bluuebunny/crossref_metadata_2025_split huggingface dataset:
Climatic and Seasonal Circumstances of Hypertensive Intracerebral Hemorrhage in a Worldwide Cohort
Authors: Herweh Christian , Nordlohne Stefan , Sykora Marek , Uhlmann Lorenz , Bendszus Martin , Steiner Thorsten 
Published: November 2017

Background and Purpose—
Numerous studies have investigated the influence of meteorologic factors and seasons on the incidence of spontaneous intracerebral hemorrhage (ICH) with ambiguous results. In the present study, data from a large, international multicenter trial in patients with ICH were used to identify seasonal and meteorologic determinants for hypertensive-ICH with greater applicability.

Methods—
Patients were grouped according to the presumptive ICH cause, that is, hypertensive when located in the basal ganglia brain stem as well as cerebellum and nonhypertensive when located lobar. Both groups were compared with regard to air temperature and air pressure and their occurrence during the year. A regression analysis was performed to identify independent predictors of hypertensive-ICH.

Results—
Only hypertensive-ICH showed a seasonal pattern and occurred with higher air pressure values and at younger age. Independent predictors of hypertensive-ICH were increased air pressure on the actual day of the event and younger age as well as higher temperature.

Conclusions—
In the present study with an international cohort, besides age air pressure, more than temperature, had an influence on the occurrence of hypertensive-ICH, only.
The Relationships among Actual Weather Events, Perceived Unusual Weather, Media Use, and Global Warming Belief Certainty in China
Authors: Wang Xiao , Lin Lin 
Published: November 2017

Abstract
Previous research revealed that if individuals personally experience an unusual weather event as a result of global warming (vs no personal experience), they may hold higher belief certainty that global warming is happening and hence develop more favorable attitudes toward mitigation actions. However, much of the previous research focused on self-reported personal experience and global warming beliefs using cross-sectional surveys; reverse causality is thus possible. Based on weather records and survey data, the present research examined whether actual weather events can influence one’s perceptions of unusual weather and belief certainty. Severe Typhoon Fitow 2013, but not hot summer temperatures, directly predicted the Chinese perceived experience of unusual weather and indirectly predicted their belief certainty and attitudes toward mitigation behavior. However, the effects were relatively small. Possible explanations and implications for environmental education are discussed.
Intra-articular Mesenchymal Stem Cell Therapy for the Human Joint: A Systematic Review
Authors: McIntyre James A. , Jones Ian A. , Han Bo , Vangsness C. Thomas 
Published: November 2017

Background: Stem cell therapy is emerging as a potential treatment of osteoarthritis (OA) and chondral defects (CDs). However, there is a great deal of heterogeneity in the literature. The indications for stem cell use, the ideal tissue source, and the preferred outcome measures for stem cell–based treatments have yet to be determined. Purpose: To provide clinicians with a comprehensive overview of the entire body of the current human literature investigating the safety and efficacy of intra-articular mesenchymal stem cell (MSC) therapy in all joints. Methods: To provide a comprehensive overview of the current literature, all clinical studies investigating the safety and efficacy of intra-articular MSC therapy were included. PubMed, MEDLINE, and Cochrane Library databases were searched for published human clinical trials involving the use of MSCs for the treatment of OA and CDs in all joints. A total of 3867 publications were screened. Results: Twenty-eight studies met the criteria to be included in this review. Fourteen studies treating osteoarthritis and 14 studies treating focal chondral defects were included. MSCs originating from bone marrow (13), adipose tissue (12), synovial tissue (2), or peripheral blood (2) were administered to 584 distinct individuals. MSCs were administered into the knee (523 knees), foot/ankle (61), and hip (5). The mean follow-up time was 24.4 months after MSC therapy. All studies reported improvement from baseline in at least 1 clinical outcome measure, and no study reported major adverse events attributable to MSC therapy. Discussion: The studies included in this review suggest that intra-articular MSC therapy is safe. While clinical and, in some cases, radiological improvements were reported for both OA and CD trials, the overall quality of the literature was poor, and heterogeneity and lack of reproducibility limit firm conclusions regarding the efficacy of these treatments. Conclusion: This review provides strong evidence that autologous intra-articular MSC therapy is safe, with generally positive clinical outcomes.
Effects of Anterior Closing Wedge Tibial Osteotomy on Anterior Cruciate Ligament Force and Knee Kinematics
Authors: Yamaguchi Kent T. , Cheung Edward C. , Markolf Keith L. , Boguszewski Daniel V. , Mathew Justin , Lama Christopher J. , McAllister David R. , Petrigliano Frank A. 
Published: November 2017

