bluuebunny/crossref_metadata_2025_split huggingface dataset:
Esketamine: new hope for the treatment of treatment-resistant depression? A narrative review
Authors: Salahudeen Mohammed S , Wright Cameron M , Peterson Gregory M 
Published: July 2020

This narrative review aims to provide an overview of the current literature on the pharmacology, safety, efficacy and tolerability of intranasal esketamine, the S-enantiomer of ketamine, for the treatment of treatment-resistant depression (TRD). A literature search using Medline, Embase, PsycINFO and Cochrane Central was conducted (January 2000 to July 2019). Product information and www.clinicaltrials.gov were also reviewed. The literature search was limited to human studies published in English. Phase I, II, and III studies of intranasal esketamine for TRD were reviewed. About a third of patients with major depressive disorder fail to achieve remission despite treatment with multiple antidepressants. This article examines the trials that led to the approval of esketamine in the United States, as well as other recent studies of esketamine for TRD. The findings from limited phase III trials illustrate that intranasal esketamine is effective and safe in reducing depressive symptoms and achieving clinical response in patients with TRD. The optimum duration and frequency of use are not fully understood. Although the nasal spray is a convenient dosage form, its use in practice may be limited by cost and administrative regulation. While it may prove beneficial to many patients who suffer from TRD, further long-term data are required, along with comparative trials with the R-isomer (arketamine). In the interim, care and monitoring should be exercised in its use in clinical practice. Plain language summary Esketamine: new therapy for severe depression Intranasal esketamine, the S-enantiomer of ketamine, was recently approved in the United States for the treatment of treatment-resistant depression (TRD). The findings from limited clinical trials indicate that intranasal esketamine is effective and safe in patients with TRD, although the optimum dose, duration and frequency of use are not fully understood. Its use in practice may be limited by cost and administrative regulation, and further long-term data are required.
COVID-19 Outbreak in a Hemodialysis Center: A Retrospective Monocentric Case Series
Authors: Mazzoleni Lionel , Ghafari Chadi , Mestrez Fabienne , Sava Roxana , Bivoleanu Elena , Delmotte Philippe , Laurent France , Roland Thomas , Rossi Camelia , Carlier Stéphane 
Published: July 2020

Background: The rapid worldwide spread of COVID-19 has posed a serious threat to patients treated with kidney replacement therapy (KRT). Moreover, the impact of the disease on hemodialysis centers, the patients, and the health care workers is still not completely understood. Objective: We present the analysis of a COVID-19 outbreak in a hemodialysis center in Belgium and report the incidence, clinical course, and outcome of the disease. Design: A retrospective cross-sectional cohort study. Setting: A hemodialysis center during the COVID-19 outbreak. Patients: A total of 62 patients on maintenance hemodialysis at a tertiary care center in Belgium attended by 26 health care workers. Measurements: Baseline patients’ characteristics were retrieved. The incidence, clinical course, and outcome were reported. The differences between COVID-19 survivors and nonsurvivors were assessed along with the differences between COVID-19-hospitalized and nonhospitalized patients. The incidence of the disease and outcome of health care workers were also reported. Methods: Proportions for categorical variables were compared using the Fisher exact test and χ2. The Mann-Whitney rank sum test was used to compare continuous variables. Univariate analysis and a binomial logistic regression were used to explore variables as predictors of death. Results: Between March 6 and April 14, 2020, 40 of 62 (65%) patients tested positive for severe acute respiratory syndrome beta coronavirus 2 (SARS-CoV-2) along with 18 of 26 (69%) health care professionals. Twenty-five (63%) of the infected patients were hospitalized with a median time for hospitalization-to-discharge of 8 (interquartile range [IQR] = 4-12) days. Eleven (28%) COVID-19-related deaths were recorded with a median time for onset of symptoms-to-death of 9 (IQR = 5-14) days. Lymphocytopenia was prevalent among the cohort and was found in 9 of 11 (82%) reported deaths ( P = .4). There was no influence of the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers on COVID-19-related deaths ( P = .3). Advanced age, cardiovascular disease (CVD), and obstructive sleep apnea syndrome were all found to be significantly related to death. Of the 18 infected health care professionals, 13 (72%) were symptomatic and 2 (11%) were hospitalized. There was no reported death among the health care workers. Limitations: Limited follow-up time compared with the course of the disease along with a small sample size. Conclusions: Patients treated with KRT show a high mortality rate secondary to COVID-19. CVD and age are shown to impact survival. Proactive measures must be taken to prevent the spread of the virus in such facilities. Trial Registration: Not applicable as this is a retrospective study.
Indirect Immunofluorescence and Tumorspheres Enrichment Technique for Identifying Cancer Stem Cell Markers in Cancer Cell Lines From Primary Oral Cancer Tissues: An In Vitro Study
Authors: Kumbar Vijay M. , Muddapur Uday M. , Bhat Kishore G. , Shwetha H.R.  , Kugaji Manohar S. , Peram Malleswara Rao 
Published: July 2020

