bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review: psychosocial factors associated with pain in inflammatory bowel disease
Authors: Sweeney L. , Moss‐Morris R. , Czuber‐Dochan W. , Meade L. , Chumbley G. , Norton C. 
Published: January 2018

SummaryBackgroundPain is a frequently reported symptom of inflammatory bowel disease (IBD) experienced by patients in active disease and remission. Psychological factors play a significant role in pain, but have not been systematically reviewed in IBD.AimTo review psychosocial factors associated with pain in adults diagnosed with IBD.MethodsElectronic (PsycInfo, MEDLINE, EMBASE, Cochrane Library, CINAHL, Web of Science), and hand‐searching were conducted February‐May 2017. Two authors carried out screening and data extraction.ResultsFifteen studies including 5539 IBD patients were identified. Emotional, cognitive‐behavioural and personality factors were associated with IBD‐pain. Depression and anxiety were the most commonly explored constructs, followed by perceived stress and pain catastrophising, all of which were positively associated with greater pain. Greater abdominal pain was associated with a concurrent mood disorder over fivefold (OR 5.76, 95% CI 1.39, 23.89). Coping strategies and pain fear avoidance correlated with pain levels. Perceived social support (r = .26) and internal locus of control (r = .33) correlated with less pain. Patients reporting pain in IBD remission more frequently had an existing diagnosis of a mood disorder, a chronic pain disorder and irritable bowel syndrome. Six studies controlled for disease activity, of which 4 found that psychosocial factors significantly predicted pain. The majority of studies (n = 10) were of high quality.ConclusionPsychosocial factors appear to play a significant role in IBD‐pain. Further research is required to explore psychosocial constructs in relation to IBD‐pain, with use of validated pain measures, large sample sizes and clearer characterisation of disease activity.
Review article: long‐term safety of oral anti‐viral treatment for chronic hepatitis B
Authors: Wong G. L.‐H. , Seto W.‐K. , Wong V. W.‐S. , Yuen M.‐F. , Chan H. L.‐Y. 
Published: January 2018

SummaryBackgroundSafety profile of nucleos(t)ide analogues is an important issue in view of its widespread use for decades in patients with chronic hepatitis B (CHB).AimTo review and evaluate the latest evidence on the safety profiles of the six approved nucleoside analogues.MethodsRelevant articles related to nucleoside analogue safety were selected for review following extensive language‐ and date‐unrestricted, electronic searches of the literature.ResultsNephrotoxicity has been well reported in patients receiving older generations of nucleotide analogues, namely adefovir dipivoxil and tenofovir disoproxil fumarate (TDF). Yet risks of renal failure and renal replacement therapy were similar in patients treated with nucleoside analogues versus nucleotide analogues in real‐life setting. Bone toxicity is closely related to nucleoside analogue effect on renal proximal tubular and phosphaturia. Real‐life data demonstrated increased risk of hip fracture in patients receiving adefovir but not TDF. The newly approved tenofovir alafenamide (TAF) has improved renal and bone safety profiles compared to TDF. Long‐term use of nucleoside analogues eg entecavir does not increase the risk of other cancers. Muscular toxicity may be seen in telbivudine‐treated patients so regular monitoring is advised. Peripheral neuropathy and lactic acidosis are rare adverse events. Latest international guidelines support the use of TDF, telbivudine and lamivudine during pregnancy; breastfeeding is not contraindicated during TDF therapy.ConclusionsLong‐term safety profile of nucleoside analogues is now better defined with more data from large real‐life cohorts and clinical trials with long‐term follow‐up. The new nucleotide analogue, TAF is now available with favourable renal and bone safety profiles.
A Utility-Based Design for Randomized Comparative Trials with Ordinal Outcomes and Prognostic Subgroups
Authors: Murray Thomas A. , Yuan Ying , Thall Peter F. , Elizondo Joan H. , Hofstetter Wayne L. 
Published: January 2018

