bluuebunny/crossref_metadata_2025 huggingface dataset:
Parallel Genomics Uncover Novel Enterococcal-Bacteriophage Interactions
Authors: Chatterjee Anushila , Willett Julia L. E. , Nguyen Uyen Thy , Monogue Brendan , Palmer Kelli L. , Dunny Gary M. , Duerkop Breck A.
Published: February 2020

We lack fundamental understanding of how phage infection influences bacterial gene expression and, consequently, how bacterial responses to phage infection affect the assembly of polymicrobial communities. Using parallel genomic approaches, we have discovered novel transcriptional regulators and metabolic genes that influence phage infection. The integration of whole-genome transcriptomic profiling during phage infection has revealed the differential regulation of genes important for group behaviors and polymicrobial interactions. Our work suggests that therapeutic phages could more broadly influence bacterial community composition outside their intended host targets.
Peptidoglycan Hydrolases RipA and Ami1 Are Critical for Replication and Persistence of Mycobacterium tuberculosis in the Host
Authors: Healy Claire , Gouzy Alexandre , Ehrt Sabine
Published: February 2020

Tuberculosis (TB) is a major global heath burden, with 1.6 million people succumbing to the disease every year. The search for new drugs to improve the current chemotherapeutic regimen is crucial to reducing this global health burden. The cell wall polymer peptidoglycan (PG) has emerged as a very successful drug target in bacterial pathogens, as many currently used antibiotics target the synthesis of this macromolecule. However, the multitude of genes encoding PG-synthesizing and PG-modifying enzymes with apparent redundant functions has hindered the identification of novel drug targets in PG synthesis in
Mycobacterium tuberculosis
. Here, we demonstrate that two PG-cleaving enzymes are important for virulence of
M. tuberculosis
. In particular, the
d
,
l
-endopeptidase RipA represents a potentially attractive drug target, as its depletion results in the clearance of
M. tuberculosis
from the host and renders the bacteria hypersusceptible to rifampin, a frontline TB drug, and to several cell wall-targeting antibiotics.
Modulation of Monocyte-Driven Myositis in Alphavirus Infection Reveals a Role for CX
3
CR1
+
Macrophages in Tissue Repair
Authors: Zaid Ali , Tharmarajah Kothila , Mostafavi Helen , Freitas Joseph R. , Sheng Kuo-Ching , Foo Suan-Sin , Chen Weiqiang , Vider Jelena , Liu Xiang , West Nicholas P. , Herrero Lara J. , Taylor Adam , Mackay Laura K. , Getts Daniel R. , King Nicholas J. C. , Mahalingam Suresh
Published: February 2020

Arthritogenic alphaviruses cause debilitating inflammatory disease, and current therapies are restricted to palliative approaches. Here, we show that following monocyte-driven muscle inflammation, tissue recovery is associated with the accumulation of CX
3
CR1
+
macrophages in the muscle. Modulating inflammatory monocyte infiltration using immune-modifying microparticles (IMP) reduced tissue damage and inflammation and enhanced the formation of tissue repair-associated CX
3
CR1
+
macrophages in the muscle. This shows that modulating key effectors of viral inflammation using microparticles can alter the outcome of disease by facilitating the accumulation of macrophage subsets associated with tissue repair.
The HIV-1 Accessory Protein Vpu Downregulates Peroxisome Biogenesis
Authors: Xu Zaikun , Lodge Robert , Power Christopher , Cohen Eric A. , Hobman Tom C.
Published: February 2020

People living with HIV can experience accelerated aging and the development of neurological disorders. Recently, we reported that HIV-1 infection results in a dramatic loss of peroxisomes in macrophages and brain tissue. This is significant because (i) peroxisomes are important for the innate immune response and (ii) loss of peroxisome function is associated with cellular aging and neurodegeneration. Accordingly, understanding how HIV-1 infection causes peroxisome depletion may provide clues regarding how the virus establishes persistent infections and, potentially, the development of neurological disorders. Here, we show that the accessory protein Vpu is necessary and sufficient for the induction of microRNAs that target peroxisome biogenesis factors. The ability of Vpu to downregulate peroxisome formation depends on the Wnt/β-catenin pathway. Thus, in addition to revealing a novel mechanism by which HIV-1 uses intracellular signaling pathways to target antiviral signaling platforms (peroxisomes), we have uncovered a previously unknown link between the Wnt/β-catenin pathway and peroxisome homeostasis.
Using Colonization Assays and Comparative Genomics To Discover Symbiosis Behaviors and Factors in Vibrio fischeri
Authors: Bongrand Clotilde , Moriano-Gutierrez Silvia , Arevalo Philip , McFall-Ngai Margaret , Visick Karen L. , Polz Martin , Ruby Edward G.
Published: February 2020

There is an increasing recognition of the importance of strain differences in the ecology of a symbiotic bacterial species and, in particular, how these differences underlie crucial interactions with their host. Nevertheless, little is known about the genetic bases for these differences, how they manifest themselves in specific behaviors, and their distribution among symbionts of different host species. In this study, we sequenced the genomes of
Vibrio fischeri
isolated from the tissues of squids and fishes and applied comparative genomics approaches to look for patterns between symbiont lineages and host colonization behavior. In addition, we identified the only two genes that were exclusively present in all
V. fischeri
strains isolated from the light organs of sepiolid squid species. Mutational studies of these genes indicated that they both played a role in colonization of the squid light organ, emphasizing the value of applying a comparative genomics approach in the study of symbioses.
Systematic Localization of Escherichia coli Membrane Proteins
Authors: Sueki Anna , Stein Frank , Savitski Mikhail M. , Selkrig Joel , Typas Athanasios
Published: February 2020

