bluuebunny/crossref_metadata_2025 huggingface dataset:
Is the South African Triage Scale valid for use in Afghanistan, Haiti and Sierra Leone?
Authors: Dalwai Mohammed , Valles Pola , Twomey Michele , Nzomukunda Yvonne , Jonjo Prince , Sasikumar Manoj , Nasim Masood , Razaaq Abdul , Gayraud Olivia , Jecrois Pierre Ronald , Wallis Lee , Tayler-Smith Katie
Published: June 2017

Objective

To assess the validity of the South African Triage Scale (SATS) in four Médecins Sans Frontières (MSF)-supported emergency departments (ED, two trauma-only sites, one mixed site (both medical and trauma cases) and one paediatric-only site) in Afghanistan, Haiti and Sierra Leone.

Methods

This was a retrospective cohort study conducted between June 2013 and June 2014. Validity was assessed by comparing patients’ SATS ratings with their final ED outcome (ie, hospital admission, death or discharge).

Results

In the two trauma settings, the SATS demonstrated good validity: it accurately predicted an increase in the likelihood of mortality and hospitalisation across incremental acuity levels (p<0.001) and ED outcomes for ‘green’ and ‘red’ patients matched the predicted ED outcomes in 84%–99% of cases. In the mixed ED, the SATS was able to predict an incremental increase in hospitalisation (p<0.001) across both trauma and non-trauma cases. In the paediatric-only settings, SATS was able to predict an incremental increase in hospitalisation in the non-trauma cases only (p<0.001). However, 87% (non-trauma) and 94% (trauma) of ‘red’ patients in the mixed-medical setting were overtriaged and 76% (non-trauma) and 100% (trauma) of ‘green’ patients in the paediatric settings were undertriaged.

Conclusion

The SATS is a valid tool for trauma-only settings in low-resource countries. Its use in mixed settings seems justified, but context-specific assessments would seem prudent. Finally, in paediatric settings with endemic malaria, adding haemoglobin level to the SATS discriminator list may help to improve the undertriage of patients with malaria.
Causes of severe visual impairment and blindness in students in schools for the blind in Northwest Ethiopia
Authors: Asferaw Mulusew , Woodruff Geoffrey , Gilbert Clare
Published: June 2017

Objectives

To determine the causes of severe visual impairment and blindness (SVI/BL) among students in schools for the blind in Northwest Ethiopia and to identify preventable and treatable causes.

Method

Students attending nine schools for the blind in Northwest Ethiopia were examined and causes assigned using the standard WHO record form for children with blindness and low vision in May and June 2015.

Results

383 students were examined, 357 (93%) of whom were severely visually impaired or blind (<6/60 in their better eye). 253 (70.9%) were aged 16 years or above and 228 (63.9%) were males. 100 students aged <16 years were blind and four were SVI, total 104. The major anatomical site of visual loss among those 0-15 years was cornea/phthisis (47.1%), usually due to measles and vitamin A deficiency, followed by whole globe (22.1%), lens (9.6%) and uvea (8.7%). Among students aged 16 years and above, corneal/phthisis (76.3%) was the major anatomical cause, followed by lens (6.3%), whole globe (4.7%), uvea (3.6%) and optic nerve (3.2%). The leading underlying aetiology among students aged <16 years was childhood factors (39.4%) (13.5% measles, 10.6% vitamin A deficiency), followed by unknown aetiology (54.8%), perinatal (2.9%) and hereditary factors (2.9%). In the older group, childhood factors (72.3%) (25% measles, 15% vitamin A deficiency) were major causes, followed by unknown aetiology (24.1%), perinatal (2.4%) and hereditary factors (0.8%). Over 80% of the causes were avoidable with majority being potentially preventable (65%).

Conclusion

Corneal blindness, mainly as the result of measles and vitamin A deficiency, is still a public health problem in Northwest Ethiopia, and this has not changed as observed in other low-income countries. More than three-fourth of causes of SVI/BL in students in schools for the blind are potentially avoidable, with measles/vitamin A deficiency and cataract being the leading causes.
Indian medical device sector: insights from patent filing trends
Authors: Markan Suchita , Verma Yogmaya
Published: June 2017

In this study, patent application filing trends in India for the last decade (2005–2014) were analysed to understand the medical device patent filing profile. As India is the key emerging market with huge market potential, this study was also undertaken to identify the top medical device companies filing patents in India, the niche technology domains with maximum filings, key gaps in medical device innovation profile and scope for business opportunities. It was observed that patent application filings in the medical device sector during the last 5 years (2009–2013) contributed only to 2% of the total patent applications filed, which may be attributed to nascent medical device sector and lack of Intellectual Property (IP) awareness or funding support for IP filings. The analysis shows increasing trends in medical device patent applications in India, with major share of patent applications being filed from the USA. The Indian applications in this sector contributed only to 17% of the total patent application filings in the last decade. Although foreign players dominate the medical device sector, this study indicates that though at a small scale, Indian applicants are actively filing patents in all key domains of the medical device sector. With the enabling environment being provided by the Government of India with recent policy initiatives such as Startup India, Make in India, 100% Foreign Direct Investment (FDI)and so on and support to start-ups for IP filings, the Indian medical device industry is expected to witness aggressive IP filing and innovation trends and is poised to grow exponentially targeting US$50 billion industry by 2025.
Associations between self-rated health and health behaviour among older adults in Estonia: a cross-sectional analysis
Authors: Abuladze Liili , Kunder Nele , Lang Katrin , Vaask Sirje
Published: June 2017

Objectives

The population of Estonia has one of the lowest life expectancies and health statuses in Europe. This is reflected in a lower perception of health among older adults. This study focuses on the role of health behaviour (smoking, alcohol consumption, physical activity and nutrition) in self-rated health, accounting for sociodemographic characteristics, activity limitations and long-term illnesses as well as satisfaction with life of older Estonian men and women.

