bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of laminar airflow heating, ventilation, and air conditioning system for particle dispersion control in operating room including staffs: A non-Boussinesq Lagrangian study
Authors: Amiraslanpour Mojtaba , Ghazanfarian Jafar , Nabaei Hamidreza , Taleghani Mohammad Hassan
Published: July 2020

Impacts of the laminar airflow ventilation system design factors on contaminant removal and thermal comfort condition in an operating room have been investigated by means of Lagrangian-based particle transport using the non-Boussinesq modeling of the buoyancy effects. An operating room including staffs and a patient with realistic human geometries and two surgery lights are included in simulations. The laminar airflow system is placed on the ceiling with a surrounding fixed-height partial wall and the air barrier supply grills. Effects of density change in mixed convection flow regime are included by the non-Boussinesq modeling of the exact air density variation. The predicted mean vote, the age of air, the colony-forming units per cubic meter, the average temperature, the average velocity, the relative humidity, the density distribution, and the positions of particles are calculated to assess the indoor air ventilation quality. A total of 27 simulation cases have been considered to determine the impact of three main design factors including the laminar airflow system area, the supply air, and the air barrier velocities on the performance of the system. It is concluded that for the curtain velocity of 2 m/s, the thermal comfort reduces with increasing the laminar airflow velocity, but for the third staff, the results show that for small laminar airflow areas, the speed of the inlet port should be reduced and for the larger sizes, the inverse of this trend is recommended. Moreover, for all cases the humidity varies within the range of 55%–56%, which agrees well with the suggested standard humidity range between 50% and 60%. It is concluded that the cases of the laminar airflow velocity equal to 0.3 and 0.5 at the curtain velocity of 1 m/s are generally more appropriate than other cases due to less accommodation of particles near the entire body of the patient.
COVID-19 human challenge trials – what research ethics committees need to consider
Authors: Tambornino Lisa , Lanzerath Dirk
Published: July 2020

To reduce the global burden of the COVID-19 pandemic, there is an urgent need to develop a safe vaccine. Vaccine development usually takes many years as it goes through several different phases. To hasten COVID-19 vaccine development, it has been suggested that the final stage could be replaced with a human challenge trial (HCT). Volunteers would be intentionally infected with SARS-CoV-2 to see how the vaccine candidate works. To intentionally infect a healthy human being with a potentially deadly virus is contrary to the highest ethical standards in medical research. This article highlights the benefits and risks of COVID-19 HCTs and summarises what research ethics committees (RECs) need to consider during the ethical assessment of such trials including risk reduction, strict containment measures, specific informed consent measures and avoiding high monetary inducements.
Estimation of parameters for load-sharing parallel systems under exponential Pareto distribution
Authors: Zhang Zhengcheng , Yang Yonghong , Li Danqing
Published: July 2020

This article deals with the estimation of parameters for the load-sharing parallel system when the underlying distribution of component lifetime is exponential Pareto. The appropriate iterative method is used to get the parameter estimators. And the asymptotic distribution of the proposed maximum likelihood estimator is presented. For the model simplified, the maximum likelihood and best asymptotic unbiased estimators of parameters are obtained. Moreover, the confidence intervals for the parameters are constructed using the parameter bootstrap technique. In the end, some appropriate simulation methods and an example are used to substantiate the proposed methods.
Oral exposure of pigs to the mycotoxin deoxynivalenol does not modulate the hepatic albumin synthesis during a LPS-induced acute-phase reaction
Authors: Dänicke Sven , Bannert Erik , Tesch Tanja , Kersten Susanne , Frahm Jana , Bühler Susanne , Sauerwein Helga , Görs Solvig , Kahlert Stefan , Rothkötter Hermann-Josef , Metges Cornelia C , Kluess Jeannette
Published: July 2020

The sensitivity of pigs to deoxynivalenol (DON) might be influenced by systemic inflammation (SI) which impacts liver. Besides following acute-phase proteins, our aim was to investigate both the hepatic fractional albumin (ALB) synthesis rate (FSR) and the ALB concentration as indicators of ALB metabolism in presence and absence of SI induced by LPS via pre- or post-hepatic venous route. Each infusion group was pre-conditioned either with a control diet (CON, 0.12 mg DON/kg diet) or with a DON-contaminated diet (DON, 4.59 mg DON/kg diet) for 4 wk. A depression of ALB FSR was observed 195 min after LPS challenge, independent of feeding group or LPS application route, which was not paralleled by a down-regulated ALB mRNA expression but by a reduced availability of free cysteine. The drop in ALB FSR only partly explained the plasma ALB concentrations which were more depressed in the DON-pre-exposed groups, suggesting that ALB levels are influenced by further mechanisms. The abundances of haptoglobin, C-reactive protein, serum amyloid A, pig major acute-phase protein, fibrinogen and LPS-binding protein mRNA were up-regulated upon LPS stimulation but not accompanied by increases in the plasma concentrations of these proteins, pointing at an imbalance between synthesis and consumption.
SGLT inhibitors in type 1 diabetes: weighing efficacy and side effects
Authors: Janssens Birgit , Caerels Simon , Mathieu Chantal
Published: July 2020

