bluuebunny/crossref_metadata_2025 huggingface dataset:
The mutational burden and oligogenic inheritance in Klippel-Feil syndrome
Authors:   DISCO (Deciphering Disorders Involving Scoliosis and COmorbidities) study, Li Ziquan , Zhao Sen , Cai Siyi , Zhang Yuanqiang , Wang Lianlei , Niu Yuchen , Li Xiaoxin , Hu Jianhua , Chen Jingdan , Wang Shengru , Wang Huizi , Liu Gang , Tian Ye , Wu Zhihong , Zhang Terry Jianguo , Wang Yipeng , Wu Nan
Published: April 2020

Background

Klippel-Feil syndrome (KFS) represents a rare anomaly characterized by congenital fusion of the cervical vertebrae. The underlying molecular etiology remains largely unknown because of the genetic and phenotypic heterogeneity.

Methods

We consecutively recruited a Chinese cohort of 37 patients with KFS. The clinical manifestations and radiological assessments were analyzed and whole-exome sequencing (WES) was performed. Additionally, rare variants in KFS cases and controls were compared using genetic burden analysis.

Results

We primarily examined rare variants in five reported genes (GDF6,MEOX1, GDF3, MYO18BandRIPPLY2) associated with KFS and detected three variants of uncertain significance inMYO18B. Based on rare variant burden analysis of 96 candidate genes related to vertebral segmentation defects, we identifiedBAZ1Bas having the highest probability of association with KFS, followed byFREM2,SUFU,VANGL1andKMT2D. In addition, seven patients were proposed to show potential oligogenic inheritance involving more than one variants in candidate genes, the frequency of which was significantly higher than that in the in-house controls.

Conclusions

Our study presents an exome-sequenced cohort and identifies five novel genes potentially associated with KFS, extending the spectrum of known mutations contributing to this syndrome. Furthermore, the genetic burden analysis provides further evidence for potential oligogenic inheritance of KFS.
Effectiveness of intramuscular gluteal glucocorticoid injection versus intra-articular glucocorticoid injection in knee osteoarthritis: design of a multicenter randomized, 24 weeks comparative parallel-group trial
Authors: Mol Marianne F. , Runhaar Jos , Bos P. Koen , Dorleijn Desirée M. J. , Vis Marijn , Gussekloo Jacobijn , Bindels Patrick J. E. , Bierma-Zeinstra Sita M. A.
Published: April 2020

Background

The knee is symptomatically the most frequent affected joint in osteoarthritis and, in the Netherlands and other Western countries, is mainly managed by general practitioners (GPs). An intra-articular glucocorticoid injection is recommended in (inter) national guidelines for patients with knee osteoarthritis as an option for a flare of knee pain and/or for those who are not responding well to pain medication. An innovative approach that could replace the intra-articular injection is an intramuscular gluteal glucocorticoid injection. An intramuscular injection is easier to perform than an intra-articular injection with lesser risk of severe local adverse reactions. We hypothesize that intramuscular gluteal glucocorticoid injection is non-inferior in reducing knee pain compared to intra-articular glucocorticoid injection, with potentially a longer lasting effect than intra-articular injection.

Methods/design

The study will be a pragmatic randomized controlled non-inferiority trial with two parallel groups. A total of 140 patients aged 45 years and older with knee osteoarthritis who contacted their general practitioner and have persistent knee pain (score ≥ 3 on 0–10 numerical rating scale; 0 = no knee pain) will be included.

Patients will be randomly allocated (1:1) to an injection of 40 mg triamcinolone acetonide intra-articular in the knee joint or intramuscular in the ipsilateral ventrogluteal area.

The effect of treatment will be evaluated by questionnaires at 2, 4, 8, 12, and 24 weeks after injection. The primary outcome is patients’ reported severity of knee pain measured with the pain subscale of the Knee injury and Osteoarthritis Outcome Score 4 weeks after injection. Statistical analysis will be based on both the per-protocol and the intention-to-treat principle.

Discussion

This study will evaluate non-inferiority of intramuscular glucocorticoid injection compared to intra-articular glucocorticoid injection for knee osteoarthritis symptoms.

Trial registration

This trial is registered in the Dutch Trial Registry (number NTR6968) at 2018-01-22 (https://www.trialregister.nl/trial/6784). Issue date: 1 October 2019.

Trial sponsor

Erasmus MC University Medical Center Rotterdam.

PO-box 2040.

3000 CA Rotterdam.

The Netherlands.
Effects and safety of the combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) in the treatment of knee osteoarthritis: a systematic review and meta-analysis
Authors: Zhao Jinlong , Huang Hetao , Liang Guihong , Zeng Ling-feng , Yang Weiyi , Liu Jun
Published: April 2020

Background

Studies have shown that the combined application of hyaluronic acid (HA) and platelet-rich plasma (PRP) can repair degenerated cartilage and delay the progression of knee osteoarthritis (KOA). The purpose of this study was to explore the efficacy and safety of the intra-articular injection of PRP combined with HA compared with the intra-articular injection of PRP or HA alone in the treatment of KOA.

