bluuebunny/crossref_metadata_2025 huggingface dataset:
Commercial insurance delays direct‐acting antiviral treatment for hepatitis C kidney transplantation into uninfected recipients
Authors: Torabi Julia , Rocca Juan P. , Ajaimy Maria , Melvin Jeffrey , Campbell Alesa , Akalin Enver , Liriano Luz E. , Azzi Yorg , Pynadath Cindy , Greenstein Stuart M. , Le Marie , Goldstein Doctor Y. , Fox Amy S. , Carrero Jin , Weiss Jeffrey M. , Powell Tia , Racine Andrew D. , Reinus John F. , Kinkhabwala Milan M. , Graham Jay A.
Published: August 2020

Introduction

The advent of direct‐acting antivirals (DAAs) has created an avenue for transplantation of hepatitis C virus (HCV)‐infected donors into uninfected recipients (D+/R−). The donor transmission of HCV is then countered by DAA administration during the post‐operative period. However, initiation of DAA treatment is ultimately dictated by insurance companies.

Methods

A retrospective chart review of 52 D+/R− kidney recipients who underwent DAA treatment post‐transplant was performed. Patients were grouped according to their prescription coverage plans, managed by either commercial or government pharmacy benefit managers (PBMs).

Results

Thirty‐nine patients had government PBMs and 13 had commercial PBMs. Demographics were similar between the two groups. All patients developed HCV viremia, but cleared the virus after treatment with DAA. Patients with government PBMs were treated earlier compared to those with commercial PBMs (11 days vs 26 days, P = .01). Longer time to DAA initiation resulted in higher peak viral loads (β = 0.39, R2 = .15, P = .01) and longer time to HCV viral load clearance (β = 0.41, R2 = .17, P = .01).

Conclusions

D+/R− transplantation offers patients an alternative strategy to increase access. However, treatment can be profoundly delayed by a third‐party payer authorization process that may be subjecting patients to unnecessary risks and worsened outcomes.
Surgical treatment of liver hydatid cyst before autologous stem cell transplantation; presentation of two cases with literature review
Authors: Zarbaliyev Elbrus , Hacısalihoğlu Payam
Published: August 2020

Hydatid cyst, caused by Echinococcus granulosus, is a parasitic disease which is frequently seen in endemic areas. The disease can be seen as an isolated entity or simultaneously with other diseases. Treatment of hydatid cyst in patients with malignancy as well as in patients in need of transplantation is still unclear. Although there is information in the form of case reports, a large number of patient data are needed to create a consensus on the management of these patients. We reviewed two cases with the need of autologuous stem cell transplantation which underwent liver hydatic cystectomy before transplantation.
Successful recovery from COVID‐19 in three kidney transplant recipients who received convalescent plasma therapy
Authors: Naeem Syed , Gohh Reginald , Bayliss George , Cosgrove Christopher , Farmakiotis Dimitrios , Merhi Basma , Morrissey Paul , Osband Adena , Bailey Jeffrey A. , Sweeney Joseph , Rogers Ralph
Published: August 2020

Novel coronavirus disease 2019 (COVID‐19) is a highly infectious, rapidly spreading viral disease that typically presents with greater severity in patients with underlying medical conditions or those who are immunosuppressed. We present a novel case series of three kidney transplant recipients with COVID‐19 who recovered after receiving COVID‐19 convalescent plasma (CCP) therapy. Physicians should be aware of this potentially useful treatment option. Larger clinical registries and randomized clinical trials should be conducted to further explore the clinical and allograft outcomes associated with CCP use in this population.
Gene silencing of BnaA09.ZEP and BnaC09.ZEP confers orange color in Brassica napus flowers
Authors: Liu Yingjun , Ye Shenhua , Yuan Gaigai , Ma Xiaowei , Heng Shuangping , Yi Bin , Ma Chaozhi , Shen Jinxiong , Tu Jinxing , Fu Tingdong , Wen Jing
Published: August 2020

Brassica napus is currently cultivated as an important ornamental crop in China. Flower color has attracted much attention in rapeseed genetics and breeding. Here, we characterize an orange‐flowered mutant of B. napus that exhibits an altered carotenoid profile in its petals. As revealed by map‐based cloning, the change in color from yellow to orange is attributed to the loss of BnaC09.ZEP (zeaxanthin epoxidase) and a 1695‐bp deletion in BnaA09.ZEP. HPLC analysis, genetic complementation and CRISPR/Cas9 experiments demonstrated that BnaA09.ZEP and BnaC09.ZEP have similar functions, and the abolishment of both genes led to a substantial increase in lutein content and a sharp decline in violaxanthin content in petals but not leaves. BnaA09.ZEP and BnaC09.ZEP are predominantly expressed in floral tissues, whereas their homologs, BnaA07.ZEP and BnaC07.ZEP, mainly function in leaves, indicating redundancy and tissue‐specific diversification of BnaZEP function. Transcriptome analysis in petals revealed differences in the expression of carotenoid and flavonoid biosynthesis‐related genes between the mutant and its complementary lines. Flavonoid profiles in the petals of complementary lines were greatly altered compared to the mutant, indicating potential cross‐talk between the regulatory networks underlying the carotenoid and flavonoid pathways. Additionally, our results indicate that there is functional compensation by BnaA07.ZEP and BnaC07.ZEP in the absence of BnaA09.ZEP and BnaC09.ZEP. Cloning and characterization of BnaZEPs provide insights into the molecular mechanisms underlying flower pigmentation in B. napus and would facilitate breeding of B. napus varieties with higher ornamental value.
Re‐estimating the effect of heterogeneous standards on trade: Endogeneity matters
Authors: Shingal Anirudh , Ehrich Malte , Foletti Liliana
Published: August 2020