Current knowledge of protein localization, particularly outer membrane proteins, is highly dependent on bioinformatic predictions. To date, no systematic experimental studies have directly compared protein localization spanning the inner and outer membranes of
E. coli
. By combining sucrose density gradient fractionation of inner membrane (IM) and outer membrane (OM) proteins with multiplex quantitative proteomics, we systematically quantified localization patterns for >1,600 proteins, providing high-confidence localization annotations for 1,368 proteins. Of these proteins, we resolve the predominant localization of 316 proteins that currently have dual annotation (cytoplasmic and IM) in protein databases and identify new annotations for 42 additional proteins. Overall, we present a novel quantitative methodology to systematically map membrane proteins in Gram-negative bacteria and use it to unravel the biological complexity of the membrane proteome architecture in
E. coli
.
Flecainide toxicity: a presentation to the emergency department with literature review
Authors: Ghataoura Rashpal , Patil Shashank
Published: February 2020

Flecainide toxicity can result in increased cardiovascular instability which can significantly alter patient outcome if not recognised early. In this case report, the management of a 68-year-old woman who took an unintentional overdose of flecainide is detailed. We look at the management she received in the emergency department and her successful recovery and follow-up since the admission. In addition, the case report outlines the ECG changes that are most commonly documented in flecainide overdose and reviews the frequently used treatment methods for the overdose as summarised in current literature.
Postcardiotomy extracorporeal membrane oxygenation in a patient with Austrian syndrome
Authors: Edlin Joy C , Metwalli Amr , Finney Simon J , Ambekar Shirish G
Published: February 2020

A 43-year-old man with Austrian syndrome, the triad of infective endocarditis (IE), pneumonia and meningitis caused byStreptococcus pneumoniae, underwent emergency aortic and mitral valve replacement and closure of an aortic root abscess. Postoperatively, he required mechanical circulatory support with veno-arterial extracorporeal membrane oxygenation and an intra-aortic balloon pump. Several days after surgery, new mitral and aortic paraprosthetic leaks (PPLs) developed. These were managed conservatively, initially, but eventually required percutaneous closure 6 weeks after the initial operation. This has enabled the patient to recover to independent mobility, 20 weeks after the operation. This case illustrates a rare clinical syndrome and the devastating impact of IE. Moreover, it illustrates the successful application of extracorporeal membrane oxygenation in postcardiotomy cardiac failure and the successful treatment of PPL in a patient unfit for redo surgery.
Differentiating 11β-hydroxylase deficiency from primary glucocorticoid resistance syndrome in male precocity: real challenge in low-income countries
Authors: Majumder Sananda , Chakraborty Partha Pratim , Ghosh Prakash Chandra , Bera Mitali
Published: February 2020

Congenital adrenal hyperplasia due to 11β-hydroxylase deficiency (11-BHD) and primary glucocorticoid resistance syndrome (PGRS) are two relatively uncommon causes of gonadotropin-releasing hormone-independent isosexual male precocity; PGRS, however, is considerably rarer than 11-BHD. Other than serum and urinary cortisol, which are elevated in PGRS and low/low–normal in 11-BHD, both of these conditions are indistinguishable by clinical, biochemical or radiological parameters. In 11-BHD, oxidation of 11-deoxycortisol (11-DOC) to cortisol is impaired, resulting in accumulation of 11-DOC and other cortisol precursors. 11-DOC shares structural homology with cortisol, and falsely elevated serum cortisol values are observed in older generation immunoassays (Siemens ADVIA Centaur) due to antibody cross-reactivity. 11-BHD, thus, may be misdiagnosed as PGRS. Structure-based cortisol assays are not widely available in low-income countries. Hence, immunoassays using highly specific antibodies against cortisol are required to ensure assay selectivity. Newer generation analysers probably are effective alternatives to liquid chromatography–tandem mass spectrometry in conditions associated with 11β-hydroxylase defect.
Role of the DNA repair genesH2AXandHMGB1in human fat distribution and lipid profiles
Authors: Rohde Kerstin , Rønningen Torunn , la Cour Poulsen Lars , Keller Maria , Blüher Matthias , Böttcher Yvonne
Published: February 2020

Introduction

Regional fat distribution strongly relates to metabolic comorbidities. We identified the DNA repair genesH2AXandHMGB1to be differentially expressed between human subcutaneous (SAT) and omental visceral adipose tissue (OVAT) depots. As increased DNA damage is linked to metabolic disease, we here sought to analyze whether depot-specificH2AXandHMGB1expression is related to anthropometric and metabolic profiles of obesity. We further tested for differentH2AXmRNA regulatory mechanisms by analyzing promoter DNA methylation and genotyped rs7350 in theH2AXlocus.

