ResearchPad - featured https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[TREC-COVID: rationale and structure of an information retrieval shared task for COVID-19]]> https://www.researchpad.co/article/elastic_article_12285 TREC-COVID is an information retrieval (IR) shared task initiated to support clinicians and clinical research during the COVID-19 pandemic. IR for pandemics breaks many normal assumptions, which can be seen by examining 9 important basic IR research questions related to pandemic situations. TREC-COVID differs from traditional IR shared task evaluations with special considerations for the expected users, IR modality considerations, topic development, participant requirements, assessment process, relevance criteria, evaluation metrics, iteration process, projected timeline, and the implications of data use as a post-task test collection. This article describes how all these were addressed for the particular requirements of developing IR systems under a pandemic situation. Finally, initial participation numbers are also provided, which demonstrate the tremendous interest the IR community has in this effort.

]]>
<![CDATA[Facedown Positioning Following Surgery for Large Full-Thickness Macular Hole]]> https://www.researchpad.co/article/elastic_article_8846 This randomized clinical trial examines the effect of postoperative facedown positioning on outcomes for large macular holes.

]]>
<![CDATA[Visualising the expansion and spread of coronavirus disease 2019 by cartograms]]> https://www.researchpad.co/article/Ne141e5cb-c20b-4aa3-93b7-6d2aa2787550

Coronavirus disease 2019 (COVID-19) has emerged as a growing focus of global attention and a critical factor in public-health decision making. Towards fighting the COVID-19 outbreak, countries worldwide and international organisations have taken various actions, including promoting the transparency of and public access to disease data. In such public communications, maps have played an important role in that a map is worth a thousand words. Most of these have taken the form of a choropleth map. Here, we propose employing cartograms to visualise both the expansion and spread of COVID-19. We designed a combination of six circular cartograms containing the data of confirmed cases every 48 hours from 24 January to 3 February 2020. Such a design conveys both spatial and temporal information more intuitively and efficiently, so it can be expected to facilitate better public participation in the fight against COVID-19.

]]>
<![CDATA[Epidemiologic Analysis of Respiratory Viral Infections Mainly in Hospitalized Children and Adults in a Midwest University Medical Center After the Implementation of a 14-Virus Multiplex Nucleic Acid Amplification Test]]> https://www.researchpad.co/article/Ndd0e6c15-3d67-4f88-abfb-3c22fa942081

Objectives: To investigate the etiology of viral respiratory tract infections mainly in hospitalized children and adults over a 12-month consecutive period after implementation of a 14-virus multiplex nucleic acid amplification test.

Methods: From January 2014 to January 2015, a total of 2,237 respiratory samples were analyzed with the US Food and Drug Administration–cleared eSensor Respiratory Viral Panel (GenMark Diagnostics, Carlsbad, CA).

Results: Of the 2,237 specimens tested, 788 specimens were positive for at least one virus, giving a positivity rate of 35.2%, and because of viral codetection, a total of 862 viral targets were identified. The age groups with the highest positivity rates were the 0- to 1-year (73.5%) and 2- to 6-year (78.4%) age groups. The overall viral codetection rate was 9.1%. Human rhinovirus (HRV) was the most prevalent respiratory virus found in children and adults. The peak of HRV seen in September 2014 represented a combination of HRV and enterovirus D68, 2014 epidemic respiratory infections.

Conclusion: The ability to detect a wider range of respiratory viruses gave us a better understanding of the etiology of respiratory infections in our population, particularly for HRV and enhanced our ability to detect viral coinfection.

]]>
<![CDATA[Estimated Worldwide Mortality Attributed to Secondhand Tobacco Smoke Exposure, 1990-2016]]> https://www.researchpad.co/article/N8277c00b-3735-47eb-9b17-88df3a287d1e

Key Points

Question

How many individuals who smoke are associated with the death of 1 individual who does not smoke but was exposed to secondhand smoke?

Findings

This cross-sectional epidemiologic assessment used Our World in Data to calculate how many individuals who smoked for a mean of 24 years were associated with the death of 1 individual who died of exposure to secondhand smoke; globally, this changed from 31.3 individuals who smoked in 1990 to 52.3 individuals who smoked in 2016.

Meaning

The findings of this study could help policy makers better understand the scale of harm associated with secondhand smoke and improve awareness in the general public.

