bluuebunny/crossref_metadata_2025 huggingface dataset:
Monosaccharides: A ToF-SIMS reference spectra database. I. Negative polarity
Authors: Bernard Laetitia , Crockett Rowena , Kawecki Maciej
Published: December 2019

The number of time-of-flight secondary ion mass spectrometry studies on biological tissues and cells has significantly increased since the development of primary ion sources that allow not only elemental but also molecular analysis. Substantial fragmentation during ionic bombardment results in a large number of peaks, rendering data analysis complex. Complete and trustable sets of reference spectra for the main biological building blocks, i.e., amino acids, monosaccharides, fatty acids, and nucleotides, are required. This work aims to provide an accurate and extensive library of reference spectra for monosaccharides, measured with the Bi3+ primary ion. Here (Paper I), the negative polarity spectra and lists of associated characteristic fragments are presented.
A catalogue of reptiles of Monfragüe National Park (Spain), with molecular characterization of populations of Blanus Wagler, 1830 in this protected area
Authors: Fernández Ortín Daniel , Sánchez Montes Gregorio , Martinez-Solano Iñigo
Published: December 2019

Monfragüe National Park (Cáceres, Extremadura, Spain) is a protected area in central-western Iberia,including some of the best preserved primary Mediterranean vegetation. Legal protection dates back to 1979 (first as a Natural Park and then as a National Park), but knowledge about its reptile communities is so far limited to sparse records. In this paper we present an updated species list based on 521 records covering 163 1x1 km UTM grids in the study area, compiled in the period 2000-2019. We detected 20 native species, representing 71.4% of the reptile fauna in Extremadura and 35% of the ibero-balearic reptile fauna. Additionally, based on molecular analyses populations of the amphisbaenid genus Blanus in the study area are assigned to the oriental Iberian taxon, B. cinereus. The new records extend the known distribution of the different reptile species in the study area in 56 10x10 km UTM grids. Species presenting more restricted distributions in Monfragüe are Lacerta schreiberi (one 1x1 grid), Emys orbicularis, and Acanthodactylus erythrurus (four 10x10 grids each).
LysR-Type Transcriptional Regulator MetR Controls Prodigiosin Production, Methionine Biosynthesis, Cell Motility, H
2
O
2
Tolerance, Heat Tolerance, and Exopolysaccharide Synthesis in Serratia marcescens
Authors: Pan Xuewei , Sun Changhao , Tang Mi , You Jiajia , Osire Tolbert , Zhao Youxi , Xu Meijuan , Zhang Xian , Shao Minglong , Yang Shangtian , Yang Taowei , Rao Zhiming
Published: December 2019

Serratia marcescens
, a Gram-negative bacterium, is found in a wide range of ecological niches and can produce several secondary metabolites, including prodigiosin, althiomycin, and serratamolide. Among them, prodigiosin shows diverse functions as an immunosuppressant, antimicrobial, and anticancer agent. However, the regulatory mechanisms behind prodigiosin synthesis in
S. marcescens
are not completely understood. Here, we adapted a transposon mutant library to identify the genes related to prodigiosin synthesis, and the
BVG90_22495
gene encoding the LysR-type regulator MetR was found to negatively regulate prodigiosin synthesis. The molecular mechanism of the
metR
mutant hyperproducing prodigiosin was investigated. Additionally, we provided evidence supporting new roles for MetR in regulating methionine biosynthesis, cell motility, heat tolerance, H
2
O
2
tolerance, and exopolysaccharide synthesis in
S. marcescens
. Collectively, this work provides novel insight into regulatory mechanisms of prodigiosin synthesis and uncovers novel roles for the highly conserved MetR protein in regulating prodigiosin synthesis, heat tolerance, exopolysaccharide (EPS) synthesis, and biofilm formation.
Severe illicit gamma-hydroxybutyric acid withdrawal in a pregnant woman: what to do?
Authors: van Mechelen JC , Dijkstra BAG , Vergouwen ACM
Published: December 2019

This case report presents the case of a 29 weeks pregnant woman in her late twenties who was seen at the emergency department of a hospital with a seizure of unknown cause. By anamnesis and hetero-anamnesis the use of illicit gamma-hydroxybutyric acid (GHB) was revealed. Examination showed dilated pupils, sweating, tremor, tachycardia and bradyphrenic thinking. Subsequently, the seizure was indicated as a severe illicit GHB withdrawal symptom. Thereafter, treatment had to be decided on in the absence of evidence-based and practiced-based guidelines and treatment options for this specific patient population. Initially diazepam was started, which was later on substituted by sodium oxybate. Despite the critical professional situation the patient gave birth to a healthy daughter after 37 weeks of pregnancy.
A case of severe relapsing sulphonylurea-induced hypoglycaemia
Authors: Mifsud Simon , Schembri Emma Louise , Fava Stephen
Published: December 2019