Summary
A design is proposed for randomized comparative trials with ordinal outcomes and prognostic subgroups. The design accounts for patient heterogeneity by allowing possibly different comparative conclusions within subgroups. The comparative testing criterion is based on utilities for the levels of the ordinal outcome and a Bayesian probability model. Designs based on two alternative models that include treatment-subgroup interactions are considered, the proportional odds model and a non-proportional odds model with a hierarchical prior that shrinks toward the proportional odds model. A third design that assumes homogeneity and ignores possible treatment-subgroup interactions also is considered. The three approaches are applied to construct group sequential designs for a trial of nutritional prehabilitation versus standard of care for esophageal cancer patients undergoing chemoradiation and surgery, including both untreated patients and salvage patients whose disease has recurred following previous therapy. A simulation study is presented that compares the three designs, including evaluation of within-subgroup type I and II error probabilities under a variety of scenarios including different combinations of treatment-subgroup interactions.
PDCD1 and CTLA4 polymorphisms affect the susceptibility to, and clinical features of, chronic immune thrombocytopenia
Authors: Kasamatsu Tetsuhiro , Ino Rumi , Takahashi Noriyuki , Gotoh Nanami , Minato Yusuke , Takizawa Makiko , Yokohama Akihiko , Handa Hiroshi , Saitoh Takayuki , Tsukamoto Norifumi , Murakami Hirokazu 
Published: January 2018

SummaryProgrammed death‐1 (PD‐1, PDCD1) and cytotoxic T lymphocyte‐associated antigen‐4 (CTLA‐4, CTLA4) play central roles in immune checkpoint pathways. Single nucleotide polymorphisms (SNPs) of PDCD1 and CTLA4 have been reported to be associated with susceptibility to some autoimmune diseases. However, the potential association between SNPs in these immune checkpoint genes and risk of chronic immune thrombocytopenia (cITP) remain controversial and obscure. The aims of this study were to clarify the influence of PDCD1 and CTLA4 SNPs on the risk of developing cITP and its clinical features. We obtained genomic DNA from 119 patients with cITP and 223 healthy controls; their genotypes were determined by the polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) method. Patients with cITP had a significantly higher frequency of the PDCD1 +7209 TT genotype compared with healthy controls. The CTLA4 −1577 GG genotype and CT60 GG genotype showed higher frequencies of platelet count <5 × 109/l at diagnosis, minimum platelet count <5 × 109/l, and bleeding symptoms. Moreover, the PDCD1 −606 AA genotype and +63379 TT genotype were significantly associated with a lower number of patients who achieved a complete response to prednisolone treatment. Our results suggest that the immune checkpoint polymorphisms may affect the susceptibility to the clinical features of cITP, and treatment response of the affected patients.
Pre‐ and post‐transplant minimal residual disease predicts relapse occurrence in children with acute lymphoblastic leukaemia
Authors: Lovisa Federica , Zecca Marco , Rossi Bartolomeo , Campeggio Mimma , Magrin Elisa , Giarin Emanuela , Buldini Barbara , Songia Simona , Cazzaniga Giovanni , Mina Tommaso , Acquafredda Gloria , Quarello Paola , Locatelli Franco , Fagioli Franca , Basso Giuseppe 
Published: January 2018

SummaryRelapse remains the leading cause of treatment failure in children with acute lymphoblastic leukaemia (ALL) undergoing allogeneic haematopoietic stem cell transplantation (HSCT). We retrospectively investigated the prognostic role of minimal residual disease (MRD) before and after HSCT in 119 children transplanted in complete remission (CR). MRD was measured by polymerase chain reaction in bone marrow samples collected pre‐HSCT and during the first and third trimesters after HSCT (post‐HSCT1 and post‐HSCT3). The overall event‐free survival (EFS) was 50%. The cumulative incidence of relapse and non‐relapse mortality was 41% and 9%. Any degree of detectable pre‐HSCT MRD was associated with poor outcome: EFS was 39% and 18% in patients with MRD positivity <1 × 10−3 and ≥1 × 10−3, respectively, versus 73% in MRD‐negative patients (P < 0·001). This effect was maintained in different disease remissions, but low‐level MRD had a very strong negative impact only in patients transplanted in second or further CR. Also, MRD after HSCT enabled patients to be stratified, with increasing MRD between post‐HSCT1 and post‐HSCT3 clearly defining cohorts with a different outcome. MRD is an important prognostic factor both before and after transplantation. Given that MRD persistence after HSCT is associated with dismal outcome, these patients could benefit from early discontinuation of immunosuppression, or pre‐emptive immuno‐therapy.
Ibrutinib resistance in mantle cell lymphoma: clinical, molecular and treatment aspects
Authors: Hershkovitz‐Rokah Oshrat , Pulver Dana , Lenz Georg , Shpilberg Ofer 
Published: January 2018