Controlling for endogeneity‐induced biases and accounting for the source of heterogeneity may both matter for the proper empirical estimation of the effect of heterogeneous standards on trade. However, existing literature on the trade effects of heterogeneity in pesticides maximum residue levels (MRLs) does not directly address the problem of endogeneity in the standards–trade relationship. Using pesticides MRL data for 53 countries over 2005–14, we thus re‐examine the trade effects of stricter (than partner) standards accounting for endogeneity using panel data methods. We find that the direction of the estimated trade effects gets reversed, thereby underlining the greater demand‐enhancing effect of more stringent regulation. We also discuss why endogeneity may bias the estimates downwards. In another original contribution, we examine the standards–trade relationship by the direction of imposition of stricter standards for a large panel. Our results suggest that stricter standards do not impede trade, irrespective of who imposes them.
Supplementation with eicosapentaenoic acid and linoleic acid increases the production of epidermal ceramides in in vitro canine keratinocytes
Authors: Yoon Ji‐Seon , Nishifuji Koji , Iwasaki Toshiro
Published: August 2020

Background

Few studies have investigated the effects of essential fatty acids on the production of epidermal ceramide (CER) in canine keratinocytes.

Hypothesis/objectives

To investigate the effects of eicosapentaenoic acid (EPA) and linoleic acid (LA) supplementation on the production of CERs using an in vitro canine keratinocyte culture system.

Methods and materials

Canine keratinocyte cells (MSCEK) were incubated with high Ca2+[1.8 mM calcium chloride (CaCl2)] serum‐free medium, supplemented with 3 µM EPA and 15 µM LA when the cells showed confluency. On Day 8 of application, lipid analysis using high‐performance thin layer chromatography and real‐time PCR for detecting glucosylceramide synthase and ceramidase were performed.

Results

It was revealed that the amounts of CER (EOS) (combination of ω‐hydroxy fatty acids and sphingosines), CER [EOP] (combination of ω‐hydroxy fatty acids and phytosphingosines) and a mixture of CER [NS] (combination of nonhydroxy fatty acids and sphingosines) and [NDS] (combination of nonhydroxy fatty acids and dihydrosphingosines), as well as total CERs, were significantly increased in cells incubated with EPA and LA compared to those of the vehicle, with increased mRNA expression of glucosylceramide synthase.

Conclusions and clinical importance

These findings suggest that EPA and LA can potentially alter the CER profile of the skin and this may contribute to its epidermal barrier function in canine skin.
Sickle cell trait among blood donors in the democratic republic of the Congo: which transfusion policy for Sickle cell patients?
Authors: Batina‐Agasa Salomon , Kambale‐Kombi Paul , Kabamba Paul , Tonen‐Wolyec Serge , Kayembe Tshilumba Charles , Marini Djang'eing'a Roland , Kabinda Maotela Jeef
Published: August 2020

Background

Prevalence of sickle cell trait is high in the Democratic Republic of Congo (DRC). Blood services, therefore, face the risk of collecting blood units from donors with sickle cell trait.

Objective

This study aimed to determine the frequency of haemoglobin S among blood donors in Kinshasa.

Materials and Methods

The study was carried out in the period from 1 January 2014 to 31 December 2015, and 250 blood donors, who gave their consent, were selected using convenience sampling method when donating blood at the National Blood Transfusion Centre in Kinshasa, the Democratic Republic of the Congo. For the testing, blood samples (2 ml) were obtained at the time of blood donation, added to EDTA tubes, mixed and processed within 24 h. The haemoglobin variants were determined by electrophoresis on alkaline agarose gel and confirmed on acid gel.

Results

Among the 250 blood donors, 20·8 % were female and 79·2%, male. Blood donors in the age range from 25 to 29 years were the most represented, accounting for 23·2%. The youngest donor was 19 years old and the oldest, 58 years old. None of the donors were aware of the HbS status and all have donated previously. According to the haemoglobin variants, 23·6% were confirmed as AS and 76·4%, as AA.

Conclusion

The proportion of blood donors with HbS is high in the DRC. The possibility of implementing the compulsory routine screening of sickle cell trait (SCT), using sickle cell rapid test, should be explored and the supply of blood units from donors with SCT to patients with sickle cell disease (SCD) should be avoided, whenever possible.
Evaluation of transanal minimally invasive surgery for submucosal rectal resection in cadaveric canine specimens
Authors: Mayhew Philipp D. , Balsa Ingrid M. , Guerzon Christian N. , Gibson Erin A. , Keel M. Kevin , Brun Maurício Veloso , Lillo Araya Felipe J.
Published: August 2020

Objective

To evaluate the feasibility of transanal minimally invasive surgery (TAMIS) for submucosal rectal resection in large breed dogs.

Study design

Cadaveric study.

Sample population

Canine cadavers (n = 6) weighing between 37.5 and 60 kg.

Methods

Dogs were positioned in sternal recumbency. After rectal cleansing, a transanal access platform was placed in the rectum, and a pneumorectum was established. An area of ventral rectal wall approximately 2 × 2 cm was resected in a submucosal plane by using laparoscopic instruments and submitted for histopathological evaluation. The rectal wall defect was closed with a single‐layer continuous suture pattern with barbed suture. Postoperatively, the rectum was removed en bloc and evaluated for suture or surgical penetration of the serosal surface.

