bluuebunny/crossref_metadata_2025 huggingface dataset:
Kleptoprotein bioluminescence:
Parapriacanthus
fish obtain luciferase from ostracod prey
Authors: Bessho-Uehara Manabu , Yamamoto Naoyuki , Shigenobu Shuji , Mori Hitoshi , Kuwata Keiko , Oba Yuichi
Published: January 2020

Bioluminescent enzyme of the golden sweeper is supplied from the luminous crustacean diet.
DNA-dependent protein kinase promotes DNA end processing by MRN and CtIP
Authors: Deshpande Rajashree A. , Myler Logan R. , Soniat Michael M. , Makharashvili Nodar , Lee Linda , Lees-Miller Susan P. , Finkelstein Ilya J. , Paull Tanya T.
Published: January 2020

DNA-dependent protein kinase regulates end processing for homologous recombination.
A potential gut punch to gastric cancer
Authors: Yadav Vikramaditya G.
Published: January 2020

Combination chemotherapies that also inhibit the proline isomerase Pin1 may overcome the notorious drug resistance of gastric cancer.
Tryptophan Trimers and Tetramers Inhibit Dengue and Zika Virus Replication by Interfering with Viral Attachment Processes
Authors: Fikatas Antonios , Vervaeke Peter , Martínez-Gualda Belén , Martí-Marí Olaia , Noppen Sam , Meyen Eef , Camarasa María-José , San-Félix Ana , Pannecouque Christophe , Schols Dominique
Published: January 2020

Here, we report a class of tryptophan trimers and tetramers that inhibit (at low micromolar range) dengue and Zika virus infection
in vitro
. These compounds (AL family) have three or four peripheral tryptophan moieties directly linked to a central scaffold through their amino groups; thus, their carboxylic acid groups are free and exposed to the periphery.
Minocycline-EDTA-Ethanol Antimicrobial Catheter Lock Solution Is Highly Effective
In Vitro
for Eradication of Candida auris Biofilms
Authors: Reitzel Ruth A. , Rosenblatt Joel , Gerges Bahgat Z. , Vargas-Cruz Nylev , Raad Issam I.
Published: January 2020

Candida auris
is an emerging pathogen that can cause virulent central-line-associated bloodstream infections. Catheter salvage through the eradication of biofilms is a desirable therapeutic option. We compared taurolidine and minocycline-EDTA-ethanol (MEE) catheter lock solutions
in vitro
for the eradication of biofilms of 10
C. auris
strains. MEE fully eradicated all
C. auris
biofilms, while taurolidine lock partially eradicated all of the
C. auris
biofilms.
Direct Electron Transfer between the
frhAGB
-Encoded Hydrogenase and Thioredoxin Reductase in the Nonmethanogenic Archaeon
Thermococcus onnurineus
NA1
Authors: Jung Hae-Chang , Lim Jae Kyu , Yang Tae-Jun , Kang Sung Gyun , Lee Hyun Sook
Published: January 2020

This study has importance in that TrxR can use H
2
as an electron donor with the aid of the
frhAGB
-encoded hydrogenase as well as NAD(P)H in
T. onnurineus
NA1. Further studies are needed to explore the physiological significance of this protein. This study also has importance as a significant step toward understanding the functionality of the
frhAGB
-encoded hydrogenase in a nonmethanogen; the hydrogenase can transfer electrons derived from oxidation of H
2
to a protein target by direct contact without the involvement of an electron carrier, which is distinct from the mechanism of its homologs, F
420
-reducing hydrogenases of methanogens.
Dual Agarolytic Pathways in a Marine Bacterium,
Vibrio
sp. Strain EJY3: Molecular and Enzymatic Verification
Authors: Yu Sora , Yun Eun Ju , Kim Dong Hyun , Park So Young , Kim Kyoung Heon
Published: January 2020

Agarose is the main polysaccharide of red macroalgae and is composed of galactose and 3,6-anhydro-
l
-galactose. Many marine bacteria possess enzymes capable of depolymerizing agarose into oligomers and then depolymerizing the oligomers into monomers. Here, we experimentally verified that both a well-known agarolytic pathway and a novel agarolytic pathway exist in a marine bacterium,
Vibrio
sp. strain EJY3. In agarolytic pathways, agarose is depolymerized mainly into 4-sugar-unit oligomers by extracellular enzymes, which are then transported into cells. The imported oligomers are intracellularly depolymerized into galactose and 3,6-anhydro-
l
-galactose by two different agarolytic pathways, using different combinations of intracellular enzymes. These results elucidate the depolymerization routes of red macroalgal biomass in the ocean by marine bacteria and provide clues for developing industrial processes for efficiently producing sugars from red macroalgae.
Interaction of Brucella abortus with Osteoclasts: a Step toward Understanding Osteoarticular Brucellosis and Vaccine Safety
Authors: Khalaf Omar H. , Chaki Sankar P. , Garcia-Gonzalez Daniel G. , Suva Larry J. , Gaddy Dana , Arenas-Gamboa Angela M.
Published: January 2020

Osteoarticular disease is a frequent complication of human brucellosis. Vaccination remains a critical component of brucellosis control, but there are currently no vaccines for use in humans, and no
in vitro
models for assessing the safety of candidate vaccines in reference to the development of bone lesions currently exist. While the effect of
Brucella
infection on osteoblasts has been extensively evaluated, little is known about the consequences of osteoclast infection.
A Genome-Wide CRISPR-Cas9 Screen Identifies the Dolichol-Phosphate Mannose Synthase Complex as a Host Dependency Factor for Dengue Virus Infection
Authors: Labeau Athena , Simon-Loriere Etienne , Hafirassou Mohamed-Lamine , Bonnet-Madin Lucie , Tessier Sarah , Zamborlini Alessia , Dupré Thierry , Seta Nathalie , Schwartz Olivier , Chaix Marie-Laure , Delaugerre Constance , Amara Ali , Meertens Laurent
Published: January 2020

