bluuebunny/crossref_metadata_2025 huggingface dataset:
The ACE Index: mapping childhood adversity in England
Authors: Lewer Dan , King Emma , Bramley Glen , Fitzpatrick Suzanne , Treanor Morag C , Maguire Nick , Bullock Miriam , Hayward Andrew , Story Al
Published: October 2019

Background

Studies of adults show that adverse childhood experiences (ACEs) are associated with health and social problems and are more common among people living in deprived areas. However, there is limited information about the geographical pattern of contemporary ACEs.

Methods

We used data from the police, social services, schools and vital statistics in England to calculate population rates of events that represent childhood adversity. We constructed an ‘ACE Index’ that summarizes the relative frequency of ACEs at local authority level, informed by the methods of the Index of Multiple Deprivation. We explored associations between the ACE Index and local characteristics in cross-sectional ecological analysis.

Results

The ACE Index was strongly associated with the proportion of children that live in income-deprived households (child poverty). In addition, the ACE Index was independently associated with higher population density and was higher in certain regions, particularly the north-east.

Conclusions

The association between ACEs and child poverty provides evidence of a process in which deprivation increases the risk of adverse experiences in childhood. The ACE Index can inform allocation of resources for prevention and mitigation of ACEs.
Overall infection risk in rheumatoid arthritis during treatment with abatacept, rituximab and tocilizumab; an observational cohort study
Authors: Grøn Kathrine L , Glintborg Bente , Nørgaard Mette , Mehnert Frank , Østergaard Mikkel , Dreyer Lene , Krogh Niels S , Hetland Merete L
Published: October 2019

Objectives

Most infections in patients with RA are treated in primary care with antibiotics. A small fraction require hospitalization. Only a few studies exist regarding the overall risk of infection (i.e. prescription of antibiotics or hospitalization due to infection) in patients initiating non-TNF-inhibitor therapy. In Danish RA patients initiating abatacept, rituximab and tocilizumab treatment in routine care, the aims were to compare adjusted incidence rates (IR) of infections and to estimate relative risk of infections across the drugs during 0–12 and 0–24 months.

Methods

This was an observational cohort study including all RA patients in the DANBIO registry starting a non-TNF-inhibitor from 2010 to 2017. Infections were defined as a prescription of antibiotics or hospitalization due to infection. Prescriptions, comorbidities and infections were captured through linkage to national registries. IRs of infections (age, gender adjusted) and rate ratios (as estimates of RR (relative risk)), adjusted for additional covariates) (Poisson regression) were calculated.

Results

We identified 3696 treatment episodes (abatacept 1115, rituximab 1017, tocilizumab 1564). At baseline, rituximab users were older and had more previous cancer. During 0–12 months, 1747 infections occurred. Age and gender-adjusted IRs per 100 person-years were as follows: abatacept: 76 (95% CI: 69, 84); rituximab: 87 (95% CI: 79, 96); tocilizumab: 77 (95% CI: 71, 84). Adjusted RRs were 0.94 (95% CI: 0.81, 1.08) for abatacept and 0.94 (95% CI: 0.81, 1.03) for tocilizumab compared with rituximab and 1.00 (95% CI: 0.88, 1.14) for abatacept compared with tocilizumab. RRs around 1 were observed after 24 months. Switchers and ever smokers had higher risk compared with biologic-naïve and never smokers, respectively.

Conclusion

Overall infections were common in non-TNF-inhibitor-treated RA patients, with a tendency towards rituximab having the highest risk, but CIs were wide in all analyses. Confounding by indication may at least partly explain any differences.
Anticardiolipin antibody and anti-β2 glycoprotein I antibody are potential risk markers of ischaemic stroke in Chinese adults
Authors: Dong Shengyong , Pei Bin , Xie Wuxiang , Wang Jing , Zeng Qiang
Published: October 2019

Objectives

aCL and anti-β2 glycoprotein I antibody (aβ2GPI) are autoantibodies associated with thromboembolic diseases. Here we investigated whether they are correlated with ischaemic cardiovascular disease in a Chinese population.

Methods

Serum total aCL and aβ2GPI isotypes (IgA, IgG or IgM, separately) were measured in 11 015 Chinese adults. Differences of antibody level between disease and non-disease groups were examined by t-test. The correlation between antibody and ischaemic cardiovascular disease was determined by logistic regression analysis. Performance of risk prediction models employed aCL or aβ2GPI isotypes was evaluated by C statistic, net reclassification improvement index and integrated discrimination improvement.

Results

Total aCL and aβ2GPI isotypes maintained low levels and increased with increasing age except total aCL and aβ2GPI IgG in participants older than 70 years. When distinguishing ischaemic cardiovascular disease by coronary heart disease (CHD) and ischaemic stroke, the stroke group had higher levels of aCL and aβ2GPI isotypes than the non-stroke group, while the CHD group only had a slightly higher aβ2GPI IgG than non-CHD groups. aCL and aβ2GPI were positively correlated with stroke but not with CHD, and improved the performance of conventional risk factors for stroke risk prediction, with C statistic from 0.769 (95% CI 0.744, 0.793) to 0.777 (95% CI 0.754, 0.800) (aβ2GPI IgG, P = 0.0091), and 0.778 (95% CI 0.754, 0.801) (aβ2GPI IgA, P = 0.0793). Stroke risk could be better reclassified by aCL and aβ2GPI, in association with both net reclassification improvement and integrated discrimination improvement statistics (P < 0.05).