Design

We use representative cross-sectional data from Wave 4 of the Estonian Survey of Health, Ageing and Retirement in Europe, conducted mainly in 2011.

Participants

Frequencies, χ2tests and logistic regression models include respondents aged 50 years and older, with no upper age limit (n=6660).

Results

Men have 20% higher odds (CI 1.02 to 1.43) of poor self-rated health. Being of foreign origin (OR 1.48; CI 1.24 to 1.77), having a basic (2.50; CI 2.06 to 3.00) or secondary (1.71; CI 1.43 to 2.04) education, being retired (2.00; CI 1.65 to 2.44) or staying at home (1.49; CI 1.16 to 1.93) and having activity limitations (3.25; CI 2.77 to 3.80) or long-term illnesses (4.78; CI 4.08 to 5.60) are related to poor self-rated health. Never being involved in vigorous (2.30; CI 1.90 to 2.79) or moderate physical activity (1.41; CI 1.02 to 1.94), and consuming legumes and eggs less frequently (1.25; CI 1.08 to 1.45) is associated with poorer self-rated health. Lower satisfaction with life accounts for some of the variation (2.28; CI 1.92 to 2.71).

Conclusions

There is a strong cumulative effect of one’s previous life course on the self-rated health of older adults in Estonia, suggesting that public health policies have long-term consequences rather than immediate consequences. Health services supporting health behaviours and targeting vulnerable population groups with specific sociodemographic characteristics and health problems may influence self-rated health for some. Public health services emphasising social activities or psychological aspects may be most successful in improving self-rated health of older Estonians through satisfaction with life.
The organisational value of diagnostic strategies using high-sensitivity troponin for patients with possible acute coronary syndromes: a trial-based cost-effectiveness analysis
Authors: Jülicher Paul , Greenslade Jaimi H , Parsonage William A , Cullen Louise
Published: June 2017

Objectives

To evaluate hospital-specific health economic implications of different protocols using high-sensitivity troponin I for the assessment of patients with chest pain.

Design

A cost prediction model and an economic microsimulation were developed using a cohort from a single centre recruited as part of the (ADAPT) trial, a prospective observational trial conducted from 2008 to 2011. The model was populated with 40 000 bootstrapped samples in five high-sensitivity troponin I-enabled algorithms versus standard care.

Setting

Adult emergency department (ED) of a tertiary referral hospital.

Participants

Data were available for 938 patients who presented to the ED with at least 5 min of symptoms suggestive of acute coronary syndrome. The analyses included 719 patients with complete data.

Main outcome(s)/measure(s)

This study examined direct hospital costs, number of false-negative and false-positive cases in the assessment of acute coronary syndrome.

Results

High-sensitivity troponin I-supported algorithms increased diagnostic accuracy from 90.0% to 94.0% with an average cost reduction per patient compared with standard care of $490. The inclusion of additional criteria for accelerated rule-out (limit of detection and the modified 2-hour ADAPT trial rules) avoided 7.5% of short-stay unit admissions or 25% of admissions to a cardiac ward. Protocols using high-sensitivity troponin I alone or high-sensitivity troponin I within accelerated diagnostic algorithms reduced length of stay by 6.2 and 13.6 hours, respectively. Overnight stays decreased up to 43%. Results were seen for patients with non-acute coronary syndrome; no difference was found for patients with acute coronary syndrome.

Conclusions

High-sensitivity troponin I algorithms are likely to be cost-effective on a hospital level compared with sensitive troponin protocols. The positive effect is conferred by patients not diagnosed with acute coronary syndrome. Implementation could improve referral accuracy or facilitate safe discharge. It would decrease costs and provide significant hospital benefits.

Trial registration

The original ADAPT trial was registered with the Australia-New Zealand Clinical trials Registry, ACTRN12611001069943.
Prevalence characteristics of cervical human papillomavirus (HPV) genotypes in the Taizhou area, China: a cross-sectional study of 37 967 women from the general population
Authors: Xu Hui hui , Lin Aifen , Chen Ya hong , Dong Shan shan , Shi Wei wu , Yu Jia zheng , Yan Wei hua
Published: June 2017

Objectives

High-risk human papillomaviruses (hrHPVs) are highly prevalent worldwide, and HPV genotypes differ between geographical regions; however, sexually transmitted HPV may lead to cervical carcinogenesis. The objective of this cross-sectional study was to estimate the prevalence characteristics of cervical HPV genotypes in Taizhou, Southeast China.

Setting and participants

A population-based sample of 37 967 eligible women (median age: 41.6; range: 15–90 years) visiting the Taizhou ENZE Medical Center in Taizhou (2012–2016) was analysed. HPV genotyping was performed on the collected specimens using a GP5+/bioGP6+-PCR/MPG assay by Luminex 200, which simultaneously identifies 27 different HPV genotypes and the β-globin gene (internal control).