Dengue disease, which is caused by dengue virus (DENV), has emerged as the most important mosquito-borne viral disease in humans and is a major global health concern. DENV encodes only few proteins and relies on the host cell machinery to accomplish its life cycle. The identification of the host factors important for DENV infection is needed to propose new targets for antiviral intervention. Using a genome-wide CRISPR-Cas9 screen, we identified DPM1 and -3, two subunits of the DPMS complex, as important host factors for the replication of DENV as well as other related viruses such as Zika virus. We established that DPMS complex plays dual roles during viral infection, both regulating viral RNA replication and promoting viral structural glycoprotein folding/stability. These results provide insights into the host molecules exploited by DENV and other flaviviruses to facilitate their life cycle.
Human Epitopes Identified from Herpes Simplex Virus Tegument Protein VP11/12 (UL46) Recall Multifunctional Effector Memory CD4+TEMCells in Asymptomatic Individuals and Protect from Ocular Herpes Infection and Disease in “Humanized” HLA-DR Transgenic Mice
Authors: Srivastava Ruchi , Coulon Pierre-Gregoire A. , Prakash Swayam , Dhanushkodi Nisha R. , Roy Soumyabrata , Nguyen Angela M. , Alomari Nuha I. , Mai Uyen T. , Amezquita Cassendra , Ye Caitlin , Maillère Bernard , BenMohamed Lbachir
Published: January 2020

We report that naturally protected HSV-1-seropositive asymptomatic individuals develop a higher frequency of antiviral effector memory CD4+TEMcells specific to two immunodominant epitopes derived from the HSV-1 tegument protein VP11/12. Immunization of HLA-DR transgenic mice with a mixture of these two immunodominant CD4+T cell epitopes induced a robust antiviral CD4+T cell response in the cornea that was associated with protective immunity against ocular herpes. The emerging concept of developing an asymptomatic herpes vaccine that would boost effector memory CD4+and CD8+TEMcell responses is discussed.
Two Functional Variants of AP-1 Complexes Composed of either γ2 or γ1 Subunits Are Independently Required for Major Histocompatibility Complex Class I Downregulation by HIV-1 Nef
Authors: Tavares Lucas A. , de Carvalho Julianne V. , Costa Cristina S. , Silveira Roberta M. , de Carvalho Andreia N. , Donadi Eduardo A. , daSilva Luis L. P.
Published: January 2020

HIV-1 Nef mediates evasion of the host immune system by inhibiting MHC-I surface presentation of viral antigens. To achieve this goal, Nef modifies the intracellular trafficking of MHC-I molecules in several ways. Despite being the subject of intense study, the molecular details underlying these modifications are not yet fully understood. Adaptor protein 1 (AP-1) plays an essential role in the Nef-mediated downregulation of MHC-I molecules such as HLA-A in different cell types. However, AP-1 has two functionally distinct variants composed of either γ1 or γ2 subunit isoforms. Because previous studies on the role of AP-1 in MHC-I downregulation by Nef focused on AP-1γ1, an important open question is the participation of AP-1γ2 in this process. Here, we show that AP-1γ2 is also essential for Nef-mediated depletion of surface HLA-A molecules in T cells. Our results indicate that Nef hijacks AP-1γ2 to modify HLA-A intracellular transport, redirecting these proteins to lysosomes for degradation.
Takayasu arteritis in a rural hospital in Indonesia
Authors: Lusida Michael , Kurniawan Mohammad Zakky , Nugroho Johanes
Published: January 2020

Takayasu arteritis (TA) is a rare chronic granulomatous inflammation of the aorta or its branches and is prevalent all around the world. It causes stenosis of large arteries and ischaemic damage to target organs. There is usually a delay in recognising TA because of the rarity and unfamiliarity with the disease, unspecific early symptoms and lack of diagnostic equipment for early diagnosis. In this report, we present a case of an 18-year-old woman from Pasuruan, East Java, Indonesia, with recurrent fever, headache, claudication of extremities and postprandial abdominal pain. She was diagnosed clinically with suspicion of TA and was sent to a tertiary hospital to confirm the diagnosis. Arteriography revealed that the patient had narrowing of the thoracic and abdominal aorta until the level of the aortic bifurcation. The patient was started on high-dose corticosteroid, cyclosporine A and diltiazem. The patient then showed improvement in her symptoms.
An unusual case of extreme thrombocytosis caused by iron deficiency
Authors: Bergmann Kristin , Bergmann Olav J
Published: January 2020

Iron deficiency is a common cause of reactive thrombocytosis resulting in usually mild to moderately increased but sometimes even in extreme thrombocytosis (ie, >1000×109/L). We report a case of a 34-year-old woman who developed an increased platelet count of 1953×109/L. Upon admission, cytoreductive therapy was initiated until an underlying chronic myeloproliferative neoplasia was ruled out. The patient had undergone bariatric surgery 5 years previously, and surprisingly, a diagnosis of reactive thrombocytosis due to iron deficiency secondary to iron malabsorption was made. It is concluded that the degree of extreme thrombocytosis may be even fourfold to fivefold increased in patients with severe iron deficiency. Our finding emphasises the importance of regular control of possible need for iron supplementation following bariatric surgery.
Swyer-James-MacLeod syndrome and pulmonary arteriovenous malformations: a rare combination
Authors: Griffiths Paul , Kumar Ayesha , Liatsikos Konstantinos
Published: January 2020