The authors report a case of a 64-year-old woman who was diagnosed with severe relapsing sulphonylurea-induced hypoglycaemia. Sulphonylureas are frequently used in patients with type 2 diabetes mellitus. They promote insulin secretion independent of the prevailing glucose level and thus are associated with an increased risk of hypoglycaemia. In patients with adequate renal function, gliclazide’s effect lasts 10–24 hours and it is usually completely eliminated within 144 hours postdose. Since our patient suffered from chronic kidney disease, gliclazide’s effect was prolonged and she was experiencing spontaneous hypoglycaemic episodes up to 21 days postomission of gliclazide. This case highlights two important aspects. Primarily, the prolonged effect of sulphonylureas in patients with impaired renal function, hence highlighting the need to be cautious prior to prescribing sulphonylureas in such patients. Secondly, the importance of prolonged observation of patients on sulphonylureas even after the initial hypoglycaemic event is corrected, due to the extended effects of such drugs.
A rare case of chondrosarcoma arising in parotid with extension to lateral skull base
Authors: Pradhan Sidharth , Sarkar Saurav , Sable Mukund N , Parida Pradipta Kumar
Published: December 2019

Chondrosarcomas of head and neck region are rare. Very few cases of chondrosarcomas arising in parotid gland have been reported and none with intracranial extension. We report a case of a female presenting with a parotid swelling and a mass in external auditory canal with extradural extension to posterior cranial fossa. With a preoperative fine needle aspiration diagnosis of pleomorphic adenoma, it was excised and the histopathology came out to be low-grade myxoid chondrosarcoma. She has not received any adjuvant chemoradiotherapy and there is no evidence of recurrence at months.
Chronic inflammatory demyelinating polyneuropathy: a rare cause of falls
Authors: Saad Toni C , Pickrell William Owen , Payne Gareth , Hamandi Khalid
Published: December 2019

This case of chronic inflammatory demyelinating polyneuropathy (CIDP) shows that a patient’s condition can evolve from the point of admission, gradually manifesting its underlying cause. Our patient’s initial presentation of backpain and lower limb weakness prompted investigations which ruled out compressive myelopathy and neuropathy. As upper limb weakness developed later, along with a more proximal and symmetrical pattern of lower limb weakness, the clinical picture suggested polyneuropathy. The diagnosis of CIDP became apparent only after numerous negative tests and nerve conduction studies which identified demyelination. Diagnosing CIDP enabled the commencement of definitive treatment which led to a good recovery.
Emphysematous gastritis associated with gastric cancer: a rare and fatal entity
Authors: Fonseca Margarida Rodrigues , Constante Mariana , Moura Anne , Melo Valadão Ivone
Published: December 2019

Emphysematous gastritis is a rare disease characterised by air in the wall of the stomach due to gas-forming microorganisms. This is a highly lethal entity for which only prompt diagnosis and treatment can avoid mortality. Different factors have been described that disrupt the integrity of the mucosa such as corrosive ingestion, alcohol abuse, recent abdominal surgery or cancer. We report a case of emphysematous gastritis in a 92-year-old woman who presented to the emergency department with abdominal pain, nausea and vomiting. Inflammatory markers were elevated and abdominal X-rays showed intramural gastric air, confirmed by CT scan. The patient received intravenous fluids, nutritional support and broad-spectrum antibiotic with resolution of gastric wall emphysema. However, the diagnosis of poorly cohesive gastric adenocarcinoma was made and the patient was referred to palliative care. This case highlights the importance of prompt recognition of this lethal entity that represents a rare and aggressive presentation of gastric cancer.
A novel role for milrinone in neonatal acute limb ischaemia: successful conservative treatment of thrombotic arterial occlusion without thrombolysis
Authors: Boyd Stephanie , Shah Vibhuti , Belik Jaques
Published: December 2019

Acute neonatal limb ischaemia (NLI) is most frequently an iatrogenic complication, however, may also occur in utero due to thromboembolism. There is no widely accepted protocol for treatment of NLI and limited evidence to guide management. Thrombolysis and surgical management have been attempted, though both are associated with significant morbidities. Milrinone is a phosphodiesterase-3 inhibitor used for its vasodilatory effects on the systemic and pulmonary vasculature. There is also emerging evidence for benefit of milrinone in ameliorating ischaemia-reperfusion injury. The authors present a case report of a term infant with spontaneous perinatal acute limb ischaemia secondary to near-completely occlusive thrombosis of the right subclavian artery. The infant was successfully managed conservatively with milrinone without requirement for thrombolysis or surgical intervention. Milrinone represents a novel treatment option for neonates with acute limb ischaemia and consideration of a trial of milrinone prior to higher risk treatment options is warranted in this patient group.
Extragastrointestinal stromal tumour (EGIST) presented as a mesenteric and retroperitoneal mass
Authors: Costa Almeida Carlos , Caroço Teresa Vieira , Albano Miguel , Carvalho Luís
Published: December 2019

Extragastrointestinal stromal tumour (EGIST) occurs outside the gastrointestinal tract and has histopathological and molecular characteristics similar to gastrointestinal stromal tumour (GIST). This tumour is rare and aggressive. A male patient was admitted with anaemia and lower limb oedema. CT scan showed a tumour in the mesentery and retroperitoneum, suspected to be a small bowel GIST. During laparotomy an unresectable mass was found compressing the retroperitoneal structures. Pathology and immunohistochemistry (CD117) confirmed an EGIST. EGIST arises from Cajal-like cells or from pluripotent stem cells outside the gastrointestinal tract. It is aggressive and has a worse prognosis than GIST. Immunohistochemistry is crucial for diagnosis. Surgery aimed at debulking as much of a tumour mass as possible is the cornerstone of treatment. The role of imatinib is not clear. EGIST is rare and has a bad prognosis, and there is no consensus on grading and management. A low threshold of suspicion is crucial for early diagnosis.
Acute retinal necrosis by herpes simplex virus type 1: an unusual presentation of a primary infection
Authors: Cruz Gonçalo Pereira , Fonseca Cristina , Oliveira Joaquim , Saraiva da Cunha José
Published: December 2019