Conclusion

aCL and aβ2GPI are associated with ischaemic stroke and have added value for stroke risk prediction.
Elucidating the drivers of genetic differentiation in Malaysian torrent frogs (Anura: Ranidae: Amolops): a landscape genomics approach
Authors: Chan Kin Onn , Brown Rafe M
Published: October 2019

The interplay between environmental attributes and evolutionary processes can provide valuable insights into how biodiversity is generated, partitioned and distributed. This study investigates the role of spatial, environmental and historical factors that could potentially drive diversification and shape genetic variation in Malaysian torrent frogs. Torrent frogs are ecologically conserved, and we hypothesize that this could impose tight constraints on dispersal routes, gene flow and consequently genetic structure. Moreover, levels of gene flow were shown to vary among populations from separate mountain ranges, indicating that genetic differentiation could be influenced by landscape features. Using genome-wide single nucleotide polymorphisms, in conjunction with landscape variables derived from Geographic Information Systems, we performed distance-based redundancy analyses and variance partitioning to disentangle the effects of isolation-by-distance (IBD), isolation-by-resistance (IBR) and isolation-by-colonization (IBC). Our results demonstrated that IBR contributed minimally to genetic variation. Intraspecific population structure can be largely attributed to IBD, whereas interspecific diversification was primarily driven by IBC. We also detected two distinct population bottlenecks, indicating that speciation events were likely driven by vicariance or founder events.
Dominant, Heritable Resistance to Stewart’s Wilt in Maize Is Associated with an Enhanced Vascular Defense Response to Infection withPantoea stewartii
Authors: Doblas-Ibáñez Paula , Deng Kaiyue , Vasquez Miguel F. , Giese Laura , Cobine Paul A. , Kolkman Judith M. , King Helen , Jamann Tiffany M. , Balint-Kurti Peter , De La Fuente Leonardo , Nelson Rebecca J. , Mackey David , Smith Laurie G.
Published: October 2019

Vascular wilt bacteria such as Pantoea stewartii, the causal agent of Stewart’s bacterial wilt of maize (SW), are destructive pathogens that are difficult to control. These bacteria colonize the xylem, where they form biofilms that block sap flow leading to characteristic wilting symptoms. Heritable forms of SW resistance exist and are used in maize breeding programs but the underlying genes and mechanisms are mostly unknown. Here, we show that seedlings of maize inbred lines with pan1 mutations are highly resistant to SW. However, current evidence suggests that other genes introgressed along with pan1 are responsible for resistance. Genomic analyses of pan1 lines were used to identify candidate resistance genes. In-depth comparison of P. stewartii interaction with susceptible and resistant maize lines revealed an enhanced vascular defense response in pan1 lines characterized by accumulation of electron-dense materials in xylem conduits visible by electron microscopy. We propose that this vascular defense response restricts P. stewartii spread through the vasculature, reducing both systemic bacterial colonization of the xylem network and consequent wilting. Though apparently unrelated to the resistance phenotype of pan1 lines, we also demonstrate that the effector WtsE is essential for P. stewartii xylem dissemination, show evidence for a nutritional immunity response to P. stewartii that alters xylem sap composition, and present the first analysis of maize transcriptional responses to P. stewartii infection.
Preparation of novel targeting nanobubbles conjugated with small interfering RNA for concurrent molecular imaging and gene therapy in vivo
Authors: Wu Bolin , Shang Haitao , Liang Xitian , Sun Yixin , Jing Hui , Han Xue , Cheng Wen
Published: October 2019

The aim of this study was to establish a novel targeting nanobubble (TNB) conjugated with small interfering RNA (siRNA)‐cyanine 5 (Cy5) and to validate its theranostic ability in vivo. The TNB conjugated with neuroepithelial transforming gene 1 (NET‐1) siRNA‐Cy5 was prepared by thin‐film hydration and mechanical sonication method. A hepatocellular carcinoma (HCC) xenograft model was established by subcutaneously injecting SMMC‐7721 cells in BALB/c nude mice. The NET‐1 siRNA‐conjugated TNB was utilized for accurate contrast‐enhanced ultrasound in vivo imaging, which was enabled by the target ligand GPC‐3 antibody and specific gene transfection with the aid of low‐frequency ultrasound (LFUS) irradiation. BALB/c nude mice bearing tumors were randomized into 5 groups and irradiated with LFUS for 5 min after TNB administration; mice were treated twiceaweek for atotal of 60 d. The mean particle size of TNB was <500 nm. Mice treated with NET‐1 siRNA‐conjugated TNB showed a significant decrease in tumor growth and the highest survival rate. Our findings offer an effective and safe gene vehicle and probe for molecular imaging in vivo. It may improve the early diagnosis and treatment effects of HCC.—Wu, B., Shang, H., Liang, X., Sun, Y., Jing, H., Han, X., Cheng, W. Preparation of novel targeting nanobubbles conjugated with small interfering RNA for concurrent molecular imaging and gene therapy in vivo. FASEB J. 33, 14129‐14136 (2019). www.fasebj.org
Drug updates and approvals
Authors: Crump Lauren Hartsell , Benfield Miranda , Ramey Caleb , Arcara Ashley , Yang Sebin , Brown Jenna , Mospan Geoffrey , Mospan Cortney
Published: October 2019

In 2019, the FDA approved several new drugs for use in primary care. This article highlights the following new drugs: risankizumab-rzaa (Skyrizi); halobetasol and tazarotene (Duobrii); dolutegravir and lamivudine (Dovato); romosozumab-aqqg (Evenity); brexanolone (Zulresso); solriamfetol (Sunosi); aclidinium and formoterol (Duaklir Pressair); and siponimod (Mayzent).
Sustained-release Oral Hydromorphone for the Treatment of Opioid Use Disorder
Authors: Braithwaite Vivian , Fairgrieve Christopher , Nolan Seonaid
Published: October 2019

Objectives:

In 2017, almost 50,000 Americans and over 4000 Canadians died from an opioid overdose. Accordingly, an urgent need exists to improve access to evidence-based treatment for opioid addiction, and also to develop and evaluate alternative treatment options for opioid use disorder (OUD). We present a case of a patient with OUD who was successfully switched and managed on oral hydromorphone after development of a prolonged QTc interval on methadone.