Even before sodium-glucose cotransporter inhibitors (SGLTi) became popular agents for the treatment of people with type 2 diabetes (T2DM), clinicians had explored their potential as adjunct therapies in type 1 diabetes (T1DM). Several trials have demonstrated improved glycemic control (compared with placebo) and a decrease in glucose variability with a clinically relevant increase of time in range. In addition, weight loss and decreased systolic blood pressure are observed. The magnitude of the effects observed depends on the type of SGLTi, the dose administrated, and the duration of observation in the studies. As seen in T2DM, there was an increase in the risk of urogenital mycotic infections, but no increase in the risk of severe hypoglycemia. However, concerns arose regarding an increase in incidence of diabetic ketoacidosis. Mitigation strategies, including careful patient selection, extensive education of patients and (para)medical personnel, adequate insulin dose titration, and the adoption of a ketone-centered approach, are suggested.

In different areas of the world, SGLTi are approved for use in T1DM with restrictions concerning patient selection and SGLTi dose. Real-world data on the effect of introduction of SGLTi in people with T1DM will yield insight on the robustness of glycemic effects over time, and allow us to determine whether the positive risk–benefit profile observed in clinical trials can be translated to the real world.
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.
An Interdisciplinary Approach for Management of Trauma-induced External Root Resorption: A Case Report with a Two-Year Follow-up
Authors: Prathap M. S. , Prathap Sruthy
Published: July 2020

Root resorption is largely pathologic and known to be initiated by several factors, including pulpal necrosis, trauma, periodontal treatment, orthodontic treatment, and bleaching agents. Incorrect diagnosis can lead to improper management and tooth loss. The treatment should involve the complete suppression of all the resorptive factors and the reconstruction of the defect using a suitable restorative material. The resorptive defect is often detected by the routine radiographic examination. A characteristic radiopaque line generally separates the image of the lesion from that of the root canal because the pulp remains protected by a thin layer of predentin until late in the process. Histopathologically, the lesions contain fibrovascular tissue with resorbing clastic cells adjacent to the dentin surface. Advanced lesions may also display fibro-osseous characteristics with deposition of ectopic bone-like calcifications. This case report presents extensive root resorption in the maxillary left lateral incisor and left canine in a 35-year-old patient. The defect was identified during the routine radiographic examination. The patient revealed a history of trauma 15 years back. Following the examination, the teeth were found to be vital and associated with the moderately deep periodontal pocket in the interdental region. The teeth were managed endodontically, and the resorption defect was restored with a biocompatible material after surgically elevating a flap. Periodontal management was also performed simultaneously by the surgical debridement of the area. Six-month postoperative radiograph revealed an arrest of the resorption and healing of the periodontal defect. Hence, an interdisciplinary management involving endodontic as well as periodontal treatment was performed that helped in saving the teeth with poor prognosis.
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

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

Background

Autosomal 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.

Methods

The 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.

Discussion

The 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 registration

NCT02848521.

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

Background

Phenylketonuria (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.

Methods

The 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.

Result

Finally, 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.

Conclusion

The 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

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

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.
Scoping review and bibliometric analysis of Big Data applications for Medication adherence: an explorative methodological study to enhance consistency in literature
Authors: Pirri Salvatore , Lorenzoni Valentina , Turchetti Giuseppe
Published: July 2020

Background

Medication adherence has been studied in different settings, with different approaches, and applying different methodologies. Nevertheless, our knowledge and efficacy are quite limited in terms of measuring and evaluating all the variables and components that affect the management of medication adherence regimes as a complex phenomenon. The study aim is mapping the state-of-the-art of medication adherence measurement and assessment methods applied in chronic conditions. Specifically, we are interested in what methods and assessment procedures are currently used to tackle medication adherence. We explore whether Big Data techniques are adopted to improve decision-making procedures regarding patients’ adherence, and the possible role of digital technologies in supporting interventions for improving patient adherence and avoiding waste or harm.

