bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Infections with Sarcocystis Species
Authors: Fayer Ronald , Esposito Douglas H. , Dubey Jitender P.
Published: February 2015

Recurrent outbreaks of muscular sarcocystosis among tourists visiting islands in Malaysia have focused international attention on sarcocystosis, a disease once considered rare in humans.
Sarcocystis
species require two hosts, definitive and intermediate, to complete their life cycle. Humans can serve as definitive hosts, with intestinal sarcocystosis for two species acquired from eating undercooked meat:
Sarcocystis hominis
, from beef, and
Sarcocystis suihominis
, from pork. Symptoms such as nausea, stomachache, and diarrhea vary widely depending on the number of cysts ingested but appear more severe with pork than with beef. Humans serve as intermediate hosts for
Sarcocystis nesbitti
, a species with a reptilian definitive host, and possibly other unidentified species, acquired by ingesting sporocysts from feces-contaminated food or water and the environment; infections have an early phase of development in vascular endothelium, with illness that is difficult to diagnose; clinical signs include fever, headache, and myalgia. Subsequent development of intramuscular cysts is characterized by myositis. Presumptive diagnosis based on travel history to tropical regions, elevated serum enzyme levels, and eosinophilia is confirmed by finding sarcocysts in muscle biopsy specimens. There is no vaccine or confirmed effective antiparasitic drug for muscular sarcocystosis, but anti-inflammatory drugs may reduce symptoms. Prevention strategies are also discussed.
Coinfection with Blood-Stage Plasmodium Promotes Systemic Type I Interferon Production during Pneumovirus Infection but Impairs Inflammation and Viral Control in the Lung
Authors: Edwards Chelsea L. , Zhang Vivian , Werder Rhiannon B. , Best Shannon E. , Sebina Ismail , James Kylie R. , Faleiro Rebecca J. , de Labastida Rivera Fabian , Amante Fiona H. , Engwerda Christian R. , Phipps Simon , Haque Ashraful
Published: February 2015

Acute lower respiratory tract infections (ALRTI) are the leading cause of global childhood mortality, with human respiratory syncytial virus (hRSV) being a major cause of viral ALRTI in young children worldwide. In sub-Saharan Africa, many young children experience severe illnesses due to hRSV orPlasmodiuminfection. Although the incidence of malaria in this region has decreased in recent years, there remains a significant opportunity for coinfection. Recent data show that febrile young children infected withPlasmodiumare often concurrently infected with respiratory viral pathogens but are less likely to suffer from pneumonia than are non-Plasmodium-infected children. Here, we hypothesized that blood-stagePlasmodiuminfection modulates pulmonary inflammatory responses to a viral pathogen but does not aid its control in the lung. To test this, we established a novel coinfection model in which mice were simultaneously infected with pneumovirus of mice (PVM) (to model hRSV) and blood-stagePlasmodium chabaudi chabaudiAS (PcAS) parasites. We found thatPcAS infection was unaffected by coinfection with PVM. In contrast, PVM-associated weight loss, pulmonary cytokine responses, and immune cell recruitment to the airways were substantially reduced by coinfection withPcAS. Importantly,PcAS coinfection facilitated greater viral dissemination throughout the lung. AlthoughPlasmodiumcoinfection induced low levels of systemic interleukin-10 (IL-10), this regulatory cytokine played no role in the modulation of lung inflammation or viral dissemination. Instead, we found thatPlasmodiumcoinfection drove an early systemic beta interferon (IFN-β) response. Therefore, we propose that blood-stagePlasmodiumcoinfection may exacerbate viral dissemination and impair inflammation in the lung by dysregulating type I IFN-dependent responses to respiratory viruses.
MrSkn7 Controls Sporulation, Cell Wall Integrity, Autolysis, and Virulence in Metarhizium robertsii
Authors: Shang Yanfang , Chen Peilin , Chen Yixiong , Lu Yuzhen , Wang Chengshu
Published: February 2015

Two-component signaling pathways generally include sensor histidine kinases and response regulators. We identified an ortholog of the response regulator protein Skn7 in the insect-pathogenic fungus
Metarhizium robertsii
, which we named MrSkn7. Gene deletion assays and functional characterizations indicated that MrSkn7 functions as a transcription factor. The
MrSkn7
null mutant of
M. robertsii
lost the ability to sporulate and had defects in cell wall biosynthesis but was not sensitive to oxidative and osmotic stresses compared to the wild type. However, the mutant was able to produce spores under salt stress. Insect bioassays using these spores showed that the virulence of the mutant was significantly impaired compared to that of the wild type due to the failures to form the infection structure appressorium and evade host immunity. In particular, deletion of
MrSkn7
triggered cell autolysis with typical features such as cell vacuolization, downregulation of repressor genes, and upregulation of autolysis-related genes such as extracellular chitinases and proteases. Promoter binding assays confirmed that MrSkn7 could directly or indirectly control different putative target genes. Taken together, the results of this study help us understand the functional divergence of Skn7 orthologs as well as the mechanisms underlying the development and control of virulence in insect-pathogenic fungi.
The CpxRA Two-Component System Is Essential for Citrobacter rodentium Virulence
Authors: Thomassin Jenny-Lee , Giannakopoulou Natalia , Zhu Lei , Gross Jeremy , Salmon Kristiana , Leclerc Jean-Mathieu , Daigle France , Le Moual Hervé , Gruenheid Samantha
Published: February 2015