Herpes simplex virus (HSV) can affect the central nervous system causing meningitis, encephalitis and, rarely, acute retinal necrosis. We present a case of a 46-year-old man, previously healthy complaining of a 5-day persistent headache and sudden loss of vision of his left eye that progressed to the right. We started ceftriaxone, methylprednisolone and acyclovir for suspected encephalitis with vasculitis. HSV-1 was identified in vitreous and aqueous humour. Therapy with acyclovir was maintained and two intravitreous boluses of foscarnet were administered, without improvement. Usually being a benign infection, HSV can, in rare cases like this, have catastrophic effects in the optic tract.
Intermediate-term outcomes of pars plana tube insertion of Aurolab aqueous drainage implant for refractory glaucoma
Authors: Babu Naresh , Baliga Girish , Wijesinghe Hiruni Kaushalya , Puthuran George Varghese
Published: December 2019

Purpose

To report the safety and efficacy of parsplana tube insertion of Aurolab aqueous drainage implant(AADI) in patients with refractory glaucoma.

Methods

Charts of patients with refractory glaucoma who underwent AADI via the parsplana route between June 2014 and June 2018with a minimum follow-up of 6 months were retrospectively reviewed. Success was defined as complete when the intraocular pressure (IOP) was ≥5 and18 mmHg or IOP reduction was
>
30%from baseline without antiglaucoma medication (AGM) andas qualified if requiring additional AGMs.

Results

The study included 63 eyes of 63 patients with a mean age of 36.1±20.6 years and a mean follow-up of 19.7±15.7 months. Glaucoma postvitreoretinal surgery was the the most common aetiology (22 eyes, 35%). The mean IOP reduced from 36.6±10.7 mmHg to15.7±8.2 (57.1%), 15.02±7.3 (60%) and 17.2±8.5 mmHg (53%)at 6 months and 1 and 2 years, respectively. Kaplan-Meier estimates showed that the cumulative probabilities of failure were 8% (95% CI4.3% to 22.4%) at 6 months, 23% (95%CI12.8% to 38.6%) at 1 year, 30% (95%CI17.4% to 45.9%) at 18 months and 47% (95% CI13.4% to 64.9%) at the 2 years time points.Vitreous blocking tube tip was noted up to 8% of eyes on follow-up.

Conclusion

Pars plana AADI insertion is a useful procedure for the control of IOP in patients with refractory glaucoma.
Adult-onset autoimmune-type enteropathy: potential relationship to an adverse drug reaction
Authors: Chetty Runjan , Cino Maria , Okrainec Allan
Published: December 2019

Objective

To describe an example of adult-onset autoimmune enteropathy (AIE) that coincided with drug-induced reaction.

Design

A 54-year-old patient was presented with Stevens-Johnson syndrome after a course of quinolones. This was followed shortly thereafter by epigastric pain, diarrhoea and weight loss. She also developed an autoimmune neutropenia.

Results

Several biopsies were performed from the upper and lower gastrointestinal tract (GIT). The duodenal biopsies showed intraepithelial lymphocytosis; therefore, coeliac disease was considered. However, confirmatory serology was negative and the patient did not respond to a gluten-free/gliadin-free diet. Both upper and lower GIT biopsies consistently showed an absence of goblet cells resembling the changes of an AIE.

Conclusion

This is an unusual case of autoimmune-pattern enteropathy in an adult that was potentially drug-induced.
Combined effect of modifiable and non-modifiable risk factors for colorectal cancer risk in a pooled analysis of 11 population-based studies
Authors: Wang Xiaoliang , O'Connell Kelli , Jeon Jihyoun , Song Mingyang , Hunter David , Hoffmeister Michael , Lin Yi , Berndt Sonja , Brenner Hermann , Chan Andrew T , Chang-Claude Jenny , Gong Jian , Gunter Marc J , Harrison Tabitha A , Hayes Richard B , Joshi Amit , Newcomb Polly , Schoen Robert , Slattery Martha L , Vargas Ashley , Potter John D , Le Marchand Loic , Giovannucci Edward , White Emily , Hsu Li , Peters Ulrike , Du Mengmeng
Published: December 2019

Objective

‘Environmental’ factors associated with colorectal cancer (CRC) risk include modifiable and non-modifiable variables. Whether those with different non-modifiable baseline risks will benefit similarly from reducing their modifiable CRC risks remains unclear.

Design

Using 7945 cases and 8893 controls from 11 population-based studies, we combined 17 risk factors to characterise the overall environmental predisposition to CRC (environmental risk score (E-score)). We estimated the absolute risks (ARs) of CRC of 10 and 30 years across E-score using incidence-rate data from the Surveillance, Epidemiology, and End Results programme. We then combined the modifiable risk factors and estimated ARs across the modifiable risk score, stratified by non-modifiable risk profile based on genetic predisposition, family history and height.

