bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetics and Physiology of Acetate Metabolism by the Pta-Ack Pathway of Streptococcus mutans
Authors: Kim Jeong Nam , Ahn Sang-Joon , Burne Robert A.
Published: May 2015

In the dental caries pathogen
Streptococcus mutans
, phosphotransacetylase (Pta) catalyzes the conversion of acetyl coenzyme A (acetyl-CoA) to acetyl phosphate (AcP), which can be converted to acetate by acetate kinase (Ack), with the concomitant generation of ATP. A Δ
ackA
mutant displayed enhanced accumulation of AcP under aerobic conditions, whereas little or no AcP was observed in the Δ
pta
or Δ
pta
Δ
ackA
mutant. The Δ
pta
and Δ
pta
Δ
ackA
mutants also had diminished ATP pools compared to the size of the ATP pool for the parental or Δ
ackA
strain. Surprisingly, when exposed to oxidative stress, the Δ
pta
Δ
ackA
strain appeared to regain the capacity to produce AcP, with a concurrent increase in the size of the ATP pool compared to that for the parental strain. The Δ
ackA
and Δ
pta
Δ
ackA
mutants exhibited enhanced (p)ppGpp accumulation, whereas the strain lacking Pta produced less (p)ppGpp than the wild-type strain. The Δ
ackA
and Δ
pta
Δ
ackA
mutants displayed global changes in gene expression, as assessed by microarrays. All strains lacking Pta, which had defects in AcP production under aerobic conditions, were impaired in their abilities to form biofilms when glucose was the growth carbohydrate. Collectively, these data demonstrate the complex regulation of the Pta-Ack pathway and critical roles for these enzymes in processes that appear to be essential for the persistence and pathogenesis of
S. mutans
.
Oxalobacter formigenes Colonization and Oxalate Dynamics in a Mouse Model
Authors: Li Xingsheng , Ellis Melissa L. , Knight John
Published: May 2015

Animal and human studies have provided compelling evidence that colonization of the intestine with
Oxalobacter formigenes
reduces urinary oxalate excretion and lowers the risk of forming calcium oxalate kidney stones. The mechanism providing protection appears to be related to the unique ability of
O. formigenes
to rely on oxalate as a major source of carbon and energy for growth. However, much is not known about the factors that influence colonization and host-bacterium interactions. We have colonized mice with
O. formigenes
OxCC13 and systematically investigated the impacts of diets with different levels of calcium and oxalate on
O. formigenes
intestinal densities and urinary and intestinal oxalate levels. Measurement of intestinal oxalate levels in mice colonized or not colonized with
O. formigenes
demonstrated the highly efficient degradation of soluble oxalate by
O. formigenes
relative to other microbiota. The ratio of calcium to oxalate in diets was important in determining colonization densities and conditions where urinary oxalate and fecal oxalate excretion were modified, and the results were consistent with those from studies we have performed with colonized and noncolonized humans. The use of low-oxalate purified diets showed that 80% of animals retained
O. formigenes
colonization after a 1-week dietary oxalate deprivation. Animals not colonized with
O. formigenes
excreted two times more oxalate in feces than they had ingested. This nondietary source of oxalate may play an important role in the survival of
O. formigenes
during periods of dietary oxalate deprivation. These studies suggest that the mouse will be a useful model to further characterize interactions between
O. formigenes
and the host and factors that impact colonization.
Two Master Switch Regulators Trigger A40926 Biosynthesis in Nonomuraea sp. Strain ATCC 39727
Authors: Lo Grasso Letizia , Maffioli Sonia , Sosio Margherita , Bibb Mervyn , Puglia Anna Maria , Alduina Rosa
Published: May 2015

The actinomycete
Nonomuraea
sp. strain ATCC 39727 produces the glycopeptide A40926, the precursor of dalbavancin. Biosynthesis of A40926 is encoded by the
dbv
gene cluster, which contains 37 protein-coding sequences that participate in antibiotic biosynthesis, regulation, immunity, and export. In addition to the positive regulatory protein Dbv4, the A40926-biosynthetic gene cluster encodes two additional putative regulators, Dbv3 and Dbv6. Independent mutations in these genes, combined with bioassays and liquid chromatography-mass spectrometry (LC-MS) analyses, demonstrated that Dbv3 and Dbv4 are both required for antibiotic production, while inactivation of
dbv6
had no effect. In addition, overexpression of
dbv3
led to higher levels of A40926 production. Transcriptional and quantitative reverse transcription (RT)-PCR analyses showed that Dbv4 is essential for the transcription of two operons,
dbv14-dbv8
and
dbv30-dbv35
, while Dbv3 positively controls the expression of four monocistronic transcription units (
dbv4
,
dbv29
,
dbv36
, and
dbv37
) and of six operons (
dbv2-dbv1
,
dbv14-dbv8
,
dbv17-dbv15
,
dbv21-dbv20
,
dbv24-dbv28
, and
dbv30-dbv35
). We propose a complex and coordinated model of regulation in which Dbv3 directly or indirectly activates transcription of
dbv4
and controls biosynthesis of 4-hydroxyphenylglycine and the heptapeptide backbone, A40926 export, and some tailoring reactions (mannosylation and hexose oxidation), while Dbv4 directly regulates biosynthesis of 3,5-dihydroxyphenylglycine and other tailoring reactions, including the four cross-links, halogenation, glycosylation, and acylation.

