bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vogt–Koyanagi–Harada disease-like uveitis following nivolumab administration treated with steroid pulse therapy: a case report
Authors: Kikuchi Ryo , Kawagoe Tatsukata , Hotta Kazuki 
Published: June 2020

Abstract
Background
Immune checkpoint inhibitors can cause various adverse effects. Recently it has been shown that Vogt–Koyanagi–Harada (VKH) disease-like uveitis can occur in patients treated with nivolumab.

Case presentation
A 69-year-old man developed bilateral panuveitis after nivolumab treatment for recurrent hypopharyngeal cancer. Slit lamp examination revealed bilateral granulomatous keratic precipitates, anterior chamber cells and partial synechiae. Fundus examination revealed bilateral optic disc edema and diffuse serous retinal detachment. His human leukocyte antigen (HLA) typing showed HLA-DRB1*04:05 allele. A lumbar puncture did not demonstrate pleocytosis. Bilateral sub-tenon injections of triamcinolone acetonide were initiated. As his panuveitis did not regress completely, steroid pulse therapy was administered. That therapy led to the resolution of his serous retinal detachment and to rapid improvement in his vision. Following this, we treated him with 50 mg/day of prednisolone for 1 week and then reduced it by 5 mg every week. No bilateral uveitis relapse had occurred by his 3-month follow-up; however, he subsequently died because of his cancer.

Conclusion
To our knowledge, this is the first report of a patient with NVKH who underwent a lumbar puncture. Unlike VKH, our case did not show meningismus or pleocytosis. NVKH may, therefore, have a different etiology from VKH.
In cases of NVKH with posterior uveitis, steroid pulse therapy may be considered as a treatment option, as it is in VKH.
Brief evidence-based interventions for universal child health services: a restricted evidence assessment of the literature
Authors: Newham James J. , McLean Karen , Ginja Samuel , Hurt Lisa , Molloy Carly , Lingam Raghu , Goldfeld Sharon 
Published: June 2020

AbstractBackgroundUniversal child health services (UCHS) provide an important pragmatic platform for the delivery of universal and targeted interventions to support families and optimize child health outcomes. We aimed to identify brief, evidence-based interventions for common health and developmental problems that could be potentially implemented in UCHS.MethodsA restricted evidence assessment (REA) of electronic databases and grey literature was undertaken covering January 2006 to August 2019. Studies were eligible if (i) outcomes related to one or more of four areas: child social and emotional wellbeing (SEWB), infant sleep, home learning environment or parent mental health, (ii) a comparison group was used, (iii) universal or targeted intervention were delivered in non-tertiary settings, (iv) interventions did not last more than 4 sessions, and (v) children were aged between 2 weeks postpartum and 5 years at baseline.ResultsSeventeen studies met the eligibility criteria. Of these, three interventions could possibly be implemented at scale within UCHS platforms: (1) a universal child behavioural intervention which did not affect its primary outcome of infant sleep but improved parental mental health, (2) a universal screening programme which improved maternal mental health, and (3) a targeted child behavioural intervention which improved parent-reported infant sleep problems and parental mental health. Key lessons learnt include: (1) Interventions should impart the maximal amount of information within an initial session with future sessions reinforcing key messages, (2) Interventions should see the family as a holistic unit by considering the needs of parents with an emphasis on identification, triage and referral, and (3) Brief interventions may be more acceptable for stigmatized topics, but still entail considerable barriers that deter the most vulnerable.ConclusionsDelivery and evaluation of brief evidence-based interventions from a UCHS could lead to improved maternal and child health outcomes through a more responsive and equitable service. We recommend three interventions that meet our criteria of “best bet” interventions.
Feasibility and acceptability of using medical and nursing students to provide Implanon NXT at the community level in Kinshasa, Democratic Republic of Congo
Authors: Hernandez Julie H. , Akilimali Pierre , Glover Annie , Bertrand Jane T. 
Published: June 2020

Abstract
Background
The use of implants has steadily increased in Kinshasa since 2013 but clinic-based access to this family planning method is limited due to distance and costs barriers. The objective of this study was to examine the feasibility and acceptability of providing Implanon NXT at the community level using medical and nursing students (M/N) as distributors, as part of a strategy to improve contraceptive uptake in the Democratic Republic of Congo.