This case describes a female patient who presented with an acute on chronic deterioration in respiratory symptoms, on a background of chronic obstructive pulmonary disease and heavy cigarette smoking. Chest radiograph demonstrated long-standing hyperlucency of the right lower lobe, with further imaging later confirming the rare combination of Swyer-James-MacLeod syndrome and multiple pulmonary arteriovenous malformations within the affected lung.
Paediatric porphyria and human hemin: a treatment challenge in a lower middle income country
Authors: Fatima Syeda Anum , Jurair Humaira , Abbas Qalab , Rehman Arshalooz Jamila
Published: January 2020

Here, we report a case of a 15-year-old girl who presented to the emergency department with symptoms of abdominal pain, nausea, vomiting and seizures. She was diagnosed with acute intermittent porphyria. Treatment was started by removing all porphogenic drugs, providing high glucose intake (oral and intravenous), which initially resulted in good clinical outcomes. However, she deteriorated again and also developed neurological manifestation (paraplegia) for which she required mechanical ventilation because of acute respiratory failure. This time she was initiated on human hemin for four consecutive days. After 2 days of therapy, her porphobilinogen levels decreased to 50% of the initial raised value. Increased lactic acid and blood urea nitrogen were the two side effects observed after the treatment, with no apparent signs of acute kidney injury. To the best of our knowledge, in paediatric population, this is the first reported case of treatment of acute intermittent porphyria with human hemin in Pakistan.
Intravenous epinephrine overdose in prehospital management of suspected anaphylaxis
Authors: Callum Jack , Rivlin Myles , Carroll Patrick
Published: January 2020

A 65-year-old woman called paramedics for stridor and neck swelling following an insect bite with a possible anaphylactic reaction. On arrival paramedics administered intramuscular epinephrine without any observed improvement in stridor. Paramedics then prepared 5 mg of 1:1000 epinephrine for nebulised administration, which was inadvertently given intravenously. The patient developed tachycardia, anxiety and a severe headache, with biochemical evidence of cardiac necrosis without any haemodynamic compromise. The patient recovered over the next 24 hours and no long-term sequelae were identified on CT coronary angiogram, electrocardiography (ECG) echocardiography or invasive angiography. This case highlights the risk of cardiac ischaemia during epinephrine administration and the importance of protocols to ensure appropriate dosing. This case also raises questions regarding appropriate management of epinephrine overdose and shines a light on the absence of guidelines on the prevention of complications from epinephrine administration.
Intraoperative mitomycin C and cryotherapy as adjunct therapy for recurrent lobular capillary haemangioma of conjunctiva
Authors: Suman Suwarna , Kumar Arushi
Published: January 2020

Recurrence of lobular capillary haemangioma of conjunctiva after surgical excision is rare but sometimes it may be difficult to manage multiple recurrences. A 31-year-old female patient presented with recurrent polypoid conjunctival lobular capillary haemangioma. Excisional biopsy was performed, followed by eye drop mitomycin C 0.04% four times a day for 1 week postoperatively. She reported again after 3 months with recurrence of vascular elongated nodular lesion. Excision of the mass with application of mitomycin C 0.02% intraoperatively for 1 min and cryotherapy using double thaw technique of the peripheral conjunctival margin was done. The histopathological examination confirmed the recurrence of lobular capillary haemangioma. On review, 1 year after treatment there was no evidence of recurrence. A combined use of cryotherapy and intraoperative mitomycin C as adjunctive therapy after surgical excision can successfully prevent further recurrence without any adverse effect.
Sexual health needs of female sex workers in Côte d’Ivoire: a mixed-methods study to prepare the future implementation of pre-exposure prophylaxis (PrEP) for HIV prevention
Authors: Becquet Valentine , Nouaman Marcellin , Plazy Mélanie , Masumbuko Jean-Marie , Anoma Camille , Kouame Soh , Danel Christine , Eholie Serge Paul , Larmarange Joseph
Published: January 2020

Objective

To describe sexual and reproductive health (SRH) needs of female sex workers (FSWs) to inform the future implementation of pre-exposure prophylaxis (PrEP) for HIV prevention in this population.

Design and setting

The ANRS 12361 PrEP-CI cross-sectional and mixed-methods study was designed and implemented with two community-based organisations in Côte d’Ivoire.

Participants

A convenience sample of 1000 FSWs aged ≥18, not known as HIV-positive, completed a standardised questionnaire assessing sociodemographic characteristics, sexual practices, use of community health services and a priori acceptability of PrEP. Twenty-two indepth interviews and eight focus group discussions were also conducted to document FSWs’ risky practices and sexual behaviours, experiences with violence and discrimination, attitudes regarding HIV and sexually transmitted infections (STIs), and barriers to SRH services.

Results

Although 87% described consistent condom use with clients, more than 22% declared accepting condomless sexual intercourse for a large sum of money. Furthermore, condom use with their steady partner and knowledge of their partner’s HIV status were low despite their acknowledged concurrent sexual partnerships. While inconsistent condom use exposed FSWs to STIs and undesired pregnancies, the prevalence of contraceptive strategies other than condoms was low (39%) due to fear of contraception causing sterility. FSWs faced obstacles to accessing SRH care and preferred advice from their peers or self-medication.

