bluuebunny/crossref_metadata_2025 huggingface dataset:
ABC Transporters Required for Hexose Uptake by Clostridium phytofermentans
Authors: Cerisy Tristan , Iglesias Alba , Rostain William , Boutard Magali , Pelle Christine , Perret Alain , Salanoubat Marcel , Fierobe Henri-Pierre , Tolonen Andrew C.
Published: May 2019

Plant-fermenting
Clostridia
are anaerobic bacteria that recycle plant matter in soil and promote human health by fermenting dietary fiber in the intestine.
Clostridia
degrade plant biomass using extracellular enzymes and then uptake the liberated sugars for fermentation. The main sugars in plant biomass are hexoses, and here, we identify how hexoses are taken in to the cell by the model organism
Clostridium phytofermentans
. We show that this bacterium uptakes hexoses using a set of highly specific, nonredundant ABC transporters. Once in the cell, the hexoses are phosphorylated by intracellular hexokinases. This study provides insight into the functioning of abundant members of soil and intestinal microbiomes and identifies gene targets to engineer strains for industrial lignocellulosic fermentation.
Metabolomics Studies To Decipher Stress Responses in Mycobacterium smegmatis Point to a Putative Pathway of Methylated Amine Biosynthesis
Authors: Rizvi Arshad , Yousf Saleem , Balakrishnan Kannan , Dubey Harish Kumar , Mande Shekhar C. , Chugh Jeetender , Banerjee Sharmistha
Published: May 2019

Alterations in metabolite levels provide fast and direct means to regulate enzymatic reactions and, therefore, metabolic pathways. This study documents, for the first time, the metabolic changes that occur in
Mycobacterium smegmatis
as a response to three stresses, namely, acidic stress, oxidative stress, and nutrient starvation. These stresses are also faced by intracellular mycobacteria during infection and therefore may be extended to frame therapeutic interventions for pathogenic mycobacteria. In addition to the purine-pyrimidine, amino acid, nicotinate-nicotinamide, and energy metabolism pathways that were found to be affected in response to different stresses, a novel putative methylamine biosynthesis pathway was identified to be present in
Mycobacterium smegmatis
.
Implications of Bacteriophage- and Bacteriophage Component-Based Therapies for the Clinical Microbiology Laboratory
Authors: Caflisch Katherine M. , Patel Robin
Published: May 2019

Treatment of bacterial infections is increasingly challenged by resistance to currently available antibacterial agents. Not only are such agents less likely to be active today than they were in the past, but their very use has selected for and continues to select for further resistance. Additional strategies for the management of bacterial illnesses must be identified. In this review, bacteriophage-based therapies are presented as one promising approach.
The New, New Daptomycin Breakpoint for
Enterococcus
spp
Authors: Humphries Romney M.
Published: May 2019

In 2019, the Clinical and Laboratory Standards Institute revised the daptomycin breakpoints for
Enterococcus
spp. twice in rapid succession.
Mx1 in Hematopoietic Cells Protects against Thogoto Virus Infection
Authors: Spitaels Jan , Van Hoecke Lien , Roose Kenny , Kochs Georg , Saelens Xavier
Published: May 2019

Mx proteins are evolutionarily conserved in vertebrates and can restrict a wide range of viruses in a cell-autonomous way. The contribution to antiviral defense of Mx1 expression in hematopoietic cells remains largely unknown. We show that protection against influenza virus infection requires
Mx1
expression in the nonhematopoietic cellular compartment. In contrast,
Mx1
in bone marrow-derived cells is sufficient to control disease and virus replication following infection with a Thogoto virus. This indicates that, in addition to its well-established antiviral activity in nonhematopoietic cells, Mx1 in hematopoietic cells can also play an important antiviral function. In addition, cells of hematopoietic origin that lack a functional
Mx1
gene contribute to Thogoto virus dissemination and associated disease.
CD4+T Cells Drive Lung Disease Enhancement Induced by Immunization with Suboptimal Doses of Respiratory Syncytial Virus Fusion Protein in the Mouse Model
Authors: Schneider-Ohrum Kirsten , Snell Bennett Angie , Rajani Gaurav Manohar , Hostetler Leigh , Maynard Sean K. , Lazzaro Michelle , Cheng Lily I. , O’Day Terrence , Cayatte Corinne
Published: May 2019

RSV poses a significant health care burden and is the leading cause of serious lower-respiratory-tract infections in young children. A formalin-inactivated RSV vaccine developed in the 1960s not only showed a complete lack of efficacy against RSV infection but also induced severe lung disease enhancement in vaccinated children. Since then, establishing safety in preclinical models has been one of the major challenges to RSV vaccine development. We recently observed in the cotton rat model that suboptimal immunizations with RSV fusion protein could induce lung disease enhancement. In the present study, we extended suboptimal dosing evaluation to the mouse model. We confirmed the induction of lung disease enhancement by vaccinations with low antigen doses and dissected the associated immune mechanisms. Our results stress the need to evaluate suboptimal dosing for any new RSV vaccine candidate developed for seronegative infants.
Complete Genome Sequence of Genotype Psittacine Beak and Feather Disease Virus, a Strain Identified from Budgerigars in China
Authors: Cheng Rujia , Mao Yaqing , Li Qiuchen , Xie Shijie , Xia Yingju , Sun Haojie , Niu Kai , Sun Shijing , Li Jie , Feng Yu , Peng Xiaowei , Jiang Hui , Zhu Liangquan , Fan Xuezheng , Lin Zhanye , Ding Jiabo , Qin Yuming , Xu Guanlong
Published: May 2019

