bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunosuppressive Drug-Associated Adverse Event Profiles in De Novo Kidney Transplant Recipients Receiving Everolimus and Reduced Tacrolimus Doses
Authors: Miranda Tamiris A. , Felipe Claudia R. , Santos Renato H. N. , Medina Pestana Jose O. , Tedesco-Silva Junior Helio 
Published: July 2020

Background:
The safety of immunosuppressive regimens is influenced by the induction agent, maintenance drug combination, and prophylactic strategy for cytomegalovirus (CMV) infection. Herein, this safety analysis compares rabbit antithymocyte globulin (r-ATG) or basiliximab (BAS) combined with everolimus (EVR) versus BAS combined with mycophenolate sodium (MPS) in kidney transplant recipients receiving tacrolimus, prednisone, and preemptive CMV therapy.

Methods:
In this single-center, prospective, randomized study, adverse events (AEs), serious AEs (SAEs), viral infections, laboratory abnormalities, dose reductions, and temporary or permanent discontinuation of the immunosuppressant were compared among patients receiving r-ATG/EVR (n = 85), BAS/EVR (n = 102), and BAS/MPS (n = 101).

Results:
A total of 2741 AEs and 344 SAEs were observed. There were no differences in the proportion of patients with at least one AE (96% versus 98% versus 96%, respectively; P > 0.05). The proportion of patients with at least one SAE was highest in the BAS/MPS group (33% versus 48% versus 69%, respectively; P < 0.05). This difference was due primarily to a high incidence of CMV infection in the BAS/MPS group (4.7% versus 10.8% versus 37.6%, respectively). The incidence of mild/moderate abnormalities in creatinine, cholesterol, and triglyceride levels was higher in both EVR groups. The cumulative freedom from dose reduction or treatment discontinuation due to an AE was higher in both EVR groups than in the BAS/MPS group (89.2% versus 92.8% versus 76.3%, respectively, P = 0.003). There was no difference in the incidence of biopsy-confirmed acute rejection (9.4% versus 18.6 versus 15.8%, respectively; P = 0.403).

Conclusions:
This analysis suggests that r-ATG induction combined with EVR is associated with a comparable incidence of acute rejection, lower incidence of CMV infection, and fewer changes in initial immunosuppressive regimen due to AEs in kidney transplant recipients receiving tacrolimus, prednisone, and preemptive CMV therapy.
ASSOCIATION BETWEEN DOME-SHAPED MACULA AND POSTERIOR STAPHYLOMA IN HIGHLY MYOPIC EYES INVESTIGATED BY ULTRA-WIDEFIELD OPTICAL COHERENCE TOMOGRAPHY
Authors: Saito Reina , Shinohara Kosei , Tanaka Noriko , Takahashi Hiroyuki , Yoshida Takeshi , Ohno-Matsui Kyoko 
Published: July 2020

Purpose:
To investigate the relationship between dome-shaped maculas (DSMs) and posterior staphylomas in highly myopic eyes.

Methods:
Five hundred and eleven eyes of 291 patients with high myopia (refractive error ≤−8.0 diopters or axial length ≥26.5 mm) were examined by ultra-widefield swept-source optical coherence tomography (UWF-OCT). Posterior staphylomas were identified by detecting the staphyloma edges in the UWF-OCT images.

Results:
Eighty-two eyes of the 511 highly myopic eyes had a DSM, and a posterior staphyloma was observed in 45 of 82 eyes with a DSM (54.9%) and in 301 of 429 eyes (70.2%) without a DSM. The incidence of staphylomas was significantly lower in eyes with a DSM than those without a DSM (P = 0.007). The wide macular type of staphyloma was the predominant type in eyes with a DSM (31/45 eyes; 68.9%), whereas the narrow macular type and wide macular type of staphylomas were present almost equally in the eyes without a DSM.

Conclusion:
The lack of staphylomas in 45% of eyes with a DSM suggests that DSMs form independently from posterior staphylomas. Dome-shaped maculas tend to occur in eyes with a large expansion of the posterior fundus and should be considered a posterior scleral curvature abnormality.
The Effects of Nicotine on Cortical Excitability After Exercise
Authors: Zandonai Thomas , Pizzolato Fabio , Tam Enrico , Bruseghini Paolo , Chiamulera Cristiano , Cesari Paola 
Published: July 2020

Abstract

Purpose
The use of smokeless tobacco/nicotine products is common among athletes, but clear evidence for their positive or negative effect on sports performance is lacking. Nicotine is a psychoactive substance involved in numerous neuronal processes including cortical excitability. The aim of this study was to evaluate its effect on cortical excitability associated with aerobic exercise in nicotine-naive healthy volunteers.

