bluuebunny/crossref_metadata_2025 huggingface dataset:
A CRISPR/LbCas12a‐based method for highly efficient multiplex gene editing in Physcomitrella patens
Authors: Pu Xiaojun , Liu Lina , Li Ping , Huo Heqiang , Dong Xiumei , Xie Kabin , Yang Hong , Liu Li
Published: July 2019

Due to their high efficiency, specificity, and flexibility, programmable nucleases, such as those of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a (Cpf1) system, have greatly expanded the applicability of editing the genomes of various organisms. Genes from different gene families or genes with redundant functions in the same gene family can be examined by assembling multiple CRISPR RNAs (crRNAs) in a single vector. However, the activity and efficiency of CRISPR/Cas12a in the non‐vascular plant Physcomitrella patens are largely unknown. Here, we demonstrate that LbCas12a together with its mature crRNA can target multiple loci simultaneously in P. patens with high efficiency via co‐delivery of LbCas12a and a crRNA expression cassette in vivo. The mutation frequencies induced by CRISPR/LbCas12a at a single locus ranged from 26.5 to 100%, with diverse deletions being the most common type of mutation. Our method expands the repertoire of genome editing tools available for P. patens and facilitates the creation of loss‐of‐function mutants of multiple genes from different gene families.
Craterostigma plantagineumcell wall composition is remodelled during desiccation and the glycine‐rich protein CpGRP1 interacts with pectins through clustered arginines
Authors: Jung Niklas U. , Giarola Valentino , Chen Peilei , Knox John Paul , Bartels Dorothea
Published: July 2019

Craterostigma plantagineumbelongs to the desiccation‐tolerant angiosperm plants. Upon dehydration, leaves fold and the cells shrink which is reversed during rehydration. To understand this process changes in cell wall pectin composition, and the role of the apoplastic glycine‐rich protein 1 (CpGRP1) were analysed. Cellular microstructural changes in hydrated, desiccated and rehydrated leaf sections were analysed using scanning electron microscopy. Pectin composition in different cell wall fractions was analysed with monoclonal antibodies against homogalacturonan, rhamnogalacturonan I, rhamnogalacturonan II and hemicellulose epitopes. Our data demonstrate changes in pectin composition during dehydration/rehydration which is suggested to affect cell wall properties. Homogalacturonan was less methylesterified upon desiccation and changes were also demonstrated in the detection of rhamnogalacturonan I, rhamnogalacturonan II and hemicelluloses. CpGRP1 seems to have a central role in cell adaptations to water deficit, as it interacts with pectin through a cluster of arginine residues and de‐methylesterified pectin presents more binding sites for the protein−pectin interaction than to pectin from hydrated leaves. CpGRP1 can also bind phosphatidic acid (PA) and cardiolipin. The binding of CpGRP1 to pectin appears to be dependent on the pectin methylesterification status and it has a higher affinity to pectin than its binding partner CpWAK1. It is hypothesised that changes in pectin composition are sensed by the CpGRP1−CpWAK1 complex therefore leading to the activation of dehydration‐related responses and leaf folding. PA might participate in the modulation of CpGRP1 activity.
Development and validation of a brachycephalic risk (BRisk) score to predict the risk of complications in dogs presenting for surgical treatment of brachycephalic obstructive airway syndrome
Authors: Tarricone Jason , Hayes Galina M. , Singh Ameet , Davis Garrett
Published: July 2019

Objective

To develop and validate a preoperative brachycephalic risk (BRisk) score that objectively and accurately predicts the risk of major complications or death in dogs undergoing corrective surgery for brachycephalic obstructive airway syndrome (BOAS).

Study design

Retrospective multicenter cohort study.

Sample population

Score development n = 233 dogs, validation n = 50 dogs.

Methods

Data were collected on signalment, medical history, reason for presentation, physical examination, and preoperative diagnostic findings. The primary outcome measures included risk of major complications (requirement for postoperative oxygen support for >48 hours or postoperative temporary/permanent tracheostomy) or death within the hospitalization period. The score was developed by using data from two centers and was validated in a third center. The 10‐point BRisk score was modeled on breed, history of previous surgery, concurrent procedures, body condition score, airway status, and admission rectal temperature.

Results

The score was associated with negative outcome (P < .0001) and discriminated well in both the construction (area under the receiver operator characteristic [AUROC] = 0.83) and validation groups (AUROC = 0.84). Dogs with scores >3 were 9.1 times more likely to have a negative outcome (95% CI = 3.9–21.2) compared with dogs with scores ≤3.

Conclusion

The BRisk score developed from admission data in this study accurately rated the risk of negative outcome of dogs undergoing corrective surgery for BOAS.