Methods
A cohort of 531 women who chose to receive Implanon NXT from a M/N student during community-based campaign days participated in three rounds of a quantitative survey administered at the time of insertion of the method, and at 6 and 12 months later. We conducted descriptive analysis to assess the feasibility and acceptability of providing the method through M/N students in terms of method choice, user profiles, contraceptive history, experience with insertion and side effects, continuation / discontinuation of the method, and overall satisfaction with FP services as well as students’ preparedness and capacity to safely offer the method, and their satisfaction with the experience..

Results
The study demonstrated the feasibility of training students for community-based provision of Implanon NXT and 95% of them were satisfied with their experience. Acceptability of both the method and the service delivery strategy was high among participants, including among young and first-time contraceptive users. Out of the 441 women with a known outcome at 12 months, 92% still had Implanon NXT inserted, despite some of them reporting experiencing side effects. The vast majority (79%) would “strongly recommend” obtaining NXT from a M/N student if a friend wanted to avoid pregnancies.

Conclusions
The provision of Implanon NXT at the community-level is a promising solution to address some of the barriers to accessing this method for women living in Kinshasa. However, strengthening pre-insertion counseling, particularly on expected side-effects and the possibility of early removal, is necessary to increase informed choice for the women and potentially limit method discontinuation.
Use of the KT-MCC strategy to improve the quality of decision making for multidisciplinary cancer conferences: a pilot study
Authors: Fahim Christine , McConnell Meghan M. , Wright Frances C. , Sonnadara Ranil R. , Simunovic Marko 
Published: June 2020

AbstractBackgroundMultidisciplinary Cancer Conferences (MCCs) are increasingly used to guide treatment decisions for patients with cancer, though numerous barriers to optimal MCC decision-making quality have been identified. We aimed to improve the quality of MCC decision making through the use of an implementation bundle titled the KT-MCC Strategy. The Strategy included use of discussion tools (standard case intake tool and a synoptic discussion tool), workshops, MCC team and chair training, and audit and feedback. Implementation strategies were selected using a theoretically-rooted and integrated KT approach, meaning members of the target population (MCC participants) assisted with the design and implementation of the intervention and strategies. We evaluated implementation quality of the KT-MCC Strategy and initial signals of impact on decision making quality.MethodsThis was a before-and-after study design among 4 MCC teams. Baseline data (before-phase) were collected for a period of 2 months to assess the quality of MCC decision making. Study teams selected the intervention strategies they wished to engage with. Post-intervention data (after-phase) were collected for 4 months. Implementation quality outcomes included reach, adherence/fidelity and adaptation. We also evaluated feasibility of data management. Decision making quality was evaluated on a per-case and per-round level using the MTB-MODe and MDT-OARS tools, respectively.ResultsThere were a total of 149 cases and 23 MCCs observed in the before phase and 260 cases and 35 MCCs observed in the after phase. Teams implemented 3/5 strategies; adherence to selected strategies varied by MCC team. The per-round quality of MCCs improved by 11% (41.0 to 47.3,p = < 0.0001). The quality of per-case decision-making did not improve significantly (32.3 to 32.6,p = 0.781).ConclusionWhile per round MCC decision making quality improved significantly, per-case decision-making quality did not. We posit that the limited improvements on decision making quality may be attributed to implementation quality gaps, including a lack of uptake of and adherence to theoretically-identified implementation strategies. Our findings highlight the importance of evaluating implementation quality and processes, iterative testing, and engagement of key gatekeepers in the implementation process.
Cost-effectiveness analysis of atezolizumab in advanced triple-negative breast cancer
Authors: Phua Lee Cheng , Lee Soo Chin , Ng Kwong , Abdul Aziz Mohamed Ismail 
Published: June 2020

Abstract
Background
The IMpassion130 trial demonstrated that adding atezolizumab to nanoparticle albumin-bound (nab)-paclitaxel improved the survival of patients with untreated, advanced, programmed death ligand 1 (PDL1)-positive triple-negative breast cancer (TNBC). In view of the high cost of immunotherapy, it is important to examine its value with respect to both benefits and costs. In this study, the cost-effectiveness of atezolizumab/nab-paclitaxel combination therapy relative to nab-paclitaxel monotherapy was evaluated for the first-line treatment of advanced, PDL1-positive TNBC, from a healthcare system perspective.