]]>
<![CDATA[Vorasidenib (AG-881): A First-in-Class, Brain-Penetrant Dual Inhibitor of Mutant IDH1 and 2 for Treatment of Glioma]]> https://www.researchpad.co/article/N05be7e59-d085-452b-8bc6-cba82e09440f

ml9b00509_0005.jpg

Inhibitors of mutant isocitrate dehydrogenase (mIDH) 1 and 2 cancer-associated enzymes prevent the accumulation of the oncometabolite d-2-hydroxyglutarate (2-HG) and are under clinical investigation for the treatment of several cancers harboring an IDH mutation. Herein, we describe the discovery of vorasidenib (AG-881), a potent, oral, brain-penetrant dual inhibitor of both mIDH1 and mIDH2. X-ray cocrystal structures allowed us to characterize the compound binding site, leading to an understanding of the dual mutant inhibition. Furthermore, vorasidenib penetrates the brain of several preclinical species and inhibits 2-HG production in glioma tissue by >97% in an orthotopic glioma mouse model. Vorasidenib represents a novel dual mIDH1/2 inhibitor and is currently in clinical development for the treatment of low-grade mIDH glioma.

]]>
<![CDATA[Meroterpenoid Synthesis via Sequential Polyketide Aromatization and Radical Anion Cascade Triene Cyclization: Biomimetic Total Syntheses of Austalide Natural Products]]> https://www.researchpad.co/article/N6ccad151-4ffd-4abb-91ed-e8a347247290

jo9b00142_0010.jpg

The first total synthesis of five austalide natural products, (±)-17S-dihydroaustalide K, (±)-austalide K, (±)-13-deacetoxyaustalide I, (±)-austalide P, and (±)-13-deoxyaustalide Q acid, was accomplished via a series of biomimetic transformations. Key steps involved polyketide aromatization of a trans,trans-farnesol-derived β,δ-diketodioxinone into the corresponding β-resorcylate, followed by titanium(III)-mediated reductive radical cyclization of an epoxide to furnish the drimene core. Subsequent phenylselenonium ion induced diastereoselective cyclization of the drimene completed the essential carbon framework of the austalides to access (±)-17S-dihydroaustalide K, (±)-austalide K, and (±)-13-deacetoxyaustalide I via sequential oxidations. Furthermore, (±)-13-deacetoxyaustalide I could serve as a common intermediate to be derivatized into other related natural products, (±)-austalide P and (±)-13-deoxyaustalide Q acid, by functionalizing the cyclic lactone moiety.

]]>
<![CDATA[Intrathecal Drug Delivery Systems for Cancer Pain: An Analysis of a Prospective, Multicenter Product Surveillance Registry]]> https://www.researchpad.co/article/N5170dbed-0005-47eb-9a41-5b3ad362e1a8

BACKGROUND:

The safety and efficacy of intrathecal drug delivery systems (IDDSs) for the treatment of cancer-related pain have been demonstrated in randomized controlled clinical trials (RCTs). Despite positive evidence for this therapy, IDDS remains underutilized to treat cancer pain. Real-world registry data augment existing safety and effectiveness data and are presented here to broaden awareness of this therapeutic option, needed for adequate cancer-related pain treatment, and as a viable tool addressing concerns with systemic opioid use.

METHODS:

This prospective, long-term, multicenter (United States, Western Europe, and Latin America) registry started in 2003 to monitor the performance of SynchroMed Infusion Systems. Patient-reported outcomes were added in 2013. Before data acquisition, all sites obtained Ethics Committee/Institutional Review Board approval and written patient consent. The study was registered (NCT01524276 at clinicaltrials.gov) before patients were enrolled. Patients who provided informed consent were enrolled in the registry at initial IDDS implant or replacement.

RESULTS:

Through July 2017, 1403 patients with cancer pain were enrolled and implanted. The average (minimum/maximum) age of patients was 59 years (13/93 years), with 56.6% female. The most frequent cancer types were lung, breast, colon/rectal, pancreatic, and prostate. The majority of patients whose registry follow-up ended (87%; 1141/1311) were followed through death, with 4.3% (n = 57) exiting due to device explant or therapy discontinuation; the remaining 113 (8.6%) discontinued for reasons such as transfer of care, lost to follow-up, and site closure. Pain scores within the cohort of patients providing baseline and follow-up data improved significantly at 6 (P = .0007; n = 103) and 12 (P = .0026; n = 55) months compared to baseline, with EuroQol with 5 dimensions (EuroQol-5D) scores showing significant improvement at 6 months (P = .0016; n = 41). Infection requiring surgical intervention (IDDS explant, replacement, pocket revision, irrigation and debridement, etc) was reported in 3.2% of patients.