Conclusions

Despite adoption of preventive behaviour in most cases, FSWs are still highly exposed to HIV. Furthermore, FSWs seem to face several barriers to accessing SRH. Implementing PrEP among FSWs in West Africa, such as in Côte d’Ivoire, constitutes an opportunity to consider the regular follow-up of HIV-negative FSWs. PrEP initiation should not condition access to SRH services; conversely, SRH services could be a way to attract FSWs into HIV prevention. Our results highlight the importance of developing a people-focused approach that integrates all SRH needs when transitioning from PrEP efficacy trials to implementation.
Risk of venous thromboembolism in patients undergoing gastric cancer surgery: protocol for a systematic review and meta-analysis
Authors: Wang Dengfeng , Yu Yang , Tao Pengxian , Wang Dan , Chen Yajing , Chen Hao
Published: January 2020

Introduction

Venous thromboembolism (VTE) is a serious life-threatening complication in patients with gastric cancer. Abnormal coagulation function and tumour-related treatment may contribute to the occurrence of VTE. Many guidelines considered that surgical treatment would put patients with cancer at high risk of VTE, so positive prevention is needed. However, there are no studies that have systematically reviewed the postoperative risk and distribution of VTE in patients with gastric cancer. We thus conduct this systematic review to determine the risk of VTE in patients with gastric cancer undergoing surgery and provide some evidence for clinical decision-making.

Methods and analysis

Studies reporting the incidence of VTE after gastric cancer surgery will be included. Primary studies of randomised controlled trials, cohort studies, population-based surveys and cross-sectional studies are eligible for this review and only studies published in Chinese and English will be included. We will search the Medline, Embase, Web of Science, CBM, CNKI and Wanfang data from their inception to November 2019. Two reviewers will independently select studies and extract data. The quality of each included study will be assessed with tools corresponding to their study design. Meta-analysis will be used to pool the incidence data from included studies. Heterogeneity of the estimates across studies will be assessed, if necessary, a subgroup analysis will be performed to explore the source of heterogeneity. The Grades of Recommendation, Assessment, Development and Evaluation method is applied to assess the level of evidence obtained from this systematic review.

Ethics and dissemination

This proposed systematic review and meta-analysis is based on published data, and thus ethical approval is not required. The results of this review will be sought for publication.

PROSPERO registration number

CRD42019144562
Sex-specific effects of nutritional supplements in infants born early or small: protocol for an individual participant data meta-analysis (ESSENCE IPD-MA)
Authors: Lin Luling , Crowther Caroline , Gamble Greg , Bloomfield Frank , Harding Jane E
Published: January 2020

Introduction

Preterm and small for gestational age (SGA) infants are at increased risk of poor growth, disability and delayed development. While growing up they are also at increased risk of obesity, diabetes and later heart disease. The risk of such adverse outcomes may be altered by how preterm and SGA infants are fed after birth. Faltering postnatal growth is common due to failure to achieve recommended high energy and protein intakes, and thus preterm and SGA infants are often provided with supplemental nutrition soon after birth. Enhanced nutrition has been associated with improved early growth and better cognitive development. However, limited evidence suggests that faster growth may increase the risk for later adiposity, metabolic and cardiovascular disease, and that such risks may differ between girls and boys.

Methods and analysis

We will search Ovid MEDLINE, Embase, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, controlled-trials.com, ClinicalTrials.gov and anzctr.org.au for randomised trials that studied the effects of macronutrient supplements for preterm and SGA infants on (i) developmental and metabolic and (ii) growth outcomes after hospital discharge. The outcomes will be (i) cognitive impairment and metabolic risk (co-primary) and (ii) body mass index. Individual participant data (IPD) from all available trials will be included using an intention-to-treat approach. A one-stage procedure for IPD meta-analysis (MA) will be used, accounting for clustering of participants within studies. Exploratory subgroup analyses will further investigate sources of heterogeneity, including sex and size of infants, different timing, duration and type of supplements.

Ethics and dissemination

This IPD-MA is approved by the University of Auckland Human Participants Ethics Committee (reference number: 019874). Individual studies have approval from relevant local ethics committees. Results will be disseminated in a peer-reviewed journal and presented at international conferences.

PROSPERO registration number

CRD42017072683
Global epidemiology of acute generalised peritonitis: a protocol for a systematic review and meta-analysis
Authors: Tochie Joel Noutakdie , Agbor Ndip Valirie , Frank Leonel Tianyi Tianyi , Mbonda Aime , Aji Abang Desmond , Danwang Celestin
Published: January 2020

Introduction

Globally, acute generalised peritonitis (AGP) is a common medical and surgical emergency which is a major contributor to non-trauma deaths despite improvements in diagnosis and surgical and intensive care management. In order to determine the global burden of AGP, geared at tailoring key interventions to curb its morbidity and mortality, we proposed this first ever systematic review and meta-analysis to estimate the contemporary prevalence, and to determine the most frequent AGP and the case fatality rate of AGP, at the global scene.

Methods and analysis

We intend to searchAfricanJournalsOnline, Americana em Ciências da Saúde, Citation index, EMBASE, Global Index Medicus, Literatura Latino Africa Index Medicus, Medline and Scientific Electronic Library Online databases from 1 January 2009 to 31 July 2019 to identify studies that reported the prevalence, types of AGP, and case fatality rate of AGP in the global population without any language restrictions. Study selection, data extraction and risk of bias assessment will be conducted independently at each level by a pair of independent investigators. Random-effects meta-analysis will be used to pool studies judged to be clinically homogeneous. The presence of heterogeneity will be evaluated using the χ² test on Cochrane’s Q statistic and quantified with the I² statistics. Publication bias will be evaluated statistically and visually using the Egger’s test and funnel plots, respectively. Findings will be reported and compared by countries, WHO regions and globally.