Background: A certain percentage of patients undergoing anterior cruciate ligament (ACL) reconstruction will experience graft failure, and there is mounting evidence that an increased posterior tibial slope (PTS) may be a predisposing factor. Theoretically, under tibiofemoral compression force (TFC), a reduced PTS would induce less anterior tibial translation (ATT) and lower ACL force. Hypothesis: Ten-degree anterior closing wedge osteotomy of the proximal tibia will significantly reduce ACL force and alter knee kinematics during robotic testing. Study Design: Controlled laboratory study. Methods: Eleven fresh-frozen human knees were instrumented with a load cell that measured ACL force as the knee was flexing continuously from 0° to 50° under 200-N TFC as our initial testing condition, followed by the addition of the following tibial loads: 45-N anterior force (AF), 5-N·m valgus moment (VM), 2-N·m internal torque (IT), and all loads combined. ACL force and knee kinematics were recorded before and after osteotomy. Results: Osteotomy produced significant changes in the tibiofemoral position at full extension (as defined by a 2-N·m knee extension moment). This resulted in apparent knee hyperextension (9.4° ± 1.9°), posterior tibial translation (7.9 mm ± 1.6 mm), internal tibial rotation (3.2° ± 2.3°), and valgus tibial rotation (3.2° ± 1.5°). During straight knee flexion with TFC alone, osteotomy reduced ACL force to 0 N beyond 5° of flexion, and ATT was reduced between 0° and 45° ( P < .05). With TFC + AF, ACL force was reduced beyond 5° of flexion, and ATT was reduced between 5° and 45° ( P < .05). With TFC + VM, ACL force was less than 10 N beyond 5° of flexion, and ATT was reduced at all flexion angles ( P < .05). Under the loading conditions TFC + IT and TFC + IT + AF + VM, osteotomy did not significantly change ACL force or ATT at any flexion angle. Conclusion: In general, osteotomy lowered ACL force and reduced ATT when IT was not present. The benefits of osteotomy were negated when IT was included possibly because the dominant mechanism of ACL force generation was cruciate impingement from internal winding and not ATT. Clinical Relevance: PTS-reducing osteotomy significantly decreased ACL force and reduced ATT for knee loads that did not include IT.
Use of Standardized Assessment Tools to Improve the Effectiveness of Palliative Care Rounds
Authors: Spaner Donna , Caraiscos Valerie B. , Muystra Christina , Furman Margaret Lynn , Zaltz-Dubin Jodi , Wharton Marilyn , Whitehead Katherine 
Published: November 2017

Background: Optimal care for patients in the palliative care setting requires effective clinical teamwork. Communication may be challenging for health-care workers from different disciplines. Daily rounds are one way for clinical teams to share information and develop care plans for patients. Objective: The objective of this initiative was to improve the structure and process of daily palliative care rounds by incorporating the use of standardized tools and improved documentation into the meeting. We chose a quality improvement (QI) approach to address this initiative. Our aims were to increase the use of assessment tools when discussing patient care in rounds and to improve the documentation and accessibility of important information in the health record, including goals of care. Methods: This QI initiative used a preintervention and postintervention comparison of the outcome measures of interest. The initiative was tested in a palliative care unit (PCU) over a 22-month period from April 2014 to January 2016. Participants were clinical staff in the PCU. Results: Data collected after the completion of several plan-do-study-act cycles showed increased use and incorporation of the Edmonton Symptom Assessment System and Palliative Performance Scale into patient care discussions as well as improvement in inclusion of goals of care into the patient plan of care. Conclusion: Our findings demonstrate that the effectiveness of daily palliative care rounds can be improved by incorporating the use of standard assessment tools and changes into the meeting structure to better focus and direct patient care discussions.
Pharmacist Intentions to Prescribe Hormonal Contraception Following New Legislative Authority in California
Authors: Vu Kevin , Rafie Sally , Grindlay Kate , Gutierrez Hialy , Grossman Daniel 
Published: November 2017

