bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal cardiovascular response to nitroglycerin in migraine
Authors: van Oosterhout Willebrordus PJ , Schoonman Guus G , Saal Dirk P , Thijs Roland D , Ferrari Michel D , van Dijk J Gert 
Published: October 2019

Introduction Migraine and vasovagal syncope are comorbid conditions that may share part of their pathophysiology through autonomic control of the systemic circulation. Nitroglycerin can trigger both syncope and migraine attacks, suggesting enhanced systemic sensitivity in migraine. We aimed to determine the cardiovascular responses to nitroglycerin in migraine. Methods In 16 women with migraine without aura and 10 age- and gender-matched controls without headache, intravenous nitroglycerin (0.5 µg·kg−1·min−1) was administered. Finger photoplethysmography continuously assessed cardiovascular parameters (mean arterial pressure, heart rate, cardiac output, stroke volume and total peripheral resistance) before, during and after nitroglycerin infusion. Results Nitroglycerin provoked a migraine-like attack in 13/16 (81.2%) migraineurs but not in controls ( p = .0001). No syncope was provoked. Migraineurs who later developed a migraine-like attack showed different responses in all parameters vs. controls (all p < .001): The decreases in cardiac output and stroke volume were more rapid and longer lasting, heart rate increased, mean arterial pressure and total peripheral resistance were higher and decreased steeply after an initial increase. Discussion Migraineurs who developed a migraine-like attack in response to nitroglycerin showed stronger systemic cardiovascular responses compared to non-headache controls. The stronger systemic cardiovascular responses in migraine suggest increased systemic sensitivity to vasodilators, possibly due to insufficient autonomic compensatory mechanisms.
Prevalence and Predictors of Distress, Anxiety, Depression, and Quality of Life in Bereaved Family Caregivers of Patients With Advanced Cancer
Authors: Oechsle Karin , Ullrich Anneke , Marx Gabriella , Benze Gesine , Wowretzko Feline , Zhang Youyou , Dickel Lisa-Marie , Heine Julia , Wendt Kim Nikola , Nauck Friedemann , Bokemeyer Carsten , Bergelt Corinna 
Published: October 2019

Objective:To investigate prevalence and predictors of postloss distress, depressive and anxiety symptoms, and quality of life among bereaved family caregivers of patients with advanced cancer.Methods:Prospective multicenter study. Family caregivers (N = 160, mean age 56.8 years, 66% female) completed validated outcome measures (Distress Thermometer, Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire depression module 9-item scale, SF-8 Health Survey Questionnaire) 6 months after patient’s discharge or death at specialist inpatient palliative care ward.Results:Clinically relevant distress was observed in 82% with sadness (89%), exhaustion (74%), sleeping problems (68%), loneliness (53%), and sorrows (52%) being the most common distress-causing problems. Moderate/severe anxiety and depressive symptoms were observed in 27% and 35%, respectively. Compared to an adjusted norm sample, quality of life was significantly impaired with exception of “bodily pain” and physical component score. Preloss caregiving (odds ratio [OR] 2.195) and higher preloss distress (OR 1.345) predicted high postloss distress. Utilization of psychosocial support services (OR 2.936) and higher preloss anxiety symptoms (OR 1.292) predicted moderate/severe anxiety symptoms, lower preloss physical quality of life (OR 0.952), and higher preloss depressive symptoms (OR 1.115) predicted moderate/severe depressive symptoms.Conclusion:Preloss mental burden showed to be a consistent predictor for postloss burden and should be addressed during palliative care. Future research should examine specific caregiver-directed interventions during specialist palliative care.
Trastuzumab/Hyaluronidase-oysk: A New Option for Patients With HER2-Positive Breast Cancer
Authors: Duco Marissa R. , Murdock Joshua L. , Reeves David J. 
Published: October 2019