Aim: The cancer stem cells (CSCs) are known to be responsible for drug resistance and cancer relapse in the treatment of cancer. Identification and isolation of CSCs and study of their properties will play a crucial role in developing an effective drug against these targets. The aim of the study was to isolate CSCs from primary cancer by the tumorspheres enrichment method, to confirm by indirect immunofluorescence and gene expression of stem cell markers by using real-time polymerase chain reaction (RT-PCR) technique. Materials and Methods: In this in vitro study, we enriched oral CSCs through tumorsphere formation assay from seven primary cultures of OSCC patients with defined serum media. The expression and localization of the cell surface markers of CD133 and CD44 were tested by indirect immunofluorescence. Gene expression of stem cell markers such as CD44, CD133, Oct4, Sox2, and Nanog were quantified by RT-PCR technique. One-way analysis of variance was applied to analyze gene expression. Results: Tumorsphere formation has been used to isolate the CSCs from the OSCC tissue culture. Both CD133 and CD44 antibody confirmed the presence of CSCs through indirect immunofluorescence. In comparison to parental cell lines, the expression levels of CD133, CD44, Oct4, Sox2, and Nanog stem cell were significantly higher in CSC-enriched subpopulations. Conclusions: The cost-effective spheroid enrichment and the indirect immunofluorescence methods are useful for the isolation of CSCs from the primary tumor.
Health Care Utilization and Costs in the Year Prior to Arthroscopic Rotator Cuff Repair
Authors: Malik Azeem Tariq , Sridharan Mathangi , Bishop Julie Y. , Khan Safdar N. , Jones Grant L. , Neviaser Andrew S. , Cvetanovich Gregory L. 
Published: July 2020

Background: A majority of cost-control strategies in arthroscopic rotator cuff repair (RCR) have been concentrated on the perioperative and post–acute care periods, with the preoperative health care period being largely overlooked. Purpose: To report the distribution of costs associated with health care utilization within the year prior to arthroscopic RCR. Study Design: Economic and decision analysis; Level of evidence, 3. Methods: The 2007 through 2015 (third quarter) Humana Administrative Claims database was queried using Current Procedural Terminology code 29827 to identify patients undergoing arthroscopic RCR for only degenerative rotator cuff tears. The study cohort was divided into 2 distinct groups based on insurance plan: commercial or Medicare Advantage (MA). Total 1-year costs, per-patient average reimbursements (PPARs), and trends in utilization for the following preoperative health care resource categories were studied: office visits, radiographs, magnetic resonance imaging (MRI) scans, computed tomography (CT) scans, steroid injections, hyaluronic acid (HA) injections, physical therapy, and pain medications (opioids + nonopioids). Results: A total of 18,457 MA and 6530 commercial beneficiaries undergoing arthroscopic RCR over the study period were included. Total 1-year preoperative costs (in US$) amounted to $16,923,595 ($916/patient) and $8,397,291 ($1285/patient) for MA and commercial beneficiaries, respectively. The largest proportion of total 1-year costs for both MA and commercial beneficiaries was accounted for by MRI scans (36% and 56%, respectively). PPARs for each health care resource category were as follows: office visits (MA, $240; commercial, $249), radiographs (MA, $60; commercial, $93), MRI scans (MA, $385; commercial, $813), CT scans (MA, $223; commercial, $562), steroid injections (MA, $97; commercial, $137), HA injections (MA, $422; commercial, $602), physical therapy (MA, $473; commercial, $551), and pain medications (MA, $208; commercial, $136). High health care utilization within the past 3 months before surgery was noted for radiographs, physical therapy, opioids, steroid injections, and office visits, with up to 40% to 90% of 1-year PPARs being accounted for within this time period alone. Conclusion: Approximately $900 to $1300 per patient was spent in rotator cuff–related health care resource use in the year prior to undergoing arthroscopic RCR. As we begin to implement value in shoulder surgery, judicious use of nonoperative treatment modalities among patients who would not benefit from nonoperative care will be an effective way of reducing costs.
Effect of anaerobic phases length on denitrifying dephosphatation biocenosis – a case study of IFAS-MBSBBR
Authors: Gnida Anna , Żubrowska-Sudoł Monika , Sytek-Szmeichel Katarzyna , Podedworna Jolanta , Surmacz-Górska Joanna , Marciocha Dorota 
Published: July 2020

