bluuebunny/crossref_metadata_2025_split huggingface dataset:
NAVIGATE I: Randomized, Placebo-Controlled, Double-Blind Trial of the Exhalation Delivery System With Fluticasone for Chronic Rhinosinusitis With Nasal Polyps
Authors: Sindwani Raj , Han Joseph K. , Soteres Daniel F. , Messina John C. , Carothers Jennifer L. , Mahmoud Ramy A. , Djupesland Per G. 
Published: November 2018

Background Chronic rhinosinusitis is a common, high-morbidity chronic inflammatory disease, and patients often experience suboptimal outcomes with current medical treatment. The exhalation delivery system with fluticasone (EDS-FLU) may improve care by increasing superior/posterior intranasal corticosteroid deposition. Objective To evaluate the efficacy and safety of EDS-FLU versus EDS-placebo in patients with nasal polyps (NP). Coprimary end points were change in nasal congestion and polyp grade. Key secondary end points were Sino-Nasal Outcome Test-22 (SNOT-22) and Medical Outcomes Study Sleep Scale-Revised (MOS Sleep-R). Other prespecified end points included all 4 cardinal symptoms of NP, 36-Item Short Form Health Survey (SF-36), Patient Global Impression of Change (PGIC), Rhinosinusitis Disability Index (RSDI), and key indicators for surgical intervention. Design Randomized, double-blind, EDS-placebo-controlled, multicenter study. Methods Three hundred twenty-three subjects with NP and moderate-severe congestion/obstruction, most with history of corticosteroid use (94.4%) and/or prior surgery (60.4%), were randomized to EDS-FLU 93 µg, 186 µg, or 372 µg or EDS-placebo twice daily (BID) for 24 weeks (16 double-blind + 8 single-arm extension with EDS-FLU 372 µg BID). Results All EDS-FLU doses produced significant improvement in both coprimary end points ( P < .05) and in SNOT-22 total score ( P ≤ .005). EDS-FLU significantly improved all 4 cardinal symptoms of NP ( P < .05), including congestion/obstruction, facial pain/pressure, rhinorrhea/post-nasal drip, and hyposmia/anosmia. Approximately 80% of subjects reported improvement with EDS-FLU, with 65% reporting “much” or “very much” improvement by week 16. Adverse events were generally local in nature and similar to other intranasal steroids studied for similar durations in similar populations, with the most common being epistaxis. Conclusions In patients with chronic rhinosinusitis with NP (CRSwNP) who were symptomatic despite high rates of prior intranasal steroid use and/or surgery, EDS-FLU produced statistically significant and clinically meaningful improvements compared to EDS-placebo in multiple subjective and objective outcomes (symptoms, SNOT-22, RSDI, SF-36, PGIC, and NP grade), including all 4 cardinal symptoms of CRSwNP.
Performance of the Acute Physiology and Chronic Health Evaluation II (APACHE II) in the prediction of hospital mortality in a mixed ICU in Singapore
Authors: Lew Charles Chin Han , Wong Gabriel Jun Yung , Tan Chee Keat , Miller Michelle 
Published: November 2018

Background: The Acute Physiology and Chronic Health Evaluation II (APACHE II) is used to quantify disease severity and hospital mortality risk in critically ill patients. It is widely used in intensive care units (ICUs) in Singapore, but its prognostic validity remains questionable as it has not been thoroughly assessed by established statistical methods. Objectives: This study aimed to: (a) evaluate the discrimination and calibration accuracy of the APACHE II in the prediction of hospital mortality in a mixed ICU, and (b) customise the APACHE II in an effort to maximise its prognostic performance. Methods: A prospective cohort study was conducted and all adult patients with >24 h of ICU admission in a tertiary care institution in Singapore were included. The outcome measure was hospital mortality, and all patients were followed-up until hospital discharge or death for up to one year after ICU admission. Results: There were 503 patients, and their mean (SD) age and APACHE II score were 61.2 (15.8) years and 24.5 (8.2), respectively. Hospital mortality was 31%, and no patients were lost to follow-up. The APACHE II has good discrimination (receiver operating characteristic: 0.76) but poor calibration (Hosmer–Lemeshow C test: <0.001). Customisation did not significantly improve calibration accuracy. Conclusions: The APACHE II and its customised version should not be used in the local setting as they both have poor calibration. There is an urgent need for larger studies to perform second-level customisation or to develop a new prognostic model tailored to the Singapore critical care setting.
Patterns of treatment with antiplatelet therapy after an acute coronary syndrome: Data from a large database in a community setting
Authors: Cimminiello Claudio , Dondi Letizia , Pedrini Antonella , Ronconi Giulia , Calabria Silvia , Piccinni Carlo , Polo Friz Hernan , Martini Nello , Maggioni Aldo P 
Published: November 2018