Research design and methods

Gene expression (OVAT n=48; SAT n=55) and DNA promoter methylation data (OVAT and SAT n=77) were extracted from an existing dataset as described elsewhere. Genotype data for the 3’untranslated region (3’UTR)H2AXvariant rs7350 were generated by using the TaqMan genotyping system in 243 subjects of the same cohort. Statistical analyses were done using SPSS statistics software 24 and GraphPad Prism 6.

Results

We identifiedH2AXbeing higher (p=0.002) andHMGB1being less expressed (p=0.0001) in OVAT compared with SAT. Further, we observed positive interdepot correlations of OVAT and SAT for bothHMGB1(p=1×10–6) andH2AXmRNA levels (p=0.024). Depot-specific associations were observed for both genes’ methylation levels with either high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides and/or with OVAT/SAT-ratio (all p<0.05). A significantly lower level of total cholesterol in minor A-Allele carriers of rs7350 compared with AG and GG carriers (p=0.001) was observed. Additionally, subjects carrying the A-allele showed lower SATHMGB1expression level (p=0.030).

Conclusion

Our results suggest a fat depot-specific regulation ofH2AXandHMGB1potentially mediated by both DNA methylation and genetic variation. Rs7350, DNA methylation and/or mRNA levels ofH2AXandHMGB1are related to lipid parameters. Further studies are warranted to evaluate the functional role of the DNA repair genesH2AXandHMGB1in obesity and fat distribution.
Availability and use of continuous positive airway pressure (CPAP) for neonatal care in public health facilities in India: a cross-sectional cluster survey
Authors: Dewez Juan Emmanuel , Nangia Sushma , Chellani Harish , White Sarah , Mathai Matthews , van den Broek Nynke
Published: February 2020

Objectives

To determine the availability of continuous positive airway pressure (CPAP) and to provide an overview of its use in neonatal units in government hospitals across India.

Setting

Cross-sectional cluster survey of a nationally representative sample of government hospitals from across India.

Primary outcomes

Availability of CPAP in neonatal units.

Secondary outcomes

Proportion of hospitals where infrastructure and processes to provide CPAP are available. Case fatality rates and complication rates of neonates treated with CPAP.

Results

Among 661 of 694 government hospitals with neonatal units that provided information on availability of CPAP for neonatal care, 68.3% of medical college hospitals (MCH) and 36.6% of district hospitals (DH) used CPAP in neonates. Assessment of a representative sample of 142 hospitals (79 MCH and 63 DH) showed that air-oxygen blenders were available in 50.7% (95% CI 41.4% to 60.9%) and staff trained in the use of CPAP were present in 56.0% (45.8% to 65.8%) of hospitals. The nurse to patient ratio was 7.3 (6.4 to 8.5) in MCH and 6.6 (5.5 to 8.3) in DH. Clinical guidelines were available in 31.0% of hospitals (22.2% to 41.4%). Upper oxygen saturation limits of above 94% were used in 72% (59.8% to 81.6%) of MCH and 59.3% (44.6% to 72.5%) of DH. Respiratory circuits were reused in 53.8% (42.3% to 63.9%) of hospitals. Case fatality rate for neonates treated with CPAP was 21.4% (16.6% to 26.2%); complication rates were 0.7% (0.2% to 1.2%) for pneumothorax, 7.4% (0.9% to 13.9%) for retinopathy and 1.4% (0.7% to 2.1%) for bronchopulmonary dysplasia.

Conclusions

CPAP is used in neonatal units across government hospitals in India. Neonates may be overexposed to oxygen as the means to detect and treat consequences of oxygen toxicity are insufficient. Neonates may also be exposed to nosocomial infections by reuse of disposables. Case fatality rates for neonates receiving CPAP are high. Complications might be under-reported. Support to infrastructure, training, guidelines implementation and staffing are needed to improve CPAP use.
‘We do not seem to engage with dentists’: a qualitative study of primary healthcare staff and patients in the North East of England on the role of pharmacists in oral healthcare
Authors: Sturrock Andrew , Preshaw Philip M , Hayes Catherine , Wilkes Scott
Published: February 2020

Objective

To explore the attitudes towards, and perceptions of, primary care healthcare staff and patients, regarding the role of clinical pharmacists in the provision of oral health advice and collaboration with dentists in general practice.

Design

Interpretivist methodology using qualitative semi-structured interviews and focus groups.

Participants

22 participants; 10 pharmacists; 3 general practitioners; 2 nurses; 1 practice manager; 6 patients.

Setting

Primary care general medical practices in the North East of England and the University of Sunderland Patient Carer and Public Involvement group.

Methods

One-to-one semi-structured interviews were performed with primary care healthcare staff. An iterative approach using constant comparative analysis facilitated the ongoing enrichment of data; salient themes were identified using Framework Analysis and related back to extant literature. A focus group was held with patients to further explore key themes.

Results

Four salient and inter-related themes emerged: enhanced clinical roles; indicating rapidly changing roles of pharmacists working in general practice, increased responsibility and accountability of pharmacist prescribers and the delivery of advanced clinical services; limited knowledge; indicating basic understanding of appropriate oral health advice, but limited insight and provision of advice to patients with regards to links with systemic diseases and medication; geographical/situational isolation of the dental team; indicating the disparate contexts and challenges of multidisciplinary working in oral health, and patients’ attitudes towards dental care; integration of oral health advice; indicating the potential of pharmacists to integrate oral health advice into current roles and to target specific patient groups in practice.