IMPORTANCE
This report expands knowledge of the regulatory mechanisms used to control the biosynthesis of the glycopeptide antibiotic A40926 in the actinomycete
Nonomuraea
sp. strain ATCC 39727. A40926 is the precursor of dalbavancin, approved for treatment of skin infections by Gram-positive bacteria. Therefore, understanding the regulation of its biosynthesis is also of industrial importance. So far, the regulatory mechanisms used to control two other similar glycopeptides (balhimycin and teicoplanin) have been elucidated, and beyond a common step, different clusters seem to have devised different strategies to control glycopeptide production. Thus, our work provides one more example of the pitfalls of deducing regulatory roles from bioinformatic analyses only, even when analyzing gene clusters directing the synthesis of structurally related compounds.
Effects of Acupuncture at St25 on Inflammatory Mediators and Nuclear Factor κB Activation in a Rat Model of Severe Acute Pancreatitis
Authors: Xue Qi-Ming , Pan Hui , Huang Lu , Li Ning
Published: May 2015

Objective

To observe the effect of electroacupuncture (EA) and manual acupuncture (MA) at ST25 on inflammatory mediators and nuclear factor κ-B (NF-κB) activation in rats with sodium taurocholate-induced severe acute pancreatitis (SAP).

Methods

Eighty-eight male Sprague–Dawley rats were randomly divided into four groups: control (sham-operated), SAP, SAP+EA and SAP+MA (n=22 each). A SAP model was established by injecting 3.5% sodium taurocholate 1 mL/kg into the pancreatic duct. In each group, animals were killed at t=3 h (n=7), 6 h (n=7) and 12 h (n=8) after the procedure. Pancreatic expression of NF-κB was examined by immunohistochemical staining. The levels of tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6) in serum were determined by ELISA. Pathological changes in the pancreas were examined microscopically.

Results

Serum levels of TNF-α and IL-6 increased and morphological changes consistent with tissue damage were observed in the pancreas of SAP rats. NF-κB p65 expression was significantly higher in the SAP group than in the sham-operated group (p<0.05). Treatment with acupuncture at ST25 attenuated morphological damage and reduced levels of TNF-α and IL-6 in serum. NF-κB p65 expression was also significantly reduced by acupuncture at ST25 in the pancreas at 6 and 12 h after the procedure (p<0.05). There were no significant differences between the SAP+EA and SAP+MA groups.

Conclusions

Acupuncture at ST25 might have a therapeutic effect on rats with SAP through inhibition of NF-κB expression and a reduction in the release of pro-inflammatory cytokines.
Electroacupuncture Attenuates Collagen-Induced Arthritis in Rats through Vasoactive Intestinal Peptide Signalling-Dependent Re-Establishment of the Regulatory T Cell/T-Helper 17 Cell Balance
Authors: Zhu Jun , Chen Xiao-Yi , Li Lian-Bo , Yu Xin-Tong , Zhou Yin , Yang Wen-Jia , Liu Zhen , Zhao Na , Fu Cong , Zhang Shu-Hui , Chen Yun-Fei
Published: May 2015

Objective

Imbalance between T-helper 17 (Th17) cells and regulatory T (Treg) cells is causally linked to the development of rheumatoid arthritis (RA). In this study, we tested the hypothesis that electroacupuncture (EA) confers therapeutic benefits in RA through activation of vasoactive intestinal peptide (VIP)-dependent signalling and restoration of the Th17/Treg cell balance.

Materials and Methods

A collagen-induced arthritis (CIA) model was induced in Sprague–Dawley rats by injection of bovine type II collagen in incomplete Freund's adjuvant on day 0 and day 7. Three days after the second injection, EA was given at acupuncture points GB39 and ST36 three times per week for 4 weeks. To block VIP signalling, [D-P-Cl-Phe(6)-Leu(17)]-VIP, a VIP receptor antagonist, was administered intraperitoneally 30 min before EA. Inflammatory and pathological responses in the joint were assessed. Synovial VIP receptor mRNA levels and Treg and Th17 cell frequencies in the spleen were determined.

Results

EA significantly reduced the severity of CIA, as evidenced by reduced paw volumes, arthritis scores and inflammation scores. EA significantly increased mRNA expression of the VIP receptor VPAC1 and led to an elevation in CD4+FOXP3+ Treg cell frequency and a reduction in CD4+IL17+ Th17 cell frequency. Pre-injection of a VIP receptor antagonist significantly reversed EA-induced expansion of Treg cells, but did not alter the frequencies of Th17 cells.

Conclusions

EA exerts anti-inflammatory effects in a collagen-induced rat model of arthritis. These effects appear to be mediated through activation of VIP signalling and re-establishment of the Th17/Treg cell balance.
Isometric exercise induces analgesia and reduces inhibition in patellar tendinopathy
Authors: Rio Ebonie , Kidgell Dawson , Purdam Craig , Gaida Jamie , Moseley G Lorimer , Pearce Alan J , Cook Jill
Published: May 2015

Background

Few interventions reduce patellar tendinopathy (PT) pain in the short term. Eccentric exercises are painful and have limited effectiveness during the competitive season. Isometric and isotonic muscle contractions may have an immediate effect on PT pain.