Citrobacter rodentium
is a murine intestinal pathogen used as a model for the foodborne human pathogens enterohemorrhagic
Escherichia coli
and enteropathogenic
E. coli
. During infection, these pathogens use two-component signal transduction systems to detect and adapt to changing environmental conditions. In
E. coli
, the CpxRA two-component signal transduction system responds to envelope stress by modulating the expression of a myriad of genes. Quantitative real-time PCR showed that
cpxRA
was expressed in the colon of C57BL/6J mice infected with
C. rodentium
. To determine whether CpxRA plays a role during
C. rodentium
infection, a
cpxRA
deletion strain was generated and found to have a colonization defect during infection. This defect was independent of an altered growth rate or a defective type III secretion system, and single-copy chromosomal complementation of
cpxRA
restored virulence. The
C. rodentium
strains were then tested in C3H/HeJ mice, a lethal intestinal infection model. Mice infected with the Δ
cpxRA
strain survived infection, whereas mice infected with the wild-type or complemented strains succumbed to infection. Furthermore, we found that the
cpxRA
expression level was higher during early infection than at a later time point. Taken together, these data demonstrate that the CpxRA two-component signal transduction system is essential for the
in vivo
virulence of
C. rodentium
. In addition, these data suggest that fine-tuned
cpxRA
expression is important for infection. This is the first study that identifies a
C. rodentium
two-component transduction system required for pathogenesis. This study further indicates that CpxRA is an interesting target for therapeutics against enteric pathogens.
Complete Biosynthetic Pathway of the C50Carotenoid Bacterioruberin from Lycopene in the Extremely Halophilic Archaeon Haloarcula japonica
Authors: Yang Ying , Yatsunami Rie , Ando Ai , Miyoko Nobuhiro , Fukui Toshiaki , Takaichi Shinichi , Nakamura Satoshi
Published: February 2015

Haloarcula japonica, an extremely halophilic archaeon that requires high concentrations of NaCl for growth, accumulates the C50carotenoid bacterioruberin (BR). By homology analysis, a gene cluster, includingc0507,c0506, andc0505, was found and predicted to be involved in the synthesis of bacterioruberin. To elucidate the function of the encoded enzymes, we constructedHa. japonicamutants of these genes and analyzed carotenoids produced by the mutants. Our research showed thatc0507,c0506, andc0505encoded a carotenoid 3,4-desaturase (CrtD), a bifunctional lycopene elongase and 1,2-hydratase (LyeJ), and a C50carotenoid 2″,3″-hydratase (CruF), respectively. The above three carotenoid biosynthetic enzymes catalyze the reactions that convert lycopene to bacterioruberin inHa. japonica. This is the first identification of functional CrtD and CruF in archaea and elucidation of the complete biosynthetic pathway of bacterioruberin from lycopene.

IMPORTANCEHaloarcula japonica, an extremely halophilic archaeon, accumulates the C50carotenoid bacterioruberin (BR). In this study, we have identified three BR biosynthetic enzymes and have elucidated their functions. Among them, two enzymes were found in an archaeon for the first time. Our results revealed the biosynthetic pathway responsible for production of BR inHa. japonicaand provide a basis for investigating carotenoid biosynthetic pathways in other extremely halophilic archaea. Elucidation of the carotenoid biosynthetic pathway inHa. japonicamay also prove useful for producing the C50carotenoid BR efficiently by employing genetically modified haloarchaeal strains.
The Ferrous Iron-Responsive BqsRS Two-Component System Activates Genes That Promote Cationic Stress Tolerance
Authors: Kreamer Naomi N. , Costa Flavia , Newman Dianne K.
Published: February 2015

The physiological resistance of pathogens to antimicrobial treatment is a severe problem in the context of chronic infections. For example, the mucus-filled lungs of cystic fibrosis (CF) patients are readily colonized by diverse antibiotic-resistant microorganisms, including
Pseudomonas aeruginosa
. Previously, we showed that bioavailable ferrous iron [Fe(II)] is present in CF sputum at all stages of infection and constitutes a significant portion of the iron pool at advanced stages of lung function decline [R. C. Hunter et al., mBio 4(4):e00557-13, 2013].
P. aeruginosa
, a dominant CF pathogen, senses Fe(II) using a two-component signal transduction system, BqsRS, which is transcriptionally active in CF sputum [R. C. Hunter et al., mBio 4(4):e00557-13, 2013; N. N. Kreamer, J. C. Wilks, J. J. Marlow, M. L. Coleman, and D. K. Newman, J Bacteriol 194:1195–1204, 2012]. Here, we show that an RExxE motif in BqsS is required for BqsRS activation. Once Fe(II) is sensed, BqsR binds a tandem repeat DNA sequence, activating transcription. The BqsR regulon—defined through iterative bioinformatic predictions and experimental validation—includes several genes whose products are known to drive antibiotic resistance to aminoglycosides and polymyxins. Among them are genes encoding predicted determinants of polyamine transport and biosynthesis. Compared to the wild type,
bqsS
and
bqsR
deletion mutants are sensitive to high levels of Fe(II), produce less spermidine in high Fe(II), and are more sensitive to tobramycin and polymyxin B but not arsenate, chromate, or cefsulodin. BqsRS thus mediates a physiological response to Fe(II) that guards the cell against positively charged molecules but not negatively charged stressors. These results suggest Fe(II) is an important environmental signal that, via BqsRS, bolsters tolerance of a variety of cationic stressors, including clinically important antimicrobial agents.