Results

Submucosal rectal resection was successfully completed by using TAMIS in all dogs. The median length of resected specimens after fixation was 24.5 mm (range 9.8‐26.5). In two of six dogs, suture was macroscopically visible on the serosal surface, but no dogs had evidence of iatrogenic full‐thickness surgical penetration of the rectum. The median distance from the aborad extent of the suture closure line to the anocutaneous junction was 35 mm (range, 35‐105).

Conclusion

Submucosal resection of the canine rectal wall was feasible in large breed dogs by using TAMIS. No evidence of full‐thickness penetration of the rectal wall was seen in these cadaveric specimens.

Clinical significance

Transanal minimally invasive surgery may provide an alternative minimally invasive approach for resection for benign adenomatous rectal polyps in large breed dogs that might otherwise require a rectal pull‐through.
Perception of health risks in Lao market vendors
Authors: Philavong Chanfong , Pruvot Mathieu , Reinharz Daniel , Mayxay Mayfong , Khammavong Kongsy , Milavong Phonesavanh , Rattanavong Sayapeth , Horwood Paul F. , Dussart Philippe , Douangngeun Bounlom , Theppangna Watthana , Fine Amanda E. , Robinson Matthew T. , Newton Paul N.
Published: August 2020

Wet markets are a critical part of South‐East Asian culture and economy. However, their role in circulation and transmission of both endemic and emerging disease is a source of concern in a region considered a hotspot of disease emergence. In the Lao People's Democratic Republic (Lao PDR, Laos), live and dead wild animals are frequently found in wet markets, despite legislation against the bushmeat trade. This is generally considered to increase the risk of disease transmission and emergence, although whether or not wildlife vendors themselves have indeed increased incidence of zoonotic disease has rarely been assessed. In preparation for a future longitudinal study of market vendors investigating vendors’ exposure to zoonotic pathogens, we conducted a pilot survey of Lao market vendors of wildlife meat, livestock meat and vegetables, to identify demographic characteristics and potential control groups within markets. We also investigated baseline risk perception for infectious diseases among market vendors and assessed the association between risk perception and risk mitigation behaviours. The surveys conducted with 177 vendors revealed similar age, sex, ethnic background and geographical origin between vendor types, but differences in professional background and work history for livestock meat vendors. The perception of disease risk was very low across all vendors, as was the reported use of personal protective equipment, and the two appeared unrelated. Personal risk discounting and assumptions about transmission routes may explain this lack of association. This information will help inform the development of future research, risk communication and risk mitigation policy, especially in the light of the COVID‐19 pandemic.
Preconditioning human pharyngeal motor cortex enhances directional metaplasticity induced by repetitive transcranial magnetic stimulation
Authors: Cheng Ivy , Scarlett Honor , Zhang Mengqing , Hamdy Shaheen
Published: August 2020

Key points

Recent studies have proposed therapeutic potential for repetitive transcranial magnetic stimulation (rTMS) in swallowing rehabilitation, yet its outcomes vary across individuals and studies. Such variability may be related to the brain state before stimulation.

Metaplasticity is a higher order plasticity which regulates cortical response to plasticity changes. Studies have shown that preconditioning of the hand motor cortex could increase cortical capacity for neuroplastic change and enhance rTMS outcomes.

We investigated, for the first time, the directional metaplastic properties in human pharyngeal motor cortex using preconditioned rTMS.

We found that preconditioned rTMS with specific time intervals between preconditioning and conditioning rTMS had stronger stimulation effects in both swallowing neurophysiology and behaviour than that without preconditioning.

Our results provide evidence for enhanced directional metaplasticity in pharyngeal motor cortex and new insights into its clinical application for dysphagia.

Despite growing evidence that repetitive transcranial magnetic stimulation (rTMS) can be used as a treatment for dysphagia, its efficacy varies across individuals. Such variability may relate to the pre‐stimulation state of neuronal activation. Previous studies found that preconditioning the hand motor cortex before rTMS could enhance stimulation outcomes through metaplasticity. No studies have investigated such mechanisms in human pharyngeal motor cortex. Therefore, we investigated the preconditioning effects of rTMS on swallowing neurophysiology and behaviour. Healthy adults were recruited for swallowing neurophysiological (n = 14) and behavioural (n = 14) experiments. They were first given eight different preconditioned (1 and 5 Hz) rTMS interventions with varying inter‐rTMS intervals. Motor evoked potentials (MEPs) were measured before and for 60 min post‐rTMS. Based on the changes in pharyngeal MEPs, the optimal preconditioned 1 Hz and 5 Hz rTMS protocols were then applied as interventions while assessing swallowing performance using a reaction time task. We found that 5 Hz rTMS preconditioned with 1 Hz rTMS with 30 min inter‐rTMS interval induced the greatest increase on pharyngeal cortical excitability (F1,13 = 21.244; P < 0.001). By comparison, 1 Hz rTMS preconditioned with 5 Hz rTMS with 90 min inter‐rTMS interval was most optimal for suppressing pharyngeal motor cortex (F1,13 = 13.547; P = 0.003). Behaviourally, swallowing accuracy was improved after preconditioned 5 Hz rTMS (F1,13 = 10.109, P = 0.007) and reduced after preconditioned 1 Hz rTMS (F1,13 = 14.108, P = 0.009) compared to sham. Thus, two optimal protocols for inducing functional metaplasticity in human pharyngeal motor cortex have been identified. These protocols appear superior to conventional rTMS and may be relevant to future clinical application in neurogenic dysphagia.
Dietary nitrate supplementation increases diaphragm peak power in old mice
Authors: Kumar Ravi A. , Kelley Rachel C. , Hahn Dongwoo , Ferreira Leonardo F.
Published: August 2020

Key points

Respiratory muscle function declines with ageing, contributing to breathing complications in the elderly.

