bluuebunny/crossref_metadata_2025 huggingface dataset:
Yolk Sac Tumor Arising in Uterine Carcinosarcoma With Endometrioid and Serous Components: A Case Report With Immunohistochemical Analysis
Authors: Grindstaff Samuel , Hanley Linda C. , Banet Natalie
Published: March 2021

Yolk sac tumor of the endometrium is an uncommon neoplasm. Here we report a case of yolk sac tumor arising in a uterine carcinosarcoma, with the carcinomatous component showing both endometrioid and serous components, and the sarcomatous component showing homologous (spindled) differentiation. The yolk sac tumor showed predominant glandular configuration and was present admixed with the epithelial components. Extensive immunostaining was performed to narrow the differential diagnosis, including potentially therapeutic testing for HER-2. To our knowledge, this is the first case of carcinosarcoma with this mix of epithelial components and corresponding reporting of these immune and therapeutic markers.
Changing Patterns of Sexual Behavior and HIV/STI Among Men Who Have Sex With Men in Seattle, 2002 to 2018
Authors: Khosropour Christine M. , Dombrowski Julia C. , Barbee Lindley A. , Kerani Roxanne P. , Berzkalns Anna , Golden Matthew R.
Published: March 2021

Background:

The extent to which uptake of biomedical HIV prevention strategies have affected population-level sexual behavior and sexually transmitted infections (STIs) among men who have sex with men (MSM) is not well understood.

Methods:

We collected data as part of routine care from MSM attending the municipal STI clinic in Seattle, Washington, 2002–2018. MSM were asked about condom use in the previous 12 months. We classified behaviors into 4 mutually exclusive categories: no anal sex; consistent condom use for anal sex; serosorting [condomless anal sex (CAS) only with HIV-concordant partners]; and CAS with serodiscordant/unknown-status partners. STI/HIV testing was performed per routine clinic protocol.

Results:

There were 45,656 and 6987 visits by MSM without HIV and MSM with HIV, respectively. The use of antiretroviral therapy and preexposure prophylaxis increased substantially during the study period to 94% and 50%, respectively, by 2018. CAS with serodiscordant/unknown-status partners decreased through 2013 but increased thereafter (to 40% among MSM without HIV; 68% among MSM with HIV). Serosorting increased among MSM without HIV but declined after 2013 among MSM with HIV. Consistent condom use declined for all MSM (from 35% to 11% among MSM without HIV; from 20% to 5% among MSM with HIV). HIV test positivity declined substantially (3.5%–0.5%), whereas STI test positivity increased over time.

Conclusions:

Since 2013, CAS with HIV-discordant/unknown-status partners increased substantially concurrent with declining HIV test positivity and increasing STI test positivity. This highlights the success of biomedical HIV prevention strategies to reduce HIV incidence while affirming the need for new approaches to STI prevention.
Exploring Sustainability in the Era of Differentiated HIV Service Delivery in Sub-Saharan Africa: A Systematic Review
Authors: Okere Nwanneka E. , Lennox Laura , Urlings Lisa , Ford Nathan , Naniche Denise , Rinke de Wit Tobias F. , Hermans Sabine , Gomez Gabriela B.
Published: March 2021

Introduction:

The World Health Organization recommends differentiated service delivery (DSD) to support resource-limited health systems in providing patient-centered HIV care. DSD offers alternative care models to clinic-based care for people living with HIV who are stable on antiretroviral therapy (ART). Despite good patient-related outcomes, there is limited evidence of their sustainability. Our review evaluated the reporting of sustainability indicators of DSD interventions conducted in sub-Saharan Africa (SSA).

Methods:

We searched PubMed and EMBASE for studies conducted between 2000 and 2019 assessing DSD interventions targeting HIV-positive individuals who are established in ART in sub-Saharan Africa. We evaluated them through a comprehensive sustainability framework of constructs categorized into 6 domains (intervention design, process, external environment, resources, organizational setting, and people involvement). We scored each construct 1, 2, or 3 for no, partial, or sufficient level of evidence, respectively. Interventions with a calculated sustainability score (overall and domain-specific) of >90% or domain-specific median score >2.7 were considered likely to be sustainable.

Results:

Overall scores ranged from 69% to 98%. Top scoring intervention types included adherence clubs (98%) and community ART groups (95%) which comprised more than half of interventions. The highest scoring domains were design (2.9) and organizational setting (2.8). The domains of resources (2.4) and people involvement (2.3) scored lowest revealing potential areas for improvement to support DSD sustainability.

Conclusions:

With the right investment in stakeholder involvement and domestic funding, DSD models generally show potential for sustainability. Our results could guide informed decisions on which DSD intervention is likely to be sustainable per setting and highlight areas that could motivate further research.
Neurologic aspects of coronavirus disease of 2019 infection
Authors: Hassett Catherine E. , Frontera Jennifer A.
Published: March 2021

Purpose of review

Central and peripheral nervous system manifestations of coronavirus disease 2019 (COVID-19) have been frequently reported and may cause significant morbidity and mortality. This review details the latest evidence on the neuropathogenesis and neurologic complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Recent findings

Commonly reported neurologic complications include toxic-metabolic encephalopathy, acute cerebrovascular disorders, seizures, and anoxic-brain injury. These complications represent secondary injury due to COVID-19 related hypoxia, sepsis, hypercoagulability, or hyperinflammation. Postinfectious complications, such as encephalitis, postinfectious demyelination, and Guillain-Barré syndrome have been reported, but are rare. Recent reports of persistent neurocognitive symptoms highlight the possibility of lasting impairment.