Methods

The PubMed, Cochrane Library, EMBASE and China National Knowledge Infrastructure (CNKI) databases were searched from inception to December 2019. Randomized controlled trials and cohort studies of PRP combined with HA for KOA were included. Two orthopaedic surgeons conducted the literature retrieval and extracted the data. Outcome indicators included the Western Ontario and McMaster Universities Arthritis Index (WOMAC), the Lequesne Index, the visual analogue scale (VAS) for pain, and adverse events (AEs). Review Manager 5.3 was used to calculate the relative risk (RR) or standardized mean difference (SMD) of the pooled data. STATA 14.0 was used for quantitative publication bias evaluation.

Results

Seven studies (5 randomized controlled trials, 2 cohort studies) with a total of 941 patients were included. In the VAS comparison after 6 months of follow-up, PRP combined with HA was more likely to reduce knee pain than PRP alone (SMD: − 0.31; 95% confidence interval (CI): − 0.55 to − 0.06;P = 0.01 < 0.05). PRP combined with HA for KOA achieved better improvements in the WOMAC Function Score (SMD: -0.32; 95% CI: − 0.54 to − 0.10;P < 0.05) and WOMAC Total Score (SMD: -0.42; 95% CI: − 0.67 to − 0.17;P < 0.05) at the 12-month follow-up than did the application of PRP alone. In a comparison of Lequesne Index scores at the 6-month follow-up, PRP combined with HA improved knee pain scores more than PRP alone (SMD: -0.42; 95% CI: − 0.67 to − 0.17;P < 0.05). In terms of AEs, PRP combined with HA was not significantly different from PRP or HA alone (P > 0.05).

Conclusions

Compared with intra-articular injection of PRP alone, that of PRP combined with HA can improve the WOMAC Function Scores, WOMAC Total Score, 6-month follow-up VAS ratings, and Lequesne Index scores. However, in terms of the incidence of AEs, PRP combined with HA is not significantly different from PRP or HA alone.
Digital anatomical study and clinical application of screw placement for quadrilateral plate fractures in the danger zone
Authors: Zhao Bei , Sun Zhongye , Zhang Wei , Xu Zhongbao , Yang Xiaofei , Mu Weidong
Published: April 2020

Background

Direct screw placement for quadrilateral plate fractures in the danger zone of the acetabulum is very difficult. This study was performed to simulate the surgical procedure and try to obtain effective and safe screw angles through the middle window of the ilioinguinal approach in Chinese patients.

Methods

We randomly collected the pelvic computed tomography (CT) scans of 100 adults. DICOM-formatted CT-scan images were imported into Mimics software. The three-dimensional reconstruction (3D) digital model of the semi-pelvis was established. A 3.5 mm cylinder was used to simulate the pathway of the screw from the designated insertion point. The angles of insertion and intersex differences were explored by statistical analyses.

Results

The screws could be inserted via three angles: medial inclination, anterior inclination and posterior inclination. The mean minimum medial inclination angle (MIMIA) of insertion point A was 4.96° ± 1.11° in males and 8.66° ± 3.40° in females, and the intersex difference was significant. The mean minimum medial inclination angle (MIMIA) of insertion point B was − 5.31° ± 3.69° in males and 1.75° ± 8.95° in females, and the intersex difference was significant. There were no differences between any of the angles for males and females at insertion point O.

Conclusions

Preoperative measurement and calculation by digital tools before screw placement for quadrilateral plate fractures of the acetabulum are feasible. Double cortical screws could be placed safely in the danger zone through the middle window of the ilioinguinal approach to increase the stability of the acetabulum.
Oncogenic seRNA functional activation: a novel mechanism of tumorigenesis
Authors: Tan Yuan , Li Yuejin , Tang Faqing
Published: April 2020

seRNA is a noncoding RNA (ncRNA) transcribed from active super-enhancer (SE), through which SE exerts biological functions and participates in various physiological and pathological processes. seRNA recruits cofactor, RNA polymerase II and mediator to constitute and stabilize chromatin loop SE and promoter region, which regulates target genes transcription. In tumorigenesis, DNA insertion, deletion, translocation, focal amplification and carcinogen factor mediate oncogenic SE generation, meanwhile, oncogenic SE transcribes into tumor-related seRNA, termed as oncogenic seRNA. Oncogenic seRNA participates in tumorigenesis through activating various signal-pathways. The recent reports showed that oncogenic seRNA implicates in a widespread range of cytopathological processes in cancer progression including cell proliferation, apoptosis, autophagy, epithelial-mesenchymal transition, extracellular matrix stiffness and angiogenesis. In this article, we comprehensively summarized seRNA’s characteristics and functions, and emphatically introduced inducible formation of oncogenic seRNA and its functional mechanisms. Lastly, some research strategies on oncogenic seRNA were introduced, and the perspectives on cancer therapy that targets oncogenic seRNA were also discussed.
The beneficial effects of nutraceuticals and natural products on small dense LDL levels, LDL particle number and LDL particle size: a clinical review
Authors: Talebi Sepide , Bagherniya Mohammad , Atkin Stephen L. , Askari Gholamreza , Orafai Hossein M. , Sahebkar Amirhossein
Published: April 2020