Methods

A scoping literature review and bibliometric analysis were used. Arksey and O’Malley’s framework was adopted to scope the review process, and a bibliometric analysis was applied to observe the evolution of the scientific literature and identify specific characteristics of the related knowledge domain.

Results

A total of 533 articles were retrieved from the Scopus academic database and selected for the bibliometric analysis. Sixty-one studies were identified and included in the final analysis. The Morisky medication adherence scale (36%) was the most frequently adopted baseline measurement tool, and cardiovascular/hypertension disease, the most investigated illness (38%). Heterogeneous findings emerged from the types of study design and the statistical methodologies used to assess and compare the results.

Conclusions

Our findings reveal a lack of Big Data applications currently deployed to address or measure medication adherence in chronic conditions. Our study proposes a general framework to select the methods, measurements and the corpus of variables in which the treatment regime can be analyzed.
LncRNA HOTAIR induces sunitinib resistance in renal cancer by acting as a competing endogenous RNA to regulate autophagy of renal cells
Authors: Li Dechao , Li Changfu , Chen Yongsheng , Teng Lichen , Cao Yan , Wang Wentao , Pan Hongxin , Xu Yongpeng , Yang Dan
Published: July 2020

Background

Cell autophagy has been proposed to be involved in drug resistance therapy. However, how the long non-coding RNA (lncRNA) reduces risks of drug resistance in renal cancer (RC) cells needs a thorough inquiry. This study was assigned to probe the effect and mechanism of HOTAIR on sunitinib resistance of RC.

Methods

Clinical RC tissues and para-carcinoma tissues were obtained to detect the expressions of miR-17-5p, HOTAIR and Beclin1. Sunitinib-resistant cells (786-O-R and ACHN-R) were constructed using parental RC cells (786-O and ACHN). The resistance of 786-O-R and ACHN-R cells to sunitinib was examined. Western blot and qRT-PCR were assayed to obtain the expressions of miR-17-5p, HOTAIR and Beclin1. The effects of HOTAIR knockdown or miR-17-5p overexpression/knockdown on cell autophagy and sunitinib resistance were measured by MDC staining, immunofluorescence and Western blot. The sensitivity of RC cells to sunitinib and change in cell clone formation after sunitinib treatment were assessed by CCK-8 assay and colony formation assay, respectively. The relationships among HOTAIR, miR-17-5p and Beclin1 were verified by dual-luciferase reporter gene and RIP assay. The role of HOTAIR knockdown in sunitinib resistance was verified in nude mice.

Results

HOTAIR expression in sunitinib-resistant cells is higher than that in parental cells. Knockdown of HOTAIR in sunitinib-resistant cells lead to refrained sunitinib resistance and cell autophagy both in vivo and in vitro. Activation of autophagy could raise resistance to sunitinib in RC cells, while inhibition of autophagy could improve the sensitivity of sunitinib-resistant cells to sunitinib. HOTAIR could compete with miR-17-5p to regulate Beclin1 expression. Knockdown of miR-17-5p in parental cells increases cell resistant to sunitinib, and overexpression of miR-17-5p in sunitinib-resistant cells increases cell sensitive to sunitinib.

Conclusion

HOTAIR negatively targets miR-17-5p to activate Beclin1-mediated cell autophagy, thereby enhancing sunitinib resistance in RC cells.
Clinical and molecular basis of hepatocerebral mitochondrial DNA depletion syndrome in Japan: evaluation of outcomes after liver transplantation
Authors: Shimura Masaru , Kuranobu Naomi , Ogawa-Tominaga Minako , Akiyama Nana , Sugiyama Yohei , Ebihara Tomohiro , Fushimi Takuya , Ichimoto Keiko , Matsunaga Ayako , Tsuruoka Tomoko , Kishita Yoshihito , Umetsu Shuichiro , Inui Ayano , Fujisawa Tomoo , Tanikawa Ken , Ito Reiko , Fukuda Akinari , Murakami Jun , Kaji Shunsaku , Kasahara Mureo , Shiraki Kazuo , Ohtake Akira , Okazaki Yasushi , Murayama Kei
Published: July 2020

Background

Hepatocerebral mitochondrial DNA depletion syndrome (MTDPS) is a disease caused by defects in mitochondrial DNA maintenance and leads to liver failure and neurological complications during infancy. Liver transplantation (LT) remains controversial due to poor outcomes associated with extrahepatic symptoms. The purposes of this study were to clarify the current clinical and molecular features of hepatocerebral MTDPS and to evaluate the outcomes of LT in MTDPS patients in Japan.