Results

Higher E-score was associated with increased CRC risk (ORquartile, 1.33; 95% CI 1.30 to 1.37). Across E-scores, 30-year ARs of CRC increased from 2.5% in the lowest quartile (Q1) to 5.9% in the highest (Q4) quartile for men, and from 2.1% to 4.5% for women. The modifiable risk score had a stronger association in those with high non-modifiable risk (relative excess risk due to interaction=1.2, 95% CI 0.5 to 1.9). For those in Q4 of non-modifiable risk, a decrease in modifiable risk reduced 30-year ARs from 8.9% to 3.4% for men and from 6.0% to 3.2% for women, a level lower or comparable to the average population risk.

Conclusions

Changes in modifiable risk factors may result in a substantial decline in CRC risk in both sexes. Those with high inherited risk may reap greater benefit from lifestyle modifications. Our results suggested comprehensive evaluation of environmental factors may facilitate CRC risk stratification.
DHOW2 score leads to significant improvement in acute stroke care management emergency department: a prospective analysis
Authors: Akhtar Naveed , Salam Abdul , Bourke Paula , Kamran Saadat , Bhutta Zain , Joseph Sujatha , Santos Mark , Morgan Deborah , Thomas Stephen , Ajwad Butt Adeel , Shuaib Ashfaq
Published: December 2019

Background

Delays in transfer of patients from emergency department (ED) to stroke ward increases medical complications. We evaluate if a new risk-score ‘DHOW2’ (dysphagia, hemiplegia, observation-required, wet (incontinence) and weight) will identify high-risk patients and whether expedited admission of ‘high-DHOW2’ score patients to SW will result in fewer complications.

Methods

The DHOW2 score was designed to determine risk of complications following acute stroke. Phase I (279 patients) tested rates of complications with increasing DHOW2. Phase II (1091 patients), evaluated if early admission to the SW of high-DHOW2 patients will lead to fewer complications. Phase III (1257 patients) monitored implementation of the DHOW2 following completion of the study.

Findings

Medical complications increased with higher-DHOW2 scores during all three phases; 0%–0.8% with DHOW2 of ≤3, 3.1%–6.5% with DHOW2 of 4–5 and 10.9%–14.1% with DHOW2 of ≥6 (p=<0.001). In phase II, more high-DHOW2 patients were admitted expeditiously to the SW from ED resulting in fewer complications, and fewer deaths. The odds of medical complications with DHOW2 of ≥6 was 36.8–58.3 compared with DHOW2 of ≤3. Expedited SW admission of ‘high-DHOW2 patients’ to within 8 hours reduced the development of complications to odds of 19.18–30.17 (p<0.001).

Interpretations

The DHOW2 score detects patients at risk of AS related medical complications. It is easy to implement in busy EDs where nurses can use the score to identify such patients. The risk stratification by DHOW2 and early transfer of high-scoring patients to SW is associated with significantly fewer complications.
Combination of pembrolizumab and BCG treatment after endoscopic ablation of high-risk superficial upper urinary tract urothelial carcinoma in patients not candidates for radical nephroureterectomy: protocol for phase-II study
Authors: Jamil Marcus L , Deebajah Mustafa , Sood Akshay , Alanee Shaheen
Published: December 2019

Introduction

The treatment standard for high-risk upper urinary tract urothelial carcinoma (UUTUC) is radical nephroureterectomy. However, some patients may be unfit or unwilling, and in such patients the available alternatives are suboptimal. Therapies targeting the programmed death (PD) pathway have shown promise in urothelial carcinom (UC). We designed the current study to determine the safety and efficacy of administering MK-3475 (a monoclonal antibody targeting interaction between PD-1 and its ligand) in combination with bacillus Calmette-Guerin (BCG) in high-risk non-muscle invasive UUTUC patients.

Methods

This represents a single-centre phase-II efficacy study of MK-3475 therapy in combination with BCG for subjects, 18 years of age or older, with pathologically documented non-muscle invasive high-risk UUTUC unfit or unwilling to be treated with radical nephroureterectomy. Twenty subjects will be enrolled; patients will receive treatment with 200 mg of MK-3475 every 21 days, starting 2 weeks from the initial endoscopic resection and continuing for 6 weeks after the final dose of BCG. The primary objective is to determine the safety and efficacy of administering MK-3475 at a fixed dose of 200 mg every 3 weeks in conjunction with intrapelvic BCG. Secondary objectives include 19 week and the 3, 12 and 24-month post-treatment completion complete response and progression-free rate assessments.

Ethics and dissemination

The study has been approved by the Institutional Review Board of the Henry Ford Hospital. The results of this study will be published in a peer-reviewed journal and presented at a scientific conference.

Trial registration number

NCT03345134
Mapping the preclinical to clinical evidence and development trajectory of the oncolytic virus talimogene laherparepvec (T-VEC): a systematic review
Authors: Lalu Manoj , Leung Garvin J , Dong Yuan Yi , Montroy Joshua , Butler Claire , Auer Rebecca C , Fergusson Dean A
Published: December 2019

Objective

This study aimed to conduct a systematic review of preclinical and clinical evidence to chart the successful trajectory of talimogene laherparepvec (T-VEC) from the bench to the clinic.

Design

This study was a systematic review. The primary outcome of interest was the efficacy of treatment, determined by complete response. Abstract and full-text selection as well as data extraction were done by two independent reviewers. The Cochrane risk of bias tool was used to assess the risk of bias in studies.

