bluuebunny/crossref_metadata_2025 huggingface dataset:
Synergistic Toxicity of Copper and Gold Compounds in Cupriavidus metallidurans
Authors: Wiesemann Nicole , Bütof Lucy , Herzberg Martin , Hause Gerd , Berthold Lutz , Etschmann Barbara , Brugger Joël , Martinez-Criado Gema , Dobritzsch Dirk , Baginsky Sacha , Reith Frank , Nies Dietrich H.
Published: September 2017

The bacterium
Cupriavidus metallidurans
can reduce toxic gold(I/III) complexes and biomineralize them into metallic gold (Au) nanoparticles, thereby mediating the (trans)formation of Au nuggets. In Au-rich soils, most transition metals do not interfere with the resistance of this bacterium to toxic mobile Au complexes and can be removed from the cell by plasmid-encoded metal efflux systems. Copper is a noticeable exception: the presence of Au complexes and Cu ions results in synergistic toxicity, which is accompanied by an increased cytoplasmic Cu content and formation of Au nanoparticles in the periplasm. The periplasmic Cu-oxidase CopA was not essential for formation of the periplasmic Au nanoparticles. As shown with the purified and reconstituted Cu efflux system CupA, Au complexes block Cu-dependent release of phosphate from ATP by CupA, indicating inhibition of Cu transport. Moreover, Cu resistance of Au-inhibited cells was similar to that of mutants carrying deletions in the genes for the Cu-exporting P
IB1
-type ATPases. Consequently, Au complexes inhibit export of cytoplasmic Cu ions, leading to an increased cellular Cu content and decreased Cu and Au resistance. Uncovering the biochemical mechanisms of synergistic Au and Cu toxicity in
C. metallidurans
explains the issues this bacterium has to face in auriferous environments, where it is an important contributor to the environmental Au cycle.

IMPORTANCE
C. metallidurans
lives in metal-rich environments, including auriferous soils that contain a mixture of toxic transition metal cations. We demonstrate here that copper ions and gold complexes exert synergistic toxicity because gold ions inhibit the copper-exporting P-type ATPase CupA, which is central to copper resistance in this bacterium. Such a situation should occur in soils overlying Au deposits, in which Cu/Au ratios usually are ≫1. Appreciating how
C. metallidurans
solves the problem of living in environments that contain both Au and Cu is a prerequisite to understand the molecular mechanisms underlying gold cycling in the environment, and the significance and opportunities of microbiota for specific targeting to Au in mineral exploration and ore processing.
Cytoplasmic Localization of Sulfide:Quinone Oxidoreductase and Persulfide Dioxygenase of Cupriavidus pinatubonensis JMP134
Authors: Gao Rui , Liu Honglei , Xun Luying
Published: September 2017

Heterotrophic bacteria have recently been reported to oxidize sulfide to sulfite and thiosulfate by using sulfide:quinone oxidoreductase (SQR) and persulfide dioxygenase (PDO). In chemolithotrophic bacteria, both SQR and PDO have been reported to function in the periplasmic space, with SQR as a peripheral membrane protein whose C terminus inserts into the cytoplasmic membrane and PDO as a soluble protein.
Cupriavidus pinatubonensis
JMP134, best known for its ability to degrade 2,4-dichlorophenoxyacetic acid and other aromatic pollutants, has a gene cluster of
sqr
and
pdo
encoding
C. pinatubonensis
SQR (CpSQR) and CpPDO2. When cloned in
Escherichia coli
, the enzymes are functional. Here we investigated whether they function in the periplasmic space or in the cytoplasm in heterotrophic bacteria. By using sequence analysis, biochemical detection, and green fluorescent protein (GFP)/PhoA fusion proteins, we found that CpSQR was located on the cytoplasmic side of the membrane and CpPDO2 was a soluble protein in the cytoplasm with a tendency to be peripherally located near the membrane. The location proximity of these proteins near the membrane in the cytoplasm may facilitate sulfide oxidation in heterotrophic bacteria. The information may guide the use of heterotrophic bacteria in bioremediation of organic pollutants as well as H
2
S.

IMPORTANCE
Sulfide (H
2
S, HS
−
, and S
2−
), which is common in natural gas and wastewater, causes a serious malodor at low levels and is deadly at high levels. Microbial oxidation of sulfide is a valid bioremediation method, in which chemolithotrophic bacteria that use sulfide as the energy source are often used to remove sulfide. Heterotrophic bacteria with SQR and PDO have recently been reported to oxidize sulfide to sulfite and thiosulfate.
Cupriavidus pinatubonensis
JMP134 has been extensively characterized for its ability to degrade organic pollutants, and it also contains SQR and PDO. This paper shows the localization of SQR and PDO inside the cytoplasm in the vicinity of the membrane. The information may provide guidance for using heterotrophic bacteria in sulfide bioremediation.
Fever, marked tachycardia and vesiculobullous rash in an infant with Chikungunya fever
Authors: Chandorkar Nirupa , Raj Dinesh , Kumar Ramesh , Warsi Sumbul
Published: September 2017

We describe a 3-month-old male infant who presented with acute onset fever, irritability and marked tachycardia. ECG was suggestive of atrial tachycardia. He developed erythematous blanchable skin rash on day 2 of illness, which progressed to vesiculobullous lesions over a few days’ time. The child was managed with intravenous adenosine, carefully monitored fluid boluses, oxygen supplementation and close monitoring. Tachycardia improved within 24 hours. Blood for Chikungunya PCR was positive. The child was discharged after 5 days of hospitalisation with bullous lesions evolving into hyperpigmented macules followed by crusts and hypopigmentation by day 10.
Catastrophic cement reaction following cementation for megaprosthesis for proximal femoral fracture
Authors: Baig Muhammad Nouman , Curtin William , Callaghan Michael Andrew , Murphy Colin G
Published: September 2017

Bone cement implantation syndrome (BCIS) is a well-described and potentially fatal complication of orthopaedic surgery involving pressurised bone cement. Although also described for certain spinal procedures, it is most commonly associated with cemented hip and knee arthroplasty and with cemented hemiarthroplasty following neck of femur fracture in particular.

