bluuebunny/crossref_metadata_2025 huggingface dataset:
Newborn Exposure to Polycyclic Aromatic Hydrocarbons Through Parenteral Nutrition
Authors: Bohrer Denise , Barichello Marcia M. , Viana Carine , Nascimento Paulo C. , Carvalho Leandro M.
Published: July 2018

Background and Objectives:

Parenteral nutrition (PN) administered to newborns (NB) may be contaminated with polycyclic aromatic hydrocarbons (PAHs) and may therefore increase the contact with these toxicants in very early life stages. The aim of the study is to determine to what extent, if any, commercial products for PN are contaminated with PAHs and to determine whether these contaminants, when present in the bag content, are delivered to NB and whether 1‐hydroxypyrene (1‐HP), the pyrene metabolite, can be detected in the urine of exposed NB.

Methods:

Commercial products and the bags administered to 10 NB during their period in the NICU were analyzed for the 16 priority US Environmental Protection Agency PAHs. Urine samples were collected and analyzed for their 1‐HP content. Urine samples of a control group composed of 8 breastfed NB were also analyzed for the determination of 1‐HP.

Results:

From 9 different commercial products used to compound PN bags, 6 were contaminated with PAHs, with total concentrations varying from 0.02 to 10.56 mg/L. In the bags administered to the NB, this sum varied from 0.01 to 6.30 mg/L with a mean of 2.62 mg/L. Therefore, for each 100 mL PN, an average load of 0.26 mg PAHs was observed. The majority of the urine samples taken from NB in the study group (80%) contained 1‐HP, but it was not detected in the urine of any baby in the control group.

Conclusions:

The contamination of PN with PAHs poses a critical toxicological risk. The elevated contaminant concentrations and the parenteral way of administration make this source of PAHs considerably worse than any other, including maternal exposure to environmental pollution or tobacco.
Colorectal Cancer Stratification in the Routine Clinical Pathway: A District General Hospital Experience
Authors: Wedden Sarah , Miller Keith , Frayling Ian M. , Thomas Teresa , Chefani Alina , Miller Karolina , Hamblin Angela , Taylor Jenny C. , D’Arrigo Corrado
Published: July 2018

Colorectal cancer (CRC) has many subtypes with different prognoses and response to treatment. Patients must be characterized to access the most appropriate treatment and improve outcomes. An increasing number of biomarkers are required for characterization but are not in routine use. We investigated whether CRC can be stratified routinely within a small district general hospital to inform clinical decision making at local multidisciplinary team meeting/tumor board level. We evaluated mismatch repair (MMR) and EGFR signaling pathways using predominantly in-house immunohistochemical (IHC) tests (MSH2, MSH6, MLH1, PMS2, BRAF-V600E, Her2, PTEN, cMET) as well as send away PCR/NGS tests (NRAS, KRAS, and BRAF). We demonstrated that many of the tests required for personalized treatment of CRC can be done locally and timely. Send away tests need to be requested shortly after cut-up and this needs to be firmly established in the tissue pathways for the results to be considered at multidisciplinary team meeting/tumor board. We have shown that MMR IHC combined with BRAFV600E IHC is practical and easy to perform in a small district general hospital, has full concordance with DNA-based tests and satisfies the latest NICE requirements for the identification of potential Lynch syndrome patients. We provide a framework for the interpretation and presentation of test results. It is a practical classification that clinical pathologists can use to communicate effectively with the clinical team. It is broadly based on molecular subtyping, firmly focused on treatment decisions and dependent on the panel of molecular tests currently available.
Brief Report: Prevalence of Peripheral Artery Disease Is Higher in Persons Living With HIV Compared With Uninfected Controls
Authors: Knudsen Andreas D. , Gelpi Marco , Afzal Shoaib , Ronit Andreas , Roen Ashley , Mocroft Amanda , Lundgren Jens , Nordestgaard Børge , Sillesen Henrik , Lebech Anne-Mette , Køber Lars , Kofoed Klaus F. , Nielsen Susanne D.
Published: July 2018

Objective:

Ankle–brachial index is an excellent tool for diagnosing peripheral artery disease (PAD). We aimed to determine the prevalence and risk factors for PAD in people living with HIV (PLWH) compared with uninfected controls. We hypothesized that prevalence of PAD would be higher among PLWH than among controls independent of traditional cardiovascular disease (CVD) risk factors.

Methods:

PLWH aged 40 years and older were recruited from the Copenhagen comorbidity in HIV infection (COCOMO) study. Sex- and age-matched uninfected controls were recruited from the Copenhagen General Population Study. We defined PAD as ankle–brachial index ≤0.9 and assessed risk factors for PAD using logistic regression adjusting for age, sex, smoking status, dyslipidemia, diabetes, hypertension, and high-sensitivity C-reactive protein.

Results:

Among 908 PLWH and 11,106 controls, PAD was detected in 112 [12% confidence interval: (95% 10 to 14)] and 623 [6% (95% 5 to 6)], respectively (P < 0.001), odds ratio = 2.4 (95% 1.9 to 2.9), and adjusted odds ratio = 1.8 (95% 1.3 to 2.3, P < 0.001). Traditional CVD risk factors, but not HIV-related variables, were associated with PAD. The strength of the association between PAD and HIV tended to be higher with older age (P = 0.052, adjusted test for interaction).