Methods
Ten nicotine-naive healthy volunteers were recruited for this double-blind, randomized, crossover study to compare the effect of snus (8 mg nicotine), an oral, smokeless tobacco product, to placebo on cortical excitability before and after aerobic exercise. Transcranial magnetic stimulation (TMS) was used to measure changes in corticomotor excitability (motor-evoked potentials, MEPs) and electromyography of leg muscles during maximal voluntary contractions (MVC) to assess changes in muscle contractions. Before and after aerobic exercise and with or without nicotine treatment, MEPs and MVCs were measured.

Results
Analysis of TMS data showed lower motor cortex activation (lower MEP amplitude) after snus administration compared with placebo, whereas electromyography data showed no difference in muscle contraction between snus and placebo treatment.

Conclusions
These findings suggest a general reduction in cortical excitability, without no relevant effect on physical performance.
Advances in lung transplantation for interstitial lung diseases
Authors: De Sadeleer Laurens J. , Verleden Stijn E. , Vos Robin , Van Raemdonck Dirk , Verleden Geert M. 
Published: July 2020

Purpose of review
Lung transplantation (LTx) is increasingly used as ultimate treatment modality in end-stage interstitial lung diseases (ILDs). This review aims to give an overview of the latest evolutions in this field.

Recent findings
In the last two years, important new findings regarding LTx outcomes in specific ILD entities have been reported. More data are available on optimization of pre-LTx management of ILD patients especially with regard to pretransplant antifibrotic treatment.

Summary
LTx is the only treatment option with curative intent for ILDs and is increasingly used for this indication. Several studies have now reported adequate outcomes in different ILD entities, although outcome is shown to be affected by underlying telomeropathies. As new studies could not replicate inferior survival with single compared with double LTx, both options remain acceptable. ILD specialists can beneficially impact on post-LTx outcome by optimizing pre-LTx management: corticosteroids should be avoided, antifibrotics should be initiated whenever possible and BMI and nutritional status optimized, rehabilitation and depression-screening strategies should be implemented in all LTx candidates, as these interventions may all improve postlung transplant survival.
Recent advances in sarcoidosis genomics: epigenetics, gene expression, and gene by environment (G × E) interaction studies
Authors: Garman Lori , Montgomery Courtney G. , Rivera Natalia V. 
Published: July 2020

Purpose of review
We aim to review the most recent findings in genomics of sarcoidosis and highlight the gaps in the field.

Recent findings
Original explorations of sarcoidosis subphenotypes, including cases associated with the World Trade Center and ocular sarcoidosis, have identified novel risk loci. Innovative gene--environment interaction studies utilizing modern analytical techniques have discovered risk loci associated with smoking and insecticide exposure. The application of whole-exome sequencing has identified genetic variants associated with persistent sarcoidosis and rare functional variations. A single epigenomics study has provided background knowledge of DNA methylation mechanisms in comparison with gene expression data. The application of machine-learning techniques has suggested new drug repositioning for the treatment of sarcoidosis. Several gene expression studies have identified prominent inflammatory pathways enriched in the affected tissue.

Summary
Certainly, sarcoidosis research has recently advanced in the exploration of disease subphenotypes, utilizing novel analytical techniques, and including measures of clinical variation. Nevertheless, large-scale and diverse cohorts investigated with advanced sequencing methods, such as whole-genome and single-cell RNA sequencing, epigenomics, and meta-analysis coupled with cutting-edge analytic approaches, when employed, will broaden and translate genomics findings into clinical applications, and ultimately open venues for personalized medicine.
Updates in diagnosis of the inherited platelet disorders
Authors: Lambert Michele P. 
Published: July 2020

Purpose of review
To provide a comprehensive update on the current available methodologies and techniques for diagnosis of inherited platelet disorders (IPD).

Recent findings
The contributions of many groups have resulted in the significant progress in the molecular diagnosis of IPD including the identification of many genes responsible for the various phenotypes. The widespread use and availability of next-generation sequencing has brought to the forefront ethical challenges associated with nontargeted sequencing as well as provided us with novel variants to functionally validate. These requirements have driven the development of novel tools for functional assessment of platelets, although none of the novel techniques beyond sequencing have yet taken clinical hold.