Donaldsonet alproposed the definition of BCIS as a syndrome “characterized by hypoxia, hypotension or both and/or unexpected loss of consciousness occurring around the time of cementation, prosthesis insertion, reduction of the joint or, occasionally, limb tourniquet deflation in a patient undergoing cemented bone surgery”. Other features include increased vascular resistance, cardiac arrhythmias and cardiac arrest post cement use.

We describe a case of a patient who suffered a catastrophic reaction to cement during surgery for a comminuted proximal femoral fracture.
Disseminated herpes zoster causing acute respiratory distress syndrome in an immunocompetent patient
Authors: Rudinsky David M , Jordan Kim
Published: September 2017

Disseminated cutaneous varicella herpes zoster with visceral involvement is rare and seen almost exclusively in immunocompromised patients. We describe an unusual case of fulminant herpes zoster (HZ) in a healthy, immunocompetent 37-year-old woman. She initially presented to an urgent care centre with a classic HZ rash localised to her neck, and upper respiratory symptoms and was treated with prednisone and cephalexin. Within 1 week, the rash became diffuse and her clinical status rapidly deteriorated with development of severe acute respiratory distress syndrome. Varicella zoster infection was confirmed via skin biopsy, bronchial viral PCR and serology for varicella antibodies. She was successfully treated with intravenous acyclovir and aggressive supportive care. Though physicians readily recognise typical zoster infection, this case reminds clinicians that HZ infection can be fulminant and potentially life-threatening in younger, immunocompetent individuals. Early recognition and antiviral therapy is important to reduce morbidity and mortality.
Extreme bony pelvic deformity in a renal transplant patient
Authors: Moffat Alexander Henry , Chauhan Priyesh , Choudhary Surabhi , Geberhiwot Tarekegn
Published: September 2017

A 35-year-old female renal transplant recipient was referred to the metabolic bone clinic because of a 15 cm loss of height. She was noted to have thoracic kyphosis and vertebral X-ray confirmed a wedge fracture of the eighth thoracic vertebra. She was managed accordingly but on subsequent follow-up mentioned in passing that her gynaecologist had been unable to obtain a cervical smear for routine screening. This led to further questioning, and the patient reported intermittent urinary stress incontinence, feelings of vaginal fullness and severe dyspareunia. It became apparent that these symptoms had been ongoing for 4 years, but the patient had not brought them to the attention of a healthcare practitioner due to feelings of embarrassment and her religious beliefs. These complaints prompted radiological investigation, which revealed extensive bony pelvic deformity, thought to be an extreme manifestation of chronic kidney disease mineral and bone disorder.
Fulminant myocardial bleeding: another clinical course of vascular Ehlers-Danlos Syndrome
Authors: Tokue Masahide , Hara Hidehiko , Kurosawa Kenji , Nakamura Masato
Published: September 2017

Vascular Ehlers-Danlos Syndrome (vEDS) is a dominantly inherited connective tissue disorder characterised by colon rupture and arterial aneurysm, dissection and rupture. A patient was diagnosed with vEDS after a spontaneous colon rupture when he was brought to our institute because of sudden chest pain. An ECG revealed wide regional ST elevation, which was initially suggestive of acute myocarditis. On the second day, haemodynamics suddenly deteriorated because of a rapid accumulation of bloody pericardial effusion, and the patient died. Autopsy revealed an excessive spontaneous myocardial haemorrhage owing to fragility, which suggested an underlying disease—vEDS.
Comparison of anterior segment optical coherence tomography angiography systems for corneal vascularisation
Authors: Ang Marcus , Devarajan Kavya , Das Suchandrima , Stanzel Tisha , Tan Anna , Girard Michael , Schmetterer Leopold , Mehta Jodhbir S
Published: September 2017

Aim

To newly describe a spectral-domain (SD) optical coherence tomography angiography (OCTA) for the cornea and directly compare two OCTA system scans of the same eyes with corneal vascularisation.

Methods

Cross-sectional, observational, comparative case series. We performed sequential OCTA scans (10 eyes of 10 subjects with corneal vascularisation,4 scans each eye) repeated using split-spectrum amplitude decorrelation algorithm angiography system (SSADA, AngioVue; Optovue Inc, USA) and SD OCTA (Angioscan; Nidek Co. Ltd, Japan) in the same region of interest. We analysed all scan images for repeatability, image quality and vessel density measurements and compared OCTA systems.

Results

We obtained substantial interobserver repeatability in terms of image quality score (κ=0.86) for all 80 OCTA scans (median age 49 years, 50% women). The correlation was moderately good (r=0.721) when comparing vessel density measurements between OCTA systems, but greater in the SSADA compared with SD OCTA system (mean vessel density 20.3±4.9% vs 15.1±4.2%, respectively; p<0.001).