Methods

This single-blinded, randomised cross-over study compared immediate and 45 min effects following a bout of isometric and isotonic muscle contractions. Outcome measures were PT pain during the single-leg decline squat (SLDS, 0–10), quadriceps strength on maximal voluntary isometric contraction (MVIC), and measures of corticospinal excitability and inhibition. Data were analysed using a split-plot in time-repeated measures analysis of variance (ANOVA).

Results

6 volleyball players with PT participated. Condition effects were detected with greater pain relief immediately from isometric contractions: isometric contractions reduced SLDS (mean±SD) from 7.0±2.04 to 0.17±0.41, and isotonic contractions reduced SLDS (mean±SD) from 6.33±2.80 to 3.75±3.28 (p<0.001). Isometric contractions released cortical inhibition (ratio mean±SD) from 27.53%±8.30 to 54.95%±5.47, but isotonic contractions had no significant effect on inhibition (pre 30.26±3.89, post 31.92±4.67; p=0.004). Condition by time analysis showed pain reduction was sustained at 45 min postisometric but not isotonic condition (p<0.001). The mean reduction in pain scores postisometric was 6.8/10 compared with 2.6/10 postisotonic. MVIC increased significantly following the isometric condition by 18.7±7.8%, and was significantly higher than baseline (p<0.001) and isotonic condition (p<0.001), and at 45 min (p<0.001).

Conclusions

A single resistance training bout of isometric contractions reduced tendon pain immediately for at least 45 min postintervention and increased MVIC. The reduction in pain was paralleled by a reduction in cortical inhibition, providing insight into potential mechanisms. Isometric contractions can be completed without pain for people with PT. The clinical implications are that isometric muscle contractions may be used to reduce pain in people with PT without a reduction in muscle strength.
Do solar cycles influence giant cell arteritis and rheumatoid arthritis incidence?
Authors: Wing Simon , Rider Lisa G , Johnson Jay R , Miller Federick W , Matteson Eric L , Crowson Cynthia S , Gabriel Sherine E
Published: May 2015

Objective

To examine the influence of solar cycle and geomagnetic effects on the incidence of giant cell arteritis (GCA) and rheumatoid arthritis (RA).

Methods

We used data from patients with GCA (1950–2004) and RA (1955–2007) obtained from population-based cohorts. Yearly trends in age-adjusted and sex-adjusted incidence were correlated with the F10.7 index (solar radiation at 10.7 cm wavelength, a proxy for the solar extreme ultraviolet radiation) and AL index (a proxy for the westward auroral electrojet and a measure of geomagnetic activity). Fourier analysis was performed on AL, F10.7, and GCA and RA incidence rates.

Results

The correlation of GCA incidence with AL is highly significant: GCA incidence peaks 0–1 year after the AL reaches its minimum (ie, auroral electrojet reaches a maximum). The correlation of RA incidence with AL is also highly significant. RA incidence rates are lowest 5–7 years after AL reaches maximum. AL, GCA and RA incidence power spectra are similar: they have a main peak (periodicity) at about 10 years and a minor peak at 4–5 years. However, the RA incidence power spectrum main peak is broader (8–11 years), which partly explains the lower correlation between RA onset and AL. The auroral electrojets may be linked to the decline of RA incidence more strongly than the onset of RA. The incidences of RA and GCA are aligned in geomagnetic latitude.

Conclusions

AL and the incidences of GCA and RA all have a major periodicity of about 10 years and a secondary periodicity at 4–5 years. Geomagnetic activity may explain the temporal and spatial variations, including east-west skewness in geographic coordinates, in GCA and RA incidence, although the mechanism is unknown. The link with solar, geospace and atmospheric parameters need to be investigated. These novel findings warrant examination in other populations and with other autoimmune diseases.
Intravenous thrombolysis guided by a telemedicine consultation system for acute ischaemic stroke patients in China: the protocol of a multicentre historically controlled study
Authors: Yuan Ziwen , Wang Bo , Li Feijiang , Wang Jing , Zhi Jin , Luo Erping , Liu Zhirong , Zhao Gang
Published: May 2015

Introduction

The rate of intravenous thrombolysis with tissue-type plasminogen activator or urokinase for stroke patients is extremely low in China. It has been demonstrated that a telestroke service may help to increase the rate of intravenous thrombolysis and improve stroke care quality in local hospitals. The aim of this study, also called the Acute Stroke Advancing Program, is to evaluate the effectiveness and safety of decision-making concerning intravenous thrombolysis via a telemedicine consultation system for acute ischaemic stroke patients in China.

Methods and analysis

This is a multicentre historically controlled study with a planned enrolment of 300 participants in each of two groups. The telestroke network consists of one hub hospital and 14 spoke hospitals in underserved regions of China. The usual stroke care quality in the spoke hospitals without guidance from the hub hospital will be used as the historical control. The telemedicine consultation system is an interactive, two-way, wireless, audiovisual system accessed on portable devices. The primary outcome is the percentage of patients treated with intravenous thrombolysis within 4.5 h of stroke onset.