IMPORTANCE
Clearing chronic infections is challenging due to the physiological resistance of opportunistic pathogens to antibiotics. Effective treatments are hindered by a lack of understanding of how these organisms survive
in situ
. Fe(II) is typically present at micromolar levels in soils and sedimentary habitats, as well as in CF sputum. All P. aeruginosa strains possess a two-component system, BqsRS, that specifically senses extracellular Fe(II) at low micromolar concentrations. Our work shows that BqsRS protects the cell against cationic perturbations to the cell envelope as well as low pH and reduction potential (Eh), conditions under which Fe
2+
is stable. Fe(II) can thus be understood as a proxy for a broader environmental state; the cellular response to its detection may help rationalize the resistance of P. aeruginosa to clinically important cationic antibiotics. This finding demonstrates the importance of considering environmental chemistry when exploring mechanisms of microbial survival in habitats that include the human body.
Chronic Superantigen Exposure Induces Systemic Inflammation, Elevated Bloodstream Endotoxin, and Abnormal Glucose Tolerance in Rabbits: Possible Role in Diabetes
Authors: Vu Bao G. , Stach Christopher S. , Kulhankova Katarina , Salgado-Pabón Wilmara , Klingelhutz Aloysius J. , Schlievert Patrick M.
Published: February 2015

Excessive weight and obesity are associated with the development of diabetes mellitus type 2 (DMII) in humans. They also pose high risks of
Staphylococcus aureus
colonization and overt infections.
S. aureus
causes a wide range of severe illnesses in both healthy and immunocompromised individuals. Among
S. aureus
virulence factors, superantigens are essential for pathogenicity. In this study, we show that rabbits that are chronically exposed to
S. aureus
superantigen toxic shock syndrome toxin-1 (TSST-1) experience impaired glucose tolerance, systemic inflammation, and elevated endotoxin levels in the bloodstream, all of which are common findings in DMII. Additionally, such DMII-associated findings are also seen through effects of TSST-1 on isolated adipocytes. Collectively, our findings suggest that chronic exposure to
S. aureus
superantigens facilitates the development of DMII, which may lead to therapeutic targeting of
S. aureus
and its superantigens.

IMPORTANCE
Obesity has a strong correlation with type 2 diabetes, in which fatty tissue, containing adipocytes, contributes to the development of the illness through altered metabolism and chronic inflammation. The human microbiome changes in persons with obesity and type 2 diabetes, including increases in
Staphylococcus aureus
colonization and overt infections. While the microbiome is essential for human wellness, there is little understanding of the role of microbes in obesity or the development of diabetes. Here, we demonstrate that the
S. aureus
superantigen toxic shock syndrome toxin-1 (TSST-1), an essential exotoxin in pathogenesis, induces inflammation, lipolysis, and insulin resistance in adipocytes both
in vitro
and
in vivo
. Chronic stimulation of rabbits with TSST-1 results in impaired systemic glucose tolerance, the hallmark finding in type 2 diabetes in humans, suggesting a role of
S. aureus
and its superantigens in the progression to type 2 diabetes.
Lumbar blood patching for proximal CSF leaks: where does the blood go?
Authors: Nesbitt Cassie , Amukotuwa Shalini , Chapman Caron , Batchelor Peter
Published: February 2015

Epidural blood patching (EBP) is an important therapeutic approach in managing spontaneous cerebrospinal fluid leaks. The mechanism of action of blood patching is likely to be twofold; fluid replacement having an immediate tamponade effect and the proximal flow of blood products having a ‘plug’ effect. The negative pressure gradient within the epidural space may be important to the rostral flow of injected blood and is possibly increased in intracranial hypotension.
Spontaneous iliopsoas haematoma: a complication of hypertensive urgency
Authors: Yogarajah Meera , Sivasambu Bhradeev , Jaffe Eric A
Published: February 2015

Iliopsoas haematoma is a rare clinical entity which can be life threatening in extreme cases. We are reporting a case of iliopsoas haematoma as a complication of hypertensive urgency. A 67-year old woman presented to emergency room with hypertensive urgency and hip pain. During hospitalisation, her haemoglobin was decreasing and on further evaluation, she did not have any signs of external bleeding and laboratory results were not suggestive of haemolysis. CT scan of abdomen and pelvis revealed a spontaneous iliopsoas haematoma. A likely explanation for this presentation in the absence of coagulopathy and trauma is very high blood pressure. Patient was on low-dose aspirin at home which could have further aggravated her bleeding due to platelet dysfunction. She was managed conservatively with blood transfusions and blood pressure was reduced to target after which she recovered.
The importance of not jumping to conclusions: syphilis as an organic cause of neurological, psychiatric and endocrine presentations
Authors: Noblett Joanne , Roberts Emmert
Published: February 2015