Conclusion

In this pilot clinical study, we describe successful delineation of corneal vessels with substantial image quality using a new SD OCTA system. The vessel density measurements were greater using the SSADA compared with SD OCTA system in the same area of corneal vascularisation. Further studies are required to confirm the advantages, limitations and differences between these OCTA systems for the anterior segment.
Do chain pharmacies perform better than independent pharmacies? Evidence from a standardised patient study of the management of childhood diarrhoea and suspected tuberculosis in urban India
Authors: Miller Rosalind , Goodman Catherine
Published: September 2017

Introduction

Pharmacies and drug stores are frequently patients’ first point of care in many low-income and middle-income countries, but their practice is often poor. Pharmacy retailing in India has traditionally been dominated by local, individually owned shops, but recent years have seen the growth of pharmacy chains. In theory, lower-powered profit incentives and self-regulation to preserve brand identity may lead to higher quality in chain stores. In practice, this has been little studied.

Methods

We randomly selected a stratified sample of chain and independent pharmacies in urban Bengaluru. Standardised patients (SPs) visited pharmacies and presented a scripted case of diarrhoea for a child and suspected tuberculosis (TB). SPs were debriefed immediately after the visit using a structured questionnaire. We measured the quality of history taking, therapeutic management and advice giving against national (Government of India) and international (WHO) guidelines. We used Pearson’s χ2tests to examine associations between pharmacy type and case management.

Findings

Management of childhood diarrhoea and suspected TB was woefully substandard. History taking of the SP was limited; unnecessary and harmful medicines, including antibiotics, were commonly sold; and advice giving was near non-existent. The performance of chains and independent shops was strikingly similar for most areas of assessment. We observed no significant differences between the management of suspected TB in chains and independents. 43% of chains and 45% of independents managed the TB case correctly; 17% and 16% of chains and independents, respectively, sold antibiotics. We found that chains sold significantly fewer harmful antibiotics and antidiarrhoeals (35% vs 48%, p=0.029) and prescription-only medicines (37% vs 49%, p=0.048) for the patient with diarrhoea compared with independent shops. Not a single shop managed the patient with diarrhoea correctly according to guidelines.

Conclusion

Our results from Bengaluru suggest that it is unlikely that chains alone can solve persisting quality challenges. However, they may offer a potential vehicle through which to deliver interventions. Future intervention research should consider recruiting chains to see whether effectiveness of interventions differ among chains compared with independents.
Association between gender and short-term outcome in patients with ST elevation myocardial infraction participating in the international, prospective, randomised Administration of Ticagrelor in the catheterisation Laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery (ATLANTIC) trial: a prespecified analysis
Authors: Venetsanos Dimitrios , Sederholm Lawesson Sofia , Alfredsson Joakim , Janzon Magnus , Cequier Angel , Chettibi Mohamed , Goodman Shaun G , van’t Hof Arnoud W , Montalescot Gilles , Swahn Eva
Published: September 2017

Objectives

To evaluate gender differences in outcomes in patents with ST-segment elevation myocardial infarction (STEMI) planned for primary percutaneous coronary intervention (PPCI).

Settings

A prespecified gender analysis of the multicentre, randomised, double-blind Administration of Ticagrelor in the catheterisation Laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery.

Participants

Between September 2011 and October 2013, 1862 patients with STEMI and symptom duration <6 hours were included.

Interventions

Patients were assigned to prehospital versus in-hospital administration of 180 mg ticagrelor.

Outcomes

The main objective was to study the association between gender and primary and secondary outcomes of the main study with a focus on the clinical efficacy and safety outcomes. Primary outcome: the proportion of patients who did not have 70% resolution of ST-segment elevation and did not meet the criteria for Thrombolysis In Myocardial Infarction (TIMI) flow 3 at initial angiography. Secondary outcome: the composite of death, MI, stent thrombosis, stroke or urgent revascularisation and major or minor bleeding at 30 days.

Results

Women were older, had higher TIMI risk score, longer prehospital delays and better TIMI flow in the infarct-related artery. Women had a threefold higher risk for all-cause mortality compared with men (5.7% vs 1.9%, HR 3.13, 95% CI 1.78 to 5.51). After adjustment, the difference was attenuated but remained statistically significant (HR 2.08, 95% CI 1.03 to 4.20). The incidence of major bleeding events was twofold to threefold higher in women compared with men. In the multivariable model, female gender was not an independent predictor of bleeding (Platelet Inhibition and Patient Outcomes major HR 1.45, 95% CI 0.73 to 2.86, TIMI major HR 1.28, 95% CI 0.47 to 3.48, Bleeding Academic Research Consortium type 3–5 HR 1.45, 95% CI 0.72 to 2.91). There was no interaction between gender and efficacy or safety of randomised treatment.

Conclusion

In patients with STEMI planned for PPCI and treated with modern antiplatelet therapy, female gender was an independent predictor of short-term mortality. In contrast, the higher incidence of bleeding complications in women could mainly be explained by older age and clustering of comorbidities.

Clinical trial registration

NCT01347580;Post-results.
Recording a diagnosis of stroke, transient ischaemic attack or myocardial infarction in primary healthcare and the association with dispensation of secondary preventive medication: a registry-based prospective cohort study
Authors: Dahlgren Cecilia , Geary Lukas , Hasselström Jan , Rehnberg Clas , Schenck-Gustafsson Karin , Wändell Per , Euler Mia von
Published: September 2017

Objectives

The aim of this study was to explore whether recording in primary care of a previously recorded hospital diagnosis was associated with increased patient utilisation of recommended medications.

Design

Registry-based prospective cohort study.