Conclusions:

Prevalence of PAD is higher among PLWH compared with uninfected controls, especially among older persons, and remains so after adjusting for traditional CVD risk factors. Our findings expand the evidence base that PLWH have excess arterial disease to also include PAD. The exact biological mechanisms causing this excess risk remain to be elucidated. Until then, focus on management of modifiable traditional risk factors is important.
Trends Over Time for Adolescents Enrolling in HIV Care in Kenya, Tanzania, and Uganda From 2001–2014
Authors: Apondi Edith , Humphrey John M. , Sang Edwin , Mwangi Ann , Keter Alfred , Musick Beverly S. , Nalugoda Fred K. , Ssali John , Bukusi Elizabeth , Yiannoutsos Constantin T. , Wools-Kaloustian Kara , Ayaya Samuel
Published: July 2018

Background:

The data needed to understand the characteristics and outcomes, over time, of adolescents enrolling in HIV care in East Africa are limited.

Setting:

Six HIV care programs in Kenya, Tanzania, and Uganda.

Methods:

This retrospective cohort study included individuals enrolling in HIV care as younger adolescents (10–14 years) and older adolescents (15–19 years) from 2001–2014. Descriptive statistics were used to compare groups at enrollment and antiretroviral therapy (ART) initiation over time. The proportion of adolescents was compared with the total number of individuals aged 10 years and older enrolling over time. Competing-risk analysis was used to estimate 12-month attrition after enrollment/pre-ART initiation; post-ART attrition was estimated by Kaplan–Meier method.

Results:

A total of 6344 adolescents enrolled between 2001 and 2014. The proportion of adolescents enrolling among all individuals increased from 2.5% (2001–2004) to 3.9% (2013–2014, P < 0.0001). At enrollment, median CD4 counts in 2001–2004 compared with 2013–2014 increased for younger (188 vs. 379 cells/mm3, P < 0.0001) and older (225 vs. 427 cells/mm3, P < 0.0001) adolescents. At ART initiation, CD4 counts increased for younger (140 vs. 233 cells/mm3, P < 0.0001) and older (64 vs. 323 cells/mm3, P < 0.0001) adolescents. Twelve-month attrition also increased for all adolescents both after enrollment/pre-ART initiation (4.7% vs. 12.0%, P < 0.001) and post-ART initiation (18.7% vs. 31.2%, P < 0.001).

Conclusions:

Expanding HIV services and ART coverage was likely associated with earlier adolescent enrollment and ART initiation but also with higher attrition rates before and after ART initiation. Interventions are needed to promote retention in care among adolescents.
The pulseless supracondylar humeral fracture: Our experience and a 1-year follow-up
Authors: Delniotis Ioannis , Ktenidis Kiriakos
Published: July 2018

BACKGROUND

Although the pulseless supracondylar humeral fracture (SHF) in children is well known in the bibliography, controversy still exists regarding the treatment strategy. The purpose of this study was: (a) to describe our policy with pulseless hands following SHF and (b) evaluate the functional outcome in a 1-year follow-up.

METHODS

During the years 2013 to 2018 in our department, 23 of 210 children with type III SHF presented with a pulseless hand (20 with a PPH and 3 with a cold, pulseless hand). Fracture reduction was attempted in all patients followed by reevaluation of the vascular clinical status (including a Doppler ultrasound).

RESULTS

In PPH, a palpable radial pulse was present in all patients in less than 48 hours after surgery. Closed reduction was able to improve the vascular status in 1 patient with pale pulseless hand but surgical exploration of the brachial artery was performed in the other two patients. A palpable radial pulse was present 24 hours after surgery in these 3 patients. All patients had good/excellent outcomes at 1-year follow-up.

CONCLUSION

With our study, we want to enhance the traditional dogma of “watchful waiting” in pink pulseless hands following SHF, and we believe that it should not be revisited. In pale pulseless hands following SHF, at least one attempt of reduction and fixation of the fracture is recommended. If the pulse does not return or the vascular status does not improve, immediate surgical exploration of the artery is strongly indicated.

LEVEL OF EVIDENCE

Case series prognostic study, level IV.
Prognosis of Periodic and Rhythmic Patterns in Adult and Pediatric Populations
Authors: Lewis Dalila W. , Johnson Emily L.
Published: July 2018

Although electrographic seizures are known to have an outcome on clinical prognosis, the implications of periodic and rhythmic patterns are less clear. The outcomes of adults with these patterns have been reported and are often poor; however, the outcomes in pediatric populations are less well characterized and may be different than in the adult population, as the etiologies of periodic and rhythmic patterns may differ in children and adults. In adults, generalized periodic discharges are highly associated with toxic–metabolic disturbances, infection, and anoxic injury; 30% to 64% of patients have poor outcomes. By contrast, in pediatric patients, generalized periodic discharges are more commonly associated with refractory status epilepticus, with good outcomes in 50% to 77%. The underlying etiology of the periodic or rhythmic pattern has a large influence on overall morbidity and mortality.
PI31 is an adaptor protein for proteasome transport in axons and required for synaptic development and function
Authors: Liu Kai , Jones Sandra , Minis Adi , Rodriguez Jose , Molina Henrik , Steller Hermann
Published: July 2018