Ethics and dissemination

Since this study will be based on published data, it does will not require an ethical approval. The findings will be published in a scientific peer-reviewed journal. They will also be presented at scientific conferences and to relevant public health actors.

PROSPERO registration number

CRD42019143331.
Medical student confidence in care of the dying and their family: a systematic review
Authors: Wells Geoffrey , Youssef Elaney , Winter Rebecca , Wright Juliet , Llewellyn Carrie
Published: January 2020

Background

The General Medical Council expects medical graduates to care for dying patients with skill, clinical judgement and compassion. UK surveys continually demonstrate low confidence and increasing distress amongst junior doctors when providing care to the dying.

Aim

This systematic review aims to determine what has been evidenced within worldwide literature regarding medical undergraduate confidence to care for dying patients.

Design

A systematic electronic search was undertaken. Data extraction included measurements of baseline confidence, associated assessment tools and details of applied educational interventions. Pre/postintervention confidence comparisons were made. Factors influencing confidence levels were explored.

Data sources

MEDLINE, CINAHL, EMBASE, ISI Web of Science, ERIC, PsycINFO, British Education Index and Cochrane Review databases were accessed, with no restrictions on publication year. Eligible studies included the terms ‘medical student’, ‘confidence’ and ‘dying’, alongside appropriate MeSH headings. Study quality was assessed using the Mixed Methods Appraisal Tool.

Results

Fifteen eligible studies were included, demonstrating a diversity of assessment tools. Student confidence was low in provision of symptom management, family support, and psycho-spiritual support to dying patients. Eight interventional studies demonstrated increased postinterventional confidence. Lack of undergraduate exposure to dying patients and lack of structure within undergraduate palliative care curricula were cited as factors responsible for low confidence.

Conclusion

This review clarifies the objective documentation of medical undergraduate confidence to care for the dying. Identifying where teaching fails to prepare graduates for realities in clinical practice will help inform future undergraduate palliative care curriculum planning.

PROSPERO registration number

CRD42019119057.
Electroacupuncture for stress-related urinary incontinence in elderly women: data analysis from two randomised controlled studies
Authors: Sun Biyun , Liu Yan , Su Tongsheng , Sun Yuanjie , Liu Zhishun
Published: January 2020

Objective

To compare the efficacy of electroacupuncture (EA) in elderly and non-elderly women with stress urinary incontinence (SUI) or stress-predominant mixed urinary incontinence (MUI).

Methods

This study was a secondary analysis of two randomised controlled trials involving 252 women with SUI and 132 women with stress-predominant MUI who were treated with the same EA regimen. Elderly women were defined as those aged >60 years. The main outcome measure was the proportion of patients with ≥50% decrease in the mean 72-hour urinary incontinence episode frequency (IEF) from baseline to week 6. Overall, 1004 women were recruited in the SUI and MUI trials. In the EA group, those with urge-predominant or balanced MUI at baseline were excluded from the current study, resulting in a sample size of 384.

Results

Out of 384 patients with SUI or stress-predominant MUI who were treated with EA, 371 completed the study. After 6-week treatment, the proportion of women who achieved ≥50% decrease in mean 72-hour IEF from baseline was 57.3% (51/89) in the elderly group and 60.70% (173/285) in the non-elderly group; the between-group difference was not significant (3.11%, 95% CI −9.83% to 16.05%; p=0.637). Similar outcomes were observed at weeks 4, 16 and 28. Both groups showed reduction in the 72 -hour IEF, amount of urine leakage (assessed by 1-hour pad test) and International Consultation on Incontinence Questionnaire-Short Form score from baseline with no significant between-group difference. No obvious EA-related adverse events were observed during the study.

Conclusion

EA may be an effective and safe alternative treatment for SUI or stress-predominant MUI in both elderly and non-elderly women. Age may not affect the treatment outcomes of acupuncture.

Trial registration numer

NCT01784172,NCT02047032.
Mifepristone and misoprostol compared to osmotic dilators for cervical preparation prior to surgical abortion at 15–18 weeks' gestation: a randomised controlled non-inferiority trial
Authors: Paris Amy E , Vragovic Olivera , Sonalkar Sarita , Finneseth Molly , Borgatta Lynn
Published: January 2020

Objective

Cervical preparation is recommended prior to second-trimester surgical abortion. Osmotic dilators are an effective means to prepare the cervix, but require an additional procedure and may cause discomfort. We compared cervical preparation with mifepristone and misoprostol to preparation with osmotic dilators.

Study design

A randomised, controlled, non-inferiority trial was performed to compare cervical preparation with mifepristone and misoprostol to preparation with osmotic dilators in women undergoing surgical abortion between 15 and 18 weeks gestation. The medication group (n=29) received mifepristone 200 mg orally 24 hours prior to uterine evacuation and misoprostol 400 μg buccally 2 hours before the procedure. The dilator group (n=20) underwent osmotic dilator insertion 24 hours prior to the procedure. The primary outcome was total procedure time, from insertion to removal of the speculum. Secondary outcomes included operative time (from intrauterine instrumentation to speculum removal), initial cervical dilation, nausea, pain, ease of procedure, and whether participants would choose the same modality in the future.