Although some neurologic complications should be treated with standard practices, further investigations are still needed to determine the optimal treatment of COVID-related neurologic complications, such as ischemic stroke. Entering into the next phase of the pandemic, investigations into the long-term neurologic and cognitive impacts of SARS-CoV-2 infection will be needed. Clinicians must have a high clinical suspicion for both acute and chronic neurologic complications among COVID-19 patients.
Potential Role of Artificial Intelligence in Cardiac Magnetic Resonance Imaging
Authors: Cau Riccardo , Cherchi Valeria , Micheletti Giulio , Porcu Michele , Mannelli Lorenzo , Bassareo Pierpaolo , Suri Jasjit S. , Saba Luca
Published: March 2021

In the era of modern medicine, artificial intelligence (AI) is a growing field of interest which is experiencing a steady development. Several applications of AI have been applied to various aspects of cardiac magnetic resonance to assist clinicians and engineers in reducing the costs of exams and, at the same time, to improve image acquisition and reconstruction, thus simplifying their analysis, interpretation, and decision-making process as well. In fact, the role of AI and machine learning in cardiovascular imaging relies on evaluating images more quickly, improving their quality, nulling intraobserver and interobserver variability in their interpretation, upgrading the understanding of the stage of the disease, and providing with a personalized approach to cardiovascular care. In addition, AI algorithm could be directed toward workflow management. This article presents an overview of the existing AI literature in cardiac magnetic resonance, with its strengths and limitations, recent applications, and promising developments. We conclude that AI is very likely be used in all the various process of diagnosis routine mode for cardiac care of patients.
“Digital Simulation of Osteotomy Reduction of a Prominent Zygomatic Arch”
Authors: Tao Qiao , Min Hou , Yangyang Lin , Jinghao Duan , Qiuyu Cao
Published: March 2021

Objective:

To analyze the value of simulated surgery in predicting the outcome of individualized surgical reduction of a prominent zygomatic arch.

Methods:

Computed tomography data were obtained from the electronic records of 15 patients who underwent surgery at Tianjin Stomatological Hospital for prominent zygoma. The data were imported into Mimics 23.0. Left and right three-dimensional (3D) zygoma models were created through standard procedures. In the 3D models, a wedge-shaped cut of the zygomatic bone was pushed inward, and the osteotomy position of the zygomatic arch was taken as a variable to simulate the reduction malarplasty. The reduction effect was calculated from the simulated movement of the fracture end of the zygomatic arch from internal pushing forces. Stable versus high-efficiency internal pushing areas were defined based on the amount of movement. Mean values with 95% confidence intervals (CI) were calculated for the areas data.

Results:

The anterior edge of the stable internal pushing osteotomy area was located in front of the articular tubercle point (95% CI: 10.64–11.89 mm). The posterior edge of the stable internal pushing area was located in front of the articular tubercle point (95% CI: 7.8–9.13 mm). The posterior edge of the high-efficiency internal pushing area was located in front of the articular tubercle point (95% CI: 4.7–5.73 mm).

Conclusion:

Stable and high-efficiency internal pushing areas were detected above the zygomatic arch. The simulation showed that osteotomy in these areas can provide different degrees of zygomatic arch reduction.
A Meta-Analysis of Traumatic Orbital Apex Syndrome and the Effectiveness of Surgical and Clinical Treatments
Authors: Talwar Ankoor A. , Ricci Joseph A.
Published: March 2021

Purpose:

Traumatic orbital apex syndrome (TOAS) commonly occurs secondary to trauma and irreversible ischemic optic neuropathy occurs as early as 2 hours after injury. Multiple treatment options have been described, however, there is a lack of consensus regarding the optimal treatment of these patients.

Methods:

A systematic review of the PubMed Database from 1970 to 2020 was conducted, using the search terms “orbital apex,” “syndrome,” and “traumatic” with the Boolean operators “AND” or “OR.” Papers that did not describe TOAS, describe patient outcomes or treatments, and those without available full English text were excluded. Patients were clustered and compared based on treatment received with the primary outcomes of improvement in vision or ophthalmoplegia.

Results:

Three hundred forty-seven papers were identified, of which 22 were included, representing 117 patients with TOAS. A total of 75.9% patients underwent decompressive surgery, 82.6% received steroids, and 72.2% received nerve growth factors. Fewer than 20% of patients were treated with antibiotics, diuretics, hormones, or hyperbaric oxygen. Overall, 51.7% of patients experienced improvement in vision and 85.2% in ophthalmoplegia at 6 months. Patients treated with surgical decompression (66.7% versus 16.7%, P < 0.01) or steroids (60.0% versus 0%; P < 0.01) were more likely to have improvement in vision than those without treatment. Nerve growth factors did not improve vision. Ophthalmoplegia did not improve with any treatment.