Aims Current guidelines strongly recommend antiplatelet therapy with aspirin plus a P2Y12 receptor inhibitor (dual therapy) for patients with acute coronary syndrome (ACS). To better understand how antiplatelet treatment is prescribed in clinical practice, the aim of this study was to provide a more detailed description of real-world patients with and without antiplatelet treatment after an ACS, their outcomes at one-year follow-up and the related integrated cost. Methods The ReS database, including more than 12 million inhabitants, was evaluated. During the accrual period ACS patients discharged alive were identified on the basis of ICD-IX-CM code. Antiplatelet drug prescriptions and healthcare costs were analysed over one-year follow-up. Results In 2014, of the 25,129 patients discharged alive after an ACS, 5796 (23%) did not receive any antiplatelet therapy during the first month after hospital discharge. Among them, 3846 (66%) subjects were prescribed an antiplatelet drug subsequently, while 7.7% did not receive any antiplatelet treatment during the whole following year. Dual therapy in the subgroup of patients undergoing a revascularization procedure ( n = 8436) was prescribed to 79.2% of cases and to 46.1% ( n = 4009) of medically managed patients. The patients not treated with an antiplatelet treatment in the first month showed the highest one-year healthcare costs, mostly due to hospital re-admissions. Conclusions This analysis of a large patient community shows that a considerable proportion of patients remained untreated with antiplatelet treatment after an ACS event. A clearer characterization of these subjects can help to improve the adherence to the current guidelines and recommendations.
A data-zone scoring system to assess the generalizability of clinical trial results to individual patients
Authors: Laffin Luke J , Besser Stephanie A , Alenghat Francis J 
Published: November 2018

Introduction Evaluating the applicability of a clinical trial to a specific patient is difficult. A novel framework, the Trial Score, was created to quantify the generalizability of a trial's result based on participants' baseline characteristics and not on the trial's inclusion and exclusion criteria. Methods For each Systolic Blood Pressure Intervention Trial (SPRINT) participant, the Euclidean distance in six-dimensional space from the theoretical “average” participant was calculated to produce an individual Trial Score that incorporates multiple distinct continuous-variable baseline characteristics. We prospectively defined the “data-rich,” “data-limited,” and “data-free” zones as Trial Scores < 90th percentile, the 90th–97.5th percentile, and >97.5th percentile, respectively. Trial Scores were then calculated for National Health and Nutrition Examination Survey participants to map data zones of the general population. Individual participant data from the Action to Control Cardiovascular Risk in Diabetes blood pressure trial (ACCORD-BP) was used to test if participants further from the average SPRINT participant behave differently than the overall SPRINT results. Results The National Health and Nutrition Examination Survey cohort and the ACCORD-BP trial demonstrate large percentages of participants in SPRINT's data-free and data-limited zones. Time-to-event rates seen with intensive and standard blood pressure control in SPRINT were the same as ACCORD-BP participants within SPRINT's data-rich zone (hazard ratio 0.97, p = 0.84 and hazard ratio 0.95, p = 0.70). However, these rates were significantly different than those of ACCORD-BP participants outside SPRINT's data-rich zone (hazard ratio 0.64, p < 0.01 and hazard ratio 0.77, p < 0.01). Conclusions ACCORD-BP participants with SPRINT Trial Scores in the 90th percentile or below have similar event rates to SPRINT participants in both the intensive and standard blood pressure groups. Quantifying the difference between an individual patient and the average clinical trial participant holds promise as a tool to more precisely determine applicability of a specific trial to individual patients.
MRI findings, including diffusion-weighted imaging and apparent diffusion coefficient value, in two cats with nasopharyngeal polyps and one cat with lymphoma
Authors: Tanaka Toshiyuki , Akiyoshi Hideo , Mie Keiichiro , Nishida Hidetaka 
Published: November 2018