Ethics and dissemination

The project has been approved by the Institutional Review Board of Xijing Hospital. The results will be published in scientific journals and presented to local government and relevant institutes.

Trial registration number

NCT02088346 (12 March 2014).
High-intensity statin therapy in patients with chronic kidney disease: a systematic review and meta-analysis
Authors: Yan Yu-Ling , Qiu Bo , Wang Jing , Deng Song-Bai , Wu Ling , Jing Xiao-Dong , Du Jian-Lin , Liu Ya-Jie , She Qiang
Published: May 2015

Objective

To evaluate the efficacy and safety of high-intensity statin therapy in patients with chronic kidney disease (CKD).

Design

A systematic review and meta-analysis.

Data sources

Randomised controlled trials (RCTs) comparing high-intensity statin therapy (atorvastatin 80 mg or rosuvastatin 20/40 mg) with moderate/mild statin treatment or placebo were derived from the databases (PubMed, Embase, Ovid, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, and ISI Web of Knowledge).

Outcome measure

Primary end points: clinical events (all-cause mortality, stroke, myocardial infarction and heart failure); secondary end points: serum lipid, renal function changes and adverse events.

Results

A total of six RCTs with 10 993 adult patients with CKD were included. A significant decrease in stroke was observed in the high-intensity statin therapy group (RR 0.69, 95% CI 0.56 to 0.85). However, the roles of high-intensity statin in decreasing all-cause mortality (RR 0.85, 95% CI 0.67 to 1.09), myocardial infarction (RR 0.69, 95% CI 0.40 to 1.18) and heart failure (RR 0.73, 95% CI 0.48 to 1.13) remain unclear with low evidence. High-intensity statin also had obvious effects on lowering the LDL-C level but no clear effects on renal protection. Although pooled results showed no significant difference between the intervention and control groups in adverse event occurrences, it was still insufficient to put off the doubts that high-intensity statin might increase adverse events because of limited data sources and low quality evidences.

Conclusions

High-intensity statin therapy could effectively reduce the risk of stroke in patients with CKD. However, its effects on all-cause mortality, myocardial infarction, heart failure and renal protection remain unclear. Moreover, it is hard to draw conclusions on the safety assessment of intensive statin treatment in this particular population. More studies are needed to credibly evaluate the effects of high-intensity statin therapy in patients with CKD.
Intrauterine insemination: a UK survey on the adherence to NICE clinical guidelines by fertility clinics
Authors: Kim Dongah , Child Tim , Farquhar Cynthia
Published: May 2015

Objective

To evaluate the awareness and response of fertility clinics in the UK to the National Institute for Health and Care Excellence (NICE) guideline recommendation that intrauterine insemination (IUI) should not be offered routinely, in order to report on current practice in the UK.

Design

Online questionnaire survey of fertility clinics in the UK regarding their current clinical practice of IUI, formal discussion of the guideline recommendations, and any alterations made since the recommendations.

Setting

66 UK fertility clinics licensed to provide IUI.

Participants

46 fertility clinics, including 6 clinic groups which represent 70% of all clinics and clinic groups licensed to provide IUI in April 2014 when the survey email was sent.

Results

Of the 46 clinics that responded, 96% (44/46) of clinics continue to offer IUI. 98% (43/44) of those offering IUI also use ovarian stimulation. The most commonly used medications for ovarian stimulation are gonadotrophins (95%), followed by clomiphene citrate (49%) and letrozole (19%). 78% (36/46) of clinics had formally discussed NICE guideline recommendations. 17 clinics (37%) had made some changes to their practices; as a result, four clinics reported a reduction in the number of IUI cycles, six clinics had restricted the indications for IUI, and five clinics had begun informing patients of the guideline recommendations, while two did not specify.

Conclusions

The majority of clinics were aware of the guideline recommendations. However, only a small proportion of clinics had made significant changes to their practice by reducing the number of IUI cycles or restricting the clinical indications for IUI. The availability of further evidence will assist NICE and clinicians in making recommendations on the use of IUI. There is a need to further explore the reasons for the lack of adherence to the recommendations.
Fructosamine measurement for diabetes mellitus diagnosis and monitoring: a systematic review and meta-analysis protocol
Authors: Nansseu Jobert Richie N , Fokom-Domgue Joël , Noubiap Jean Jacques N , Balti Eric V , Sobngwi Eugène , Kengne André Pascal
Published: May 2015

Introduction

Fructosamine is a marker of glucose control reflecting the average glycaemic level over the preceding 2–3 weeks. Fructosamine has not gained as much popularity as glycated haemoglobin (HbA1c) for diabetes mellitus (DM) control monitoring, and the related underlying reasons remain unclear. We aim to search for and summarise available evidence on the accuracy of fructosamine measurements to diagnose and monitor DM.