Case:

A 51-year-old man with longstanding polysubstance use presented to an urban hospital in Vancouver, Canada, for management of alcohol intoxication and hyponatremia. At the time of admission, the patient was stable on 100 mg of methadone daily, but was found to have a persistently elevated QTc (>550 milliseconds), putting him at increased risk for Torsades de Pointes. In an effort to find an alternative opioid agonist therapy for maintenance, a trial of slow-release oral morphine was attempted, but discontinued due to the development of myoclonus. Once-daily sustained-release oral hydromorphone was then started, which was found to manage cravings well without notable side effects.

Discussion:

The case presented offers promise for the use of once-daily sustained-release oral hydromorphone as a viable treatment option for patients with OUD for whom first-line therapies are not suitable or tolerated. This case report is the first to our knowledge to demonstrate the successful use of oral hydromorphone for treatment of opioid use disorder.
Fresh Frozen Plasma versus Crystalloid Priming of Cardiopulmonary Bypass Circuit in Pediatric Surgery
Authors: Dieu Audrey , Rosal Martins Maria , Eeckhoudt Stephane , Matta Amine , Kahn David , Khalifa Céline , Rubay Jean , Poncelet Alain , Haenecour Astrid , Derycke Emilien , Thiry Dominique , Gregoire André , Momeni Mona
Published: October 2019

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New

Background

In congenital cardiac surgery, priming cardiopulmonary bypass (CPB) with fresh frozen plasma (FFP) is performed to prevent coagulation abnormalities. The hypothesis was that CPB priming with crystalloids would be different compared with FFP in terms of bleeding and/or need for blood product transfusion.

Methods

In this parallel-arm double-blinded study, patients weighing between 7 and 15 kg were randomly assigned to a CPB priming with 15 ml · kg−1 PlasmaLyte or 15 ml · kg−1 FFP in addition to a predefined amount of packed red blood cells used in all patients. The decision to transfuse was clinical and guided by point-of-care tests. The primary endpoints included postoperative bleeding tracked by chest tubes, number of patients transfused with any additional blood products, and the total number of additional blood products administered intra- and postoperatively. The postoperative period included the first 6 h after intensive care unit arrival.

Results

Respectively, 30 and 29 patients in the FFP and in the crystalloid group were analyzed in an intention-to-treat basis. Median postoperative blood loss was 7.1 ml · kg−1 (5.1, 9.4) in the FFP group and 5.7 ml · kg−1 (3.8, 8.5) in the crystalloid group (P = 0.219); difference (95% CI): 1.2 (−0.7 to 3.2). The proportion of patients additionally transfused was 26.7% (8 of 30) and 37.9% (11 of 29) in the FFP and the crystalloid groups, respectively (P = 0.355; odds ratio [95% CI], 1.7 [0.6 to 5.1]). The median number of any blood products transfused in addition to priming was 0 (0, 1) and 0 (0, 2) in the FFP and crystalloid groups, respectively (P = 0.254; difference [95% CI], 0 [0 to 0]). There were no study-related adverse events.

Conclusions

The results demonstrate that in infants and children, priming CPB with crystalloids does not result in a different risk of postoperative bleeding and need for transfusion of allogeneic blood products.
Addressing the Complications Associated With the Use of Arthrex TightRope RT in Anterior Cruciate Ligament Reconstruction
Authors: Maredupaka Siddhartha , Kumar Vijay , Nayak Mayur , Yadav Rahul
Published: October 2019

TightRope Reverse Tension is a second-generation suspensory fixation device that is used for graft fixation in anterior cruciate ligament reconstruction, with distinct advantages compared with fixed-loop devices. However, despite adhering to standard precautions, there are certain complications associated with its use, such as the button getting stuck in the guide-pin hole, button being pulled out too far laterally beyond the femoral cortex, and transverse impaction of the button in the region of corticocancellous bone-bridge. Furthermore, complete loop discontinuity or breakage can also possibly occur during cycling, when appropriate precautionary measures are not taken during graft preparation and passage. In this article, we present various techniques to prevent and a bailout from potential complications that occur with the use of TightRope Reverse Tension with extensive first-hand experience in using this implant.
Collaborating with Families and Law Enforcement Agencies to Improve Outcomes for Individuals with Autism Spectrum Disorder
Authors: Soares Neelkamal , White Kathryn E. , Christensen Robert T. , Christiansen Audrey , Apple Roger
Published: October 2019

Increased visibility of adverse encounters between individuals with autism spectrum disorder (ASD) and law enforcement (LE) has stimulated a dialog among providers. There are a variety of contributing factors to the increase, including the recognized lack of training of LE professionals on the needs of individuals with ASD and the paucity of awareness of resources by the families of these individuals. The aim of this article is to provide insight into developmental-behavioral pediatric professionals, to enhance safety and reduce adverse outcomes for individuals with ASD in schools and the community.
Ginsenoside Rb1 Alleviates Oxidative Low-Density Lipoprotein–Induced Vascular Endothelium Senescence via the SIRT1/Beclin-1/Autophagy Axis
Authors: Shi Guangyao , Liu Dinghui , Zhou Bin , Liu Yong , Hao Baoshun , Yu Shujie , Wu Lin , Wang Min , Song Zhiming , Wu Chaodong , Zhu Jieming , Qian Xiaoxian
Published: October 2019

