, which produced CTX-M-15 extended-spectrum β-lactamase, CMY-23 type AmpC cephalosporinase and was resistant to ciprofloxacin. Comparative genome analysis indicated that EC958 encodes virulence genes commonly associated with uropathogenic E. coli (UPEC). The genome sequence of EC958 revealed a transposon insertion in the fimB gene encoding the activator of type 1 fimbriae, an important UPEC bladder colonization factor. We identified the same fimB transposon insertion in 59% of the ST131 UK isolates, as well as 71% of ST131 isolates from Australia, suggesting this mutation is common among E. coli ST131 strains. Insertional inactivation of fimB resulted in a phenotype resembling a slower off-to-on switching for type 1 fimbriae. Type 1 fimbriae expression could still be induced in fimB-null isolates; this correlated strongly with adherence to and invasion of human bladder cells and bladder colonisation in a mouse UTI model. We conclude that E. coli ST131 is a geographically widespread, antibiotic resistant clone that has the capacity to produce numerous virulence factors associated with UTI

Mechanisms involved in acquisition of blaNDM genes by IncA/C2 and IncFIIY plasmids

blaNDM genes confer carbapenem resistance and have been identified on transferable plasmids belonging to different incompatibility (Inc) groups. Here we present the complete sequences of four plasmids carrying a blaNDM gene, pKP1-NDM-1, pEC2-NDM-3, pECL3-NDM-1, and pEC4-NDM-6, from four clinical samples originating from four different patients. Different plasmids carry segments that align to different parts of the blaNDM region found on Acinetobacter plasmids. pKP1-NDM-1 and pEC2-NDM-3, from Klebsiella pneumoniae and Escherichia coli, respectively, were identified as type 1 IncA/C2 plasmids with almost identical backbones. Different regions carrying blaNDM are inserted in different locations in the antibiotic resistance island known as ARI-A, and ISCR1 may have been involved in the acquisition of blaNDM-3 by pEC2-NDM-3. pECL3-NDM-1 and pEC4-NDM-6, from Enterobacter cloacae and E. coli, respectively, have similar IncFIIY backbones, but different regions carrying blaNDM are found in different locations. Tn3-derived inverted-repeat transposable elements (TIME) appear to have been involved in the acquisition of blaNDM-6 by pEC4-NDM-6 and the rmtC 16S rRNA methylase gene by IncFIIY plasmids. Characterization of these plasmids further demonstrates that even very closely related plasmids may have acquired blaNDM genes by different mechanisms. These findings also illustrate the complex relationships between antimicrobial resistance genes, transposable elements, and plasmids and provide insights into the possible routes for transmission of blaNDM genes among species of the Enterobacteriaceae family

An analysis of baseline data from the PROUD study: an open-label randomised trial of pre-exposure prophylaxis

Background: Pre-exposure prophylaxis (PrEP) has proven biological efficacy to reduce the sexual acquisition of the human immunodeficiency virus (HIV). The PROUD study found that PrEP conferred higher protection than in placebo-controlled trials, reducing HIV incidence by 86 % in a population with seven-fold higher HIV incidence than expected. We present the baseline characteristics of the PROUD study population and place the findings in the context of national sexual health clinic data. Methods: The PROUD study was designed to explore the real-world effectiveness of PrEP (tenofovir-emtricitabine) by randomising HIV-negative gay and other men who have sex with men (GMSM) to receive open-label PrEP immediately or after a deferral period of 12 months. At enrolment, participants self-completed two baseline questionnaires collecting information on demographics, sexual behaviour and lifestyle in the last 30 and 90 days. These data were compared to data from HIV-negative GMSM attending sexual health clinics in 2013, collated by Public Health England using the genitourinary medicine clinic activity database (GUMCAD). Results: The median age of participants was 35 (IQR: 29–43). Typically participants were white (81 %), educated at a university level (61 %) and in full-time employment (72 %). Of all participants, 217 (40 %) were born outside the UK. A sexually transmitted infection (STI) was reported to have been diagnosed in the previous 12 months in 330/515 (64 %) and 473/544 (87 %) participants reported ever having being diagnosed with an STI. At enrolment, 47/280 (17 %) participants were diagnosed with an STI. Participants reported a median (IQR) of 10 (5–20) partners in the last 90 days, a median (IQR) of 2 (1–5) were condomless sex acts where the participant was receptive and 2 (1–6) were condomless where the participant was insertive. Post-exposure prophylaxis had been prescribed to 184 (34 %) participants in the past 12 months. The number of STI diagnoses was high compared to those reported in GUMCAD attendees. Conclusions: The PROUD study population are at substantially higher risk of acquiring HIV infection sexually than the overall population of GMSM attending sexual health clinics in England. These findings contribute to explaining the extraordinary HIV incidence rate during follow-up and demonstrate that, despite broad eligibility criteria, the population interested in PrEP was highly selective. Trial registration: Current Controlled TrialsISRCTN94465371. Date of registration: 28 February 2013

The BRICS (Bronchiectasis Radiologically Indexed CT Score)- a multi-center study score for use in idiopathic and post infective bronchiectasis