SummaryMantle cell lymphoma (MCL) is a lymphoproliferative disorder comprising about 6–10% of all B cell lymphoma cases. Ibrutinib is an inhibitor of Bruton tyrosine kinase (BTK), a key component of early B‐cell receptor (BCR) signalling pathways. Although treatment with ibrutinib has significantly improved the outcome of MCL patients, approximately one‐third of the patients have primary drug resistance while others appear to develop acquired resistance. Understanding the molecular events leading to the primary and acquired resistance to ibrutinib is essential for achieving better outcomes in patients with MCL. In this review, we describe the biology of the BCR signalling pathway and summarize the landmark clinical trials that have led to the approval of ibrutinib. We review the molecular mechanisms underlying primary and acquired ibrutinib resistance as well as recent studies dealing with overcoming ibrutinib resistance.
External validation of the prostascore model in patients with metastatic hormone‐sensitive prostate cancer recruited to the CHAARTED study
Authors: Abdel‐Rahman Omar , Cheung Winson Y. 
Published: January 2018

ObjectiveTo externally validate ‘prostascore’ in patients with metastatic hormone‐sensitive prostate cancer recruited to the phase III CHAARTED study.MethodsWe conducted a retrospective analysis of the prospectively collected data from patients with metastatic hormone‐sensitive prostate cancer in the CHAARTED study, a phase III multicentre study conducted between 2006 and 2014. The main outcome of the present analysis was overall survival, assessed using Kaplan–Meier analysis or log‐rank testing, in the whole cohort according to different prostascores. In addition, patients with different scores were compared according to treatment arm.ResultsA total of 702 cases had complete baseline data, allowing calculation of prostascores and inclusion in the present analysis. Overall survival was assessed according to prostascores in the entire cohort and the P value for overall survival trend was significant (P < 0.001). Likewise, progression‐free survival was assessed according to prostascores in the entire cohort and the P value for progression‐free survival trend was also significant (P < 0.001). Overall survival comparisons according to treatment arm were evaluated among different prostascores. Notably, the P value for overall survival difference was not significant for a prostascore = 2 (P = 0.702), but was significant for scores of 3, 4 and 5 (P < 0.05). The cause‐specific hazard ratio for cancer‐specific survival (adjusted for treatment arm used) was also evaluated. The P value for pairwise comparisons between different scores was significant (P < 0.01) except for the comparison between scores 4 and 5.ConclusionThe present study further confirms the role of prostascore in predicting the outcomes of patients with metastatic hormone‐sensitive prostate cancer and also highlights its potential role in therapeutic decision‐making.
Robot‐assisted partial nephrectomy for large renal masses: a multi‐institutional series
Authors: Delto Joan C. , Paulucci David , Helbig Michael W. , Badani Ketan K. , Eun Daniel , Porter James , Abaza Ronney , Hemal Ashok K. , Bhandari Akshay 
Published: January 2018

ObjectivesTo compare peri‐operative outcomes after robot‐assisted partial nephrectomy (RAPN) for cT2a (7 to <10 cm) to cT1 tumours.Materials and MethodsPatients with a cT1a (n = 1 358, 76.4%), cT1b (n = 379, 21.3%) or cT2a (n = 41, 2.3%) renal mass were identified from a multi‐institutional RAPN database. Intra‐ and postoperative outcomes were compared for cT2a masses vs cT1a and cT1b masses using multivariable regression models (linear, logistic, Poisson etc.), adjusting for operating surgeon and a modified R.E.N.A.L. nephrometry score that excluded the radius component.ResultsThe median sizes for cT1a, cT1b and cT2a tumours were 2.5, 5.0 and 8.0 cm, respectively (P < 0.001) with modified R.E.N.A.L. nephrometry scores being 6.0, 6.5 and 7.0, respectively (cT1a, P < 0.001; cT1b, P = 0.105). RAPN for cT2a vs cT1a masses was associated with a 12% increase in operating time (P < 0.001), a 32% increase in estimated blood loss (P < 0.001), a 7% increase in ischaemia time (P = 0.008), a 3.93 higher odds of acute kidney injury at discharge (95% confidence interval [CI] 1.33, 8.76; P = 0.009) and a higher risk of recurrence (hazard ratio [HR] 10.9, 95% CI 1.31, 92.2; P = 0.027). RAPN for cT2a vs cT1b masses was associated with a 12% increase in blood loss (P = 0.036), a 5% increase in operating time (P = 0.062) and a marginally higher risk of recurrence (HR 11.2, 95% CI 0.77, 11.5; P = 0.059). RAPN for cT2a tumours was not associated with differences in complications (cT1a, P = 0.535; cT1b, P = 0.382), positive margins (cT1a, P = 0.972; cT1b, P = 0.681), length of stay (cT1a, P = 0.507; cT1b, P = 0.513) or renal function decline up to 24 months post‐RAPN (cT1a, P = 0.124; cT1b, P = 0.467).ConclusionFor T2a tumours RAPN is a feasible treatment option in a select patient population when performed by experienced surgeons in institutions equipped to manage postoperative complications. Although RAPN was associated with greater blood loss and longer operating and ischaemia time in T2a tumours, it was not associated with greater complication or positive surgical margin rates compared with T1 tumours. Renal function preservation rates were equivalent for up to 24 months postoperatively; however, 12‐month recurrence‐free survival was significantly lower in the T2a group. Extended follow‐up is required to further evaluate long‐term survival.
Open radical cystectomy in England: the current standard of care – an analysis of the British Association of Urological Surgeons (BAUS) cystectomy audit and Hospital Episodes Statistics (HES) data
Authors: Jefferies Edward R. , Cresswell Joanne , McGrath John S. , Miller Catherine , Hounsome Luke , Fowler Sarah , Rowe Edward W. ,   BAUS Section on Oncology
Published: January 2018