Oxidative low-density lipoprotein (ox-LDL) induces endothelium senescence and promotes atherosclerosis. Ginsenoside Rb1 (gRb1) has been proved to protect human umbilical vein cells (HUVECs), but its effect on ox-LDL–induced endothelium senescence and the underlying mechanism remains unknown. This study is to explore the involvement of the SIRT1/Beclin-1/autophagy axis in the effect of gRb1 on protecting endothelium against ox-LDL–induced senescence. Hyperlipidemia of Sprague Dawley rats was induced by high-fat diet, and gRb1 was intraperitoneal injected. A senescence model of HUVECs induced by ox-LDL was also established. The results showed that gRb1 alleviated hyperlipidemia-induced endothelium senescence and ox-LDL-induced HUVECs senescence. GRb1 also restored the reductions in SIRT1 and autophagy, which were involved in the anti-senescence effects. Beclin-1 acetylation was reduced, and the correlation between SIRT1 and Beclin-1 was increased by gRb1. Results of our study demonstrated the anti-senescence function of gRb1 against hyperlipidemia in the endothelium, and the underlying mechanism involves the SIRT1/Beclin-1/autophagy axis.
HLA-B*58:01 carrier status of Hmong in Minnesota: first in Hmong genotyping for prevalence of this biomarker of risk for severe cutaneous adverse reactions caused by allopurinol
Authors: Peng Kerui , Bjork Jonathan , Wen Ya-Feng , Roman Youssef M. , Culhane-Pera Kathleen , Lo May Xia , Gertner Elie , Straka Robert J.
Published: October 2019

Allopurinol, a common medication to treat gout, is associated with severe cutaneous adverse reactions, and the occurrence is highly predicted by an individual’s HLA-B*58:01 carrier status. Guidelines endorse preemptive testing in select Asian populations before initiating allopurinol. The Hmong, an Asian subpopulation originally from China who now live dispersed around the world, have a 2.5-fold higher risk of gout when compared to non-Hmong in Minnesota. Given the concern for severe cutaneous adverse reactions when prescribing allopurinol, we quantified the carrier status of HLA-B*58:01 in Hmong from two independent cohorts in Minnesota. Using a community-based participatory research approach, HLA-B*58:01 carrier status was determined in 49 US-born Hmong without a history of gout or allopurinol use. Further, 47 Hmong patients undergoing clinical evaluation to receive gout pharmacotherapy were also tested. The frequency of HLA-B*58:01 positive carrier status in these two cohorts were compared to published data from a Han Chinese (n = 2910) and a Korean cohort (n = 485) using a Fisher’s exact test with a Bonferroni-corrected P-value <0.025 for significance. With one uninterpretable result, we identified two out of 95 people (2.1%) who carried HLA-B*58:01. This 2.1% incidence in these Hmong adults is notably lower than Han Chinese (19.6%, P < 0.0001) and Korean (12.2%, P = 0.0016) populations. Though commonly understood to be of Chinese descent, the lower prevalence within the Hmong underscores the risk of generalizing genotypic findings from Chinese to Asian subpopulations. We suggest no change to the current guidelines recommending which populations should be tested for HLA-B*58:01 before allopurinol use until further validation.
Dose to Medical Personnel
Authors: Misdaq M.A. , Harrass H. , Saikouk H. , Matrane A.
Published: October 2019

Radioiodine 131I is successfully used in nuclear medicine for the treatment of hyperthyroidism and thyroid cancer. This radionuclide emits β− particles used for the treatment and gamma photons used for diagnosis. The aim of this study is to determine gamma radiation doses received by medical personnel situated at a distance of 1 m from patients having ingested 131I for the treatment of hyperthyroidism diseases. Indeed, gamma doses were calculated using a Monte Carlo code based on simulating the interaction processes of gamma photons emitted by 131I in the thyroid gland, air, and an ambient flow meter placed at a distance of 1 m from the thyroid gland to measure the administered 131I activity. The thyroid volume of patients was measured by means of a gamma camera. Gamma dose equivalent rates were measured by means of an ambient flow meter situated at a distance of 1 m from the thyroid of the treated patients. Data obtained by the Monte Carlo and experimental methods were found to be in good agreement with each other.
Effect of Teflon Transmittance on Sensitivity of Thermoluminescence Dosimeter Cards
Authors: Podobedov V.B. , Romanyukha A. , Miller C.C. , Hoy A.
Published: October 2019

Thermoluminescence dosimeter cards purchased by the US Navy in recent years have different radiation sensitivities, e.g., they exhibit a different amount of light per dose unit. Presented tests indicate that the optical transparency of the Teflon encapsulation is partially responsible for the significant variation of the DT-702/PD radiation sensitivity. It was confirmed also that the Teflon transparency is in fact a primary cause of the radiation sensitivity increase in the most recently produced dosimetric cards. This conclusion is based on the correlation found between the calibrated radiation sensitivity of the dosimeter card element and the optical transparency of its Teflon encapsulation. The transparency measurements were performed at the wavelength of 400 nm within a 10 nm spectral interval effectively covering the spectral range of the thermoluminescence. It is anticipated that the experimentally determined correlation will help to approve the acceptance of new thermoluminescence dosimeter cards in the Naval Dosimetry Center inventory as well as improve the production process.
Comparison of Biomicroscopy and Light Microscopy Findings in Demodex Diagnosis in Patients With Chronic Blepharitis
Authors: Tanriverdi Cafer , Balci Ozlem , Demirci Goktug , Odabasi Mahmut , Ozsutcu Mustafa , Nurozler Tabakci Burcu
Published: October 2019

Objectives:

We aimed to compare the results of biomicroscopic examination and light microscopy in the diagnosis of Demodex infestation in chronic blepharitis cases.