Methods and analysis

This systematic review will include randomised control trials, controlled before-and-after studies, time series designs, cohort studies, case–control studies and cross-sectional surveys reporting the diagnosis and/or monitoring of DM (type 1 DM, type 2 DM and gestational DM) with fructosamine compared with other measures of glycaemia (fasting glucose, oral glucose tolerance test, random glucose, HbA1c), without any language restriction. We will perform electronic searches in PubMed, Scopus and other databases, supplemented with manual searches. Articles published from 1 January 1980 to 30 June 2015 will be eligible for inclusion in this review. Two authors will independently screen, select studies, extract data and assess the risk of bias with discrepancies resolved by consensus. We will assess clinical heterogeneity by examining the types of interventions and outcomes in each study, and pool studies judged to be clinically homogeneous. We will also assess statistical heterogeneity using the χ2test of homogeneity and quantify it using the I2statistic. Absolute accuracy measures (sensitivity, specificity) will be pooled in a bivariate random-effects model, allowing for intersetting variability. Negative and positive predictive values will be computed for fructosamine, compared with another measure of glycaemia from the pooled estimates of sensitivity and specificity, using Bayes’ theorem.

Ethics and dissemination

This systematic review will use data from published studies and does not require ethics approval. Findings will be published in a peer-reviewed journal and presented at scientific conferences.

Trial registration number

PROSPERO (ID=CRD42015015930).
Protocol for the CHEST Australia Trial: a phase II randomised controlled trial of an intervention to reduce time-to-consult with symptoms of lung cancer
Authors: Murray Sonya R , Murchie Peter , Campbell Neil , Walter Fiona M , Mazza Danielle , Habgood Emily , Kutzer Yvonne , Martin Andrew , Goodall Stephen , Barnes David J , Emery Jon D
Published: May 2015

Introduction

Lung cancer is the most common cancer worldwide, with 1.3 million new cases diagnosed every year. It has one of the lowest survival outcomes of any cancer because over two-thirds of patients are diagnosed when curative treatment is not possible. International research has focused on screening and community interventions to promote earlier presentation to a healthcare provider to improve early lung cancer detection. This paper describes the protocol for a phase II, multisite, randomised controlled trial, for patients at increased risk of lung cancer in the primary care setting, to facilitate early presentation with symptoms of lung cancer.

Methods/analysis

The intervention is based on a previous Scottish CHEST Trial that comprised of a primary-care nurse consultation to discuss and implement a self-help manual, followed by self-monitoring reminders to improve symptom appraisal and encourage help-seeking in patients at increased risk of lung cancer. We aim to recruit 550 patients from two Australian states: Western Australia and Victoria. Patients will be randomised to the Intervention (a health consultation involving a self-help manual, monthly prompts and spirometry) or Control (spirometry followed by usual care). Eligible participants are long-term smokers with at least 20 pack years, aged 55 and over, including ex-smokers if their cessation date was less than 15 years ago. The primary outcome is consultation rate for respiratory symptoms.

Ethics and dissemination

Ethical approval has been obtained from The University of Western Australia's Human Research Ethics Committee (RA/4/1/6018) and The University of Melbourne Human Research Committee (1 441 433). A summary of the results will be disseminated to participants and we plan to publish the main trial outcomes in a single paper. Further publications are anticipated after further data analysis. Findings will be presented at national and international conferences from late 2016.

Trial registration number

Australian New Zealand Clinical Trial Registry ACTRN 1261300039 3752.
Improving the care of patients with a hip fracture: a quality improvement report
Authors: Hawkes David , Baxter Jonathan , Bailey Claire , Holland Gemma , Ruddlesdin Jennifer , Wall Alun , Wykes Philip
Published: May 2015

Introduction

Hip fractures are associated with high rates of morbidity and mortality and their incidence is set to increase. The National Hip Fracture Database and the Best Practice Tariff were introduced with the aim of improving patient care. This complete audit cycle charts the substantial clinical improvements that were achieved in a busy district general hospital.

Methods

The first audit cycle comprised 379 patients who were admitted between May 2012 and April 2013. The primary audit criterion was operative intervention within 36 h of admission. Variation according to the day of the week of admission was assessed to evaluate specific deficiencies in local service provision. The principle audit intervention was the introduction of two additional morning trauma lists. A re-audit of 162 patients was conducted prospectively between January 2014 and June 2014.

Results

Mean time to theatre was 49±39 h during the first audit cycle compared with 27±19 h (p<0.0001) during the second. Consequently, the proportion of patients undergoing operative intervention within 36 h of admission improved from 41% to 78% (p<0.0001). Overall achievement of Best Practice Tariff was significantly higher during the second cycle: 28% vs 73% (p<0.0001).

Conclusions

Significant improvements in the quality of hip fracture care were achieved following this audit. These were accomplished by rigorously analysing the variation in Best Practice Tariff achievement according to the day of the week on which patients were admitted. Targeted interventions could therefore be introduced that addressed specific problems in local service provision.
Introduction of a Venous Thromboembolism Prophylaxis Protocol for Older Adult Psychiatric Patients.
Authors: Croxford Anna , Clare Adam , McCurdy Kathleen
Published: May 2015

Hospital-Acquired venous thromboembolism (VTE) is a common cause of morbidity and mortality in older adults. In psychiatric patients these risks are increased due to multiple factors including poor mobility, restraint, catatonia, sedation, and conventional antipsychotic use. Diagnosis and treatment of psychiatric patients presenting with signs and symptoms of a VTE can be delayed due to a patient’s communication difficulties, non-compliance, or attribution of symptoms to a psychosomatic cause.

