bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient Satisfaction with Medication for Gastroesophageal Reflux Disease: A Systematic Review
Authors: van Zanten Sander Veldhuyzen , Henderson Catherine , Hughes Nesta 
Published: March 2016

BACKGROUND: Patient satisfaction is increasingly regarded as an important aspect of measuring treatment success in individuals with gastroesophageal reflux disease (GERD).OBJECTIVE: To review how satisfied patients with GERD are with their medication, and to analyze the usefulness of patient satisfaction as a clinical end point by comparing it with symptom improvement.METHODS: Systematic searches of the PubMed and EMBASE databases identified clinical trials and patient surveys published between 1966 and 2009.RESULTS: Twelve trials reported that 56% to 100% of patients were ‘satisfied’ or ‘very satisfied’ with proton pump inhibitor (PPI) treatment for GERD. Patient satisfaction levels were higher for PPIs than other GERD medications in two trials. The sample-size-weighted average proportion of patients ‘satisfied’ with their PPI after four weeks of treatment in trials was 93% (95% CI 87% to 99%), with 73% (95% CI 62% to 83%) being ‘very satisfied’. In four surveys, the average proportion of patients ‘satisfied’ with their PPI treatment was 82% (95% CI 73% to 90%) and 62% (95% CI 48% to 75%) were ‘very satisfied’. Seven trials found a positive association between patient satisfaction and symptom improvement, and two surveys between satisfaction and improved health-related quality of life. Three trials found that continuous treatment yielded higher rates of satisfaction than on-demand therapy.CONCLUSIONS: More than one-half of patients were satisfied with their PPI medication in trials, and more patients were satisfied with PPIs than other medication types. An association between patient satisfaction and symptom resolution was found, suggesting that patient satisfaction is a useful end point for evaluating GERD treatment success.
Autoimmune Hepatitis: Focusing on Treatments other than Steroids
Authors: Czaja Albert J 
Published: March 2016

BACKGROUND: Corticosteroid therapy has been the time-honoured treatment for autoimmune hepatitis; however, the emergence of new immunosuppressive agents has afforded opportunities to improve or replace the standard regimens.OBJECTIVE: To describe technological advances and feasible treatment interventions that promise to supplant the current generation of corticosteroids.METHODS: A review of the MEDLINE database for published experiences from 1984 to 2011 was conducted.RESULTS: Cyclosporine and tacrolimus have been uniformly successful as salvage therapies for steroid-refractory autoimmune hepatitis. Ten reports of cyclosporine therapy involving 133 patients had positive outcomes in 93%, whereas therapy with tacrolimus in three reports involving 41 patients had positive outcomes in 98%. Salvage therapy with mycophenolate mofetil had a favourable outcome in 47%, especially in patients with azathioprine intolerance. Front-line therapy with mycophenolate mofetil normalized liver parameters in 88% and allowed corticosteroid tapering in 58%. Front-line therapy with budesonide combined with azathioprine for six months normalized liver parameters more frequently (47% versus 18%) and with fewer side effects (28% versus 53%) than prednisone combined with azathioprine. Monoclonal antibodies to CD3 and recombinant cytotoxic T lymphocyte antigen 4 fused with immunoglobulin represent feasible molecular interventions for study in autoimmune hepatitis.DISCUSSION: Nonstandard drug therapies must be used in highly selected clinical situations including steroid failure (calcineurin inhibitors), azathioprine intolerance (mycophenolate mofetil), and mild disease or fragile patients (budesonide combined with azathioprine). Molecular interventions for autoimmune hepatitis are feasible for study because of their use in other immune-mediated diseases.CONCLUSION: Opportunities to improve or replace standard corticosteroid regimens have emerged.
Chemical Neurolysis of the Inferior Hypogastric Plexus for the Treatment of Cancer‐Related Pelvic and Perineal Pain
Authors: Mohamed Sahar Abd-Elbaky , Ahmed Doaa Gomaa , Mohamad Mohamad Farouk 
Published: March 2016