Here we report greater in vitro respiratory muscle contractile function in old mice receiving supplemental NaNO3 for 14 days compared with age‐matched controls.

Myofibrillar protein phosphorylation, which enhances contractile function, did not change in our study – a finding inconsistent with the hypothesis that this post‐translational modification is a mechanism for dietary nitrate to improve muscle contractile function.

Nitrate supplementation did not change the abundance of calcium‐handling proteins in the diaphragm of old mice, in contrast with findings from the limb muscles of young mice in previous studies.

Our findings suggest that nitrate supplementation enhances myofibrillar protein function without affecting the phosphorylation status of key myofibrillar proteins.

Inspiratory muscle (diaphragm) function declines with age, contributing to ventilatory dysfunction, impaired airway clearance, and overall decreased quality of life. Diaphragm isotonic and isometric contractile properties are reduced with ageing, including maximal specific force, shortening velocity and peak power. Contractile properties of limb muscle in both humans and rodents can be improved by dietary nitrate supplementation, but effects on the diaphragm and mechanisms behind these improvements remain poorly understood. One potential explanation underlying the nitrate effects on contractile properties is increased phosphorylation of myofibrillar proteins, a downstream outcome of nitrate reduction to nitrite and nitric oxide. We hypothesized that dietary nitrate supplementation would improve diaphragm contractile properties in aged mice. To test our hypothesis, we measured the diaphragm function of old (24 months) mice allocated to 1 mm NaNO3 in drinking water for 14 days (n = 8) or untreated water (n = 6). The maximal rate of isometric force development (∼30%) and peak power (40%) increased with nitrate supplementation (P < 0.05). There were no differences in the phosphorylation status of key myofibrillar proteins and abundance of Ca2+‐release proteins in nitrate vs. control animals. In general, our study demonstrates improved diaphragm contractile function with dietary nitrate supplementation and supports the use of this strategy to improve inspiratory function in ageing populations. Additionally, our findings suggest that dietary nitrate improves diaphragm contractile properties independent of changes in abundance of Ca2+‐release proteins or phosphorylation of myofibrillar proteins.
Temporally‐precise basolateral amygdala activation is required for the formation of taste memories in gustatory cortex
Authors: Arieli Elor , Gerbi Ron , Shein‐Idelson Mark , Moran Anan
Published: August 2020

Key points

The basolateral amygdala (BLA), the nucleus basalis magnocellularis (NBM), and the gustatory cortex (GC) are involved in taste processing, taste memory formation and conditioned taste aversion (CTA) learning, but their fine‐temporal interactions that support these cognitive functions are not well understood.

We found that the formation of novel‐taste and CTA memories in the GC depend on a distinct late response (700–3000 ms) of BLA projection neurons.

In contrast, BLA activity was not essential for palatability‐related behaviour and coding in the GC prior to CTA.

We identified the BLA→NBM pathway as a potential pathway for the transmission of taste novelty information, required for the formation of taste and CTA memories in the GC.

Our results demonstrate how neuronal dynamics across multiple brain regions support long‐term memory formation.

Learning to associate malaise with the intake of novel food is critical for survival. Since food poisoning may take hours to take effect, animals developed brain circuits to transform the current novel taste experience into a taste memory trace (TMT) and bridge this time lag. Ample studies showed that the basolateral amygdala (BLA), the nucleus basalis magnocellularis (NBM) and the gustatory cortex (GC) are involved in TMT formation and taste–malaise association. However, how dynamic activity across these brain regions during novel taste experience promotes the formation of these memories is currently unknown. We used the conditioned taste aversion (CTA) learning paradigm in combination with short‐term optogenetics and electrophysiological recording in rats to test the hypothesis that temporally specific activation of BLA projection neurons is essential for TMT formation in the GC, and consequently CTA. We found that a short late epoch (LE, 700–3000 ms), but not the early epoch (EE, 0–500 ms), of BLA activation during novel taste experience is essential for normal CTA, for early c‐Fos expression in the GC (a marker of TMT formation) and for the post‐CTA changes in GC ensemble palatability coding. Interestingly, BLA activity was not required for intact taste identity or palatability perceptions before CTA. We further show that BLA‐LE information is transmitted to GC through the BLA→NBM pathway where it affects the formation of taste memories. These results expose the dependence of long‐term memory formation on specific temporal windows during sensory responses and the distributed circuits supporting this dependence.
Superiority of blind over sighted listeners in voice recognition
Authors: Pang Wenbin , Xing Hongbing , Zhang Linjun , Shu Hua , Zhang Yang
Published: August 2020

The current study examined whether the blind are superior to sighted listeners in voice recognition. Three subject groups, including 17 congenitally blind, 18 late blind, and 18 sighted, showed no significant differences in the immediate voice recognition test. In the delayed test conducted two weeks later, however, both congenitally blind and late blind groups performed better than the sighted with no significant difference between the two blind groups. These results partly confirmed the anecdotal observation about the blind's superiority in voice recognition, which resides mainly in delayed memory phase but not in immediate recall and generalization phase.
A Clinical Trial Based on Reward Contingency to Improve Prone Tolerance and Motor Development is Feasible in 3- to 6-Month-Old Infants
Authors: Tripathi Tanya , Dusing Stacey C. , Pidcoe Peter E. , Xu Yaoying , Shall Mary S. , Riddle Daniel L.
Published: August 2020