Abstract
Background
The study aimed to evaluate the influence of the duration times of anaerobic phases on the bacterial biocenosis characterisation while denitrifying dephosphatation in the Integrated Fixed-Film Activated Sludge – Moving-Bed Sequencing Batch Biofilm Reactor (IFAS-MBSBBR). The experiment was conducted in a laboratory model. The study consisted of four series, which differed in terms of the ratio of the anaerobic phases.
duration concerning the overall reaction time in the cycle. The anaerobic phases covered from 18 to 30% of the whole cycle duration. During the reactor performance that took 9 months, the influent and effluent were monitored by analysis of COD, TKN, NH4-N, NO2-N, NO3-N, TP, PO4-P, pH, alkalinity and the phosphorus uptake batch tests. Characterisation of the activated sludge and the biofilm biocenosis was based on fluorescent in situ hybridisation (identification of PAO and GAO) and the denaturing gradient gel electrophoresis patterns.

Results
The organic compounds removal was high (more than 95.7%) independently of cycle configuration. The best efficiency for nitrogen (91.1%) and phosphorus (98.8%) removal was achieved for the 30% share of the anaerobic phases in the reaction time. Denitrifying PAO (DPAO) covered more than 90% of PAO in the biofilm and usually around 70% of PAO in the activated sludge. A substantial part of the polyphosphate accumulating organisms (PAO) community were Actinobacteria. The denitrifying dephosphatation activity was performed mainly by Accumulibacter phosphatis.

Conclusions
High nutrient removal efficiencies may be obtained in IFAS-MBSBBR using the denitrifying dephosphatation process. It was found that the length of anaerobic phases influenced denitrification and the biological phosphorus removal. The extension of the anaerobic phases duration time in the reaction time caused an increase in the percentage share of denitrifying PAO (DPAO) in PAO. The biocenosis of the biofilm and the activated sludge reveal different species patterns and domination of the EBPR community.
Rationale and study protocol of ACQUIRE, a prospective, observational study measuring quality of life, treatment preference and treatment satisfaction of autosomal dominant polycystic kidney disease (ADPKD) patients in Europe
Authors: Joly Dominique , Quinn Jennifer , Mokiou Stella , O’Reilly Karl , Sánchez-Covisa Joaquín , Wang-Silvanto Jing , Doll Helen 
Published: July 2020