Conclusions

The lack of integration between oral and general healthcare services potentially impacts negatively on patient care, requiring further interprofessional oral health education. The developing role of the pharmacist in general practice represents an opportunity to integrate oral health advice and/or interventions into the management of patients in this setting.
Diet quality during preconception or pregnancy and gestational weight gain: protocol for a systematic review and meta-analysis
Authors: Yu Yamei , Hardy Isabelle , Sun Wenguang , Fergusson Dean A , Fraser William , Dubois Lise
Published: February 2020

Introduction

Inappropriate gestational weight gain (GWG), including inadequate and excessive GWG, has become pandemic across nations and continents. This review aims to synthesise the evidence on the correlation between diet quality and GWG. If this association is confirmed, improving diet quality could become an intervention target in the efforts to reduce inappropriate GWG.

Methods and analysis

We will conduct a systematic review of all prospective cohort studies on diet quality in preconception or pregnancy and GWG. Our secondary outcomes include gestational diabetes, pre-eclampsia and birth weight. A comprehensive search of all published articles in MEDLINE ALL (Ovid), Embase (Ovid), Food Science and Technology Abstracts (Ovid) and CINAHL (EBSCOHost), from database creation to 20 April 2019, will be conducted. Studies will be screened for eligibility by title, abstract and full text in duplicate by two independent reviewers. Study quality and risk of bias will be assessed using the adapted Newcastle–Ottawa Scale. Results will be reported following the meta-analysis of observational studies in epidemiology guidelines. If sufficient data are available, a meta-analysis will be conducted to synthesise the effect size reported as OR with 95% CI using both fixed-effect and random-effect models. I2statistics and visual inspection of the forest plots will be used to assess heterogeneity and identify the potential sources of heterogeneity. Publication bias will be assessed by visual inspections of funnel plots and Egger’s test.

Ethics and dissemination

Formal ethical approval is not required as no primary data will be collected. We aim to publish the results of this study in a peer-reviewed journal and present them at conferences and scientific meetings to promote knowledge transfer.

PROSPERO registration number

CRD42019128732
The INternet ThERapy for deprESsion Trial (INTEREST): protocol for a patient-preference, randomised controlled feasibility trial comparing iACT, iCBT and attention control among individuals with comorbid chronic pain and depression
Authors: Bell Louise V , Cornish Peter , Flusk David , Garland Sheila N , Rash Joshua A
Published: February 2020

Introduction

Approximately one-third of adults with chronic pain also report clinically relevant levels of depression. Internet-delivered psychological therapies such as Cognitive Behavioural Therapy (iCBT) and Acceptance and Commitment Therapy (iACT) have been developed to overcome barriers of access to services and ensure the timely delivery of care. The objective of this trial is to collect data on feasibility, acceptability and range of probable effect sizes for iCBT and iACT interventions tailored towards the treatment of depression and chronic pain using a randomised controlled patient-preference design.

Methods and analysis

Community dwelling adults with chronic non-cancer pain (CNCP) and major depression will be recruited from pain clinics and primary care providers in Newfoundland and Labrador, Canada. The study is a randomised controlled patient-preference trial. Eligible patients will be randomly assigned to a ‘preference’ or ‘no-preference’ arm during the first step of randomisation and to intervention or control in the second step of randomisation. Two interventions (ie, iCBT or iACT) will be evaluated relative to attention control. iCBT and iACT involve the completion of 7-weekly online modules augmented with one session of motivational enhancement and weekly therapy sessions. Primary outcomes include (1) feasibility and acceptability parameters and (2) change in symptoms of depression. Secondary outcomes include pain, physical function, emotional function and quality of life. We will recruit 60 participants and examine the range of effect sizes obtained from the trial but will not conduct significance testing as per recommendations for behavioural trial development.

Ethics and dissemination

Ethics was approved by the provincial Health Research Ethics Board. Dissemination of results will be published in a peer-reviewed academic journal and presented at scientific conferences.

Trial registration number

NCT04009135.
Association between depressive symptoms and arterial stiffness: a cross-sectional study in the general Chinese population
Authors: Peng Liming , Bi Sisi , Liu Xiangwei , Long Tianyi , Zhao Yixia , Li Fei , Yang Tianlun , Zhang Chenglong
Published: February 2020

Objectives

To determine the independent relationship between depressive symptoms and arterial stiffness in the general Chinese population, and to explore possible interactive factors in the relationship.

Design

A cross-sectional study.

Setting and participants

Consecutive participants who received routine health physical examination in an affiliated hospital of a comprehensive university in Hunan Province, China, between September 2013 and March 2014 were examined. After exclusion of subjects not meeting the criteria, a total of 1334 subjects aged 22–77 years were recruited for final analysis.

Measures

The Patient Health Questionnaire-9 was employed to assess the degree of depressive symptoms: 0–4 no depressive symptoms, 5–9 mild depressive symptoms and 10–27 moderate to severe depressive symptoms. Brachial-ankle pulse wave velocity (baPWV) was measured to determine arterial stiffness.