Conclusions:

Outcomes of TOAS tend to be poor, with overall low recovery of vision, though surgical decompression or steroid treatment did suggest improved visual outcomes. Further standardized patient data is needed to elucidate the comparative effectiveness of these interventions.
Analysis of Facial Movement in Repaired Unilateral Cleft Lip Using Three-Dimensional Motion Capture
Authors: Zhao Connie , Hallac Rami R. , Seaward James R.
Published: March 2021

Unilateral cleft lip (UCL) is one of the most common craniofacial deformities. Surgical intervention reconstructs lip and nose anatomy; however, some degree of asymmetry persists after repair. This demonstrates a need for a model for studying and improving outcomes for patients with orofacial clefts. This study's main question was whether there is a significant difference in dynamic facial asymmetry between participants with repaired UCLs and control participants during smiling. Ten pediatric subjects with repaired left UCLs and 12 with no craniofacial diagnoses were recorded performing maximum smiles using a markerless 4D video stereophotogrammetrical system. A facial mesh template containing 884 landmarks was conformed to each initial frame and tracked throughout. Kinetic analysis of smiles was performed by calculating landmark 3D Euclidean distance between frames. Patients with left repaired UCL showed increasing facial asymmetry throughout smiling. Oral commissures, upper, and lower lips demonstrated significantly greater movement on the right side (P < 0.05). Control patients showed facial asymmetry during the first half of smiling, with greater movement on the left side. Displacement difference between right and left was significantly greater at oral commissures and upper lips in patients with repaired ULC compared to control patients. This study provides a highly detailed, quantitative analysis of postoperative UCLs, and help improve outcomes of future repair surgeries.
Bundled Payments for Care Improvement Efficacy Across 3 Common Operations
Authors: Chopra Zoey , Gulseren Baris , Chhabra Karan R. , Dimick Justin B. , Ryan Andrew M.
Published: March 2021

Objective:

The aim of this study was to evaluate associations between hospital participation in Bundled Payments for Care Improvement (BPCI) and 30-day total episode and post-acute care spending for lower extremity joint replacement (LEJR), coronary artery bypass graft (CABG), and colec-tomy.

Summary Background Data:

BPCI has been shown to reduce spending for LEJR episodes largely from reductions in post-acute care. However, BPCI efficacy in other common elective procedures, including CABG and colec-tomy, remains unclear. It is also unknown whether post-acute care spending reductions drive total spending reductions outside of LEJR.

Methods:

Retrospective cohort study using 100% Medicare claims data to identify BPCI (312 total) and non-BPCI (1,977 total) acute care hospitals from January 1, 2010 to November 30, 2016 with Medicare-enrolled patient discharges for at least one of the following BPCI episodes: LEJR (454,369 episodes), CABG (107,307 episodes), or colectomy (73,717 episodes). Along with difference-in-differences (DiD) analysis, we constructed generalized synthetic controls in the presence of nonparallel trends to estimate associations between BPCI participation and 30-day total and post-acute care spending.

Results:

DiD estimates indicated reduced spending for LEJR (–$541.6 [95% confidence interval (CI): –718.0 to –365.3]) and colectomy (–$582.1 [95% CI: –927.3 to –236.8]) but not CABG (–$268.9 [95% CI: –831.5 to 293.7]). Generalized synthetic control estimates indicated reduced spending for LEJR (–$795.3 [95% CI: –10,22.1 to –582.2]) but not colectomy (–$251.3 [95% CI: –997.9 to 335.2]) or CABG (–$257.8 [95% CI: –10,24.6 to 414.8]).

Post-acute care comprised 42.6% of LEJR spending reductions and 53.0% of colectomy spending reductions.

Conclusions:

BPCI participation was associated with significant spending reductions for LEJR and colectomy but not CABG. We conclude that BPCI has episode-dependent efficacy, largely determined by post-acute care.
Novel Presenilin-1 Mutation (Ala275Ser) Associated With Clinical Features of Dementia With Lewy Bodies
Authors: Joshi Purwa , Gardner McKinlay , Lintott Caroline , Anderson Tim
Published: March 2021

We report a case of familial dementia having some clinical features characteristic of dementia with Lewy bodies, in which a novel mutation Ala275Ser within the presenilin-1 (PSEN1) gene was identified. We review the association of PSEN1 mutation with dementia with Lewy bodies features, noting this to be an uncommonly reported observation.
Correlation Between Ophthalmologic and Neuroradiologic Findings in Type 1 Neurofibromatosis
Authors: Godinho Gonçalo , Esteves-Leandro João , Alves Gonçalo , Madeira Carolina , Faria Olinda , Brandão Elisete , Magalhães Augusto , Falcão-Reis Fernando , Penas Susana
Published: March 2021

Background:

Neurofibromatosis Type 1 (NF-1) is a genetic disease affecting the eye, and ocular findings such as Lisch nodules (LN) or optic pathway gliomas (OPGs) are a part of its diagnostic criteria. Recent imaging technologies such as infrared (IR) imaging and optical coherence tomography (OCT) have highlighted the visualization of choroidal focal abnormalities in these patients, even in the absence of other ocular lesions. This study aimed to establish a morphological multimodal evaluation of choroidal findings in patients with NF-1, correlating them with central nervous system (CNS) findings.