BACKGROUND: Various interventions, including the superior hypogastric plexus block and ganglion impar block, are commonly used for the treatment of pelvic or perineal pain caused by cancer. The inferior hypogastric plexus block (performed using a trans‐sacral approach under fluoroscopy and using a local anesthetics/steroid combination) for the diagnosis and treatment of chronic pain conditions involving the lower pelvic viscera was first described in 2007. Neurolysis of the inferior hypogastric plexus may be useful for the treatment of pelvic and perineal pain caused by cancer.OBJECTIVES: To assess the feasibility, safety and efficacy of the newly introduced inferior hypogastric plexus block, performed using a trans‐sacral approach, for the relief of cancer‐related pelvic and perineal pain.METHODS: A total of 20 patients with cancer pain in the pelvis and/or perineum were injected with 6 mL to 8 mL of 10% phenol bilaterally by passing a spinal needle through the sacral foramen to perform the inferior hypogastric block. Pain intensity (measured using a visual analogue scale), sleep score, activity score, psychological score and oral morphine consumption pre‐ and postprocedure were measured.RESULTS: Two of the 20 patients died during the follow‐up period and were, therefore, excluded from the study. All patients presented with cancer‐related pelvic, perineal or pelviperineal pain. Pain scores were reduced from a mean (± SD) of 7.22±1.31 preprocedurally to 4.06±1.73 one week postprocedurally (P<0.05). In addition, the mean consumption of morphine (delivered via 30 mg sustained‐release morphine tablets) was reduced from 106.67±32.90 mg to 61.67±40.48 mg after one week (P<0.05). No complications or serious side effects were encountered during or after the block.DISCUSSION AND CONCLUSION: The approach provides a good alternative technique for the treatment of low pelvic and perineal cancer‐related pain. Additional studies are required for evaluation and refinement of the technique using other radiological techniques.
2012 Canadian Guidelines for the Diagnosis and Management of Fibromyalgia Syndrome: Executive Summary
Authors: Fitzcharles Mary-Ann , Ste-Marie Peter A , Goldenberg Don L , Pereira John X , Abbey Susan , Choinière Manon , Ko Gordon , Moulin Dwight E , Panopalis Pantelis , Proulx Johanne , Shir Yoram , the National Fibromyalgia Guideline Advisory Panel  
Published: March 2016

BACKGROUND: Recent neurophysiological evidence attests to the validity of fibromyalgia (FM), a chronic pain condition that affects >2% of the population.OBJECTIVES: To present the evidence‐based guidelines for the diagnosis, management and patient trajectory of individuals with FM.METHODS: A needs assessment following consultation with diverse health care professionals identified questions pertinent to various aspects of FM. A literature search identified the evidence available to address these questions; evidence was graded according to the standards of the Oxford Centre for Evidence‐Based Medicine. Drafted recommendations were appraised by an advisory panel to reflect meaningful clinical practice.RESULTS: The present recommendations incorporate the new clinical concepts of FM as a clinical construct without any defining physical abnormality or biological marker, characterized by fluctuating, diffuse body pain and the frequent symptoms of sleep disturbance, fatigue, mood and cognitive changes. In the absence of a defining cause or cure, treatment objectives should be patient‐tailored and symptom‐based, aimed at reducing global complaints and enhancing function. Healthy lifestyle practices with active patient participation in health care forms the cornerstone of care. Multimodal management may include nonpharmacological and pharmacological strategies, although it must be acknowledged that pharmacological treatments provide only modest benefit. Maintenance of function and retention in the workforce is encouraged.CONCLUSIONS: The new Canadian guidelines for the treatment of FM should provide health professionals with confidence in the complete care of these patients and improve clinical outcomes.
Six Minute Walk Distance Is a Predictor of Survival in Patients with Chronic Obstructive Pulmonary Disease Undergoing Pulmonary Rehabilitation
Authors: Dajczman Esther , Wardini Rima , Kasymjanova Goulnar , Préfontaine David , Baltzan Marc Alexander , Wolkove Norman 
Published: March 2016