Setting

Embase, Embase Classic and OvidMedline were searched from inception until May 2016 to assess its development trajectory to approval in 2015.

Participants

Preclinical and clinical controlled comparison studies, as well as observational studies.

Interventions

T-VEC for the treatment of any malignancy.

Results

8852 records were screened and five preclinical (n=150 animals) and seven clinical studies (n=589 patients) were included. We saw large decreases in T-VEC’s efficacy as studies moved from the laboratory to patients, and as studies became more methodologically rigorous. Preclinical studies reported complete regression rates up to 100% for injected tumours and 80% for contralateral tumours, while the highest degree of efficacy seen in the clinical setting was a 24% complete response rate, with one study experiencing a complete response rate of 0%. We were unable to reliably assess safety due to the lack of reporting, as well as the heterogeneity seen in adverse event definitions. All preclinical studies had high or unclear risk of bias, and all clinical studies were at a high risk of bias in at least one domain.

Conclusions

Our findings illustrate that even successful biotherapeutics may not demonstrate a clear translational road map. This emphasises the need to consider increasing rigour and transparency along the translational pathway.

PROSPERO registration number

CRD42016043541.
Design, development and randomised controlled trial of a smartphone application, ‘QinTB’, for smoking cessation in tuberculosis patients: study protocol
Authors: Lin Haoxiang , Lin Yan , Zheng Yunting , Liu Zhao , Chang Chun
Published: December 2019

Introduction

Providing smoking cessation treatment is an important intervention for tuberculosis (TB) patients. Mobile technologies, such as smartphone applications, have shown promising potential. However, there are few effective applications that could support TB patients in their efforts to quit smoking. To address this problem, we will develop a smartphone application ‘QinTB’ to help TB patients quit smoking, and we will evaluate the clinical efficacy of this application by using a randomised controlled trial (RCT).

Methods and analysis

This is a two-step study. In the first step, we will develop a smartphone application based on an interactive application of the transtheoretical model and protection motivation theory. Then, we will perform an RCT using a two-arm design; a total of 400 patients will be randomly assigned to the application group or the doctors’ advice group; both treatments will be 6 months and follow-up will be 12 months; the primary outcome is the biochemically verified 6 month sustained abstinence rate; data will be analysed on an intention-to-treat basis.

Ethics and dissemination

This study was approved by the Ethics Committee of Beijing Research Institute for Tuberculosis Control and Prevention. We will disseminate the findings of this study through peer-reviewed publications and conference presentations.

Trial registration number

This study was registered in the Chinese Clinical Trial Registry (ChiCTR1900022008) and the stage is Pre-results.
Cohort profile: HealthWise Wales. A research register and population health data platform with linkage to National Health Service data sets in Wales
Authors: Hurt Lisa , Ashfield-Watt Pauline , Townson Julia , Heslop Luke , Copeland Lauren , Atkinson Mark D , Horton Jeffrey , Paranjothy Shantini
Published: December 2019

Purpose

Recruitment and follow-up in epidemiological studies are time-consuming and expensive. Combining online data collection with a register of individuals who agree to be contacted about research opportunities provides an efficient, cost-effective platform for population-based research. HealthWise Wales (HWW) aims to facilitate research by recruiting a cohort of individuals who have consented to be informed about research projects, advertising studies to participants, supporting data collection on specific topics and providing access to linked healthcare data for secondary analyses. In this paper, we describe the design of the project, ongoing data collection, methods of data linkage to routine healthcare records, baseline characteristics of participants, the strengths and limitations of the register, and the ways in which the project can support researchers.

Participants

Adults (aged 16 years and above) living or receiving their healthcare in Wales are eligible for inclusion. Participants consent to be contacted for follow-up data collection and for their details to be used to access their routinely collected National Health Service records for research purposes. Data are collected using a web-based application, with new questionnaires added every 6 months. Data collection on sociodemographic and lifestyle factors is repeated at intervals of 2–3 years. Recruitment is ongoing, with 21 779 participants alive and currently registered.

Findings to date

99% of participants have complete information on age and sex, and 64% have completed questionnaires on sociodemographic and lifestyle factors. These data can be linked with national health databases within the Secure Anonymised Information Linkage (SAIL) databank, with 93% of participants matching a record in SAIL. HWW has facilitated the recruitment of 43 826 participants to 15 different studies.

Future plans

The medium-term goal for the project is to enrol at least 50 000 adults. Recruitment strategies are being devised to achieve a study sample that closely models the population of Wales. Potential biosampling methods are also currently being explored.
Effectiveness of home or hospital initiation of treatment at diagnosis for children with type 1 diabetes (DECIDE trial): a multicentre individually randomised controlled trial
Authors: Gregory John W , Townson Julia , Channon Sue , Cohen David , Longo Mirella , Davies Justin , Harman Nicola , Hood Kerenza , Pickles Timothy , Playle Rebecca , Randell Tabitha , Robling Michael , Touray Morro , Trevelyan Nicola , Warner Justin , Lowes Lesley
Published: December 2019

Objective

To determine whether, in children with newly diagnosed type 1 diabetes who were not acutely unwell, management at home for initiation of insulin treatment and education of the child and family, would result in improved clinical and psychological outcomes at 2 years postdiagnosis.