Psittacine beak and feather disease virus (PBFDV) has been reported in many countries, such as Australia, Poland, the United States, South Africa, etc. In this study, the complete genome of a PBFDV isolate was determined and characterized from budgerigars in China.
Draft Genome Sequence of Enterococcus faecalis Strain CECT7121, a Corn Silage Isolate with Antibacterial Activity against Gram-Positive Pathogens
Authors: Delpech Gastón , Hebert Elvira M. , Sparo Mónica , Saavedra Lucila
Published: May 2019

Enterococcus faecalis
CECT7121 is a corn silage probiotic bacterium that shows antibacterial activity against Gram-positive pathogens from different origins. Its genome sequence is 2.9 Mb long with a G+C content of 37.3%.
Draft Genome Sequences of
Leishmania
(
Leishmania
)
amazonensis
,
Leishmania
(
Leishmania
)
mexicana
, and
Leishmania
(
Leishmania
)
aethiopica
, Potential Etiological Agents of Diffuse Cutaneous Leishmaniasis
Authors: Batra Dhwani , Lin Wuling , Narayanan Vidhya , Rowe Lori A. , Sheth Mili , Zheng Yueli , Loparev Vladimir , de Almeida Marcos
Published: May 2019

We present here the draft genome sequences of
Leishmania
(
Leishmania
)
amazonensis
,
Leishmania
(
Leishmania
)
mexicana
, and
Leishmania
(
Leishmania
)
aethiopica
, potential etiological agents of diffuse cutaneous leishmaniasis (DCL). Sequence data were obtained using PacBio and MiSeq platforms.
Complete Genome Sequence of Escherichia coli MT102, a Plasmid-Free Recipient Resistant to Rifampin, Azide, and Streptomycin, Used in Conjugation Experiments
Authors: Valcek Adam , Overballe-Petersen Søren , Hansen Frank , Dolejska Monika , Hasman Henrik
Published: May 2019

We present here the complete genome sequence of
Escherichia coli
MT102, which is resistant to rifampin, azide, and streptomycin and is used as a recipient in plasmid transfer experiments. The sequence will be utilized for chromosomal read removal in plasmid sequence analyses obtained from transconjugants within this strain and in comprehensive genetic studies.
Draft Genome Sequences of Type VI Secretion System-Encoding Vibrio fischeri Strains FQ-A001 and ES401
Authors: Bultman Katherine M. , Cecere Andrew G. , Miyashiro Tim , Septer Alecia N. , Mandel Mark J.
Published: May 2019

The type VI secretion system (T6SS) facilitates lethal competition between bacteria through direct contact. Comparative genomics has facilitated the study of these systems in
Vibrio fischeri
, which colonizes the squid host
Euprymna scolopes
.
Complete Genome Sequences of Nine Mycobacteriophages from New Zealand, Beatrix, Carthage, Daegal, Dulcie, Fancypants, Fenn, Inca, Naira, and Robyn
Authors: Davies C. G. , Wojtus J. K. , Gilligan C. E. R. , Latu S. F. , Manning T. J. , Meyer C. E. , Nersesyan J. , Tennent R. I. , Oosthuizen L. , Palmer E. , Hoskin A. F. M. , Turnbull J. , Sweatman J. A. , Elliston-Boyes N. , Wallace C. J. , Baxter A. , Borrie Z. , Elder J. S. , Massey O. , Wong A. , Silander O. K. , Freed N. E. , Hendrickson H. L.
Published: May 2019

Beatrix, Carthage, Daegal, Dulcie, Fancypants, Fenn, Inca, Naira, and Robyn are newly isolated bacteriophages capable of infecting
Mycolicibacterium smegmatis
mc
2
155. We discovered, sequenced, and annotated these New Zealand bacteriophages.
Identification of an Immunogenic Broadly Inhibitory Surface Epitope of the Plasmodium vivax Duffy Binding Protein Ligand Domain
Authors: George Miriam T. , Schloegel Jesse L. , Ntumngia Francis B. , Barnes Samantha J. , King Christopher L. , Casey Joanne L. , Foley Michael , Adams John H.
Published: May 2019

Vivax malaria is the second leading cause of malaria worldwide and the major cause of non-African malaria. Unfortunately, efforts to develop antimalarial vaccines specifically targeting
Plasmodium vivax
have been largely neglected, and few candidates have progressed into clinical trials. The Duffy binding protein is considered a leading blood-stage vaccine candidate because this ligand’s recognition of the Duffy blood group reticulocyte surface receptor is considered essential for infection. This study identifies a new target epitope on the ligand’s surface that may serve as the target of vaccine-induced binding-inhibitory antibody (BIAb). Understanding the potential targets of vaccine protection will be important for development of an effective vaccine.
Disarming Pore-Forming Toxins with Biomimetic Nanosponges in Intraocular Infections
Authors: Coburn Phillip S. , Miller Frederick C. , LaGrow Austin L. , Land Craig , Mursalin Huzzatul , Livingston Erin , Amayem Omar , Chen Yijie , Gao Weiwei , Zhang Liangfang , Callegan Michelle C.
Published: May 2019