Results

We retrospectively assessed the clinical and genetic findings, as well as the clinical courses, of 23 hepatocerebral MTDPS patients from a pool of 999 patients who were diagnosed with mitochondrial diseases between 2007 and 2019. Causative genes were identified in 18 of 23 patients: MPV17 (n = 13), DGUOK (n = 3), POLG (n = 1), and MICOS13 (n = 1). Eight MPV17-deficient patients harbored c.451dupC and all three DGUOK-deficient patients harbored c.143-307_170del335. The most common initial manifestation was failure to thrive (n = 13, 56.5%). The most frequent liver symptom was cholestasis (n = 21, 91.3%). LT was performed on 12 patients, including nine MPV17-deficient and two DGUOK-deficient patients. Among the 12 transplanted patients, five, including one with mild intellectual disability, survived; while seven who had remarkable neurological symptoms before LT died. Five of the MPV17-deficient survivors had either c.149G > A or c.293C > T.

Conclusions

MPV17 was the most common genetic cause of hepatocerebral MTDPS. The outcome of LT for MTDPS was not favorable, as previously reported, however, patients harboring MPV17 mutations associated with mild phenotypes such as c.149G > A or c.293C > T, and exhibiting no marked neurologic manifestations before LT, had a better prognosis after LT.
Characterization of a Monanema nematode in Ixodes scapularis
Authors: Tokarz Rafal , Tagliafierro Teresa , Ian Lipkin W. , Marques Adriana R.
Published: July 2020

Background

Metagenomic studies have revealed the presence of a filarial nematode in Ixodes scapularis. The phylogeny of this agent, and its potential for human infection, are unknown.

Methods

We used existing metagenomic data from I. scapularis to determine the phylogeny of this tick-associated nematode and employed quantitative PCR to determine if the presence of this agent had an effect on the burden of Borrelia burgdorferi. We also developed a Luciferase Immunoprecipitation System assay using the Av33 antigen as a target to investigate the presence of antibodies against this nematode in 128 serum specimens from patients with Lyme disease and babesiosis. To demonstrate assay utility, we used 15 sera from patients with onchocerciasis as controls.

Results

We show that this agent is a new species in the genus Monanema and its presence in vector ticks does not impact the burden of B. burgdorferi. We did not detect IgG antibodies to this agent in 127 of 128 sera from patients with Lyme disease or babesiosis. One sample had reactivity above the threshold, but at the low-level equivalent to the least reactive onchocerciasis sera. This low positive signal could be a result of cross-reacting antibodies, antibodies from a previous infection with a filarial nematode, or, less likely, a exposure to the Ixodes scapularis-associated nematode.

Conclusions

We found no evidence that this nematode contributes to the spectrum of human tick-borne infections.
Validation for using electronic health records to identify community acquired pneumonia hospitalization among people with and without HIV
Authors: Rodriguez-Barradas Maria C. , McGinnis Kathleen A. , Akgün Kathleen , Tate Janet P. , Brown Sheldon T. , Butt Adeel A. , Fine Michael , Goetz Matthew Bidwell , Graber Christopher J. , Huang Laurence , Rimland David , Justice Amy , Crothers Kristina
Published: July 2020

Background

Cohort studies identifying the incidence, complications and co-morbidities associated with community acquired pneumonia (CAP) are largely based on administrative datasets and rely on International Classification of Diseases (ICD) codes; however, the reliability of ICD codes for hospital admissions for CAP in people with HIV (PWH) has not been systematically assessed.

Methods

We used data from the Veterans Aging Cohort Study survey sample (N = 6824; 3410 PWH and 3414 uninfected) to validate the use of electronic health records (EHR) data to identify CAP hospitalizations when compared to chart review and to compare the performance in PWH vs. uninfected patients. We used different EHR algorithms that included a broad set of CAP ICD-9 codes, a set restricted to bacterial and viral CAP codes, and algorithms that included pharmacy data and/or other ICD-9 diagnoses frequently associated with CAP. We also compared microbiologic workup and etiologic diagnosis by HIV status among those with CAP.