Protein degradation by the ubiquitin-proteasome system (UPS) is critical for neuronal development, plasticity and function. Neurons utilize microtubule-dependent molecular motors to allocate proteasomes to synapses, but how proteasomes are coupled to motor proteins and how this transport is regulated to meet changing demand for protein breakdown remains largely unknown. We show that the conserved proteasome-binding protein PI31 serves as an adaptor to directly couple proteasomes with dynein light chain proteins (DYNLL1/2). Inactivation of PI31 inhibits proteasome motility in axons and disrupts synaptic protein homeostasis, structure and function. Moreover, phosphorylation of PI31 at a conserved site by p38 MAP kinase promotes binding to DYNLL1/2, and a non-phosphorable PI31 mutant impairs proteasome movement in axons, suggesting a mechanism to regulate loading of proteasomes onto motor proteins. Because mutations affecting PI31 activity are associated with human neurodegenerative diseases, impairment of PI31-mediated axonal transport of proteasomes may be the root cause of these disorders.
Development of a core outcome set for trials on induction of labour: an international multistakeholder Delphi study
Authors: Dos Santos F , Drymiotou S , Antequera Martin A , Mol BW , Gale C , Devane D , van't Hooft J , Johnson MJ , Hogg M , Thangaratinam S
Published: July 2018

Objective

To develop a set of core outcomes to be minimally reported in trials on induction of labour.

Design

Two‐round Delphi survey and consensus meeting.

Population

Four stakeholder groups: midwives, obstetricians, neonatologists, and women's representatives.

Methods

Protocol registered with COMET (Registration Number: 695). Stakeholders rated reported outcomes for importance (1—limited to 9—critical). The median rating of each outcome was calculated. The consensus criteria to include outcomes were as follows: ≥70% participants rated outcomes as critical and <15% rated outcomes as limited importance. Outcomes that did not achieve consensus were taken to round two and, if there was still no consensus, to the final consensus meeting.

Main outcome measures

Outcomes in trials of induction of labour.

Results

Of the 159 invited participants, 54% (86/159) completed the first round, and 83% completed the second round (71/86). The core outcome set included 28 core outcomes in four domains: Short‐term maternal outcomes (n = 18)—cardiorespiratory arrest, damage to internal organs, death, haemorrhage, hysterectomy, infection, intensive care admission, length of hospital stay, mode of delivery, need for more than one induction agent, oxytocin augmentation, postnatal depression, pulmonary embolus, satisfaction with care, stroke, time from induction to delivery, uterine hyperstimulation, uterine scar dehiscence/rupture; short‐term offspring outcomes (n = 8)—admission to the neonatal unit, birth trauma, death, hypoxic ischaemic encephalopathy/need for therapeutic hypothermia, meconium aspiration syndrome, need for respiratory support, infection, and seizures; long‐term maternal outcomes (n = 1)—operative pelvic floor repair; long‐term offspring outcomes (n = 1)—disability including neurodevelopmental delay.

Conclusion

Trials on induction of labour should include this core outcome set to standardise reporting.

Tweetable abstract

International multistakeholder Delphi study identifies a core outcome set for trials on induction of labour.
Angiotensin II, a stress‐related neuropeptide in the CNS, facilitates micturition reflex in rats
Authors: Shimizu Shogo , Shimizu Takahiro , Nakamura Kumiko , Higashi Youichirou , Saito Motoaki
Published: July 2018

Background and Purpose

We investigated the effects of centrally administered stress‐related neuropeptide, angiotensin II, on the micturition reflex and the downstream signalling pathways in rats.

Experimental Approach

Male Wistar rats were anaesthetized with urethane for cystometry before and after i.c.v. administration of vehicle or angiotensin II (30 pmol). Muscimol (a GABAA receptor agonist) or baclofen (a GABAB receptor agonist) was i.c.v. administered 30 min before or 15 min after central angiotensin II administration. Telmisartan [an angiotensin II type 1 (AT1) receptor antagonist], valsartan (an AT1 receptor antagonist), PD123319 (an AT2 receptor antagonist), U‐73122 (a PLC inhibitor), chelerythrine chloride (a PKC inhibitor), apocynin (a NADPH oxidase inhibitor) or tempol (an antioxidant) was centrally administered 30 min before central angiotensin II administration.

Key Results

Centrally administered angiotensin II significantly shortened the intercontraction interval and decreased the voided volume and bladder capacity without altering the maximum voiding pressure, post‐voiding residual urine volume or voiding efficacy. Muscimol, baclofen, telmisartan, valsartan, U‐73122, chelerythrine chloride, apocynin or tempol pretreatment significantly suppressed the reduction in intercontraction interval induced by central angiotensin II. Post‐treatment with muscimol or baclofen also ameliorated the decrease in intercontraction interval induced by central angiotensin II.

Conclusions and Implications

Angiotensin II in the CNS facilitates micturition reflex by inhibiting central GABAergic activity and activating the AT1 receptor/PLC/PKC/NADPH oxidase/superoxide anion pathway.
Three‐dimensional transesophageal echocardiography vs cardiac magnetic resonance in the assessment of planimetric mitral valve area in rheumatic mitral stenosis
Authors: Uygur Begum , Celik Omer , Ustabasioglu Fethi Emre , Akinci Okan , Erturk Mehmet
Published: July 2018

Aim

Rheumatic heart disease is a common cause of valvular disease, especially in developing countries. Echocardiography is the gold standard investigation modality for cardiac valves. In rheumatic mitral stenosis (MS), three‐dimensional transesophageal echocardiography (3D TEE) provides better alignment of the image plane at the mitral tips and more accurate and reproducible planimetric measurement of mitral valve area (MVA). Cardiac magnetic resonance (CMR) is a new method that provides evaluation of cardiac anatomy and function noninvasively. Previous studies showed strong correlation between planimetric MVA measured by two‐dimensional transthoracic echocardiography and CMR. We aimed to compare the planimetric MVAs assessed by 3D TEE and CMR in rheumatic MS patients. To best of our knowledge, this is the first study that compares 3D TEE and CMR for the assessment of the planimetric MVA in rheumatic MS.