Objective: To assess the use of subcutaneous trastuzumab/hyaluronidase-oysk (SQ trastuzumab) in comparison to intravenous (IV) trastuzumab. Data Sources: A comprehensive PubMed literature search was performed from August 2012 to August 2019 using search terms Herceptin Hylecta, trastuzumab, hyaluronidase, subcutaneous, preference, safety, efficacy, and cost. Study Selection & Data Extraction: English-language clinical trials focusing on SQ trastuzumab were evaluated. Data Synthesis: In phase III trials, adverse event (AE) rates ranged from 64% to 97.6% of patients receiving SQ trastuzumab in 3 studies compared to 94.6% of patients receiving IV trastuzumab. In the phase III trial comparing SQ trastuzumab to IV trastuzumab, six-year overall survival (OS) was 84% in both groups. In pharmacokinetic analyses, trough concentrations and AUC0-21 were slightly higher in patients receiving SQ trastuzumab and differences were larger at the extremes of body weight. Two pharmacoeconomic analyses reported cost-savings associated with a 52-week treatment cycle of trastuzumab of $2,090 USD and $4,600 USD. Relevance to Patient Care and Clinical Practice: Food and Drug Administration (FDA)-approved in February 2019, SQ trastuzumab, a monoclonal antibody that binds to human epidermal growth factor receptor 2 (HER2) protein in combination with hyaluronidase, offers an alternative dosage form for patients with breast tumors overexpressing HER2. Conclusions: SQ trastuzumab has a similar safety profile to IV trastuzumab. Although it may be slightly more cost-effective, its role in the treatment of HER2-overexpressing tumors requires further study in those at the extremes of body weight due to differences in drug exposure compared to IV trastuzumab.
Major obstacles to doxorubicin therapy: Cardiotoxicity and drug resistance
Authors: Al-malky Hamdan S , Al Harthi Sameer E , Osman Abdel-Moneim M 
Published: October 2019

Background Doxorubicin is one of the most commonly prescribed and time-tested anticancer drugs. Although being considered as a first line drug in different types of cancers, the two main obstacles to doxorubicin therapy are drug-induced cardiotoxicity and drug resistance. Method The study utilizes systemic reviews on publications of previous studies obtained from scholarly journal databases including PubMed, Medline, Ebsco Host, Google Scholar, and Cochrane. The study utilizes secondary information obtained from health organizations using filters and keywords to sustain information relevancy. The study utilizes information retrieved from studies captured in the peer-reviewed journals on “doxorubicin-induced cardiotoxicity” and “doxorubicin resistance.” Discussion and results The exact mechanisms of cardiotoxicity are not known; various hypotheses are studied. Doxorubicin can lead to free radical generation in various ways. The commonly proposed underlying mechanisms promoting doxorubicin resistance are the expression of multidrug resistance proteins as well as other causes. Conclusion In this review, we have described the major obstacles to doxorubicin therapy, doxorubicin-induced cardiotoxicity as well as the mechanisms of cancer drug resistance and in following the treatment failures.
Brinzolamide/brimonidine fixed-dose combination bid as an adjunct to a prostaglandin analog for open-angle glaucoma/ocular hypertension
Authors: Topouzis Fotis , Goldberg Ivan , Bell Katharina , Tatham Andrew J , Ridolfi Antonia , Hubatsch Douglas , Nicolela Marcelo , Denis Phillipe , Lerner S Fabian 
Published: October 2019

