bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical study reports of randomised controlled trials: an exploratory review of previously confidential industry reports
Authors: Doshi Peter , Jefferson Tom 
Published: February 2013

ObjectiveTo explore the structure and content of a non-random sample of clinical study reports (CSRs) to guide clinicians and systematic reviewers.Search strategyWe searched public sources and lodged Freedom of Information requests for previously confidential CSRs primarily written by the industry for regulators.Selection criteriaCSRs reporting sufficient information for extraction (‘adequate’).Primary outcome measuresPresence and length of essential elements of trial design and reporting and compression factor (ratio of page length for CSRs compared to its published counterpart in a scientific journal).Data extractionData were extracted on standard forms and crosschecked for accuracy.ResultsWe assembled a population of 78 CSRs (covering 90 randomised controlled trials; 144 610 pages total) dated 1991–2011 of 14 pharmaceuticals. Report synopses had a median length of 5 pages, efficacy evaluation 13.5 pages, safety evaluation 17 pages, attached tables 337 pages, trial protocol 62 pages, statistical analysis plan 15 pages and individual efficacy and safety listings had a median length of 447 and 109.5 pages, respectively. While 16 (21%) of CSRs contained completed case report forms, these were accessible to us in only one case (765 pages representing 16 individuals). Compression factors ranged between 1 and 8805.ConclusionsClinical study reports represent a hitherto mostly hidden and untapped source of detailed and exhaustive data on each trial. They should be consulted by independent parties interested in a detailed record of a clinical trial, and should form the basic unit for evidence synthesis as their use is likely to minimise the problem of reporting bias. We cannot say whether our sample is representative and whether our conclusions are generalisable to an undefined and undefinable population of CSRs.
Hemopexin Therapy Improves Cardiovascular Function by Preventing Heme-Induced Endothelial Toxicity in Mouse Models of Hemolytic Diseases
Authors: Vinchi Francesca , De Franceschi Lucia , Ghigo Alessandra , Townes Tim , Cimino James , Silengo Lorenzo , Hirsch Emilio , Altruda Fiorella , Tolosano Emanuela 
Published: February 2013

Background—
Hemolytic diseases are characterized by enhanced intravascular hemolysis resulting in heme-catalyzed reactive oxygen species generation, which leads to endothelial dysfunction and oxidative damage. Hemopexin (Hx) is a plasma heme scavenger able to prevent endothelial damage and tissue congestion in a model of heme overload. Here, we tested whether Hx could be used as a therapeutic tool to counteract heme toxic effects on the cardiovascular system in hemolytic diseases.

Methods and Results—
By using a model of heme overload in Hx-null mice, we demonstrated that heme excess in plasma, if not bound to Hx, promoted the production of reactive oxygen species and the induction of adhesion molecules and caused the reduction of nitric oxide availability. Then, we used β-thalassemia and sickle cell disease mice as models of hemolytic diseases to evaluate the efficacy of an Hx-based therapy in the treatment of vascular dysfunction related to heme overload. Our data demonstrated that Hx prevented heme-iron loading in the cardiovascular system, thus limiting the production of reactive oxygen species, the induction of adhesion molecules, and the oxidative inactivation of nitric oxide synthase/nitric oxide, and promoted heme recovery and detoxification by the liver mainly through the induction of heme oxygenase activity. Moreover, we showed that in sickle cell disease mice, endothelial activation and oxidation were associated with increased blood pressure and altered cardiac function, and the administration of exogenous Hx was found to almost completely normalize these parameters.