Results

The overall HPV infection rate was 22.8% in the Taizhou-based population, and the prevalence of high-risk HPV, low-risk HPV and mixed high-risk and low-risk HPV infection was 14.2%, 5.7% and 3.0%, respectively. The most prevalent genotypes were HPV52 (19.7%), 16 (11.9%), 58 (11.5%), 39 (7.2%), 18 (6.6%) and 56 (5.6%). The rate of multiple-type HPV infection was 5.7% in the whole population, and the HPV52+58, HPV16+52 and HPV16+18 mixed genotypes were most common in women with multiple infections. The age-specific HPV prevalence showed a bimodal curve, with a first peak below the age of 21 years (41.6%), followed by a second peak in the age group of 56–60 years (28.5%). Moreover, the HPV infection rate differed significantly between the outpatient and physical examination groups (24.0% vs 19.5%, p<0.0001). Further data comparisons showed that the distribution of HPV genotypes varied markedly between the two groups.

Conclusions

Data from this study could be valuable for HPV-based cervical cancer screening efforts in certain areas, support the local vaccination programme in the Taizhou region and facilitate future diagnosis and treatment of HPV diseases.
Liquorice-induced hypokalaemia in patients treated with Yokukansan preparations: identification of the risk factors in a retrospective cohort study
Authors: Shimada Saori , Arai Tetsuaki , Tamaoka Akira , Homma Masato
Published: June 2017

Objective

To evaluate serum potassium levels and rates of hypokalaemia in patients treated with liquorice-containing Japanese traditional Kampo-medicines Yokukansan (YK) and Yokukansan-ka-chinpihange (YKCH).

Design

Retrospective cohort study.

Setting

Patients receiving YK preparations for dementia and other psychiatric disorders in the University of Tsukuba Hospital in Japan.

Participants

389 patients (male/female: 174/215, 68.6±16.1 years) were treated with YK preparations for 231 days (range 6–2788 days). Patients whose potassium levels were <3.6 mEq/L before administration of YK preparations, and drug non-compliant patients, were excluded.

Main outcome measure

The occurrence rate of hypokalaemia and assessment of the risk factors for YK preparation-induced hypokalaemia.

Results

Of the 389 patients treated with YK preparations, 94 (24.2%) developed hypokalaemia (potassium levels <3.6 mEq/L) 34 days (range 1–1600 days) after administration of the preparations. 36 (38.3%) patients had co-administration with lower potassium-inducing drugs (LPIDs; diuretics, glucocorticoids, mineralocorticoids and glycyrrhizin), which was more frequent in the patients without hypokalaemia (17.3%) (p<0.05). A Cox proportional hazard model identified four risk factors for hypokalaemia: YK administration (not YKCH) (HR 3.093, 95% CI 1.408 to 6.798), co-administration of LPIDs (HR 2.743, 95% CI 1.754 to 4.289), hypoalbuminaemia at baseline (HR 2.145, 95% 1.360 to 3.384), and full dosage administration (7.5 g/day) (HR 1.600, 95% CI 1.005 to 2.549).

Conclusions

Serum potassium monitoring should be done at least monthly in patients with the following risk factors: LPID co-administration, YK administration, hypoalbuminaemia, and full dosage administration.
Axillary versus innominate artery cannulation for antegrade cerebral perfusion in aortic surgery: design of the Aortic Surgery Cerebral Protection Evaluation (ACE) CardioLink-3 randomised trial
Authors: Garg Vinay , Peterson Mark D , Chu Michael WA , Ouzounian Maral , MacArthur Roderick GG , Bozinovski John , El-Hamamsy Ismail , Victor Chu F , Garg Ankit , Hall Judith , Thorpe Kevin E , Dhingra Natasha , Teoh Hwee , Marotta Thomas R , Latter David A , Quan Adrian , Mamdani Muhammad , Juni Peter , David Mazer C , Verma Subodh
Published: June 2017

Introduction

Neurological injury remains the major cause of morbidity and mortality following open aortic arch repair. Systemic hypothermia along with antegrade cerebral perfusion (ACP) is the accepted cerebral protection approach, with axillary artery cannulation being the most common technique used to establish ACP. More recently, innominate artery cannulation has been shown to be a safe and efficacious method for establishing ACP. Inasmuch as there is a lack of high-quality data comparing axillary and innominate artery ACP, we have designed a randomised, multi-centre clinical trial to compare both cerebral perfusion strategies with regards to brain morphological injury using diffusion-weighted MRI (DW-MRI).

Methods and analysis

110 patients undergoing elective aortic surgery with repair of the proximal arch requiring an open distal anastamosis will be randomised to either the innominate artery or the axillary artery cannulation strategy for establishing unilateral ACP during systemic circulatory arrest with moderate levels of hypothermia. The primary safety endpoint of this trial is the proportion of patients with new radiologically significant ischaemic lesions found on postoperative DW-MRI compared with preoperative DW-MRI. The primary efficacy endpoint of this trial is the difference in total operative time between the innominate artery and the axillary artery cannulation group.

Ethics and dissemination

The study protocol and consent forms have been approved by the participating local research ethics boards. Publication of the study results is anticipated in 2018 or 2019. If this study shows that the innominate artery cannulation technique is non-inferior to the axillary artery cannulation technique with regards to brain morphological injury, it will establish the innominate artery cannulation technique as a safe and potentially more efficient method of antegrade cerebral perfusion in aortic surgery.