Methods:

The study was performed with retrospective data and included patients with chronic blepharitis and who were admitted to the Medipol University Ophthalmology Outpatient Clinic. Biomicroscopic evaluation was performed intentionally under 40x magnification to investigate the presence of Demodex ectoparasites. Three or four pieces of eyelashes were obtained from all cases with epilation technique, and Demodex parasites were examined under ×100 and ×400 magnifications with light microscopy. The presence of one or more Demodex parasites in the examined area under light microscopy was considered to be positive for infestation. We calculated sensitivity, specificity, false-positive rate, false-negative rate, and positive and negative predictive values of biomicroscopic examination compared with those of positive light microscopy.

Results:

Of the 255 subjects included in the study, 134 (52.5%) were men and 121 (47.5%) were women. The mean age was 43.9±11.9 years. Of the 255 chronic blepharitis cases, 130 (51%) presented Demodex infestation on light microscopy. We calculated the sensitivity, specificity, false-positive rate, false-negative rate, positive predictive value, and negative predictive value and were found to be 83.07%, 90.4%, 9.6%, 16.9%, 90%, and 83.7%, respectively, for the biomicroscopic examination.

Conclusions:

Careful biomicroscopic examination can be time-efficient and cost-effective, and the need for more advanced and invasive procedures for the identification of Demodex in patients with chronic blepharitis can be reduced.
Multiple-Image Deep Learning Analysis for Neuropathy Detection in Corneal Nerve Images
Authors: Scarpa Fabio , Colonna Alessia , Ruggeri Alfredo
Published: October 2019

Purpose:

Automated classification of corneal confocal images from healthy subjects and diabetic subjects with neuropathy.

Methods:

Over the years, in vivo confocal microscopy has established itself as a rapid and noninvasive method for clinical assessment of the cornea. In particular, images of the subbasal nerve plexus are useful to detect pathological conditions. Currently, clinical information is derived through a manual or semiautomated process that traces corneal nerves and achieves their descriptors (eg, density and tortuosity). This is tedious and subjective. To overcome this limitation, a method based on a convolutional neural network (CNN) for the classification of images from healthy subjects and diabetic subjects with neuropathy is proposed. The CNN simultaneously analyzes 3 nonoverlapping images, from the central region of the cornea. The algorithm automatically extracts features, without the need for neither nerve tracing nor parameter extraction nor montage/mosaicking, and provides an overall classification for each image trio.

Results:

On a dataset composed by images from 50 healthy subjects and 50 subjects with neuropathy, the algorithm achieves a classification accuracy of 96%. The proposed method improves the results obtained using a traditional method that traces nerves and evaluates their density and tortuosity.

Conclusions:

The proposed method provides a completely automated analysis of corneal confocal images. Results demonstrate the potentiality of the CNN in identifying clinically useful features for corneal nerves by analysis of multiple images.
Intraocular Pressure in the Eyes of Patients With Carotid-Cavernous Fistulas: Profile, Intereye Asymmetry, and Treatment Outcomes
Authors: Khurana Mona , Alam Md. Shahid , Balekudaru Shantha , Vijaya Lingam , Madhuri Manapakkam B. , Halbe Swatee V. , Noronha Veena O. , George Ronnie J. , Mukherjee Bipasha
Published: October 2019

Precis:

Secondary ocular hypertension (OHT) is common in carotid-cavernous fistulas (CCFs). Management of elevated intraocular pressure (IOP) is possible with a multidisciplinary approach. The ipsilateral normal eyes may have higher IOP than the contralateral eyes.

Purpose:

To study the IOP profile of the eyes of patients with a CCF, treatment outcomes for elevated IOP, and intereye IOP asymmetry in the eyes with normal IOP.

Methods:

This was a retrospective case series. A total of 64 eyes of 60 patients with digital subtraction angiography-proven CCF diagnosed from the year 2000 to 2016 were included. The demographics, clinical features, management, and outcomes were recorded. The primary outcome included understanding of the cause of elevated IOP. The secondary outcomes included comparison of the IOP between contralateral eyes and ipsilateral normal eyes (IOP <21 mm Hg) and management outcomes for elevated IOP.

Results:

The mean age of the patients was 45.6±18.2 years. In the study population, 70% of the patients were males. Indirect CCF was present in 55% of the eyes. It was found that 64.06% (n=41) of the eyes had elevated IOP, glaucoma, or were glaucoma suspects. Among all the eyes, 40.62% (n=26) of the eyes had secondary OHT due to elevated episcleral venous pressure, whereas 7.81% (n=5) of the eyes had secondary open-angle glaucoma. The mean IOP was higher in the ipsilateral eyes than in the other eyes (22.95±7.1vs. 15.11±2.99 mm Hg; P<0.001). The mean IOP in the ipsilateral normal eyes was higher than that in the contralateral eyes, with a mean difference of 2.92±2.29 mm Hg (confidence interval of the mean difference: 1.90-3.94 mm Hg; P<0.0001). IOP reduction (<21 mm Hg) was achieved in 70.7% of the patients following CCF management with intermittent carotid massage, endovascular treatment, IOP-lowering medications, or a combination among these.

Conclusions:

Secondary OHT due to elevated episcleral venous pressure was more common than secondary open-angle glaucoma. Ipsilateral normal eyes had higher IOP than contralateral eyes. IOP-lowering agents and management of CCF resulted in IOP control in most patients.
Interaction of CYP2C19 G681A polymorphism and omeprazole on clopidogrel responsiveness and impact in patients with acute coronary syndrome
Authors: Jirungda Sornsith , Pussadhamma Burabha , Komanasin Nantarat , Senthong Vichai , Leuangwatthananon Wit
Published: October 2019

Objective

The aim of this study was to explore the individual effects of the CYP2C19 G681A polymorphism and omeprazole use and their interaction on clopidogrel responsiveness in acute coronary syndrome (ACS). The CYP2C19 G681A polymorphism and omeprazole use were both known for retarding the effects of clopidogrel under broad cardiovascular conditions; however, data from ACS patients were limited.