Methods:

This retrospective study included 44 eyes from 22 patients with NF-1. Central 30° IR imaging was obtained, and the number and total area of detectable lesions were calculated. Both macular and optic disc scanning with OCT were performed, with and without the enhanced depth imaging technique, to assess the presence of choroidal focal hyperreflective lesions. Central macular thickness, ganglion cell layer, and outer nuclear layer thickness were assessed, as well as subfoveal choroidal thickness. The peripapillary retinal nerve fiber layer (RNFL) thickness was also assessed. Patients' magnetic resonance images (MRI) were reviewed and categorized by a neuroradiology specialist, determining the presence of OPGs and CNS hamartomas. Correlations between the ophthalmological and neuroradiological findings were established.

Results:

Patients' mean age was 16.4 ± 7.3 years and 59.1% were women. On the MRI, 86.4% of the patients had CNS hamartomas, and 34.1% of the eyes had OPGs. LN were described in 29.5% of the eyes, whereas a total of 63.4% of the eyes presented the characteristic hyperreflective lesions in IR imaging, all of them matching the underlying choroidal lesions. A mean of 2.9 ± 3.3 lesions per eye and a median total lesion area of 1.52 mm2 were found. The presence of OPGs was correlated with a greater number (P = 0.004) and a larger area (P = 0.006) of IR lesions. For a cut-off of 3.5 lesions per eye, the sensitivity and specificity for the presence of OPGs were 75% and 80%, respectively. For a total lesion area of 2.77 mm2, the sensitivity and specificity for the presence of OPGs were 69.2% and 93.1%, respectively. Eyes with OPGs presented a significant reduction in the temporal RNFL (P = 0.018) thickness, as well as a reduction in subfoveal choroid thickness (P = 0.04). No relations were found between CNS hamartomas and ophthalmological findings.

Conclusions:

This study suggests that focal choroidal abnormalities are correlated with the presence of CNS lesions as OPGs in patients with NF-1, and it might be a surrogate for the need for CNS imaging in these patients.
Supporting COVID-19 policy response with large-scale mobility-based modeling
Authors: Chang Serina , Wilson Mandy L. , Lewis Bryan , Mehrab Zakaria , Dudakiya Komal K. , Pierson Emma , Koh Pang Wei , Gerardin Jaline , Redbird Beth , Grusky David , Marathe Madhav , Leskovec Jure
Published: March 2021

Social distancing measures, such as restricting occupancy at venues, have been a primary intervention for controlling the spread of COVID-19. However, these mobility restrictions place a significant economic burden on individuals and businesses. To balance these competing demands, policymakers need analytical tools to assess the costs and benefits of different mobility reduction measures.In this paper, we present our work motivated by our interactions with the Virginia Department of Health on a decision-support tool that utilizes large-scale data and epidemiological modeling to quantify the impact of changes in mobility on infection rates. Our model captures the spread of COVID-19 by using a fine-grained, dynamic mobility network that encodes the hourly movements of people from neighborhoods to individual places, with over 3 billion hourly edges. By perturbing the mobility network, we can simulate a wide variety of reopening plans and forecast their impact in terms of new infections and the loss in visits per sector. To deploy this model in practice, we built a robust computational infrastructure to support running millions of model realizations, and we worked with policymakers to develop an intuitive dashboard interface that communicates our model’s predictions for thousands of potential policies, tailored to their jurisdiction. The resulting decision-support environment provides policymakers with much-needed analytical machinery to assess the tradeoffs between future infections and mobility restrictions.
Three-dimensional cranio-facial landmark detection in CT slices from a publicly available database, using multi-phased regression networks on a personal computer
Authors: Nishimoto Soh , Saito Takuya , Ishise Hisako , Fujiwara Toshihiro , Kawai Kenichiro , Kakibuchi Maso
Published: March 2021

Aim

Geometrical assessments to comprehend the shape of an object are done based on characteristic landmarks. Computer assisted tomography (CT) images, horizontal slices as two-dimensional pictures, can be digitally restructured into virtual three-dimensional objects. Automatic detection of the landmarks, if developed, will be a great help not only medically, but also for anthropologically. The aim of this study is to develop an automated system to predict three-dimensional coordinate values of cranio-facial landmarks in sequences of CT slices.

Methods

CT images were obtained from a publicly available database. Digital reconstruction was done to obtain three dimensional models. Sixteen landmarks were plotted on the models and coordinate values of them were recorded. Multi-phased deep learning system was constructed. For the first phase, 512 x 512 pixels images were resized to 96 x 96 pixels. A regression deep learning network was trained with 90 training data. For the second phase, for each landmark, 100 x 100 pixels images were cropped from the original images. Sixteen models were trained. For the third phase, 50 x 50 pixels images were cropped, and models were trained.

Results

Three-dimensional error for the first phase, testing 30 data, was 11.60 pixels in average. (1 pixel = 500 / 512 mm) For the second phase, it was significantly improved to 4.66 pixels. For the third phase, it was significantly progressed to 2.89. This was comparable to the gaps between the landmarks, plotted by two experienced practitioners.