Aims: The American Academy of Pediatrics recommends “parents to incorporate supervised, awake ‘prone play’ in their infant’s routine to support motor development and minimize the risk of plagiocephaly”. The purpose of this feasibility study was to compare usual care to a reward contingency–based intervention, developed to increase prone tolerance and improve motor skills. Methods: Ten full-term infants, 3–6- months old, with poor prone tolerance were randomized to either the Education group or Reward contingency group. Each group participated in three parent education sessions and 15 intervention sessions, over the period of three weeks. Infants in the Reward contingency group used the Prone Play Activity Center, a technology developed to reinforce motor behavior of infants in prone position. Intervention frequency and parent feedback data determined the feasibility of the interventions. Results: Infants in the Reward contingency group practiced a median of 12 of the 15 anticipated intervention sessions in the Prone Play Activity Center. These infants used the device for a mean of 18 minutes per day. Parents of infants in the Education group practiced a median of 10 sessions of the 15 anticipated intervention sessions. Conclusion: The reward contingency–based intervention is feasible for use in a future clinical trial with some modifications.
Effect of Evidence-Based Materials and Access to Local Resources on Physical Activity Levels, Beliefs, and Motivation During Pregnancy in a Rural Setting
Authors: Tinius Rachel , Edens Kolbi , Link Kim , Jones M. Susan , Lyons Scott , Rebelle Tatum , Pearson Kevin J. , Maples Jill
Published: August 2020

Background: The purpose of this study was to determine the impact of evidence-based educational materials and access to local resources on physical activity (PA) levels, beliefs, and motivation (including self-efficacy) regarding PA during pregnancy in a rural setting. Methods: Information on PA levels (step counts, Pregnancy Physical Activity Questionnaire) and beliefs and motivation regarding PA (main surveys: Exercise Beliefs Questionnaire, Protection Motivation Theory and Health Action Process Approach) were collected between 8 and 16 weeks gestation. Women from a rural community were randomly assigned to the PA group (PAG, n = 38) or control group (n = 32). The PAG participants received an evidence-based educational brochure and access (at no charge to them) to local fitness facilities. At approximately 34 to 37 weeks gestation, baseline assessments were repeated. Results: Sedentary time was significantly different between groups over time, with control participants increasing sedentary time and PAG participants decreasing sedentary time (P = .04). Sixteen women (42%) in the PAG utilized the resources provided (prenatal yoga being utilized most). Postintervention, there was a significant group × time interaction for Perceived Self-Efficacy scores; scores in the PAG remained consistent with baseline values, whereas scores in the control group decreased (P = .03). Conclusions: The intervention reduced sedentary time and maintained self-efficacy scores during pregnancy.
Impact of “JolinchenKids—Fit and Healthy in Daycare” on Children’s Objectively Measured Physical Activity: A Cluster-Controlled Study
Authors: Brandes Berit , Buck Christoph , Wright Marvin N. , Pischke Claudia R. , Brandes Mirko
Published: August 2020

Background:To evaluate a multicomponent health promotion program targeting preschoolers’ physical activity (PA).Methods:PA of children from 23 German daycare facilities (DFs; 13 intervention DFs, 10 control DFs) was measured via accelerometry at baseline and after 12 months. Children’s sedentary time, light PA, and moderate to vigorous PA were estimated. Adherence was tracked with paper-and-pencil calendars. Mixed-model regression analyses were used to assess intervention effects.Results:PA data were analyzed from 183 (4.2 [0.8] y, 48.1% boys) children. At follow-up, children in DF groups with more than 50% adherence to PA intervention components showed an increase of 9 minutes of moderate to vigorous PA per day (β = 9.28; 95% confidence interval [CI], −0.16 to 18.72) and a 19-minute decrease in sedentary time (β = −19.25; 95% CI, −43.66 to 5.16) compared with the control group, whereas children’s PA of those who were exposed to no or less than 50% adherence remained unchanged (moderate to vigorous PA: β = 0.34; 95% CI, −13.73 to 14.41; sedentary time: β = 1.78; 95% CI, −26.54 to 30.09). Notable effects were found in children with migration background.Conclusions:Only small benefits in PA outcomes were observed after 1 year. A minimum of 50% adherence to the intervention seems to be crucial for facilitating intervention effects.
Measles Vaccine-Associated Rash Illness in China: an Emerging Issue in the Process of Measles Elimination
Authors: Cui Aili , Wang Huiling , Zhu Zhen , Mao Naiying , Song Jinhua , Zhang Yan , Xu Wenbo
Published: August 2020

Along with the implementation of measles case-based surveillance, measles vaccine-associated rash illness (VARI) cases were detected in China. To better understand the characteristics of VARI, 101 VARI cases confirmed by measles virus genotyping in 2011 to 2018 were analyzed in this study. With the decrease in measles incidence, the detection rate of VARI cases increased among the cases confirmed by genotyping. Compared with genotype H1 wild-type measles, VARI occurred throughout the year, without obvious seasonal distribution.
Effects of preconditioning by nasal splint and mouth breathing on emergence delirium after functional endoscopic sinus surgery in Chinese adults: a study protocol for a randomised controlled trial
Authors: Xu Hongjiao , Li Xiang , Yang Bin , Shen Zhenyuan , Li Weiwen , Zhou Yachun , Jiang Jihong , Chen Xia , Gu Yuyu , Pei Zhi , Li Jinbao
Published: August 2020

Introduction

Emergence delirium (ED) is a common adverse manifestation after general anaesthesia and may result in undesirable consequences. Its causes and mechanisms are diverse and complex, and it is still unavoidable in clinical work. There is a high incidence of ED after otorhinolaryngology surgery, which may result from the sudden loss of functional senses and discomfort of surgical organs. This study aims to test a non-invasive, non-drug treatment modality of nose clamping and mouth-breathing training before surgery to reduce ED.