Endophthalmitis is a blinding consequence of bacterial invasion of the interior of the eye. Because of increases in the numbers of ocular surgeries and intraocular injections, the incidence of endophthalmitis is steadily increasing.
Staphylococcus aureus
,
Enterococcus faecalis
,
Streptococcus pneumoniae
, and
Bacillus cereus
are leading causes of infection following ocular procedures and trauma and are increasingly more difficult to treat due to multidrug resistance. Each of these pathogens produces pore-forming toxins that contribute to the pathogenesis of endophthalmitis. Treatment of these infections with antibiotics alone is insufficient to prevent damage to the retina and vision loss. Therefore, novel therapeutics are needed that include agents that neutralize bacterial pore-forming toxins. Here, we demonstrate that biomimetic nanosponges neutralize pore-forming toxins from these ocular pathogens and aid in preserving retinal function. Nanosponges may represent a new form of adjunct antitoxin therapy for serious potentially blinding intraocular infections.
Ethnic and socioeconomic variation in cause-specific preterm infant mortality by gestational age at birth: national cohort study
Authors: Kroll Mary E , Kurinczuk Jennifer J , Hollowell Jennifer , Macfarlane Alison , Li Yangmei , Quigley Maria A
Published: May 2019

Objective

To describe ethnic and socioeconomic variation in cause-specific infant mortality of preterm babies by gestational age at birth.

Design

National birth cohort study.

Setting

England and Wales 2006–2012.

Subjects

Singleton live births at 24–36 completed weeks’ gestation (n=256 142).

Outcome measures

Adjusted rate ratios for death in infancy by cause (three groups), within categories of gestational age at birth (24–27, 28–31, 32–36 weeks), by baby’s ethnicity (nine groups) or area deprivation score (Index of Multiple Deprivation quintiles).

Results

Among 24–27 week births (5% of subjects; 47% of those who died in infancy), all minority ethnic groups had lower risk of immaturity-related death than White British, the lowest rate ratios being 0.63 (95% CI 0.49 to 0.80) for Black Caribbean, 0.74 (0.64 to 0.85) for Black African and 0.75 (0.60 to 0.94) for Indian. Among 32–36 week births, all minority groups had higher risk of death from congenital anomalies than White British, the highest rate ratios being 4.50 (3.78 to 5.37) for Pakistani, 2.89 (2.10 to 3.97) for Bangladeshi and 2.06 (1.59 to 2.68) for Black African; risks of death from congenital anomalies and combined rarer causes (infection, intrapartum conditions, SIDS and unclassified) increased with deprivation, the rate ratios comparing the most with the least deprived quintile being, respectively, 1.54 (1.22 to 1.93) and 2.05 (1.55 to 2.72). There was no evidence of socioeconomic variation in deaths from immaturity-related conditions.

Conclusions

Gestation-specific preterm infant mortality shows contrasting ethnic patterns of death from immaturity-related conditions in extremely-preterm babies, and congenital anomalies in moderate/late-preterm babies. Socioeconomic variation derives from congenital anomalies and rarer causes in moderate/late-preterm babies. Future research should examine biological origins of extremely preterm birth.
Pfeifer-Weber-Christian disease and successful treatment with mycophenolate mofetil: a case report
Authors: Somalanka Subash , Udo Ini , Nair Hari , Baikunje Shashidhar
Published: May 2019

Inflammatory conditions manifest with a broad spectrum of signs and symptoms. Panniculitis is such a condition affecting the subcutaneous fat and presents as tender erythematous nodules. It is also associated with a systemic response and has been described in the literature as early as in 1892 by Pfeifer and in the 1920s by Weber and Christian. We present an unusual case of a Caucasian man with recurrent febrile illness, systemic inflammatory response and renal dysfunction requiring acute high dependency care. The authors successfully treated him with an antiproliferative agent, mycophenolate mofetil, which resulted in preventing him from having further episodes.
Determinants of the decline in mortality from acute stroke in England: linked national database study of 795 869 adults
Authors: Seminog Olena O , Scarborough Peter , Wright F Lucy , Rayner Mike , Goldacre Michael J
Published: May 2019

Objectives

To study trends in stroke mortality rates, event rates, and case fatality, and to explain the extent to which the reduction in stroke mortality rates was influenced by changes in stroke event rates or case fatality.

Design

Population based study.

Setting

Person linked routine hospital and mortality data, England.

Participants

795 869 adults aged 20 and older who were admitted to hospital with acute stroke or died from stroke.

Main outcome measures

Stroke mortality rates, stroke event rates (stroke admission or stroke death without admission), and case fatality within 30 days after stroke.

Results

Between 2001 and 2010 stroke mortality rates decreased by 55%, stroke event rates by 20%, and case fatality by 40%. The study population included 358 599 (45%) men and 437 270 (55%) women. Average annual change in mortality rate was −6.0% (95% confidence interval −6.2% to −5.8%) in men and −6.1% (−6.3% to −6.0%) in women, in stroke event rate was −1.3% (−1.4% to −1.2%) in men and −2.1% (−2.2 to −2.0) in women, and in case fatality was −4.7% (−4.9% to −4.5%) in men and −4.4% (−4.5% to −4.2%) in women. Mortality and case fatality but not event rate declined in all age groups: the stroke event rate decreased in older people but increased by 2% each year in adults aged 35 to 54 years. Of the total decline in mortality rates, 71% was attributed to the decline in case fatality (78% in men and 66% in women) and the remainder to the reduction in stroke event rates. The contribution of the two factors varied between age groups. Whereas the reduction in mortality rates in people younger than 55 years was due to the reduction in case fatality, in the oldest age group (≥85 years) reductions in case fatality and event rates contributed nearly equally.