Results

There was a slight increase in baPWV across elevated degrees of depressive symptoms (p=0.025). Multivariate linear regression analysis revealed that mild depressive symptoms and moderate to severe depressive symptoms were independently associated with baPWV compared with no depressive symptoms after adjusting for baseline confounders (beta-coefficient: 40.3, 95% CI 6.6 to 74.1; beta-coefficient: 87.7, 95% CI 24.0 to 151.5, respectively). Further stratified analyses indicated that the relationship between degree of depressive symptoms and baPWV was predominant in subjects who had normal or normal-high blood pressure, or combined with hypertension (p for interaction=0.016), or in subjects with diabetes mellitus (p for interaction=0.004), examined in multivariate linear regressions. In addition, after adjustment, a significant association between moderate to severe depressive symptoms and baPWV was also found in female subjects younger than 60 years, although the interactive effect was not significant (p for interaction=0.056).

Conclusions

Depressive symptoms are independently associated with arterial stiffness, especially in subjects whose blood pressures are beyond the optimal range and combined with diabetes mellitus.
Pharmacist and Data-Driven Quality Improvement in Primary Care (P-DQIP): a qualitative study of anticipated implementation factors informed by the Theoretical Domains Framework
Authors: Tang Jason , Toma Madalina , Gray Nicola M , Delvaux Joke , Guthrie Bruce , Grant Aileen , Duncan Eilidh M , Dreischulte Tobias
Published: February 2020

Objectives

The quality and safety of drug therapy in primary care are global concerns. The Pharmacist and Data-Driven Quality Improvement in Primary Care (P-DQIP) intervention aims to improve prescribing safety via an informatics tool, which facilitates proactive management of drug therapy risks (DTRs) by health-board employed pharmacists with established roles in general practices. Study objectives were (1) to identify and prioritise factors that could influence P-DQIP implementation from the perspective of practice pharmacists and (2) to identify potentially effective, acceptable and feasible strategies to support P-DQIP implementation.

Design

Semistructured face-to-face interviews using a Theoretical Domains Framework informed topic guide. The framework method was used for data analysis. Identified implementation factors were prioritised for intervention based on research team consensus. Candidate intervention functions, behavioural change techniques (BCTs) and policies targeting these were identified from the behavioural change wheel. The final intervention content and modes of delivery were agreed with local senior pharmacists.

Setting

General practices from three Health and Social Care Partnerships in National Health Service (NHS) Tayside.

Participants

14 NHS employed practice pharmacists.

Results

Identified implementation factors were linked to thirteen theoretical domains (all except intentions) and six (skill, memory/attention/decision making, behavioural regulation, reinforcement, environmental context/resources, social influences) were prioritised. Three intervention functions (training, enablement and environmental restructuring) were relevant and were served by two policy categories (guidelines, communication/marketing) and eight BCTs (instructions on how to perform a behaviour, problem solving, action planning, prompt/cues, goal setting, self-monitoring, feedback and restructuring the social environment). Intervention components encompass an informatics tool, written educational material, a workshop for pharmacists, promotional activities and small financial incentives.

Conclusions

This study explored pharmacists’ perceptions of implementation factors which could influence management of DTRs in general practices to inform implementation of P-DQIP, which will initially be implemented in one Scottish health board with parallel evaluation of effectiveness and implementation.
Household food insecurity among patients with pulmonary tuberculosis and its associated factors in South India: a cross-sectional analysis
Authors: Ayiraveetil Reshma , Sarkar Sonali , Chinnakali Palanivel , Jeyashree Kathiresan , Vijayageetha Mathavaswami , Thekkur Pruthu , Lakshminarayanan Subitha , Knudsen Selby , Hochberg Natasha S , Horsburgh C Robert , Ellner Jerrold , Roy Gautam
Published: February 2020

Objectives

Food insecurity is ‘the limited or uncertain availability of nutritionally adequate, safe foods or inability to acquire foods in socially acceptable ways’. Majority of tuberculosis (TB) cases of resource-poor settings experience food insecurity, which impacts treatment adherence and outcomes. We aimed to determine level of household food insecurity (HFI) and its associated factors in patients with pulmonary TB.

Design

This is a cross-sectional analysis of data from an ongoing cohort study.

Setting

National Tuberculosis Programme (NTP) in three districts of South India.

Participants

All newly diagnosed pulmonary TB cases of the cohort enrolled in the NTP at the Designated Microscopy Centres (DMCs) and Primary Health Centres (PHCs) from October 2015 to October 2018.

Primary outcome measures

The proportion of baseline HFI assessed using a validated HFI Access Scale was summarised as percentage with 95% CI. Possible association of sociodemographic, morbidity and behavioural characteristics with HFI was assessed using χ2test, and unadjusted prevalence ratios with 95% CI were calculated. The characteristics with values of p<0.2 in the univariate model were included in the multivariable generalised linear model (binomial function, log link) to derive adjusted prevalence ratios (aPRs) with 95% CI.

Result

Of a total of 765 patients, 261 had HFI and the proportion was 34.1% (95% CI 30.8% to 37.6%). Mild, moderate and severe food insecurity was found in 17 (2.2%), 67 (8.8%) and 177 (23.1%) TB cases, respectively. Patients with TB who had monthly family income less than rupees 3000 (aPR 2.0; 95% CI 1.3 to 3.0), Karnofsky Score of 60 or less (aPR 1.5; 95% CI 1.1 to 1.9) and those who were employed (aPR 1.4; 95% CI 1.0 to 2.0) were independently associated with HFI.