Setting and participants

19 072 patients with a hospital discharge diagnosis of transient ischaemic attack (TIA), stroke or acute coronary syndrome from hospitals in Stockholm County 2010–2013 were included in the study.

Main outcome measure

The outcome of the study was medication dispensation as a marker of adherence to recommended medications. Adherence was defined as having had at least two filled prescriptions in the third year following hospital discharge.

Results

Recording a diagnosis was associated with higher utilisation of all recommended medications with the exception of antihypertensives in patients with TIA. The differences between the groups with and without a recorded diagnosis remained after adjusting for age, sex, index year and visits to private practitioners. Dispensation of antithrombotics was high overall, 80%–90% in patients without a recorded diagnosis and 90%–94% for those with a diagnosis. Women with recorded ischaemic stroke/TIA/acute coronary syndrome were dispensed more statins (56%–71%) than those with no recorded diagnosis (46%–59%). Similarly, 68%–83% of men with a recorded diagnosis were dispensed statins (57%–77% in men with no recorded diagnosis). The rate of diagnosis recording spanned from 15% to 47% and was especially low in TIA (men 15%, women 16%).

Conclusion

Recording a diagnosis of TIA/stroke or acute coronary syndrome in primary care was found to be associated with higher dispensation of recommended secondary preventive medications. Further study is necessary in order to determine the mechanisms underlying our results and to establish the utility of our findings.
Is increasing urbanicity associated with changes in breastfeeding duration in rural India? An analysis of cross-sectional household data from the Andhra Pradesh children and parents study
Authors: Oakley Laura , Baker Christopher P , Addanki Srivalli , Gupta Vipin , Walia Gagandeep Kaur , Aggarwal Aastha , Bhogadi Santhi , Kulkarni Bharati , Wilson Robin T , Prabhakaran Dorairaj , Ben-Shlomo Yoav , Davey Smith George , Radha Krishna K V , Kinra Sanjay
Published: September 2017

Objective

To investigate whether village-level urbanicity and lower level socioeconomic factors are associated with breastfeeding practices in transitioning rural communities in India.

Setting

29 villages in Ranga Reddy district, southern India between 2011 and 2014.

Participants

7848 children under 6 years identified via a cross-sectional household survey conducted as part of the Andhra Pradesh Children and Parents Study.

Outcome measures

Two key indicators of optimal breastfeeding: termination of exclusive breastfeeding before 6 months and discontinuation of breastfeeding by 24 months. Village urbanicity was classified as low, medium or high according to satellite assessed night-light intensity.

Results

Breastfeeding initiation was almost universal, and approximately two in three children were exclusively breastfed to 6 months and a similar proportion breastfed to 24 months. Using multilevel logistic regression, increasing urbanicity was associated with breastfeeding discontinuation before 24 months (medium urbanicity OR 1.45, 95% CI 0.71 to 2.96; high urbanicity OR 2.96, 95% CI 1.45 to 6.05) but not with early (<6 months) termination of exclusive breastfeeding. Increased maternal education was independently associated with both measures of suboptimal breastfeeding, and higher household socioeconomic position was associated with early termination of exclusive breastfeeding.

Conclusion

In this transitional Indian rural community, early stage urbanicity was associated with a shorter duration of breastfeeding. Closer surveillance of changes in breastfeeding practices alongside appropriate intervention strategies are recommended for emerging economies.
Usage of purchased self-tests for HIV and sexually transmitted infections in Amsterdam, the Netherlands: results of population-based and serial cross-sectional studies among the general population and sexual risk groups
Authors: Bil Janneke P , Prins Maria , Stolte Ineke G , Dijkshoorn Henriëtte , Heijman Titia , Snijder Marieke B , Davidovich Udi , Zuure Freke R
Published: September 2017

Objectives

There are limited data on the usage of commercially bought self-tests for HIV and other sexually transmitted infections (STIs). Therefore, we studied HIV/STI self-test usage and its determinants among the general population and sexual risk groups between 2007 and 2015 in Amsterdam, the Netherlands.

Setting

Data were collected in four different studies among the general population (S1–2) and sexual risk groups (S3–4).

Participants

S1–Amsterdam residents participating in representative population-based surveys (2008 and 2012; n=6044) drawn from the municipality register; S2–Participants of a population-based study stratified by ethnicity drawn from the municipality register of Amsterdam (2011–2015; n=17 603); S3–Men having sex with men (MSM) participating in an HIV observational cohort study (2008 and 2013; n=597) and S4–STI clinic clients participating in a cross-sectional survey (2007–2012; n=5655).

Primary and secondary outcome measures

Prevalence of HIV/STI self-test usage and its determinants.

Results

The prevalence of HIV/STI self-test usage in the preceding 6–12 months varied between 1% and 2% across studies. Chlamydia self-tests were most commonly used, except among MSM in S3. Chlamydia and syphilis self-test usage increased over time among the representative sample of Amsterdam residents (S1) and chlamydia self-test usage increased over time among STI clinic clients (S4). Self-test usage was associated with African Surinamese or Ghanaian ethnic origin (S2), being woman or MSM (S1 and 4) and having had a higher number of sexual partners (S1–2). Among those in the general population who tested for HIV/STI in the preceding 12 months, 5–9% used a self-test.