Methods

We conducted a cross-sectional study of 102 ACS patients who received clopidogrel before percutaneous coronary intervention. The platelet function was assessed by a Platelet Function Analyzer-200, in which clopidogrel hyporesponsiveness was defined as a closure time (CT) of ≤ 106 s. The CYP2C19 G681A polymorphism was investigated using the PCR-RFLP technique. Statistical analysis was performed by using χ
2 test, Student’s t-test, binary logistic regression, and receiver-operating characteristic (ROC) curve.

Results

Carriages of the CYP2C19 681A allele and omeprazole use were present in 47.1 and 37.3% patients, respectively. The mean CT ± SD was 103.1 ± 1.7 s and the prevalence of clopidogrel hyporesponsiveness was 66.7%. The CT was significantly shorter in carriages of the 681A allele compared with the 681G allele (P = 0.002), but had no significant difference in patients with vs. without omeprazole use (P = 0.467). The ROC analysis of an effect on clopidogrel hyporesponsiveness of CYP2C19 G681A alone and combination with omeprazole use had area under the curve values of 0.654 and 0.672, respectively.

Conclusion

In ACS patients, the effect of the CYP2C19 G681A polymorphism on clopidogrel responsiveness, but not omeprazole use, is strong. However, a combination of both factors enhances clopidogrel hyporesponsiveness.
Weighing the potential late benefits versus early hazard associated with bioresorbable vascular scaffolds in percutaneous coronary interventions: a Markov decision analytic model
Authors: Fazel Reza , Vilain Katherine A. , Cohen David J. , Yeh Robert W.
Published: October 2019

Objective

Use of poly-L-lactic acid-based bioresorbable scaffolds (BRS) has been associated with increased risk of device thrombosis during the first 3 years after implantation as compared to metallic everolimus-eluting stents (EES). The long-term performance of BRS relative to EES remains unknown.

Methods

We used a Markov decision analysis model to evaluate the effectiveness of BRS vs. EES over a lifetime horizon. In addition to one-way sensitivity analyses of key variables, we evaluated the impact of optimal implantation technique and limiting procedures to larger vessels (>2.6 mm in diameter) on model results.

Results

Assuming no risk of target lesion revascularization for BRS after 3 years, we found a small increment in quality-adjusted life expectancy (QALE) of 0.02 with the use of BRS relative to EES, with benefit being observed after 21.8 years. Optimal implantation technique and limiting to larger vessels resulted in larger gains in QALE (0.08 and 0.06, respectively) with BRS and shorter times to equipoise (6.7 and 8.3 years, respectively). Model results were highly sensitive to variations in the relative risk of stent thrombosis (BRS vs. EES).

Conclusions

Based on currently available data, it would take approximately 21.8 years for the presumed late benefits of current BRS relative to EES to overcome the early hazard associated with their use under favorable assumptions. Optimal implantation technique and limiting procedures to larger vessels improved BRS performance and reduced time to equipoise. Eliminating the higher BRS thrombosis risk is necessary in developing future generations of BRS as an acceptable alternative to EES.
SWEDEHEART-1-year data show no benefit of newer generation drug-eluting stents over bare-metal stents in patients with severe kidney dysfunction following percutaneous coronary intervention
Authors: Edfors Robert , James Stefan , Szummer Karolina , Evans Marie , Carrero Juan-Jesus , Faxén Jonas , Persson Jonas , Spaak Jonas , Varenhorst Christoph , Jernberg Tomas , Lagerqvist Bo
Published: October 2019

Background

We hypothesized that the transition from bare-metal stents (BMS) to newer generation drug-eluting stents (n-DES) in clinical practice may have reduced the risk also in patients with kidney dysfunction.

Methods:

Observational study in the national SWEDEHEART registry, that compared the 1-year risk of in-stent restenosis (RS) and stent thrombosis (ST) in all percutaneous coronary intervention treated patients(n = 92 994) during 2007–2013.

Results:

N-DES patients were younger than BMS, but had more often diabetes, previous myocardial infarction, previous revascularization and were more often treated with potent platelet inhibition. N-DES versus BMS, was associated with lower 1-year risk of RS in patients with estimated glomerular filtration rate (eGFR) >60 with a cumulative probability of 2.1% versus 5.3%, adjusted hazard ratio 0.30, 95% CI (0.27–0.34) and with eGFR 30–60: 3.0% versus 4.9%; hazard ratio 0.46 (0.36–0.60) but not in patients with eGFR <30: 8.1% versus 6.0%; hazard ratio 1.32 (0.71–2.45) (pinteraction = 0.009) as well as lower risk of ST for eGFR >60 and eGFR 30–60: 0.5% versus 0.9%; hazard ratio 0.52 (0.40–0.68) and 0.6% versus 1.3%; hazard ratio 0.54 (0.54–0.72) but not for eGFR <30; 2.1% versus 1.1%; hazard ratio 1.49 (0.56–3.98) (pinteraction = 0.027).