Results

For mean total procedure time, medication preparation (14.0 min, 95% CI 12.0–16.1) was not inferior to dilators (14.3 min, 95% CI 11.7 to 16.8, p<0.001). Mean operative time and ease of procedure were also similar between groups. More women in the medication group than the dilator group would prefer to use the same method in the future (86% vs 30%, p=0.003).

Conclusion

Prior to surgical abortion at 15–18 weeks, use of mifepristone and misoprostol did not result in longer procedure times than overnight osmotic dilators.

Trial registration number

NCT01462.
Hormonal contraception and HIV acquisition among women: an updated systematic review
Authors: Curtis Kathryn M , Hannaford Philip C , Rodriguez Maria Isabel , Chipato Tsungai , Steyn Petrus S , Kiarie James N
Published: January 2020

Objective

To update a 2016 systematic review on hormonal contraception use and HIV acquisition.

Methods

We searched Pubmed and Embase between 15 January 2016 and 26 June 2019 for longitudinal studies comparing incident HIV infection among women using a hormonal contraceptive method and either non-users or users of another specific hormonal contraceptive method. We extracted information from newly identified studies, assessed study quality, and updated forest plots and meta-analyses.

Results

In addition to 31 previously included studies, five more were identified; three provided higher quality evidence. A randomised clinical trial (RCT) found no statistically significant differences in HIV risk among users of intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel implant (LNG implant) or the copper intrauterine device (Cu-IUD). An observational study found no statistically significant differences in HIV risk among women using DMPA, norethisterone enanthate (NET-EN), implants (type not specified) or Cu-IUD. Updated results from a previously included observational study continued to find a statistically significant increased HIV risk with oral contraceptives and DMPA compared with no contraceptive use, and found no association between LNG implant and HIV risk.

Conclusions

High-quality RCT data comparing use of DMPA, LNG implant and Cu-IUD does not support previous concerns from observational studies that DMPA-IM use increases the risk of HIV acquisition. Use of other hormonal contraceptive methods (oral contraceptives, NET-EN and implants) is not associated with an increased risk of HIV acquisition.
What does the ideal urgent and emergency care system look like? A qualitative study of service user perspectives
Authors: Ablard Suzanne , Kuczawski Maxine , Sampson Fiona C , Mason Suzanne M
Published: January 2020

Background

Policies aimed at diverting care from EDs to alternative services have not been successful in reducing ED attendances and have contributed to confusion for service users when making care-seeking decisions. It is important that service users are at the heart of decision making to ensure new services meet the needs of those who will be accessing them. In this study, service users were encouraged to think freely about the desirable qualities of an ideal urgent and emergency care (UEC) system.

Methods

From September to February 2019, an open inductive methodology was used to conduct focus groups with service users who had used UK UEC services within the previous year. Service users that had contact with NHS111, ambulance service, General Practice out-of-hours, minor injuries unit, walk-in centre or ED were purposively sampled and stratified into the following groups: (1) 18–45 years; (2)≥75 years; (3) adults with young children; (4) adults with long-term conditions. Focus groups were structured around experiences of accessing UEC services and perspectives of an ‘ideal’ UEC system.

Results

30 service users took part in the study, across four focus groups. The ideal UEC system centred around three themes: a simplified UEC system (easier to understand and a single-point of access); more ‘joined-up’ UEC services and better communication between health staff and patients.

Conclusion

Desirable qualities of an ideal UEC system from a service user perspective related to simplifying access for example, through a single point of access system where health professionals decide the appropriate service required and improving continuity of care through better integration of UEC services. Service users value reassurance and communication from health professionals about care pathways and care choices, and this helps service users feel more in control of their healthcare journey.
Are referrals to hospital from out-of-hours primary care associated with National Early Warning Scores?
Authors: Finnikin Samuel , Hayward Gail , Wilson Fay , Lasserson Daniel
Published: January 2020

Background

The National Early Warning Scores (NEWS) is used in various healthcare settings to augment clinical decision making, and there is growing interest in its application in primary care. This research aimed to determine the distribution of NEWS among patients in UK out-of-hours (OOH) general practice and explore the relationship between NEWS and referral of patients to hospital.

Methods

A historical cohort study using routinely collected data from the Birmingham Out-of-hours general practice Research Database. This includes patients who attended a large out-of-hours general practice provider in the West Midlands, UK, between July 2013 and July 2018. All adults who were seen face to face who had a full set of physiological observations recorded were included. NEWS was calculated post hoc, and subsequent hospital referral was the outcome of interest.

Results

A NEWS was calculated for 74 914 consultations. 46.9% of patients had a NEWS of 0, while 30.6% had a NEWS of 1. Patients were referred to hospital in 8.5% of all encounters. Only 6.9% (95% CI 6.3% to 7.5%) of the 6878 patients referred to hospital had a NEWS of ≥5. Of the 1509 patients with a NEWS ≥5, 68.6% (95%CI 66.2% to 70.9%) were not referred to hospital. When considering how NEWS was related to hospital referral, the area under the receiver operating characteristic (AUROC) for patients seen in their own home was 0.731 (95%CI 0.681 to 0.787). For patient seen in treatment centres, the AUROC was 0.589 (95% CI 0.582 to 0.596).