Objective: Following a California law expanding pharmacists’ scope of practice to include directly providing self-administered hormonal contraception to patients pursuant to a statewide protocol, this study aimed to assess California pharmacists’ intentions to provide this new service prior to the protocol development and implementation. Design: Descriptive, nonexperimental, cross-sectional study. Setting: California between August and September 2014. Participants: California pharmacists working in community pharmacies. Intervention: Invitations to participate in the online survey were sent to 1774 pharmacists. Main Outcome Measures: Main outcomes included pharmacists’ current practices, intentions to prescribe hormonal contraception, comfort performing various activities, knowledge about contraceptive methods, training needs, and barriers to prescribing. Results: A total of 257 responses (14.5% response rate) were received. Of those, 121 respondents met inclusion criteria and were included in the analysis. About half of the respondents (49.6%) reported working in a community chain pharmacy, 46.3% in an independent pharmacy, and 4.1% in other community pharmacy settings. The majority (72.7%) of pharmacists reported that they would likely provide this new service. Respondents reported being comfortable educating patients on short-acting (94.2%) and long-acting reversible contraception (81.7%), as well as identifying drug interactions with hormonal contraception (96.7%). Respondents indicated time constraints (74.4%), lack of reimbursement (63.6%), and liability concerns (62.0%) as barriers to prescribing hormonal contraception. Conclusions: California pharmacists expressed strong intentions and comfort in prescribing hormonal contraception. Pharmacists’ additional training needs and barriers should be addressed for successful implementation. This new service has great potential to increase access to contraception, potentially fostering increased use and adherence.
Provider Perspectives on Advance Care Planning Documentation in the Electronic Health Record: The Experience of Primary Care Providers and Specialists Using Advance Health-Care Directives and Physician Orders for Life-Sustaining Treatment
Authors: Dillon Ellis , Chuang Judith , Gupta Atul , Tapper Sharon , Lai Steve , Yu Peter , Ritchie Christine , Tai-Seale Ming 
Published: November 2017

Context: Advance care planning (ACP) is valued by patients and clinicians, yet documenting ACP in an accessible manner is problematic. Objectives: In order to understand how providers incorporate electronic health record (EHR) ACP documentation into clinical practice, we interviewed providers in primary care and specialty departments about ACP practices (n = 13) and analyzed EHR data on 358 primary care providers (PCPs) and 79 specialists at a large multispecialty group practice. Methods: Structured interviews were conducted with 13 providers with high and low rates of ACP documentation in primary care, oncology, pulmonology, and cardiology departments. The EHR problem list data on Advance Health Care Directives (AHCDs) and Physician Orders for Life-Sustaining Treatment (POLST) were used to calculate ACP documentation rates. Results: Examining seriously ill patients ≥65 years with no preexisting ACP documentation seen by providers during 2013 to 2014, 88.6% (AHCD) and 91.1% (POLST) of 79 specialists had zero ACP documentations. Of 358 PCPs, 29.1% (AHCD) and 62.3% (POLST) had zero ACP documentations. Interviewed PCPs often believed ACP documentation was beneficial and accessible, while specialists more often did not. Specialists expressed more confusion about documenting ACP, whereas PCPs reported standard clinic workflows. Problems with interoperability between outpatient and inpatient EHR systems and lack of consensus about who should document ACP were sources of variations in practices. Conclusion: Results suggest that providers desire standardized workflows for ACP discussion and documentation. New Medicare reimbursement for ACP and an increasing number of quality metrics for ACP are incentives for health-care systems to address barriers to ACP documentation.
Fospropofol Disodium for Procedural Sedation: Emerging Evidence of its Value?
Authors: Mueller Scott W. , Moore Gina D. , MacLaren Robert 
Published: November 2017