Objectives Most nasopharyngeal masses in cats are lymphomas or polyps. To our knowledge, there is no report of MRI findings, including diffusion-weighted imaging (DWI) or apparent diffusion coefficient (ADC) values, of nasopharyngeal lymphomas and nasopharyngeal polyps in cats. This study aimed to evaluate the MRI findings of nasopharyngeal lymphomas and nasopharyngeal polyps, including DWI and ADC values. Methods MRI examination was performed on two cats with a histologically confirmed nasopharyngeal polyp and one cat with lymphoma. The magnetic resonance scanning protocol included T2-weighted imaging (T2WI), T1-weighted imaging (T1WI) and DWI. An ADC map was created based on DWI. ADC values were then calculated. Results MRI of the nasopharyngeal polyps revealed well-defined masses with strong rim enhancement, mass-associated stalk-like structures and asymmetric tympanic bulla lesions. The polyps appeared hyperintense on T2WI, hypo- to isointense on T1WI, and of mixed intensity or hypointense on DWI. On the ADC map, the masses appeared hyperintense. The ADC values of the polyps were 2.07 × 10−3 mm2/s and 2.28 × 10−3 mm2/s. MRI examination of the nasopharyngeal lymphoma revealed a strongly enhancing heterogeneous lesion. The mass appeared mildly hyperintense on T2WI, isointense on T1WI and hyperintense on DWI. On the ADC map, the mass appeared hypointense. The ADC value of the mass was 0.46 ×10−3 mm2/s. The ADC values of the nasopharyngeal polyps were higher than the ADC value of the nasopharyngeal lymphoma. Conclusions and relevance Measurement of ADC values may be useful for differentiating between nasopharyngeal polyps and nasopharyngeal lymphomas.
Can a stress management programme reduce stress and improve quality of life in people diagnosed with multiple sclerosis?
Authors: Agland Susan , Lydon Amanda , Shaw Sally , Lea Rodney , Mortimer-Jones Sheila , Lechner-Scott Jeannette 
Published: November 2018

Background Despite evidence of perceived stress as a risk factor for multiple sclerosis activity, the evidence for managing stress is limited. Objective To evaluate a stress management programme on perceived stress and quality of life, over 6 months. Methods One hundred people with multiple sclerosis were randomly assigned to either a stress management programme of mindfulness, meditation and progressive muscle relaxation, or wait list. Perceived stress and quality of life were assessed at three intervals across 6 months. Salivary cortisol levels were assessed at two intervals: baseline and first follow-up. Results The stress management programme did not significantly reduce perceived stress, when comparing mean scores. Secondary analysis using median scores found a significant improvement for quality of life, favouring the intervention group. Conclusion Stress management had no significant effect on the primary outcome of perceived stress but did improve quality of life in a secondary analysis of median scores.
Carfilzomib vs bortezomib in patients with multiple myeloma and renal failure: a subgroup analysis of ENDEAVOR
Authors: Dimopoulos Meletios , Siegel David , White Darrell J. , Boccia Ralph , Iskander Karim S. , Yang Zhao , Kimball Amy S. , Mezzi Khalid , Ludwig Heinz , Niesvizky Ruben 
Published: November 2018