ObjectiveTo establish the current standard for open radical cystectomy (ORC) in England, as data entry by surgeons performing RC to the British Association of Urological Surgeons (BAUS) database was mandated in 2013 and combining this with Hospital Episodes Statistics (HES) data has allowed comprehensive outcome analysis for the first time.Patients and MethodsAll patients were included in this analysis if they were uploaded to the BAUS data registry and reported to have been performed in the 2 years between 1 January 2014 and 31 December 2015 in England (from mandate onwards) and had been documented as being performed in an open fashion (not laparoscopic, robot assisted or the technique field left blank). The HES data were accessed via the HES website. Office of Population Censuses and Surveys Classification of Surgical Operations and Procedures version 4 (OPCS‐4) Code M34 was searched during the same 2‐year time frame (not including M34.4 for simple cystectomy or with additional minimal access codes Y75.1‐9 documenting a laparoscopic or robotic approach was used) to assess data capture.ResultsA total of 2 537 ORCs were recorded in the BAUS registry and 3 043 in the HES data. This indicates a capture rate of 83.4% of all cases. The median operative time was 5 h, harvesting a median of 11–20 lymph nodes, with a median blood loss of 500–1 000 mL, and a transfusion rate of 21.8%. The median length of stay was 11 days, with a 30‐day mortality rate of 1.58%.ConclusionsThis is the largest, contemporary cohort of ORCs in England, encompassing >80% of all performed operations. We now know the current standard for ORC in England. This provides the basis for individual surgeons and units to compare their outcomes and a standard with which future techniques and modifications can be compared.
A clinician‐centred programme for behaviour change in the optimal use of staging investigations for newly diagnosed prostate cancer
Authors: Rutledge Alison B. , McLeod Nicholas , Mehan Nicholas , Regan Timothy W. , Ainsworth Paul , Chong Peter , Doyle Terrence , White Martin , Sanson‐Fisher Rob W. , Martin Jarad M. 
Published: January 2018

ObjectivesTo improve imaging utilisation and reduce the widespread overuse of staging investigations, in the form of computed tomography (CT) and whole‐body bone scans for men with newly diagnosed prostate cancer in the Hunter region of NSW, Australia, by implementation of a multifaceted clinician‐centred behaviour change programme.Patients and MethodsRecords of all patients with a new diagnosis of prostate cancer were reviewed prior to the intervention (July 2014 to July 2015), and the results of this audit were presented to participating urologists by a clinical champion. Urologists then underwent focused education based on current guidelines. Patterns of imaging use for staging were then re‐evaluated (November 2015 to July 2016). Patients were stratified into low‐, intermediate‐ and high‐risk groups as described by the D'Amico classification system.ResultsA total of 144 patients were retrospectively enrolled into the study cohort. The use of diagnostic imaging for staging purposes significantly decreased in men with low‐ and intermediate‐risk disease post intervention. In low‐risk patients, the use of CT decreased from 43% to 0% (P = 0.01). A total of 21% of patients underwent bone scans in the pre‐intervention group compared with18% in the post‐intervention group (P = 0.84). In intermediate‐risk patients, the use of CT decreased from 89% to 34% (P < 0.001), whilst the use of bone scan decreased from 63% to 37% (P = 0.02). In high‐risk patients, the appropriate use of imaging was maintained, with CT performed in 87% compared with 85% and bone scan in 87% compared with 65% (P = 0.07).ConclusionOur results show that a focused, clinician‐centred education programme can lead to improved guideline adherence at a regional level. The assessment of trends and application of such a programme at a state‐based or national level could be further assessed in the future with the help of registry data. This will be particularly important in future with the advent of advanced imaging, such as prostate‐specific membrane antigen positron‐emission tomography.
Radiotherapy‐related complications presenting to a urology department: a more common problem than previously thought?
Authors: Ma Joyce L. , Hennessey Derek B. , Newell Bradley P. , Bolton Damien M. , Lawrentschuk Nathan 
Published: January 2018