A 66-year-old Caucasian man was admitted to an acute psychiatric ward under section 2 of the Mental Health Act after presenting with auditory hallucinations and partition delusions. He had been known to mental health services since 2005 but had never been treated with psychotropic medication or given a formal psychiatric diagnosis. He was also diagnosed with hypopituitarism of unknown aetiology in 2002. In light of this presentation, his medical history was reviewed in full, hormone levels and a full delirium screen including blood borne virus and syphilis serology was completed to ensure no organic cause had been missed. The treponemal antibody was positive, and he reported no previous syphilis treatment, as such a diagnosis of neurosyphilis was performed. This case demonstrates a patient presenting with two potential complications of syphilis; psychosis and hypopituitarism where screening for this infection had not been previously considered.
Sideroblastic anaemia and primary adrenal insufficiency due to a mitochondrial respiratory chain disorder in the absence of mtDNA deletion
Authors: O'Grady Michael J , Monavari Ahmad A , Cotter Melanie , Murphy Nuala P
Published: February 2015

A fatigued 8-year-old boy was found to have sideroblastic anaemia (haemoglobin 7.8 g/dL) which over time became transfusion dependent. Subtle neurological dysfunction, initially manifesting as mild spastic diplegia, was slowly progressive and ultimately led to wheelchair dependence. Elevated plasma lactate and urinary 3-methylglutaconate led to a muscle biopsy which confirmed partial complex IV deficiency. PCR in leucocytes and muscle was negative for mitochondrial DNA (mtDNA) deletions. Faltering growth prompted an insulin tolerance test which confirmed growth hormone sufficiency and adrenal insufficiency. Plasma renin was elevated and adrenal androgens were low, suggesting primary adrenal insufficiency. Glucocorticoid and mineralocorticoid replacement therapy was initiated. A renal tubular Fanconi syndrome and diabetes mellitus developed subsequently. Sideroblastic anaemia and primary adrenal insufficiency, both individually and collectively, are associated with mtDNA deletion; however, absence of the same does not exclude the possibility that sideroblastic anaemia and primary adrenal insufficiency are of mitochondrial origin.
Pseudoaneurysm: an unusual cause of post-traumatic hand swelling
Authors: Shah Sonali , Powell-Brett Sarah , Garnham Andrew
Published: February 2015

Pseudoaneurysms of the hand are a rare presentation with potentially devastating consequences. We present a case of a hand pseudoaneurysm following a single episode of blunt trauma that was effectively managed by simply suspending the patient's warfarin therapy.
Superior mesenteric artery syndrome as a cause for recurrent abdominal pain and vomiting in a 9-year-old girl
Authors: Forsyth James Michael , Muhammad Karim , Mahmood Khalid
Published: February 2015

A 9-year-old girl was admitted under our general surgical team with 2 days of diffuse abdominal pain and vomiting. This was one of multiple admissions for similar symptoms over the past 5 years. She was feverish on admission but haemodynamically stable. On examination, she had a diffusely tender and hypersensitive abdomen, with no guarding or peritonism, and no palpable masses. Of note, the patient was very thin, with almost no body fat. Blood tests were otherwise normal, with a normal abdominal X-ray and abdominal ultrasound. She had undergone three previous abdominal ultrasounds over the past 5 years for similar symptoms, all of which were normal. Following this, CT revealed a diagnosis of superior mesenteric artery syndrome. The patient was transferred to our regional children's hospital for analgaesia, nasogastric decompression and nutritional supplementation. She made a swift improvement with plans for ongoing follow-up by the paediatric team.
Provider beliefs about diabetes treatment have little impact on glycemic control of their patients with diabetes
Authors: LeBlanc Erin S , Rosales A Gabriela , Kachroo Sumesh , Mukherjee Jayanti , Funk Kristine L , Schneider Jennifer L , Nichols Gregory A
Published: February 2015

Objective

To improve the health of people with diabetes, it is essential to identify why patients experience extended periods of poor glycemic control before therapeutic intensification.

Research design and methods

We surveyed 252 primary care providers at Kaiser Permanente Northwest to determine their beliefs about the glycemic goals of their patients, treatment intensification behavior, and barriers to achieving optimal glycemic control. We linked the responses of 149 providers to the health records of their 18 346 patients with diabetes.

Results

Patient glycemic levels were not related to either individualized glycemic goals or provider intensification behavior. Providers’ beliefs about diabetic treatment and glycated hemoglobin (HbA1c) goals were poorly associated with patient HbA1c levels. Providers identified patients’ resistance to lifestyle behaviors and taking insulin, lack of medication adherence, and psychosocial issues as the main barriers to optimal glycemic control. Lack of time to care for complex patients was also a barrier. Providers who agreed that “current research did not support A1C levels <7%” were less likely to have patients with HbA1c levels <7% (OR=0.87, 95% CI 0.78 to 0.97) and patients of providers who disagreed that “some patients will have an A1C >9% no matter what I do” were 16% more likely to have patients with HbA1c <7% (1.16, 1.03 to 1.30) compared with providers who were neutral about those statements.

