bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and Clinical Activity of a Combination Therapy Comprising Two Antibody-Based Targeting Agents for the Treatment of Non-Hodgkin Lymphoma: Results of a Phase I/II Study Evaluating the Immunoconjugate Inotuzumab Ozogamicin With Rituximab
Authors: Fayad Luis , Offner Fritz , Smith Mitchell R. , Verhoef Gregor , Johnson Peter , Kaufman Jonathan L. , Rohatiner Ama , Advani Anjali , Foran James , Hess Georg , Coiffier Bertrand , Czuczman Myron , Giné Eva , Durrant Simon , Kneissl Michelle , Luu Kenneth T. , Hua Steven Y. , Boni Joseph , Vandendries Erik , Dang Nam H. 
Published: January 2013

Purpose Inotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. We performed a phase I/II study to determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics of INO plus rituximab (R-INO) for treatment of relapsed/refractory CD20+/CD22+ B-cell non-Hodgkin lymphoma (NHL). Patients and Methods A dose-escalation phase to determine the MTD of R-INO was followed by an expanded cohort to further evaluate the efficacy and safety at the MTD. Patients with relapsed follicular lymphoma (FL), relapsed diffuse large B-cell lymphoma (DLBCL), or refractory aggressive NHL received R-INO every 4 weeks for up to eight cycles. Results In all, 118 patients received one or more cycles of R-INO (median, four cycles). Most common grade 3 to 4 adverse events were thrombocytopenia (31%) and neutropenia (22%). Common low-grade toxicities included hyperbilirubinemia (25%) and increased AST (36%). The MTD of INO in combination with rituximab (375 mg/m2) was confirmed to be the same as that for single-agent INO (1.8 mg/m2). Treatment at the MTD yielded objective response rates of 87%, 74%, and 20% for relapsed FL (n = 39), relapsed DLBCL (n = 42), and refractory aggressive NHL (n = 30), respectively. The 2-year progression-free survival (PFS) rate was 68% (median, not reached) for FL and 42% (median, 17.1 months) for relapsed DLBCL. Conclusion R-INO demonstrated high response rates and long PFS in patients with relapsed FL or DLBCL. This and the manageable toxicity profile suggest that R-INO may be a promising option for CD20+/CD22+ B-cell NHL.
Palliative Radiation Therapy Practice in Patients With Metastatic Non–Small-Cell Lung Cancer: A Cancer Care Outcomes Research and Surveillance Consortium (CanCORS) Study
Authors: Chen Aileen B. , Cronin Angel , Weeks Jane C. , Chrischilles Elizabeth A. , Malin Jennifer , Hayman James A. , Schrag Deborah 
Published: January 2013

Purpose Randomized data suggest that single-fraction or short-course palliative radiation therapy (RT) is sufficient in the majority of patients with metastatic cancer. We investigated population-based patterns in the use of palliative RT among patients with metastatic non–small-cell lung cancer (NSCLC). Patients and Methods From patients diagnosed with lung cancer from 2003 to 2005 at a participating geographic or organizational site and who consented to the Cancer Care Outcomes Research and Surveillance Consortium study, we identified patients with metastatic NSCLC who had complete medical records abstractions. Patient characteristics and clinical factors associated with receipt of palliative RT and RT intensity (total dose and number of treatments) were evaluated with multivariable regression. Results Of 1,574 patients with metastatic NSCLC, 780 (50%) received at least one course of RT, and 21% and 12% received RT to the chest and bone, respectively. Use of palliative RT was associated with younger age at diagnosis and receipt of chemotherapy and surgery to metastatic sites. Among patients receiving palliative bone RT, only 6% received single-fraction treatment. Among patients receiving palliative chest RT, 42% received more than 20 fractions. Patients treated in integrated networks were more likely to receive lower doses and fewer fractions to the bone and chest. Conclusion When palliative RT is used in patients with metastatic NSCLC, a substantial proportion of patients receive a greater number of treatments and higher doses than supported by current evidence, suggesting an opportunity to improve care delivery.
Hospital and Surgeon Volume in Relation to Survival After Esophageal Cancer Surgery in a Population-Based Study
Authors: Derogar Maryam , Sadr-Azodi Omid , Johar Asif , Lagergren Pernilla , Lagergren Jesper 
Published: January 2013