Cardiovascular diseases (CVDs) are globally the major causes of morbidity and mortality. Evidence shows that smaller and denser low-dense lipoprotein (sdLDL) particles are independent atherogenic risk factors for CVD due to their greater susceptibility to oxidation, and permeability in the endothelium of arterial walls. sdLDL levels are an independent risk factor and of more predictive value than total LDL-C for the assessment of coronary artery disease and metabolic syndrome. Functional food ingredients have attracted significant attention for the management of dyslipidemia and subsequently increase cardio-metabolic health. However, to date there is no study that has investigated the effect of these bioactive natural compounds on sdLDL levels. Therefore, the aim of the present review is to summarize the evidence accrued on the effect of special dietary ingredients such as omega-3 polyunsaturated fatty acids, nutraceuticals and herbal medicines on the levels of sdLDL, LDL particle number, and LDL particle size. Based on the results of the existing clinical trials this review suggests that natural products such as medicinal plants, nutraceuticals and omega-3 fatty acids can be used as adjunct or complementary therapeutic agents to reduce sdLDL levels, LDL particle numbers or increase LDL particle size and subsequently may prevent and treat CVD, with the advantage that theses natural agents are generally safe, accessible, and inexpensive.
A new ureteroileal anastomosis technique in modified ileal orthotopic bladder substitution after radical cystectomy
Authors: Wu Bin , Pan Chunyu , Yao Zichuan , Zhu Xianqing , Bai Song
Published: April 2020

Background

The aim of this study is to describe a modified technique in ileal orthotopic bladder substitution with a new ureteroileal anastomosis.

Case presentation

After a classic open radical cystectomy with bilateral pelvic lymphadenectomy was performed extraperitoneally, a 56-cm ileal segment was used to construct the spheroidal shape bladder substitution. The 8-cm long proximal and distal ends of the ileal segment were used as afferent limbs. Two-centimeter ileal segments of afferent limbs were detubularized and transversally tubularized. The elongated ileal tube was anastomosed with the ureter in an end-to-end fashion. The pathway of the ureteroileal anastomosis was placed between the abdominal cutaneous fat and the anterior rectus muscular sheath. Perioperative data and long-term functional outcomes were assessed. Between December 2011 and December 2015, seven male patients underwent this procedure with a median 46 (30–77) months follow-up in our hospital. There was no difference between preoperative and postoperative estimated glomerular filtration rates (Z = − 1.693, P = 0.09). One of 14 sides had ureteroileal anastomotic stenosis; two of 14 sides in one patient had ureteroileal anastomotic stenosis caused by invasion of pelvic recurrence 15 months postoperatively. Reflux was completely prevented by placing pressure on the corresponding point on the abdominal surface when voiding urine in all patients.

Conclusions

We describe a feasible technique modification in detail, which provides some advantages for effective anti-reflux by mechanical finger pressing and abdominal contraction, a low incidence of stricture, and ease for a secondary operation in the long-term follow-up period.
Iron overload contributes to general anaesthesia-induced neurotoxicity and cognitive deficits
Authors: Wu Jing , Yang Jian-Jun , Cao Yan , Li Huihui , Zhao Hongting , Yang Shuofei , Li Kuanyu
Published: April 2020

Background

Increasing evidence suggests that multiple or long-time exposure to general anaesthesia (GA) could be detrimental to cognitive development in young subjects and might also contribute to accelerated neurodegeneration in the elderly. Iron is essential for normal neuronal function, and excess iron in the brain is implicated in several neurodegenerative diseases. However, the role of iron in GA-induced neurotoxicity and cognitive deficits remains elusive.

Methods

We used the primary hippocampal neurons and rodents including young rats and aged mice to examine whether GA impacted iron metabolism and whether the impact contributed to neuronal outcomes. In addition, a pharmacological suppression of iron metabolism was performed to explore the molecular mechanism underlying GA-mediated iron overload in the brain.

Results

Our results demonstrated that GA, induced by intravenous ketamine or inhalational sevoflurane, disturbed iron homeostasis and caused iron overload in both in vitro hippocampal neuron culture and in vivo hippocampus. Interestingly, ketamine- or sevoflurane-induced cognitive deficits, very likely, resulted from a novel iron-dependent regulated cell death, ferroptosis. Notably, iron chelator deferiprone attenuated the GA-induced mitochondrial dysfunction, ferroptosis, and further cognitive deficits. Moreover, we found that GA-induced iron overload was activated by NMDAR-RASD1 signalling via DMT1 action in the brain.

Conclusion

We conclude that disturbed iron metabolism may be involved in the pathogenesis of GA-induced neurotoxicity and cognitive deficits. Our study provides new vision for consideration in GA-associated neurological disorders.
Transcriptomic analysis of brain tissues identifies a role for CCAAT enhancer binding protein β in HIV-associated neurocognitive disorder
Authors: Canchi Saranya , Swinton Mary K. , Rissman Robert A. , Fields Jerel Adam
Published: April 2020

Background

HIV-associated neurocognitive disorders (HAND) persist in the era of combined antiretroviral therapy (ART) despite reductions in viral load (VL) and overall disease severity. The mechanisms underlying HAND in the ART era are not well understood but are likely multifactorial, involving alterations in common pathways such as inflammation, autophagy, neurogenesis, and mitochondrial function. Newly developed omics approaches hold potential to identify mechanisms driving neuropathogenesis of HIV in the ART era.