Methods

We retrospectively evaluated 28 rheumatic MS patients who underwent 3D TEE and ECG‐gated CMR. 3D TEE planimetric MVAs were measured manually by multiplanar reconstruction (MPR) method and CMR planimetric MVAs were measured manually on short‐axis cine images. Then, 3D TEE and CMR measurements were compared.

Results

A total of 28 patients’ (mean age 44 ± 12, 82.1% female) planimetric 3D TEE MVAs (1.00 ± 0.20 cm2) and CMR MVAs (1.04 ± 0.17 cm2) were found to be highly correlated (P < 0.0001, r: 0.744) with Pearson correlation analysis. Bland–Altman analysis showed strong agreement between two techniques.

Conclusion

For the diagnosis and the follow‐up of rheumatic MS, planimetric CMR MVA is an alternative noninvasive method which highly correlates with planimetric 3D TEE MVA.
Cellular localization of the K+‐dependent Na+–Ca2+ exchanger NCKX5 and the role of the cytoplasmic loop in its distribution in pigmented cells
Authors: Rogasevskaia Tatiana P. , Szerencsei Robert T. , Jalloul Ali H. , Visser Frank , Winkfein Robert J. , Schnetkamp Paul P. M.
Published: July 2018

NCKX5 is a bidirectional K+‐dependent Na+–Ca2+ exchanger, which belongs to the SLC24A gene family. In particular, the A111T mutation of NCKX5 has been associated with reduced pigmentation in European populations. In contrast to other NCKX isoforms, which function in the plasma membrane (PM), NCKX5 has been shown to localize either in the trans‐Golgi network (TGN) or in melanosomes. Moreover, sequences responsible for retaining its intracellular localization are unknown. This study addresses two major questions: (i) clarification of intracellular location of NCKX5 and (ii) identification of sequences that retain NCKX5 inside the cell. We designed a set of cDNA constructs representing NCKX5 loop deletion mutants and NCKX2–NCKX5 chimeras to address these two questions after expression in pigmented MNT1 cells. Our results show that NCKX5 is not a PM resident and is exclusively located in the TGN. Moreover, the large cytoplasmic loop is the determinant for retaining NCKX5 in the TGN.
Photophysics of Xanthene Dyes at High Concentrations in Solid Environments: Charge Transfer Assisted Triplet Formation
Authors: Litman Yair E. , Rodríguez Hernán B. , Braslavsky Silvia E. , San Román Enrique
Published: July 2018

The photophysical behavior of two xanthene dyes, Eosin Y and Phloxine B, included in microcrystalline cellulose particles is studied in a wide concentration range, with emphasis on the effect of dye concentration on fluorescence and triplet quantum yields. Absolute fluorescence quantum yields in the solid‐state were determined by means of diffuse reflectance and steady‐state fluorescence measurements, whereas absolute triplet quantum yields were obtained by laser‐induced optoacoustic spectroscopy and their dependence on dye concentration was confirmed by diffuse reflectance laser flash photolysis and time‐resolved phosphorescence measurements. When both quantum yields are corrected for reabsorption and reemission of radiation, ΦF values decrease strongly on increasing dye concentration, while a less pronounced decay is observed for ΦT. Fluorescence concentration quenching is attributed to the formation of dye aggregates or virtual traps resulting from molecular crowding. Dimeric traps are however able to generate triplet states. A mechanism based on the intermediacy of charge‐transfer states is proposed and discussed. Calculation of parameters for photoinduced electron transfer between dye molecules within the traps evidences the feasibility of the proposed mechanism. Results demonstrate that photoactive energy traps, capable of yielding dye triplet states, can be formed even in highly‐concentrated systems with random dye distributions.
Alterations in maternally perceived fetal movement and their association with late stillbirth: findings from the Midland and North of England stillbirth case–control study
Authors: Heazell Alexander E P , Budd Jayne , Li Minglan , Cronin Robin , Bradford Billie , McCowan Lesley M E , Mitchell Edwin A , Stacey Tomasina , Martin Bill , Roberts Devender , Thompson John M D
Published: July 2018

Objective

To report perception of fetal movements in women who experienced a stillbirth compared with controls at a similar gestation with a live birth.

Design

Case–control study.

Setting

41 maternity units in the UK.

Participants

Cases were women who had a late stillbirth ≥28 weeks gestation (n=291) and controls were women with an ongoing pregnancy at the time of the interview (n=733). Controls were frequency matched to cases by obstetric unit and gestational age.

Methods

Data were collected using an interviewer-administered questionnaire which included questions on maternal perception of fetal movement (frequency, strength, increased and decreased movements and hiccups) in the 2 weeks before the interview/stillbirth. Five fetal movement patterns were identified incorporating the changes in strength and frequency in the last 2 weeks by combining groups of similar pattern and risk. Multivariable analysis adjusted for known confounders.

Primary outcome measure

Association of maternally perceived fetal movements in relation to late stillbirth.

Results

In multivariable analyses, women who reported increased strength of movements in the last 2 weeks had decreased risk of late stillbirth compared with those whose movements were unchanged (adjusted OR (aOR) 0.18, 95% CI 0.13 to 0.26). Women with decreased frequency (without increase in strength) of fetal movements were at increased risk (aOR 4.51, 95% CI 2.38 to 8.55). Daily perception of fetal hiccups was protective (aOR 0.31, 95% CI 0.17 to 0.56).