Conclusions—
Hemopexin treatment is a promising novel therapy to protect against heme-induced cardiovascular dysfunction in hemolytic disorders.
Comparison of Supination External Rotation Type IV Ankle Fractures in Geriatric Versus Nongeriatric Populations
Authors: Little Milton T. M. , Berkes Marschall B. , Lazaro Lionel E. , Sculco Peter K. , Cymerman Rachel M. , Pardee Nadine , Helfet David L. , Lorich Dean G. 
Published: February 2013

Background: Geriatric patients’ (defined as those older than 65 years old) inherent comorbidities, functional limitations, and bone quality present obstacles to successful clinical outcomes for operatively treated supination external rotation (SER) ankle fractures. We retrospectively reviewed a prospectively collected series of SER injuries between 2004 and 2010. This is a comparison of the radiographic and clinical outcomes of our geriatric (27 patients) and nongeriatric (81 patients) populations. We hypothesized that geriatric patients would have worse outcomes when compared to nongeriatric patients. Methods: All SER ankle fractures (176) treated by a single surgeon were enrolled in a prospective database. All patients fulfilled inclusion criteria (108) consisting of 1 year of having clinical follow-up, postoperative radiographs, and Foot & Ankle Outcome Scores (FAOS). The primary outcome evaluated was functional outcome as exhibited by the FAOS. The secondary outcomes included adequacy of reduction, loss of reduction, postoperative complications (wound complications, infection, pain-driven hardware removal), and range of motion. Results: Despite significantly higher rates of diabetes ( P < .001) and peripheral vascular disease ( P < .001), there were statistically significantly better FAOS outcomes in the symptoms subcategory among the geriatric population. There was no significant difference in the articular reduction, syndesmotic reduction, wound complications, postoperative infections, or range of motion between these groups. Conclusion: Geriatric patients exhibited equivalent complication rates, radiographic outcomes, and functional outcomes compared to nongeriatric patients in this series. Anatomic fixation and soft tissue management counter the inherent risks of operative intervention in geriatric populations that report higher rates of comorbidities. This study supports aggressive fracture- and ligament-specific operative intervention in geriatric patients presenting with unstable SER injuries. Level of Evidence: Level III, retrospective case control study of prospectively collected data.
Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study
Authors: Murri Mora , Leiva Isabel , Gomez-Zumaquero Juan Miguel , Tinahones Francisco J , Cardona Fernando , Soriguer Federico , Queipo-Ortuño María Isabel 
Published: February 2013

Abstract

Background
A recent study using a rat model found significant differences at the time of diabetes onset in the bacterial communities responsible for type 1 diabetes modulation. We hypothesized that type 1 diabetes in humans could also be linked to a specific gut microbiota. Our aim was to quantify and evaluate the difference in the composition of gut microbiota between children with type 1 diabetes and healthy children and to determine the possible relationship of the gut microbiota of children with type 1 diabetes with the glycemic level.

Methods
A case-control study was carried out with 16 children with type 1 diabetes and 16 healthy children. The fecal bacteria composition was investigated by polymerase chain reaction-denaturing gradient gel electrophoresis and real-time quantitative polymerase chain reaction.

Results
The mean similarity index was 47.39% for the healthy children and 37.56% for the children with diabetes, whereas the intergroup similarity index was 26.69%. In the children with diabetes, the bacterial number of Actinobacteria and Firmicutes, and the Firmicutes to Bacteroidetes ratio were all significantly decreased, with the quantity of Bacteroidetes significantly increased with respect to healthy children. At the genus level, we found a significant increase in the number of Clostridium, Bacteroides and Veillonella and a significant decrease in the number of Lactobacillus, Bifidobacterium, Blautia coccoides/Eubacterium rectale group and Prevotella in the children with diabetes. We also found that the number of Bifidobacterium and Lactobacillus, and the Firmicutes to Bacteroidetes ratio correlated negatively and significantly with the plasma glucose level while the quantity of Clostridium correlated positively and significantly with the plasma glucose level in the diabetes group.

Conclusions
This is the first study showing that type 1 diabetes is associated with compositional changes in gut microbiota. The significant differences in the number of Bifidobacterium, Lactobacillus and Clostridium and in the Firmicutes to Bacteroidetes ratio observed between the two groups could be related to the glycemic level in the group with diabetes. Moreover, the quantity of bacteria essential to maintain gut integrity was significantly lower in the children with diabetes than the healthy children. These findings could be useful for developing strategies to control the development of type 1 diabetes by modifying the gut microbiota.
Identification of mouse colony-forming endothelial progenitor cells for postnatal neovascularization: a novel insight highlighted by new mouse colony-forming assay
Authors: Tsukada Shizu , Kwon Sang-Mo , Matsuda Takenori , Jung Seok-Yun , Lee Jun-Hee , Lee Sang-Hun , Masuda Haruchika , Asahara Takayuki 
Published: February 2013

Abstract
Introduction
Endothelial progenitor cells (EPCs) play a critical role in restoration of ischemic diseases. However, the actual status of EPC development and the mechanisms of EPC dysfunctions in patients with various ischemic diseases remain unknown.