Purpose: To evaluate the additive intraocular pressure–lowering effect of twice-daily brinzolamide 1%/brimonidine 0.2% fixed-dose combination (BBFC) as an adjunct to a prostaglandin analog (PGA) in patients with open-angle glaucoma or ocular hypertension insufficiently controlled with PGA monotherapy. Methods: In this Phase 4, double-masked trial, patients aged ⩾18 years, with a mean intraocular pressure of ⩾19 and <32 mm Hg in at least one eye were randomized (1:1) to receive BBFC + PGA ( n = 96) or vehicle + PGA ( n = 92) for 6 weeks. The primary endpoint was the mean change in diurnal intraocular pressure from baseline (averaged over 09:00 and 11:00 h) at Week 6. Results: The mean diurnal intraocular pressure at baseline was similar in the BBFC + PGA (22.8 mm Hg) and vehicle + PGA (22.9 mm Hg) groups. The least squares mean change in diurnal intraocular pressure from baseline at Week 6 was greater with BBFC + PGA (−5.59 mm Hg (95% confidence interval: −6.2 to −5.0)) than with vehicle + PGA (−2.15 mm Hg (95% confidence interval: −2.7 to −1.6)); the treatment difference was statistically significant in favor of BBFC + PGA (−3.44 mm Hg, (95% confidence interval: −4.2 to −2.7); p < 0.001). Ocular adverse events were reported in 21.1% and 8.7% of patients in the BBFC + PGA and vehicle + PGA groups, respectively. The most frequent ocular adverse event was ocular hyperemia (5.3%) in the BBFC + PGA group and blurred vision (2.2%) in the vehicle + PGA group. Conclusion: BBFC + PGA significantly reduced mean diurnal intraocular pressure than PGA alone in patients with open-angle glaucoma or ocular hypertension. The safety findings with BBFC + PGA were consistent with the known safety profile of the individual medications.
Lamellar macular hole in diabetic retinopathy
Authors: Kuo Bo-I , Yang Chung-May , Hsieh Yi-Ting 
Published: October 2019

Purpose: To describe the clinical features and surgical outcomes of diabetic retinopathy–associated lamellar macular hole and compare them with those of idiopathic lamellar macular hole. Methods: A total of 17 eyes with diabetic retinopathy–associated lamellar macular hole and 30 eyes with idiopathic lamellar macular hole undergoing surgery were retrospectively enrolled. Baseline best-corrected visual acuity, preoperative optical coherence tomography characteristics, and final best-corrected visual acuity were compared between two groups. Results: Both the baseline and the final best-corrected visual acuity in the diabetic retinopathy group were significantly worse than those in the idiopathic group (p = 0.029 for baseline, p = 0.002 for final). Lamellar macular hole in diabetic retinopathy tended to have a wider opening (p < 0.001) and a thinner residual base (p = 0.023). The width and height of parafoveal schisis in diabetic retinopathy–associated lamellar macular hole were both larger than those in idiopathic lamellar macular hole (p < 0.001 for both). After operation, both groups achieved significant improvement in best-corrected visual acuity (p < 0.01 for both). Conclusion: Compared with idiopathic group, diabetic retinopathy–associated lamellar macular hole had worse baseline best-corrected visual acuity, wider defect, and more pronounced parafoveal schisis. However, significant visual improvement could be obtained after operation. All cases in both groups achieved good anatomical outcomes with normalization of foveal contour and reduction of parafoveal schisis.
Stroke in the Middle-East and North Africa: A 2-year prospective observational study of intravenous thrombolysis treatment in the region. Results from the SITS-MENA Registry
Authors: Al-Rukn S , Mazya M , Akhtar N , Hashim H , Mansouri B , Faouzi B , Aref H , Abdulrahman H , Kesraoui S , Hentati F , Gebelly S , Ahmed N , Wahlgren N , Abd-Allah F , Almekhlafi M , Moreira T 
Published: October 2019

Background and methods Intravenous thrombolysis for acute ischemic stroke in the Middle-East and North African (MENA) countries is still confined to the main urban and university hospitals. This was a prospective observational study to examine outcomes of intravenous thrombolysis-treated stroke patients in the MENA region compared to the non-MENA stroke cohort in the SITS International Registry. Results Of 32,160 patients with ischemic stroke registered using the SITS intravenous thrombolysis protocol between June 2014 and May 2016, 500 (1.6%) were recruited in MENA. Compared to non-MENA (all p < 0.001), median age in MENA was 55 versus 73 years, NIH Stroke Scale score 12 versus 9, onset-to-treatment time 138 versus 155 min and door-to-needle time 54 min versus 64 min. Hypertension was the most reported risk factor, but lower in MENA (51.7 vs. 69.7%). Diabetes was more frequent in MENA (28.5 vs. 20.8%) as well as smoking (20.8 vs. 15.9%). Hyperlipidemia was less observed in MENA (17.6 vs. 29.3%). Functional independence (mRS 0–2) at seven days or discharge was similar (53% vs. 52% in non-MENA), with mortality slightly lower in MENA (2.3% vs. 4.8%). SICH rates by SITS-MOST definition were low (<1.4%) in both groups. Conclusions Intravenous thrombolysis patients in MENA were younger, had more severe strokes and more often diabetes. Although stroke severity was higher in MENA, short-term functional independency and mortality were not worse compared to non-MENA, which could partly be explained by younger age and shorter OTT in MENA. Decreasing the burden of stroke in this young population should be prioritized.
Serum MMP-9: a novel biomarker for prediction of clinical relapse in patients with quiescent Crohn’s disease, a post hoc analysis
Authors: Yablecovitch Doron , Kopylov Uri , Lahat Adi , Amitai Michal M. , Klang Eyal , Ben-Ami Shor Dana , Neuman Sandra , Levhar Nina , Fudim Ella , Avidan Benjamin , Laish Ido , Selinger Limor , Zingboim-Orbach Noam , Picard Orit , Yavzori Miri , Eliakim Rami , Ben-Horin Shomron 
Published: October 2019