ObjectiveTo quantify the burden of the side effects of radiotherapy on a tertiary referral urology department.Patients and MethodsA prospective study of all urology admissions to a public urology department at a tertiary hospital in a 6‐month period was performed. Patients admitted with complications attributable to radiotherapy were included in the study. Data obtained included patient demographics, radiotherapy details, complication type and management required.ResultsA total of 1198 patients were admitted; 921 (77%) were elective and 277 (23%) were emergency admissions. Thirteen out of the 921 (1.4%) elective admissions and 20 out of the 277 (7.2%) emergency admissions were attributable to radiotherapy complications. Radiotherapy complications was the fourth most common reason for emergency admission, ahead of acute urinary retention. These 33 admissions were accounted for by 21 patients. A total of 39 separate complications attributable to radiotherapy were diagnosed, with some patients having multiple complications. The median (interquartile range) time to onset of complications was 4 (1–9) years. The surgical intervention rate was 67%. The commonest procedures were washout with/without clot evacuation or diathermy in theatre (15.8%) and urethral dilatation/bladder neck incision (15.8%). Two urinary diversions and two cystoprostatectomies plus urinary diversion were performed.ConclusionRadiotherapy complications are consequential and account for a substantial proportion of a tertiary urology department's emergency workload. These complications generally occur years after radiotherapy and frequently require surgical intervention.
Performance comparison of two androgen receptor splice variant 7 (AR‐V7) detection methods
Authors: Bernemann Christof , Steinestel Julie , Humberg Verena , Bögemann Martin , Schrader Andres Jan , Lennerz Jochen K. 
Published: January 2018

ObjectivesTo compare the performance of two established androgen receptor splice variant 7 (AR‐V7) mRNA detection systems, as paradoxical responses to next‐generation androgen‐deprivation therapy in AR‐V7 mRNA‐positive circulating tumour cells (CTC) of patients with castration‐resistant prostate cancer (CRPC) could be related to false‐positive classification using detection systems with different sensitivities.Materials and MethodsWe compared the performance of two established mRNA‐based AR‐V7 detection technologies using either SYBR Green or TaqMan chemistries. We assessed in vitro performance using eight genitourinary cancer cell lines and serial dilutions in three AR‐V7‐positive prostate cancer cell lines, as well as in 32 blood samples from patients with CRPC.ResultsBoth assays performed identically in the cell lines and serial dilutions showed identical diagnostic thresholds. Performance comparison in 32 clinical patient samples showed perfect concordance between the assays. In particular, both assays determined AR‐V7 mRNA‐positive CTCs in three patients with unexpected responses to next‐generation anti‐androgen therapy. Thus, technical differences between the assays can be excluded as the underlying reason for the unexpected responses to next‐generation anti‐androgen therapy in a subset of AR‐V7 patients.ConclusionsIrrespective of the method used, patients with AR‐V7 mRNA‐positive CRPC should not be systematically precluded from an otherwise safe treatment option.
Children's Early Decontextualized Talk Predicts Academic Language Proficiency in Midadolescence
Authors: Uccelli Paola , Demir‐Lira Özlem Ece , Rowe Meredith L. , Levine Susan , Goldin‐Meadow Susan 
Published: January 2018

This study examines whether children's decontextualized talk—talk about nonpresent events, explanations, or pretend—at 30 months predicts seventh‐grade academic language proficiency (age 12). Academic language (AL) refers to the language of school texts. AL proficiency has been identified as an important predictor of adolescent text comprehension. Yet research on precursors to AL proficiency is scarce. Child decontextualized talk is known to be a predictor of early discourse development, but its relation to later language outcomes remains unclear. Forty‐two children and their caregivers participated in this study. The proportion of child talk that was decontextualized emerged as a significant predictor of seventh‐grade AL proficiency, even after controlling for socioeconomic status, parent decontextualized talk, child total words, child vocabulary, and child syntactic comprehension.