CONCLUSIONS:

Adequate and improved pain control in patients with cancer, even in advanced stages, with concurrent quality of life maintenance is attainable. Results from this large-scale, multicenter, single-group cohort supplement existing RCT data that support IDDS as a safe and effective therapeutic option with a positive benefit–risk ratio in the treatment of cancer pain.

]]>
<![CDATA[Clinical Effectiveness of Intravitreal Therapy With Ranibizumab vs Aflibercept vs Bevacizumab for Macular Edema Secondary to Central Retinal Vein Occlusion]]> https://www.researchpad.co/article/N8f28c822-11fb-4230-83c3-a2d1f8840b49

This randomized clinical trial compares the clinical effectiveness of intravitreal therapy with ranibizumab vs aflibercept vs bevacizumab for the management of macular edema secondary to central retinal vein occlusion.

]]>
<![CDATA[Alzheimer's disease pathology explains association between dementia with Lewy bodies and APOE‐ε4/TOMM40 long poly‐T repeat allele variants]]> https://www.researchpad.co/article/Nd17f15ba-f88c-465d-8167-a90a062a24c0

Introduction

The role of TOMM40-APOE 19q13.3 region variants is well documented in Alzheimer's disease (AD) but remains contentious in dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD).

Methods

We dissected genetic profiles within the TOMM40-APOE region in 451 individuals from four European brain banks, including DLB and PDD cases with/without neuropathological evidence of AD-related pathology and healthy controls.

Results

TOMM40-L/APOE-ε4 alleles were associated with DLB (ORTOMM40-L = 3.61; P value = 3.23 × 10−9; ORAPOE-ε4 = 3.75; P value = 4.90 × 10−10) and earlier age at onset of DLB (HRTOMM40-L = 1.33, P value = .031; HRAPOE-ε4 = 1.46, P value = .004), but not with PDD. The TOMM40-L/APOE-ε4 effect was most pronounced in DLB individuals with concomitant AD pathology (ORTOMM40-L = 4.40, P value = 1.15 × 10−6; ORAPOE-ε4 = 5.65, P value = 2.97 × 10−8) but was not significant in DLB without AD. Meta-analyses combining all APOE-ε4 data in DLB confirmed our findings (ORDLB = 2.93, P value = 3.78 × 10−99; ORDLB+AD = 5.36, P value = 1.56 × 10−47).

Discussion

APOE-ε4/TOMM40-L alleles increase susceptibility and risk of earlier DLB onset, an effect explained by concomitant AD-related pathology. These findings have important implications in future drug discovery and development efforts in DLB.

]]>
<![CDATA[Amyloid‐β oligomers suppress subunit‐specific glutamate receptor increase during LTP]]> https://www.researchpad.co/article/Nc7eaa483-4806-4c73-beaf-d13c7a0f09cd

Introduction

Amyloid-β oligomers (AβOs) are assumed to impair the ability of learning and memory by suppressing the induction of synaptic plasticity, such as long-term potentiation (LTP) in the early stage of Alzheimer's disease. However, the direct molecular mechanism of how AβOs affect excitatory synaptic plasticity remains to be elucidated.

Methods

In order to study the effects of AβOs on LTP-associated changes of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptor (AMPAR) movement, we performed live-cell imaging of fluorescently labeled AMPAR subunit GluA1 or GluA2 with total internal reflection fluorescence microscopy.

Results

Incubation of cultured hippocampal neurons with AβOs for 1–2 days inhibited the increase in GluA1 number and GluA1 exocytosis frequency in both postsynaptic and extrasynaptic membranes during LTP. In contrast, AβOs did not inhibit the increase in GluA2 number or exocytosis frequency.

Discussion

These results suggest that AβOs primarily inhibit the increase in the number of GluA1 homomers and suppress hippocampal LTP expression.