Conclusions

Despite low HIV/STI self-test usage, we observed increases over time in chlamydia and syphilis self-test usage. Furthermore, self-test usage was higher among high-risk individuals in the general population. It is important to continue monitoring self-test usage and informing the public about the unknown quality of available self-tests in the Netherlands and about the pros and cons of self-testing.
Is the Salut Programme an effective and cost-effective universal health promotion intervention for parents and their children? A register-based retrospective observational study
Authors: Häggström Jenny , Sampaio Filipa , Eurenius Eva , Pulkki-Brännström Anni-Maria , Ivarsson Anneli , Lindkvist Marie , Feldman Inna
Published: September 2017

Objectives

This study investigates the effectiveness and cost-effectiveness of the Salut Programme, a universal health promotion intervention, compared with care-as-usual, over the periods of pregnancy, delivery and the child’s first 2 years of life.

Method

We adopted a register-based retrospective observational design using existing data sources with respect to both exposures and outcomes. Health outcomes and costs were compared between geographical areas that received care-as-usual (non-Salut area) and areas where the programme was implemented (Salut area). We included mothers and their children from both the Salut and non-Salut areas if: (1) the child was born 2002–2004 (premeasure period) or (2) the child was born 2006–2008 (postmeasure period). The effectiveness study adopted two strategies: (1) a matched difference-in-difference analysis using data from all participants and (2) a longitudinal analysis restricted to mothers who had given birth twice, that is, both in the premeasure and postmeasure periods. The economic evaluation was performed from a healthcare and a limited societal perspective. Outcomes were clustered during pregnancy, delivery and birth and the child’s first 2 years.

Results

Difference-in-difference analyses did not yield any significant effect on the outcomes. Longitudinal analyses resulted in significant positive improvement in Apgar scores, reflecting the newborn’s physical condition, with more children having a normal Apgar score (1 min +3%, 5 min +1%). The cost of the programme was international dollar (INT$)308/child. From both costing perspectives, the programme yielded higher effects and lower costs than care-as-usual, being thus cost-saving (probability of around 50%).

Conclusions

Our findings suggest that the Salut Programme is an effective universal intervention to improve maternal and child health, and it may be good value for money; however, there is large uncertainty around the cost estimates.
Long-term risk of recurrence after discontinuing anticoagulants for a first unprovoked venous thromboembolism: protocol for a systematic review and meta-analysis
Authors: Khan Faizan , Rahman Alvi , Carrier Marc , Kearon Clive , Schulman Sam , Couturaud Francis , Prandoni Paolo , Eichinger Sabine , Becattini Cecilia , Agnelli Giancarlo , Büller Harry R , Brighton Timothy A , Palareti Gualtiero , Pinede Laurent , Sabri Elham , Hutton Brian , Wells George A , Rodger Marc A
Published: September 2017

Introduction

For patients with a first unprovoked venous thromboembolism (VTE), the optimal duration of anticoagulation is a crucial clinical dilemma which has yet to be resolved. The decision to stop anticoagulant therapy (AT) after the initial 3–6 months or to continue AT indefinitely, is primarily governed by the long-term risk of recurrence when treatment is discontinued. This risk however, is not well established, hindering decision making.

Methods and analysis

We will conduct a systematic review and a meta-analysis of studies involving patients diagnosed with a first, symptomatic unprovoked VTE or VTE provoked by minor transient risk factors, who have completed at least 3 months of initial AT; and who were followed-up for standardised time intervals of 1, 2, 5, 10 and 20 years (±3 months) after stopping AT. We will search (from inception to January 2017) MEDLINE, Embase and the Cochrane library for randomised controlled trials and prospective observational studies. Two reviewers will conduct all screening and data collection independently. The primary outcome of the rate of recurrent VTE at the standardised time intervals will be calculated for each study from the total number of recurrent events and the corresponding number of patient-years of follow-up. We will use a random-effects model to pool study results and report a weighted estimate of the absolute rate of recurrent VTE (events per 100 patient-years) over standardised time intervals of 1, 2, 5, 10 and 20 years after discontinuing anticoagulants.

Ethics and dissemination

Ethical approval is not applicable for this study. Findings from this study will be disseminated through peer-reviewed journal publication as well as relevant national and international conference presentations.

PROSPERO registration number

CRD42017056309.
Reporting of conflicts of interest in oral presentations at medical conferences: a delegate-based prospective observational study
Authors: Grey Andrew , Avenell Alison , Dalbeth Nicola , Stewart Fiona , Bolland Mark J
Published: September 2017

Objective

To assess the prevalence, location, presentation and consistency of conflict of interest statements in oral presentations at medical conferences

Design

Prospective, delegate-based observational study

Sample

201 oral presentations at 5 medical conferences in 2016

Main outcome measures

Presence of a conflict of interest statement, its location within the presentation and its duration of display. Concordance between conflict of interest disclosures in oral presentations and written abstracts or meeting speaker information

Results

Conflict of interest statements were present in 143/201 (71%) presentations (range for conferences 26%–100%). 118 of the 141 evaluable statements (84%) were reported on a specific slide. Slides containing conflict of interest statements were displayed for a median (IQR) 2 s (1–5), range for conferences 1.25–7.5 s. Duration of display was shorter when the slide contained only the conflict of interest statement, 2 s (1–3.5), than when it contained other information, 8 s (3–17), but was not affected by type of presentation or whether a conflict of interest was disclosed. When a conflict of interest was disclosed, 27/84 (32%) presenters discussed an aspect of it. Discordance between the presence of a conflict of interest disclosure in the oral presentation and written formats occurred for 22% of presentations.