Conclusions

A high level of food insecurity was seen in households with TB cases. Additional food or cash assistance for this subgroup might improve food insecurity and thereby nutritional status.
Risk of diabetic foot ulcer and its associated factors among Bangladeshi subjects: a multicentric cross-sectional study
Authors: Banik Palash Chandra , Barua Lingkan , Moniruzzaman Mohammad , Mondal Rajib , Zaman Farhana , Ali Liaquat
Published: February 2020

Objective

To assess the risk of diabetic foot ulcer (DFU) and find out its associated factors among subjects with type 2 diabetes (T2D) of Bangladesh.

Design, setting and participants

This cross-sectional study recruited 1200 subjects with T2D who visited 16 centres of Health Care Development Project run by Diabetic Association of Bangladesh.

Primary and secondary outcome measures

Risk of DFU was assessed using a modified version of International Working Group on the Diabetic Foot (IWGDF) Risk Classification System. The modified system was based on five parameters, namely peripheral neuropathy (PN), peripheral arterial diseases (PAD), deformity, ulcer history and amputation. The risks were categorised as group 0 (no PN, no PAD), group 1 (PN, no PAD and no deformity), group 2A (PN and deformity, no PAD), group 2B (PAD), group 3A (ulcer history) and group 3B (amputation). The associated factors of DFU risk were determined using multinomial logistic regression for each risk category separately.

Results

Overall, 44.5% of the subjects were found ‘at risk’ of DFU. This risk was higher among men (45.6%) than women and among those who lived in rural areas (45.5%) as compared with the urban population. According to IWGDF categories, the risk was distributed as 55.5%, 4.2%, 11.6%, 0.3%, 20.6% and 7.9% for group 0, group 1, group 2A, group 2B, group 3A and group 3B, respectively. The associated factors of DFU (OR >1) were age ≥50 years, rural area, low economic status, insulin use, history of trauma, diabetic retinopathy and diabetic nephropathy.

Conclusion

A significant number of the subjects with T2D under study were at risk of DFU, which demands an effective screening programme to reduce DFU-related morbidity and mortality.
A qualitative approach in determining the patient-centered information and supportive care needs of cancer patients in Singapore
Authors: Chua Gek Phin , Tan Hiang Khoon
Published: February 2020

Objectives

To qualitatively interpret the information and supportive care needs perceived by cancer patients undergoing treatment in order to get a deeper appreciation of patients’ needs and concerns. The intended outcome is to provide baseline knowledge for improving patient-centred strategies to better meet the information and supportive needs of patients.

Design

A qualitative research approach, based on conventional content analysis, was used throughout the research process. The three open-ended questions obtained from a previous quantitative study guided the researchers to explore the information and supportive care needs of patients. Data from patients’ responses were analysed and coded in themes.

Participants and setting

Patients attending the Ambulatory Treatment Unit of the National Cancer Centre Singapore were invited to participate in the study. We determined from these subjects the type of information that cancer patients need, and to measure the extent to which these information needs are met by measuring patients’ level of satisfaction. Included in the quantitative study were three open-ended questions designed to gain a deeper understanding of their needs and concerns. All subjects were aged 21 years and above and able to understand and communicate in English/Mandarin. They were also aware of their diagnosis, they were not cognitively impaired and were not at the end-of-life situation.

Results

A variety of information and supportive care needs were identified, and three specific areas of concerns were identified: (1) psychosocial and supportive care needs, (2) information needs and (3) information delivery by professionals.

Conclusion

The information and supportive care needs expressed were consistent with issues of cancer patients undergoing treatment. The strategies to improve patients’ coping abilities through patient-centred care are discussed. Further studies assessing the barriers of information provision by healthcare professionals should provide more detailed knowledge about unmet information needs.
How defensive medicine is defined and understood in European medical literature: protocol for a systematic review
Authors: Baungaard Nathalie , Skovvang Pia , Assing Hvidt Elisabeth , Gerbild Helle , Kirstine Andersen Merethe , Lykkegaard Jesper
Published: February 2020

Introduction

The term defensive medicine, referring to actions motivated primarily by litigious concerns, originates from the USA and has been used in medical research literature since the late 1960s. Differences in medical legal systems between the US and most European countries with no tort legislation raise the question whether the US definition of defensive medicine holds true in Europe.

Aim

To present the protocol of a systematic review investigating variations in definitions and understandings of the term ‘defensive medicine’ in European research articles.

Methods and analysis

In concordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of all medical research literature that investigate defensive medicine will be performed by two independent reviewers. The databases PubMed, Embase and Cochrane will be systematically searched on the basis of predetermined criteria. Data from all included European studies will systematically be extracted including the studies’ definitions and understandings of defensive medicine, especially the motives for doing medical actions that the study regards as ‘defensive’.

Ethics and dissemination

No ethics clearance is required as no primary data will be collected. The results of the systematic review will be published in a peer-reviewed, international journal.