Background Fospropofol is a phosphate-ester water soluble prodrug of propofol approved in the United States for the short-term sedation of adults undergoing diagnostic or therapeutic procedures with monitored anesthesia care. Fospropofol may be advantageous for procedural sedation because it is not a lipid formulation, it lacks pain on injection, it possesses a different pharmacokinetic profile due to in vivo conversion of fospropofol to propofol, and it offers rapid recovery from sedation. Objective To review published pharmacokinetic data, clinical trials, and the safety profile of fospropofol and provide comment on its use for sedation. Clinical trials Fospropofol has been studied for sedation in colonoscopy and bronchoscopy with fentanyl for analgesia. Results indicate that a 6.5 mg/kg bolus dose with repeated doses of 25% of the original bolus dose up to every 4 minutes produces an effective and safe level of sedation. Fospropofol comparisons to midazolam were not assessed. Patient satisfaction is high for those treated with the recommended dosage regimen. Most commonly reported adverse effects included pruritus and paresthesia. Sedation related side effects such as hypoxia and apnea were rarely reported and generally mild in scope. Conclusion Fospropofol represents an alternative sedative agent to midazolam and propofol for short-term sedation. However, the efficacy and safety of fospropofol compared to midazolam or propofol has not been assessed, therefore use will be based on practitioner preference. Restrictive package labelling requiring MAC poses medico-legal and cost-benefit issues thereby not conferring a benefit over propofol which caries similar labelling. Additional studies designed to compare fospropofol to propofol and/or midazolam for procedural sedation are needed.
In silico modeling to optimize interpretation of liver safety biomarkers in clinical trials
Authors: Church Rachel J , Watkins Paul B 
Published: November 2017

Current strategies to delineate the risk of serious drug-induced liver injury associated with drugs rely on assessment of serum biomarkers that have been utilized for many decades. In particular, serum alanine aminotransferase and total bilirubin levels are typically used to assess hepatic integrity and function, respectively. Parallel measurement of these biomarkers is utilized to identify patients with drug-induced hepatocellular jaundice (“Hy’s Law” cases) which carries at least a 10% risk of death or liver transplant. However, current guidelines regarding use of these biomarkers in clinical trials can put study subjects at risk for life-threatening drug-induced liver injury, or result in over estimation of risk that may halt development of safe drugs. In addition, pharmaceutical companies are increasingly being required to conduct large and expensive clinical trials to “defend” the safety of their new drug when results from smaller trials are inconclusive. Innovative approaches and some novel biomarkers are now being employed to maximize the value of traditional biochemical tests. DILIsym®, a product of the DILIsim Initiative, utilizes serial serum alanine aminotransferase values, along with serum biomarkers of apoptosis vs necrosis, to estimate percent hepatocyte loss and total bilirubin elevations resulting from loss of global liver function. The results from analyses conducted with DILIsym have been reported to the FDA to support the safety of entolimod and cimaglermin alfa after elevations in serum alanine aminotransferase and/or bilirubin halted clinical development. DILIsym can also be utilized to determine whether rises in serum conjugated and unconjugated bilirubin are consistent with mechanisms unrelated to toxicity ( i.e. inhibition of bilirubin transport or metabolism). In silico modeling of traditional and novel drug-induced liver injury biomarker data obtained in clinical trials may be the most efficient and accurate way to define the liver safety profile of new drug candidates. Impact statement Blood tests used in clinical trials to detect and monitor drug-induced liver injury (DILI) have not changed in half a century. These tests have several shortcomings: their use has not completely prevented clinical trial participants from risk of life-threatening DILI, they can give false positive results that halt the development of safe drug candidates, and they can create liver safety “concerns” that require large additional clinical trials to accurately define DILI risk. This review highlights the use of in silico modeling to improve interpretation of the blood tests currently available to detect DILI risk in new drug candidates. This approach is increasingly being applied in clinical trials to more precisely assess the degree of hepatocellular injury and its functional impact. This new approach holds the promise of more accurately defining DILI risk in smaller clinical trials.
First‐in‐child use of the oral soluble guanylate cyclase stimulator riociguat in pulmonary arterial hypertension
Authors: Spreemann Till , Bertram Harald , Happel Christoph M. , Kozlik‐Feldmann Rainer , Hansmann Georg 
Published: November 2017