Methods
A three-state partitioned-survival model was developed to compare the clinical and economic outcomes of treatment with atezolizumab/nab-paclitaxel combination therapy with nab-paclitaxel monotherapy in patients with advanced TNBC. Clinical data were obtained from the IMpassion130 trial and extrapolated to 5 years. Health state utilities were retrieved from the literature, while direct costs (in Singapore dollars, S$) were sourced from public healthcare institutions in Singapore. The primary outcomes of the model were life years (LYs), quality-adjusted LYs (QALYs), costs and incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses and scenario analyses were conducted to explore the impact of specific assumptions and uncertainties.

Results
Adding atezolizumab to nab-paclitaxel resulted in an additional 0.361 QALYs (0.636 LYs) at an ICER of S$324,550 per QALY gained. The ICER remained high at S$67,092 per QALY even when atezolizumab was priced zero. One-way sensitivity analysis showed that the ICER was most sensitive to variations in the cost of atezolizumab and the time horizon. Scenario analyses confirmed that the ICERs remained high even under extremely favourable assumptions.

Conclusions
Given the exceedingly high ICER, adding atezolizumab to nab-paclitaxel was unlikely to represent good value for money for the treatment of advanced PDL1-positive TNBC. Our findings will be useful in informing funding policy decisions alongside other considerations such as comparative effectiveness, unmet need and budget impact.
Systematic reviews and meta-analyses comparing mortality in restrictive and liberal haemoglobin thresholds for red cell transfusion: an overview of systematic reviews
Authors: Trentino Kevin M. , Farmer Shannon L. , Leahy Michael F. , Sanfilippo Frank M. , Isbister James P. , Mayberry Rhonda , Hofmann Axel , Shander Aryeh , French Craig , Murray Kevin 
Published: June 2020

Abstract
Background
There are no overviews of systematic reviews investigating haemoglobin thresholds for transfusion. This is important as the literature on transfusion thresholds has grown considerably in recent years. Our aim was to synthesise evidence from systematic reviews and meta-analyses of the effects of restrictive and liberal transfusion strategies on mortality.

Methods
This was a systematic review of systematic reviews (overview). We searched MEDLINE, Embase, Web of Science Core Collection, PubMed, Google Scholar, and the Joanna Briggs Institute EBP Database, from 2008 to 2018. We included systematic reviews and meta-analyses of randomised controlled trials comparing mortality in patients assigned to red cell transfusion strategies based on haemoglobin thresholds. Two independent reviewers extracted data and assessed methodological quality. We assessed the methodological quality of included reviews using AMSTAR 2 and the quality of evidence pooled using an algorithm to assign GRADE levels.

Results
We included 19 systematic reviews reporting 33 meta-analyses of mortality outcomes from 53 unique randomised controlled trials. Of the 33 meta-analyses, one was graded as high quality, 15 were moderate, and 17 were low. Of the meta-analyses presenting high- to moderate-quality evidence, 12 (75.0%) reported no statistically significant difference in mortality between restrictive and liberal transfusion groups and four (25.0%) reported significantly lower mortality for patients assigned to a restrictive transfusion strategy. We found few systematic reviews addressed clinical differences between included studies: variation was observed in haemoglobin threshold concentrations, the absolute between group difference in haemoglobin threshold concentration, time to randomisation (resulting in transfusions administered prior to randomisation), and transfusion dosing regimens.

Conclusions
Meta-analyses graded as high to moderate quality indicate that in most patient populations no difference in mortality exists between patients assigned to a restrictive or liberal transfusion strategy.

Trial registration
PROSPERO CRD42019120503
Identification of long noncoding RNA RP11-89K21.1 and RP11-357H14.17 as prognostic signature of endometrial carcinoma via integrated bioinformatics analysis
Authors: Gao Lingling , Nie Xin , Zhang Wenchao , Gou Rui , Hu Yuexin , Qi Yue , Li Xiao , Liu Qing , Liu Juanjuan , Lin Bei 
Published: June 2020

Abstract
Background
Endometrial carcinoma (EC) is one of the most common malignant tumors in gynecology. The potential functions and mechanisms of long noncoding RNAs (lncRNAs) in the occurrence and progression of EC remains unclear. It’s meaningful to explore lncRNAs signature for providing prognostic value of EC.