Conclusions

Patients seen in out-of-hours general practice have low physiological acuity. Those referred to hospital have a slightly higher NEWS overall. NEWS is poorly associated with hospital referral, although the association is stronger for patients seen in at home compared with patients seen in treatment centres. Implementing NEWS-based referral from OOH general practice is likely to increase hospital admissions.
S100A11/ANXA2 belongs to a tumour suppressor/oncogene network deregulated early with steatosis and involved in inflammation and hepatocellular carcinoma development
Authors: Sobolewski Cyril , Abegg Daniel , Berthou Flavien , Dolicka Dobrochna , Calo Nicolas , Sempoux Christine , Fournier Margot , Maeder Christine , Ay Anne-Sophie , Clavien Pierre-Alain , Humar Bostjan , Dufour Jean-François , Adibekian Alexander , Foti Michelangelo
Published: January 2020

Objective

Hepatocellular carcinoma (HCC) development occurs with non-alcoholic fatty liver disease (NAFLD) in the absence of cirrhosis and with an increasing incidence due to the obesity pandemic. Mutations of tumour suppressor (TS) genes and oncogenes (ONC) have been widely characterised in HCC. However, mounting evidence indicates that non-genomic alterations of TS/ONC occur early with NAFLD, thereby potentially promoting hepatocarcinogenesis in an inflammatory/fibrotic context. The aim of this study was to identify and characterise these alterations.

Design

The proteome of steatotic liver tissues from mice spontaneously developing HCC was analysed. Alterations of TSs/ONCs were further investigated in various mouse models of NAFLD/HCC and in human samples. The inflammatory, fibrogenic and oncogenic functions of S100A11 were assessed through in vivo, in vitro and ex-vivo analyses.

Results

A whole set of TSs/ONCs, respectively, downregulated or upregulated was uncovered in mice and human with NAFLD. Alterations of these TSs/ONCs were preserved or even exacerbated in HCC. Among them, overexpression of S100A11 was associated with high-grade HCC and poor prognosis. S100A11 downregulation in vivo significantly restrains the development of inflammation and fibrosis in mice fed a choline/methionine-deficient diet. Finally, in vitro and ex-vivo analyses revealed that S100A11 is a marker of hepatocyte de-differentiation, secreted by cancer cells, and promoting cell proliferation and migration.

Conclusion

Cellular stress associated with NAFLD triggers non-genomic alterations of a whole network of TSs/ONCs fostering hepatocarcinogenesis. Among those, overexpression of the oncogenic factor S100A11 promotes inflammation/fibrosis in vivo and is significantly associated with high-grade HCC with poor prognosis.
Correlation of mismatch repair protein deficiency, PD-L1 and CD8 expression in high-grade urothelial carcinoma of the bladder
Authors: Hodgson Anjelica , Vesprini Danny , Liu Stanley K , Xu Bin , Downes Michelle R
Published: January 2020

Mismatch repair-deficient (d-MMR) tumours have been reported to show susceptibility to immune checkpoint inhibitors targeting programmed death-1/PD ligand-1 (PD-1/PD-L1). In this study, we sought to correlate the association of d-MMR, PD-L1 and CD8 expression in muscle invasive, high-grade urothelial carcinoma (HGUC) of bladder. A tissue microarray (TMA) was constructed from 201 cases and sequentially stained with PD-L1, CD8, MSH2, MSH6, MLH1 and PMS2. PD-L1 was assessed in tumour and immune cells. CD8 was assessed in a hotspot fashion with results averaged across cores. Loss of nuclear MMR expression on TMA sections was further assessed using corresponding whole tissue sections. d-MMR was identified in four cases (2%). The mean CD8 count was significantly higher in d-MMR tumours (10 vs 35, p=0.007) as was the proportion of PD-L1 positivity (75% vs 20%, p=0.031). d-MMR is uncommon in HGUC of bladder but shows strong correlation with cytotoxic T lymphocyte infiltration and PD-L1 tissue expression.
Individual and county-level variation in outcomes following non-fatal opioid-involved overdose
Authors: Lowder Evan Marie , Amlung Joseph , Ray Bradley R
Published: January 2020

Background

A lack of large-scale, individually linked data often has impeded efforts to disentangle individual-level variability in outcomes from area-level variability in studies of many diseases and conditions. This study investigated individual and county-level variability in outcomes following non-fatal overdose in a state-wide cohort of opioid overdose patients.

Methods

Participants were 24 031 patients treated by emergency medical services or an emergency department for opioid-involved overdose in Indiana between 2014 and 2017. Outcomes included repeat non-fatal overdose, fatal overdose and death. County-level predictors included sociodemographic, socioeconomic and treatment availability indicators. Individual-level predictors included age, race, sex and repeat non-fatal opioid-involved overdose. Multilevel models examined outcomes following non-fatal overdose as a function of patient and county characteristics.

Results

10.9% (n=2612) of patients had a repeat non-fatal overdose, 2.4% (n=580) died of drug overdose and 9.2% (n=2217) died overall. Patients with a repeat overdose were over three times more likely to die of drug-related causes (OR=3.68, 99.9% CI 2.62 to 5.17, p<0.001). County-level effects were limited primarily to treatment availability indicators. Higher rates of buprenorphine treatment providers were associated with lower rates of mortality (OR=0.82, 95% CI 0.68 to 0.97, p=0.024), but the opposite trend was found for naltrexone treatment providers (OR=1.20, 95% CI 1.03 to 1.39, p=0.021). Cross-level interactions showed higher rates of Black deaths relative to White deaths in counties with high rates of naltrexone providers (OR=1.73, 95% CI 1.09 to 2.73, p=0.019).