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a progressive and distressing disease with a trajectory that is often difficult to predict.OBJECTIVE: To determine whether initial 6 min walk distance (6MWD) or change in 6MWD following inpatient pulmonary rehabilitation (PR) predicted survival.METHODS: Patients referred for PR in 2010 were studied in a retrospective chart review. Measures of 6MWD before and following PR were recorded. Initial 6MWD was categorized as ≥250 m, 150 m to 249 m and ≤149 m. Government databases provided survival status up until December 2013 and survival analyses were performed. Initial 6MWD and a minimally important difference (MID) of ≥30 m were used for survival analysis.RESULTS: The cohort consisted of 237 patients (92 men, 145 women) with severe COPD. Mean (± SD) forced expiratory volume in 1 s (FEV1) was 0.75±0.36 L, with a mean FEV1/forced vital capacity (FVC) ratio of 0.57±0.16. Overall three‐year survival was 58%. Mean survival for the study period as per predefined categories of 6MWD of ≥250 m, 150 m to 249 m and ≤149 m was 42.2, 37.0 and 27.8 months (P<0.001), respectively, with a three‐year survival of 81%, 66% and 34% observed, respectively. Overall mean change in 6MWD was 62±57 m, and a minimal improvement of ≥30 m was observed in 72% of patients. In the lowest walking group, early mortality was significantly higher among those who did not achieve minimal improvement. Older age, male sex and shorter initial 6MWD were negative predictors of survival.CONCLUSION: In patients with severe COPD, initial 6MWD was predictive of survival. Overall survival at three years was only 58% and was especially poor (34%) in patients with low (<150 m) initial walk distance.
Antimicrobial Use Over a Four‐Year Period Using Days of Therapy Measurement at a Canadian Pediatric Acute Care Hospital
Authors: Dalton Bruce R , MacTavish Sandra J , Bresee Lauren C , Rajapakse Nipunie , Vanderkooi Otto , Vayalumkal Joseph , Conly John 
Published: March 2016

BACKGROUND: Antimicrobial resistance is a concern that is challenging the ability to treat common infections. Surveillance of antimicrobial use in pediatric acute care institutions is complicated because the common metric unit, the defined daily dose, is problematic for this population.OBJECTIVE: During a four‐year period in which no specific antimicrobial stewardship initiatives were conducted, pediatric antimicrobial use was quantified using days of therapy (DOT) per 100 patient days (PD) (DOT/100 PD) at the Alberta Children’s Hospital (Calgary, Alberta) for benchmarking purposes.METHODS: Drug use data for systemic antimicrobials administered on wards at the Alberta Children’s Hospital were collected from electronic medication administration records. DOT were calculated and rates were determined using 100 PD as the denominator. Changes over the surveillance period and subgroup proportions were represented graphically and assessed using linear regression.RESULTS: Total antimicrobial use decreased from 93.6 DOT/100 PD to 75.7 DOT/100 PD (19.1%) over the 2010/2011 through to the 2013/2014 fiscal years. During this period, a 20.0% increase in PD and an essentially stable absolute count of DOT (2.9% decrease) were observed. Overall, antimicrobial use was highest in the pediatric intensive care and oncology units.DISCUSSION: The exact changes in prescribing patterns that led to the observed reduction in DOT/100 PD with associated increased PD are unclear, but may be a topic for future investigations.CONCLUSION: Antimicrobial use data from a Canadian acute care pediatric hospital reported in DOT/100 PD were compiled for a four‐year time period. These data may be useful for benchmarking purposes.
Pilot and Feasibility Trial Evaluating Immuno-Gene Therapy of Malignant Mesothelioma Using Intrapleural Delivery of Adenovirus-IFNα Combined with Chemotherapy
Authors: Sterman Daniel H. , Alley Evan , Stevenson James P. , Friedberg Joseph , Metzger Susan , Recio Adri , Moon Edmund K. , Haas Andrew R. , Vachani Anil , Katz Sharyn I. , Sun Jing , Heitjan Daniel F. , Hwang Wei-Ting , Litzky Leslie , Yearley Jennifer H. , Tan Kay See , Papasavvas Emmanouil , Kennedy Paul , Montaner Luis J. , Cengel Keith A. , Simone Charles B. , Culligan Melissa , Langer Corey J. , Albelda Steven M. 
Published: March 2016

Abstract
Purpose: “In situ vaccination” using immunogene therapy has the ability to induce polyclonal antitumor responses directed by the patient's immune system.
Experimental Design: Patients with unresectable malignant pleural mesothelioma (MPM) received two intrapleural doses of a replication-defective adenoviral vector containing the human IFNα2b gene (Ad.IFN) concomitant with a 14-day course of celecoxib followed by chemotherapy. Primary outcomes were safety, toxicity, and objective response rate; secondary outcomes included progression-free and overall survival. Biocorrelates on blood and tumor were measured.
Results: Forty subjects were treated: 18 received first-line pemetrexed-based chemotherapy, 22 received second-line chemotherapy with pemetrexed (n = 7) or gemcitabine (n = 15). Treatment was generally well tolerated. The overall response rate was 25%, and the disease control rate was 88%. Median overall survival (MOS) for all patients with epithelial histology was 21 months versus 7 months for patients with nonepithelial histology. MOS in the first-line cohort was 12.5 months, whereas MOS for the second-line cohort was 21.5 months, with 32% of patients alive at 2 years. No biologic parameters were found to correlate with response, including numbers of activated blood T cells or NK cells, regulatory T cells in blood, peak levels of IFNα in blood or pleural fluid, induction of antitumor antibodies, nor an immune-gene signature in pretreatment biopsies.
Conclusions: The combination of intrapleural Ad.IFN, celecoxib, and chemotherapy proved safe in patients with MPM. OS rate was significantly higher than historical controls in the second-line group. Results of this study support proceeding with a multicenter randomized clinical trial of chemo-immunogene therapy versus standard chemotherapy alone. Clin Cancer Res; 22(15); 3791–800. ©2016 AACR.
Hope in the Long Road Toward the Development of a Therapeutic Human Papillomavirus Vaccine
Authors: Karaki Soumaya , Pere Helene , Badoual Cecile , Tartour Eric 
Published: March 2016