Conclusions

Declines in case fatality, probably driven by improvements in stroke care, contributed more than declines in event rates to the overall reduction in stroke mortality. Mortality reduction in men and women younger than 55 was solely a result of a decrease in case fatality, whereas stroke event rates increased in the age group 35 to 54 years. The increase in stroke event rates in young adults is a concern. This suggests that stroke prevention needs to be strengthened to reduce the occurrence of stroke in people younger than 55 years.
Physicians’ role in the development of inappropriate polypharmacy among older adults in Iran: a qualitative study
Authors: Mortazavi Seyede Salehe , Shati Mohsen , Malakouti Seyed Kazem , Khankeh Hamid Reza , Mehravaran Shiva , Ahmadi Fazlollah
Published: May 2019

Objectives

The use of unnecessary or excessive medications (inappropriate polypharmacy) is a major health challenge among older adults which is driven by several factors. This study aims to provide in-depth descriptions of the physician’s role in the development of inappropriate polypharmacy among older adults in Iran.

Design

Qualitative content analysis of interviews, field notes and other relevant documents available (eg, medical records). Data collection and analyses were done concurrently to guide the sampling process.

Setting

Three purposively selected referral hospitals in Tehran, Iran.

Participants

A total of 7 physicians, 10 older adults, 3 caregivers and 3 pharmacists with a median age of 54 (IQR 23) years were recruited through convenience sampling.

Results

Emerged categories included misdiagnosis, inappropriate prescribing, insufficient patient education, poor communication, unprofessional behaviour and limited perspectives which highlight the role of physicians in the development of inappropriate polypharmacy among older adults in Iran under the main concept of poor medical practice.

Conclusion

This study provides valuable insight on the role of physicians in the development of inappropriate polypharmacy among the elderly in the healthcare setting in Iran by exploring the viewpoints of physicians, patients, caregivers and pharmacists. Physicians can be an influential factor in tackling this challenge through proper diagnosis, prescription, patient education and follow-up. In Iran, physicians’ practice styles are affected by potentially adverse factors such as the novelty of geriatric medicine, lack of a referral system, patient unfamiliarity with the system and lack of a monitoring system for multiple prescriptions. Furthermore, clinics tend to be overcrowded and visit fees can be low; in this setting, lack of physician assistants leads to limited time allocation to each patient and physician dissatisfaction with their income.
Melatonin, temazepam and placebo in hospitalised older patients with sleeping problems (MATCH): a study protocol of randomised controlled trial
Authors: Stenveld Fiona , Bosman Sjanne , van Munster Barbara C , Beishuizen Sara J , Hempenius Liesbeth , van der Velde Nathalie , Smidt Nynke , de Rooij Sophia E
Published: May 2019

Introduction

Hospitalised older patients frequently suffer from inadequate sleep, which can lead to patient distress and delayed recovery from acute illness or surgical procedure. Currently, no evidence-based treatments exist for sleeping problems in hospitalised older patients. Benzodiazepines, such as temazepam, are regularly prescribed by physicians, although they have serious side effects; for older patients in particular. Melatonin is proposed as a safe alternative for sleeping problems in hospitalised older patients, but the efficacy of melatonin is unclear in this population. Therefore, the aim of this study is to investigate the effects of melatonin and temazepam compared with placebo on sleep quality among hospitalised older patients with sleeping problems.

Methods and analysis

This study is a multicentre, randomised, placebo-controlled trial. A total of 663 patients will be randomised in a 1:1:1 fashion to receive either melatonin (n=221), temazepam (n=221) or placebo (n=221). The study population consists of hospitalised patients aged 60 years and older, with new or aggravated sleeping problems for which an intervention is needed. The primary outcome is sleep quality measured with the Leeds Sleep Evaluation Questionnaire (LSEQ). Secondary outcomes include sleep parameters measured with actigraphy and medication-related adverse effects.

Ethics and dissemination

This study was approved by the Medical Ethics Committee of the Academic Medical Centre Amsterdam, (No 2015_302). Study findings will be disseminated through presentations at professional and scientific conferences and publications in peer-reviewed journals.

Trial registration number

NTR6908; Pre-results.
Evaluation of the digital diabetes prevention programme pilot: uncontrolled mixed-methods study protocol
Authors: Murray Elizabeth , Daff Kerry , Lavida Anthi , Henley William , Irwin Jenny , Valabhji Jonathan
Published: May 2019

Introduction

The prevalence of type 2 diabetes is rising steeply. National Health Service England (NHSE) is exploring the potential of a digital diabetes prevention programme (DDPP) and has commissioned a pilot with embedded evaluation.