Conclusion

In oral presentations at the medical conferences we assessed, conflict of interest statements were often missing, displayed too briefly to be read and understood, or not discussed/explained by the presenter. They were sometimes discordant with statements in the corresponding written formats. Conference delegates’ ability to assess the objectivity and quality of the information in oral presentations may therefore have been diminished.
Frequency and nature of coroners’ recommendations from injury-related deaths among nursing home residents: a retrospective national cross-sectional study
Authors: Bugeja Lyndal , Woolford Marta H , Willoughby Melissa , Ranson David , Ibrahim Joseph E
Published: September 2017

Background

Coroners are tasked with the investigation of unnatural and unexpected deaths. In Australia, the coroner’s role also includes making recommendations for promoting interventions to improve public safety. However, the coroners’ role in public health and safety in the aged care setting is an underexplored area of research.

Objectives

To describe the frequency and nature of coroners’ recommendations for prevention of harm from injury-related deaths among nursing home residents in Australia.

Setting

Accredited nursing homes in Australia.

Subjects

Nursing home residents whose deaths resulted from external causes occurring between 1 July 2000 and 31 December 2013 and notified to a coroner.

Measurements

Coroners’ recommendations were identified and extracted from the National Coronial Information System. Descriptive statistical techniques were used to calculate the frequency and proportion of recommendations made. The nature of recommendations was quantified using a method comprising seven elements derived from internationally accepted and applied public health conceptual models of mortality causation and prevention.

Results

Coroners made recommendations about the prevention of harm in 53 of the 3289 (1.6%) external cause deaths of nursing home residents. Recommendations were most frequently made for deaths resulting from falls; however, the rate of recommendations per 1000 deaths was highest for thermal mechanisms and complications of clinical care. Most recommendations described the ‘countermeasure’ element, but rarely specified a timeframe for implementation.

Conclusion

Coroners’ recommendations need to be further enhanced in the age care setting. The development of national and international guidelines on best practice in the formulation of effective recommendations should be undertaken.
Mechanisms of poststroke fatigue
Authors: De Doncker William , Dantzer Robert , Ormstad Heidi , Kuppuswamy Annapoorna
Published: September 2017

Poststroke fatigue is a debilitating symptom and is poorly understood. Here we summarise molecular, behavioural and neurophysiological changes related to poststroke fatigue and put forward potential theories for mechanistic understanding of poststroke fatigue.
Health and well-being management in the military: a systematic review of genetic studies
Authors: Parnell Nathan , Rye K , Greenberg N
Published: September 2017

Background

Genetic research may have therapeutic value for mental and physical disorders and could have an indicative or preventative capacity. Little is known about the extent, form and utility of military-specific genetic research.

Method

A systematic review was conducted to evaluate existing genetic well-being studies of service personnel. The review specifically aimed to ascertain the current state of knowledge and feasibility of using genetics to aid recruitment and health management within military populations. Databases searched included MEDLINE, Embase, PsycINFO and Web of Science for relevant studies. Papers were rated using a genetics-specific quality assessment framework.

Results

Ten papers were included within the final review, with seven mental-health-focused and three physical-health-focused genetic studies found within military populations. Eight papers considered candidate genes, one gene expression and one study was an outline of a future study of significant interest. Genetic commonalties were derived to yield shared physiological pathways. The 10 reviewed papers revealed moderate quality based on quality assessment.

Conclusions

Current genetic research within military populations is limited. Further studies on genetics, cost effectiveness, ethics and continual monitoring need to be explored before considering any movement toward clinical translation.
Intracardiac light catheter for rapid scanning transmural absorbance spectroscopy of perfused myocardium: measurement of myoglobin oxygenation and mitochondria redox state
Authors: Femnou Armel N. , Kuzmiak-Glancy Sarah , Covian Raul , Giles Abigail V. , Kay Matthew W. , Balaban Robert S.
Published: September 2017

Absorbance spectroscopy of intrinsic cardiac chromophores provides nondestructive assessment of cytosolic oxygenation and mitochondria redox state. Isolated perfused heart spectroscopy is usually conducted by collecting reflected light from the heart surface, which represents a combination of surface scattering events and light that traversed portions of the myocardium. Reflectance spectroscopy with complex surface scattering effects in the beating heart leads to difficulty in quantitating chromophore absorbance. In this study, surface scattering was minimized and transmural path length optimized by placing a light source within the left ventricular chamber while monitoring transmurally transmitted light at the epicardial surface. The custom-designed intrachamber light catheter was a flexible coaxial cable (2.42-Fr) terminated with an encapsulated side-firing LED of 1.8 × 0.8 mm, altogether similar in size to a Millar pressure catheter. The LED catheter had minimal impact on aortic flow and heart rate in Langendorff perfusion and did not impact stability of the left ventricule of the working heart. Changes in transmural absorbance spectra were deconvoluted using a library of chromophore reference spectra to quantify the relative contribution of specific chromophores to the changes in measured absorbance. This broad-band spectral deconvolution approach eliminated errors that may result from simple dual-wavelength absorbance intensity. The myoglobin oxygenation level was only 82.2 ± 3.0%, whereas cytochrome c and cytochrome a + a3were 13.3 ± 1.4% and 12.6 ± 2.2% reduced, respectively, in the Langendorff-perfused heart. The intracardiac illumination strategy permits transmural optical absorbance spectroscopy in perfused hearts, which provides a noninvasive real-time monitor of cytosolic oxygenation and mitochondria redox state.