Summary
Much work is ongoing on functional and molecular assessment of platelet disorders and the incorporation of combined assessments is likely to yield the highest diagnostic results.
Diagnosing and Managing Sacroiliac Joint Pain
Authors: Gusfa Donald , Bashir Daniyal A. , Saffarian Mathew R. 
Published: July 2020

Abstract
Sacroiliac joint pain commonly occurs because of anatomic disruption within the joint. Sacroiliac joint pain and sacroiliac joint mimics create a broad differential, adding difficulty to diagnosis. Clinically, this disruption presents with a mobility limitation relative to baseline and sharp pain inferolateral to the posterior superior iliac spine. While attempting to rule out other causes of low back pain, provocation tests such as FABRE, distraction, thigh thrust, sacral compression, Gaenslen’s, and sacral thrust can be a useful diagnostic tool for the diagnosis of sacroiliac joint pain. Although recently, the provocation tests’ validity has been challenged. Currently, the most accurate way to assess sacroiliac joint pain is with image-guided injections of local anesthetic. Pain reduction after the injection indicates the pain originating from the sacroiliac joint. Once confirmed, it is recommended to use a patient-centered approach that focuses on pain control, followed by restoration of function through noninvasive measures such as therapeutic exercise, manual medicine, sacroiliac joint belts, and orthotics. If these noninvasive procedures have not provided adequate treatment, then more invasive procedures should be considered.
Price, Cost, and Value of Cancer Medicines
Authors: Rothenberg Mace L. , McCarthy Justin , Holmes Patrick 
Published: July 2020

Abstract
More than 1.8 million cancer diagnoses will be made in 2020 driving substantial health and economic burden for patients. The financial impact of out-of-pocket payments for hospital stays, outpatient services, physician appointments, and prescription drugs is a particular challenge. At the same time, the treatment of cancer is undergoing substantial transformation with growing benefits for patients. The complex factors contributing to the economic burden must be addressed so that patients have broad access to innovative oncology medicines both today and tomorrow. There are 2 parallel actions that are needed to drive broad reductions in costs while not putting at risk the incredible potential innovation awaiting these same patients: (i) the private sector must work together across the health care sector to accelerate innovative value-based partnerships; and (2) policymakers need to drive policy reforms that help ease out-of-pocket costs and remove barriers to and enable scaling of value-based care.
Bending Versus Transforming the Drug Cost Curve
Authors: Major Ajay , Polite Blase N. 
Published: July 2020

Abstract
There is increasing consensus that comprehensive reforms are needed to curb the rising costs of specialty drugs and growing bipartisan agreement on the basic principles that these reforms must address (1) constraints on yearly inflation of drug prices, (2) limits on practices to extend patents and restrict generic competition, (3) increased transparency of rebates provided by pharmaceutical companies to pharmacy benefit managers and insurance companies, and (4) caps on the total yearly out-of-pocket costs for Medicare patients. While such reforms will improve the current system, they are unlikely to be truly transformative. Transformative change requires that all the relevant stakeholders be forced, by a legislative or administrative mandate, to come to an agreement on value. Whether federal policy makers have the will to do so will determine whether we truly change the trajectory of the currently unsustainable drug cost curve.
Marginal Zone Lymphomas
Authors: Bertoni Francesco , Rossi Davide , Raderer Markus , Zucca Emanuele 
Published: July 2020

AbstractThere are three different marginal zone lymphoma (MZLs) entities: the extranodal MZL of mucosa- associated lymphoid tissue, the splenic MZL, and the nodal MZL. The 3 MZLs share common lesions (trisomies of chromosomes 3 and 18, deletions at 6q23), and alterations of the nuclear factor κB pathway are frequent events in all of them, but they also differ in the presence of recurrent translocations, mutations affecting the NOTCH pathway, and the transcription factor Kruppel-like factor 2 (KLF2)or the receptor-type protein tyrosine phosphatase delta (PTPRD). This review outlines the most recent and main advances in our understanding of the genetics and biology of MZLs and summarizes the clinical activity of the novel therapeutic approaches targeting the main druggable pathways. The current principles of the standard management of MZL at different anatomic sites are also discussed.
Improving Patient Handoffs and Transitions through Adaptation and Implementation of I-PASS Across Multiple Handoff Settings
Authors: Blazin Lindsay J. , Sitthi-Amorn Jitsuda , Hoffman James M. , Burlison Jonathan D. 
Published: July 2020