However, despite the increased risk, approved VTE prophylaxis protocols are infrequently used on Psychiatric wards. On one Older Adult Psychiatric Ward, two patients presented with VTE (a fatal pulmonary embolism and a symptomatic deep vein thrombosis) over a 6 month period demonstrating the necessity for prophylactic assessment. A baseline audit over 3 months showed that 63-83% of patients on the ward had received no assessment of VTE risk, on any given week, although this improved slightly following the critical incidents.

A VTE prophylaxis protocol, based on NICE guidance for VTE risk assessment in Medical and Surgical patients, was developed with consideration given to additional Psychiatric risk factors. This took the form of a pro-forma with a tick-box design that included mobility assessment, VTE risk factors, bleeding risk factors, and guidance on prescribing decisions. This was implemented on an Older Adult Psychiatric ward and prophylaxis was provided to those meeting the threshold.

Weekly audit of all pro-formas (including assessments completed within 48 hours of admission and prophylaxis prescription) was conducted after the pro-forma introduction from 1st February 2013 to 24th May 2013. Frequency of assessments increased after protocol implementation with between 36% and 85% of all patients being assessed for VTE risk post intervention. Fluctuations in numbers assessed may have related to ward pressures, staff changes, and practicalities of pro-forma use.

After completion of the PDSA cycles the initiative was handed over to a specialist registrar for implementation across the other trust Older Adult Psychiatry wards, and further audit was planned to be conducted via junior doctors and established Quality Assurance systems. Discussion of integration of a condensed pro-forma into the trust electronic notes system is ongoing.
Coagulation assessment with the new generation of oral anticoagulants
Authors: Pollack Charles V
Published: May 2015

Long-term oral anticoagulant (OAC) therapy is used for the treatment and prevention of thrombosis and thromboembolism. As OAC use is so widespread, emergency physicians are likely to encounter patients on anticoagulant therapy in the emergency department (ED) on a regular basis, either for the same reasons as the population in general or as a result of the increased bleeding risk that OAC use entails.

The vitamin K antagonist warfarin has been the standard OAC for several decades, but recently, the newer agents dabigatran etexilate, rivaroxaban and apixaban (collectively, novel OACs, non-vitamin K OACs, or simply ‘NOACs’) have become available for long-term use. Protocols for assessing and managing warfarin-treated patients in the ED are well established and include international normalised ratio (INR) testing, which helps guide patient management. However, the INR does not give an accurate evaluation of coagulation status with NOACs, and alternative tests are therefore needed for use in emergency settings. This paper discusses what information the INR provides for a patient taking warfarin and which coagulation tests can guide the physician when treating patients on one of the NOACs, as well as other differences in emergency anticoagulation management.
IDENTIFICATION OF TRAUMATIC BRAIN INJURY (TBI) IN THE PRE-HOSPITAL SETTING
Authors: Trebilcock Hannah
Published: May 2015

Background

Identification of TBI is extremely difficult and is often missed in the pre-hospital setting. Major trauma triage tool (MTTT) criteria specifies the suspicion of an open or depressed skull fracture as indicating a major trauma patient. However, it is often the case that patients with TBI recorded on the Trauma Audit and Research Network (TARN) data with an ISS>15, indicating major trauma, are not identified by the MTTT. This results in many patients with significant TBI being undertriaged and not receiving definitive care as rapidly as possible. Early intervention in patients suffering TBI is essential in ensuring the best possible outcome.

A retrospective clinical record review is being conducted to establish whether there are clinical or behavioural indicators of TBI that could be incorporated into clinical guidance to improve identification.

Method

The sample consists of 193 patients on the trauma database who have sustained a head injury between January–March 2014. For each of these incidents the patient clinical record (PCR) has been reviewed to provide data on many different demographic, physiological and behavioural aspects. All data has now been entered ready for analysis. Using the TARN data, patients will be divided into 2 groups. The experimental group will consist of those patients who have significant head injuries recorded by TARN. The control group will include the patients who have been identified as suspected major trauma with a head injury but have no corresponding injuries recorded on TARN.

Results

It is anticipated that at least one demographic, physiological or behavioural aspect will be a reliable indicator of TBI.

Implications

This retrospective clinical record review could greatly improve the identification of major trauma patients who have sustained a serious head injury. In turn this will mean more patients being appropriately conveyed to the MTC where specialised neurosurgeons are available.
SNAPSHOT OF INITIATIVES TO SUPPORT TIMELY PATIENT HANDOVER FROM AMBULANCES TO THE EMERGENCY DEPARTMENT
Authors: Wells Bridget , Evans Bridie Angela , Porter Alison , Gammon Becky , Mayes Robert Harris , Poulden Mark , Rees Nigel , Snooks Helen , Toghill Alun , Whitfield Richard
Published: May 2015

Background

Increasing pressure on the emergency care system contributes to delays in patient handover from ambulances to emergency departments. The impact of these delays includes ambulance queues, sub-optimal care for patients, staffing and operational challenges, and (in England) financial penalties.

New models of care have the potential to reduce handover delay. We surveyed ambulance services across England and Wales to produce a snapshot of initiatives under development or being trialled in order to address problems associated with handover delay.

Methods

During 2014, we carried out semi-structured telephone interviews with R&D leads in all 11 independent ambulance service trusts in England and Wales. We asked respondents about initiatives taking place within their area, what evaluation was taking place, and what they believed to be the challenges to evaluation. Interviews were recorded and transcribed, and analysed using the Framework approach.