AbstractBackgroundAutosomal dominant polycystic kidney disease (ADPKD) is considered the most common inherited renal disease. Patient-Reported Outcomes (PROs) and patient experience in ADPKD are difficult to quantify and have not been well studied, particularly in the early stages of the disease. There is evidence to suggest that early-stage ADPKD patients have a lower Health-Related Quality of Life (HRQoL) than the general population due to the signs and symptoms of early-stage ADPKD. However, no research has been carried out on the HRQoL of early-stage ADPKD patients using validated ADPKD-specific PRO measures. Additionally, a new disease progression delaying treatment option has recently emerged for ADPKD. Patient preference for this treatment and unmet treatment needs have not yet been investigated.MethodsThe ACQUIRE study is a prospective, observational study investigating the influence of early-stage ADPKD-related symptoms and treatments on PROs. It aims to collect real-world data on patient demographics, treatment patterns, clinical outcomes, and PROs such as HRQoL, treatment satisfaction and treatment preference in early-stage ADPKD. Adult ADPKD patients in stages 1–3 of chronic kidney disease (CKD) with evidence of rapidly progressing disease are being recruited from seven European countries. At baseline and every 3 months, for a follow-up period of 18 months, general and disease-specific questionnaires are completed remotely to capture patients’ own assessment of their overall and ADPKD-related HRQoL. A Discrete Choice Experiment (DCE) is also used to investigate the value patients place on different attributes of hypothetical treatment options (e.g. treatment outcomes, side effects) and the role each attribute plays in determining overall patient treatment preference.DiscussionThe results of this study will highlight the real-world effects of ADPKD-related challenges on PROs including HRQoL, treatment experience and satisfaction; and help physicians gain greater insight into likely disease outcomes based on early-stage patient symptoms and patients’ experience with treatment. Data captured by the DCE may inform ADPKD treatment decision-making from a patient perspective. The DCE will also provide insights into which patients are more likely to perceive benefit from treatments based on the value and trade-offs they place on specific treatment attributes.Trial registrationNCT02848521.Protocol Number/Version: 156–303-00096/Final
Phenylketonuria screening in Iranian newborns: a systematic review and meta-analysis
Authors: Shokri Mehdi , Karimi Parviz , Zamanifar Hadis , Kazemi Fatemeh , Badfar Gholamreza , Azami Milad 
Published: July 2020

AbstractBackgroundPhenylketonuria (PKU), which is characterized by a deficiency of phenylalanine hydroxylase activity, is an autosomal recessive disorder of phenylalanine (Phe) metabolism. Newborn screening is the main population-based public health screening program that allows successful identification and treatment of PKU with low-Phe diet. The aim of this study was to evaluate the epidemiology of PKU screening in Iranian newborns.MethodsThe present study was designed based on MOOSE protocol and reporting was done in accordance with the PRISMA guidelines. The protocol of this systematic review was published in PROSPERO before it was performed (CRD42020162626). A comprehensive search was done in 10/10/2019 to find related literature on international online databases Web of Science, Scopus, EMBASE, Science Direct, PubMed/Medline, EBSCO, CINAHL, Cochrane Library, national online databases and the Google Scholar search engine. Heterogeneity among studies was assessed by I2index and Q test. All meta-analyses were performed using Comprehensive Meta-Analysis Software ver. 2.P < 0.05 was considered significant.ResultFinally, 18 studies with 3,339,327 Iranian neonates were included. The prevalence of suspected hyperphenylalaninemia(HPA) was estimated to be 45.6/100,000 (95% CI: 23.9–87.1). The prevalence of suspected HPA in girls and boys infants in Iran was estimated to be 38.0/100,000 (95% CI: 15.1-95.5) and 43.3/100,000 (95% CI: 16.2-116.2), respectively. The prevalence of PKU was estimated to be 16.5/100,000 (95% CI: 12.9–21.2). The prevalence of PKU in girls and boys infants was estimated to be 13.3/100,000 (95% CI: 7.5–15.8) and 10.9/100,000 (95% CI: 7.5–15.8), respectively. The prevalence of mild to moderate HPA was estimated 9.7/100,000 (95% CI: 5.1–18.4) and the prevalence of classical PKU was estimated 4.4/100,000 (95% CI: 2.5–7.8). Sensitivity analysis for all meta-analysis with the omission of one study showed that overall estimation is still robust.ConclusionThe results of this meta-analysis showed that PKU is prevalent in Iranian neonates.It should be considered that for PKU there is a highly effective dietary treatment which can prevent the clinical symptoms of PKU if initiated early after detection by newborn screening.
Real-time monitoring and just-in-time intervention for adherence to pre-exposure prophylaxis among men who have sex with men in China: a multicentre RCT study protocol
Authors: Jin Xia , Wang Hongyi , Li Hang , Chu Zhenxing , Zhang Jing , Hu Qinghai , Lv Wei , Huang Xiaojie , Chen Yaokai , Wang Hui , He Xiaoqing , Zhang Lukun , Hu Zhili , Bao Rantong , Li Shangcao , Ding Haibo , Geng Wenqing , Jiang Yongjun , Shang Hong , Xu Junjie ,   for the CROPrEP Study Team, Shi Xiaoyun , Li Rui , Gao Yangyang , Ma Yanni , Duan Yi , Zhang Guanghui , Li Yao , Zhao Fang 
Published: July 2020