Methods

In this study, using 33 postmortem frontal cortex (FC) tissues, neuropathological, molecular, and biochemical analyses were used to determine cellular localization and validate expression levels of the prolific transcription factor (TF), CCAAT enhancer binding protein (C/EBP) β, in brain tissues from HIV+ cognitively normal and HAND cases. RNA sequencing (seq) and transcriptomic analyses were performed on FC tissues including 24 specimens from well-characterized people with HIV that had undergone neurocognitive assessments. In vitro models for brain cells were used to investigate the role of C/EBPβ in mediating gene expression.

Results

The most robust signal for TF dysregulation was observed in cases diagnosed with minor neurocognitive disorder (MND) compared to cognitive normal (CN) cases. Of particular interest, due to its role in inflammation, autophagy and neurogenesis, C/EBPβ was significantly upregulated in MND compared to CN brains. C/EBPβ was increased at the protein level in HAND brains. C/EBPβ levels were significantly reduced in neurons and increased in astroglia in HAND brains compared to CN. Transfection of human astroglial cells with a plasmid expressing C/EBPβ induced expression of multiple targets identified in the transcriptomic analysis of HAND brains, including dynamin-1-like protein (DNM1L) and interleukin-1 receptor-associated kinase 1. Recombinant HIV-Tat reduced and increased C/EBPβ levels in neuronal and astroglial cells, respectively.

Conclusions

These findings are the first to present RNAseq-based transcriptomic analyses of HIV+ brain tissues, providing further evidence of altered neuroinflammation, neurogenesis, mitochondrial function, and autophagy in HAND. Interestingly, these studies confirm a role for CEBPβ in regulating inflammation, metabolism, and autophagy in astroglia. Therapeutic strategies aimed at transcriptional regulation of astroglia or downstream pathways may provide relief to HIV+ patients at risk for HAND and other neurological disorders.
Independent and inter-dependent immunoregulatory effects of NCF1 and NOS2 in experimental autoimmune encephalomyelitis
Authors: Zhong Jianghong , Yau Anthony C. Y. , Holmdahl Rikard
Published: April 2020

Background

Increasing evidence has suggested that a single nucleotide polymorphism in the Ncf1 gene is associated with experimental autoimmune encephalomyelitis (EAE). However, the mechanisms of NCF1-induced immunoregulatory effects remain poorly understood. In this study, we focus on NCF1 deficiency-mediated effects on EAE in NOS2 dependent and independent ways.

Methods

To determine the effects of NCF1 and NOS2 during EAE development, we have established recombinant mouse strains deficient at NCF1 and/or NOS2 in a crossbreeding system. Different strains allow us to examine the entire course of the disease in the Nos2-null mice bearing a Ncf1 gene that encodes a mutated NCF1, deficient in triggering oxidative burst, after immunization with recombinant myelin oligodendrocyte glycoprotein (MOG)79-96 peptides. The peptide-induced innate and adaptive immune responses were analyzed by flow cytometry.

Results

NCF1-deficient mice developed a reduced susceptibility to EAE, whereas NCF1-NOS2 double-deficient mice developed an enhanced EAE, as compared with NOS2-deficient mice. Flow cytometry analyses show that double deficiencies resulted in an increase of neutrophils in the spleen, accompanied with higher release of interleukin-1β in neutrophils prior to EAE onset. The additional deficiency in NCF1 had no added effect on either interleukin-17 or interferon-γ secretion of T cells during the priming phase.

Conclusions

These studies show that NCF1 and NOS2 interact to regulate peptide-induced EAE.
Aggravated brain injury after neonatal hypoxic ischemia in microglia-depleted mice
Authors: Tsuji Shunichiro , Di Martino Elena , Mukai Takeo , Tsuji Shoko , Murakami Takashi , Harris Robert A. , Blomgren Klas , Åden Ulrika
Published: April 2020

Background

Neuroinflammation plays an important role in neonatal hypoxic-ischemic encephalopathy (HIE). Although microglia are largely responsible for injury-induced inflammatory response, they play beneficial roles in both normal and disease states. However, the effects of microglial depletion on neonatal HIE remain unclear.

Methods

Tamoxifen was administered to Cx3cr1CreER/+Rosa26DTA/+(microglia-depleted model) and Cx3cr1CreER/+Rosa26DTA/−(control) mice at P8 and P9 to assess the effect of microglial depletion. The density of microglia was quantified using Iba-1 staining. Moreover, the proportion of resident microglia after the HI insult was analyzed using flow cytometric analysis. At P10, the HI insult was conducted using the Rice-Vannucci procedure at P10. The infarct size and apoptotic cells were analyzed at P13. Cytokine analyses were performed using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA) at P13.

Results

At P10, tamoxifen administration induced > 99% microglial depletion in DTA+mice. Following HI insult, there was persisted microglial depletion over 97% at P13. Compared to male DTA−mice, male DTA+mice exhibited significantly larger infarct volumes; however, there were no significant differences among females. Moreover, compared to male DTA−mice, male DTA+mice had a significantly higher density of TUNEL+cells in the caudoputamen, cerebral cortex, and thalamus. Moreover, compared to female DTA−mice, female DTA+mice showed a significantly greater number of TUNEL+cells in the hippocampus and thalamus. Compared to DTA−mice, ELISA revealed significantly lower IL-10 and TGF-β levels in both male and female DTA+mice under both normal conditions and after HI (more pronounced).