Discussion

The calculation volume required to process three-dimensional pile of images is tremendous. One solution may be to compress the images, but detailed information may be lost during the process. Our proposing method of multi-phased prediction, coarse detection first and narrowing down the detection area, may be a possible solution, within the physical limitation of memory and computation.
Reportable range of quantitative assays for SARS-CoV-2 antibodies determination. An overlooked issue?
Authors: Dittadi Ruggero , Bertoli Isabella , Carraro Paolo
Published: March 2021

In order to identify the quantization capability of two methods for SARS-CoV-2 IgG determination (Anti-SARS-CoV-2 QuantiVac ELISA IgG from Euroimmun and SARS-CoV-2 IgG anti-RBD from SNIBE), the linearity of the reportable range with respect to the calibration curve was evaluated.
COVID-19 reinfection: A Rapid Systematic Review of Case Reports and Case Series
Authors: Wang Jingzhou , Kaperak Christopher , Sato Toshiro , Sakuraba Atsushi
Published: March 2021

The COVID-19 pandemic has infected millions of people worldwide and many countries have been suffering from a large number of deaths. Acknowledging the ability of SARS-CoV-2 to mutate into distinct strains as an RNA virus and investigating its potential to cause reinfection is important for future health policy guidelines. It was thought that individuals who recovered from COVID-19 generate a robust immune response and develop protective immunity, however, since the first case of documented reinfection of COVID-19 in August 2020, there have been a number of cases with reinfection. Many cases are lacking genomic data of the two infections and it remains unclear whether they were caused by different strains. In the present study, we undertook a rapid systematic review to identify cases infected with different genetic strains of SARS-CoV-2 confirmed by polymerase-chain reaction and viral genome sequencing. A total of 17 cases of genetically confirmed COVID-19 reinfection were found. One immunocompromised patient had mild symptoms with the first infection, but developed severe symptoms resulting in death with the second infection. Overall, 68.8% (11/16) had similar severity, 18.8% (3/16) had worse symptoms, and 12.5% (2/16) had milder symptoms with the second episode. Our case series shows that reinfection with different strains is possible and some cases may experience more severe infections with the second episode. The findings also suggest that COVID-19 may continue to circulate even after achieving herd immunity through natural infection or vaccination suggesting the need for longer term transmission mitigation efforts.
Pregnancy and risk of COVID-19
Authors: Magnus Maria C. , Oakley Laura , K. Gjessing Håkon , Stephansson Olof , Engjom Hilde M. , Macsali Ferenc , Juliusson Petur B. , Andersen Anne-Marie Nybo , Håberg Siri E.
Published: March 2021

Background

Studies report that pregnant women with coronavirus disease 2019 (COVID-19) are at increased risk of severe disease, intensive-care and death. Whether pregnant women in general are more susceptible of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear.

Methods

Linked registry-data on all women ages 15 to 45 living in Norway on March 1st, 2020 (N=1,033,699) were used in Cox regression models to estimate hazard ratios (HR) comparing pregnant to non-pregnant women, of having a positive test for SARS-CoV-2, a diagnosis of COVID-19 in specialist healthcare, or hospitalization with COVID-19, adjusting for age, marital status, education, income, country of birth and underlying medical conditions.

Results

Compared to non-pregnant women, pregnant women had a similar risk of a positive SARS-CoV-2 test (adjusted HR, 0.99; 95% confidence interval [CI], 0.92 to 1.07), a higher risk of a COVID-19 diagnosis in specialist care (HR, 3.46; 95% CI, 2.89 to 4.14), and to be hospitalized (HR, 4.70; 95% CI, 3.51 to 6.30). Pregnant women were in general not more likely to be tested for SARS-CoV-2. Pregnant women born outside Scandinavia were less likely to be tested, but at higher risk of a positive test (HR, 2.37; 95% CI, 2.51 to 8.87) and of hospitalization with COVID-19 (HR, 4.72; 95% CI, 2.51 to 8.87) than pregnant Scandinavian born women.

Conclusion

Pregnant women were not more likely to be infected with SARS-CoV-2. However, pregnant women with COVID-19, especially those born outside of Scandinavia, were more likely to receive specialist care and to be hospitalized.
Direct Primary Care: Family Physician Perceptions of a Growing Model
Authors: Brekke Gayle , Saint Onge Jarron M. , Kimminau Kim S. , Ellis Shellie
Published: March 2021

Purpose

Direct Primary Care (DPC) is a relatively new primary care practice model in which patients receive unlimited access to a defined set of primary care services in exchange for a monthly practice-specific membership fee. DPC is a bottom-up physician-driven approach that contrasts to typical top-down insurer-centric health care delivery reform efforts. The degree to which physicians are aware of this practice model and whether they believe it addresses two key challenges facing primary care, access and administrative burden, are unclear.

Methods

An online survey distributed in July 2017 gauged family physicians’ awareness of DPC and views about the model.

Results

Most respondents (85%) had heard of DPC and eight percent practiced in a DPC model at the time of the survey. In general, respondents reported that DPC can offer positive outcomes through lower administrative burden for physicians, improved doctor-patient relationships, and better access. Respondents also suggested DPC may result in improved patient health outcomes and lower overall healthcare spending. Respondents’ concerns included inappropriateness of the model for vulnerable populations and physician shortages. Survey responses differed depending on whether the respondent practiced in a DPC model; DPC physicians had a more favorable view of the model and were focused on benefits to patients rather than benefits to physicians.