Conclusions

Increased strength of fetal movements and fetal hiccups is associated with decreased risk of stillbirth. Alterations in frequency of fetal movements are important in identifying pregnancies at increased risk of stillbirth, with the greatest risk in women noting a reduction in fetal activity. Clinical guidance should be updated to reflect that increase in strength and frequency of fetal movements is associated with the lowest risk of stillbirth, and that decreased fetal movements are associated with stillbirth.

Trial registrationnumber

NCT02025530.
Framework to construct and interpret latent class trajectory modelling
Authors: Lennon Hannah , Kelly Scott , Sperrin Matthew , Buchan Iain , Cross Amanda J , Leitzmann Michael , Cook Michael B , Renehan Andrew G
Published: July 2018

Objectives

Latent class trajectory modelling (LCTM) is a relatively new methodology in epidemiology to describe life-course exposures, which simplifies heterogeneous populations into homogeneous patterns or classes. However, for a given dataset, it is possible to derive scores of different models based on number of classes, model structure and trajectory property. Here, we rationalise a systematic framework to derive a ‘core’ favoured model.

Methods

We developed an eight-step framework: step 1: a scoping model; step 2: refining the number of classes; step 3: refining model structure (from fixed-effects through to a flexible random-effect specification); step 4: model adequacy assessment; step 5: graphical presentations; step 6: use of additional discrimination tools (‘degree of separation’; Elsensohn’s envelope of residual plots); step 7: clinical characterisation and plausibility; and step 8: sensitivity analysis. We illustrated these steps using data from the NIH-AARP cohort of repeated determinations of body mass index (BMI) at baseline (mean age: 62.5 years), and BMI derived by weight recall at ages 18, 35 and 50 years.

Results

From 288 993 participants, we derived a five-class model for each gender (men: 177 455; women: 111 538). From seven model structures, the favoured model was a proportional random quadratic structure (model F). Favourable properties were also noted for the unrestricted random quadratic structure (model G). However, class proportions varied considerably by model structure—concordance between models F and G were moderate (Cohen κ: men, 0.57; women, 0.65) but poor with other models. Model adequacy assessments, evaluations using discrimination tools, clinical plausibility and sensitivity analyses supported our model selection.

Conclusion

We propose a framework to construct and select a ‘core’ LCTM, which will facilitate generalisability of results in future studies.
Initial use of supplementary oxygen for trauma patients: a systematic review
Authors: Eskesen Trine Grodum , Baekgaard Josefine Stokholm , Steinmetz Jacob , Rasmussen Lars S
Published: July 2018

Objective

This systematic review aimed to identify and describe the evidence for supplementary oxygen for spontaneously breathing trauma patients, and for high (0.60–0.90) versus low (0.30–0.50) inspiratory oxygen fraction (FiO2) for intubated trauma patients in the initial phase of treatment.

Methods

Several databases were systematically searched in September 2017 for studies fulfilling the following criteria: trauma patients (Population); supplementary oxygen/high FiO2(Intervention) versus no supplementary oxygen/low FiO2(Control) for spontaneously breathing or intubated trauma patients, respectively, in the initial phase of treatment; mortality, complications, days on mechanical ventilation and/or length of stay (LOS) in hospital/intensive care unit (ICU) (Outcomes); prospective interventional trials (Study design). Two independent reviewers screened and identified studies and extracted data from included studies.

Results

6142 citations were screened with an inter-rater reliability (Cohen’s kappa) of 0.88. One interventional trial of intubated trauma patients was included. 68 trauma patients were randomised to receive an FiO2of 0.80 (intervention group) or 0.50 (control group) during mechanical ventilation (first 6 hours). There was no significant difference in hospital or ICU LOS between the groups. No patient died in either group. Another interventional trial, not strictly fulfilling the inclusion criteria, was presented for descriptive purposes. 21 trauma patients were alternately assigned to two types of mechanical ventilation (first 48 hours), both aiming at an FiO2of 0.40, but resulted in estimated mean FiO2s of 0.45 (intervention group) and 0.60 (control group). No difference in days on mechanical ventilation was found. Two patients in the control group died, none in the intervention group. No prospective, interventional trials on spontaneously breathing trauma patients were identified.

Conclusions

Evidence for the use of supplementary oxygen for spontaneously breathing trauma patients is lacking, and the evidence for low versus high FiO2for intubated trauma patients is limited.

PROSPERO registration number

42016050552
Protocol for a meta-integration: investigating positive aspects of caregiving in dementia
Authors: Branger Camille , O’Connell Megan E , Peacock Shelley
Published: July 2018

Introduction

The current work describes the protocol for a meta-integration investigating the positive aspects of providing care to someone living with dementia. We aim to understand the position of positive aspects in the caregiver experience as well as identify how positive aspects are commonly conceptualised, investigated and measured in literature.

Methods and analyses

Meta-integration is a method of investigation that synthesises findings from meta-analysis or systematic review of quantitative studies and meta-synthesis of qualitative studies, to provide a coherent and holistic account of a phenomenon. As a relatively new method, terminology and methodological approaches are varied. The current work describes the process of conducting an advanced convergent meta-integration, including protocol for systematic search, inclusion/exclusion screening phases, intramethod analysis synthesis and intermethod synthesis on quantitative, qualitative and mixed methods research pertaining to the positive aspects of providing care to someone living with dementia.