Introduction:Communication failures are common root causes of serious medical errors. Standardized, structured handoffs improve communication and patient safety. I-PASS is a handoff program that decreases medical errors and preventable patient harm. The I-PASS mnemonic is defined as illness severity, patient information, action list, situational awareness and contingency plans, and synthesis by receiver. I-PASS was validated for physician handoffs, yet has the potential for broader application. The objectives of this quality improvement initiative were to adapt and implement I-PASS to handoff contexts throughout a pediatric hospital, including those with little or no known evidence of using I-PASS.Methods:We adapted and implemented I-PASS for inpatient nursing bedside report, physician handoff, and imaging/procedures handoff. Throughout the initiative, end-user stakeholders participated as team members and informed the adaptation of the I-PASS mnemonic, handoff processes, written handoff documents, and performance evaluation methods. Peers observed handoffs, scored performance, and provided formative feedback. Adherence to I-PASS was the primary outcome. We also evaluated changes in handoff-related error frequency and clinician attitudes about the effects of I-PASS on personal and overall handoff performance.Results:All 5 elements of the I-PASS mnemonic were used in 87% of inpatient nursing, 76% of physician, and 89% of imaging/procedures handoffs. Inpatient nurses reported reductions in handoff-related errors following I-PASS implementation. Clinicians across most handoff settings reported that using I-PASS improved both general and personal handoff performance.Conclusions:I-PASS is adaptable to many handoff settings, which expands its potential to improve patient safety. Clinicians reported reductions in errors and improvements in handoff performance. We identified broad institutional support, customized written handoff documents, and peer observations with feedback as crucial factors in sustaining I-PASS usage.
HIV and risk of dementia in older veterans
Authors: Bobrow Kirsten , Xia Feng , Hoang Tina , Valcour Victor , Yaffe Kristine 
Published: July 2020

Objective:
People living with HIV (PLWH) may be at an increased risk for dementia as they age. Surprisingly, it remains unclear whether PLWH have a higher risk of developing dementia in late life than those without. We explored whether HIV-infection is associated with incident dementia diagnosis in older U.S. veterans accounting for potential confounders and competing risk of death.

Methods:
We included 1114 veterans diagnosed with HIV, ages at least 55 years (mean = 62 years, SD = 6), followed in the Veterans Health Administration healthcare system from 2004 to 2015, and a propensity-matched comparison group (n = 1114) without HIV. HIV and dementia diagnoses were determined using electronic medical records. Using Fine-Gray proportional hazards models, we examined whether HIV status was associated with a greater risk of incident dementia.

Results:
During follow-up (mean = 7 years, SD = 4 from date of HIV diagnosis), 5% of veteran PLWH developed dementia compared with 3% without (P = 0.01). Accounting for the competing risk of death and adjusted for demographics, substance use, education and income, PLWH remained 50% more likely to receive a dementia diagnosis [adjusted hazard ratio (aHR) = 1.50, 95% confidence interval 0.96–2.35]. Although combination antiretroviral therapy (cART) exposure was associated with an increased risk of incident dementia, this was driven by differences in illness severity as captured by CD4+ cell count. There was no evidence of a differential effect by cART class.

Conclusion:
In a cohort of older USA veterans, HIV infection increased risk of dementia by 50%, while exposure to cART did not offset this risk. It is critical to understand the mechanisms by which HIV increases risk for developing dementia in later life.
Coronavirus disease 2019 attack rate in HIV-infected patients and in preexposure prophylaxis users
Authors: Charre Caroline , Icard Vinca , Pradat Pierre , Brochier Corinne , Lina Bruno , Chidiac Christian , Cotte Laurent 
Published: July 2020

Objective:
A new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) emerged in China during late 2019 and resulted in the coronavirus disease 2019 (COVID-19) pandemic which peaked in France in March–April 2020. Immunodeficiency, precariousness and promiscuity could increase the risk of COVID-19 in HIV-infected patients and in preexposure prophylaxis (PrEP) users. No epidemiological data are available in these two populations. We report COVID-19 attack rate in HIV-infected patients and in PrEP users in the Rhône department, France, and compared it with the general population.