PROSPERO registration number

This review has been submitted to International Prospective Register of Systematic Reviews (PROSPERO) and is awaiting registration.
Study protocol of a randomised controlled trial of prostate radiotherapy in high-risk and node-positive disease comparing moderate and extreme hypofractionation (PRIME TRIAL)
Authors: Murthy Vedang , Mallick Indranil , Gavarraju Abhilash , Sinha Shwetabh , Krishnatry Rahul , Telkhade Tejshri , Moses Arunsingh , Kannan Sadhna , Prakash Gagan , Pal Mahendra , Menon Santosh , Popat Palak , Rangarajan Venkatesh , Agarwal Archi , Kulkarni Sheetal , Bakshi Ganesh
Published: February 2020

Introduction

There has been an interest in studying the efficacy of extreme hypofractionation in low and intermediate risk prostate cancer utilising the low alpha/beta ratio of prostate. Its role in high-risk and node-positive prostate cancer, however, is unknown. We hypothesise that a five-fraction schedule of extreme hypofractionation will be non-inferior to a moderately hypofractionated regimen over 5 weeks in efficacy and will have acceptable toxicity and quality of life while reducing the cost implications during treatment.

Methods and analysis

This is an ongoing, non-inferiority, multicentre, randomised trial (NCT03561961) of two schedules for National Cancer Control Network high-risk and/or node-positive non-metastatic carcinoma of the prostate. The standard arm will be a schedule of 68 Gy/25# over 5 weeks while the test arm will be extremely hypofractionated radiotherapy with stereotactic body radiation therapy to 36.25 Gy/5# (7 to 10 days). The block randomisation will be stratified by nodal status (N0/N+), hormonal therapy (luteinizing hormone-releasing hormone therapy/orchiectomy) and centre. All patients will receive daily image-guided radiotherapy.

The primary end point is 4-year biochemical failure free survival (BFFS). The power calculations assume 4-year BFFS of 80% in the moderate hypofractionation arm. With a 5% one-sided significance and 80% power, a total of 434 patients will be randomised to both arms equally (217 in each arm). The secondary end points include overall survival, prostate cancer specific survival, acute and late toxicities, quality of life and out-of-pocket expenditure.

Discussion

The trial aims to establish a therapeutically efficacious and cost-efficient modality for high-risk and node-positive prostate cancer with an acceptable toxicity profile. Presently, this is the only trial evaluating and answering such a question in this cohort.

Ethics and dissemination

The trial has been approved by IEC-III of Tata Memorial Centre, Mumbai.

Trial registration number

Registered with CTRI/2018/05/014054 (http://ctri.nic.in) on 24 May 2018
Prevalence and determinants of current cigarette smoking and secondhand smoking among Greek adolescents: the Global Youth Tobacco Survey (GYTS) 2013 study
Authors: Rachiotis George , Barbouni Anastasia , Basagiannis Athanasios , Katsioulis Antonis , Kostikas Konstantinos , Mouchtouri Varvara , Merakou Kyriakoula , Kremastinou Jenny , Hadjichristodoulou Christos S
Published: February 2020

Objectives

Smoking prevalence in Greece is considered high within the European Union and the collection of evidence on tobacco use among adolescents is of vital importance in order to develop effective smoking prevention and cessation programmes.

Design

Cross-sectional.

Setting

Greece.

Primary and secondary outcome measures

Global Youth Tobacco Survey (GYTS) is a national representative, paper-and-pencil, cross-sectional, school-based study of students at ages 13–15 years. The survey employed a multistage cluster sample design with schools selected proportional to enrolment size. Finally, 4618/5127 students aged 13–15 years participated in the survey. The school response rate was 98.1%, the student response rate was 90.1% and the overall response rate was 88.4%.

Results

The prevalence of current cigarette smoking was estimated at 10.1% (10.4% in GYTS 2005) and of exposure to secondhand smoking in public places at 67.4% (94.1% in GYTS 2005). The vast majority of the adolescents (82.1%) supported the banning of smoking inside enclosed public places. Most of the current smokers (90.8%) were not prevented/refused purchase because of their age according to existing law. Multivariate analysis showed that peer influence (OR=48.32; 95% CI 36.2 to 64.48), pocket money (OR=2.63; 95% CI 1.28 to 3.41), increasing age (OR=2.35; 95% CI 1.63 to 3.39) and low educational level of father (OR=2.82; 95% CI 1.7 to 4.68) were risk factors independently associated with current cigarette smoking.

Conclusions

Despite the existence of strict laws related to tobacco control, exposure to secondhand smoking among Greek students remained high even when compared with GYTS in 2005. This is likely a result of weak enforcement, what is really missing is the enforcement of the related legislation.
Medroxyprogesterone acetate plus metformin for fertility-sparing treatment of atypical endometrial hyperplasia and endometrial carcinoma: trial protocol for a prospective, randomised, open, blinded-endpoint design, dose-response trial (FELICIA trial)
Authors: Mitsuhashi Akira , Kawasaki Yohei , Hori Makoto , Fujiwara Tadami , Hanaoka Hideki , Shozu Makio
Published: February 2020

Introduction

Progestin therapy is the only fertility-sparing treatment option for patients with atypical endometrial hyperplasia (AEH) and endometrial cancer (EC). However, the results of three meta-analyses revealed a high remission rate, as well as an association with a high rate of relapse. We previously conducted a phase II of medroxyprogesterone acetate (MPA) plus metformin as a fertility-sparing treatment for AEH and EC patients, and reported that metformin inhibited disease relapse after remission.