Methods and analysis

This study aims to determine whether, and if so, how, should NHSE implement a national DDPP, using a mixed-methods pretest and post-test design, underpinned by two theoretical frameworks: the Coventry, Aberdeen and London - Refined (CALO-RE) taxonomy of behavioural change techniques for the digital interventions and the Consolidated Framework for Implementation Research (CFIR) for implementation processes. In eight pilot areas across England, adults with non-diabetic hyperglycaemia (NDH) (glycated haemoglobin (HbA1c) 42–47 mmol/mol or fasting plasma glucose 5.5–6.9 mmol/L) and adults without NDH who are overweight (body mass index (BMI) >25 kg/m2) or obese (BMI >30 kg/m2) will be referred to one of five digitally delivered diabetes prevention interventions. The primary outcomes are reduction in HbA1c and weight (for people with NDH) and reduction in weight (for people who are overweight or obese) at 12 months. Secondary outcomes include use of the intervention, satisfaction, physical activity, patient activation and resources needed for successful implementation. Quantitative data will be collected at baseline, 6 months and 12 months by the digital intervention providers. Qualitative data will be collected through semistructured interviews with commissioners, providers, healthcare professionals and patients. Quantitative data will be analysed descriptively and using generalised linear models to determine whether changes in outcomes are associated with demographic and intervention factors. Qualitative data will be analysed using framework analysis, with data pertaining to implementation mapped onto the CFIR.

Ethics and dissemination

The study has received ethical approval from the Public Health England Ethics and Research Governance Group (reference R&D 324). Dissemination will include a report to NHSE to inform future policy and publication in peer-reviewed journals.
School-based physical activity intervention for older adolescents: rationale and study protocol for the Burn 2 Learn cluster randomised controlled trial
Authors: Leahy Angus A , Eather Narelle , Smith Jordan J , Hillman Charles , Morgan Philip J , Nilsson Michael , Lonsdale Chris , Plotnikoff Ronald C , Noetel Michael , Holliday Elizabeth , Shigeta Tatsuya T , Costigan Sarah A , Walker Frederick R , Young Sarah , Valkenborghs Sarah R , Gyawali Prajwal , Harris Nigel , Kennedy Sarah G , Lubans David R
Published: May 2019

Introduction

This trial aims to investigate the impact of a school-based physical activity programme, involving high-intensity interval training (HIIT), on the physical, mental and cognitive health of senior school students.

Methods and analysis

The Burn 2 Learn (B2L) intervention will be evaluated using a two-arm parallel group cluster randomised controlled trial with allocation occurring at the school level (to treatment or wait-list control). Schools will be recruited in two cohorts from New South Wales, Australia. The trial will aim to recruit ~720 senior school students (aged 16–18 years) from 20 secondary schools (ie, 10 schools per cohort). A range of implementation strategies will be provided to teachers (eg, training, equipment and support) to facilitate the delivery of HIIT sessions during scheduled classes. In phase I and II (3 months each), teachers will facilitate the delivery of at least two HIIT sessions/week during lesson-time. In phase III (6 months), students will be encouraged to complete sessions outside of lesson-time (teachers may continue to facilitate the delivery of B2L sessions during lesson-time). Study outcomes will be assessed at baseline, 6 months (primary end point) and 12 months. Cardiorespiratory fitness (shuttle run test) is the primary outcome. Secondary outcomes include: vigorous physical activity, muscular fitness, cognition and mental health. A subsample of students will (i) provide hair samples to determine their accumulated exposure to stressful events and (ii) undergo multimodal MRI to examine brain structure and function. A process evaluation will be conducted (ie, recruitment, retention, attendance and programme satisfaction).

Ethics and dissemination

This study has received approval from the University of Newcastle (H-2016–0424) and the NSW Department of Education (SERAP: 2017116) human research ethics committees.

Trial registration number

ACTRN12618000293268; Pre-results.
Patients’ decision-making, experiences and preferences regarding pixantrone treatment in relapsed or refractory diffuse large B-cell lymphoma: study protocol for a longitudinal mixed methods study
Authors: van Hoogdalem Lothar E , Siemes Claire , Lugtenburg Pieternella J , Busschbach Jan J V , Ismail Sohal Y
Published: May 2019

Introduction

There is a lot of speculation about why and how patients decide to use invasive treatment in an advanced stage of cancer, but the body of research is limited. The present longitudinal qualitative and quantitative study reflects real-life practice of pixantrone use and aims to collect data on patients’ considerations for, expectations of and experiences with pixantrone and trajectories in their quality-of-life (QoL) values in a Dutch clinical setting. Hence, two questions emerge. Why do patients choose for this treatment, while the treatment success rate is limited and curation cannot be achieved? And second, once chosen, what conditions would patients like to satisfy and how do they experience the treatment?

Methods and analysis

This is a non-interventional longitudinal and multicentre study. Patients are eligible if they are >18 years, have never been treated with pixantrone before, have an Eastern Cooperative Oncology Group performance score ≤2, have a relapsed or refractory diffuse large B-cell lymphoma and have been treated with at least two prior regimens. The decision to treat patients with pixantrone has been taken by the treating physician before patients are asked to participate in the study. If patients refuse study participation after being informed by the investigator, reasons for refusal (if given) will be recorded. Participants will receive at least three interviews accompanied by three QOL questionnaires. Based on the required sample size, we aim to include 20 patients over a period of 2 years.