Trial registration number

NCT02554032.
Study protocol: Comparison of the effect of treatment with Nonsteroidal anti-inflammatory drugs added to anti-tumour necrosis factor a therapy versus anti-tumour necrosis factor a therapy alone on progression of Structural damage in the spine over two years in patients with ankyLosing spondylitis (CONSUL) – an open-label randomized controlled multicenter trial
Authors: Proft Fabian , Muche Burkhard , Listing Joachim , Rios-Rodriguez Valeria , Sieper Joachim , Poddubnyy Denis
Published: June 2017

Introduction

There is some evidence that non-steroidal anti-inflammatory drugs (NSAIDs), in particular celecoxib, might possess not only a symptomatic efficacy but also disease-modifying properties in ankylosing spondylitis (AS), retarding the progression of structural damage in the spine if taken continuously. In contrast, this remains controversial for tumour necrosis factor alpha (TNF-α) inhibitors, despite their good clinical efficacy. The impact of a combined therapy (a TNF inhibitor plus an NSAID) on radiographic spinal progression in AS is unclear.

Methods and analysis

The aim of this study is to evaluate the impact of treatment with an NSAID (celecoxib) when added to a TNF inhibitor (golimumab) compared with TNF inhibitor (golimumab) alone on progression of structural damage in the spine over 2 years in patients with AS. The study consists of a 6-week screening period, a 12-week period (phase I: run-in phase) of treatment with golimumab for all subjects followed by a 96-week controlled treatment period (phase II: core phase) with golimumab plus celecoxib versus golimumab alone, and a safety follow-up period of 4 weeks. At week 108, the primary study endpoint radiographic spinal progression (as assessed by the change in the modified Stoke Ankylosing Spondylitis Spine Score after 2 years) will be evaluated.

Ethics and dissemination

The study will be performed according to the principles of good clinical practice and the German drug law. The written approval of the independent ethics committee and of the German federal authority have been obtained. On study completion, results are expected to be published in a peer-reviewed journal.

Trial registration number

ClinicalTrials.gov register (NCT02758782) and European Union Clinical Trials Register (EudraCT No 2016-000615-33).
Effectiveness of a ‘Workshop on Decluttering and Organising’ programme for teens and middle-aged adults with difficulty decluttering: a study protocol of an open-label, randomised, parallel-group, superiority trial in Japan
Authors: Aso Yasuko , Yamaoka Kazue , Nemoto Asuka , Naganuma Yuki , Saito Masashige
Published: June 2017

Introduction

Hoarding disorder can cause problems with work performance, personal hygiene, health and well-being. The disorder is a growing social problem in Japan. Having difficulty discarding rubbish, decluttering and organising can signal a future hoarding disorder, and early intervention is important. We developed an educational workshop on decluttering and organising for teens and adults with difficulty organising. The objective of this study is to evaluate the effectiveness of a workshop for reducing clutter and improving quality of life among younger people with difficulty decluttering and organising.

Methods and analysis

An open-label, parallel-group, randomised controlled trial will be conducted among volunteers aged 12–55 years with mild difficulty decluttering and organising. Those in the intervention group will attend the workshop and receive a visit from a professional cleaning company to declutter their living space. The control group will have only the latter. The primary outcome will be the score on the Japanese version of the Saving Inventory-Revised. Secondary outcomes will be scores on the Clutter Image Rating Scale, the Japanese version of the Rosenberg Self-Esteem Scale and the Roles of Private Space Scale. The results will be examined for differences between the two groups in changes from baseline to 7 months. We will examine crude effects and adjust for gender and age using a general linear model for continuous variables and a logistic regression model for dichotomous variables. Sample size was calculated assuming a significance level of 5% (two tailed), a power of 80% and an effect size of 0.75. In total, 60 subjects (30 in each group) will be required.

Ethics and dissemination

The study protocol has been approved by the Medical Ethical Committee of Teikyo University (No. 15-065). The findings will be disseminated widely through peer-reviewed publication and conference presentations.

Trial registration number

UMIN000020568. Issue date: 16 January 2016.
Diagnostic value of the antiglycoprotein-2 antibody for Crohn’s disease: a PRISMA-compliant systematic review and meta-analysis
Authors: Deng Chuiwen , Li Wenli , Li Jing , Zhang Shulan , Li Yongzhe
Published: June 2017

Objectives

To perform a meta-analysis to evaluate the diagnostic performance of the antiglycoprotein-2 (GP2) antibody for Crohn's disease (CD).

Methods

Three databases (EMBASE, ISI Web of Knowledge and PubMed) were systematically searched. There were 17 eligible studies included in the meta-analysis. A total of 2439 patients with CD and 3184 controls were involved in these studies. STATA V.11.2 and Meta-DiSc V.1.4 were used to perform the meta-analysis.

Results

The area under the summary receiver operating characteristic curve was 0.68–0.72. The pooled diagnostic sensitivity of the anti-GP2 antibody ranged from 14% to 24%, and the specificity was 96%–98%.

Conclusions

The anti-GP2 antibody is a specific biomarker for CD, and further exploration of its prevalence among different clinical phenotypes of CD will provide a better understanding of its diagnostic performance.
A systematic review of economic evaluations of seasonal influenza vaccination for the elderly population in the European Union
Authors: Shields Gemma E , Elvidge Jamie , Davies Linda M
Published: June 2017

Objectives

The Council of the European Union (EU) has recommended that action should be taken to increase influenza vaccination in the elderly population. The aims were to systematically review and critically appraise economic evaluations for influenza vaccination in the elderly population in the EU.