Clinical significance

Preoperative determination of the BRisk score may assist triage, management of owner expectations, decision making regarding intervention selection, and characterization of populations in clinical research.
The beneficial effect of traditional Japanese herbal (Kampo) medicine, Hochu‐ekki‐to (Bu‐Zhong‐Yi‐Qi‐Tang), for patients with chronic wounds refractory to conventional therapies: A prospective, randomized trial
Authors: Akita Shinsuke , Namiki Takao , Kawasaki Yohei , Rikihisa Naoaki , Ogata Hideyuki , Tokumoto Hideki , Tezuka Takafumi , Kubota Yoshitaka , Kuriyama Motone , Nakamura Michimi , Mitsukawa Nobuyuki
Published: July 2019

Hochu‐ekki‐to (HET) is a traditional Japanese herbal (Kampo) medicine for the treatment of severe weakness, loss of appetite, and indigestion in elderly patients and for the prevention of opportunistic infections. The impact of HET on patients with chronic wounds refractory to conventional therapies was investigated in a prospective, randomized trial, including 18 patients divided into medication (7.5 g oral HET per day, n = 9) and control (n = 9) groups. Wound healing during the 12‐week study period was scored based on depth, exudate, size, inflammation/infection, granulation tissue, necrotic tissue, and pocket size. At 12 weeks, wound healing progressed in all nine patients in the medication group, whereas wound healing progressed in only three patients in the control group (significant difference, p < 0.01; relative risk: 3.00). In the medication group, the total score decreased significantly at 8 weeks and later. To the best of our knowledge, this study was the first to show that HET promoted the healing of chronic wounds resistant to conventional treatments. HET may be a choice as an adjunctive therapy for chronic wounds, particularly for patients with malnutrition. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000031620).
Histotoxic Clostridial Infections
Authors: Nagahama Masahiro , Takehara Masaya , Rood Julian I.
Published: July 2019

The pathogenesis of clostridial myonecrosis or gas gangrene involves an interruption to the blood supply to the infected tissues, often via a traumatic wound, anaerobic growth of the infecting clostridial cells, the production of extracellular toxins, and toxin-mediated cell and tissue damage. This review focuses on host-pathogen interactions in
Clostridium perfringens
-mediated and
Clostridium septicum
-mediated myonecrosis. The major toxins involved are
C. perfringens
α-toxin, which has phospholipase C and sphingomyelinase activity, and
C. septicum
α-toxin, a β-pore-forming toxin that belongs to the aerolysin family. Although these toxins are cytotoxic, their effects on host cells are quite complex, with a range of intracellular cell signaling pathways induced by their action on host cell membranes.
Incisive dental implant migration into the nasal septum
Authors: Sousa Menezes Ana , Costa Nuno Daniel Ribeiro Martins da , Moreira Filipa Carvalho , Ribeiro Daniela
Published: July 2019

We report the clinical case of a female patient who presented to our emergency department due to a septal abscess caused by the displacement of a dental implant into the nasal septum. The patient underwent surgical treatment for endoscopic foreign body excision and septal abscess drainage. Despite the presence of septal cartilage destruction, the L-shaped structure was preserved and no reconstruction was required. Postoperative healing was uneventful.
Congenital band adhesion causing a proximal jejunal obstruction: an uncommon presentation and diagnosis
Authors: Cruise David Ashley , Goddard Kim
Published: July 2019

A 20-year-old woman with no medical or surgical history presented with acute onset crampy abdominal pain on a background of uninvestigated similar chronic abdominal pain. She became obstructed during her admission and a contrast swallow showed a complete obstruction at the level of the proximal jejunum. A diagnostic laparoscopy revealed a congenital band adhesion from the greater omentum to the proximal jejunum to be the cause, and dissection of the band relieved her obstruction. This case presents a rare cause of mechanical obstruction, and highlights the seriousness of investigating obstructive symptoms even in atypical patient populations.
Subcutaneous mass concerning for sarcoma: a peculiar presentation of diffuse large B-cell lymphoma
Authors: Mayo John , Bogenberger Kenneth , Raj Thomas , Reha Jeffrey
Published: July 2019

Diffuse large B-cell lymphoma (DLBCL) can present in a number of different ways, including as a primary cutaneous lesion or at various other extranodal sites. However, it is rare for a DLBCL to present as a clinically subcutaneous mass without visible skin changes or nodal involvement. A 36-year-old man presented with a 4×4×1 cm subcutaneous mass to his shoulder with normal overlying skin which had been enlarging over 6 months. Physical exam and imaging together made a strong case for sarcoma, and the patient underwent a radical resection. The final pathological diagnosis returned as a diffuse B-cell lymphoma (germinal centre type). The patient subsequently healed and tolerated chemotherapy well. DLBCL can masquerade as a soft tissue mass at initial presentation. If the diagnosis is not clear, a biopsy should be pursued.
Delayed conservative treatment of an acute lateral ankle sprain in a non-athlete female following walking boot immobilisation
Authors: Matherne Tyler , Cooke Jennifer , McMorris Michael , Gross Michael
Published: July 2019

Lateral ankle sprains are a common injury with an estimated occurrence rate of 23 000 per day in the USA. Prolonged immobilisation and delayed referral to physical therapy are associated with poorer outcomes. The patient was a 49-year-old woman working as a surgical technologist. She sustained an inversion injury to her left ankle while descending from a stool. Her primary care physician examined her, issued a Controlled Ankle Movement (CAM) walking boot and immobilised her ankle for 6 weeks. Patients with grade I and II lateral ankle sprains who are treated with early mobilisation and referral to physical therapy have demonstrated earlier return to function compared with patients who are treated with prolonged immobilisation and delayed referral. Nevertheless, it remains common for individuals who have sustained a lateral ankle sprain to be immobilised. This case study highlights the importance of early mobilisation and early physical therapy referral for patients with lateral ankle sprains.
Treatment of inoperable hepatocellular carcinoma with immunotherapy
Authors: Tighe Sean P , Iqbal Umair , Fernandes Christopher T , Ahmed Aijaz
Published: July 2019