Ethics and dissemination

The Medical Ethical Committee of Erasmus MC, Rotterdam, The Netherlands, has approved this study. The results will be disseminated in peer-reviewed journals and major international conferences. The study is non-interventional and falls therefore not under Medical Research Involving Human Subjects Act (In Dutch: Wet medisch-wetenschappelijk onderzoek met mensen; WMO). Hence, this study is approved to be carried out in the Erasmus MC. Each other participating centre will receive this approval and will separately undergo the ethical approval to be able to participate. In addition to the ethical approval, the participating centres need to obtain written informed consent of their patients. Given the non-interventional nature of this study, a study registration was considered but deemed unnecessary. The study will be conducted in accordance with the Declaration of Helsinki (Tokyo, Venice, Hong Kong and Somerset West amendments). A sequential identification number will be automatically attributed to each patient that has given consent to participate in the study. This number will identify the patient and must be included on all documents. Only the main researcher can link the code to the patient’s identity.
Performance of host blood transcriptomic signatures for diagnosing and predicting progression to tuberculosis disease in HIV-negative adults and adolescents: a systematic review protocol
Authors: Mulenga Humphrey , Bunyasi Erick Wekesa , Mbandi Stanley Kimbung , Mendelsohn Simon C , Kagina Benjamin , Penn-Nicholson Adam , Scriba Thomas , Hatherill Mark
Published: May 2019

Introduction

One-quarter of the global population, including the majority of adults in tuberculosis (TB) endemic countries, are estimated to beMycobacterium tuberculosis(MTB) infected. An estimated 10 million new TB cases occurred in 2017. One of the biggest challenges confronting TB control is the lack of accurate diagnosis and prediction of prevalent and incident TB disease, respectively. Several host blood transcriptomic messenger RNA (mRNA) signatures that reflect the host immune response following infection with MTB and progression to TB disease in different study populations have recently been published, but these TB biomarkers have not been systematically described. We will conduct a systematic review of the performance of host blood transcriptional signatures for TB diagnosis and prediction of progression to TB disease.

Methods and analysis

This systematic review will involve conducting a comprehensive literature search of cohort, case–control, cross-sectional and randomised-controlled studies of the performance of host blood transcriptomic signatures for TB diagnosis and prediction of progression to TB disease. We will search Medline via PubMed, Scopus, Web of Science and EBSCO libraries, complemented by a search of bibliographies of selected articles for other relevant articles. The literature search will be restricted to studies published in English from 2005 to 2018 and conducted in HIV-uninfected adults and adolescents (≥12 years old). Forest plots and a narrative synthesis of the findings will be provided. The primary outcomes will be sensitivity, specificity, as well as true/false positives and true/false negatives. Heterogeneity resulting from differences in the design, composition and structure of individual signatures will preclude meta-analysis and pooling of results.

Ethics and dissemination

Ethics approval is not required for this systematic review protocol. The results of this review will be disseminated through a peer-reviewed journal as well as conference presentations.

PROSPERO registration number

CRD42017073817.
Retrospective evaluation of healthcare utilisation and mortality of two post-discharge care programmes in Singapore
Authors: Ang Ian Yi Han , Tan Chuen Seng , Nurjono Milawaty , Tan Xin Quan , Koh Gerald Choon-Huat , Vrijhoef Hubertus Johannes Maria , Tan Shermin , Ng Shu Ee , Toh Sue-Anne
Published: May 2019

Objective

To evaluate the impact on healthcare utilisation frequencies and charges, and mortality of a programme for frequent hospital utilisers and a programme for patients requiring high acuity post-discharge care as part of an integrated healthcare model.

Design

A retrospective quasi-experimental study without randomisation where patients who received post-discharge care interventions were matched 1:1 with unenrolled patients as controls.

Setting

The National University Health System (NUHS) Regional Health System (RHS), which was one of six RHS in Singapore, implemented the NUHS RHS Integrated Interventions and Care Extension (NICE) programme for frequent hospital utilisers and the NUHS Transitional Care Programme (NUHS TCP) for high acuity post-discharge care. The programmes were supported by the Ministry of Health in Singapore, which is a city-state nation located in Southeast Asia with a 5.6 million population.

Participants

Linked healthcare administrative data, for the time period of January 2013 to December 2016, were extracted for patients enrolled in NICE (n=554) or NUHS TCP (n=270) from June 2014 to December 2015, and control patients.

Interventions

For both programmes, teams conducted follow-up home visits and phone calls to monitor and manage patients’ post-discharge.

Primary outcome measures

One-year pre- and post-enrolment healthcare utilisation frequencies and charges of all-cause inpatient admissions, emergency admissions, emergency department attendances, specialist outpatient clinic (SOC) attendances, total inpatient length of stay and mortality rates were compared.

Results

Patients in NICE had lower mortality rate, but higher all-cause inpatient admission, emergency admission and emergency department attendance charges. Patients in NUHS TCP did not have lower mortality rate, but had higher emergency admission and SOC attendance charges.

Conclusions

Both NICE and NUHS TCP had no improvements in 1 year healthcare utilisation across various setting and metrics. Singular interventions might not be as impactful in effecting utilisation without an overhauling transformation and restructuring of the hospital and healthcare system.
Perioperative Pain and Addiction Interdisciplinary Network (PAIN): protocol of a practice advisory for the perioperative management of buprenorphine using a modified Delphi process
Authors: Goel Akash , Azargive Saam , Weissman Joel S , Shanthanna Harsha , Ladha Karim S , Lamba Wiplove , Duggan Scott , Hanlon John G , Di Renna Tania , Peng Philip , Clarke Hance
Published: May 2019

Introduction

The ongoing opioid epidemic has necessitated increasing prescriptions of buprenorphine, which is an evidence-based treatment for opioid use disorder, and also shown to reduce harms associated with unsafe opioid administration. A systematic review of perioperative management strategies for patients taking buprenorphine concluded that there was little guidance for managing buprenorphine perioperatively. The aim of this project is to develop consensus guidelines on the optimal perioperative management strategies for this group of patients. In this paper, we present the design for a modified Delphi technique that will be used to gain consensus among patients and multidisciplinary experts in addiction, pain, community and perioperative medicine.