Abstract
A pool of long synthetic peptides derived from HPV16 proteins induce objective partial or complete histologic regression of lesions in more than 50% of patients with high-grade vulvar (VuVIN3) and vaginal intraepithelial neoplasia (VaIN3). The intensity of T-cell response induced by the vaccine was correlated with clinical response. Clin Cancer Res; 22(10); 2317–9. ©2016 AACR.
See related article by van Poelgeest et al., p. 2342
Clinical Response of Carcinomas Harboring the BRD4–NUT Oncoprotein to the Targeted Bromodomain Inhibitor OTX015/MK-8628
Authors: Stathis Anastasios , Zucca Emanuele , Bekradda Mohamed , Gomez-Roca Carlos , Delord Jean-Pierre , de La Motte Rouge Thibault , Uro-Coste Emmanuelle , de Braud Filippo , Pelosi Giuseppe , French Christopher A. 
Published: March 2016

AbstractThe antineoplastic, prodifferentiative effects of bromodomain and extra-terminal (BET) bromodomain (BRD) inhibitors were initially discovered in NUT midline carcinoma (NMC), an aggressive subtype of squamous cancer driven by the BRD4–NUT fusion oncoprotein. BRD4–NUT blocks differentiation and maintains tumor growth through a potent chromatin-modifying mechanism. OTX015/MK-8628, a novel oral BET inhibitor, targets BRD2/3/4/T with preclinical activity in NMC and several other tumor types and is currently in clinical development. Antitumor activity was evaluated in four patients with advanced-stage NMC with confirmed BRD4–NUT fusions who were treated with 80 mg OTX015/MK-8628 once daily in a compassionate-use context. Two patients responded rapidly with tumor regression and symptomatic relief, and a third had meaningful disease stabilization with a minor metabolic response. The main side effects were mild to moderate gastrointestinal toxicity and fatigue, and reversible grade 3 thrombocytopenia. This is the first proof-of-concept evidence of clinical activity of a BRD inhibitor in targeting BRD4–NUT.Significance: We present the first clinical proof-of-concept that targeting BRD4–NUT with a BET inhibitor results in impressive and rapid antitumor activity in NMC. It offers strong potential for future clinical application in this rare patient population as either a single agent or in combination with other agents. Cancer Discov; 6(5); 492–500. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 461
Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC
Authors: Gabrielson Andrew , Wu Yunan , Wang Hongkun , Jiang Jiji , Kallakury Bhaskar , Gatalica Zoran , Reddy Sandeep , Kleiner David , Fishbein Thomas , Johnson Lynt , Island Eddie , Satoskar Rohit , Banovac Filip , Jha Reena , Kachhela Jaydeep , Feng Perry , Zhang Tiger , Tesfaye Anteneh , Prins Petra , Loffredo Christopher , Marshall John , Weiner Louis , Atkins Michael , He Aiwu Ruth 
Published: March 2016