Abstract
Background
Pre-exposure prophylaxis (PrEP) is an effective biomedical strategy to prevent transmission of HIV infection, although medication adherence remains a challenge. We present the protocol for a multicentre randomised controlled trial to measure the effectiveness of a real-time monitoring and just-in-time intervention on medication adherence among PrEP users in China.

Methods
Study participants will include 1000 men who have sex with men (MSM) from four cites in China (Shenyang, Beijing, Chongqing and Shenzhen) attending a tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) PrEP project as part of a real-world, prospective multicentre cohort study (CROPrEP). Participants will be randomised into the intervention and control arms in a 1:1 ratio. Participants in the intervention arm will be provided with remote real-time monitoring equipment that triggers twice just-in-time SMS (Short Messaging Service) medication reminders to PrEP users every half an hour when a scheduled dosage is missed, and followed with just-in-time SMS medication reminders to clinicians half an hour when there is no supplement after the second just-in-time SMS reminder to PrEP users. Clinicians will initiate individualised telephone intervention as soon as possible upon receipt of the just-in-time SMS missed dose alert. Those in the control arm will only receive generic weekly SMS reminders. The study will last 6 months. Participants will be seen at follow-up visits at three and 6 months. Trial outcomes to be measured include self-reported adherence assessed via questionnaire and pill counts, as well as drug concentration test results.

Discussion
Medication adherence is critical to achieve optimal benefits from PrEP. This study will be the first individualised behaviour intervention using real-time technology to increase adherence among MSM PrEP users globally. If found effective, a real-time monitoring and just-in-time intervention system may be utilized for improving adherence and thus effectiveness of global PrEP application.

Trial registration
This study registered at ClinicalTrials.gov (ChiCTR1900025604) on September 2, 2019.
Goals of care or goals of life? A qualitative study of clinicians’ and patients’ experiences of hospital discharge using Patient-Oriented Discharge Summaries (PODS)
Authors: Hattangadi Nayantara , Kurdyak Paul , Solomon Rachel , Soklaridis Sophie 
Published: July 2020

Abstract
Background
Recognizing the need for improved communication with patients at the point of hospital discharge, a group of clinicians, patients, and designers in Toronto, Canada collaborated to develop a standardized tool known as the Patient-Oriented Discharge Summary (PODS). Although quantitative results suggest PODS helps mitigate gaps in knowledge, a qualitative inquiry from the clinician and patient perspective of psychiatric hospital discharge using PODS has not been widely explored. Our aim was to explore clinicians’ and patients’ experiences with PODS.

Methods
We used a qualitative thematic analysis to explore clinicians’ (n = 10) and patients’ (n = 6) experiences with PODS. We used convenience sampling to identify and invite potential participants at the Center for Addiction and Mental Health in Toronto, Canada to participate in semi-structured interviews between February 2019 and September 2019. Data were analyzed using a thematic analysis approach to develop descriptive themes.

Results
Emerging themes from the data between clinicians and patients were both different and complementary. Clinicians described PODS using the concept of “goals of care.” They relayed their experiences with PODS as a discrete event and emphasized its role in meeting their “goals of care” for discharge planning. Patients provided more of a “goals of life” perspective on recovery. They characterized PODS as only one facet of their recovery journey and not necessarily as a discrete or memorable event. Patients focused on their outcomes post-discharge and situated their experiences with PODS through its relation to their overall recovery.

Conclusions
PODS was experienced differently by clinicians and patients. Clinicians experienced PODS as helpful in orienting them to the fulfillment of goals of care. Patients did not experience PODS as a particularly memorable intervention. Due to the information advantage that clinicians have about PODS, it is not surprising that clinicians and patients experienced the PODS differently. This study expanded our understanding of hospital discharge from clinicians and patients perspectives, and suggests that there are additional areas that need improvement.