In the USA, mortality associated with hepatocellular carcinoma (HCC) continues to rise. Globally, HCC is the third most common cause of cancer-related death. In early stages of HCC, hepatic resection or liver transplantation are the preferred treatment options with a high probability of recurrence-free postoperative course. However, ineffective screening of chronic liver diseases in high-risk populations, poor linkage to care and suboptimal HCC surveillance has led to increasing rates of late-stage HCC at clinical presentation or diagnosis amenable only to palliative and experimental treatment options. Our case is a 66-year-old man with chronic hepatitis C virus infection complicated by cirrhosis and inoperable HCC which was non-responsive to selective intrahepatic trans-arterial chemoembolisation by interventional radiology. Therefore, he was treated with nivolumab immunotherapy and demonstrated normalisation of previously elevated alpha-fetoprotein levels suggestive of at least a partial response to immunotherapy. No adverse events related to nivolumab immunotherapy were encountered.
Hypothermia-triggered biventricular Takotsubo cardiomyopathy: the octopus that survived the polar vortex
Authors: Ajam Mustafa , Shokr Mohamed , Ajam Firas , Afonso Luis
Published: July 2019

Takotsubo cardiomyopathy (TTC) is most commonly characterised by transient apical ballooning in response to physical or emotional stress without significant coronary artery disease (CAD). Various physical and emotional factors can trigger TTC. We report a case of hypothermia-induced biventricular TTC in an 84-year-old man admitted with a core body temperature of 29.8°C, followed by quick recovery of systolic function and resolution of wall motion abnormality after discharge. TTC should be suspected in hypothermic patients presenting with evidence of new onset heart failure and be added to the expanding list of factors triggering TTC. Similar to TTC induced by various other factors, hypothermia-induced TTC also carries a favourable prognosis with relatively quick recovery of wall motion abnormalities.
Niemann-Pick disease type C presenting as very early onset inflammatory bowel disease
Authors: Dike Chinenye Rebecca , Bernat John , Bishop Warren , DeGeeter Catherine
Published: July 2019

Niemann-Pick disease type C (NPC) has been reported in association with inflammatory bowel disease. In cases where colitis has been reported in association with NPC, the neurological manifestations of NPC often precede the development of colitis. We report a rare case of a child who presented at age 2 with perianal Crohn’s disease. Initial imaging studies to characterise the disease revealed an incidental finding of splenomegaly. Extensive workup for splenomegaly revealed NPC1 mutations consistent with NPC disease. He did not have any typical neurological symptoms at the time of his diagnosis. He is currently doing well on biweekly adalimumab injections for his Crohn’s disease and biweekly intrathecal injections of 2-hydroxypropyl-β-cyclodextrin (VTS-270) for the NPC.
Enlarging left atrial haemangioma in a patient with Cowden syndrome
Authors: Lamanna Anthony , Lim Ruth P , Yap Lee Pheng , Maingard Julian , Seevenayagam Siven
Published: July 2019

A 53-year-old female patient known to have Cowden disease (PTENmutation positive) was found to have a mass at the left atrium on a CT coronary angiography performed as part of a preoperative workup for an unrelated surgery. Further radiological characterisation of the lesion was achieved using MRI and positron emission tomography. Interval growth prompted surgical excision; however, surgery was expedited after the patient presented with haemopericardium and cardiac tamponade. The patient was discharged home 8 days postoperatively, and no intraoperative or postoperative complications were encountered. A diagnosis of cavernous haemangioma was made on histology.
Common bile duct stone development due to a Hem-o-lok clip migration: a rare complication of laparoscopic cholecystectomy
Authors: Roh Yong Jun , Kim Jong Whan , Jeon Tae Joo , Park Ji Young
Published: July 2019

Surgical clip migration is a rare complication of laparoscopic cholecystectomy (LC). Surgical clips migrating into the common bile duct (CBD) can lead to stone formation and obstruction. Here, we report a case of acute cholangitis caused by surgical Hem-o-lok clip migration into the bile duct with stone formation 13 months after LC. A 65-year-old man who underwent LC presented with upper abdominal pain and fever for 3 days. Abdominal CT scan showed a radiopaque material in the CBD, diffuse wall thickening and dilatation of intrahepatic and extrahepatic duct. Emergency percutaneous transhepatic biliary drainage was performed. Twodays later, an endoscopic retrograde cholangio-pancreatography was implemented, and muddy stones and one surgical clip were successfully removed by extraction balloon catheter.
Challenge of diagnosing pyoderma gangrenosum after caesarean section
Authors: Foessleitner Philipp , Just Ulrike , Kiss Herbert , Farr Alex
Published: July 2019