Methods
The differentially expressed lncRNAs and their prognostic values in EC were investigated based on The Cancer Genome Atlas (TCGA) database; the transcriptional factors (TFs), the competing endogenous RNA (ceRNA) mechanism, functional regulatory network and immune infiltration of RP11-89K21.1 and RP11-357H14.17 were further explored by various bioinformatics tools and databases.

Results
We firstly identified high expression of RP11-89K21.1 and RP11-357H14.17 were closely associated with shorten overall survival (OS) and poor prognosis in patients with EC. We also elucidated the networks of transcription factor and co-expression genes associated with RP11-89K21.1 and RP11-357H14.17. Furthermore, the ceRNA network mechanism was successfully constructed through 2 lncRNAs (RP11-89K21.1 and RP11-357H14.17), 11 miRNAs and 183 mRNAs. Functional enrichment analysis revealed that the targeting genes of RP11-89K21.1 and RP11-357H14.17 were strongly associated with microRNAs in cancer, vessel development, growth regulation, growth factor and cell differentiation, and involved in pathways including pathways in cancer, microRNAs in cancer and apoptotic signaling pathway.

Conclusions
We demonstrated for the first time that RP11-89K21.1 and RP11-357H14.17 may play crucial roles in the occurrence, development and malignant biological behavior of EC, and can be regarded as potential prognostic biomarkers for EC.
Coverage of intermittent preventive treatment of malaria in pregnancy (IPTp) influences delivery outcomes among women with obstetric referrals at the district level in Ghana
Authors: Amoakoh-Coleman Mary , Arhinful Daniel K. , Klipstein-Grobusch Kerstin , Ansah Evelyn K. , Koram Kwadwo A. 
Published: June 2020

Abstract
Background
The aim of the study was to determine the coverage of intermittent preventive treatment of malaria in pregnancy (IPTp) and its relationship with delivery outcomes among obstetric referral cases at the district level of healthcare.

Methods
An implementation research within three districts of the Greater Accra region was conducted from May 2017 to February 2018, to assess the role of an enhanced inter-facility communication system on processes and outcomes of obstetric referrals. A cross-sectional analysis of the data on IPTp coverage as well as delivery outcomes for the period of study was conducted, for all the referrals ending up in deliveries. Primary outcomes were maternal and neonatal complications at delivery. IPTp coverage was determined as percentages and classified as adequate or inadequate. Associated factors were determined using Chi square. Odds ratios (OR, 95% CI) were estimated for predictors of adequate IPTp dose coverage for associations with delivery outcomes, with statistical significance set at p = 0.05.

Results
From a total of 460 obstetric referrals from 16 lower level facilities who delivered at the three district hospitals, only 223 (48.5%) received adequate (at least 3) doses of IPTp. The district, type of facility where ANC is attended, insurance status, marital status and number of antenatal clinic visits significantly affected IPTp doses received. Adjusted ORs show that adequate IPTp coverage was significantly associated with new-born complication [0.80 (0.65–0.98); p = 0.03], low birth weight [0.51 (0.38–0.68); p < 0.01], preterm delivery [0.71 (0.55–0.90); p = 0.01] and malaria as indication for referral [0.70 (0.56–0.87); p < 0.01]. Positive association with maternal complication at delivery was seen but was not significant.

Conclusion
IPTp coverage remains low in the study setting and is affected by type of health facility that ANC is received at, access to health insurance and number of times a woman attends ANC during pregnancy. This study also confirmed earlier findings that, as an intervention IPTp prevents bad outcomes of pregnancy, even among women with obstetric referrals. It is important to facilitate IPTp service delivery to pregnant women across the country, improve coverage of required doses and maximize the benefits to both mothers and newborns.
Prevalence and proportion of Plasmodium spp. triple mixed infections compared with double mixed infections: a systematic review and meta-analysis
Authors: Kotepui Manas , Kotepui Kwuntida Uthaisar , Milanez Giovanni D. , Masangkay Frederick R. 
Published: June 2020

Abstract
Background
Although mixed infection by two Plasmodium species has been recognized, mixed infection by three different Plasmodium species within one individual has not been clarified. This study sought to determine the pooled prevalence and proportion of triple mixed Plasmodium spp. infection compared with double mixed infection.

Methods
Articles from PubMed, Scopus, and Web of Science were searched for cross-sectional studies of triple mixed infection by Plasmodium species and then were retrieved and extracted. The pooled proportion and prevalence of triple mixed infection by Plasmodium species were subjected to random-effects analysis. The secondary outcomes were differences in the pooled proportion between triple mixed infection and double mixed infection by Plasmodium species reported in the included studies.