Methods and analysis

A randomised, open, blinded-endpoint design phase IIb dose response trial was planned to commence in July 2019. The trial aims to identify the appropriate dose of metformin to be combined with MPA therapy for fertility-sparing treatment of patients with AEH and EC. The primary endpoint of the trial is the 3-year relapse-free survival (RFS) rate. The secondary endpoints are RFS rate, the overall rate of response to MPA therapy, the conception rate after treatment, the outcome of pregnancy, toxicity evaluation and changes in insulin resistance and body mass index. A total of 120 patients will be enrolled from 15 Japanese institutions within a 2.5-year period and followed up for at least 3 years.

Ethics and dissemination

The protocol was approved by the institutional review board at Chiba University Hospital and boards at 14 other institutions. The trial will be conducted according to the principles of the World Medical Association’s Declaration of Helsinki and in accordance with Good Clinical Practice (GCP) standards. The trial findings will be published in a peer-reviewed journal.

Trial registration number

Japan Registry of Clinical Trials (jRCT2031190065).
i-Move, a personalised exercise intervention for patients with advanced melanoma receiving immunotherapy: a randomised feasibility trial protocol
Authors: Hyatt Amelia , Gough Karla , Murnane Andrew , Au-Yeung George , Dawson Tamara , Pearson Elizabeth , Dhillon Haryana , Sandhu Shahneen , Williams Narelle , Paton Elizabeth , Billett Alex , Traill Anya , Andersen Hayley , Beedle Victoria , Milne Donna
Published: February 2020

Introduction

There is increasing evidence demonstrating the benefits of exercise in counteracting cancer treatment-related fatigue. Immunotherapy is an established treatment for advanced melanoma, and is associated with fatigue in a third of patients. The safety and efficacy of exercise in counteracting treatment-related fatigue in patients with advanced melanoma receiving immunotherapy are yet to be determined. This study aims to assess the safety, adherence to and acceptability of a mixed-methods parallel-group, pilot randomised controlled trial of a personalised, 12-week semi-supervised exercise programme prescribed by an exercise physiologist (iMove) in 30 patients with stage IV melanoma scheduled to commence immunotherapy: single agent ipilimumab, nivolumab or pembrolizumab, or combination ipilimumab and nivolumab. The trial will be used to provide preliminary evidence of the potential efficacy of exercise for managing fatigue.

Methods and analysis

Thirty participants will be recruited from a specialist cancer centre between May and September, 2019. Participants will be randomised 1:1 to receive iMove, or usual care (an information booklet about exercise for people with cancer). Feasibility data comprise: eligibility; recruitment and retention rates; adherence to and acceptability of exercise consultations, personalised exercise programme and study measures; and exercise-related adverse events. Patient-reported outcome measures assess potential impact of the exercise intervention on: fatigue, role functioning, symptoms and quality of life. Follow-up will comprise five time points over 24 weeks. Physical assessments measure physical fitness and functioning.

Ethics and dissemination

This study was reviewed and approved by the Peter MacCallum Cancer Centre Human Research Ethics Committee (HREC/48927/PMCC-2019). The findings from this trial will be disseminated via conference presentations and publications in peer-reviewed journals, and by engagement with clinicians, media, government and consumers. In particular, we will promote the outcomes of this work among the oncology community should this pilot indicate benefit for patients.

Trial registration number

ACTRN12619000952145; Pre-results.
Serious bacterial infections and antibiotic prescribing in primary care: cohort study using electronic health records in the UK
Authors: Gulliford Martin C , Sun Xiaohui , Charlton Judith , Winter Joanne R , Bunce Catey , Boiko Olga , Fox Robin , Little Paul , Moore Michael , Hay Alastair D , Ashworth Mark
Published: February 2020

Objective

This study evaluated whether serious bacterial infections are more frequent at family practices with lower antibiotic prescribing rates.

Design

Cohort study.

Setting

706 UK family practices in the Clinical Practice Research Datalink from 2002 to 2017.

Participants

10.1 million registered patients with 69.3 million patient-years’ follow-up.

Exposures

All antibiotic prescriptions, subgroups of acute and repeat antibiotic prescriptions, and proportion of antibiotic prescriptions associated with specific-coded indications.

Main outcome measures

First episodes of serious bacterial infections. Poisson models were fitted adjusting for age group, gender, comorbidity, deprivation, region and calendar year, with random intercepts representing family practice-specific estimates.

Results

The age-standardised antibiotic prescribing rate per 1000 patient-years increased from 2002 (male 423; female 621) to 2012 (male 530; female 842) before declining to 2017 (male 449; female 753). The median family practice had an antibiotic prescribing rate of 648 per 1000 patient-years with 95% range for different practices of 430–1038 antibiotic prescriptions per 1000 patient-years. Specific coded indications were recorded for 58% of antibiotic prescriptions at the median family practice, the 95% range at different family practices was from 10% to 75%. There were 139 759 first episodes of serious bacterial infection. After adjusting for covariates and the proportion of coded consultations, there was no evidence that serious bacterial infections were lower at family practices with higher total antibiotic prescribing. The adjusted rate ratio for 20% higher total antibiotic prescribing was 1.03, (95% CI 1.00 to 1.06, p=0.074).

Conclusions

We did not find population-level evidence that family practices with lower total antibiotic prescribing might have more frequent occurrence of serious bacterial infections overall. Improving the recording of infection episodes has potential to inform better antimicrobial stewardship in primary care.