Pyoderma gangrenosum is a neutrophilic skin disease that leads to extensive, painful, necrotic ulcerations, particularly at surgical sites. As obstetric cases with pyoderma gangrenosum are rare and, therefore, often misdiagnosed initially, it is important to raise awareness about this rare complication. Here, we describe a patient who presented with pyoderma gangrenosum at the surgical site 4 days after undergoing a caesarean section. The erythema was initially misdiagnosed as wound infection, and the patient, who was experiencing pain, underwent antibiotic treatment and surgical wound debridement. When the wound was unresponsive to these treatments, a dermatologist was consulted who suspected pyoderma gangrenosum and began a high-dose corticosteroids therapy, which led to a fulminant improvement of the local wound. In conclusion, the rare diagnosis of pyoderma gangrenosum should be considered in the differential diagnosis of a suspected surgical wound infection. Early interdisciplinary treatment is essential to avoid further complications.
Severe proximal myopathy secondary to Hashimoto’s thyroiditis
Authors: Jervis William , Shah Najeeb , Mongolu Shiva Kumar , Sathyapalan Thozhukat
Published: July 2019

Muscular symptoms in hypothyroidism are common, including myalgia, fatigue and cramps; however, a significantly raised creatine kinase and muscle weakness are rare. Differential diagnosis of patients presenting with muscle weakness and a raised creatine kinase is wide, and hypothyroidism is rarely considered. We report this case of a 30-year-old female presenting with proximal muscle weakness as her primary symptom, hypothyroid symptoms of 3-month duration and a significantly raised creatine kinase. After ruling out other causes of a raised creatine kinase, thyroxine replacement was commenced, which led to complete resolution of her proximal weakness, myalgia and normalisation of creatine kinase level. This case illustrates severe proximal myopathy can be secondary to hypothyroidism, symptoms can resolve with thyroxine replacement and emphasises the importance of measuring thyroid function in patients with proximal weakness/myalgia and a significantly raised creatine kinase.
Citrobacter kosericausing osteomyelitis in a diabetic foot with concomitant acute gouty arthritis successfully treated with ertapenem
Authors: Tinevez Dillon , Knezevic Nebojsa Nick
Published: July 2019

We present an elderly diabetic man with left hallux pain and drainage who was initially diagnosed with acute gouty arthritis using the diagnostic rule for acute gout and monosodium urate crystals presented on synovial fluid analysis. Further investigation with surgical debridement, plain X-ray, MRI and wound culture revealed concomitantCitrobacter koseriseptic arthritis with osteomyelitis.C. koseriis considered an opportunistic infection that rarely causes musculoskeletal infections. Acute gouty arthritis and septic arthritis are rarely seen occurring concomitantly in the same joint and are often difficult to differentiate due to similar findings on exam and imaging. The present case illustrates that osteomyelitis with an opportunistic organism can present concomitantly with acute gouty arthritis, and the diagnosis of one should not exclude the other.
Clinical and epidemiological indicators and spatial analysis of leprosy cases in patients under 15 years old in an endemic area of Northeast Brazil: an ecological and time series study
Authors: Santos Márcio Bezerra , Santos Allan Dantas dos , Barreto Aline Silva , Souza Mariana do Rosário , Goes Marco Aurélio de Oliveira , Barreto Alves José Antônio , Barreto Ikaro Daniel Carvalho , Silva José-Rodrigo S , Oliveira Daniela Teles de , Araújo Karina C G Machado de , Duthie Malcolm S , Jesus Amélia Ribeiro de
Published: July 2019

Objective

This study aimed to analyse the clinical and epidemiological indicators, temporal trends and the spatial distribution of leprosy in patients under 15 years old in an endemic area of Northeast Brazil.

Design

Regional surveillance study of all reported cases.

Setting

State of Sergipe, endemic area of Northeast Brazil.

Methods

An ecological and time series study was conducted, based on secondary data reported by the Brazilian Information System on Notifiable Diseases for leprosy cases diagnosed in Sergipe state (2002–2015). The analysis of temporal trends was performed using the Joinpoint Regression Programme through Poisson regression. We performed spatial analysis by Kernel estimator and Moran index.

Results

The incidence rate was reduced from 6.29 to 3.78 cases per 100 000 inhabitants in 2002 and 2015, respectively. However, Sergipe was still classified as highly endemicity in 2015. The mean number of household contacts (HHC) examined was significantly lower than those registered. Clinical data indicated that 21.4% of the patients developed leprosy reactions, and 31.3% presented with some physical disability in the multibacillary groups. Patients diagnosed by examination within the HHC presented better indicators, such as lower percentage of leprosy reaction and physical disability. Spatial analysis showed the most risk areas distributed on the northeast and cities around the capital, Aracaju.

Conclusion

The data indicate that there is a persistence of activeMyobacterium lepraetransmission and a delay in disease detection, following a pattern of high endemicity in many municipalities. The early detection by HHC examination is important to stop transmission and also to detect the cases in a less severe state.
Kerala Atrial Fibrillation Registry: a prospective observational study on clinical characteristics, treatment pattern and outcome of atrial fibrillation in Kerala, India, cohort profile
Authors: Charantharayil Gopalan Bahuleyan , Namboodiri Narayanan , Abdullakutty Jabir , Lip Gregory YH , Koshy Allumootil George , Krishnan Nair Venugopal , Babu Shifas , Muhammed Shaffi , Azariah Jinbert Lordson , George Raju , Nambiar Ashokan , Govindan Unni , Zachariah Geevar , Kumaraswamy Natarajan , Chakanalil Govindan Sajeev , Natesan Syam , Roby Anil , Velayudhan Nair Krishnakumar , Pillai Anand M , Daniel Rachel
Published: July 2019

Purpose

Limited published data exist on the clinical epidemiology of atrial fibrillation (AF) in South Asia including India. Most of the published data are from the Western countries and the Far East. The Kerala AF registry was initiated to collect systematic, prospective data on clinical characteristics, risk factors, treatment pattern and outcomes of consecutive AF patients who consulted cardiologists across the state of Kerala, India.