]]>
<![CDATA[Differing Modes of Biotic Connectivity within Freshwater Ecosystem Mosaics]]> https://www.researchpad.co/article/Nf75f7eab-6f34-4015-885c-af5ce71fa6b1

Abstract

We describe a collection of aquatic and wetland habitats in an inland landscape, and their occurrence within a terrestrial matrix, as a “freshwater ecosystem mosaic” (FEM). Aquatic and wetland habitats in any FEM can vary widely, from permanently ponded lakes, to ephemerally ponded wetlands, to groundwater‐fed springs, to flowing rivers and streams. The terrestrial matrix can also vary, including in its influence on flows of energy, materials, and organisms among ecosystems. Biota occurring in a specific region are adapted to the unique opportunities and challenges presented by spatial and temporal patterns of habitat types inherent to each FEM. To persist in any given landscape, most species move to recolonize habitats and maintain mixtures of genetic materials. Species also connect habitats through time if they possess needed morphological, physiological, or behavioral traits to persist in a habitat through periods of unfavorable environmental conditions. By examining key spatial and temporal patterns underlying FEMs, and species‐specific adaptations to these patterns, a better understanding of the structural and functional connectivity of a landscape can be obtained. Fully including aquatic, wetland, and terrestrial habitats in FEMs facilitates adoption of the next generation of individual‐based models that integrate the principles of population, community, and ecosystem ecology.

]]>
<![CDATA[The Brain Health Champion study: Health coaching changes behaviors in patients with cognitive impairment]]> https://www.researchpad.co/article/Ne963b650-cefa-4762-8360-70eb20081476

Introduction

Converging evidence suggests that increasing healthy behaviors may slow or prevent cognitive decline.

Methods

We piloted a six-month, randomized, controlled investigation of 40 patients with mild dementia, mild cognitive impairment, or subjective cognitive decline. The intervention consisted of weekly motivational interviewing phone calls and three visits with a “Brain Health Champion” health coach, who guided participants to achieve personalized goals. Changes in behavior were measured using validated questionnaires.

Results

Compared with the standard-of-care control group, Brain Health Champion participants had statistically significant and clinically meaningful increases in physical activity (Cohen's d = 1.37, P < .001), adherence to the Mediterranean diet (Cohen's d = 0.87, P = .016), cognitive/social activity (Cohen's d = 1.09, P = .003), and quality of life (Cohen's d = 1.23, P < .001). The magnitude of behavior change strongly predicted improvement in quality of life.

Discussion

Our results demonstrate the feasibility and potential efficacy of a health coaching approach in changing health behaviors in cognitively impaired and at-risk patients.

]]>
<![CDATA[The Alzheimer's disease THErapy with NEuroaid (ATHENE) study protocol: Assessing the safety and efficacy of Neuroaid II (MLC901) in patients with mild-to-moderate Alzheimer's disease stable on cholinesterase inhibitors or memantine-A randomized, double-bl]]> https://www.researchpad.co/article/5c686358d5eed0c4840236a2

Background

Dementia is a large and growing health care burden globally, and its major cause is Alzheimer's disease (AD). MLC901 (Neuroaid II) is a simplified form of MLC601 (Neuroaid), a Traditional Chinese Medicine with neuroprotective and neuroproliferative properties in cellular and animal models of brain injury. MLC601 has been shown to modulate amyloid precursor protein (APP) processing in human neuroblastoma cell cultures and increase the levels of soluble APPα. In addition, MLC901 has been shown to reduce tau phosphorylation in vitro. Hence, MLC901 may have possible multimodal actions and a disease-modifying effect in AD. In previous clinical studies, MLC601 has shown promising effects in AD.

Objective

To investigate the safety and efficacy of MLC901 add-on therapy to standard treatment in mild-to-moderate probable AD patients stable on standard treatment and to evaluate if MLC901 has a disease-modifying effect in AD.

Methods

This is a 6-month randomized, double-blind, placebo-controlled trial in mild-to-moderate probable AD where MLC901 will be given as an add-on therapy to standard AD treatment, followed by an extension study for another 6 months, where all subjects will be treated with open-label MLC901 in addition to standard treatment. The primary outcome is safety as measured by adverse events, vital signs, electrocardiogram, laboratory tests, and physical and neurological examinations. Secondary outcomes evaluating cognition, behavior, and activities of daily living at various time points include the Alzheimer's Disease Assessment Scale–cognitive subscale, Alzheimer's Disease Cooperative Study–Clinical Global Impression of Change, Alzheimer's Disease Cooperative Study–Activities of Daily Living Inventory, Neuropsychiatric Inventory, and Mini–Mental State Examination.

Conclusion

MLC901 has the potential to improve cognition in AD patients. It may also have a role in delaying disease progression. This study will be the first to provide safety and efficacy data for MLC901 in mild-to-moderate probable AD patients already receiving standard therapy.