Methods and analysis

This prospective randomised controlled trial (RCT) will include 200 patients who undergo functional endoscopic sinus surgery (FESS) at Shanghai General Hospital, China. Study participants will be randomly assigned in two groups with a 1:1 ratio. The pretreatment group (P-group) will receive an intervention by nasal splint and mouth-breathing training before surgery, while the control group (C-group) will not receive any intervention; following which both groups will undergo FESS under general anaesthesia in accordance with the same anaesthesia scheme. After surgery, we will perform a single-blinded assessment of ED occurrence with stratification. IBM SPSS Statistics V.20 statistical software will be used for statistical analyses. A X2 test will be used to compare the two groups, and t-tests will determine the statistical significance of continuous variables.

Ethics and dissemination

This RCT was designed in accordance with the principles of the Declaration of Helsinki and has been approved by the Ethics Committee of Shanghai General Hospital, ID: 2019KY039.We expect to release the original data in February 2022 on the ResMan original data sharing platform (IPD sharing platform) of the China clinical trial registry, which can be viewed at the following website:http://www.medresman.org.cn/pub/cn/proj/projectshow.aspx?proj=6293.

Trial registration number

ChiCTR1900024925
What is the optimum systemic treatment for advanced/metastatic renal cell carcinoma of favourable, intermediate and poor risk, respectively? A systematic review and network meta-analysis
Authors: Cao Guanghui , Wu Xiaoqiang , Wang Zhiwei , Tian Xiangyong , Zhang Chan , Wu Xuan , Zhang Haotian , Jing Gaopeng , Yan Tianzhong
Published: August 2020

Purpose

The optimum systemic therapies for advanced/metastatic renal cell carcinoma (RCC) of favourable, intermediate and poor risk have not been established. We aimed to compare and rank the effects associated with systemic therapies in the first-line setting.

Methods

We searched PubMed, Cochrane databases, Web of Science and ClinicalTrials.gov for randomised controlled trials (RCT) published up to February 2020 of all available treatments for advanced/metastatic RCC. Analysis was done on a Bayesian framework.

Results

15 unique RCTs including 8995 patients were identified. For advanced/metastatic RCC of favourable risk, avelumab plus axitinib was associated with a significantly higher improvement in progression-free survival (PFS) than sunitinib (HR 0.57, 95% CI 0.34 to 0.96). For intermediate-risk patients, cabozantinib, nivolumab plus ipilimumab, pembrolizumab plus axitinib and avelumab plus axitinib were associated with significantly higher improvement in PFS than sunitinib (HR 0.63, 95% CI 0.44 to 0.97; HR 0.66, 95% CI 0.53 to 0.81; HR 0.58, 95% CI 0.44 to 0.80; HR 0.62, 95% CI 0.47 to 0.83, respectively); pembrolizumab plus axitinib and nivolumab plus ipilimumab were associated with significantly higher improvement in overall survival (OS) than sunitinib (HR 0.53, 95% CI 0.34 to 0.81; HR 0.66, 95% CI 0.50 to 0.87, respectively). For poor-risk patients, nivolumab plus ipilimumab and pembrolizumab plus axitinib were associated with significantly higher improvement in PFS than sunitinib (HR 0.57, 95% CI 0.43 to 0.76; HR 0.48, 95% CI 0.30 to 0.82, respectively); nivolumab plus ipilimumab and pembrolizumab plus axitinib were significantly more efficacious for OS than sunitinib (HR 0.57, 95% CI 0.39 to 0.883; HR 0.43, 95% CI 0.23 to 0.80, respectively). For OS, there were 81% and 78% probabilities that pembrolizumab plus axitinib was the best option for intermediate-risk and poor-risk patients, respectively.

Conclusion

Avelumab plus axitinib might be the optimum treatment for advanced/metastatic RCC of favourable risk. Pembrolizumab plus axitinib might be the optimum treatment for intermediate-risk and poor-risk patients.
The economic burden of infections following intramedullary nailing for a tibial shaft fracture in England
Authors: Galvain Thibaut , Chitnis Abhishek , Paparouni Konstantina , Tong Cindy , Holy Chantal E , Giannoudis Peter V
Published: August 2020

Objectives

Determine the impact of infections on direct costs and healthcare resource use in England for patients undergoing intramedullary nailing (IMN) for tibial shaft fractures.

Design

Non-concurrent cohort based on retrospectively collected data with 2-year follow-up.

Setting

England.

Participants

The study population included adult patients (≥18 years) in England with a diagnosis of tibial shaft fracture (International Classification of Diseases-10, S822) in the inpatient setting between May 2003 and June 2017 followed by a procedure for IMN for tibial shaft fracture within 30 days. Patient data were derived from the Clinical Practice Research Datalink linked to National Health Service Hospital Episode Statistics datasets.