Conclusions

While some perceive challenges of DPC, others think that this model may benefit both patients and physicians.
Environment-wide association study (EWAS) on cardiometabolic traits: A systematic assessment of the association of lifestyle variables on a longitudinal setting
Authors: Poveda Alaitz , Chen Yan , Pomares-Millan Hugo , Kurbasic Azra , Patel Chirag J , Renström Frida , Hallmans Göran , Johansson Ingegerd , Franks Paul W.
Published: March 2021

The present study aims to assess the over-time association of ∼300 lifestyle exposures with nine cardiometabolic traits with the ultimate aim of identifying exposures/exposure groups that could inform lifestyle interventions aiming at controlling cardiometabolic diseases. The analyses were undertaken in a longitudinal sample comprising >31000 adults living in northern Sweden. Linear mixed models were used to assess the average associations of lifestyle exposures and linear regression models were used to test association with 10-year change of the cardiometabolic traits. ‘Physical activity’ and ‘General Health’ were the exposure categories containing the highest number of ‘tentative signals’ in analyses assessing the average association of lifestyle variables, while ‘Tobacco use’ was the top-category for the 10-year change association analyses. Thirteen modifiable variables showed a consistent average association among the majority of cardiometabolic traits. These variables belonged to four main groups: i) Smoking, ii) Diet (secoisolariciresinol intake and brewed coffee), iii) Leisure time physical activity and iv) a group of variables more specific to the Swedish lifestyle (snuff status, hunting/fishing during leisure time and boiled coffee). Interestingly, sweet drinks, fish intake and salt content, all lifestyle exposures frequently mentioned in public health recommendations were not broadly associated with the analysed cardiometabolic traits.
A global database of COVID-19 vaccinations
Authors: Mathieu Edouard , Ritchie Hannah , Ortiz-Ospina Esteban , Roser Max , Hasell Joe , Appel Cameron , Giattino Charlie
Published: March 2021

An effective rollout of vaccinations against COVID-19 offers the most promising prospect of bringing the pandemic to an end. We present the Our World in Data COVID-19 vaccination dataset, a global public dataset that tracks the scale and rate of the vaccine rollout across the world. This dataset is updated regularly, and includes data on the total number of vaccinations administered; first and second doses administered; daily vaccination rates; and population-adjusted coverage for all countries for which data is available (138 countries as of 17 March 2021). It will be maintained as the global vaccination campaign continues to progress. This resource aids policymakers and researchers in understanding the rate of current and potential vaccine rollout; the interactions with non-vaccination policy responses; the potential impact of vaccinations on pandemic outcomes such as transmission, morbidity, and mortality; and global inequalities in vaccine access.
Bridging the polar and hydrophobic metabolome in single-run untargeted liquid chromatography-mass spectrometry dried blood spot metabolomics for clinical purposes
Authors: Skogvold Hanne Bendiksen , Mørk Sandås Elise , Østeby Anja , Løkken Camilla , Rootwelt Helge , Rønning Per Ola , Wilson Steven Ray , Prestø Elgstøen Katja Benedikte
Published: March 2021

Dried blood spot (DBS) metabolite analysis is a central tool for the clinic, e.g. newborn screening. Instead of applying multiple analytical methods, a single liquid chromatography-mass spectrometry (LC-MS) method was developed for metabolites spanning from highly polar glucose to hydrophobic long-chain acylcarnitines. For liquid chromatography, a diphenyl column and a multi-linear solvent gradient operated at elevated flow rates allowed for an even-spread resolution of diverse metabolites. Injecting moderate volumes of DBS organic extracts directly, in contrast to evaporation and reconstitution, provided substantial increases in analyte recovery. Q Exactive MS settings were also tailored for sensitivity increases, and the method allowed for analyte retention time and peak area repeatabilities of 0.1-0.4 % and 2-10 %, respectively, for a wide polarity range of metabolites (logP −4.4 to 8.8). The method’s performance was suited for both untargeted analysis as well as targeted approaches, evaluated in clinically relevant experiments.

Graphical Abstract
Predicting disability progression and cognitive worsening in multiple
sclerosis using grey matter network measures
Authors: Colato Elisa , Stutters Jonathan , Tur Carmen , Sridar Narayanan , Arnold Douglas , Kingshott Claudia Wheeler , Barkhof Frederik , Ciccarelli Olga , Chard Declan , Eshaghi Arman
Published: March 2021

Objective

In multiple sclerosis (MS), magnetic resonance imaging (MRI) measures at
the whole brain or regional level are only modestly associated with
disability, while network-based measures are emerging as promising
prognostic markers. We sought to demonstrate whether data-driven
network-based measures of regional grey matter (GM) volumes predict future
disability in secondary progressive MS (SPMS).

Methods

We used cross-sectional structural MRI, and baseline and longitudinal
data of Expanded Disability Status Scale [EDSS], 9-Hole Peg Test [9HPT], and
Symbol Digit Modalities Test [SDMT], from a clinical trial in 988 people
with progressive MS. We processed T1-weighted scans to obtain GM probability
maps and applied spatial independent component analysis (ICA) to identify
co-varying patterns of GM volume change. We used survival models to
determine whether baseline GM network measures predict cognitive and motor
worsening.