Design

A multicentre randomised controlled trial (January 2008/October 2013).

Setting

Eight paediatric diabetes centres in England, Wales and Northern Ireland.

Participants

203 clinically well children aged under 17 years, with newly diagnosed type 1 diabetes and their carers.

Intervention

Management of the initiation period from diagnosis at home, for a minimum of 3 days, to include at least six supervised injections and delivery of pragmatic educational care.

Main outcome measures

Primary outcome was glycosylated haemoglobin (HbA1c) concentration at 24 months postdiagnosis. Secondary outcomes included coping, anxiety, quality of life and use of NHS resources.

Results

203 children, newly diagnosed, were randomised to commence management at home (n=101) or in hospital (n=102). At the 24 month primary end point, there was one withdrawal and a follow-up rate of 194/202 (96%). Mean HbA1c in the home treatment arm was 72.1 mmol/mol and in the hospital treated arm 72.6 mmol/mol. There was a negligible difference between the mean HbA1c levels in the two arms adjusted for baseline (1.01, 95% CI 0.93 to 1.09). There were mostly no differences in secondary outcomes at 24 months, apart from better child self-esteem in the home-arm. No home-arm children were admitted to hospital during initiation and there were no adverse events at that time. The number of investigations was higher in hospital patients during the follow-up period. There were no differences in insulin regimens between the two arms.

Conclusions

There is no evidence of a difference between home-based and hospital-based initiation of care in children newly diagnosed with type 1 diabetes across relevant outcomes.

Trial registration number

ISRCTN78114042.
Development of summary indices of antenatal care service quality in Haiti, Malawi and Tanzania
Authors: Sheffel Ashley , Zeger Scott , Heidkamp Rebecca , Munos Melinda Kay
Published: December 2019

Introduction

Measuring quality of care in low-income and middle-income countries is complicated by the lack of a standard, universally accepted definition for ‘quality’ for any particular service, as well as limited guidance on which indicators to include in measures of quality of care, and how to incorporate those indicators into summary indices. The aim of this paper is to develop, characterise and compare a set of antenatal care (ANC) indices for facility readiness and provision of care.

Methods

We created nine indices for facility readiness using three methods for selecting items and three methods for combining items. In addition, we created three indices for provision of care using one method for selecting items and three methods for combining items. For each index, we calculated descriptive statistics, categorised the continuous index scores using tercile cut points to assess comparability of facility classification, and examined the variability and distribution of scores.

Results

Our results showed that, within a country, the indices were quite similar in terms of mean index score, facility classification, coefficient of variation, floor and ceiling effects, and the inclusion of items in an index with a range of variability. Notably, the indices created using principal components analysis to combine the items were the most different from the other indices. In addition, the index created by taking a weighted average of a core set of items had lower agreement with the other indices when looking at facility classification.

Conclusions

As improving quality of care becomes integral to global efforts to produce better health outcomes, demand for guidance on creating standardised measures of service quality will grow. This study provides health systems researchers with a comparison of methodologies commonly used to create summary indices of ANC service quality and it highlights the similarities and differences between methods.
Uptake of routine viral load testing among people living with HIV and its implementation challenges in Yangon region of Myanmar: a mixed-methods study
Authors: Thinn Khine Khine , Thekkur Pruthu , Kyaw Nang Thu Thu , Aye Nyein Su , Zaw Tin Maung , Soan Pyae , Hone San , Oo Htun Nyunt
Published: December 2019

Objectives

In 2017, Myanmar implemented routine viral load (VL) monitoring for assessing the response to antiretroviral therapy (ART) among people living with HIV (PLHIV). The performance of routine VL testing and implementation challenges has not yet assessed. We aimed to determine the uptake of VL testing and factors associated with it among PLHIV initiated on ART during 2017 in ART clinics of Yangon region and to explore the implementation challenges as perceived by the healthcare providers.

Design

An explanatory mixed-methods study was conducted. The quantitative component was a cohort study, and the qualitative part was a descriptive study with in-depth interviews.

Setting

Six ART clinics operated by AIDS/sexually transmitted infection teams under the National AIDS Programme.

Primary outcome measures

(1) The proportion who underwent VL testing by 30 March 2019 and the proportion with virological suppression (plasma VL <1000 copies/mL); (2) association between patient characteristics and ‘not tested’ was assessed using log binomial regression and (3) qualitative codes on implementation challenges.

Results

Of the 567 PLHIV started on ART, 498 (87.8%) retained in care for more than 6 months and were eligible for VL testing. 288 (57.8%, 95% CI: 53.3% to 62.2%) PLHIV underwent VL testing, of which 263 (91.3%, 95% CI: 87.1% to 94.4%) had virological suppression. PLHIV with WHO clinical stage 4 had significantly higher rates of ‘not being tested’ for VL. Collection of sample for VL testing only twice a month, difficulties in sample collection and transportation, limited trained workforce, wage loss and out-of-pocket expenditure for patients due to added visits were major implementation challenges.