AbstractImmune cells that infiltrate a tumor may be a prognostic factor for patients who have had surgically resected hepatocellular carcinoma (HCC). The density of intratumoral total (CD3+) and cytotoxic (CD8+) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage I to IV HCC tissue specimens from a single cohort. Immune cell density in the interior and margin was converted to a binary score (0, low; 1, high), which was correlated with tumor recurrence and relapse-free survival (RFS). In addition, the expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) was correlated with the density of CD3+ and CD8+ cells and clinical outcome. High densities of both CD3+ and CD8+ T cells in both the interior and margin, along with corresponding Immunoscores, were significantly associated with a low rate of recurrence (P = 0.007) and a prolonged RFS (P = 0.002). In multivariate logistic regression models adjusted for vascular invasion and cellular differentiation, both CD3+ and CD8+ cell densities predicted recurrence, with odds ratios of 5.8 [95% confidence interval (CI), 1.6–21.8] for CD3+ and 3.9 (95% CI, 1.1–14.1) for CD8+. Positive PD-L1 staining was correlated with high CD3 and CD8 density (P = 0.024 and 0.005, respectively) and predicted a lower rate of recurrence (P = 0.034), as well as prolonged RFS (P = 0.029). Immunoscore and PD-L1 expression, therefore, are useful prognostic markers in patients with HCC who have undergone primary tumor resection. Cancer Immunol Res; 4(5); 419–30. ©2016 AACR.
TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination
Authors: Hsu Melody S. , Sedighim Shaina , Wang Tina , Antonios Joseph P. , Everson Richard G. , Tucker Alexander M. , Du Lin , Emerson Ryan , Yusko Erik , Sanders Catherine , Robins Harlan S. , Yong William H. , Davidson Tom B. , Li Gang , Liau Linda M. , Prins Robert M. 
Published: March 2016

Abstract
Although immunotherapeutic strategies are emerging as adjunctive treatments for cancer, sensitive methods of monitoring the immune response after treatment remain to be established. We used a novel next-generation sequencing approach to determine whether quantitative assessments of tumor-infiltrating lymphocyte (TIL) content and the degree of overlap of T-cell receptor (TCR) sequences in brain tumors and peripheral blood were predictors of immune response and overall survival in glioblastoma patients treated with autologous tumor lysate–pulsed dendritic cell immunotherapy. A statistically significant correlation was found between a higher estimated TIL content and increased time to progression and overall survival. In addition, we were able to assess the proportion of shared TCR sequences between tumor and peripheral blood at time points before and after therapy, and found the level of TCR overlap to correlate with survival outcomes. Higher degrees of overlap, or the development of an increased overlap following immunotherapy, was correlated with improved clinical outcome, and may provide insights into the successful, antigen-specific immune response. Cancer Immunol Res; 4(5); 412–8. ©2016 AACR.
Durable Clinical Effectiveness With Paclitaxel-Eluting Stents in the Femoropopliteal Artery
Authors: Dake Michael D. , Ansel Gary M. , Jaff Michael R. , Ohki Takao , Saxon Richard R. , Smouse H. Bob , Machan Lindsay S. , Snyder Scott A. , O’Leary Erin E. , Ragheb Anthony O. , Zeller Thomas 
Published: March 2016

Background—
This randomized controlled trial evaluated clinical durability of Zilver PTX, a paclitaxel-coated drug-eluting stent (DES), for femoropopliteal artery lesions. Outcomes compare primary DES versus percutaneous transluminal angioplasty (PTA), overall DES (primary and provisional) versus standard care (PTA and provisional Zilver bare metal stent [BMS]), and provisional DES versus provisional BMS.

Methods and Results—

Patients with symptomatic femoropopliteal artery disease were randomly assigned to DES (n=236) or PTA (n=238). Approximately 91% had claudication; 9% had critical limb ischemia. Patients experiencing acute PTA failure underwent secondary randomization to provisional BMS (n=59) or DES (n=61). The 1-year primary end points of event-free survival and patency showed superiority of primary DES in comparison with PTA; these results were sustained through 5 years. Clinical benefit (freedom from persistent or worsening symptoms of ischemia; 79.8% versus 59.3%,
P
<0.01), patency (66.4% versus 43.4%,
P
<0.01), and freedom from reintervention (target lesion revascularization, 83.1% versus 67.6%,
P
<0.01) for the overall DES group were superior to standard care in nonrandomized comparisons. Similarly, clinical benefit (81.8% versus 63.8%,
P
=0.02), patency (72.4% versus 53.0%,
P
=0.03), and freedom from target lesion revascularization (84.9% versus 71.6%,
P
=0.06) with provisional DES were improved over provisional BMS. These results represent >40% relative risk reduction for restenosis and target lesion revascularization through 5 years for the overall DES in comparison with standard care and for provisional DES in comparison with provisional BMS.

Conclusions—
The 5-year results from this large study provide long-term information previously unavailable regarding endovascular treatment of femoropopliteal artery disease. The Zilver PTX DES provided sustained safety and clinical durability in comparison with standard endovascular treatments.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00120406.