Results
Of 5621 identified studies, triple mixed infection data were available for 35 records, including 601 patients from 22 countries. The overall pooled prevalence of triple mixed infection was 4% (95% Confidence Interval (CI) 3–5%; I2 = 92.5%). The pooled proportion of triple mixed infection compared with double mixed infection was 12% (95% CI 9–18; I2 = 91%). Most of the included studies (29/35; 82.9%) presented a lower proportion of triple mixed infection than double mixed infection. Subgroup analysis demonstrated that the proportion of triple mixed infection was the highest in Oceania (23%; 95% CI 15–36%) and Europe (21%; 95% CI 5–86%), but the lowest in the USA (3%; 95% CI 2–4%). Moreover, the proportion of triple mixed infection was higher in residents (20%; 95% CI 14–29%) than in febrile patients (7%; 95% CI 4–13%), when compared with the proportion of double mixed infection. Subgroup analysis of the age groups demonstrated that, compared with the proportion of double mixed infection, triple mixed infection was lower in patients aged ≤ 5 years (OR = 0.27; 95% CI 0.13–0.56; I2 = 31%) and > 5 years (OR = 0.09; 95% CI 0.04–0.25, I2 = 78%).

Conclusions
The present study suggested that, in areas where triple mixed infection were endemic, PCR or molecular diagnosis for all residents in communities where malaria is submicroscopic can provide prevalence data and intervention measures, as well as prevent disease transmission and enhance malaria elimination efforts.
High expression of AMAP1, an ARF6 effector, is associated with elevated levels of PD-L1 and fibrosis of pancreatic cancer
Authors: Tsutaho Akio , Hashimoto Ari , Hashimoto Shigeru , Hata Soichiro , Kachi Shion , Hirano Satoshi , Sabe Hisataka 
Published: June 2020

Abstract
Background
Not merely the onset of immune evasion, but other factors, such as acidosis and fibrosis, are also major barriers in cancer therapeutics. Dense fibrosis is a hallmark of pancreatic ductal carcinoma (PDAC), in which hyperactivation of focal adhesion kinase (FAK) in tumor cells was shown to be crucial. Double mutations of KRAS/ TP53 are characteristic to PDAC. We previously showed that high protein expression of ARF6 and its downstream effector AMAP1, as well as processes involved in the ARF6 activation by cell surface tyrosine kinase receptors, are major targets of the KRAS/TP53 mutations to promote PDAC invasion, metastasis, and immune evasion. This notion was recaptured by KPC mouse model of human PDAC (LSL-Kras(G12D/+); LSL-Trp53(R172H/+)); Pdx-1-Cre). Mechanistically, the ARF6-AMAP1 pathway is primarily involved in cellular dynamics of PD-L1, β1-integrins, and E-cadherin; and hence modulates cell-adhesion properties when ARF6 is activated. Here, with an aim to understand whether the ARF6-AMAP1 pathway is critically involved in the elevated levels of PD-L1 and fibrosis of PDAC, we analyzed relationship between AMAP1 and these malignant phenotypes. Moreover, because the ARF6 pathway may closely be related to focal adhesion dynamics and hence to FAK, we also investigated whether AMAP1 employs FAK in fibrosis.

Methods
Clinical specimens, as well as KPC cells/tumors and their shAMAP1 or shFAK derivatives were analyzed.

Results
Elevated levels of PD-L1 and fibrosis correlated with poor outcome of our patient cohort, to be consistent with previous reports; in which high AMAP1 expression statistically correlated with the elevated PD-L1 and fibrosis. To be consistent, silencing of AMAP1 (shAMAP1) in KPC cells resulted in reduced PD-L1 expression and fibrosis in their tumors. On the other hand, shAMAP1 only slightly affected FAK activation in KPC cells, and phosphorylated FAK did not correlate with enhanced fibrosis or with poor outcome of our patients.

Conclusions
Together with our previous data, our results collectively indicated that the ARF6-AMAP1 pathway, empowered by the KRAS/TP53 mutations, is closely associated with elevated PD-L1 expression and fibrosis of human PDACs, to be recaptured in the KPC mouse model. The ARF6 pathway may promote fibrosis independent of FAK.