Results

Initiatives fell into three groups: prehospital; at the ED; and whole system. Prehospital initiatives comprised clinical decision support tools (n=6); alternative pathways (n=6); hospital capacity monitoring (n=3); automated data transfer (n=3). Initiatives at ED included handover screens (n=8); rapid access models (n=7); hospital ambulance liaison officers (n=6); corridor care (n=3). Whole system approaches included new models of collaborative working (n=2); service review (n=2). Challenges to implementing and evaluating change included the lack of standardised approaches to handover across multiple hospital trusts within an ambulance service area; many of the reported initiatives took place only in a small part of the ambulance service's operational area. Only five respondents reported evaluation of handover initiatives, and of these two were described as informal evaluation only. The need to report and comply with performance targets was reported as a more immediate pressure than evaluation of new developments.

Conclusions

While there is a range of activity taking place across England and Wales to address handover delays, there is little formal evaluation and there are missed opportunities for transferable learning.
THE IMPACT OF INCREASING THE RUNNING TIME TO THE MAJOR TRAUMA CENTRE (MTC) TO 60 MINUTES IN THE SOUTH WEST
Authors: Trebilcock Hannah
Published: May 2015

Background

Major trauma guidelines specify that if the patient can be safely managed and the MTC can be reached within 45 minutes of leaving scene then the patient should be conveyed to the MTC. However, there is no evidence that supports the 45 minute timeframe. Given the rurality of the South West, an increase in the running time to the MTC to 60 minutes has been discussed amongst major trauma experts.

Method

An audit was conducted to identify how many patients could benefit from an increase in running time to 60 minutes. The sample included all suspected major trauma patients identified between April 2013–March 2014 who were conveyed to the nearest trauma unit (TU). Travelling times to the TU and MTC were analysed. Patients were split into network areas to quantify the impact if any.

Results

A maximum of 354 patients were identified as potentially benefitting from an increase to 60 minutes based on the travelling times to the TU and MTC. A minimum of 90 patients could have benefitted from an increase to 60 minutes. This was quantified by the patients who triggered the major trauma triage tool but were unable to reach the MTC in 45 minutes, and those confirmed by the Trauma Audit and Research Network (TARN) as having an ISS>15. The biggest impact would be seen in the Peninsula area where a total of 205 extra patients would be able to reach the MTC if the running time was increased.

Conclusion

An increase in running time to 60 minutes to the MTC for patients in the South West could significantly improve the level of care that many patients receive in the first few hours following major trauma injuries. With the information available it is not possible to quantify the operational impact such a change would have.
EMERGENCY MEDICAL DISPATCH EFFECTIVENESS: A NEW UTSTEIN TYPE ANALYTICAL TOOL FOR STUDYING THE SPECIFIC STAGES IN THE CALL TAKING PROCESS
Authors: Barron Tracey , Fivaz Conrad , Overton Jerry
Published: May 2015

Background

Whether a cardiac arrest treated by the ambulance service results in return of spontaneous circulation (ROSC), is dependent on the actions of the emergency call handler and their ability to induce bystander CPR.

The objective was to develop an Utstein style reporting tool as a stand-alone software reporting module that also allows users and researchers to enrich current data collection by integrating standardised call handling data from the software version of the Medical Priority Dispatch System protocol (ProQA) into current Utstein based reports, resulting in a more accurate and detailed analysis of the specific stages of call taking.

Methods

A consensus group met on two occasions to review the existing Utstein literature. Drawing on the published research as the foundation of their evidence, and the accumulated experience of the group in relation to the call handling process, they developed a template of specific data elements generated by the software for the Utstein style reporting tool. The template was then reviewed by technical experts to confirm that a tool with these elements could be developed.

Results

A total of eight time measurements (e.g., time at which a cardiac arrest is recognised), and 13 demographic/processing measurements (e.g., whether Pre-Arrival Instructions were given) were identified. These measurements are consistent between users, regardless of how they organise their dispatch processes. Each case contains a unique identifying number that allows users to integrate the data into their current Utstein reporting.

Conclusions

The newly developed reporting tool makes analysis and comparison of Emergency Medical Dispatch resuscitation data possible and meaningful using universal measurements. It allows for more detailed evaluation between cardiac arrest variables, including comparison between individual staff and centres, with a view to identifying areas for performance and system improvements.
ENSURING AN APPROPRIATE PRE-HOSPITAL RESPONSE TO PATIENTS IN SICKLE CELL CRISIS
Authors: Shaw Joanna , Fothergill Rachael , Virdi Gurkamal
Published: May 2015

Introduction

Some ambulance services in the UK use the Medical Priority Dispatch System (MPDS) to triage 999 calls and determine the response allocated to patients. When MPDS was developed in the 1970s Sickle Cell Disease (SCD) was not common in the UK and was therefore not included in the system. As ethnic diversity in the UK increased so did the prevalence of SCD, yet ambulance services were still unable to identify this group of patients and assess their specific needs.

Patients with SCD usually contact the ambulance service when they experience a Sickle Cell Crisis (SCC), which is characterised by severe pain. It is important ambulances arrive quickly to allow patients' pain to be managed in a timely manner. However, not having a way to identify these patients at the time of the 999 call means that patients potentially receives variable responses.