Conclusion

We established a microglial depletion model that aggravated neuronal damage and apoptosis after the HI insult, which was predominantly observed in males.
Investigation of a thermostable multi-domain xylanase-glucuronoyl esterase enzyme from Caldicellulosiruptor kristjanssonii incorporating multiple carbohydrate-binding modules
Authors: Krska Daniel , Larsbrink Johan
Published: April 2020

Background

Efficient degradation of lignocellulosic biomass has become a major bottleneck in industrial processes which attempt to use biomass as a carbon source for the production of biofuels and materials. To make the most effective use of the source material, both the hemicellulosic as well as cellulosic parts of the biomass should be targeted, and as such both hemicellulases and cellulases are important enzymes in biorefinery processes. Using thermostable versions of these enzymes can also prove beneficial in biomass degradation, as they can be expected to act faster than mesophilic enzymes and the process can also be improved by lower viscosities at higher temperatures, as well as prevent the introduction of microbial contamination.

Results

This study presents the investigation of the thermostable, dual-function xylanase-glucuronoyl esterase enzymeCkXyn10C-GE15A from the hyperthermophilic bacteriumCaldicellulosiruptor kristjanssonii. Biochemical characterization of the enzyme was performed, including assays for establishing the melting points for the different protein domains, activity assays for the two catalytic domains, as well as binding assays for the multiple carbohydrate-binding domains present inCkXyn10C-GE15A. Although the enzyme domains are naturally linked together, when added separately to biomass, the expected boosting of the xylanase action was not seen. This lack of intramolecular synergy might suggest, together with previous data, that increased xylose release is not the main beneficial trait given by glucuronoyl esterases.

Conclusions

Due to its thermostability,CkXyn10C-GE15A is a promising candidate for industrial processes, with both catalytic domains exhibiting melting temperatures over 70 °C. Of particular interest is the glucuronoyl esterase domain, as it represents the first studied thermostable enzyme displaying this activity.
Simple, rapid, and accurate malaria diagnostic platform using microfluidic-based immunoassay of Plasmodium falciparum lactate dehydrogenase
Authors: Lee Wang Sik , Kang Taejoon , Kwak Kyung Jin , Park Kyoungsook , Yi So Yeon , Lee Ui Jin , Shin Yong Beom , Jeong Jinyoung
Published: April 2020

This work reports on a rapid diagnostic platform for the detection of Plasmodium falciparum lactate dehydrogenase (PfLDH), a representative malaria biomarker, using a microfluidic microplate-based immunoassay. In this study, the microfluidic microplate made it possible to diagnose PfLDH with a small volume of sample (only 5 μL) and short time (< 90 min) compared to conventional immunoassays such as enzyme-linked immunosorbent assay (ELISA). Moreover, the diagnostic performance of PfLDH showed high sensitivity, specificity, and selectivity (i.e., 0.025 pg/μL in phosphate-buffered saline and 1 pg/μL in human serum). The microfluidic-based microplate sensing platform has the potential to adapt simple, rapid, and accurate diagnoses to the practical detection of malaria.
Random walk model simulates the increased drowsiness of children with obstructive sleep apnea
Authors: Guo Shu , Dvir Hila , Havlin Shlomo , Li Daqing , Kang Rui , Bartsch Ronny P.
Published: April 2020

Obstructive sleep apnea (OSA) is a common sleep disorder, which is particularly harmful to children as it may lead to learning deficits, attention deficit hyperactivity disorder (ADHD) and growth retardation. Furthermore, OSA alters the dynamics of sleep-stage transitions and in particular increases the transition time from being awake to falling asleep (“drowsiness”). In this letter, we show that sleep bout durations during this transient state can be described by an exponential distribution with a longer characteristic time scale for OSA compared to healthy children. This finding can be simulated and better understood by using a random walk model of the integrated neuronal voltage of wake-promoting neurons, and by introducing a new concept of a light sleep threshold parameter L that distinguishes between drowsiness and deeper forms of light sleep. Our analysis also shows that the value of L correlates well with OSA severity. Moreover, we find that after OSA treatment, the parameter L returns to normal values similar to those we detected for healthy children. We anticipate that our methodology can help in better understanding and modeling sleep dynamics, and may improve diagnostics and treatment monitoring of OSA.
Rare health conditions 34: Zellweger syndrome, Stickler syndrome, mucormycosis and Zollinger-Ellison syndrome
Authors: Barber Chris
Published: April 2020

The purpose of this series is to highlight a range of rare health conditions. Rare health conditions are those that affect no more and usually fewer than 1 person in every 2000 and many healthcare assistants (HCAs) and nurses will encounter some of these conditions, given the high number of these conditions. This 34th article will briefly explore four of these conditions: Zellweger syndrome, Stickler syndrome, mucormycosis and Zollinger-Ellison syndrome.
Dementia 7. When dementia is diagnosed, supporting the person and family caregivers
Authors: Nazarko Linda
Published: April 2020

The impact of a dementia diagnosis can be devastating to the person with dementia and his or her family. The person and their loved ones have been informed that the person has a progressive disease that affects memory, thinking, orientation, comprehension, calculation, learning capacity, language, and judgement ( World Health Organization (WHO), 2017 ). It is often thought of as a diagnosis of despair; however, if managed well, the diagnosis is an opportunity to enable the person to experience the best possible quality of life and to inform the family of his or her wishes in relation to end-of-life care.
COVID-19 and gloves: when to wear and when not to wear
Authors: Nazarko Linda
Published: April 2020