Methods and analysis

A national panel of experts identified by perioperative, pain and/or addiction systematic review authorship established an international profile in perioperative, pain and/or addiction research, community clinical excellence and by peer referral. A steering group will develop the first round with a list of indications to be rated by the panel of national experts, patients and allied healthcare professionals. In round 1, the expert panel will rate the appropriateness of each individual item and provide additional suggestions for revisions, additions or deletions. The definition of consensus will be seta priori. Consensus will be gauged for both appropriateness and inappropriateness of treatment strategies. Where an agreement is not reached and items are suggested for addition/deletion/modification, round 2 will take place over teleconference in order to obtain consensus.

Ethics and dissemination

Institutional research ethics board provided a waiver for this modified Delphi protocol. We plan on developing a national guideline for the management of patients taking buprenorphine in the perioperative period that will be generalisable across three sets of preoperative diagnoses including opioid use disorder and/or co-occurring pain disorders. The findings will be published in peer-reviewed publications and conference presentations.
Proactive healthcare for frail elderly persons: study protocol for a prospective controlled primary care intervention in Sweden
Authors: Marcusson Jan , Nord Magnus , Johansson Maria M , Alwin Jenny , Levin Lars-Åke , Dannapfel Petra , Thomas Kristin , Poksinska Bonnie , Sverker Annette , Olaison Anna , Cedersund Elisabet , Kelfve Susanne , Motel-Klingebiel Andreas , Hellström Ingrid , Kullberg Agneta , Böttiger Ylva , Dong Huan-Ji , Peolsson Anneli , Wass Malin , Lyth Johan , Andersson Agneta
Published: May 2019

Introduction

The provision of healthcare services is not dedicated to promoting maintenance of function and does not target frail older persons at high risk of the main causes of morbidity and mortality. The aim of this study is to evaluate the effects of a proactive medical and social intervention in comparison with conventional care on a group of persons aged 75 and older selected by statistical prediction.

Methods and analysis

In a pragmatic multicentre primary care setting (n=1600), a prediction model to find elderly (75+) persons at high risk of complex medical care or hospitalisation is used, followed by proactive medical and social care, in comparison with usual care. The study started in April 2017 with a run-in period until December 2017, followed by a 2-year continued intervention phase that will continue until the end of December 2019. The intervention includes several tools (multiprofessional team for rehabilitation, social support, medical care home visits and telephone support). Primary outcome measures are healthcare cost, number of hospital care episodes, hospital care days and mortality. Secondary outcome measures are number of outpatient visits, cost of social care and informal care, number of prescribed drugs, health-related quality of life, cost-effectiveness, sense of security, functional status and ability. We also study the care of elderly persons in a broader sense, by covering the perspectives of the patients, the professional staff and the management, and on a political level, by using semistructured interviews, qualitative methods and a questionnaire.

Ethics and dissemination

Approved by the regional ethical review board in Linköping (Dnr 2016/347-31). The results will be presented in scientific journals and scientific meetings during 2019–2022 and are planned to be used for the development of future care models.

Trial registration number

NCT03180606.
Feasibility of wearable cameras to assess screen time and time spent restrained in children aged 3 to 5 years: a study protocol
Authors: Downing Katherine L , Janssen Xanne , Reilly John J
Published: May 2019

Introduction

Wearable cameras may help overcome the limitations of existing tools to measure young children’s sedentary behaviour, but their use introduces a range of ethical challenges. The primary aim of this study is to determine the feasibility of using wearable cameras to measure the two aspects of sedentary behaviour currently included in evidence-based guidelines (ie, screen time and time spent restrained). If shown to be feasible, a secondary aim will be to validate subjective measures against the directly measured screen time and time spent restrained.

Methods and analysis

A convenience sample (n=20) will be recruited via flyers at the University of Strathclyde and advertisements on online forums for parents of young children (aged 3 to 5 years). Children will be provided with a wearable camera, attached to the front of their clothing with a clip, to be worn for 3 days (2 non-childcare days and 1 weekend day) in non-public settings. Once switched on, the camera will record continuous video footage. Parents will complete an online survey providing their feedback on their own and their child’s experience of the wearable camera. They will also report their own and their child’s demographical characteristics and their child’s usual daily screen time and time spent restrained in the past week. Data will be downloaded using specialised software and second-by-second coding will be undertaken. Feasibility and acceptability will be assessed using percentages and by analysing qualitative data. If feasibility is shown, intraclass coefficients will be used to determine agreement between video data and parent-reported sedentary behaviours.