Participants

All newly diagnosed and previously reported patients aged ≥18 years with documented evidence of AF on ECG were included. Patients with transient AF due to infection, acute myocardial infarction, alcohol intoxication, metabolic abnormalities and AF seen in postoperative cases and critically ill patients with life expectancy less than 30 days were excluded.

Findings to date

A total of 3421 patients were recruited from 53 hospitals across Kerala from April 2016 to April 2017. There were 51% (n=1744) women. The median age of the cohort was 65 (IQR 56–74) years. Hypertension, diabetes mellitus and dyslipidaemia were present in 53.8%, 34.5% and 42.2% patients, respectively. Chronic kidney disease was observed in 46.6%, coronary artery disease in 34.8% and heart failure (HF) in 26.5% of patients. Mean CHA2DS2-VASc score of the cohort was 2.9, and HAS-BLED score was 1.7. Detailed information of antithrombotic and antiarrhythmic drugs was collected at baseline and on follow-up. During 1-year follow-up, 443 deaths (12.9%) occurred of which 332 (9.7%) were cardiac death and 63 (1.8%) were due to stroke. There were 578 (16.8%) hospitalisations mainly due to acute coronary syndrome, arrythmias and HF.

Future plans

Currently, this is the largest prospective study on AF patients from India, and the cohort will be followed for 5 years to observe the treatment patterns and clinical outcomes. The investigators encourage collaborations with national and international AF researchers.

Trial registration number

CTRI/2017/10/010097.
Developing and validating an instrument to assess non-hospital health centers’ preparedness to provide initial emergency care: a study protocol
Authors: Amir Behghadami Mehrdad , Janati Ali , Sadeghi-Bazargani Homayoun , Gholizadeh Masoumeh , Rahmani Farzad , Arab-Zozani Morteza
Published: July 2019

Introduction

Basic emergency management in urban and rural areas is a critical challenge. This paper presents the protocol for developing, validating and piloting an instrument to assess the preparedness of non-hospital health centres which deliver initial emergency care.

Methods and analysis

This study will be designed based on a sequential exploratory mixed method in two phases, in each of which there are three steps. In the first step of phase I, an extensive systematic review will be conducted. In the second step, through focus group discussions (FGDs), the experts’ views on the definition of domains and items of the instrument will be compiled. In addition, semistructured interviews with the target group will be performed. Then, qualitative framework analysis will be performed. In the last step of phase I, the results of both steps will be triangulated by a panel of experts to define the domains and items to be included in the instrument. Phase II will include content validity, feasibility and reliability of the instrument. Content validity of the instrument will be assessed using modified Kappa coefficient based on clarity and relevance criteria. Feasibility of the instrument will be assessed through its implementation in 10 non-hospital health centres in Tabriz, which will be selected randomly. Reliability will be assessed in a pilot on 30 non-hospital health centres through using stratified random sampling method. Reliability of the instrument will be assessed through measuring internal consistency, test-retest reliability and inter-rater agreement. The main statistical methods for assessing reliability will include Cronbach’s alpha, intraclass correlation coefficient and Kendall’s tau-b. All the statistical analyses will be performed using Stata V.14.

Ethics and dissemination

This study is approved by Tabriz University of Medical Sciences Research Ethics Committee (IR.TBZMED.REC.1397.145). The results of the study will be presented at national scientific conferences and published in peer-reviewed journals.
Early medical therapy for acute laryngeal injury (ALgI) following endotracheal intubation: a protocol for a prospective single-centre randomised controlled trial
Authors: Lowery Anne S , Kimura Kyle , Shinn Justin , Shannon Chevis , Gelbard Alexander
Published: July 2019

Introduction

Respiratory failure requiring endotracheal intubation accounts for a significant proportion of intensive care unit (ICU) admissions. Little attention has been paid to the laryngeal consequences of endotracheal intubation. Acute laryngeal injury (ALgI) after intubation occurs at the mucosal interface of the endotracheal tube and posterior larynx and although not immediately manifest at extubation, can progress to mature fibrosis, restricted glottic mobility and clinically significant ventilatory impairment. A recent prospective observational study has shown that >50% of patients intubated >24 hours in an ICU develop ALgI. Strikingly, patients with AlgI manifest significantly worse subjective breathing at 12 weeks. Current ALgI treatments are largely surgical yet offer a marginal improvement in symptoms.In this study, we will examine the ability of a postextubation medical regime (azithromycin and inhaled budesonide) to improve breathing 12 weeks after ALgI.

Methods and analysis

A prospective, single-centre, double-blinded, randomised, control trial will be conducted at Vanderbilt Medical Center. Participants will be recruited from adult patients in ICUs. Participants will undergo a bedside flexible nasolaryngoscopy for the identification of ALgI within 72 hours postextubation. In addition, participants will be asked to complete peak expiratory flow measurements immediately postintubation. Patients found to have ALgI will be randomised to the placebo control or medical therapy group (azithromycin 250 mg and budesonide 0.5 mg for 14 days). Repeat peak expiratory flow, examination of the larynx and patient-reported Clinical COPD (chronic obstructive pulmonary disease) Questionnaire, Voice Handicap Index and 12-Item Short Form Health Survey questionnaires will be conducted at 12 weeks postextubation. Consented patients will also have patient-specific, disease-specific and procedure-specific covariates abstracted from their medical record.