Primary independent variable

Infection.

Primary and secondary outcome measures

The primary outcome was total inpatient costs from index stay admission through 1 year of follow-up. Secondary outcome included cumulative total healthcare costs, and resource utilisation at 30 days, 90 days, 1 year and 2 years.

Results

Overall, 805 patients met the inclusion criteria. At index inpatient stay, 3.7% had a post-IMN infection, rising to 11.7% at 1 year. One-year inpatient costs were 80% higher for patients with infection (p<0.001). Total costs were estimated to be £14 756 (95% CI £13 123 to £16 593) for patients with infection versus £8279 (95% CI £7946 to £8626). Length of stay (LOS), readmission and reoperation were the key drivers of healthcare costs (all p<0.001). After adjustment, LOS was higher by 109% (95% CI 62% to 169%), from 10.5 days to 21.9 days, for patients with infection. The odds of being readmitted or requiring reoperation were higher by 5.18 times (95% CI 3.01 to 9.13) and 2.47 times (95% CI 1.48 to 4.09), respectively, for patients with infection versus those without infection.

Conclusions

Post-IMN infection significantly increases inpatient costs, LOS, readmissions and reoperations associated with tibial fracture fixation. Healthcare burden could be reduced through novel surgical site infection prevention strategies.
Factors affecting mothers’ intentions to visit healthcare facilities before hospitalisation of children with pneumonia in Biliran province, Philippines: a qualitative study
Authors: Sato Mari , Oshitani Hitoshi , Tamaki Raita , Oyamada Nobuko , Sato Kineko , Nadra Alkaff Raihana , Landicho Jhoys , Alday Portia P , Lupisan Socorro P , Tallo Veronica L
Published: August 2020

Background and objectives

Despite a substantial reduction in the mortality rate of children under 5 years in the past 25 years, pneumonia remains the single-largest infectious cause of child deaths worldwide. This study explored the chronological order of visited healthcare facilities and practitioners, and the factors affecting mothers’ intention to seek care before the hospitalisation of children with pneumonia.

Methods and analysis

A qualitative research design was employed using theory of planned behaviour as a framework for the analysis. Using purposive sampling technique, 11 mothers, whose children under 5 years old were hospitalised with severe pneumonia, were recruited for individual semi-structured interviews. Their socio-demographic information was analysed using descriptive statistics.

Results

Mothers brought their sick children to multiple facilities, and 1 to 19 days had passed before hospitalisation. We identified four major factors determining mothers’ intentions: (1) doing something useful for the sick child, (2) expecting the child to receive the necessary assessment and treatment, (3) accepting advice to visit a healthcare facility and be referred to a hospital and (4) considering issues and benefits associated with hospitalisation. Mothers noticed their children’s unusual symptoms and monitored them while applying home remedies. They also took their children to traditional healers despite knowing that the treatments were not necessarily effective. Mothers expected children to be checked by health professionals and listened to advice from family members regarding the facilities to visit, and from healthcare staff to be referred to a hospital. Financial issues and the double burden of housework and caring for the hospitalised child were mothers’ major concerns about hospitalisation.

Conclusion

Children were hospitalised after several days because they visited multiple healthcare facilities, including traditional healers. Improving care quality at healthcare facilities and reducing financial and mothers’ burden may reduce the hospitalisation delay for children with pneumonia.
Adaptive design methods in dialysis clinical trials: a systematic review protocol
Authors: Judge Conor , Murphy Robert P , Cormican Sarah , Smyth Andrew , O'Halloran Martin , O'Donnell Martin
Published: August 2020

Introduction

Adaptive design methods are a potential solution to improve efficiency of clinical trials but their uptake in dialysis is unknown. We aim to investigate the use of adaptive design methods in dialysis clinical trials and to cultivate further adoption of adaptive design methods by the nephrology community.

Methods and analysis

We will adhere to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines and the Cochrane Collaboration Handbook. We will perform a literature search through MEDLINE (PubMed), EMBASE and CENTRAL, a detailed data extraction of trial characteristics and a narrative synthesis of the data. There will be no language restrictions. We will estimate the percentage of adaptive clinical trials per year in dialysis. Subgroup analysis will be performed by dialysis modality, funder and geographical location.

Ethics and dissemination

Ethical approval will not be required for this study as data will be obtained from publicly available clinical trials. We will disseminate our results in a peer-reviewed publication.

PROSPERO registration number
Evaluation of propensity score used in cardiovascular research: a cross-sectional survey and guidance document
Authors: Samuel Michelle , Batomen Brice , Rouette Julie , Kim Joanne , Platt Robert W , Brophy James M , Kaufman Jay S
Published: August 2020

Background

Propensity score (PS) methods are frequently used in cardiovascular clinical research. Previous evaluations revealed poor reporting of PS methods, however a comprehensive and current evaluation of PS use and reporting is lacking. The objectives of the present survey were to (1) evaluate the quality of PS methods in cardiovascular publications, (2) summarise PS methods and (3) propose key reporting elements for PS publications.

Methods

A PubMed search for cardiovascular PS articles published between 2010 and 2017 in high-impact general medical (top five by impact factor) and cardiovascular (top three by impact factor) journals was performed. Articles were evaluated for the reporting of PS techniques and methods. Data extraction elements were identified from the PS literature and extraction forms were pilot tested.