Methods

Electronic searches of the NHS Economic Evaluation, Health Technology Assessment, MEDLINE and Embase databases were run to identify full economic evaluations. Two levels of screening were used, with explicit inclusion criteria applied by two independent reviewers at each stage. Prespecified data extraction and critical appraisal were performed on identified studies. Results were summarised qualitatively.

Results

Of the 326 search results, screening identified eight relevant studies. Results varied widely, with the incremental cost-effectiveness ratio ranging from being both more effective and cheaper than no intervention to costing €4 59 350 per life-year gained. Cost-effectiveness was most sensitive to variations in influenza strain, vaccination type and strategy, population and modelling characteristics.

Conclusions

Most studies suggest that vaccination is cost-effective (seven of eight studies identified at least one cost-effective scenario). All but one study used economic models to synthesise data from different sources. The results are uncertain due to the methods used and the relevance and robustness of the data used. Sensitivity analysis to explore these aspects was limited. Integrated, controlled prospective clinical and economic evaluations and surveillance data are needed to improve the evidence base. This would allow more advanced modelling techniques to characterise the epidemiology of influenza more accurately and improve the robustness of cost-effectiveness estimates.
Study protocol of a phase IB/II clinical trial of metformin and chloroquine in patients withIDH1-mutated orIDH2-mutated solid tumours
Authors: Molenaar Remco J , Coelen Robert JS , Khurshed Mohammed , Roos Eva , Caan Matthan WA , van Linde Myra E , Kouwenhoven Mathilde , Bramer Jos AM , Bovée Judith VMG , Mathôt Ron A , Klümpen Heinz-Josef , van Laarhoven Hanneke WM , van Noorden Cornelis JF , Vandertop W Peter , Gelderblom Hans , van Gulik Thomas M , Wilmink Johanna W
Published: June 2017

Introduction

High-grade chondrosarcoma, high-grade glioma and intrahepatic cholangiocarcinoma are aggressive types of cancer with a dismal outcome. This is due to the lack of effective treatment options, emphasising the need for novel therapies. Mutations in the genesIDH1andIDH2(isocitrate dehydrogenase 1 and 2) occur in 60% of chondrosarcoma, 80% of WHO grade II–IV glioma and 20% of intrahepatic cholangiocarcinoma.IDH1/2-mutated cancer cells produce the oncometaboliteD-2-hydroxyglutarate (D-2HG) and are metabolically vulnerable to treatment with the oral antidiabetic metformin and the oral antimalarial drug chloroquine.

Methods and analysis

We describe a dose-finding phase Ib/II clinical trial, in which patients withIDH1/2-mutated chondrosarcoma, glioma and intrahepatic cholangiocarcinoma are treated with a combination of metformin and chloroquine. Dose escalation is performed according to a 3+3 dose-escalation scheme. The primary objective is to determine the maximum tolerated dose to establish the recommended dose for a phase II clinical trial. Secondary objectives of the study include (1) determination of pharmacokinetics and toxic effects of the study therapy, for which metformin and chloroquine serum levels will be determined over time; (2) investigation of tumour responses to metformin plus chloroquine inIDH1/2-mutated cancers using CT/MRI scans; and (3) whether tumour responses can be measured by non-invasiveD-2HG measurements (mass spectrometry and magnetic resonance spectroscopy) of tumour tissue, serum, urine, and/or bile or next-generation sequencing of circulating tumour DNA (liquid biopsies). This study may open a novel treatment avenue forIDH1/2-mutated high-grade chondrosarcoma, glioma and intrahepatic cholangiocarcinoma by repurposing the combination of two inexpensive drugs that are already approved for other indications.

Ethics and dissemination

This study has been approved by the medical-ethical review committee of the Academic Medical Center, Amsterdam, The Netherlands. The report will be submitted to a peer-reviewed journal.

Trial registration number

This article was registered at ClinicalTrials.gov identifier (NCT02496741): Pre-results.
Colorectal cancer with Synchronous liver-limited Metastases: the protocol of an Inception Cohort study (CoSMIC)
Authors: Siriwardena Ajith K , Chan Anthony K C , Ignatowicz Agnieszka M , Mason James M
Published: June 2017

Introduction

Colorectal cancer is the fourth most common cancer in the UK and an important cause of cancer-related death. In 20% of patients, there is metastasis to the liver or beyond at the time of diagnosis. The management of synchronous disease is complex. Conventional surgery removes the colorectal primary first, followed by chemotherapy, with resection of liver metastases as a final step. Advances in the availability and safety of liver surgery, anaesthesia and critical care have made two alternative options feasible. The first is synchronous resection of the primary and liver metastases. The second is resection of the metastatic disease as the first step, termed the reverse or liver-first approach. Currently, evidence is inadequate to inform the selection of care pathway for patients with colorectal cancer and synchronous liver-limited metastases. Specifically, optimal pathways are not defined and there is a dearth of prospectively recorded cohort-defining factors influencing treatment selection or outcome.

Methods and analysis

Colorectal cancer with Synchronous liver-limited Metastases: an Inception Cohort (CoSMIC) is an inception cohort study of patients with a new diagnosis of colorectal cancer with synchronous liver-limited metastases. The sequence of treatment received, and factors influencing treatment decisions, will be evaluated against European Society of Medical Oncology guidelines. Clinical data will be collected, and quality of life, morbidity, mortality and long-term outcome compared for different treatment sequences adjusted for prognostic factors. Disease-free survival or progression will be measured at 1, 2 and 5 years. A nested qualitative study will ascertain patient experiences and clinician perspectives on delivery of care.