NEW & NOTEWORTHY Here, a novel nondestructive real-time approach for monitoring intrinsic indicators of cardiac metabolism and oxygenation is described using a catheter-based transillumination of the left ventricular free wall together with complete spectral analysis of transmitted light. This approach is a significant improvement in the quality of cardiac optical absorbance spectroscopic metabolic analyses.
Mediating Effect of Postsurgical Chemotherapy on Presence of Dementia and Survival among Patients 65 and Older with Stage III Colon Cancer
Authors: Chen Yingjia , Cress Rosemary D. , Stewart Susan L. , Semrad Thomas J. , Harvey Danielle , Tencredi Daniel J. , Beckett Laurel
Published: September 2017

Introduction: Both colon cancer and dementia are prevalent among the elderly and have a high risk of cooccurrence. Previous studies found that patients with dementia were treated less aggressively. In this study, we hypothesized that presence of preexisting dementia was associated with worse survival for stage III colon cancer patients, and that postoperative chemotherapy was on the causal pathway.

Methods: We defined preexisting dementia in Surveillance Epidemiology and End Results Medicare data through either a formal diagnosis or a prescription for dementia drugs or both before the diagnosis of cancer. We applied multivariable Cox regression to estimate the effect of preexisting dementia on survival, adjusting for demographic factors, tumor characteristics, and receipt of chemotherapy. We assessed mediating effects in the context of the counterfactual framework using the accelerated failure time model.

Results: There were 4,573 patients diagnosed with stage III colon cancer between 2007 and 2009 identified. A preexisting diagnosis of dementia significantly increased the risk of death by 45% (HR = 1.45, 95% CI: 1.29–1.63). Patients with either a formal diagnosis of dementia or a related prescription had significantly lower cause-specific survival than their cognitively healthy counterparts. Receipt of chemotherapy was a significant mediator on the causal pathway. The effect of presence of dementia was mediated by receipt of chemotherapy by 13% for preexisting dementia.

Conclusions: Preexisting dementia is significantly associated with worse survival for stage III colon cancer patients, and its deleterious effect is partially explained by decreased likelihood of postoperative chemotherapy receipt.

Impact: This is the first study that provides estimate of the mediating effect of diminished chemotherapy in patients with stage III colon cancer and dementia, simultaneously demonstrating the cancer-specific survival benefit of chemotherapy in the presence of dementia. Cancer Epidemiol Biomarkers Prev; 26(10); 1558–63. ©2017 AACR.
Metabolic Obesity Phenotypes and Risk of Breast Cancer in Postmenopausal Women
Authors: Kabat Geoffrey C. , Kim Mimi Y. , Lee Jennifer S. , Ho Gloria Y. , Going Scott B. , Beebe-Dimmer Jennifer , Manson JoAnn E. , Chlebowski Rowan T. , Rohan Thomas E.
Published: September 2017

Background: Obesity and the metabolic syndrome (MetS) have both been linked to increased risk of postmenopausal breast cancer; however, their relative contributions are poorly understood.

Methods: We examined the association of metabolic phenotypes of obesity defined by presence of the MetS (yes and no) and body mass index (BMI; normal, overweight, obese) with risk of postmenopausal breast cancer in a prospective analysis of a cohort of postmenopausal women (n ∼ 21,000) with baseline measurements of blood glucose, triglycerides, HDL-cholesterol, blood pressure, waist circumference, and BMI. Women were classified into 6 metabolic obesity phenotypes according to their BMI (18.5–<25.0, 25.0–<30.0, ≥30.0 kg/m2) and presence of the MetS (≥3 of the following: waist circumference ≥88 cm, triglycerides ≥150 mg/dL, HDL-C <50 mg/dL, glucose ≥100 mg/dL, and systolic/diastolic blood pressure ≥130/85 mmHg or treatment for hypertension). HRs for incident breast cancer and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models.

Results: Over 15 years of follow-up, 1,176 cases of invasive breast cancer were diagnosed. Obesity, regardless of metabolic health, was associated with increased risk of breast cancer. Being obese and metabolically unhealthy was associated with the highest risk: HR, 1.62; 95% CI, 1.33–1.96. These associations were stronger in women who had never used hormone therapy.

Conclusions: Our findings suggest that both obesity and metabolic dysregulation are associated with breast cancer risk.

Impact: Beyond BMI, metabolic health should be considered a clinically relevant and modifiable risk factor for breast cancer. Cancer Epidemiol Biomarkers Prev; 26(12); 1730–5. ©2017 AACR.
Childhood Socioeconomic Position and Pubertal Onset in a Cohort of Multiethnic Girls: Implications for Breast Cancer
Authors: Hiatt Robert A. , Stewart Susan L. , Hoeft Kristin S. , Kushi Lawrence H. , Windham Gayle C. , Biro Frank M. , Pinney Susan M. , Wolff Mary S. , Teitelbaum Susan L. , Braithwaite Dejana
Published: September 2017

Background: Higher socioeconomic position (SEP) has been associated with increased risk of breast cancer. Its relationship with earlier age of pubertal onset, a risk factor for breast cancer, is less clear.

Methods: We studied the relationship of SEP to pubertal onset in a multiethnic cohort of 1,237 girls ages 6 to 8 years at baseline. Girls in three U.S. cities were followed for 5 to 8 years with annual clinical examinations from 2004 to 2012. SEP measures were examined for associations with pubertal onset, assessed by breast budding (thelarche) and pubic hair development (adrenarche). Analyses were conducted with accelerated failure time models using a Weibull distribution, with left, right, and interval censoring.