Results

Five hundred forty-nine patients were identified as having an ICD-9 code compatible with a CAP diagnosis (13% of PWH and 4% of the uninfected, p < 0.01). The EHR algorithm with the best overall positive predictive value (82%) was obtained by using the restricted set of ICD-9 codes (480–487) in primary position or secondary only to selected codes as primary (HIV disease, respiratory failure, sepsis or bacteremia) with the addition of EHR pharmacy data; this algorithm yielded PPVs of 83% in PWH and 73% in uninfected (P = 0.1) groups. Adding aspiration pneumonia (ICD-9 code 507) to any of the ICD-9 code/pharmacy combinations increased the number of cases but decreased the overall PPV. Allowing COPD exacerbation in the primary position improved the PPV among the uninfected group only (to 76%). More PWH than uninfected patients underwent microbiologic evaluation or had respiratory samples submitted.

Conclusions

ICD-9 code-based algorithms perform similarly to identify CAP in PLWH and uninfected individuals. Adding antimicrobial use data and allowing as primary diagnoses ICD-9 codes frequently used in patients with CAP improved the performance of the algorithms in both groups of patients. The algorithms consistently performed better among PWH.
Global research status and trends of UKA for knee osteoarthritis: a bibliometric analysis
Authors: Liu Peidong , Zhang Chen , Lu Zhan , Feng Jiangfeng , Xu Wenjie , Yang Ziquan
Published: July 2020

Objective

As an alternative of knee-protection surgery, unicompartmental knee arthroplasty has been widely used for the treatment of knee osteoarthritis and has achieved good clinical results. However, reports on its data and trend are scanty. This article reviewed current status and trend in the research of UKA, and compared different regions, organizations and authors in terms of their contributions to the field.

Methods

The literature on UKA ranging from 2009 to 2019 was searched in the “Web of Science” database, and the search results were visually presented by using Excel and VOS-viewer software packages, and the status quo and development trends of relevant studies were analyzed.

Results

A total of 1264 articles on UKA were identified, of which 330 were the larger studies conducted in the United States. The institution that published most papers was Oxford University, with a total of 109 papers published. MURRAY DW was the largest contributor in this field. The National Institutes of Health was the largest funding agencies of the UKA. Studies could be divided into six clusters in terms of prosthesis design, follow-up investigation, OA etiology, hip-knee association, joint replacement registration, and computer navigation. “Computer-aided navigation” and “gait analysis” promise to be future hot spots in the field of UKA research.

Conclusion

Global trend analysis suggests that UKA research is gradually deepening and the number of papers has been on the rise. The USA was the largest contributor to this field. More research effort should be directed to “Computer-aided navigation”and “gait analysis”, which might be the popular topics in the UKA field in not very distant future.
Additional diagnostic role of MRI spectroscopy, diffusion and susceptibility imaging in differentiation of CPA masses: our experience with emphasis on schwannomas and meningiomas
Authors: Khaled Marwa , Moghazy Khaled , Elsaadany Waleed , Eissa Lamya
Published: July 2020

Background

CPA masses are uncommon lesions and usually have quite distinctive imaging features. Still, diagnosis can be challenging in some cases, carrying a significant impact on the choice of treatment and surgical approach. The purpose of this study was to validate the usefulness of MRI spectroscopy, diffusion, and susceptibility in the characterization of CPA masses with the emphasis on the two commonest lesions: schwannomas and meningiomas.

Results

The study included a total of 27 cases: schwannomas (n= 12), meningiomas (n= 7), epidermoid cysts (n= 2), two chondrosarcomas (n= 2), arachnoid cyst (n= 1), glomus tumor (n= 1), a meningeal metastasis (n= 1), and an endolymphatic sac tumor (n= 1). DWI revealed: eight lesions showed low ADC (<1 × 10−3 mm2/s), 15 lesions with intermediate ADC values (1–1.8 × 10−3 mm2/s), and 4 lesions had high ADC (>1.8 × 10−3 mm2/s.) Meningiomas showed low to intermediate ADC values while schwannomas showed intermediate to high ADC values. A cut-off ADC value of (1 × 10−3 mm2/s) is statistically significant in the differentiation of meningioma from schwannoma. A myoinositol peak was in all 12 schwannomas and single meningioma while 6 meningiomas displayed alanine peak, with a very good statistical significance. Remaining lesions revealed non-specific spectra. SWI made in 18 lesions revealed signal voids in three schwannomas and glomus.

Conclusions

Though MRI features of CPA masses are distinctive in most clinical settings; MRI spectroscopy, diffusion, and susceptibility can provide highly informative additional data in problematic cases. An intermediate to high ADC value plus myoinositol peak and signal voids of micro-bleeds are highly suggestive of schwannomas. This is in contrary to meningiomas displaying low to intermediate ADC and an alanine peak with no micro-bleeds. The less common lesions revealed non-specific data.