Purpose The influence of hospital and surgeon volume on survival after esophageal cancer surgery deserves clarification, particularly the prognosis after the early postoperative period. The interaction between hospital and surgeon volume, and the influence of known prognostic factors need to be taken into account. Methods A nationwide Swedish population-based cohort study of 1,335 patients with esophageal cancer who underwent esophageal resection in 1987 to 2005, with follow-up for survival until February 2011, was conducted. The associations between annual hospital volume, annual surgeon volume, and cumulative surgeon volume and risk of mortality were calculated with multivariable parametric survival analysis, providing hazard ratios (HRs) with 95% CIs. HRs were mutually adjusted for the surgery volume variables and further adjusted for the prognostic factors age, sex, comorbidity, calendar period, tumor stage, tumor histology, and neoadjuvant therapy. Results There was no independent association between annual hospital volume and overall survival, and hospital volume was not associated with short-term mortality after adjustment for hospital clustering effects. A combination of higher annual and cumulative surgeon volume reduced the mortality occurring at least 3 months after surgery (P trend < .01); the HR was 0.78 (95% CI, 0.65 to 0.92) comparing surgeons with both annual and cumulative volume above the median with those below the median. These results remained when hospital and surgeon clustering were taken into account. Conclusion Because surgeon volume rather than hospital volume independently influences the prognosis after esophageal cancer surgery, centralization of this surgery to fewer surgeons seems warranted.
Patients’ views on improving sickle cell disease management in primary care: focus group discussion
Authors: Aljuburi Ghida , Phekoo Karen J , Okoye Nv Ogo , Anie Kofie , Green Stuart A , Nkohkwo Asaah , Ojeer Patrick , Ndive Comfort , Banarsee Ricky , Oni Lola , Majeed Azeem 
Published: January 2013

Objectives To assess sickle cell disease (SCD) patient and carer perspectives on the primary care services related to SCD that they receive from their general practitioner (GP). Design A focus group discussion was used to elicit the views of patients about the quality of care they receive from their primary healthcare providers and what they thought was the role of primary care in SCD management. The focus group discussion was video recorded. The recording was then examined by the project team and recurring themes were identified. A comparison was made with notes made by two scribes also present at the discussion. Setting Sickle Cell Society in Brent, UK. Participants Ten participants with SCD or caring for someone with SCD from Northwest London, UK. Main outcome measures Patients’ perceptions about the primary care services they received, and a list of key themes and suggestions. Results Patients and carers often bypassed GPs for acute problems but felt that GPs had an important role to play around repeat prescriptions and general health care. These service users believed SCD is often ignored and deemed unimportant by GPs. Conclusion Participants wanted the health service to support primary healthcare providers to improve their knowledge and understanding of SCD. Key themes and suggestions from this focus group have been used to help develop an educational intervention for general practice services that will be used to improve SCD management in primary care.
The effects of age on patient-reported outcome measures in total knee replacements
Authors: Williams D. P. , Price A. J. , Beard D. J. , Hadfield S. G. , Arden N. K. , Murray D. W. , Field R. E. 
Published: January 2013

We present a comparison of patient-reported outcomes (PROMs) in relation to patient age, in patients who had received a total (TKR) or unicompartmental knee replacement (UKR). The outcome was evaluated using the Oxford knee score (OKS), EuroQol (EQ-5D) and satisfaction scores. Patients aged 65 to 84 years demonstrated better pre-operative function scores than those aged < 65 years (OKS, p = 0.03; EQ-5D, p = 0.048) and those aged ≥ 85 years (OKS, p = 0.03). Post-operative scores were comparable across age groups, but a linear trend for greater post-operative improvement in OKS and EQ-5D was seen with decreasing age (p < 0.033). The overall mean satisfaction score at six months was 84.9, but those aged < 55 years exhibited a lower mean level of satisfaction (78.3) compared with all other age groups (all p < 0.031). The cumulative overall two-year revision rate was 1.3%. This study demonstrates that good early outcomes, as measured by the OKS and EQ-5D, can be anticipated following knee replacement regardless of the patient’s age, although younger patients gain greater improvement. However, the lower satisfaction in those aged < 55 years is a concern, and suggests that outcome is not fully encapsulated by the OKS and EQ-5D evaluation, and raises the question whether the OKS alone is an appropriate measure of pain and function in younger, more active individuals.Cite this article: Bone Joint J 2013;95-B:38–44.
Arthroscopic hip preservation surgery
Authors: Bedi A. , Kelly B. T. , Khanduja V. 
Published: January 2013