Ethics and dissemination

The Institutional Review Board (IRB) Committee of the Vanderbilt University Medical Center has approved this protocol (IRB #171066). The findings of the trial will be disseminated through peer-reviewed journals, national and international conferences.

Trial registration number

NCT03250975
Impact of general anaesthesia in overall and disease-free survival compared to other types of anaesthesia in patients undergoing surgery for cutaneous melanoma: a systematic review and meta-analysis protocol
Authors: Araujo Bruno Luís de Castro , de Oliveira Jadivan Leite , Corrêa Flavia de Miranda , Fontes Luis Eduardo Santos , de Melo Andreia Cristina , Thuler Luiz Claudio Santos
Published: July 2019

Introduction

Cutaneous melanoma is an aggressive type of skin cancer. Anaesthetic agents may have an impact on the immune response, postoperative neurohumoral response and tumour progression. This systematic review aims to evaluate the impact of general anaesthesia on overall and disease-free survival compared with other types anaesthesia in patients undergoing surgery for cutaneous melanoma.

Methods and analysis

The review will analyse data from controlled and observational studies of patients undergoing surgery for melanoma under general anaesthesia compared with other types of anaesthesia. The primary outcomes are overall survival and disease-free survival. The secondary outcomes are health-related quality of life, time to tumour progression, distant disease-free survival, time to treatment failure, cancer-specific survival, biochemical recurrence, return of intended oncological therapy, days alive and out of the hospital at 90 days, cost analysis and adverse events. A comprehensive literature search will be performed using the MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, LILACS and IBECS databases. Grey literature will also be searched. Risk of methodological bias will be assessed using The Cochrane Collaboration’s revised tool for assessing risk of bias in randomised trials (RoB 2.0) and the Newcastle–Ottawa scale. Two reviewers will independently assess the eligibility of studies and risk of bias; a third author will solve discrepancies. One author will perform data extraction and the other will check the process and data. Qualitative analysis will be carried out using all included studies. A meta-analysis using a random-effects model for pooled risk estimates will be carried out for the two main outcomes and for selected secondary outcomes if they conform to previously stated criteria. The GRADE approach will be used to summarise the quality of evidence.

Ethics and dissemination

Ethics approval is not required as we analyse data from previously reported studies.

PROSPERO registration number

CRD42018114918.
Bragatston study protocol: a multicentre cohort study on automated quantification of cardiovascular calcifications on radiotherapy planning CT scans for cardiovascular risk prediction in patients with breast cancer
Authors: Emaus Marleen J , Išgum Ivana , van Velzen Sanne G M , van den Bongard H J G Desirée , Gernaat Sofie A M , Lessmann Nikolas , Sattler Margriet G A , Teske Arco J , Penninkhof Joan , Meijer Hanneke , Pignol Jean-Philippe , Verkooijen Helena M
Published: July 2019

Introduction

Cardiovascular disease (CVD) is an important cause of death in breast cancer survivors. Some breast cancer treatments including anthracyclines, trastuzumab and radiotherapy can increase the risk of CVD, especially for patients with pre-existing CVD risk factors. Early identification of patients at increased CVD risk may allow switching to less cardiotoxic treatments, active surveillance or treatment of CVD risk factors. One of the strongest independent CVD risk factors is the presence and extent of coronary artery calcifications (CAC). In clinical practice, CAC are generally quantified on ECG-triggered cardiac CT scans. Patients with breast cancer treated with radiotherapy routinely undergo radiotherapy planning CT scans of the chest, and those scans could provide the opportunity to routinely assess CAC before a potentially cardiotoxic treatment. The Bragatston study aims to investigate the association between calcifications in the coronary arteries, aorta and heart valves (hereinafter called ‘cardiovascular calcifications’) measured automatically on planning CT scans of patients with breast cancer and CVD risk.

Methods and analysis

In a first step, we will optimise and validate a deep learning algorithm for automated quantification of cardiovascular calcifications on planning CT scans of patients with breast cancer. Then, in a multicentre cohort study (University Medical Center Utrecht, Utrecht, Erasmus MC Cancer Institute, Rotterdam and Radboudumc, Nijmegen, The Netherlands), the association between cardiovascular calcifications measured on planning CT scans of patients with breast cancer (n≈16 000) and incident (non-)fatal CVD events will be evaluated. To assess the added predictive value of these calcifications over traditional CVD risk factors and treatment characteristics, a case-cohort analysis will be performed among all cohort members diagnosed with a CVD event during follow-up (n≈200) and a random sample of the baseline cohort (n≈600).

Ethics and dissemination

The Institutional Review Boards of the participating hospitals decided that the Medical Research Involving Human Subjects Act does not apply. Findings will be published in peer-reviewed journals and presented at conferences.

Trial registration number

NCT03206333.
Novel ACT-based eHealth psychoeducational intervention for students with mental distress: a study protocol for a mixed-methodology pilot trial
Authors: Edwards Darren J , Rainey Elinor , Boukouvala Vasiliki , Wells Yasmin , Bennett Paul , Tree Jeremy , Kemp Andrew H
Published: July 2019

Introduction

Recent studies have revealed a high prevalence of depression, anxiety and stress symptoms among university students, highlighting an urgent need for preventative measures at low cost to better support often overwhelmed support services.