]]>
<![CDATA[Association of Legal Intervention Injuries With Race and Ethnicity Among Patients Treated in Emergency Departments in California]]> https://www.researchpad.co/article/5c637014d5eed0c484b29827

Key Points

Question

What were the trends in legal intervention injuries from 2005 to 2015 in California?

Findings

A cross-sectional analysis of all hospital visits in California indicated that rates of legal intervention injuries per capita increased until 2009 and were in decline through 2015. Black individuals were consistently at greatest risk of legal intervention injury per capita, although rates per arrest were broadly similar across race and ethnicity. Injuries involving firearms declined.

Meaning

Hospital data provide an opportunity to monitor the magnitude and characteristics of legal intervention injuries, although efforts are needed to ensure complete reporting on this public health problem disproportionately associated with communities of color.

]]>
<![CDATA[Legionnaires Disease Surveillance in US Department of Veterans Affairs Medical Facilities and Assessment of Health Care Facility Association]]> https://www.researchpad.co/article/5c50f63dd5eed0c48462c138

Key Points

Question

What is the Legionnaires disease burden in the US Department of Veterans Affairs medical facilities, a health care system that has prioritized Legionnaires disease prevention with policy?

Findings

In this cohort study, the number of Legionnaires disease cases was low (n = 491) and 91% of cases had no VA exposure or only outpatient VA exposure. Total rates of Legionnaires disease significantly increased from 2014 to 2016, but rates in cases with overnight health care system exposure significantly decreased.

Meaning

Although total Legionnaires disease rates increased, health care system–associated (overnight stay) rates decreased significantly, suggesting that prevention efforts may have contributed to improved patient safety in these settings.

]]>
<![CDATA[Effect of Greening Vacant Land on Mental Health of Community-Dwelling Adults]]> https://www.researchpad.co/article/5c50f61dd5eed0c48462bdc4

Key Points

Question

Does the greening of vacant urban land reduce self-reported poor mental health in community-dwelling adults?

Findings

In this cluster randomized trial of urban greening and mental health, 110 randomly sampled vacant lot clusters were randomly assigned to 3 study groups. Among 342 participants included in the analysis, feeling depressed significantly decreased by 41.5% and self-reported poor mental health showed a reduction of 62.8% for those living near greened vacant lots compared with control participants.

Meaning

The remediation of vacant and dilapidated physical environments, particularly in resource-limited urban settings, can be an important tool for communities to address mental health problems, alongside other patient-level treatments.

]]>
<![CDATA[Prevalence of and Factors Associated With Long-term Concurrent Use of Stimulants and Opioids Among Adults With Attention-Deficit/Hyperactivity Disorder]]> https://www.researchpad.co/article/5c50f47ed5eed0c484629d61

This cross-sectional analysis of US Medicaid files from 29 states investigates the prevalence of and risk factors associated with concurrent stimulant and opioid use among Medicaid-enrolled adults with attention-deficit/hyperactivity disorder.

]]>
<![CDATA[Coverage of Nonpharmacologic Treatments for Low Back Pain Among US Public and Private Insurers]]> https://www.researchpad.co/article/5c50f5cad5eed0c48462b7e1

Key Points

Question

Among US insurers, what are the coverage and utilization management policies for nonpharmacologic treatments for chronic, noncancer low back pain?

Findings

In this cross-sectional study of 45 Medicaid, commercial, and Medicare Advantage plans, most plans covered at least physical and occupational therapy and chiropractic care for chronic noncancer pain, but there was little evidence of coverage of acupuncture and psychological interventions. Utilization management strategies such as visit limits and prior authorization were common, but criteria varied widely across the plans examined.

Meaning

The lack of consistent coverage and utilization management policies underscores the need for best practices to improve comprehensive, multimodal coverage of treatments for chronic, noncancer low back pain.

]]>
<![CDATA[The Burden of Opioid-Related Mortality in the United States]]> https://www.researchpad.co/article/5c50f59dd5eed0c48462b3b5

Key Points

Question

What has been the burden of opioid-related deaths in the United States over a recent 15-year period?

Findings

In this serial cross-sectional study, we found that the percentage of all deaths attributable to opioids increased 292% (from 0.4% to 1.5%) between 2001 and 2016, resulting in approximately 1.68 million person-years of life lost in 2016 alone (5.2 per 1000 population). The burden was particularly high among adults aged 24 to 35 years; in 2016, 20% of deaths in this age group involved opioids.

Meaning

Premature death from opioids imposes an enormous and growing public health burden across the United States.

]]>