Design:
Retrospective analysis of a laboratory database.

Methods:
COVID-19 testing strategy in France was centered on symptomatic infections, hospitalized patients and symptomatic healthcare workers while most asymptomatic cases were not confirmed. SARS-CoV-2 positivity rate on PCR assays and COVID-19 attack rate were determined in HIV-infected patients and in PrEP users. COVID-19 attack rate in the general population was estimated from health authorities’ database and demographic data. A corrected attack rate taking into account the laboratory representativeness was calculated.

Results:
From March to April 2020, 24 860 samples from 19 113 patients (HIV-infected 77, PrEP users 27, others 19 009) were assessed for SARS-CoV-2 PCR assay. The positivity rate appeared similar in HIV-infected patients (15.6%), in PrEP users (14.8%) and in other patients (19.1%). The crude/corrected COVID-19 attack rate appeared similar in HIV-infected patients (0.31/0.38%) and in PrEP users (0.38/0.42%), and of the same order as the estimated attack rate in the general population (0.24%).

Conclusion:
The risk of symptomatic COVID-19 in France appeared similar in HIV-infected patients and in PrEP users compared with the general population.
Reducing the Discussion Divide by Digital Questionnaires in Health Care Settings: Disruptive Innovation for HIV Testing and PrEP Screening
Authors: John Steven A. , Petroll Andrew E. , Walsh Jennifer L. , Quinn Katherine G. , Patel Viraj V. , Grov Christian 
Published: July 2020

Background:
Health care provider assessment of patient sexual behavior and substance use is essential for determining appropriate prevention interventions—including HIV pre-exposure prophylaxis (PrEP)—for sexual minority men (SMM). We sought to explore acceptability and utility of using electronic surveys to conduct health behavior assessments in clinical settings among SMM.

Methods:
Among a US nationwide sample of SMM (n = 4187; mean age = 38.3 years; 60% white; 82% HIV-negative), we examined associations of demographics, recruitment venue, sexual behavior characteristics, and recent substance use with participants' comfort communicating verbally and through electronic survey with a health care provider about sexual and substance use behavior.

Results:
On average, SMM had greater comfort communicating through electronic survey vs. verbally. In our fully adjusted analysis, preference favoring electronic surveys more strongly than verbal communication differed by age (β = −0.07, P ≤ 0.001). SMM with a bachelor's degree or more (β = 0.04, P < 0.05), those recruited from nonclinical settings (β = 0.06, P ≤ 0.001), and those without primary care providers (β = 0.04, P < 0.05) favored electronic surveys more strongly in the fully adjusted multivariable model. SMM who reported any recent casual sex partners (β = 0.05, P < 0.01), those never tested for HIV (β = 0.03, P < 0.05), and HIV-negative/unknown men not on PrEP (compared with PrEP users; β = 0.09, P ≤ 0.001) also favored electronic surveys in the fully adjusted model.

Conclusions:
Reducing communication barriers by incorporating electronic surveys into patient assessments could help identify HIV testing and PrEP needs for SMM most susceptible to HIV acquisition. Nonetheless, no one screening strategy is likely to work for most SMM, and multiple approaches are needed.
Supportive and palliative care of adults with respiratory problems experiencing structural vulnerability from homelessness, prison or other criminal justice system involvement
Authors: Gardener Carole , Kuhn Isla , Micklewright Kerry , Farquhar Morag 
Published: July 2020

Purpose of review
This review seeks to identify the current prevalence of potentially life-limiting respiratory conditions among those who have experienced homelessness, incarceration or had criminal justice involvement, and current developments in, and barriers to, delivery of supportive and palliative respiratory care to these populations. These structurally vulnerable populations are known to be growing, their health behaviours more risky, and their morbidity and mortality higher, with evidence of accelerated ageing.

Recent findings
Most studies identified investigated prevalence of respiratory conditions, which were found to be high. In contrast, only one study directly explored supportive and palliative care (in a prison population) and none considered or addressed palliative and end-of-life needs of these populations, or mechanisms to address them. There was an absence of qualitative work and studies of the impact on, or role of, family, friends or informal networks.

Summary
There is a need for evidence-based interventions to reduce the risk of communicable respiratory conditions and a greater understanding of disease trajectories and management for these vulnerable populations, including provision of accessible appropriate supportive, palliative and end-of-life care.