Conclusion:

N-DES is associated with lower 1-year risk of in-stent restenosis and stent thrombosis in patients with normal or moderately reduced kidney function but not in patients with severe kidney dysfunction, where stenting is associated with worse outcomes regardless of stent type.
Effect of intracoronary tirofiban following aspiration thrombectomy on infarct size, in patients with large anterior ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention
Authors: Basuoni Ahmed , El-Naggar Wael , Mahdy Mohamed , Al-Kaffas Sameh
Published: October 2019

Background

Myocardial recovery following primary percutaneous coronary intervention is often suboptimal despite of restoration of thrombolysis in myocardial infarction (TIMI) 3 flow, in part due to thrombus embolization which results in impairing microvascular reperfusion besides increasing infarct size. The purpose of the present study was to estimate the effect of aspiration thrombectomy followed by intracoronary delivery of tirofiban on decreasing the infarct size utilizing cardiac MRI (cMR) in large anterior ST-segment elevation myocardial infarction (STEMI) patients.

Patients

A prospective randomized controlled study of 100 patients with large anterior STEMI were randomized to (Study group) using intracoronary tirofiban (intracoronary) and (control group) without intocoronary tirofiban. A 6 F thrombus aspiration catheter was used in all patients. Tirofiban was injected locally at the place of the highly thrombus burden through the aspiration device after flushing the aspiration device well.

Results

Patients of intracoronary tirofiban group compared with control group had a significant difference in decreasing the infarct size at 30 days [median, 15.451 g – interquartile range (IQR), 17.404 gm – n = 50] vs (median, 43.828 g – IQR, 49.599 g – n = 50) P value = 0.002.

Conclusion

In patients early presented with large anterior STEMI, infarct size at 30 days was significantly decreased by intracoronary tirofiban delivered to the infarct lesion site followed aspiration thrombectomy.
Vascular reactivity to mental stress is associated with poor cardiovascular disease outcomes in females following acute coronary syndrome
Authors: Widmer Robert J. , Prasad Megha , Gomaa Mohammed , Sara Jaskanwal Deep S. , Reriani Martin K. , Lerman Lilach O. , Suwaidi Jassim Al , Lerman Amir
Published: October 2019

Background:

We aimed to test the hypothesis that peripheral endothelial dysfunction induced by mental stress may predict cardiovascular events after acute coronary syndrome beyond traditional cardiovascular disease risk factors.

Methods:

This was a prospective study in which 417 patients who had acute coronary syndrome were enrolled in two sites at the US and Qatar. Cardiovascular disease risk factors such as past medical history, blood pressure, heart rate, peripheral endothelial dysfunction, and response to three different mental stress examinations (Stroop Color Word, Arithmetic, and Spiral Omnibus) as assessed by ratio of reactive hyperemia tonometry (EndoPAT) with stress over EndoPAT at rest were obtained at baseline. Major adverse cardiac events were then recorded at 1 year after the index event.

Results:

There were no differences in baseline peripheral endothelial dysfunction or vascular response to mental stress between the US vs. Qatar patients. Women were more likely to experience major adverse cardiac events in the year following acute coronary syndrome (relative risk 2.42, 95% confidence interval 1.53–3.84, P = 0.044), and had a significantly lower mental stress ratio compared to women who did not (1.0 ± 0.17 vs. 1.20 ± 0.17, P = 0.04). In multivariate analyses stratified by sex, baseline peripheral endothelial dysfunction (EndoPAT < 1.7) (χ2 = 8.0, P = 0.005) and mental stress ratio (χ2 = 7.7, P = 0.006), were independently predictive of major adverse cardiac events in women, but not men.

Conclusion:

The current study demonstrates that in women both baseline endothelial function and vascular function in response to mental stress ratio are predictive of worse cardiovascular disease outcomes 1 year after acute coronary syndrome. The study may suggest an important mechanism for adverse clinical outcomes in women following acute coronary syndrome.
Profiling the patient with autoimmune hepatitis on calcineurin inhibitors: a real-world-experience
Authors: Pape Simon , Nevens Frederik , Verslype Chris , Mertens Caroline , Drenth Joost P.H. , Tjwa Eric T.T.L.
Published: October 2019

Objective

Therapy for autoimmune hepatitis (AIH) consists of steroid induction therapy, followed by maintenance therapy with azathioprine. However, up to 20% of patients experience either insufficient response or intolerance on first-line therapy. Calcineurin inhibitors (CNIs) are frequently used when first-line therapy fails. Although a number of studies report on efficacy, less is known on the patient trajectory before switch to CNIs. Our aim was to describe the road toward CNI therapy in AIH patients.

Methods

Patients with an AIH diagnosis who used CNIs as either second- or third-line treatment were included in the study. Reason for switch to CNI was assessed as either an insufficient response or intolerance to prior therapy. Efficacy was assessed by normalization of transaminases at last moment of follow-up.

Results

Final analysis included 20 patients who were treated with CNIs. Ten patients were treated with tacrolimus and ten patients received cyclosporine. In patients who used CNI treatment as third-line therapy (n = 13), duration of first-line therapy was almost twice as long as duration of second-line therapy (2.58 years vs. 1.33 years; P = 0.67). Patients treated with tacrolimus had relatively high trough levels (7.6 ng/mL) and more (minor) adverse events. Fifty-five percent of patients had normalization of transaminases at last moment of follow-up.

Conclusion

CNI treatment in AIH as second- or third-line therapy is effective in ~50% of patients. The trajectory before switch varies considerably between patients.
Cascade of Provider-Initiated Human Immunodeficiency Virus Testing and Counselling at Specific Life Events (Pregnancy, Sexually Transmitted Infections, Marriage) in Côte d'Ivoire
Authors: Inghels Maxime , Kouassi Arsène Kra , Niangoran Serge , Bekelynck Anne , Carillon Séverine , Sika Lazare , Danel Christine , Kone Mariatou , du Loû Annabel Desgrées , Larmarange Joseph
Published: October 2019

Background

Despite the implementation of Provider Initiated Testing and Counselling (PITC) in 2009, PITC coverage remains low in Cote d'Ivoire. The purpose of this study is to determine whether an human immunodeficiency virus (HIV) test was offered and performed at specific life events where PITC is recommended by national guidelines.