Objective

Here we propose a protocol for assessing the feasibility of a randomised controlled trial (RCT) for an online transdiagnostic psychoeducational intervention called ‘A Bite of ACT’ compared with a waitlist control.

Methods and analysis

This is an RCT with crossover design involving baseline assessments and two follow-up periods. The primary outcome measure will be the Acceptance Checklist for Clinical Effectiveness Pilot Trials (ACCEPT) for measuring the feasibility of the trial design and methods. Secondary outcomes include measures of well-being, social connectedness, quality of life (EuroQol Five Dimensions), depression, anxiety and stress (Depression Anxiety Stress Scales-21), as well as the process measures: psychological flexibility (Acceptance and Action Questionnaire-Second Version and the Mindful Attention Awareness Scale) and heart rate variability. Analysis will involve calculating descriptive statistics, examining trial feasibility outcomes through ACCEPT, and determining effect size measures to determine the sample size needed in a future trial (if indicated). Qualitative interviews and preliminary health economics analysis will provide additional insights into the feasibility of the intervention and trial methods.

Ethics and dissemination

This study has been approved by the Department of Psychology Research Ethics Committee in the College of Human and Health Sciences at Swansea University. Dissemination will involve publication in international peer-reviewed journals, presentation of findings at relevant local, national and international conferences, and promotion of study outcomes using social media and other channels for disseminating findings to the wider community.

Trial registration number

NCT03810131; Pre-results.
Changes in the upper airway following induction of anaesthesia: a prospective observational study protocol to determine the use of ultrasound in the assessment of a difficult airway in China
Authors: Dong Fang , Wang Yong , Wang Xia , Zhao Huanyi , Ma Wuhua
Published: July 2019

Introduction

Difficult airway management is closely related to the safety and quality of medical care. However, the low incidence of correct prediction of difficult airway in clinical screening tests presents physicians with a dilemma. Depressed airway neuromuscular tension during sleep and anaesthesia tends to cause collapse of fragile parts of the upper airway. Although previous studies have confirmed that anterior cervical tissue thickness is associated with difficult airways, there is no evidence to support a correlation between a difficult airway and specific patterns or findings of anaesthesia-induced airway collapse. Thus, this study aims to examine changes in airway dimensions before and after induction of general anaesthesia to explore whether it could provide useful information regarding the specific anatomic changes occurring which may cause difficult airways.

Methods and analysis

This will be a single-centre prospective observational single-blinded study, conducted in a tertiary teaching hospital in Guangzhou, China. Subjects will be recruited from patients (aged 18–65 years) scheduled for elective surgery under general anaesthesia. Sonographic measurement will be performed to detect changes in the thickness of the anterior cervical soft tissue before and after anaesthetic induction. Based on the resulting data distribution, analyses will initially compare these changes using a paired t-test or the Wilcoxon signed-rank test. The correlation of sonographic changes and Cormack–Lehane grade will be evaluated by using receiver-operating characteristic curves to detect the sensitivity and specificity of a measurement for detecting difficulties. Linear stepwise regression analysis will be used to assess the correlation between airway changes and demographic variables as well as clinical tests.

Ethics and dissemination

Ethical approval has been obtained from the Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine (ZYYECK (2018) 041). The results will be disseminated through conference presentations, professional journals and peer-reviewed publications.

Trial registration number

ChiCTR1900021123; Pre-results.
Primary Palliative Care for Emergency Medicine (PRIM-ER): Protocol for a Pragmatic, Cluster-Randomised, Stepped Wedge Design to Test the Effectiveness of Primary Palliative Care Education, Training and Technical Support for Emergency Medicine
Authors: Grudzen Corita R , Brody Abraham A , Chung Frank R , Cuthel Allison M , Mann Devin , McQuilkin Jordan A , Rubin Ada L , Swartz Jordan , Tan Audrey , Goldfeld Keith S
Published: July 2019

Introduction

Emergency departments (ED) care for society’s most vulnerable older adults who present with exacerbations of chronic disease at the end of life, yet the clinical paradigm focuses on treatment of acute pathologies. Palliative care interventions in the ED capture high-risk patients at a time of crisis and can dramatically improve patient-centred outcomes. This study aims to implement and evaluate Primary Palliative Care for Emergency Medicine (PRIM-ER) on ED disposition, healthcare utilisation and survival in older adults with serious illness.

Methods and analysis

This is the protocol for a pragmatic, cluster-randomised stepped wedge trial to test the effectiveness of PRIM-ER in 35 EDs across the USA. The intervention includes four core components: (1) evidence-based, multidisciplinary primary palliative care education; (2) simulation-based workshops; (3) clinical decision support; and (4) audit and feedback. The study is divided into two phases: a pilot phase, to ensure feasibility in two sites, and an implementation and evaluation phase, where we implement the intervention and test the effectiveness in 33 EDs over 2 years. Using Centers for Medicare and Medicaid Services (CMS) data, we will assess the primary outcomes in approximately 300 000 patients: ED disposition to an acute care setting, healthcare utilisation in the 6 months following the ED visit and survival following the index ED visit. Analysis will also determine the site, provider and patient-level characteristics that are associated with variation in impact of PRIM-ER.