The technical advances in arthroscopic surgery of the hip, including the improved ability to manage the capsule and gain extensile exposure, have been paralleled by a growth in the number of conditions that can be addressed. This expanding list includes symptomatic labral tears, chondral lesions, injuries of the ligamentum teres, femoroacetabular impingement (FAI), capsular laxity and instability, and various extra-articular disorders, including snapping hip syndromes. With a careful diagnostic evaluation and technical execution of well-indicated procedures, arthroscopic surgery of the hip can achieve successful clinical outcomes, with predictable improvements in function and pre-injury levels of physical activity for many patients. This paper reviews the current position in relation to the use of arthroscopy in the treatment of disorders of the hip. Cite this article: Bone Joint J 2013;95-B:10–19.
Iatropathic brachial plexus injury
Authors: Jeyaseelan L. , Singh V. K. , Ghosh S. , Sinisi M. , Fox M. 
Published: January 2013

We present our experience of managing patients with iatropathic brachial plexus injury after delayed fixation of a fracture of the clavicle. It is a retrospective cohort study of patients treated at our peripheral nerve injury unit and a single illustrative case report. We identified 21 patients in whom a brachial plexus injury occurred as a direct consequence of fixation of a fracture of the clavicle between September 2000 and September 2011. The predominant injury involved the C5/C6 nerves, upper trunk, lateral cord and the suprascapular nerve. In all patients, the injured nerve was found to be tethered to the under surface of the clavicle by scar tissue at the site of the fracture and was usually associated with pathognomonic neuropathic pain and paralysis. Delayed fixation of a fracture of the clavicle, especially between two and four weeks after injury, can result in iatropathic brachial plexus injury. The risk can be reduced by thorough release of the tissues from the inferior surface of the clavicle before mobilisation of the fracture fragments. If features of nerve damage appear post-operatively urgent specialist referral is recommended. Cite this article: Bone Joint J 2013;95-B:106–10.
Segmental mobility, disc height and patient-reported outcomes after surgery for degenerative disc disease
Authors: Johnsen L. G. , Brinckmann P. , Hellum C. , Rossvoll I. , Leivseth G. 
Published: January 2013

This prospective multicentre study was undertaken to determine segmental movement, disc height and sagittal alignment after total disc replacement (TDR) in the lumbosacral spine and to assess the correlation of biomechanical properties to clinical outcomes. A total of 173 patients with degenerative disc disease and low back pain for more than one year were randomised to receive either TDR or multidisciplinary rehabilitation (MDR). Segmental movement in the sagittal plane and disc height were measured using distortion compensated roentgen analysis (DCRA) comparing radiographs in active flexion and extension. Correlation analysis between the range of movement or disc height and patient-reported outcomes was performed in both groups. After two years, no significant change in movement in the sagittal plane was found in segments with TDR or between the two treatment groups. It remained the same or increased slightly in untreated segments in the TDR group and in this group there was a significant increase in disc height in the operated segments. There was no correlation between segmental movement or disc height and patient-reported outcomes in either group. In this study, insertion of an intervertebral disc prosthesis TDR did not increase movement in the sagittal plane and segmental movement did not correlate with patient-reported outcomes. This suggests that in the lumbar spine the movement preserving properties of TDR are not major determinants of clinical outcomes. Cite this article: Bone Joint J 2013;95-B:81–9.
Predicting the cost-effectiveness of total hip and knee replacement
Authors: Jenkins P. J. , Clement N. D. , Hamilton D. F. , Gaston P. , Patton J. T. , Howie C. R. 
Published: January 2013