Results

We identified 15 networks of regionally co-varying GM features. Compared
with whole brain GM, deep GM, and lesion volumes, ICA-components correlated
more closely with clinical outcomes. A mainly basal ganglia component had
the highest correlations at baseline with the SDMT and was associated with
cognitive worsening (HR= 1.29, 95% CI [1.09-1.52], p< 0.005). Two
ICA-components were associated with 9HPT worsening (HR=1.30, 95% CI
[1.06:1.60], p<0.01; and HR= 1.21, 95%CI [1.01:1.45], p<0.05).
Post-hoc analyses revealed that for 9HPT and SDMT survival models including
network-based measures reported a higher discrimination power (respectively,
C-index= 0.69, se= 0.03; C-index= 0.71, se= 0.02) compared to models
including only whole and regional MRI measures (respectively, C-index= 0.65,
se= 0.03; C-index= 0.69, se= 0.02).

Conclusions

The disability progression was better predicted by networks of covarying
GM regions, rather than by single regional or whole-brain measures. Network
analysis can be applied in future clinical trials and may play a role in
stratifying participants who have the most potential to show a treatment
effect.
Development of a Codebook of Online Anti-Vaccination Rhetoric to Manage COVID-19 Vaccine Misinformation
Authors: Hughes B. , Miller-Idriss C. , Piltch-Loeb R. , White K. , Creizis M. , Cain Caleb , Savoia E.
Published: March 2021

Vaccine hesitancy (delay in obtaining a vaccine, despite availability) represents a significant hurdle to managing the COVID-19 pandemic. Vaccine hesitancy is in part related to the prevalence of anti-vaccine misinformation and disinformation, which are spread through social media and user-generated content platforms. This study uses qualitative coding methodology to identify salient narratives and rhetorical styles common to anti-vaccine and COVID-denialist media. It organizes these narratives and rhetorics according to theme, imagined antagonist, and frequency. Most frequent were narratives centered on “corrupt elites” and rhetorics appealing to the vulnerability of children. The identification of these narratives and rhetorics may assist in developing effective public health messaging campaigns, since narrative and emotion have demonstrated persuasive effectiveness in other public health communication settings.
Behavioral and Magnetoencephalographic Correlates of Fear Generalization Are Associated with Responses to Later Virtual Reality Exposure Therapy in Spider Phobia
Authors: Roesmann Kati , Leehr Elisabeth Johanna , Böhnlein Joscha , Steinberg Christian , Seeger Fabian , Schwarzmeier Hanna , Gathmann Bettina , Siminski Niklas , Herrmann Martin J. , Dannlowski Udo , Lueken Ulrike , Klucken Tim , Hilbert Kevin , Straube Thomas , Junghöfer Markus
Published: March 2021

As overgeneralization of fear is a pathogenic marker of anxiety disorders, we investigated whether pre-treatment levels of fear generalization in spider-phobic patients are associated with their response to exposure-based treatment, in order to identify pre-treatment correlates of treatment success. Ninety patients with spider phobia completed pre-treatment clinical and magnetoencephalography (MEG) assessments, one session of virtual reality exposure therapy, and a post-treatment clinical assessment. Based on the primary outcome (30% symptom reduction in self-reported symptoms from pre-to post-treatment) they were categorized as responders or non-responders. In a pre-treatment MEG fear generalization paradigm involving fear conditioning with two unconditioned stimuli (UCS), we obtained fear ratings, UCS-expectancy ratings, and event-related fields to conditioned stimuli (CS+, CS-) and 7 different generalization stimuli (GS) on a perceptual continuum from CS+ to CS-. Prior to treatment, non-responders showed behavioral overgeneralization indicated by more linear generalization gradients in fear ratings. Analyses of MEG source estimations revealed that non-responders showed a decline of their (inhibitory) frontal activations to safety-signaling CS- and GS compared to CS+ over time, while responders maintained these activations at early (<300ms) and late processing stages. Results provide initial evidence that pre-treatment differences of behavioral and neural markers of fear generalization are associated with later responses to behavioral exposure. Findings demonstrate the relevance of inhibitory learning functions and their spatio-temporal neural reflections in this interplay. Findings stimulate research on mechanism-based augmentation strategies for behavioral therapies.
How to quantify deaths averted derived from interrupted time-series analyses
Authors: Jiang Huan , Tran Alexander , Gmel Gerhard , Lange Shannon , Manthey Jakob , Room Robin , Rovira Pol , Štelemėkas Mindaugas , Telksnys Tadas , Rehm Jürgen
Published: March 2021

Background

Interrupted time series (ITS) are an important tool for determining whether alcohol control policies, as well as other policy interventions, are successful over and above secular trends or chance. Subsequent to estimating whether a policy has had an effect, quantifying the key outcomes, such as the number of prevented deaths, is of primary practical importance. The current paper compares the results of two different methodological approaches to quantify deaths averted using different two standard populations.