Conclusions

Given the consistency of HbA1c levels across providers despite differences in beliefs and intensification behaviors, these barriers may be best addressed by instituting changes at the system level (ie, instituting institutional glycemic targets or outreach for dysglycemia) rather than targeting practice patterns of individual providers.
Mental illness, poverty and stigma in India: a case–control study
Authors: Trani Jean-Francois , Bakhshi Parul , Kuhlberg Jill , Narayanan Sreelatha S , Venkataraman Hemalatha , Mishra Nagendra N , Groce Nora E , Jadhav Sushrut , Deshpande Smita
Published: February 2015

Objective

To assess the effect of experienced stigma on depth of multidimensional poverty of persons with severe mental illness (PSMI) in Delhi, India, controlling for gender, age and caste.

Design

Matching case (hospital)–control (population) study.

Setting

University Hospital (cases) and National Capital Region (controls), India.

Participants

A case–control study was conducted from November 2011 to June 2012. 647 cases diagnosed with schizophrenia or affective disorders were recruited and 647 individuals of same age, sex and location of residence were matched as controls at a ratio of 1:2:1. Individuals who refused consent or provided incomplete interview were excluded.

Main outcome measures

Higher risk of poverty due to stigma among PSMI.

Results

38.5% of PSMI compared with 22.2% of controls were found poor on six dimensions or more. The difference in multidimensional poverty index was 69% between groups with employment and income of the main contributors. Multidimensional poverty was strongly associated with stigma (OR 2.60, 95% CI 1.27 to 5.31), scheduled castes/scheduled tribes/other backward castes (2.39, 1.39 to 4.08), mental illness (2.07, 1.25 to 3.41) and female gender (1.87, 1.36 to 2.58). A significant interaction between stigma, mental illness and gender or caste indicates female PSMI or PSMI from ‘lower castes’ were more likely to be poor due to stigma than male controls (p<0.001) or controls from other castes (p<0.001).

Conclusions

Public stigma and multidimensional poverty linked to SMI are pervasive and intertwined. In particular for low caste and women, it is a strong predictor of poverty. Exclusion from employment linked to negative attitudes and lack of income are the highest contributors to multidimensional poverty, increasing the burden for the family. Mental health professionals need to be aware of and address these issues.
Association between C reactive protein level and depressive symptoms in an elderly Korean population: Korean Social Life, Health and Aging Project
Authors: Song Bo Mi , Lee Ju-Mi , Choi Wungrak , Youm Yoosik , Chu Sang Hui , Park Yeong-Ran , Kim Hyeon Chang
Published: February 2015

Objective

The relationship between inflammatory markers and depressive symptoms has been reported inconsistently. Moreover, there were only a few studies conducted in an Asian population. The purpose of this study was to examine the association between C reactive protein (CRP) and depressive symptoms in an elderly Korean population.

Design, setting and participants

This study used data from the Korean Social Life, Health and Aging Project Health Examination Cohort, which started in 2011. Among participants aged 60 or over recruited from a rural community, 569 (224 men and 345 women) without a history of stroke, angina pectoris, myocardial infarction or CRP≥20 mg/L were employed for cross-sectional analyses. As a marker of systemic inflammation, CRP was measured. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression (CES-D) scale. Multiple linear regression analysis was used to investigate the relationship between CRP and depressive symptoms.

Results

In men, CRP levels had significant associations with depressive symptoms before (β=0.420, p=0.010) and after (β=0.336, p=0.025) adjusting for age, body mass index, systolic blood pressure, number of comorbidities, smoking status, alcohol intake, marital status, education and sleep duration. However, in women, the association between CRP and depressive symptoms was not significant before (p=0.250) and after (p=0.256) adjustment.

Conclusions

Our findings suggest that elevated CRP levels are independently associated with the presence of depressive symptoms in elderly Korean men.
What do external consultants from private and not-for-profit companies offer healthcare commissioners? A qualitative study of knowledge exchange
Authors: Wye Lesley , Brangan Emer , Cameron Ailsa , Gabbay John , Klein Jonathan H , Anthwal Rachel , Pope Catherine
Published: February 2015

Objectives

The use of external consultants from private and not-for-profit providers in the National Health Service (NHS) is intended to improve the quality of commissioning. The aim of this study was to learn about the support offered to healthcare commissioners, how external consultants and their clients work together and the perceived impact on the quality of commissioning.

Setting

NHS commissioning organisations and private and not-for-profit providers.

Design

Mixed methods case study of eight cases.

Data collection

92 interviews with external consultants (n=36), their clients (n=47) and others (n=9). Observation of 25 training events and meetings. Documentation, for example, meeting minutes and reports.

Analysis

Constant comparison. Data were coded, summarised and analysed by the research team with a coding framework to facilitate cross-case comparison.

Results

In the four contracts presented here, external providers offered technical solutions (eg, software tools), outsourcing and expertise including project management, data interpretation and brokering relationships with experts. In assessing perceived impact on quality of commissioning, two contracts had limited value, one had short-term benefits and one provided short and longer term benefits. Contracts with commissioners actively learning, embedding and applying new skills were more valued. Other elements of success were: (1) addressing clearly agreed problems of relevance to managerialandoperational staff (2) solutions co-produced at all organisational levels (3) external consultants working directly with clients to interpret data outputs to inform locally contextualised commissioning strategies. Without explicit knowledge exchange strategies, outsourcing commissioning to external providers resulted in the NHS clients becoming dependent.