The first rule of healthcare is to do no harm and some staff working in hospitals and in shops are wearing blue nitrile gloves. The aim is to protect themselves and people they come into contact with, but is indiscriminate use of gloves part of the problem rather than part of the solution?
COVID-19: implications for NHS Staff
Authors: Glasper Alan
Published: April 2020

In light of the emergence in China of COVID-19, the novel corona virus, emeritus professor Alan Glasper, from the University of Southampton discusses the role of the World Health Organization and other public health institutions in responding to potential new global pandemics and deliberates on the role of NHS staff in coping with infectious disease in clinical environments.
Transanal irrigation: is it the magic intervention for bowel management in individuals with bowel dysfunction?
Authors: Yates Ann
Published: April 2020

Historically, the use of colonic irrigation or transanal irrigation (TAI) has been viewed as an alternative therapy for the treatment of a wide variety of conditions not relating to bowel dysfunction, including nausea, fatigue, depression, headache, anxiety and rheumatism. However, these days it is viewed as an effective treatment in individuals who may present with bowel dysfunction and related symptoms of constipation and faecal incontinence. Such individuals would include people with neuropathic bowel disorders, conditions that affect sphincter control or bowel motility disorders. injury to the rectum, sphincter or bowel, slow transit times, evacuation difficulties or prolapse due to a weak/damaged pelvic floor, and chronic faecal incontinence. TAI may be performed by the person with bowel dysfunction, or by a carer or health professional. An individual's ability to use a device to undertake the procedure will be influenced by a range of factors, which are explored in this article.
The potential role of nurses in leading positive behaviour support
Authors: Savarimuthu Darren
Published: April 2020

Positive behaviour support (PBS) has become the preferred intervention in the management of challenging behaviour in learning disability and mental health services. However, there is an absence of literature on nurses' views and experience of PBS. Nurses are passive in PBS plan development while other professionals, such as clinical psychologists, often take the lead. While nurses see clinical psychologists as experts in PBS, they feel this could create a barrier that hinders its full potential and a more multidisciplinary approach would be beneficial. Nurses could take a pivotal role in delivering PBS plans if they were able to take a leading role, and this would benefit service users as nurses work far more closely with them than other professionals.
Organisational empowerment and assertive communication behaviours: a survey of Jordanian newly qualified nurses
Authors: Darawad Muhammad W , Mansour Mansour , Al-Niarat Tahany
Published: April 2020

Background:

Newly qualified nurses (NQNs) face several challenges in their early years of practice. Being empowered and able to speak up against unsafe practice are two important pillars for practising nursing safely and competently. Little research has examined the potential correlation between those two dimensions in the context of NQNs in Jordan.

Aims:

To investigate the correlation between NQNs' perceived structural empowerment in their work setting and their willingness to challenge unsafe practice in some hypothetical clinical scenarios.

Methods:

A cross-sectional survey involved 233 NQNs, who completed a self-administered questionnaire between January and March 2016.

Findings:

Participants reported moderate levels of both perceived structural empowerment and willingness to speak up against unsafe practice. There was a statistically significant positive correlation between the total structural empowerment score and the mean score for speaking up against unsafe practice.

Conclusion:

The findings highlight the impact of peer, managerial and overall organisational support on enabling NQNs to become more empowered and assertive. Concrete, collaborative and organisation-wide efforts must be considered to foster greater empowerment of NQNs, but also revisiting work priorities to include supporting and advocating assertive communication skills among the more vulnerable of the newly qualified cohort.
Traditional and complementary medicine in a nephrology department: practitioner knowledge and advice
Authors: Pedreira-Robles Guillermo , Vasco-Gómez Ana , Martínez-Delgado Yaiza , Herrera-Morales Cristina , Junyent-Iglesias Ernestina
Published: April 2020

Background:

Knowledge of traditional and complementary medicine (TCM) and its use by patients are essential for patient safety.

Aims:

To examine knowledge of TCM among practitioners in a nephrology unit and their advice to patients.

Methods:

This was a descriptive, observational, cross-sectional study. Sociodemographic data were collected and an ad hoc closed response survey was used.

Findings:

This study included 62 practitioners, of whom: 32.26% had been trained in TCM, with no significant differences between professional groups; 41.93% used TCM and 67.74% recommended TCM to patients, with no significant difference between personal use and training received. The majority (62.90%) approved of TCM being included in clinical practice, 77.42% were in favour of it being included in formal health teaching programmes, 27.42% said patients had requested information on TCM and 50% knew it could interact with conventional treatment.

Conclusion:

Although the majority of practitioners had not been trained in TCM, they were interested in including such treatments in clinical practice. They recommended TCM to patients, but neither training nor personal experience were significant factors in relation to these recommendations. Training in TCM is required to ensure advice is safe.
How to undertake a literature search: a step-by-step guide
Authors: Watson Mandy
Published: April 2020

Undertaking a literature search can be a daunting prospect. Breaking the exercise down into smaller steps will make the process more manageable. This article suggests 10 steps that will help readers complete this task, from identifying key concepts to choosing databases for the search and saving the results and search strategy. It discusses each of the steps in a little more detail, with examples and suggestions on where to get help. This structured approach will help readers obtain a more focused set of results and, ultimately, save time and effort.
An exploration of pre-operative fasting practices in adult patients having elective surgery
Authors: Denkyi Lovejoy
Published: April 2020

Background:

Patients fast routinely before elective surgery in order to reduce gastric volume and acidity. The standard fasting time is ‘nil by mouth’ from midnight before surgery. In recent years, new guidelines have recommended that patients remain nil by mouth from clear fluids for 2 hours and from solids for 6 hours. This literature review explored preoperative fasting practices in adult patients from an international perspective.