Ethics and dissemination

There are no ethics or safety concerns about dissemination, which includes plans for a conference presentation and publication.
Oral propranolol for prevention of threshold retinopathy of prematurity (ROPROP): protocol of a randomised controlled trial
Authors: Bührer Christoph , Erdeve Ömer , Bassler Dirk , Bar-Oz Benjamin
Published: July 2018

Introduction

Retinopathy of prematurity (ROP) is a disease observed in extremely premature infants characterised by visioning-threatening retinal vessel proliferation. Propranolol, a drug used for decades in newborn infants with heart diseases, hypertension and thyrotoxicosis and licenced for infantile haemangiomas, may be effective in halting progression of ROP to severe stages, as suggested by preliminary data from small studies.

Methods and analysis

ROPROP is an investigator-initiated, multicentre, placebo-controlled double-blind, randomised controlled trial aiming to assess the safety and efficacy of orally administered propranolol to reduce the risk of threshold ROP (stage 3) in extremely preterm infants at 48 weeks postmenstrual age (primary objective) and the rate of infants requiring local interventions for severe ROP (secondary objective). Key inclusion criteria: gestational age <28 weeks, birth weight <1250 g, postmenstrual age ≥31 and <37 weeks, incipient ROP (stage 1 or 2, with or without plus disease) and written informed consent by parents or legal guardian. Key exclusion criteria: requirement for open-label propranolol treatment, major congenital malformations (including those with cerebrovascular malformations), known chromosomal anomalies, colobomas and other eye malformations, atrioventricular block grade 2 or 3 and comedication with antiarrhythmics, clonidine, insulin (pharmacodynamic interaction), phenobarbital or rifampicin (pharmacokinetic interaction). The intervention consists of oral propranolol-hydrochloride (1.6 mg/kg/day in three to four divided dosages) or placebo until discharge, for a maximum of 10 weeks. Analysis is by intention to treat.

Ethics and dissemination

The protocol has received ethical and regulatory approval. Results will be published after peer review irrespective of the study outcome.

Trial registration numbers

NCT03083431, EudraCT# 2017‐002124‐24 (EUCTR), 00013730 (DRKS); Pre-results.
Early Life Interventions for Childhood Growth and Development in Tanzania (ELICIT): a protocol for a randomised factorial, double-blind, placebo-controlled trial of azithromycin, nitazoxanide and nicotinamide
Authors: DeBoer Mark Daniel , Platts-Mills James A , Scharf Rebecca J , McDermid Joann M , Wanjuhi Anne W , Gratz Jean , Svensen Erling , Swann Jon R , Donowitz Jeffrey R , Jatosh Samwel , Houpt Eric R , Mduma Estomih
Published: July 2018

Introduction

In many developing areas in the world, a high burden of enteric pathogens in early childhood are associated with growth deficits. The tryptophan-kynurenine-niacin pathway has been linked to enteric inflammatory responses to intestinal infections. However, it is not known in these settings whether scheduled antimicrobial intervention to reduce subclinical enteric pathogen carriage or repletion of the tryptophan-kynurenine-niacin pathway improves linear growth and development.

Methods and analysis

We are conducting a randomised, placebo-controlled, factorial intervention trial in the rural setting of Haydom, Tanzania. We are recruiting 1188 children within the first 14 days of life, who will be randomised in a 2×2 factorial design to administration of antimicrobials (azithromycin and nitazoxanide, randomised together) and nicotinamide. The nicotinamide is administered as a daily oral dose, which for breast-feeding children aged 0–6 months is given to the mother and for children aged 6–18 months is given to the child directly. Azithromycin is given to the child as a single oral dose at months 6, 9, 12 and 15; nitazoxanide is given as a 3-day course at months 12 and 15. Mother/child pairs are followed via monthly in-home visits. The primary outcome is the child’s length-for-age Z-score at 18 months. Secondary outcomes for the child include additional anthropometry measures; stool pathogen burden and bacterial microbiome; systemic and enteric inflammation; blood metabolomics, growth factors, inflammation and nutrition; hydrogen breath assessment to estimate small-intestinal bacterial overgrowth and assessment of cognitive development. Secondary outcomes for the mother include breastmilk content of nicotinamide, other vitamins and amino acids; blood measures of tryptophan-kynurenine-niacin pathway and stool pathogens.

Ethics and dissemination

This trial has been approved by the Tanzanian National Institute for Medical Research, the Tanzanian FDA and the University of Virginia IRB. Findings will be presented at national and international conferences and published in peer-review journals.

Protocol version

5.0, 4 December 2017.

Protocol sponsor

Haydom Lutheran Hospital, Haydom, Manyara, Tanzania.

Trial registration number

NCT03268902; Pre-results.
Influence of health literacy on acceptance of influenza and pertussis vaccinations: a cross-sectional study among Spanish pregnant women
Authors: Castro-Sánchez Enrique , Vila-Candel Rafael , Soriano-Vidal Francisco J , Navarro-Illana Esther , Díez-Domingo Javier
Published: July 2018

Objectives

Immunisations against influenza andBordetella pertussisinfection are recommended to pregnant women in Valencia (Spain), yet vaccination rates remain low. Health literacy (HL) appears as a crucial factor in vaccination decision-making. We explored the relation between HL of pregnant women and decisions to receive influenza and pertussis immunisations.

Setting

University hospital in Valencia (Spain).

Participants

119 women who gave birth at a hospital in Valencia (Spain) between November 2015 and May 2016. Women in the immediate postpartum period (more than 27 weeks of gestation), between November 2015 and May 2016 were included in the study. Women with impairments, language barriers or illiteracy which prevented completion of the questionnaires, or those who were under 18 years were excluded from enrolment.