Ethics and dissemination

The full study protocol was independently peer reviewed by Professor Kees de Jong (University of Maastricht, Holland). CoSMIC has ethical approval from the National Health Service Research Ethics Committee (14/NW/1397). Results will be disseminated to healthcare professionals and patient groups, and may be used to design a definitive trial addressing areas of equipoise in treatment pathways, as well as optimising current pathways to improve outcomes and experiences.

Trial registration number

NCT02456285, pre-results.
Serum fibrinogen and cardiovascular events in Chinese patients with type 2 diabetes and stable coronary artery disease: a prospective observational study
Authors: Yang Sheng-Hua , Du Ying , Zhang Yan , Li Xiao-Lin , Li Sha , Xu Rui-Xia , Zhu Cheng-Gang , Guo Yuan-Lin , Wu Na-Qiong , Qing Ping , Gao Ying , Cui Chuan-Jue , Dong Qian , Sun Jing , Li Jian-Jun
Published: June 2017

Objectives

The aim of this study was to investigate the association of serum fibrinogen with cardiovascular events (CVE) in Chinese patients with type 2 diabetes mellitus (T2DM) and stable coronary artery disease (CAD).

Design

An observational study.

Setting

FuWai Hospital in Beijing, China.

Participants

A cohort of 1466 patients with T2DM and angiographic-proven stable CAD was evaluated.

Outcome measures

Baseline serum fibrinogen levels were measured and trisected into ‘low’, ‘middle’ and ‘high’. Their association with CVE was explored using Cox proportional hazard models.

Results

With 20.2 months (average) follow-up, 44 (3%) were lost to follow-up and 96 patients developed CVE. Compared with the patients without CVE, the ones who developed CVE had higher levels of fibrinogen. Univariable regression revealed a significant relation of fibrinogen to CVE (HR (HR) 1.25, 95% CI 1.06 to 1.47, p=0.010) per SD increase of fibrinogen at baseline. After adjusting for multiple established cardiovascular disease (CVD) risk factors, the association persisted (HR 1.30, 95% CI 1.02 to 1.66, p=0.037). Moreover, after adjusting for CVD risk factors, the HRs for middle-serum and high-serum fibrinogen concentration, using ‘low’ group as reference, were 1.23 (95% CI 0.69 to 2.20) and 2.20 (95% CI 1.11 to 3.36, p=0.049).

Conclusions

We first indicated that elevated fibrinogen level was independently associated with increased CVE in Chinese patients with T2DMand stable CAD.
Risk factor modifications and depression incidence: a 4-year longitudinal Canadian cohort of the Montreal Catchment Area Study
Authors: Meng Xiangfei , Brunet Alain , Turecki Gustavo , Liu Aihua , D'Arcy Carl , Caron Jean
Published: June 2017

Objective

Few studies have examined the effect of risk factor modifications on depression incidence. This study was to explore psychosocial risk factors for depression and quantify the effect of risk factor modifications on depression incidence in a large-scale, longitudinal population-based study.

Methods

Data were from the Montreal Longitudinal Catchment Area study (N=2433). Multivariate modified Poisson regression was used to estimate relative risk (RR). Population attributable fractions were also used to estimate the potential impact of risk factor modifications on depression incidence.

Results

The cumulative incidence rate of major depressive disorder at the 2-year follow-up was 4.8%, and 6.6% at the 4-year follow-up. Being a younger adult, female, widowed, separated or divorced, Caucasian, poor, occasional drinker, having a family history of mental health problems, having less education and living in areas with higher unemployment rates and higher proportions of visible minorities, more cultural community centres and community organisations, were consistently associated with the increased risk of incident major depressive disorder. Although only 5.1% of the disease incidence was potentially attributable to occasional drinking (vs abstainers) at the 2-year follow-up, the attribution of occasional drinking doubled at the 4-year follow-up. A 10% reduction in the prevalence of occasional drinking in this population could potentially prevent half of incident cases.

Conclusions

Modifiable risk factors, both individual and societal, could be the targets for public depression prevention programmes. These programmes should also be gender-specific, as different risk factors have been identified for men and women. Public health preventions at individual levels could focus on the better management of occasional drinking, as it explained around 5%~10% of incident major depressive disorders. Neighbourhood characteristics could also be the target for public prevention programmes. However, this could be very challenging. A cost-effectiveness analysis of a variety of prevention efforts is warranted.
Retrospective cohort study of all deaths among infants born between 22 and 27 completed weeks of gestation in Switzerland over a 3-year period
Authors: Berger T M , Steurer M A , Bucher H U , Fauchère J C , Adams M , Pfister R E , Baumann-Hölzle R , Bassler D
Published: June 2017

Objectives

The aim of this research is to assess causes and circumstances of deaths in extremely low gestational age neonates (ELGANs) born in Switzerland over a 3-year period.

Design

Population-based, retrospective cohort study.

Setting

All nine level III perinatal centres (neonatal intensive care units (NICUs) and affiliated obstetrical services) in Switzerland.

Patients

ELGANs with a gestational age (GA) <28 weeks who died between 1 July 2012 and 30 June 2015.

Results

A total of 594 deaths were recorded with 280 (47%) stillbirths and 314 (53%) deaths after live birth. Of the latter, 185 (59%) occurred in the delivery room and 129 (41%) following admission to an NICU. Most liveborn infants dying in the delivery room had a GA ≤24 weeks and died following primary non-intervention. In contrast, NICU deaths occurred following unrestricted life support regardless of GA. End-of-life decision-making and redirection of care were based on medical futility and anticipated poor quality of life in 69% and 28% of patients, respectively. Most infants were extubated before death (87%).