Conclusion

Although patient-level differences account for most variability in opioid-related outcomes, treatment availability may contribute to county-level differences, necessitating multifaceted approaches for the treatment and prevention of opioid abuse.
Dose–response relationship between hand–arm vibration exposure and vibrotactile thresholds among roadworkers
Authors: Clemm Thomas , Færden Karl , Ulvestad Bente , Lunde Lars-Kristian , Nordby Karl-Christian
Published: January 2020

Background

Testing of vibration perception threshold (VPT) at the fingertips as a quantitative measure of tactile sensitivity is a commonly used tool in diagnosing hand–arm vibration syndrome. There is limited research on dose–response relationships between hand–arm vibration (HAV) exposure and VPT on an individual level.

Aims

Assess possible dose–response relationships on an individual level between HAV exposure and VPT at the fingertips.

Methods

We assessed average daily vibration exposure (m/s2A8) and cumulative lifetime HAV exposure for 104 participants from different departments in a road maintenance company based on vibration measurements and questionnaires. VPT was measured based on the technical method described in ISO 13091-1:2005 using octave frequencies 8–500 Hz. We investigated associations using linear regression models with significance level p≤0.05.

Results

The participants were either exposed to rock drills (n=33), impact wrenches (n=52) or none of these tools (n=19). Exposure to rock drills and impact wrenches was associated with elevated VPT for all seven test frequencies in the second and fifth fingers of both hands. A dose–response with the daily exposure measure m/s2(A8) was found based on 1.2 m/s2(A8) for impact wrenches, and 5.4 m/s2(A8) for rock drills. A stronger association was found with the cumulative exposure for rock drills compared with impact wrenches, and for the second finger compared with the fifth finger.

Conclusions

HAV exposure was associated with elevated VPT, also at exposure levels below the common exposure action value of 2.5 m/s2(A8). Lowering the HAV exposure can contribute to prevent increasing VPTs in these workers.
Cost–utility analysis of learning and coping versus standard education in cardiac rehabilitation: a randomised controlled trial with 3 years of follow-up
Authors: Tayyari Dehbarez Nasrin , Palmhøj Nielsen Camilla , Risør Bettina Wulff , Vinther Nielsen Claus , Lynggaard Vibeke
Published: January 2020

Objectives

To enhance adherence to cardiac rehabilitation (CR), a patient education programme called ‘learning and coping’ (LC-programme) was implemented in three hospitals in Denmark. The aim of this study was to investigate the cost–utility of the LC-programme compared with the standard CR-programme.

Methods

825 patients with ischaemic heart disease or heart failure were randomised to the LC-programme or the standard CR-programme and were followed for 3 years.

A societal cost perspective was applied and quality-adjusted life years (QALY) were based on SF-6D measurements. Multiple imputation technique was used to handle missing data on the SF-6D. The statistical analyses were based on means and bootstrapped SEs. Regression framework was employed to estimate the net benefit and to illustrate cost-effectiveness acceptability curves.

Results

No statistically significant differences were found between the two programmes in total societal costs (4353 Euros; 95% CI –3828 to 12 533) or in QALY (–0.006; 95% CI –0.053 to 0.042). At a threshold of 40 000 Euros, the LC-programme was found to be cost-effective at 15% probability; however, for patients with heart failure, due to increased cost savings, the probability of cost-effectiveness increased to 91%.

Conclusions

While the LC-programme did not appear to be cost-effective in CR, important heterogeneity was noted for subgroups of patients. The LC-programme was demonstrated to increase adherence to the rehabilitation programme and to be cost-effective among patients with heart failure. However, further research is needed to study the dynamic value of heterogeneity due to the small sample size in this subgroup.
Human papillomavirus and abnormal cervical lesions among HIV-infected women in HIV-discordant couples from Kenya
Authors: Guthrie Brandon L , Rositch Anne F , Cooper Joy Alison , Farquhar Carey , Bosire Rose , Choi Robert , Kiarie James , Smith Jennifer S
Published: January 2020

Objective

HIV infection increases the risk of high-grade cervical neoplasia and invasive cervical carcinoma. The study addresses the limited data describing human papillomavirus (HPV) infection and cervical neoplasia among HIV-infected women in HIV-discordant relationships in sub-Saharan Africa, which is needed to inform screening strategies.

Methods

A cross-sectional study of HIV-infected women with HIV-uninfected partners was conducted to determine the distribution of type-specific HPV infection and cervical cytology. This study was nested in a prospective cohort recruited between September 2007 and December 2009 in Nairobi, Kenya. Cervical cells for HPV DNA testing and conventional cervical cytology were collected. HPV types were detected and genotyped by Roche Linear Array PCR assay.

Results

Among 283 women, the overall HPV prevalence was 62%, and 132 (47%) had ≥1 high-risk (HR)-HPV genotype. Of 268 women with cervical cytology results, 18 (7%) had high-grade cervical lesions or more severe by cytology, of whom 16 (89%) were HR-HPV-positive compared with 82 (41%) of 199 women with normal cytology (p<0.001). The most common HR-HPV types in women with a high-grade lesion or more severe by cytology were HPV-52 (44%), HPV-31 (22%), HPV-35 (22%), HPV-51 (22%) and HPV-58 (22%). HR-HPV genotypes HPV-16 or HPV-18 were found in 17% of women with high-grade lesions or more severe. HR-HPV screening applied in this population would detect 89% of those with a high-grade lesion or more severe, while 44% of women with normal or low-grade cytology would screen positive.

Conclusion

HR-HPV prevalence was high in this population of HIV-infected women with an uninfected partner. Choice of screening for all HR genotypes versus a subset of HR genotypes in these HIV-infected women will strongly affect the performance of an HPV screening strategy relative to cytological screening. Regional and subpopulation differences in HR-HPV genotype distributions could affect screening test performance.