Methods:

A literature search was undertaken of databases, including CINAHL Plus, PubMed, Medline, the Cochrane Central Register of Controlled Trials, Science Direct, Sage Journals and Embase.

Results:

Anaesthetists were found to possess greater knowledge of reduced preoperative fasting than other health professionals including nurses.

Conclusion:

Actual fasting time was found to be relatively longer than prescribed fasting times.
Patient safety and litigation in the NHS post-COVID-19
Authors: Tingle John
Published: April 2020

John Tingle, Lecturer in Law, Birmingham Law School, University of Birmingham, discusses patient safety during the present coronavirus pandemic
Leadership in the time of crisis
Authors: Foster Sam
Published: April 2020

Sam Foster, Chief Nurse, Oxford University Hospitals, considers what leaders need to do in this time of COVID-19
Unna boot therapy impact on wellbeing, hope and spirituality in venous leg ulcer patients: a prospective clinical trial
Authors: Faria Elaine Cristina , Loiola Tatiana , Salomé Geraldo Magela , Ferreira Lydia Masako
Published: April 2020

Objective:

To assess the impact of Unna boot therapy on subjective wellbeing, hope and spirituality in patients with venous leg ulcers (VLU).

Method:

This was a prospective, descriptive, analytical, multicentre clinical trial conducted in a nursing care and education centre, an outpatient wound care clinic and a primary health care unit in Brazil. Adult patients with VLUs took part in the study. Patients with diabetic foot ulcers and mixed ulcers were excluded. A questionnaire assessing sociodemographic and religious characteristics of patients, the Subjective Wellbeing Scale, the Spirituality Self-Rating Scale (SSRS), and the Herth Hope Index (HHI) were administered to all patients.

Results:

A total of 60 patients (63.3% female; 86.7% aged ≥60 years) participated. Before Unna boot therapy, 65%, 66.7% and 65% of patients reported a score of one on positive affect, negative affect and life satisfaction, respectively, indicating poor subjective wellbeing. After one month of compression therapy, 66.7%, 50.0%, and 80.0% of patients reported a score of three for each element positive affect, negative affect and life satisfaction, respectively, showing a significant improvement in subjective wellbeing (p=0.029). A significant increase in total SSRS scores (p=0.017) was found between baseline (mean: 9.77) and one month of treatment (mean: 25.47), indicating a significant increase in a sense of spirituality. There was also a significant increase in total HHI values (p=0.009) between baseline (mean: 15.68) and one month of compression therapy (mean: 39.38), suggesting a significant increase in hope among patients.

Conclusion:

Patients with VLUs treated with Unna boot therapy in this study showed significant improvement in subjective wellbeing, spirituality and hope for cure.
Cost-effectiveness of superabsorbent wound dressing versus standard of care in patients with moderate-to-highly exuding leg ulcers
Authors: Veličković Vladica M. , Chadwick Paul , Rippon Mark G. , Ilić Ivana , McGlone Emma Rose , Gebreslassie Mihretab , Csernus Mariann , Streit Iris , Bordeanu Adriana , Kaspar Daniela , Linder Jörg , Smola Hans
Published: April 2020

Objective:

To determine the cost-effectiveness/utility of a superabsorbent wound dressing (Zetuvit Plus Silicone) versus the current standard of care (SoC) dressings, from the NHS perspective in England, in patients with moderate-to-high exudating leg ulcers.

Method:

A model-based economic evaluation was conducted to analyse the cost-effectiveness/utility of a new intervention. We used a microsimulation state-transition model with a time horizon of six months and a cycle length of one week. The model uses a combination of incidence base and risk prediction approach to inform transition probabilities. All clinical efficiency, health-related quality of life (HRQoL), cost and resource use inputs were informed by conducting a systematic review of UK specific literature.

Results:

Treatment with the superabsorbent dressing leads to a total expected cost per patient for a six month period of £2887, associated with 15.933 expected quality adjusted life weeks and 10.9% healing rate. When treated with SoC, the total expected cost per patient for a six month period is £3109, 15.852 expected quality adjusted life weeks and 8% healing rate. Therefore, the superabsorbent dressing leads to an increase in quality-adjusted life weeks, an increase in healing rate by 2.9% and a cost-saving of £222 per single average patient over six months. Results of several scenario analyses, one-way deterministic sensitivity analysis, and probabilistic sensitivity analysis confirmed the robustness of base-case results. The probabilistic analysis confirmed that, in any combination of variable values, the superabsorbent dressing leads to cost saving results.

Conclusion:

According to the model prediction, the superabsorbent dressing leads to an increase in health benefits and a decrease in associated costs of treatment.
Benefits of negative pressure wound therapy with instillation in the treatment of hard-to-heal wounds: a case series
Authors: Latouche Valérie , Devillers Hervé
Published: April 2020

Objective:

Impaired wound healing can lead to hard-to-heal wounds, which impact on patients, clinicians and healthcare systems. Negative pressure wound therapy with instillation and dwell time (NPWTi-d) was developed to manage wounds through early-stage cleansing. This study describes the use of NPWTi-d to help manage hard-to-heal wounds in patients with risk factors for impaired wound healing.