Conclusions

NHS commissioning will be disadvantaged if commissioners both fail to learn in the short term from the knowledge of external providers and in the longer term lose local skills. Knowledge exchange mechanisms are a vital component of commissioning and should be embedded in external provider contracts.
Large regional differences in incidence of arthroscopic meniscal procedures in the public and private sector in Denmark
Authors: Hare Kristoffer Borbjerg , Vinther Jesper Høeg , Lohmander L Stefan , Thorlund Jonas Bloch
Published: February 2015

Objectives

A recent study reported a large increase in the number of meniscal procedures from 2000 to 2011 in Denmark. We examined the nation-wide distribution of meniscal procedures performed in the private and public sector in Denmark since different incentives may be present and the use of these procedures may differ from region to region.

Setting

We included data on all patients who underwent an arthroscopic meniscal procedure performed in the public or private sector in Denmark.

Participants

Data were retrieved from the Danish National Patient Register on patients who underwent arthroscopic meniscus surgery as a primary or secondary procedure in the years 2000 to 2011. Hospital identification codes enabled linkage of performed procedures to specific hospitals.

Primary and secondary outcome measures

Yearly incidence of meniscal procedures per 100 000 inhabitants was calculated with 95% CIs for public and private procedures for each region.

Results

Incidence of meniscal procedures increased at private and at public hospitals. The private sector accounted for the largest relative and absolute increase, rising from an incidence of 1 in 2000 to 98 in 2011. In 2011, the incidence of meniscal procedures was three times higher in the Capital Region than in Region Zealand.

Conclusions

Our study identified a large increase in the use of meniscal procedures in the public and private sector in Denmark. The increase was particularly conspicuous in the private sector as its proportion of procedures performed increased from 1% to 32%. Substantial regional differences were present in the incidence and trend over time of meniscal procedures.
‘Do Well B.’: Design Of WELL Being monitoring systems. A study protocol for the application in autism
Authors: Dutheil Frédéric , Chambres Patrick , Hufnagel Cédric , Auxiette Catherine , Chausse Pierre , Ghozi Raja , Paugam Guillaume , Boudet Gil , Khalfa Nadia , Naughton Geraldine , Chamoux Alain , Mermillod Martial , Bertrand Pierre Raphael
Published: February 2015

Introduction

Individuals with autism spectrum disorder (ASD) have difficulties in communication and social interaction resulting from atypical perceptual and cognitive information processing, leading to an accumulation of anxiety. Extreme overloading experienced internally may not be externally visible. Identifying stressful situations at an early stage may avoid socially problematic behaviour from occurring, such as self-injurious behaviour. Activation of the autonomous nervous system (ANS) is involved in the response to anxiety, which can be measured through heart rate variability and skin conductance with the use of portable devices, non-intrusively and pain-free. Thus, developing innovative analysis of signal perception and reaction is necessary, mainly for non-communicative individuals with autism.

Methods and analysis

The protocol will take place in real life (home and social environments). We aim to associate modifications of the ANS with external events that will be recorded in a synchronous manner through a specific design (spy glasses with video/audio recording). Four phases will be carried out on ASD participants and aged-matched controls: (1) 24-hour baseline pre-experiment (physical activity, sleep), (2) 2 h in a real life situation, (3) 30 min in a quiet environment, interrupted by a few seconds of stressful sound, (4) an interview to record feelings about events triggering anxiety. ASD and control participants will be together for phases 2 and 3, revealing different physiological responses to the same situations, and thus identifying potentially problematic events. The novelty will be to apply time-series analyses (which led to several Nobel Prizes in quantitative finance) on ANS series (heart rate, heart rate variability, skin conductance) and wrist motion.

Ethics and dissemination

Ethical approval has been obtained from Ethics Committee of Clermont-Ferrand (South-East I), France (2014-A00611–46). Trial findings will be disseminated via open-access peer-reviewed publications, conferences, clinical networks, public lectures and our websites.

Trial registration number

ClinicalTrials identifierNCT02275455.
Patients’ practices and experiences of using nebuliser therapy in the management of COPD at home
Authors: Alhaddad B , Smith F J , Robertson T , Watman G , Taylor K M G
Published: February 2015

Background and aim

How patients use their nebulisers at home is vital to ensure effective treatment and optimal health outcomes for patients with chronic obstructive pulmonary disease (COPD). The aim of the study was to identify the practicalities and problems associated with nebuliser use by patients with COPD at home, which may impact on the safety and effectiveness of therapy.

Design and setting

A cross-sectional descriptive study in which participants were recruited from two levels of care: primary care, involving 38 GP practices in North West London, and intermediate care with a major acute hospital.

Method

In-depth interviews were conducted with a representative sample of 50 patients with COPD using nebulisers in their home, recruited from general practice populations and at hospital discharge. A checklist was used to record activities and patients demonstrated use of their nebuliser. Qualitative procedures were employed to identify the range of problems experienced with nebuliser use.

Results

A wide range of practical issues was identified at all stages: problems prior to nebulisation: setting up equipment, lack of instructions, manual dexterity and time required. Problems during medication administration: inhalation technique, duration of nebulisation and understanding how to achieve optimal efficacy. Problems post-administration: inadequate cleaning of nebuliser components, access to accessories and use of damaged parts or self-repairs. Other problems included noise, weight and non-portability of equipment.