Primary and secondary outcome measures

HL level; influenza and pertussis immunisation rate; reasons for rejection of vaccination.

Results

119 participants were included (mean age 32.3±5.5 years, 52% primiparous, 95% full-term deliveries). A higher education level was associated with Short Assessment of Health Literacy for Spanish Adults _50 (adjusted R2=0.22, p=0.014) and Newest Vital Sign (adjusted R2=0.258, p=0.001) scores. Depending on the scale, 56%–85% of participants had adequate HL. 52% (62/119) and 94% (112/119) of women received influenza and pertussis immunisation, respectively. Women rejecting influenza vaccine had a higher HL level (measured by SALHSA_50 tool) than those accepting it (Kruskal-Wallis test p=0.022). 24% of women who declined influenza vaccination felt the vaccine was unnecessary, and 23% claimed to have insufficient information.

Conclusions

Influenza vaccination rate was suboptimal in our study. Women with high HL were more likely to decline immunisation. Information from professionals needs to match patients' HL levels to reduce negative perceptions of vaccination.
Effect of albumin-globulin score and albumin to globulin ratio on survival in patients with heart failure: a retrospective cohort study in China
Authors: Li Kuan , Fu Wanrong , Bo Yacong , Zhu Yongjian
Published: July 2018

Objective

To investigate the combined effect of albumin (ALB) and globulin (GLB) on the overall survival (OS) of patients with heart failure (HF).

Design

Retrospective cohort study.

Setting

A hospital.

Participants

404 patients first diagnosed with HF.

Measurements

Serum ALB and GLB were measured within 3 days after admission. The albumin to globulin ratio (AGR) was calculated as the ALB divided by the GLB. The receiver operating characteristic curve was used to calculate the cut-off points for ALB, GLB and AGR. Patients with low ALB levels (≤35.3 g/L) and high GLB levels (>27.0 g/L) were assigned an albumin-globulin score (AGS) of 2, those with only one of the two abnormalities were assigned an AGS of 1 and those with neither of the two abnormalities were assigned an AGS of 0.

Results

The mean age of the 404 patients was 62.69±15.62, and 54.5% were male. 14 patients were lost to follow-up. 120 patients died from HF and 211 patients were readmitted to the hospital for worsening HF. Multivariate Cox regression analysis showed that higher AGR was significantly associated with favourable OS (HR, 0.61, 95% CI 0.38 to 0.98, p=0.040) but not AGS.

Conclusion

Serum levels of ALB and GLB are objective and easily measurable biomarkers which can be used in combination to predict the survival of patients with HF.
Improving wait time from referral to opiate replacement therapy in a drug recovery service
Authors: Beattie Michelle , Hookway Gavin , Perera Michael , Calder Suzy , Hunter-Rowe Carolyn , van Woerden Hugo
Published: July 2018

While the reported incidence of heroin use in the UK has reduced, related hospital admissions and associated mortality have continued to increase. Prompt access to treatment (opiate replacement therapy (ORT) and counselling support) have been shown to reduce risk and offer clients the optimal route to recovery. The Specialist Drug and Alcohol Recovery Service (Osprey House) within National Health Service Highland had lengthy delays from referral to commencing ORT (median wait 56 days), which this project aimed to reduce.

A rapid process improvement workshop (RPIW) was undertaken to redesign the patient pathway from referral to recovery. The RPIW consisted of three phases: phase I, planning and preparation (12 weeks before the workshop week); phase II, the workshop week; and phase III, the follow-up. Metrics included the lead time from referral to initiating ORT and other process measures at baseline, and then repeated at 30, 60, 90 and 180 days, respectively. Additionally, data were routinely collected on the percentage of clients treated within 3 weeks, as was weekly data on the new process of screening clients within 1 day of referral. Multiple lean tools and techniques, including Plan, Do, Study, Act cycles, were used to test and implement new ways of working.

Results at 180 days found the median time from referral to initiating ORT improved from a baseline of 56 to 21 days (63% improvement), room usage improved from 49% to 65% (32% increase) and standard work improved from level 1 to level 3. Increases in the number of clients treated within 3 weeks were demonstrated. Other metrics remained static or reported fluctuations too inconsistent to claim improvement at this point.

By applying the Lean principles of removing waste and increasing value, we have redesigned our service, reducing the length of time clients with drug problems wait from referral to commencing ORT.
Implementation of a whole of hospital sepsis clinical pathway in a cancer hospital: impact on sepsis management, outcomes and costs
Authors: Thursky Karin , Lingaratnam Senthil , Jayarajan Jasveer , Haeusler Gabrielle M , Teh Benjamin , Tew Michelle , Venn Georgina , Hiong Alison , Brown Christine , Leung Vivian , Worth Leon J , Dalziel Kim , Slavin Monica A
Published: July 2018

Infection and sepsis are common problems in cancer management affecting up to 45% of patients and are associated with significant morbidity, mortality and healthcare utilisation.

Objective

To develop and implement a whole of hospital clinical pathway for the management of sepsis (SP) in a specialised cancer hospital and to measure the impact on patient outcomes and healthcare utilisation.

Methods

A multidisciplinary sepsis working party was established. Process mapping of practices for recognition and management of sepsis was undertaken across all clinical areas. A clinical pathway document that supported nurse-initiated sepsis care, prompt antibiotic and fluid resuscitation was implemented. Process and outcome measures for patients with sepsis were collected preimplementation (April–December 2012), postimplementation cohorts (April–December 2013), and from January to December 2014.