Background: Matrix metalloproteinase-9 (MMP-9) is a novel marker of intestinal inflammation. The aim of this study was to assess if serum MMP-9 levels predict clinical flare in patients with quiescent Crohn’s disease (CD). Methods: This study was a post hoc analysis of a prospective observational study in which quiescent CD patients were included and followed until clinical relapse or the end of a 2-year follow-up period. Serial C-reactive protein (CRP) and fecal calprotectin (FC) levels were measured, and the patients underwent repeated capsule endoscopies (CEs) every 6 months. Small bowel inflammation was quantified by Lewis score (LS) for CE. A baseline magnetic resonance enterography was also performed, and MaRIA score was calculated. Serum MMP-9 levels in baseline blood samples were quantified by ELISA. Results: Out of 58 eligible enrolled patients, 16 had a flare. Higher levels of baseline MMP-9 were found in patients who developed subsequent symptomatic flare compared with patients who did not [median 661 ng/ml, 25–75 interquartile range (IQR; 478.2–1441.3) versus 525.5 ng/ ml (339–662.7), respectively, p = 0.01]. Patients with serum MMP-9 levels of 945 ng/ ml or higher were at increased risk for relapse within 24 months [area under the curve (AUC) of 0.72 [95% confidence interval (CI): 0.56–0.88]; hazard ratio 8.1 (95% CI 3.0–21.9, p < 0.001)]. Serum MMP-9 concentrations showed weak and moderate correlation to baseline LS and FC, respectively ( r = 0.31, p = 0.02; r = 0.46, p < 0.001). No correlation was found between serum MMP-9 to CRP and MaRIA score. Conclusions: Serum MMP-9 may be a promising biomarker for prediction of clinical flare in CD patients with quiescent disease.
Public Attitudes Toward the Secondary Uses of Patient Records for Pharmaceutical Companies’ Activities in Japan
Authors: Nakada Haruka , Inoue Yusuke , Yamamoto Keiichiro , Matsui Kenji , Ikka Tsunakuni , Tashiro Shimon 
Published: October 2019

Objective:The objective of this study is to assess public attitudes toward pharmaceutical companies’ secondary uses of patient records and public preferences regarding consent approaches.Method:3000 responses to an online survey were collected from adults in Japan. The questionnaire included 32 items related to (1) awareness of “clinical trials”; (2) awareness of the processes of drug development, such as cost, time, and the number of candidate substances in a new drug; (3) knowledge of the laws and regulations for use of patient records in Japan; (4) assessment of the public benefit of the secondary use of patient records; (5) preferences for consent for the secondary use of patient records; and (6) basic characteristics of the respondents.Results:The public benefit from secondary use of records by academic institutions for scientific research was rated highest. All of the activities by pharmaceutical companies were rated higher than those by governmental institutions and other for-profit companies. Regarding consent approaches, 37.9% preferred an “opt-in” approach for new drug development by pharmaceutical companies, 79.7% of whom would change their preference to an “opt-out” approach under specific conditions, such as ensuring intended uses only.Conclusion:Our respondents consider the “public benefit” as dependent on the relative distance from “promoting public health” when assessing the secondary purpose of patient record use. Pharmaceutical companies should include the beneficial purposes when using patient records with “opt-out” approach. Policy makers should pay more attention to the purposes of use when developing personal information protection policies.
Malpractice litigation, quality improvement, and the University Hospitals Obstetric Quality Network
Authors: Cossler Nancy , Liu James , Porter Steven , Albertini Megan , Katz Tyler , Pronovost Peter 
Published: October 2019