Results: Higher body mass index percentage at entry to the study and black or Hispanic race/ethnicity were the strongest predictors of age at pubertal onset. An SEP index comprising household family income, mother's education, and home ownership was an independent predictor of thelarche in adjusted models for all girls together and for white and Latina, separately, but not black girls, and the relationship varied by study site. The SEP index was not related to adrenarche in adjusted models. Overall, girls from the lowest quintile of SEP entered puberty on average 6% earlier than girls from the highest quintile (time ratio = 0.94; 95% confidence interval 0.91–0.97) in adjusted models.

Conclusions: Our results suggest that early-life SEP may influence the timing of pubertal development.

Impact: Factors related to lower SEP in childhood can adversely affect early development in ways that may increase the risk of breast cancer. Cancer Epidemiol Biomarkers Prev; 26(12); 1714–21. ©2017 AACR.
Amplification of 1q32.1 Refines the Molecular Classification of Endometrial Carcinoma
Authors: Depreeuw Jeroen , Stelloo Ellen , Osse Elisabeth M. , Creutzberg Carien L. , Nout Remi A. , Moisse Matthieu , Garcia-Dios Diego A. , Dewaele Michael , Willekens Karen , Marine Jean-Christophe , Matias-Guiu Xavier , Amant Frédéric , Lambrechts Diether , Bosse Tjalling
Published: September 2017

Purpose: Molecular classification of endometrial cancer identified distinct molecular subgroups. However, the largest subset of endometrial cancers remains poorly characterized and is referred to as the “nonspecific molecular profile” (NSMP) subgroup. Here, we aimed at refining the classification of this subgroup by profiling somatic copy-number aberrations (SCNAs).

Experimental Design: SCNAs were analyzed in 141 endometrial cancers using whole-genome SNP arrays and pooled with 361 endometrial cancers from The Cancer Genome Atlas. Genomic Identification of Significant Targets in Cancer (GISTIC) identified statistically enriched SCNAs and penalized Cox regression assessed survival effects. The prognostic significance of relevant SCNAs was validated using multiplex ligation-dependent probe amplification in 840 endometrial cancers from the PORTEC-1/2 trials. Copy-number status of genes was correlated with gene expression to identify potential cancer drivers. One plausible oncogene was validated in vitro using antisense oligonucleotide-based strategy.

Results: SCNAs affecting chromosome 1q32.1 significantly correlated with worse relapse-free survival (RFS) in the NSMP subgroup (HR, 2.12; 95% CI, 1.26–3.59; P = 0.005). This effect was replicated in NSMP endometrial cancers from PORTEC-1/2 (HR, 2.34; 95% CI, 1.17–4.70; P = 0.017). A new molecular classification including the 1q32.1 amplification improved risk prediction of recurrence. MDM4 gene expression strongly correlated with 1q32.1 amplification. Silencing MDM4 inhibited cell growth in cell lines carrying 1q32.1 amplification, but not in those without MDM4 amplification. Vice versa, increasing MDM4 expression in nonamplified cell lines stimulated cell proliferation.

Conclusions: 1q32.1 amplification was identified as a prognostic marker for poorly characterized NSMP endometrial cancers, refining the molecular classification of this subgroup. We functionally validated MDM4 as a potential oncogenic driver in the 1q32.1 region. Clin Cancer Res; 23(23); 7232–41. ©2017 AACR.
Phase III Clinical Trial (RERISE study) Results of Efficacy and Safety of Radotinib Compared with Imatinib in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia
Authors: Kwak Jae-Yong , Kim Sung-Hyun , Oh Suk Joong , Zang Dae Young , Kim Hawk , Kim Jeong-A , Do Young Rok , Kim Hyeoung Joon , Park Joon Seong , Choi Chul Won , Lee Won Sik , Mun Yeung-Chul , Kong Jee Hyun , Chung Joo Seop , Shin Ho-Jin , Kim Dae-Young , Park Jinny , Jung Chul Won , Bunworasate Udomsak , Comia Narcisa Sonia , Jootar Saengsuree , Reksodiputro Arry Harryanto , Caguioa Priscilla B. , Lee Sung-Eun , Kim Dong-Wook
Published: September 2017

Purpose: Radotinib is a second-generation BCR-ABL1 tyrosine kinase inhibitor (TKI) approved in Korea for chronic phase chronic myeloid leukemia (CML-CP) in patients newly diagnosed or with insufficient response to other TKIs. This study was conducted to evaluate the efficacy and safety of radotinib as first-line therapy for CML-CP.

Experimental Design: This multinational, open-label study assigned patients (1:1:1) to one of two twice-daily radotinib doses, or imatinib daily. The primary endpoint was major molecular response (MMR) by 12 months.

Results: Two hundred forty-one patients were randomized to receive radotinib 300 mg (n = 79) or 400 mg twice-daily (n = 81), or imatinib 400 mg daily (n = 81). MMR rates by 12 months were higher in patients receiving radotinib 300 mg (52%) or radotinib 400 mg twice-daily (46%) versus imatinib (30%; P = 0.0044 and P = 0.0342, respectively). Complete cytogenetic response (CCyR) rates by 12 months were higher for radotinib 300 mg (91%) versus imatinib (77%; P = 0.0120). Early molecular response at 3 months occurred in 86% and 87% of patients receiving radotinib 300 mg and radotinib 400 mg, respectively, and 71% of those receiving imatinib. By 12 months, no patients had progression to accelerated phase or blast crisis. Most adverse events were manageable with dose reduction.

Conclusions: Radotinib demonstrated superiority over imatinib in CCyR and MMR in patients newly diagnosed with Philadelphia chromosome–positive CML-CP. This trial was registered at www.clinicaltrials.gov as NCT01511289. Clin Cancer Res; 23(23); 7180–8. ©2017 AACR.