Conclusions

In Switzerland, most deaths among infants born at less than 24 weeks of gestation occurred in the delivery room. In contrast, most deaths of ELGANs with a GA ≥24 weeks were observed following unrestricted provisional intensive care, end-of-life decision-making and redirection of care in the NICU regardless of the degree of immaturity.
In patients with severe uncontrolled asthma, does knowledge of adherence and inhaler technique using electronic monitoring improve clinical decision making? A protocol for a randomised controlled trial
Authors: Mokoka Matshediso C , Lombard Lorna , MacHale Elaine M , Walsh Joanne , Cushen Breda , Sulaiman Imran , Carthy Damien Mc , Boland Fiona , Doyle Frank , Hunt Eoin , Murphy Desmond M , Faul John , Butler Marcus , Hetherington Kathy , Mark FitzGerald J , Boven Job FM van , Heaney Liam G , Reilly Richard B , Costello Richard W
Published: June 2017

Introduction

Many patients with asthma remain poorly controlled despite the use of inhaled corticosteroids and long-acting beta agonists. Poor control may arise from inadequate adherence, incorrect inhaler technique or because the condition is refractory. Without having an objective assessment of adherence, clinicians may inadvertently add extra medication instead of addressing adherence. This study aims to assess if incorporating objectively recorded adherence from the Inhaler Compliance Assessment (INCA) device and lung function into clinical decision making provides more cost-effective prescribing and improves outcomes.

Methods and analysis

This prospective, randomised, multicentre study will compare the impact of using information on adherence to influence asthma treatment. Patients with severe uncontrolled asthma will be included. Data on adherence, inhaler technique and electronically recorded peak expiratory flow rate will be used to promote adherence and guide a clinical decision protocol to guide management in the active group. The control group will receive standard inhaler and adherence education. Medications will be adjusted using a protocol based on Global Initiativefor Asthma (GINA) recommendations. The primary outcome is the between-group difference in the proportion of patients who have refractory disease and are prescribed appropriate medications at the end of 32 weeks. A co-primary outcome is the difference between groups in the rate of adherence to salmeterol/fluticasone inhaler over the last 12 weeks. Secondary outcomes include changes in symptoms, lung function, type-2 cytokine biomarkers and clinical outcomes between both groups. Cost-effectiveness and cost-utility analyses of the INCA device intervention will be performed. The economic impact of a national implementation of the INCA-SUN programme will be evaluated.

Ethics and dissemination

The results of the study will be published as a manuscript in peer-reviewed journals. The study has been approved by the ethics committees in the five participating hospitals.

Trial registration

NCT02307669; Pre-results.
Targeted simplification versus antipseudomonal broad-spectrum beta-lactams in patients with bloodstream infections due toEnterobacteriaceae(SIMPLIFY): a study protocol for a multicentre, open-label, phase III randomised, controlled, non-inferiority clinical trial
Authors: López-Cortés Luis Eduardo , Rosso-Fernández Clara , Núñez-Núñez María , Lavín-Alconero Lucía , Bravo-Ferrer José , Barriga Ángel , Delgado Mercedes , Lupión Carmen , Retamar Pilar , Rodríguez-Baño Jesús
Published: June 2017

Introduction

Within the context of antimicrobial stewardship programmes, de-escalation of antimicrobial therapy is one of the proposed strategies for reducing the unnecessary use of broad-spectrum antibiotics (BSA). The empirical treatment of nosocomial and some healthcare-associated bloodstream infections (BSI) frequently includes a beta-lactam with antipseudomonal activity as monotherapy or in combination with other drugs, so there is a great opportunity to optimise the empirical therapy based on microbiological data. De-escalation is assumed as standard of care for experts in infectious diseases. However, it is less frequent than it would desirable.

Methods and analysis

The SIMPLIFY trial is a multicentre, open-label, non-inferiority phase III randomised controlled clinical trial, designed as a pragmatic ‘real-practice’ trial. The aim of this trial is to demonstrate the non-inferiority of de-escalation from an empirical beta-lactam with antipseudomonal activity to a targeted narrow-spectrum antimicrobial in patients with BSI due toEnterobacteriaceae. The primary outcome is clinical cure, which will be assessed at the test of cure visit. It will be conducted at 19 Spanish public and university hospitals.

Ethics and dissemination

Each participating centre has obtained the approval of the ethics review committee, the agreement of the directors of the institutions and authorisation from the Spanish Regulatory Agency (Agencia Española del Medicamento y Productos Sanitarios). Data will be presented at international conferences and published in peer-reviewed journals.

Discussion

Strategies to reduce the use of BSA should be a priority. Most of the studies that support de-escalation are observational, retrospective and heterogeneous. A recent Cochrane review stated that well-designed clinical trials should be conducted to assess the safety and efficacy of de-escalation.