Results

323 patients were evaluated (111 preimplementation, 212 postimplementation). More patients with sepsis had lactate measured (75.0% vs 17.2%) and appropriate first dose antibiotic (90.1% vs 76.1%) (all p<0.05). Time to antibiotics was halved (55 vs 110 min, p<0.05). Patients with sepsis had lower rates of intensive care unit admission (17.1% vs 35.5%), postsepsis length of stay (7.5 vs 9.9 days), and sepsis-related mortality (5.0% vs 16.2%) (all p<0.05). Mean total hospital admission costs were lower in the SP cohort, with a significant difference in admission costs between historical and SP non-surgical groups of $A8363 (95% CI 81.02 to 16645.32, p=0.048) per patient on the pathway. A second cohort of 449 patients with sepsis from January to December 2014 demonstrated sustained improvement.

Conclusions

The SP was associated with significant improvement in patient outcomes and reduced costs. The SP has been sustained since 2013, and has been successfully implemented in another hospital with further implementations underway in Victoria.
Fluoroscopy-guided removal of a bitten endotracheal tube in an adult sheep
Authors: Lipiski Miriam , Fleischmann Thea , Sauer Mareike , Cesarovic Nikola
Published: July 2018

A 60 kg female white alpine sheep accidentally bit its endotracheal tube during the recovery phase after an experimental surgical intervention. The distal tube portion had slipped down the trachea and was no longer visible in the laryngeal opening. The distal tube part could be recovered rapidly under fluoroscopic guidance using endoscopic forceps. The remaining recovery time was uneventful and the animal was able to complete the study with no complications.
Efficiency and duality for vector optimization problem on Riemannian manifolds involving KT-B-invexity
Authors: Kumari Babli , Jayswal Anurag
Published: July 2018

In this paper, we consider a vector optimization problem on Riemannian manifolds for which we define KT-B-invex and KT-B-pseudoinvex functions. Further, we prove that every vector Kuhn–Tucker point is a weak efficient solution for considered vector optimization problem under the suitable assumptions. Moreover, we also study the Mond–Weir dual problem for the aforesaid problem and establish its weak, strong and converse duality results.
International Validation of the Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention in Post‐MI Patients: A Collaborative Analysis of the Chronic Kidney Disease Prognosis Consortium and the Risk Validation Scientific Committee
Authors: Mok Yejin , Ballew Shoshana H. , Bash Lori D. , Bhatt Deepak L. , Boden William E. , Bonaca Marc P. , Carrero Juan Jesus , Coresh Josef , D'Agostino Ralph B. , Elley C. Raina , Fowkes F. Gerry R. , Jee Sun Ha , Kovesdy Csaba P. , Mahaffey Kenneth W. , Nadkarni Girish , Peterson Eric D. , Sang Yingying , Matsushita Kunihiro
Published: July 2018

Background

The Thrombolysis in Myocardial Infarction (TIMI) Risk Score for Secondary Prevention (TRS2°P), a 0‐to‐9‐point system based on the presence/absence of 9 clinical factors, was developed to classify the risk of major adverse cardiovascular events (
MACE
) (a composite of cardiovascular death, recurrent myocardial infarction, or ischemic stroke) among patients with a recent myocardial infarction. Its performance has not been examined internationally outside of a clinical trial setting.

Methods and Results

We evaluated the performance of TRS2°P for predicting
MACE
in 53 599 patients with recent myocardial infarction in 5 international cohorts from New Zealand, South Korea, Sweden, and the United States participating in the Chronic Kidney Disease Prognosis Consortium. Overall, there were 19 444 cases of
MACE
across 5 cohorts over a mean follow‐up of 5 years, and the overall
MACE
rate ranged from 5.0 to 18.4 (per 100 person‐years). The TRS2°P showed modest calibration (Brier score ranged from 0.144 to 0.173) and discrimination (C‐statistics >0.61 in all studies except 1 from Korea with 0.55) across cohorts relative to its original Brier score of 0.098 and C‐statistic of 0.67 in the derived data set. Although there was some heterogeneity across cohorts, the 9 predictors in the TRS2°P were generally associated with higher
MACE
risk, with strongest associations observed (meta‐analyzed adjusted hazard ratio 1.6–1.7) for history of heart failure, age ≥75 years, and prior stroke, followed by peripheral artery disease, kidney dysfunction, diabetes mellitus, and hypertension (hazard ratio 1.3–1.4). Prior coronary bypass graft surgery and smoking did not reach statistical significance (hazard ratio ≈1.1).

Conclusions

TRS2°P, a simple scoring system with 9 routine clinical factors, was modestly predictive of secondary events when applied in patients with recent myocardial infarction from diverse clinical and geographic settings.
Unintentional Cooperation
Authors: Kita Terry
Published: July 2018

This study of the Friendship Doll Mission of 1926-1927 shows how, in the United States, the Japanese doll was part of the inescapable image of a kimono-clad little Japanese girl, and functioned to further existing anti-Japanese implications of that image. It further shows how an American popular-culture mission to improve relations with Japan by having American children exchange dolls with Japanese children, created an official, Japanese government response that presented the United States with Japanese dolls that were objects of Fine Art. Despite the different views of the Doll Mission in Japan and the US, an interchange resulted that, now nearly a century later, continues. The article uses Japanese dolls to demonstrate how genuine cultural exchange can occur even when the methods, approaches, and the very intent of those involved in it differ, in order to highlight the importance of considering both perspectives to understand phenomena such as Japonisme.