Ethics and dissemination

Ethical approval has been granted by the School of Psychological Sciences and Health Ethics Committee at the University of Strathclyde. Results will be used to inform future studies and will be disseminated in peer-reviewed journals and at major international conferences.
Clinical value of cerebrospinal fluid neurofilament light chain in semantic dementia
Authors: Meeter Lieke H H , Steketee Rebecca M E , Salkovic Dina , Vos Maartje E , Grossman Murray , McMillan Corey T , Irwin David J , Boxer Adam L , Rojas Julio C , Olney Nicholas T , Karydas Anna , Miller Bruce L , Pijnenburg Yolande A L , Barkhof Frederik , Sánchez-Valle Raquel , Lladó Albert , Borrego-Ecija Sergi , Diehl-Schmid Janine , Grimmer Timo , Goldhardt Oliver , Santillo Alexander F , Hansson Oskar , Vestberg Susanne , Borroni Barbara , Padovani Alessandro , Galimberti Daniela , Scarpini Elio , Rohrer Jonathan D , Woollacott Ione O C , Synofzik Matthis , Wilke Carlo , de Mendonca Alexandre , Vandenberghe Rik , Benussi Luisa , Ghidoni Roberta , Binetti Giuliano , Niessen Wiro J , Papma Janne M , Seelaar Harro , Jiskoot Lize C , de Jong Frank Jan , Donker Kaat Laura , Del Campo Marta , Teunissen Charlotte E , Bron Esther E , Van den Berg Esther , Van Swieten John C
Published: May 2019

Background

Semantic dementia (SD) is a neurodegenerative disorder characterised by progressive language problems falling within the clinicopathological spectrum of frontotemporal lobar degeneration (FTLD). The development of disease-modifying agents may be facilitated by the relative clinical and pathological homogeneity of SD, but we need robust monitoring biomarkers to measure their efficacy. In different FTLD subtypes, neurofilament light chain (NfL) is a promising marker, therefore we investigated the utility of cerebrospinal fluid (CSF) NfL in SD.

Methods

This large retrospective multicentre study compared cross-sectional CSF NfL levels of 162 patients with SD with 65 controls. CSF NfL levels of patients were correlated with clinical parameters (including survival), neuropsychological test scores and regional grey matter atrophy (including longitudinal data in a subset).

Results

CSF NfL levels were significantly higher in patients with SD (median: 2326 pg/mL, IQR: 1628–3593) than in controls (577 (446–766), p<0.001). Higher CSF NfL levels were moderately associated with naming impairment as measured by the Boston Naming Test (rs=−0.32, p=0.002) and with smaller grey matter volume of the parahippocampal gyri (rs=−0.31, p=0.004). However, cross-sectional CSF NfL levels were not associated with progression of grey matter atrophy and did not predict survival.

Conclusion

CSF NfL is a promising biomarker in the diagnostic process of SD, although it has limited cross-sectional monitoring or prognostic abilities.
Thalamic arousal network disturbances in temporal lobe epilepsy and improvement after surgery
Authors: González Hernán F J , Chakravorti Srijata , Goodale Sarah E , Gupta Kanupriya , Claassen Daniel O , Dawant Benoit , Morgan Victoria L , Englot Dario J
Published: May 2019

Objective

The effects of temporal lobe epilepsy (TLE) on subcortical arousal structures remain incompletely understood. Here, we evaluate thalamic arousal network functional connectivity in TLE and examine changes after epilepsy surgery.

Methods

We examined 26 adult patients with TLE and 26 matched control participants and used resting-state functional MRI (fMRI) to measure functional connectivity between the thalamus (entire thalamus and 19 bilateral thalamic nuclei) and both neocortex and brainstem ascending reticular activating system (ARAS) nuclei. Postoperative imaging was completed for 19 patients >1 year after surgery and compared with preoperative baseline.

Results

Before surgery, patients with TLE demonstrated abnormal thalamo-occipital functional connectivity, losing the normal negative fMRI correlation between the intralaminar central lateral (CL) nucleus and medial occipital lobe seen in controls (p < 0.001, paired t-test). Patients also had abnormal connectivity between ARAS and CL, lower ipsilateral intrathalamic connectivity, and smaller ipsilateral thalamic volume compared with controls (p < 0.05 for each, paired t-tests). Abnormal brainstem–thalamic connectivity was associated with impaired visuospatial attention (ρ = −0.50, p = 0.02, Spearman’s rho) while lower intrathalamic connectivity and volume were related to higher frequency of consciousness-sparing seizures (p < 0.02, Spearman’s rho). After epilepsy surgery, patients with improved seizures showed partial recovery of thalamo-occipital and brainstem–thalamic connectivity, with values more closely resembling controls (p < 0.01 for each, analysis of variance).

Conclusions

Overall, patients with TLE demonstrate impaired connectivity in thalamic arousal networks that may be involved in visuospatial attention, but these disturbances may partially recover after successful epilepsy surgery. Thalamic arousal network dysfunction may contribute to morbidity in TLE.
Protecting privacy to protect mental health: the new ethical imperative
Authors: Aboujaoude Elias
Published: May 2019

Confidentiality is a central bioethical principle governing the provider–patient relationship. Dating back to Hippocrates, new laws have interpreted it for the age of precision medicine and electronic medical records. This is where the discussion of privacy and technology often ends in the scientific health literature when Internet-related technologies have made privacy a much more complex challenge with broad psychological and clinical implications. Beyond the recognised moral duty to protect patients’ health information, clinicians should now advocate a basic right to privacy as a means to safeguard psychological health. The article reviews empirical research into the functions of privacy, the implications for psychological development and the resigned sentiment taking hold regarding the ability to control personal data. The article concludes with a call for legislative, educational and research steps to readjust the equilibrium between the individual and ‘Big Data’.