Results

Of the 306 PS articles identified, most were published inJournal of the American College of Cardiology(29%; n=88), andCirculation(27%, n=81), followed byEuropean Heart Journal(15%; n=47). PS matching was performed most often, followed by direct adjustment, inverse probability of treatment weighting and stratification. Most studies (77%; n=193) selected variables to include in the PS model a priori. A total of 38% (n=116) of studies did not report standardised mean differences, but instead relied on hypothesis testing. For matching, 92% (n=193) of articles presented the balance of covariates. Overall, interpretations of the effect estimates corresponded to the PS method conducted or described in 49% (n=150) of the reviewed articles.

Discussion

Although PS methods are frequently used in high-impact medical journals, reporting of methodological details has been inconsistent. Improved reporting of PS results is warranted and these proposals should aid both researchers and consumers in the presentation and interpretation of PS methods.
Economic evaluation protocol for a multicentre randomised controlled trial to compare Smartphone Cardiac Rehabilitation, Assisted self-Management (SCRAM) versus usual care cardiac rehabilitation among people with coronary heart disease
Authors: Gao Lan , Maddison Ralph , Rawstorn Jonathan , Ball Kylie , Oldenburg Brian , Chow Clara , McNaughton Sarah , Lamb Karen , Amerena John , Nadurata Voltaire , Neil Christopher , Cameron Stuart , Moodie Marj
Published: August 2020

Introduction

It is important to ascertain the cost-effectiveness of alternative services to traditional cardiac rehabilitation while the economic credentials of the Smartphone Cardiac Rehabilitation, Assisted self-Management (SCRAM) programme among people with coronary heart disease (CHD) are unknown. This economic protocol outlines the methods for undertaking a trial-based economic evaluation of SCRAM in the real-world setting in Australia.

Methods and analysis

The within-trial economic evaluation will be undertaken alongside a randomised controlled trial (RCT) designed to determine the effectiveness of SCRAM in comparison with the usual care cardiac rehabilitation (UC) alone in people with CHD. Pathway analysis will be performed to identify all the costs related to the delivery of SCRAM and UC. Both a healthcare system and a limited societal perspective will be adopted to gauge all costs associated with health resource utilisation and productivity loss. Healthcare resource use over the 6-month participation period will be extracted from administrative databases (ie, Pharmaceutical Benefits Scheme and Medical Benefits Schedule). Productivity loss will be measured by absenteeism from work (valued by human capital approach). The primary outcomes for the economic evaluation are maximal oxygen uptake (VO2max, mL/kg/min, primary RCT outcome) and quality-adjusted life years estimated from health-related quality of life as assessed by the Assessment of Quality of Life-8D instrument. The incremental cost-effectiveness ratio will be calculated using the differences in costs and benefits (ie, primary and secondary outcomes) between the two randomised groups from both perspectives with no discounting. All costs will be valued in Australian dollars for year 2020.

Ethics and dissemination

The study protocol has been approved under Australia’s National Mutual Acceptance agreement by the Melbourne Health Human Research Ethics Committee (HREC/18/MH/119). It is anticipated that SCRAM is a cost-effective cardiac telerehabilitation programme for people with CHD from both a healthcare and a limited societal perspective in Australia. The evaluation will provide evidence to underpin national scale-up of the programme to a wider population. The results of the economic analysis will be submitted for publication in a peer-reviewed journal.

Trial registration number

Australian New Zealand Clinical Trials Registry (ACTRN12618001458224).
Sudden death in individuals with obstructive sleep apnoea: protocol for a systematic review and meta-analysis
Authors: Heilbrunn Emily , Ssentongo Paddy , Chinchilli Vernon M , Ssentongo Anna E
Published: August 2020

Introduction

Obstructive sleep apnoea (OSA) is a form of sleep-disordered breathing, characterised by blockage of the airway, snoring, gasping for air during sleep, daytime sleepiness and fatigue. OSA is associated with increased risk of cardiovascular and cerebrovascular morbidity and mortality, and sudden cardiac death (SCD). The magnitude of this risk varies in the literature and therefore we aim to systematically assess this risk. This study protocol proposes a meta-analysis and systematic review aimed to estimate the magnitude of the association between OSA, ‘sudden death’ and cardiovascular death.

Methods

We will conduct a systematic review and meta-analysis of studies published from the inception of each database, which report the risk of ‘sudden death’ or cardiovascular death (including SCD) in individuals diagnosed with OSA versus persons without OSA. The primary outcome of interest in this study will be the relative risk of ‘sudden death’ in patients diagnosed with OSA in comparison to those without an OSA diagnosis. We will search the following electronic research databases: PubMed (MEDLINE), Cochrane, OVID (Healthstar), OVID (Medline), Scopus and Joana Briggs Institute EBP Database. This protocol was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol guidelines. The checklist for this document is included in the supplemental material. Two reviewers will screen articles for inclusion criteria, extracting appropriate data and evaluating the quality of the included studies. The methodological quality of studies will be appraised using an appropriate tool. Funnel plots and the Egger’s test will be employed to evaluate potential publication bias. We will fit random-effects model with inverse-variance methods for the pooling effect estimates. We will conduct a meta-regression analysis, using numerous variables of interest including age, gender, race, body mass index, hypertension and diabetes, to explore sources of study heterogeneity.

PROSPERO registration number

CRD42020164941.

Ethics and dissemination

No ethics clearance was required for this protocol, for no primary data are being collected on research subjects. Only secondary analysis of pre-existing data in scientific databases will be evaluated. The findings of this meta-analysis will be published in a peer-reviewed journal and presented at scientific conferences. These results may assist professionals in the prevention and management of OSA and SCD.