Trial registration number

The European Union Clinical Trials Register: EudraCT number 2015-004219-19. Clinical trials.gov:NCT02795949. Protocol version: V.2.0, dated 16 May 2016. All items from the WHO Trial Registration Data Set are included in the registry.
Screening for cancer in patients with unprovoked venous thromboembolism: protocol for a systematic review and individual patient data meta-analysis
Authors: van Es Nick , Gal Grégoire Le , Otten Hans-Martin , Robin Philippe , Piccioli Andrea , Lécumberri Ramon , Palomares Luis Jara , Religa Piotr , Rieu Viriginie , Rondina Matthew T. , Beckers Mariëlle M , Prandoni Paolo , Salaun Pierre-Yves , Nisio Marcello Di , Bossuyt Patrick M , Büller Harry R , Carrier Marc
Published: June 2017

Introduction

Occult cancer is present in 4%–9% of patients with unprovoked venous thromboembolism (VTE). Screening for cancer may be considered in these patients, with the aim to diagnose cancers in an early, potentially curable stage. Information is needed about the risk of occult cancer, overall and in specific subgroups, additional risk factors and on the performance of different screening strategies.

Methods and analysis

MEDLINE, Embase and CENTRAL databases were searched from November 2007 to January 2016 for prospective studies that had evaluated protocol-mandated screening for cancer in patients with unprovoked VTE and with at least 12 months’ follow-up. Two reviewers independently assessed articles for eligibility. Ten eligible studies were identified and individual patient data were obtained from each of them. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool . Generalised linear mixed-effects models was used to calculate estimates in a one-stage meta-analytic approach, overall and in a number of subgroups, including patients undergoing limited screening only, elderly patients, patients with previous VTE, smokers and patients using oestrogens.

Ethics and dissemination

Ethical approval is not required for this systematic review and individual patient data meta-analysis. Findings have been submitted for publication in peer-reviewed journals and presentations at national and international conferences to provide clinicians and other decision-makers with valid and precise risk estimates of occult cancer, overall and in specific clinical subgroups, with risk factors for occult cancer, with estimates of the diagnostic performance of limited screening and with an exploration of the benefit of extensive screening strategies.
Contextual and individual inequalities of multimorbidity in Brazilian adults: a cross-sectional national-based study
Authors: Nunes Bruno P , Chiavegatto Filho Alexandre D P , Pati Sanghamitra , Cruz Teixeira Doralice S , Flores Thaynã R , Camargo-Figuera Fabio A , Munhoz Tiago N , Thumé Elaine , Facchini Luiz A , Rodrigues Batista Sandro R
Published: June 2017

Objectives

The study aims to evaluate the magnitude of multimorbidity in Brazilian adults, as well to measure their association with individual and contextual factors stratified by Brazilian states and regions.

Methods

A national-based cross-sectional study was carried out in 2013 with Brazilian adults. Multimorbidity was evaluated by a list of 22 physical and mental morbidities (based on self-reported medical diagnosis and Patient Health Questionnaire-9 for depression). The outcome was analysed taking ≥2 and ≥3 diseases as cut-off points. Factor analysis (FA) was used to identify disease patterns and multilevel models were used to test association with individual and contextual variables.

Results

The sample comprised 60 202 individuals. Multimorbidity frequency was 22.2% (95% CI 21.5 to 22.9) for ≥2 morbidities and 10.2% (95% CI 9.7 to 10.7) for ≥3 morbidities. In the multilevel adjusted models, females, older people, those living with a partner and having less schooling presented more multiple diseases. No linear association was found according to wealth index but greater outcome frequency was found in individuals with midrange wealth index. Living in states with higher levels of education and wealthier states was associated with greater multimorbidity. Two patterns of morbidities (cardiometabolic problems and respiratory/mental/muscle–skeletal disorders) explained 92% of total variance. The relationship of disease patterns with individual and contextual variables was similar to the overall multimorbidity, with differences among Brazilian regions.

Conclusions

In Brazil, at least 19 million adults had multimorbidity. Frequency is similar to that found in other Low and and Middle Income Countries. Contextual and individual social inequalities were observed.
What stage are low-income and middle-income countries (LMICs) at with patient safety curriculum implementation and what are the barriers to implementation? A two-stage cross-sectional study
Authors: Ginsburg Liane R , Dhingra-Kumar Neelam , Donaldson Liam J
Published: June 2017

Objectives

The improvement of safety in healthcare worldwide depends in part on the knowledge, skills and attitudes of staff providing care. Greater patient safety content in health professional education and training programmes has been advocated internationally. While WHO Patient Safety Curriculum Guides (for Medical Schools and Multi-Professional Curricula) have been widely disseminated in low-income and middle-income countries (LMICs) over the last several years, little is known about patient safety curriculum implementation beyond high-income countries. The present study examines patient safety curriculum implementation in LMICs.

Methods

Two cross-sectional surveys were carried out. First, 88 technical officers in Ministries of Health and WHO country offices were surveyed to identify the pattern of patient safety curricula at country level. A second survey followed that gathered information from 71 people in a position to provide institution-level perspectives on patient safety curriculum implementation.

Results

The majority, 69% (30/44), of the countries were either considering whether to implement a patient safety curriculum or actively planning, rather than actually implementing, or embedding one. Most organisations recognised the need for patient safety education and training and felt a safety curriculum was compatible with the values of their organisation; however, important faculty-level barriers to patient safety curriculum implementation were identified. Key structural markers, such as dedicated financial resources and relevant assessment tools to evaluate trainees’ patient safety knowledge and skills, were in place in fewer than half of organisations studied.

Conclusions

Greater attention to patient safety curriculum implementation is needed. The barriers to patient safety curriculum implementation we identified in LMICs are not unique to these regions. We propose a framework to act as a global standard for patient safety curriculum implementation. Educating leaders through the system in order to embed patient safety culture in education and clinical settings is a critical first step.