Ethics and dissemination

Institutional Review Board approval was obtained at New York University School of Medicine to evaluate the CMS data. Oversight will also be provided by the National Institutes of Health, an Independent Monitoring Committee and a Clinical Informatics Advisory Board. Trial results will be submitted for publication in a peer-reviewed journal.

Trial registration number

NCT03424109; Pre-results
Repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy (ePIPAC) with oxaliplatin as a palliative monotherapy for isolated unresectable colorectal peritoneal metastases: protocol of a Dutch, multicentre, open-label, single-arm, phase II study (CRC-PIPAC)
Authors: Rovers Koen P , Lurvink Robin J , Wassenaar Emma CE , Kootstra Thomas JM , Scholten Harm J , Tajzai Rudaba , Deenen Maarten J , Nederend Joost , Lahaye Max J , Huysentruyt Clément JR , van ’t Erve Iris , Fijneman Remond JA , Constantinides Alexander , Kranenburg Onno , Los Maartje , Thijs Anna MJ , Creemers Geert-Jan M , Burger Jacobus WA , Wiezer Marinus J , Boerma Djamila , Nienhuijs Simon W , de Hingh Ignace HJT
Published: July 2019

Introduction

Repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX) is offered as a palliative treatment option for patients with isolated unresectable colorectal peritoneal metastases (PM) in several centres worldwide. However, little is known about its feasibility, safety, tolerability, efficacy, costs and pharmacokinetics in this setting. This study aims to explore these parameters in patients with isolated unresectable colorectal PM who receive repetitive ePIPAC-OX as a palliative monotherapy.

Methods and analysis

This multicentre, open-label, single-arm, phase II study is performed in two Dutch tertiary referral hospitals for the surgical treatment of colorectal PM. Eligible patients are adults who have histologically or cytologically proven isolated unresectable PM of a colorectal or appendiceal carcinoma, a good performance status, adequate organ functions and no symptoms of gastrointestinal obstruction. Instead of standard palliative treatment, enrolled patients receive laparoscopy-controlled ePIPAC-OX (92 mg/m2body surface area (BSA)) with intravenous leucovorin (20 mg/m2BSA) and bolus 5-fluorouracil (400 mg/m2BSA) every 6 weeks. Four weeks after each procedure, patients undergo clinical, radiological and biochemical evaluation. ePIPAC-OX is repeated until disease progression, after which standard palliative treatment is (re)considered. The primary outcome is the number of patients with major toxicity (grade ≥3 according to the Common Terminology Criteria for Adverse Events v4.0) up to 4 weeks after the last ePIPAC-OX. Secondary outcomes are the environmental safety of ePIPAC-OX, procedure-related characteristics, minor toxicity, postoperative complications, hospital stay, readmissions, quality of life, costs, pharmacokinetics of oxaliplatin, progression-free survival, overall survival, and the radiological, histopathological, cytological, biochemical and macroscopic tumour response.

Ethics and dissemination

This study is approved by an ethics committee, the Dutch competent authority and the institutional review boards of both study centres. Results are intended for publication in peer-reviewed medical journals and for presentation to patients, healthcare professionals and other stakeholders.

Trial registration number

NCT03246321, Pre-results;ISRCTN89947480, Pre-results; NTR6603, Pre-results; EudraCT: 2017-000927-29, Pre-results.
Barriers and facilitators experienced by patients, carers and healthcare professionals when managing symptoms in infants, children and young people at end-of-life: a mixed methods systematic review protocol
Authors: Greenfield Katie , Holley Simone , Schoth Daniel Eric , Harrop Emily , Howard Richard , Bayliss Julie , Brook Lynda , Jassal Satbir , Johnson Margaret , Wong Ian , Liossi Christina
Published: July 2019

Introduction

This protocol describes the objective and methods of a systematic review of barriers and facilitators experienced by patients, carers and healthcare professionals when managing symptoms in infants, children and young people (ICYP) at end-of-life.

Methods and analysis

The Cochrane Library, PROSPERO, CINAHL, MEDLINE, PsycINFO, Web of Science Core Collection, ProQuest Dissertations & Theses Database, Evidence Search and OpenGrey will be electronically searched. Reference screening of relevant articles and inquiries to researchers in the field will be undertaken. Studies will be selected if they apply qualitative, quantitative or mixed-methods designs to explore barriers and facilitators experienced by patients, carers and healthcare professionals when managing symptoms in ICYP at end-of-life.

Articles will be screened by title and abstract by one reviewer with a second reviewer assessing 10% of the articles. Both reviewers will read and screen all remaining potentially relevant articles. For included articles, one reviewer will extract study characteristics and one will check this.

Both reviewers will undertake independent quality assessments of included studies using established and appropriate checklists including The Critical Appraisal Skills Programme Qualitative Checklist; The evaluative criteria of credibility, transferability, dependability and confirmability; The Quality Assessment Tool for Quantitative Studies, and The Mixed Methods Appraisal Tool. Data synthesis methods will be decided after data extraction and assessment.

Ethics and dissemination

This review will inform our understanding of symptom management in ICYP at end-of-life. The findings will be reported in a peer-reviewed journal and presented at conferences. The study raises no ethical issues.

PROSPERO registration number

CRD42019124797