AbstractIn ENDEAVOR, carfilzomib (56 mg/m2) and dexamethasone (Kd56) demonstrated longer progression-free survival (PFS) over bortezomib and dexamethasone (Vd) in patients with relapsed/refractory multiple myeloma (RRMM). Here we evaluated Kd56 vs Vd by baseline renal function in a post hoc exploratory subgroup analysis. The intent-to-treat population included 929 patients (creatinine clearance [CrCL] ≥15 to &lt;50 mL/min, n = 85 and n = 99; CrCL 50 to &lt;80 mL/min, n = 186 and n = 177; and CrCL ≥80 mL/min, n = 193 and n = 189 for Kd56 and Vd arms, respectively). In these respective subgroups, median PFS was 14.9 vs 6.5 months (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.320-0.757), 18.6 vs 9.4 months (HR, 0.48; 95% CI, 0.351-0.652), and not reached (NR) vs 12.2 months (HR, 0.60; 95% CI, 0.434-0.827) for those receiving Kd56 vs Vd, respectively; median overall survival (OS) was 42.1 vs 23.7 months (HR, 0.66; 95% CI, 0.443-0.989), 42.5 vs 32.8 months (HR, 0.83; 95% CI, 0.626-1.104), and NR vs 42.3 months (HR, 0.75; 95% CI, 0.554-1.009). Complete renal response (ie, CrCL improvement to ≥60 mL/min in any 2 consecutive visits if baseline CrCL &lt;50 mL/min) rates were 15.3% (95% CI, 8.4-24.7) and 14.1% (95% CI, 8.0-22.6) for those receiving Kd56 vs Vd, respectively. In a combined Kd56 and Vd analysis, complete renal responders had longer median PFS (14.1 vs 9.4 months; HR, 0.805; 95% CI, 0.438-1.481) and OS (35.3 vs 29.7 months; HR, 0.91; 95% CI, 0.524-1.577) vs nonresponders. Grade ≥3 adverse event rates in the respective subgroups were 87.1% vs 79.4%, 84.4% vs 71.8%, and 77.1% vs 65.9% for those receiving Kd56 vs Vd, respectively. Thus, Kd56 demonstrated PFS and OS improvements over Vd in RRMM patients regardless of their baseline renal function. The ENDEAVOR trial was registered at www.clinicaltrials.gov as #NCT01568866.
No free rides: management of toxicities of novel immunotherapies in ALL, including financial
Authors: Jain Tania , Litzow Mark R. 
Published: November 2018

Abstract
Therapeutic options for acute lymphoblastic leukemia, especially in the relapsed/refractory setting, have expanded significantly in recent times. However, this comes at the cost of toxicities: medical as well as financial. We highlight some of the unique toxicities associated with the novel agents to apprise our readers about what to expect, how to recognize them, and how to manage these toxicities. One of the toxicities seen with inotuzumab, a CD22 antibody drug conjugate, is sinusoidal obstruction syndrome, which can be fatal in &gt;80% of patients if associated with multiorgan failure. Blinatumomab, a monoclonal antibody targeting CD19, is associated with cytokine release syndrome (CRS) and neurotoxicity, both of which require prompt recognition and management primarily with corticosteroids. CRS and neurotoxicity are more common and more severe with chimeric antigen receptor T-cell therapy (CAR-T). The fact that CAR-T cannot be discontinued on demand adds a layer of complexity to the management of related toxicities of this therapy. Tocilizumab, an interleukin-6 receptor blocker, is used to treat severe CRS from CAR-T, whereas corticosteroids remain the mainstay for neurotoxicity management. Although effective, these drugs carry a high price tag, and we review the available data on cost-effectiveness of these agents, keeping in mind that median follow-up on most of these studies is limited and that long-term data on durability of response remain to be seen.
Clinical consequences of clonal hematopoiesis of indeterminate potential
Authors: Steensma David P. 
Published: November 2018

Abstract
Clonally restricted hematopoiesis is a common aging-associated biological state that predisposes to subsequent development of a hematological malignancy or cardiovascular death. Clonal expansion driven by leukemia-associated somatic mutations, such as DNMT3A, ASXL1, or TET2, is best characterized, but oligoclonality can also emerge without recognized leukemia-driver mutations, perhaps as a result of stochastic neutral drift. Murine models provide compelling evidence that a major mechanism of increased cardiovascular mortality in the context of clonal hematopoiesis is accelerated atherogenesis driven by inflammasome-mediated endothelial injury, resulting from proinflammatory interactions between endothelium and macrophages derived from circulating clonal monocytes. Altered inflammation likely influences other biological processes as well. The rate of development of overt neoplasia in patients with clonal hematopoiesis of indeterminate potential (CHIP), as currently defined, is 0.5% to 1% per year. Contributing factors to clonal progression other than acquisition of secondary mutations in hematopoietic cells (ie, stronger leukemia drivers) are incompletely understood. Disordered endogenous immunity in the context of increased proliferative pressure, short telomeres leading to chromosomal instability, an unhealthy marrow microenvironment that favors expansion of clonal stem cells and acquisition of new mutations while failing to support healthy hematopoiesis, and aging-associated changes in hematopoietic stem cells, including altered DNA damage response, an altered transcriptional program, and consequences of epigenetic alterations, are all potential contributors to clonal progression. Clinical management of patients with CHIP includes monitoring for hematological changes and reduction of modifiable cardiovascular risk factors; eventually, it will also likely include anti-inflammatory therapies and targeted approaches to prune emergent dangerous clones.
Personal Genome Project UK (PGP-UK): a research and citizen science hybrid project in support of personalized medicine
Authors:   PGP-UK Consortium, Beck Stephan , Berner Alison M. , Bignell Graham , Bond Maggie , Callanan Martin J. , Chervova Olga , Conde Lucia , Corpas Manuel , Ecker Simone , Elliott Hannah R. , Fioramonti Silvana A. , Flanagan Adrienne M. , Gaentzsch Ricarda , Graham David , Gribbin Deirdre , Guerra-Assunção José Afonso , Hamoudi Rifat , Harding Vincent , Harrison Paul L. , Herrero Javier , Hofmann Jana , Jones Erica , Khan Saif , Kaye Jane , Kerr Polly , Libertini Emanuele , Marks Lauren , McCormack Laura , Moghul Ismail , Pontikos Nikolas , Rajanayagam Sharmini , Rana Kirti , Semega-Janneh Momodou , Smith Colin P. , Strom Louise , Umur Sevgi , Webster Amy P. , Williams Elizabeth H. , Wint Karen , Wood John N. 
Published: November 2018