Conclusions

The VL test uptake was low, with only six out of ten PLHIV tested. The VL testing uptake needs to be improved by strengthening sample collection and transportation, adopting point-of-care VL tests, increasing trained workforce, providing compensation to patients for wage loss and travel costs for additional visits.
Road to recovery: a study protocol quantifying neurological outcome in cardiac surgery patients and the role of cerebral oximetry
Authors: Semrau Joanna S , Scott Stephen H , Hamilton Andrew G , Petsikas Dimitri , Payne Darrin M , Bisleri Gianluigi , Saha Tarit , Boyd John Gordon
Published: December 2019

Introduction

Patients undergoing cardiac surgery may experience both short-term and long-term postoperative neurological problems. However, the underlying cause of this impairment is unclear. Regional cerebral oxygen saturation (rSO2) levels may play a role in the development of acute dysfunction, known as postoperative delirium, in addition to longer term outcomes after cardiac surgery. Yet the degree of impairment has been difficult to define, partly due to subjective methods of assessments. This study aims to fill this knowledge gap by determining the relationship between rSO2, postoperative delirium and long-term neurological outcome after cardiac surgery using quantitative robotic technology.

Methods and analysis

95 patients scheduled for elective cardiac surgery will be recruited for this single-centre prospective observational study. Patients will be assessed before as well as 3 and 12 months after their surgery using the Kinarm End-Point Lab and standardised tasks. Intraoperatively, rSO2 and other haemodynamic data will be collected for the duration of the procedure. Following their operation, patients will also be screened daily for delirium during their hospital stay.

Ethics and dissemination

This study has been approved by the Health Sciences Research Ethics Board at Queen’s University (DMED-1672–14). The results of this study will be published in a peer-review journal and presented at international and/or national conferences as poster or oral presentations. Participants wishing to know the results of this study will be contacted directly on data publication.

Trial registration number

NCT04081649
Development of a revised Jalowiec Coping Scale for use by emergency clinicians: a cross-sectional scale development study
Authors: Greenslade Jaimi H , Wallis Marianne C , Johnston Amy , Carlström Eric , Wilhelms Daniel , Thom Ogilvie , Abraham Louisa , Crilly Julia
Published: December 2019

Objectives

The aim of this study was to develop and validate a scale to measure the coping strategies used by emergency staff in response to workplace stress. To achieve this aim, we developed a refined Jalowiec Coping Scale (JCS), termed the Jalowiec Coping Scale-Emergency Department (JCS-ED) and validated this scale on a sample of emergency clinicians.

Design

A cross-sectional survey incorporating the JCS, the working environment scale-10 and a measure of workplace stressors was administered between July 2016 and June 2017. The JCS-ED was developed in three stages: 1) item reduction through content matter experts, 2) exploratory factor analysis for further item reduction and to identify the factor structure of the revised scale and 3) confirmatory factor analyses to confirm the factors identified within the exploratory factor analysis.

Setting

Six Emergency Departments (EDs) in Australia and four in Sweden. There were three tertiary hospitals, five large urban hospitals and two small urban hospitals.

Participants

Participants were eligible for inclusion if they worked full-time or part-time as medical or nursing staff in the study EDs. The median age of participants was 35 years (IQR: 28–45 years) and they had been working in the ED for a median of 5 years (IQR: 2–10 years). 79% were females and 76% were nurses.

Results

A total of 875 ED staff completed the survey (response rate 51%). The content matter experts reduced the 60-item scale to 32 items. Exploratory factor analyses then further reduced the scale to 18 items assessing three categories of coping: problem-focussed coping, positive emotion-focussed coping and negative emotion-focussed coping. Confirmatory factor analysis supported this three-factor structure. Negative coping strategies were associated with poor perceptions of the work environment and higher ratings of stress.

Conclusions

The JCS-ED assesses maladaptive coping strategies along with problem-focussed and emotion-focussed coping styles. It is a short instrument that is likely to be useful in measuring the types of coping strategies employed by staff.
Induced pluripotent stem cell–based Drug Repurposing for Amyotrophic lateral sclerosis Medicine (iDReAM) study: protocol for a phase I dose escalation study of bosutinib for amyotrophic lateral sclerosis patients
Authors: Imamura Keiko , Izumi Yuishin , Banno Haruhiko , Uozumi Ryuji , Morita Satoshi , Egawa Naohiro , Ayaki Takashi , Nagai Makiko , Nishiyama Kazutoshi , Watanabe Yasuhiro , Hanajima Ritsuko , Oki Ryosuke , Fujita Koji , Takahashi Naoto , Ikeda Takafumi , Shimizu Akira , Morinaga Akiko , Hirohashi Tomoko , Fujii Yosuke , Takahashi Ryosuke , Inoue Haruhisa
Published: December 2019

Introduction

Amyotrophic lateral sclerosis (ALS) is a progressive and severe neurodegenerative disease caused by motor neuron death. There have as yet been no fundamental curative medicines, and the development of a medicine for ALS is urgently required. Induced pluripotent stem cell (iPSC)-based drug repurposing identified an Src/c-Abl inhibitor, bosutinib, as a candidate molecular targeted therapy for ALS. The objectives of this study are to evaluate the safety and tolerability of bosutinib for the treatment of patients with ALS and to explore the efficacy of bosutinib on ALS. This study is the first clinical trial of administered bosutinib for patients with ALS.