The aim of this study was to perform a cost–utility analysis of total hip (THR) and knee replacement (TKR). Arthritis is a disabling condition that leads to long-term deterioration in quality of life. Total joint replacement, despite being one of the greatest advances in medicine of the modern era, has recently come under scrutiny. The National Health Service (NHS) has competing demands, and resource allocation is challenging in times of economic restraint. Patients who underwent THR (n = 348) or TKR (n = 323) between January and July 2010 in one Scottish region were entered into a prospective arthroplasty database. A health–utility score was derived from the EuroQol (EQ-5D) score pre-operatively and at one year, and was combined with individual life expectancy to derive the quality-adjusted life years (QALYs) gained. Two-way analysis of variance was used to compare QALYs gained between procedures, while controlling for baseline differences. The number of QALYs gained was higher after THR than after TKR (6.5 vs 4.0 years, p < 0.001). The cost per QALY for THR was £1372 compared with £2101 for TKR. The predictors of an increase in QALYs gained were poorer health before surgery (p < 0.001) and younger age (p < 0.001). General health (EQ-5D VAS) showed greater improvement after THR than after TKR (p < 0.001). This study provides up-to-date cost-effectiveness data for total joint replacement. THR and TKR are extremely effective both clinically and in terms of cost effectiveness, with costs that compare favourably to those of other medical interventions. Cite this article: Bone Joint J 2013;95-B:115–21.
Should all twins and multiple births undergo ultrasound examination for developmental dysplasia of the hip?
Authors: Barr L. V. , Rehm A. 
Published: January 2013

Twins are often considered to be at an increased risk of developmental dysplasia of the hip (DDH); we therefore investigated whether multiple births have a higher incidence of DDH, and if selective ultrasound scanning should be considered for these infants. We reviewed our records of all live births between 1 January 2004 and 31 December 2008 and included 25 246 single and 990 multiple births. Multiple births did not have a significantly higher incidence of DDH compared with single births (0.0030 vs 0.0023, p = 0.8939). Of the 990 multiple births, 267 had neonatal ultrasound scans and one case of DDH was diagnosed and treated successfully with a Pavlik harness. There were two late-presenting cases at eight and 14 months of age, neither of whom had risk factors for DDH and consequently had not had a neonatal scan. Whereas selective ultrasound scanning of multiple births would have led to earlier detection and treatment of the late-presenting cases, they did not have a significantly higher incidence of DDH compared with single births. We conclude that being a twin or triplet in itself is not a risk factor for DDH and that selective ultrasound scanning is not indicated for this population. Cite this article: Bone Joint J 2013;95-B:132–4.
A comparative study of the outcomes of primary and revision lumbar discectomy surgery
Authors: Patel M. S. , Braybrooke J. , Newey M. , Sell P. 
Published: January 2013

The outcome of surgery for recurrent lumbar disc herniation is debatable. Some studies show results that are comparable with those of primary discectomy, whereas others report worse outcomes. The purpose of this study was to compare the outcome of revision lumbar discectomy with that of primary discectomy in the same cohort of patients who had both the primary and the recurrent herniation at the same level and side. A retrospective analysis of prospectively gathered data was undertaken in 30 patients who had undergone both primary and revision surgery for late recurrent lumbar disc herniation. The outcome measures used were visual analogue scales for lower limb (VAL) and back (VAB) pain and the Oswestry Disability Index (ODI). There was a significant improvement in the mean VAL and ODI scores (both p < 0.001) after primary discectomy. Revision surgery also resulted in improvements in the mean VAL (p < 0.001), VAB (p = 0.030) and ODI scores (p < 0.001). The changes were similar in the two groups (all p > 0.05). Revision discectomy can give results that are as good as those seen after primary surgery. Cite this article: Bone Joint J 2013;95-B:90–4.
Severe open tibial fractures in combat trauma
Authors: Penn-Barwell J. G. , Bennett P. M. , Fries C. A. , Kendrew J. M. , Midwinter M. J. , Rickard R. F. 
Published: January 2013

The aim of this study was to report the pattern of severe open diaphyseal tibial fractures sustained by military personnel, and their orthopaedic–plastic surgical management.The United Kingdom Military Trauma Registry was searched for all such fractures sustained between 2006 and 2010. Data were gathered on demographics, injury, management and preliminary outcome, with 49 patients with 57 severe open tibial fractures identified for in-depth study. The median total number of orthopaedic and plastic surgical procedures per limb was three (2 to 8). Follow-up for 12 months was complete in 52 tibiae (91%), and half the fractures (n = 26) either had united or in the opinion of the treating surgeon were progressing towards union. The relationship between healing without further intervention was examined for multiple variables. Neither the New Injury Severity Score, the method of internal fixation, the requirement for vascularised soft-tissue cover nor the degree of bone loss was associated with poor bony healing. Infection occurred in 12 of 52 tibiae (23%) and was associated with poor bony healing (p = 0.008). This series characterises the complex orthopaedic–plastic surgical management of severe open tibial fractures sustained in combat and defines the importance of aggressive prevention of infection.Cite this article: Bone Joint J 2013;95-B:101–5.
Alcune riflessioni sull' ἐνάργεıα dall' Ars rhetorica di Pseudo-Dionigi di Alicarnasso
Authors: Berardi Francesco 
Published: January 2013