AbstractBackgroundMolecular analyses such as whole-genome sequencing have become routine and are expected to be transformational for future healthcare and lifestyle decisions. Population-wide implementation of such analyses is, however, not without challenges, and multiple studies are ongoing to identify what these are and explore how they can be addressed.MethodsDefined as a research project, the Personal Genome Project UK (PGP-UK) is part of the global PGP network and focuses on open data sharing and citizen science to advance and accelerate personalized genomics and medicine.ResultsHere we report our findings on using an open consent recruitment protocol, active participant involvement, open access release of personal genome, methylome and transcriptome data and associated analyses, including 47 new variants predicted to affect gene function and innovative reports based on the analysis of genetic and epigenetic variants. For this pilot study, we recruited 10 participants willing to actively engage as citizen scientists with the project. In addition, we introduce Genome Donation as a novel mechanism for openly sharing previously restricted data and discuss the first three donations received. Lastly, we present GenoME, a free, open-source educational app suitable for the lay public to allow exploration of personal genomes.ConclusionsOur findings demonstrate that citizen science-based approaches like PGP-UK have an important role to play in the public awareness, acceptance and implementation of genomics and personalized medicine.
Associations of adverse childhood experiences and social support with self-injurious behaviour and suicidality in adolescents
Authors: Wan Yuhui , Chen Ruoling , Ma Shuangshuang , McFeeters Danielle , Sun Ying , Hao Jiahu , Tao Fangbiao 
Published: November 2018

BackgroundThere is little investigation on the interaction effects of adverse childhood experiences (ACEs) and social support on non-suicidal self-injury (NSSI), suicidal ideation and suicide attempt in community adolescent populations, or gender differences in these effects.AimsTo examine the individual and interaction effects of ACEs and social support on NSSI, suicidal ideation and suicide attempt in adolescents, and explore gender differences.MethodA school-based health survey was conducted in three provinces in China between 2013–2014. A total of 14 820 students aged 10–20 years completed standard questionnaires, to record details of ACEs, social support, NSSI, suicidal ideation and suicide attempt.ResultsOf included participants, 89.4% reported one or more category of ACEs. The 12-month prevalence of NSSI, suicidal ideation and suicide attempt was 26.1%, 17.5% and 4.4%, respectively; all were significantly associated with increased ACEs and lower social support. The multiple adjusted odds ratio of NSSI in low versus high social support was 2.27 (95% CI 1.85–2.67) for girls and 1.81 (95% CI 1.53–2.14) for boys, and their ratio (Ratio of two odds ratios, ROR) was 1.25 (P = 0.037). Girls with high ACEs scores (5–6) and moderate or low social support also had a higher risk of suicide attempt than boys (RORs: 2.34, 1.84 and 2.02, respectively; all P < 0.05).ConclusionsACEs and low social support are associated with increased risk of NSSI and suicidality in Chinese adolescents. Strategies to improve social support, particularly among female adolescents with a high number of ACEs, should be an integral component of targeted mental health interventions.Declaration of interestNone.