Conclusions

Patients with COPD using nebulisers at home experienced problems with all aspects, many of which may be anticipated to compromise clinical outcomes. Healthcare providers should be aware of these problems to effectively support patients with COPD with the use of their nebulisers at home.
BET 1: role of vinegar in Irukandji syndrome
Authors: Doshi Deepak , Foëx Bernard A , Nataly Yogesh
Published: February 2015

A shortcut review was carried out to establish whether dousing areas of contact with vinegar could relieve the symptoms of Irukandji syndrome. Four studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is there is a lack of evidence for effectiveness and the latest local guidelines should be followed.
BET 2: In patients presenting with an exacerbation of COPD can a normal venous blood gas pCO2rule out arterial hypercarbia?
Authors: Woods Mark , Hodgson David
Published: February 2015

A shortcut review was carried out to establish whether a normal partial pressure of carbon dioxide (pCO2) on a venous blood sample could be used to rule out hypercarbia. Eleven studies were directly relevant to the question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these papers are tabulated. The clinical bottom line is that a normal venous pCO2effectively rules out arterial hypercarbia.
Angiotensin II causes cellular proliferation in infantile haemangioma via angiotensin II receptor 2 activation
Authors: Itinteang Tinte , Marsh Reginald , Davis Paul Frank , Tan Swee Thong
Published: February 2015

Aims

To investigate the effect of the angiotensin peptides and their agonists and antagonists on cellular proliferation in proliferating infantile haemangioma (IH) in vitro explants.

Methods

Proliferating IH samples from six patients were cultured in vitro in the presence of angiotensin I (ATI) alone, or AT1 and the ACE inhibitor, ramipril, or ATII alone, or ATII with the ATII receptor 1 (ATIIR1) blocker, losartan, or ATII with the ATIIR2 blocker, PD123319, or the ATIIR2 agonist, CGP42112. After 6 days in culture, the IH tissue pieces were harvested, formalin-fixed and paraffin-embedded. The effect of each treatment type on cellular proliferation was evaluated by immunohistochemical staining of these tissue pieces using the proliferation marker, Ki67.

Results

There was a significant increase in cellular proliferation in the ATI and ATII treated IH tissues compared with control samples. Their effect on cellular proliferation was reduced by adding ramipril and PD123319, respectively. CGP42112, but not losartan, significantly increased cellular proliferation.

Conclusions

Our findings suggest a key regulatory role of ATI and ATII in promoting cellular proliferation in IH, and establish a role for ACE and ATIIR2 in the proliferation of this tumour.
Are fluoride levels in drinking water associated with hypothyroidism prevalence in England? A large observational study of GP practice data and fluoride levels in drinking water
Authors: Peckham S , Lowery D , Spencer S
Published: February 2015

Background

While previous research has suggested that there is an association between fluoride ingestion and the incidence of hypothyroidism, few population level studies have been undertaken. In England, approximately 10% of the population live in areas with community fluoridation schemes and hypothyroidism prevalence can be assessed from general practice data. This observational study examines the association between levels of fluoride in water supplies with practice level hypothyroidism prevalence.

Methods

We used a cross-sectional study design using secondary data to develop binary logistic regression models of predictive factors for hypothyroidism prevalence at practice level using 2012 data on fluoride levels in drinking water, 2012/2013 Quality and Outcomes Framework (QOF) diagnosed hypothyroidism prevalence data, 2013 General Practitioner registered patient numbers and 2012 practice level Index of Multiple Deprivation scores.

Findings

We found that higher levels of fluoride in drinking water provide a useful contribution for predicting prevalence of hypothyroidism. We found that practices located in the West Midlands (a wholly fluoridated area) are nearly twice as likely to report high hypothyroidism prevalence in comparison to Greater Manchester (non-fluoridated area).

Interpretation

In many areas of the world, hypothyroidism is a major health concern and in addition to other factors—such as iodine deficiency—fluoride exposure should be considered as a contributing factor. The findings of the study raise particular concerns about the validity of community fluoridation as a safe public health measure.
Case ascertainment of heat illness in the British Army: evidence of under-reporting from analysis of Medical and Command notifications, 2009–2013
Authors: Stacey Michael J , Brett S , Woods D , Jackson S , Ross D
Published: February 2015

Background

Heat illness in the Armed Forces is considered preventable. The UK military relies upon dual Command and Medical reporting for case ascertainment, investigation of serious incidents and improvement of preventive practices and policy. This process could be vulnerable to under-reporting.

Objectives

To establish whether heat illness in the British Army has been under-reported, by reviewing concordance of reporting to the Army Incident Notification Cell (AINC) and the Army Health Unit (AHU) and to characterise the burden of heat illness reported by these means.

Methods

Analysis of anonymised reporting databases held by the AHU and AINC, for the period 2009–2013.

Results

565 unique cases of heat illness were identified. Annual concordance of reporting ranged from 9.6% to 16.5%. The overall rate was 13.3%. July was the month with the greatest number of heat illness reports (24.4% of total reporting) and the highest concordance rate (30%). Reports of heat illness from the UK (n=343) exceeded overseas notifications (n=221) and showed better concordance (17.1% vs 12.8%). The annual rate of reported heat illness varied widely, being greater in full-time than reservist personnel (87 vs 23 per100 000) and highest in full-time untrained personnel (223 per100 000).