Many modern scholars have studied in detail the phenomenon of vividness (gr. ἐνάργεıα; lat. evidentia) in ancient rhetorical texts; however, they have neglected to examine two important testimonies included in an Ars rhetorica ascribed to Dionysius of Halicarnassus, but in fact to be ascribed to an anonymous rhetorician who probably lived in the third century AD.
In these two passages the anonymous rhetorician faces some issues concerning the stylistic evidence that have not been previously studied. He analyzes the relationship between the vividness of the text and the use of everyday language, aimed to enhance realistic effects of discourse. This paper aims to present a detailed analysis of the comments offered by the anonymous rhetorician, that will help to define some peculiar aspects of stylistic vividness of the language in discourse.
The GH-releasing effect of acylated ghrelin in normal subjects is refractory to GH acute auto-feedback but is inhibited after short-term GH administration inducing IGF1 increase
Authors: Benso A , Gramaglia E , Olivetti I , Tomelini M , Gigliardi V Ramella , Frara S , Calvi E , Belcastro S , St Pierre D H , Ghigo E , Broglio F 
Published: January 2013

ObjectiveGH secretion is regulated by an interplay between GH-releasing hormone (GHRH), somatostatin (SST), and other central and peripheral signals. Acylated ghrelin (AG) amplifies GH pulsatility acting, at least partially, independently from GHRH and SST. The GH response to GHRH is inhibited by recombinant human GH (rhGH), likely due to a SST-mediated negative GH auto-feedback. The effect of exogenous rhGH on the GH-releasing effect of AG has never been tested.Design and methodsIn six healthy volunteers, we studied the GH response to acute AG administration (1.0 μg/kg i.v.) during saline or rhGH infusion (4.0 μg/kg per h i.v.) or after 4-day rhGH (10.0 μg/kg s.c.) administration.ResultsCompared with saline, rhGH infusion increased GH levels (P<0.01). During saline, acute i.v. AG induced a marked increase (P<0.01) in GH levels similar to those observed after AG administration during rhGH infusion. During s.c. rhGH, IGF1 levels rose from day 0 to day 5 (P<0.01). After 4-day s.c. rhGH, i.v. AG increased (P<0.01) GH levels, though significantly (P<0.05) less than on day 0.ConclusionsThe marked somatotroph-releasing effect of AG is refractory to a direct GH auto-feedback whereas is markedly inhibited after 4-day rhGH administration, suggesting the possibility of a selective IGF1-mediated inhibitory feedback.
Characteristics of the Strengths and Difficulties Questionnaire in Preschool Children
Authors: Theunissen Meinou H.C. , Vogels Anton G.C. , de Wolff Marianne S. , Reijneveld Sijmen A. 
Published: January 2013

OBJECTIVES:
Validated questionnaires help the preventive child healthcare (PCH) system to identify psychosocial problems. This study assesses the psychometric properties and added value of the Strengths and Difficulties Questionnaire (SDQ) for the identification of psychosocial problems among preschool-aged children by PCH.

METHODS:
We included 839 children (response 66%) 3 to 4 years of age undergoing routine health assessments in 18 PCH services across the Netherlands. Child healthcare professionals interviewed and examined children and parents. Before the interview, parents completed the SDQ and the Child Behavior Checklist (CBCL). We assessed the internal consistency, the scale structure, and validity (correlation coefficients, sensitivity, and specificity), with CBCL and treatment status as criteria, and the degree to which the SDQ could improve identification solely on the basis of clinical assessment.

RESULTS:
The internal consistency of the SDQ total difficulties score was good (Cronbach’s α, 0.78), but it was worse for some subscales of the SDQ (range, 0.50–0.74). The area under the receiver operating characteristic curve using the CBCL as a criterion was 0.94 (95% confidence interval 0.91–0.97), and sensitivity and specificity were 0.79 and 0.93, respectively. The SDQ added information to the clinical assessment; the odds ratio was 36.48 for added information by using the CBCL as a criterion.

CONCLUSIONS:
The SDQ is a valid tool for the identification of psychosocial problems in preschool-aged children by PCH. However, the low reliability of some SDQ subscales does not justify use of these subscales for decisions about further treatment.