OBJECTIVES: The goal of this study was to develop a simplified radiological score that could assess clinical disease severity in bronchiectasis. METHODS: The Bronchiectasis Radiologically Indexed CT Score (BRICS) was devised based on a multivariable analysis of the Bhalla score and its ability in predicting clinical parameters of severity. The score was then externally validated in six centers in 302 patients. RESULTS: A total of 184 high-resolution CT scans were scored for the validation cohort. In a multiple logistic regression model, disease severity markers significantly associated with the Bhalla score were percent predicted FEV1, sputum purulence, and exacerbations requiring hospital admission. Components of the Bhalla score that were significantly associated with the disease severity markers were bronchial dilatation and number of bronchopulmonary segments with emphysema. The BRICS was developed with these two parameters. The receiver operating-characteristic curve values for BRICS in the derivation cohort were 0.79 for percent predicted FEV1, 0.71 for sputum purulence, and 0.75 for hospital admissions per year; these values were 0.81, 0.70, and 0.70, respectively, in the validation cohort. Sputum free neutrophil elastase activity was significantly elevated in the group with emphysema on CT imaging. CONCLUSIONS: A simplified CT scoring system can be used as an adjunct to clinical parameters to predict disease severity in patients with idiopathic and postinfective bronchiectasis

Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD) : effectiveness results from the pilot phase of a pragmatic open-label randomised trial

Background Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. Methods PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). Findings We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64-96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3-11·3). 13 men (90% CI 9-23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients. Interpretation In this high incidence population, daily tenofovir-emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection. Funding MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences

Earlier diagnosis of lung cancer in a randomised trial of an autoantibody blood test followed by imaging

The EarlyCDT-Lung test is a high specificity blood-based autoantibody biomarker that could contribute to predicting lung cancer risk. Here we report on the results of a phase IV biomarker evaluation of whether using the EarlyCDT-Lung test and any subsequent CT scanning to identify those at high risk of lung cancer reduces the incidence of patients with stage III/IV/Unspecified lung cancer at diagnosis, compared with the standard clinical practice at the time the study began.ECLS was a randomised controlled trial of 12,208 participants at risk of developing lung cancer in Scotland. The intervention arm received the EarlyCDT-Lung test and, if test positive, low-dose CT scanning six-monthly for up to two years. EarlyCDT-Lung test negative and control arm participants received standard clinical care. Outcomes wereassessed at two years post-randomisation using validated data on cancer occurrence, cancer staging, mortality and comorbidities. At two years, 127 lung cancers were detected in the study population (1.0%). In the intervention arm, 33/56 (58.9%) lung cancers were diagnosed at stage III/IV compared to 52/71 (73.2%) in the control arm. The hazard ratio for stage III/IV presentation was 0.64 (95% confidence interval 0.41, 0.99). There were non-significant differences in lung cancer and all-cause mortality after two years.ECLS compared EarlyCDT-Lung plus CT screening to standard clinical care (symptomatic presentation), and was not designed to assess the incremental contribution of the EarlyCDT-Lung test. The observation of a stage-shift towards earlier-stage lung cancer diagnosis merits further investigations to evaluate whether the EarlyCDT-Lung test adds anything to the emerging standard of LDCT.Registration: ClinicalTrials.Gov registration number NCT01925625

Automated data capture from free-text radiology reports to enhance accuracy of hospital inpatient stroke codes

Purpose Much potentially useful clinical information for pharmacoepidemiological research is contained in unstructured free-text documents and is not readily available for analysis. Routine health data such as Scottish Morbidity Records (SMR01) frequently use generic 'stroke' codes. Free-text Computerised Radiology Information System (CRIS) reports have potential to provide this missing detail. We aimed to increase the number of stroke-type-specific diagnoses by augmenting SMR01 with data derived from CRIS reports and to assess the accuracy of this methodology.Methods SMR01 codes describing first-ever-stroke admissions in Tayside, Scotland from 1994 to 2005 were linked to CRIS CT-brain scan reports occurring with 14 days of admission. Software was developed to parse the text and elicit details of stroke type using keyword matching. An algorithm was iteratively developed to differentiate intracerebral haemorrhage (ICH) from ischaemic stroke (IS) against a training set of reports with pathophysiologically precise SMR01 codes. This algorithm was then applied to CRIS reports associated with generic SMR01 codes. To establish the accuracy of the algorithm a sample of 150 ICH and 150 IS reports were independently classified by a stroke physician.Results There were 8419 SMR01 coded first-ever strokes. The proportion of patients with pathophysiologically clear diagnoses doubled from 2745 (32.6%) to 5614 (66.7%). The positive predictive value was 94.7% (95%CI 89.8-97.3) for IS and 76.7% (95%CI 69.3-82.7) for haemorrhagic stroke.Conclusions A free-text processing approach was acceptably accurate at identifying IS, but not ICH. This approach could be adapted to other studies where radiology reports may be informative. Copyright (C) 2010 John Wiley &amp; Sons, Ltd.</p

<i>Escherichia</i> genomes analysed and CU fimbrial operons identified per strain.

<p>UPEC: uropathogenic <i>E.coli</i>, ABU: asymptomatic bacteriuria <i>E.coli</i>, NMEC: neonatal meningitis <i>E.coli</i>, APEC: avian pathogenic <i>E.coli</i>, EAEC: enteroaggregative <i>E.coli</i>, EPEC: enteropathogenic <i>E.coli</i>, EHEC: enterohaemorrhagic <i>E.coli</i>.</p

Prevalence and genetic organisation of CU fimbrial types identified in <i>Escherichia</i>.

<p>The genetic organisation of the different fimbrial types is depicted diagrammatically. Fimbriae are grouped according to the Nuccio clading scheme <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052835#pone.0052835-Nuccio1" target="_blank">[3]</a>. Fimbrial prevalence is represented as a percentage of all the strains in the genome dataset. Plasmid-borne fimbriae not part of a genome are highlighted as ‘Plasmid DB’. Genes are colour coded according to predicted function of the corresponding protein product, with associated Pfam and COG domains indicated. The scale represents DNA length in kilo base pair. Reference operon locus tags for individual fimbrial types are displayed on the right. ¹PAI and plasmid-borne operons are highlighted in blue and red, respectively.</p