Methods and analysis

An open-label, multicentre phase I dose escalation study has been designed. The study consists of a 12-week observation period, a 1-week transitional period, a 12-week study treatment period and a 4-week follow-up period. After completion of the transitional period, subjects whose total ALS Functional Rating Scale-Revised (ALSFRS-R) score decreased by 1–3 points during the 12-week observation period receive bosutinib for 12 weeks. Three to six patients with ALS are enrolled in each of the four bosutinib dose levels (100, 200, 300 or 400 mg/day) to evaluate the safety and tolerability under a 3+3 dose escalation study design. Dose escalation and maximum tolerated dose are determined by the safety assessment committee comprising oncologists/haematologists and neurologists based on the incidence of dose-limiting toxicity in the first 4 weeks of the treatment at each dose level. A recommended phase II dose is determined by the safety assessment committee on completion of the 12-week study treatment in all subjects at all dose levels. The efficacy of bosutinib is also evaluated exploratorily using ALS clinical scores and biomarkers.

Ethics and dissemination

This study received full ethical approval from the institutional review board of each participating site. The findings of the study will be disseminated in peer-reviewed journals and at scientific conferences.

Trial registration number

UMIN000036295; Pre-results, JMA-IIA00419; Pre-results.
Implementation of clinical decision support to manage acute kidney injury in secondary care: an ethnographic study
Authors: Bailey Simon , Hunt Carianne , Brisley Adam , Howard Susan , Sykes Lynne , Blakeman Thomas
Published: December 2019

Background

Over the past decade, acute kidney injury (AKI) has become a global priority for improving patient safety and health outcomes. In the UK, a confidential inquiry into AKI led to the publication of clinical guidance and a range of policy initiatives. National patient safety directives have focused on the mandatory establishment of clinical decision support systems (CDSSs) within all acute National Health Service (NHS) trusts to improve the detection, alerting and response to AKI. We studied the organisational work of implementing AKI CDSSs within routine hospital care.

Methods

An ethnographic study comprising non-participant observation and interviews was conducted in two NHS hospitals, delivering AKI quality improvement programmes, located in one region of England. Three researchers conducted a total of 49 interviews and 150 hours of observation over an 18-month period. Analysis was conducted collaboratively and iteratively around emergent themes, relating to the organisational work of technology adoption.

Results

The two hospitals developed and implemented AKI CDSSs using very different approaches. Nevertheless, both resulted in adaptive work and trade-offs relating to the technology, the users, the organisation and the wider system of care. A common tension was associated with attempts to maximise benefit while minimise additional burden. In both hospitals, resource pressures exacerbated the tensions of translating AKI recommendations into routine practice.

Conclusions

Our analysis highlights a conflicted relationship between external context (policy and resources), and organisational structure and culture (eg, digital capability, attitudes to quality improvement). Greater consideration is required to the long-term effectiveness of the approaches taken, particularly in light of the ongoing need for adaptation to incorporate new practices into routine work.
Simulation-based evaluation of anaesthesia residents: optimising resource use in a competency-based assessment framework
Authors: Fleming Melinda , McMullen Michael , Beesley Theresa , Egan Rylan , Field Sean
Published: December 2019

Introduction

Simulation training in anaesthesiology bridges the gap between theory and practice by allowing trainees to engage in high-stakes clinical training without jeopardising patient safety. However, implementing simulation-based assessments within an academic programme is highly resource intensive, and the optimal number of scenarios and faculty required for accurate competency-based assessment remains to be determined. Using a generalisability study methodology, we examine the structure of simulation-based assessment in regard to the minimal number of scenarios and faculty assessors required for optimal competency-based assessments.

Methods

Seventeen anaesthesiology residents each performed four simulations which were assessed by two expert raters. Generalisability analysis (G-analysis) was used to estimate the extent of variance attributable to (1) the scenarios, (2) the assessors and (3) the participants. The D-coefficient and the G-coefficient were used to determine accuracy targets and to predict the impact of adjusting the number of scenarios or faculty assessors.

Results

We showed that multivariate G-analysis can be used to estimate the number of simulations and raters required to optimise assessment. In this study, the optimal balance was obtained when four scenarios were assessed by two simulation experts.

Conclusion

Simulation-based assessment is becoming an increasingly important tool for assessing the competency of medical residents in conjunction with other assessment methods. G-analysis can be used to assist in planning for optimal resource use and cost-efficacy.
Risk orientation predicts hypoxic time during difficult airway simulation: a mixed-methods pilot study
Authors: Hayward Jake , Velmurugiah Niresha , Duff Jonathan
Published: December 2019

Personality factors may explain some of the practice variation observed in medicine. In this pilot study, we used simulation to investigate the relationship between risk orientation and airway management. We hypothesised that higher risk tolerance would predict earlier intervention.

Ten emergency medicine residents from the University of Alberta participated in a standardised difficult airway simulation. There was a constant rate of oxygen desaturation necessitating eventual airway intervention. A debriefing interview and a risk orientation questionnaire followed. Time of hypoxia prior to intervention was the outcome measure. Audio interview transcripts underwent thematic analysis.

Nine participants were included; one did not complete the simulation as instructed. Higher risk tolerance predicted longer hypoxic time prior to intubation (r=0.72, p=0.03). Theme analysis revealed consistent fears regarding patient instability and chances of a failed airway intervention. Patient instability was emphasised more so by those who intervened earlier.

We show that personality characteristics influence resuscitation decision-making at an early stage of training. Trainees may therefore be susceptible to certain types of medical error based on their risk aversion. Implications for resident training, care quality and patient safety are discussed.