Methods

In 2017, a cross-sectional telephone survey was conducted among a representative sample of 3,867 adults from the general population in Côte d'Ivoire. The occurrences of the following events over the past 5 years were documented: pregnancy (event A) or partner's pregnancy (event B) of the last child, sexually transmitted infection (event C) and marriage (event D). For each of these events, participants were asked (i) if they consulted a health care professional, (ii) if they were offered an HIV test during that consultation and (iii) if they accepted it.

Results

Consulting a health care provider was reported by 94.9%, 58.3%, 70.3% and 19.1% of those who reported events A, B, C and D respectively. In case of medical consultations following events A, B, C and D, respectively 70.1%, 33.1%, 28.1%, and 78.8% of individuals were offered an HIV test. The testing acceptance was high regardless of the event. Overall, testing coverage was 63.7%, 16.9%, 13.4% and 14.5% for events A, B, C and D respectively.

Conclusions

Increasing HIV testing coverage in Côte d'Ivoire requires (i) facilitating attendance to health services in case of sexually transmitted infections, marriage and pregnancy—for men—and (ii) strengthening routine testing offer on these occasions.
Brief Report: Yield and Efficiency of Intensified Tuberculosis Case-Finding Algorithms in 2 High-Risk HIV Subgroups in Uganda
Authors: Semitala Fred C. , Cattamanchi Adithya , Andama Alfred , Atuhumuza Elly , Katende Jane , Mwebe Sandra , Asege Lucy , Nakaye Martha , Kamya Moses Robert , Yoon Christina
Published: October 2019

Background:

Tuberculosis (TB) risk varies among different HIV subgroups, potentially impacting intensified case finding (ICF) performance. We evaluated the performance of the current ICF algorithm [symptom screening, followed by Xpert MTB/RIF (Xpert) testing] in 2 HIV subgroups and evaluated whether ICF performance could be improved if TB screening was based on C-reactive protein (CRP) concentrations.

Methods:

We enrolled consecutive adults with CD4 counts ≤350 cells/µL initiating antiretroviral therapy and performed symptom screening, CRP testing using a low-cost point-of-care (POC) assay, and collected sputum for Xpert testing. We compared the yield and efficiency of the current ICF algorithm to POC CRP-based ICF among patients new to HIV care and patients engaged in care.

Results:

Of 1794 patients, 126/1315 (10%) new patients and 21/479 (4%) engaged patients had Xpert-positive TB. The current ICF algorithm detected ≥98% of all TB cases in both subgroups but required ≥85% of all patients to undergo Xpert testing. POC CRP-based ICF halved the proportion of patients in both subgroups requiring Xpert testing relative to the current ICF algorithm and had lower yield among patients engaged in care [81% vs. 100%, difference −19% (95% confidence interval: −41 to 3)]. Among patients new to care, POC CRP-based ICF had similar yield as the current ICF algorithm [93% vs. 98%, difference −6% (95% confidence interval: −11 to 0)].

Conclusions:

Among patients new to care, POC CRP-based screening can improve ICF efficiency without compromising ICF yield, whereas symptom-based screening may be necessary to maximize ICF yield among patients engaged in care.
The Fight Against HIV Is a Fight for Human Rights: A Personal Reflection
Authors: Coates Thomas J.
Published: October 2019

The fight against HIV started and continues to be a fight for human rights. AIDS was observed first in the United States in marginalized and stigmatized populations such as men who have sex with men, injection drug users, and commercial sex workers. Next were the observations of generalized epidemics in sub-Saharan Africa, a continent crippled by the legacy of colonialism. AIDS appeared in post-World War II, which witnessed independence of the former European colonies and the creation of the United Nations. There was remarkable advocacy that led to important advances in the rights of ethnic and racial minorities, sexual minorities, and women. This foundation of activism laid the groundwork to ensure that AIDS, and those infected with HIV, were addressed using the best of human rights frameworks. Social and behavioral sciences contributed important data to the human rights advances in the second half of the 20th century, and to the tools and resources needed for a human rights-based response to HIV. Remarkable investment in science have brought us new tools to treat and prevent HIV. Vigorous social and behavioral science research continues to be needed to ensure that the continued response to the HIV epidemic remains evidence-based, recognizing human rights, and ensuring that the scientific advances are available to everyone who needs them. Generations of scientists and activists need to continue as we are far from finished in the fight against HIV and for human rights.
Getting to Zero Begins With Getting to Ten
Authors: Auerbach Judith D.
Published: October 2019

Background Statement:

The global “90-90-90” targets introduced by UNAIDS in 2014—90% of people living with HIV will know their HIV status; 90% of those will be on antiretroviral treatment; and 90% of those will achieve viral suppression by 2020—have become more than a useful heuristic device, and now are the predominant framework for monitoring progress in the HIV response. Although this allows for important reflection on where HIV treatment gaps and opportunities exist in any particular context and globally, it deflects attention away from other very important aspects of HIV epidemics and their often-disproportionate impact on specific populations. Most significantly, it begs the question, what about the other 10-10-10?

Approach:

This article takes a critical look at the 90-90-90 targets and what is known about the 10-10-10 left behind to highlight some core issues and attendant questions that should be prioritized if we really intend to “get to zero.”

Findings and Conclusions:

These issues include how the targets are measured in the first place, the limitations of focusing the global response only on antiretroviral treatment and only on people already living with HIV, and the need for more, basic social research to address the range of factors underlying disparities in who are and are not reached in the 90-90-90 framework.