Method:

In this case series, patients were treated between October 2015 and March 2018 at a community hospital in western France. Normal saline solution was instilled into wounds with a dwell time of 10 minutes, followed by the application of negative pressure at −75 mmHg to −125 mmHg for 2–3 hours. If needed, patients were given appropriate oral or intravenous antibiotic treatment in conjunction with NPWTi-d and subsequent wound therapies.

Results:

A total of 15 patients participated in the study. Mean age was 81±13 years, and 12 (80%) patients were malnourished with blood albumin levels of 30.1±5.7g/l, and 12 (80%) patients were given antibiotic therapy. The mean duration of NPWTi-d was 19.4±20.8 days, with a mean number of dressing changes of 6.6±6.8; the duration of NPWTi-d and the number of dressing changes for pressure ulcers was three times that of the other wound types. The mean cost of NPWTi-d in this study was €1643.40±€1709.13. Overall, NPWTi-d provided early-stage wound cleansing and helped achieve adequate granulation tissue formation and progression to the next phase of wound healing.

Conclusion:

In these cases, NPWTi-d was a beneficial and effective method of treating hard-to-heal wounds that were resistant to traditional treatments, yielding favourable clinical outcomes.
Surgical wound assessment in Vietnam: a think-aloud technique and interview analysis
Authors: Do Hien Thi Thu , Finlayson Kathleen , Edwards Helen
Published: April 2020

Objective:

To identify the key components of a surgical wound assessment tool that nurses in Vietnam could use when conducting a surgical wound assessment. The study also explored Vietnamese nurses' perceptions of current practices in surgical wound assessment and assessed their requirements for a surgical wound assessment tool.

Method:

Registered nurses from surgical wards in a Vietnamese hospital were invited to participate in this descriptive, qualitative study. A combination of the think-aloud technique and semi-structured interviews was undertaken. Transcribed responses were analysed using inductive content analysis to indicate how Vietnamese nurses undertook wound assessment and the data they collected.

Results:

A total of 13 nurses took part. Data from both the think-aloud process and interviews indicated that nurses evaluated surgical wounds based on their experience and observation without using standard guidelines. Some components, such as wound edge, periwound skin, exudate volume and signs of infection, were identified by the nurses. Other wound characteristics, such as wound site, wound bed, exudate and pain, and risk factors were less frequently collected. Nurses expressed their need for a tool with comprehensive content, precise terms, user-friendly language and a scoring system to facilitate their wound assessment.

Conclusion:

Hospitals in Vietnam need a standard tool to help nurses improve surgical wound assessment in daily nursing practice, and to enhance multidisciplinary communication and patient care.
Validation of Harikrishna Periwound Skin Classification for wound assessment
Authors: Nair Harikrishna K. R. , Chong Sylvia SY , Othman Abdul Manan
Published: April 2020

Objective:

To validate the accuracy and reliability of Harikrishna Periwound Skin Classification (HPSC) for wound assessment.

Method:

Post-basic students (staff nurses and medical assistants) were given real life pictures showing the wound and periwound area. The students were asked to classify all pictures according to the HPSC at zero months (before attachment) and after two months of attachment. The images were the same but the answers were never given or discussed after the first test.

Results:

A total of 30 post-basic students participated in the study, assessing wound 30 images. The results showed that there was an increase of 25.42% in accuracy of wound assessment using the HSPC after two months of clinical attachment compared to pre-attachment. The reliability of the HPSC in wound assessment 79.87%.

Conclusion:

Health professionals have to be able to assess and classify wounds accurately to be able to manage them accordingly. Assessment and classifications of the periwound skin are important and need to be validated and integrated as a part of a full wound assessment. With experience and adequate training, health professionals are able to comprehensively assess wounds using the validated tool, to enable effective wound management and treatment, accelerating wound healing and improving the quality of life for patients.
Drug Breakdown: Furosemide
Authors: Rees Sharon
Published: April 2020

In this column, Sharon Rees aims to refresh knowledge and interest in some of the commonly used drugs in a series of tweets. This month she is talking about #furosemide
Research Roundup
Authors: Paterson Ruth
Published: April 2020

Ruth Paterson provides an overview of recently published articles that may be of interest to non-medical prescribers. Should you wish to look at any of the papers in more detail, a full reference is provided
Prescribing for persistent cancer pain: focus on chemotherapy-induced peripheral neuropathy
Authors: Galligan Martin
Published: April 2020

Chemotherapy-Induced peripheral neuropathy is rapidly becoming a growing problem faced by healthcare processionals and individuals living with and beyond cancer. The incidence of cancer diagnoses is increasing and, as a result, so is the incidence of individuals living with the consequences of cancer treatment. Chemotherapy-induced peripheral neuropathy is a complex symptom, and its incidence and impact on quality of life varies across treatment modalities. This complexity continues into its assessment and management, and healthcare professionals require more support and guidance when presented with this pain state. This article will explore the current literature surrounding assessment methods and management strategies that will enable prescribers to make informed decision when encountering chemotherapy-induced peripheral neuropathy.