Conclusions

The risk of heat illness was global, year-round and showed dynamic local variation. Failure to dual-report casualties impaired case ascertainment of heat illness across Command and Medical chains. Current preventive guidance, as applied in training and on operations, should be critically evaluated to ensure that risk of heat illness is reduced as low as possible. Clear procedures for casualty notification and surveillance are required in support of this and should incorporate communication within and between the two reporting chains.
Open abdomen and VAC®in severe diffuse peritonitis
Authors: Mutafchiyski Ventsislav M , Popivanov G I , Kjossev K T , Chipeva S
Published: February 2015

Background

Currently, the open abdomen technique is the widely recognised method for treatment of life-threatening trauma, intra-abdominal sepsis, abdominal compartment syndrome and wound dehiscence. The techniques for temporary closure using negative pressure have gained increasing popularity. Although negative pressure wound therapy has been proved as an effective method in trauma, the results in diffuse peritonitis are contradictory.

Methods

Overall, 108 patients with diffuse peritonitis and open abdomen were prospectively enrolled from January 2006 to December 2013—69 treated with mesh-foil laparostomy without negative pressure and 49 with vacuum-assisted closure (VAC®) The primary endpoints were the rate of primary fascial closure and mortality. The secondary outcomes were the rate of complications—enteroatmospheric fistulas, intra-abdominal abscesses, wound infection and necrotising fasciitis, intensive care unit (ICU) and overall hospital stay.

Results

VAC was associated with higher overall (73% vs 53%) and late primary fascial closure rates (31% vs 7%), lower rates of necrotising fasciitis (2% vs 15%, p=0.012), intra-abdominal abscesses (10% vs 20%), enteroatmospheric fistulas (8% vs 19%), overall mortality (31% vs 53%, p<0.05), shorter ICU (6.1 vs 10.6 days, p=0.002) and hospital stay (15.1 vs 25.9 days, p=0.000).

Conclusions

The results clearly suggest the obvious advantage of VAC in comparison to the temporary abdominal closure without negative pressure in the cases with severe diffuse peritonitis. However, to a large extent, our results might be attributed to the combination of VAC with dynamic fascial closure.
EULAR Sjögren's syndrome disease activity index (ESSDAI): a user guide
Authors: Seror Raphaèle , Bowman Simon J , Brito-Zeron Pilar , Theander Elke , Bootsma Hendrika , Tzioufas Athanasios , Gottenberg Jacques-Eric , Ramos-Casals Manel , Dörner Thomas , Ravaud Philippe , Vitali Claudio , Mariette Xavier
Published: February 2015

The EULAR Sjögren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. With the growing use of the ESSDAI, some domains appear to be more challenging to rate than others. The ESSDAI is now in use as a gold standard to measure disease activity in clinical studies, and as an outcome measure, even a primary outcome measure, in current randomised clinical trials. Therefore, ensuring an accurate and reproducible rating of each domain, by providing a more detailed definition of each domain, has emerged as an urgent need. The purpose of the present article is to provide a user guide for the ESSDAI. This guide provides definitions and precisions on the rating of each domain. It also includes some minor improvement of the score to integrate advance in knowledge of disease manifestations. This user guide may help clinicians to use the ESSDAI, and increase the reliability of rating and consequently of the ability to detect true changes over time. This better appraisal of ESSDAI items, along with the recent definition of disease activity levels and minimal clinically important change, will improve the assessment of patients with primary SS and facilitate the demonstration of effectiveness of treatment for patients with primary SS.
Determination of the minimum infusion rate of alfaxalone during its co‐administration with midazolam in goats
Authors: Dzikiti T. B. , Ndawana P. S. , Zeiler G. , Bester L. , Dzikiti L. N.
Published: February 2015

Introduction

The minimum infusion rate (MIR) of alfaxalone when co‐administered with midazolam in goats was evaluated.

Materials and methods

Eight goats (four does and four wethers) were anaesthetised, on separate occasions, with alfaxalone at an initial dose of 9.6 mg/kg/hour combined with one of three midazolam treatments: a bolus of 0.1 mg/kg followed by constant rate infusion (CRI) of 0.1 mg/kg/hour (treatment LMID), 0.3 mg/kg followed by CRI of 0.3 mg/kg/hour (MMID), 0.9 mg/kg followed by CRI of 0.9 mg/kg/hour (HMID), intravenously. Responses to stimulation (clamping on the proximal part of one digit of the hoof with Vulsellum forceps for 60 seconds) were tested every 30 minutes. In the absence or presence of a response to stimulation, the infusion rate was reduced or increased by 1.9 mg/kg/hour. Alfaxalone MIR was calculated as the mean of the infusion rates that allowed and abolished movement. Cardiopulmonary parameters were measured.

Results

Alfaxalone MIR was 6.7 (6.7–8.6) mg/kg/hour, 6.7 (4.8–6.7) mg/kg/hour and 2.9 (1.0–4.8) mg/kg/hour for LMID, MMID and HMID respectively. Cardiopulmonary function was minimally affected, with hypoxaemia observed two minutes into anaesthesia during all treatments. Recovery from anaesthesia was excitement‐free.

Conclusions

Midazolam causes a dose‐dependent reduction of alfaxalone MIR in goats. Oxygen supplementation is recommended during anaesthesia with alfaxalone and midazolam in goats.