Riociguat has been approved for use in adults with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension. No clinical data on its therapeutic use in children with PAH are currently available. We report the case of a now four‐year‐old boy who initially presented at the age of 10 months with suprasystemic pulmonary hypertension (PH) and right ventricular (RV) failure, vomiting, peripheral cyanosis, and failure to thrive. Cardiac catheterization revealed severe PAH. At radiologic suspicion of interstitial lung disease, repeated CT scan and an open lung biopsy were performed but could not clarify the entity of PAH. Given the demonstrated vasoreactivity, the boy was started on the calcium channel blocker amlodipine, in combination with the endothelin‐1 receptor antagonist bosentan. Two years later, based on persistently systemic PAH with lost vasoreactivity, PAH therapy was changed to bosentan and phosphodiesterase‐5 inhibitor sildenafil. No significant improvement on the aforementioned therapy was seen, so that the patient was referred to our institution. Invasive hemodynamic evaluation showed suprasystemic PAH and marked acute vasoreactivity (PAP 127/103/83 mmHg, PVRi 23.48 WU·m2 and PVR/SVR ratio 1.59 at baseline vs. PVRi 5.89 WU·m2 and PVR/SVR ratio 0.93 under O2/NO). Subsequently, we switched the patient from sildenafil to riociguat. After six months on bosentan/riociguat, the patient showed a marked decrease in PVR/SVR and transpulmonary pressure gradients, in RV hypertrophy, PA acceleration time, and left ventricular‐eccentricity index. Clinically, the patient improved in pediatric functional class from 2/3 to 1. In conclusion, off‐label use of oral riociguat may be considered in selected children with severe PAH.
Association of Neutrophil-to-Lymphocyte Ratio With Inflammation and Erythropoietin Resistance in Chronic Dialysis Patients
Authors: Pineault Jérôme , Lamarche Caroline , Bell Robert , Lafrance Jean-Philippe , Ouellet Georges , Leblanc Martine , Pichette Vincent , Bezzaoucha Sarah , Vallée Michel 
Published: November 2017

Background: Neutrophil-to-lymphocyte ratio (NLR) was widely studied as a prognostic marker in various medical and surgical specialties, but its significance in nephrology is not yet established. Objective: We evaluated its accuracy as an inflammation biomarker in a dialysis population. Design setting: Single-center retrospective study. Patients: The records of all 550 patients who were treated with hemodialysis (HD) or peritoneal dialysis (PD) from September 2008 to March 2011 were included. Measurements: NLR was calculated from the monthly complete blood count. Methods: Association between NLR and markers of inflammation (C-reactive protein [CRP], serum albumin, and erythropoietin resistance index [ERI]) was measured using Spearman coefficient. Results: In total, 120 patients were eligible for the correlation analyses. We found a positive correlation between NLR and CRP (all patients: r = 0.45, P < .001; HD: r = 0.47, P < .001; PD: r = 0.48, P = .13). NLR and albumin were inversely correlated ( r = −0.51, P < .001). Finally, high NLR was associated with a nonsignificant increased ERI, but we have not demonstrated a direct correlation. Limitations: CRP and albumin are not measured routinely and were ordered for a specific clinical reason leading to an indication bias. Also, no relationship with clinical outcome was established. Conclusions: NLR seems to be a good inflammatory biomarker in dialysis in addition to being easily available. However, controlled studies should be conducted to properly assess and validate NLR levels that would be clinically significant and relevant, as well as its prognostic significance and utility in a clinical setting.
Human NOTCH4 is a key target of RUNX1 in megakaryocytic differentiation
Authors: Li Yueying , Jin Chen , Bai Hao , Gao Yongxing , Sun Shu , Chen Lei , Qin Lei , Liu Paul P. , Cheng Linzhao , Wang Qian-Fei 
Published: November 2017

Key PointsNOTCH4 is a RUNX1 direct target the expression of which is negatively regulated by RUNX1 during human megakaryopoiesis. Inhibition of NOTCH4 by genetic approach or chemical inhibitors enhances MK production from human iPSCs and cord-blood CD34+ cells.
HRI coordinates translation by eIF2αP and mTORC1 to mitigate ineffective erythropoiesis in mice during iron deficiency
Authors: Zhang Shuping , Macias-Garcia Alejandra , Velazquez Jason , Paltrinieri Elena , Kaufman Randal J. , Chen Jane-Jane 
Published: November 2017

Key Points
Erythroid eIF2αP and ATF4 are essential for iron-restricted erythropoiesis, and HRI-eIF2αP is responsible for microcytic hypochromic anemia. HRI activates integrated stress response and represses mTORC1 signaling in ID to mitigate ineffective erythropoiesis.