Objective A healthcare organization’s medical malpractice data can help identify patient safety risks and drive improvement. In most organizations, obstetric malpractice losses are assumed to be part of the risk of delivering obstetric care. We describe a systematic approach to mitigating risks for obstetric patients and their newborns while simultaneously improving patient outcomes and reducing obstetric litigation costs at University Hospitals, a northeast Ohio-based health system of 18 hospitals, including seven hospitals providing obstetric services and delivering approximately 8000 women per year. Methods From multiple data sources, including malpractice claims data, the team identified four key drivers of risk on the obstetric service: hypoxic ischemic encephalopathy, obstetric hemorrhage, hypertensive disorders of pregnancy, and shoulder dystocia. Collectively, these contributed to multiple adverse maternal and neonatal outcomes and accounted for 71% of obstetric litigation costs from 2009 to 2015. In response, the team built a regional obstetric quality network and implemented interventions to mitigate the four major risk areas. Results We achieved a substantial reduction in serious safety events from 2010 to 2018, defined as any event where the standard of care was not met and the level of harm to mother or baby was one (death) or two (severe permanent or temporary harm). We also achieved a reduction in obstetric litigation costs between 2009–2012 and 2015–2018. Discussion This multifaceted intervention was associated with decreased patient harm and reduced obstetric litigation costs. Application of this approach to other hospitals could result in improvements in obstetric patient safety and reduced obstetric litigation costs.
Alpha-Catenin Is Dispensable for Normal Hematopoietic Stem Cell Function.
Authors: Mikhalkevich Natallia , Becker Michael W. 
Published: October 2019

Abstract
Abstract 1438
Poster Board I-461
We previously demonstrated the loss of expression of alpha-E-Catenin, the product of the CTNNA1 gene, in primary leukemic stem cells isolated from patients with advanced Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) associated with loss of all or part of the long arm of chromosome 5. To formally assess the impact of loss of Ctnna1 expression on hematopoiesis, we employed a murine model for the hematopoietic specific conditional loss of Ctnna1 expression. We demonstrate that Ctnna1 deficiency is associated with normal hematopoietic maturation and proliferation as assessed by peripheral blood examination and methycellulose colony assays. We assessed stem cell and early progenitor frequencies using both flow cytometry and functional assays. Ctnna1 deficiency was associated with equivalent frequencies of Sca1+C-Kit+CD135-Lineage- HSCs in both experimental animals and controls. Short term HSC and MPP frequencies were likewise unaltered. We assessed HSC function using transplantation studies. In competitive repopulation experiments, HSCs deficient for Ctnna1 maintained stable engraftment of recipient mice for up to 1 year. Limiting dilution analyses detected no significant difference in HSC frequency between wild type and Ctnna1 deficient mice. We examined the potential role of Ctnna1 deficient hematopoietic stem cells in two murine models for myeloid neoplasms 1.) exposure to mutagen ENU and 2.) a model for murine AML driven by the HoxA9-Nup98 fusion product. Following exposure of HSCs to ENU, loss of Ctnna1 was not associated with an increased risk of development of a myeloid neoplasm. Expression of the HoxA9-Nup98 fusion product by retroviral infection of Ctnna1 deficient and wild type Sca1+C-Kit+Lineage- cells resulted in no difference in time to development of the previously characterized myeloproliferative disorder or acute leukemia. Taken together, these data demonstrate that in the absence of specific genetic abnormalities, loss of Ctnna1 expression in primary murine HSCs is not associated with aberrant HSC function or the development of myeloid neoplasms. Further studies are necessary to define a role for of loss of Ctnna1 expression in human myeloid malignancies.

Disclosures
No relevant conflicts of interest to declare.