Method

To determine the level of care provided, a retrospective clinical audit was undertaken for patients who reported SCC. A questionnaire was sent to patients with SCD which was used to inform the development of an override to MPDS allowing Emergency Medical Dispatchers to allocate a faster response to patients reporting SCC at the time of the 999 call. Following the introduction of the over-ride, a re-audit was conducted.

Results

The re-audit showed the majority of patients (62%) received an equal or a faster response in line with the updated MPDS protocol. This increase resulted in reduced waiting time for patients; from 11 minutes and 20 seconds to 9 minutes, an average of 2 minutes and 20 seconds faster than before the over-ride.

Conclusion

The over-ride resulted in a quicker ambulance response which reduced the chances of the patient's condition worsening before the arrival of an ambulance. This project also provided evidence and allowed for the SCC override to be adopted nationally.
Measurement of nucleated red blood cells in the peripheral blood as a marker of hypoxia in sudden unexpected death in infancy
Authors: Zapata Vazquez Rita E , Coetzee André , Harlock Edward , Simmerson Mark , Cohen Marta C
Published: May 2015

Aims

A recently proposed classification of sudden unexpected infant death incorporates consideration of possibly asphyxia. This depends on an adequate postmortem, scene investigation and history. A reliable marker of asphyxia has yet to be identified. Such a marker could assist in classifying these deaths. Our aim was to determine if the level of nucleated red blood cells (nRBCs) in the peripheral blood could help identify those possibly asphyxia-related deaths and if risk factors could influence this level in the peripheral blood.

Methods

Cases of sudden unexpected deaths in infancy and sudden infant death syndrome (SIDS) which occurred over a period of 6 years (2007–2013) and were autopsied at Sheffield Children's Hospital were reviewed and categorised according to a new classification proposed by Randallet al. The cases were then correlated with the blood level of nRBCs determined at the time of post mortem examination. The study was approved by the Clinical Governance Department, number SE331.

Results

139 deaths were classified into Group A (true SIDS, 67 cases), Group B (possible asphyxia related, 24 cases), Group C (non-asphyxia-related, 6 cases), Group D (no crime scene investigation, 0 cases) and Group E (identifiable cause, 42 cases). The levels were significantly increased in ex-premature babies, in infants with an underlying condition (Group C) and in deaths related to illness or trauma (Group E). There was a trend towards higher levels of nRBCs in younger age groups and in babies born to smoking mothers.

Conclusions

SIDS remains a difficult diagnosis to make despite the current medical technological advances where no marker of hypoxia has yet been identified.
Overview of contemporary guidelines in digital pathology: what is available in 2015 and what still needs to be addressed?
Authors: Hanna Matthew G , Pantanowitz Liron , Evans Andrew J
Published: May 2015

As technological advancements continue to transform the practice of pathology, new adopters of these technologies will look to guidelines on how best to incorporate them with an eye to preserving and enhancing patient safety and diagnostic quality. Telepathology, using a variety of digital pathology modalities, has tremendous potential to achieve that goal. Pathology departments are increasingly looking to implement different digital pathology platforms, whole slide imaging (WSI) systems in particular, for a broad range of applications in patient care. WSI allows for the acquisition, management and review of completely digitised slides as would be done with a light microscope. WSI also facilitates image analysis that cannot be carried out by a pathologist using traditional microscopy. Over the last few years, the Digital Pathology Association, The Royal College of Pathologists, College of American Pathologists, Canadian Association of Pathologists, the American Telemedicine Association and the Society of Toxicologic Pathology have published guidelines for validating and implementing digital pathology systems. This review summarises, compares and contrasts these published guidelines and discusses pertinent issues that need to be addressed as the guidelines are revised in the future.
What's in a Word? Concept mapping: a graphical tool to reinforce learning of epidemiological concepts
Authors: Berglund Anita
Published: May 2015

Epidemiology is founded on central concepts and principles, essential for conducting, reporting and critically assessing epidemiological studies. Definitions of the many concepts used in the field can be found in textbooks and via the Dictionary of Epidemiology. However, central epidemiological concepts are labelled and used in multiple ways, leading to potential misunderstanding when communicating in different fora. The aim here is to describe collaborative concept mapping, and illustrate how it can be used in teaching and learning epidemiology. Concept mapping is a cognitive technique that is widely used in the education of medical and allied health professions as a tool for critical thinking, and to assimilate new knowledge, but it is still under-utilised in epidemiology. A specific concept map is defined by the aim and question in focus; it is thus framed by a context. The concept map is constructed using a set of concepts (nodes) that are linked with arrows or lines (links). Words and phrases (connective terms) are used to explain relationships between the concepts linked. Different domains can be interconnected by linking concepts in different areas (cross-links). The underlying structure of knowledge is often complex, and consequently concept maps can be constructed using different topological features. Here we provide an illustrative example of concept mapping, based on a set of ‘basic’ concepts introduced in a doctoral course in epidemiology. In summary, concept mapping is a compelling, active learning tool, which can promote shared deeper knowledge of concepts and their complex interconnections, thereby facilitating a better understanding of epidemiological research.