Methods

Time series methodologies were used to estimate the effect size in deaths averted of a substantial increase in excise taxation in Lithuania in 2017. We compare the impact of a) using ITS methodology vs. fitting the trend before the intervention to predict the following 12 months and comparing the predicted monthly estimates of deaths with the actual numbers; and b) adjusting the time series either using the World Health Organization standard or the age distribution of Lithuania in the month before the intervention. The effect was estimated by sex.

Results

The increase in excise taxation was associated with a substantial decrease in all-cause mortality in all models considered. ITS methodology and using the age-distribution of Lithuania were consistently associated with higher estimates of deaths averted. Although confidence and prediction intervals were highly overlapping, the point estimates differed substantially. The taxation increase was associated with 1,155 deaths averted in the year following the intervention (95% prediction interval: 729, 1,582), corresponding to 2.80% of all deaths in Lithuania in the respective year, for the model selected as best for planning policy interventions in Lithuania.

Conclusions

Fitting a time series model for the time until the intervention, and then comparing the predicted time points with the actual mortality, standardizing to country-specific weights, was chosen as the best way to derive practically relevant effect sizes.
A New Causal Approach to Account for Treatment Switching in Randomized Experiments under a Structural Cumulative Survival Model
Authors: Ying Andrew , Tchetgen Tchetgen Eric J.
Published: March 2021

Background

Treatment switching in a randomized controlled trial is said to occur when a patient randomized to one treatment arm switches to another treatment arm during follow-up. This can occur at the point of disease progression, whereby patients in the control arm may be offered the experimental treatment. It is widely known that failure to account for treatment switching can seriously dilute the estimated effect of treatment on overall survival. In this paper, we aim to account for the potential impact of treatment switching in a re-analysis evaluating the treatment effect of Nucleoside Reverse Transcriptase Inhibitors (NRTIs) on a safety outcome (time to first severe or worse sign or symptom) in participants receiving a new antiretroviral regimen that either included or omitted NRTIs in the Optimized Treatment That Includes or Omits NRTIs (OPTIONS) trial.

Methods

We propose an estimator of a treatment causal effect under a structural cumulative survival model (SCSM) that leverages randomization as an instrumental variable to account for selective treatment switching. Unlike Robins’ accelerated failure time model often used to address treatment switching, the proposed approach avoids the need for artificial censoring for estimation. We establish that the proposed estimator is uniformly consistent and asymptotically Gaussian under standard regularity conditions. A consistent variance estimator is also given and a simple resampling approach provides uniform confidence bands for the causal difference comparing treatment groups over time on the cumulative intensity scale. We develop an R package named “ivsacim” implementing all proposed methods, freely available to download from R CRAN. We examine the finite performance of estimator via extensive simulations.

Results

357 participants in the OPTIONS trial were randomly assigned at baseline to add-NRTIs or omit-NRTIs treatment group; 93% subsequently completed a 48-week visit. Using the proposed methods, we found statistically significant evidence against the sharp null hypothesis of no treatment effect on the safety outcome (P value 0.034) and our SCSM estimator revealed an increased risk for a safety outcome in participants receiving a new antiretroviral regimen that included NRTIs when compared to participants receiving a regimen that omitted NRTIs. In fact, under an SCSM encoding a constant additive hazards model, we estimated a hazards difference equal to 0.0039 (95% CI 0.0002, 0.0075) over the 48-week follow-up.

Conclusions

Treatment-experienced patients with HIV infection starting a new optimized regimen will experience a higher risk of severe or worse sign or symptom. Previous analyses concluded that treatment-experienced patients with HIV infection starting a new optimized regimen can safely omit NRTIs without compromising virologic efficacy. Our analysis suggests that adding NRTIs is not only unnecessary to achieve optimal outcomes but may increase the risk for a safety outcome.
Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a fourplex real-time quantitative reverse transcription-PCR assays
Authors: Durand Mathieu , Thibault Philippe , Lévesque Simon , Brault Ariane , Carignan Alex , Valiquette Louis , Martin Philippe , Labbé Simon
Published: March 2021

The early diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is required to identify and isolate contagious patients to prevent further transmission of the coronavirus disease 2019 (COVID-19). In this study, we present a multitarget real-time TaqMan reverse transcription PCR (rRT-PCR) assay for the quantitative detection of SARS-CoV-2 and some of its circulating variants harboring mutations that give SARS-CoV-2 a selective advantage. Seven different primer-probe sets that included probes containing locked nucleic acid (LNA) nucleotides were designed to amplify specific wild-type and mutant sequences in Orf1ab, Envelope (E), Spike (S), and Nucleocapsid (N) genes. Furthermore, a newly developed primer-probe set targeted human β2-microglobulin (B2M) as a highly sensitive internal control for RT efficacy. All singleplex and fourplex assays detected ≤ 14 copies/reaction of quantified synthetic RNA transcripts, with a linear amplification range of 9 logarithmic orders. Primer-probe sets for detection of SARS-CoV-2 exhibited no false-positive amplifications with other common respiratory pathogens, including human coronaviruses NL63, 229E, OC43, and HKU-1. Given the emergence of SARS-CoV-2 variants and their rapid spread in some populations, fourplex rRT-PCR assay containing four primer-probe sets represents a reliable approach to detect multiple viral target sequences containing typical mutations of SARS-CoV-2 variants in a single reaction, allowing quicker detection of circulating relevant variants.