Methods
To investigate the detailed function of EPCs in experimental murine models, we have established an EPC colony forming assay (EPC-CFA) in murine EPCs. The abilities of murine EPCs in differentiation, adhesive capacity, proliferative potency, and transplantation in vitro and in vivo were then examined.

Results
Peripheral blood mononuclear cells (PB-MNCs), bone marrow mononuclear cells (BM-MNCs) or bone marrow c-Kit+/Sca-1+ lineage negative (BM-KSL) cells differentiated into two types of EPC colony forming units (EPC-CFUs), large sized EPC (large-EPC)-CFUs and small sized EPC (small-EPC)-CFUs. Gene expression analysis demonstrated that both EPC-CFU-derived cells expressed eNOS, Flk-1 and VE-cadherin, markers of endothelial cells (ECs), although the small-EPCs derived from small-EPC-CFU were higher in number and showed more immature features (higher population of KSL cells). Functionally, the large-EPCs derived from large-EPC-CFU had higher adhesive capacity but lower proliferative potency than small-EPCs, showing improved tubular forming capacity and incorporation potency into primary EC-derived tube formation. Importantly, hindlimb ischemia increased the frequencies of large-EPC-CFUs differentiated from PB-MNCs and bone marrow. Actually, transplantation of large-EPCs into ischemic hindlimb enhanced neovascularization in hindlimb ischemia model, although small-EPCs or murine ECs did not, suggesting that large-EPC-CFUs might play an important role in restoration of ischemic diseases.

Conclusions
We demonstrated, using a murine ischemia model, that the EPC-CFA could be a useful way to investigate the differentiation levels of murine EPCs, further providing a crucial clue that large-EPC-CFU status may be more functional or effective EPCs to promote neovascularization.
Outcome of arthrodesis of the hindfoot as a salvage procedure for complex ankle pathology using the Ilizarov technique
Authors: Kugan R. , Aslam N. , Bose D. , McNally M. A. 
Published: February 2013

Achieving arthrodesis of the ankle can be difficult in the presence of infection, deformity, poor soft tissues and bone loss. We present a series of 48 patients with complex ankle pathology, treated with the Ilizarov technique. Infection was present in 30 patients and 30 had significant deformity before surgery. Outcome was assessed clinically and with patient-reported outcome measures (Modified American Orthopaedic Foot and Ankle Society (MAOFAS) scale and the Short-Form (SF-36)).Arthrodesis was achieved in 40 patients with the Ilizarov technique alone and in six further patients with additional surgery. Infection was eradicated in all patients at a mean follow-up of 46.6 months (13 to 162). Successful arthrodesis was less likely in those with comorbidities and in tibiocalcaneal fusion compared with tibiotalar fusion.These patients had poor general health scores compared with the normal population before surgery. The mean MAOFAS score improved significantly from 24.3 (0 to 90) pre-operatively to 56.2 (30 to 90) post-operatively, but there was only a modest improvement in general health; the mean SF-36 improved from 44.8 (19 to 66) to 50.1 (21 to 76). There was a major benefit in terms of pain relief.Arthrodesis using the Ilizarov technique is an effective treatment for complex ankle pathology, with good clinical outcomes and eradication of infection. However, even after successful arthrodesis general health scores remain limited.Cite this article: Bone Joint J 2013;95-B:371–7.
The use of ceramic-on-ceramic bearings in isolated revision of the acetabular component
Authors: Jack C. M. , Molloy D. O. , Walter W. L. , Zicat B. A. , Walter W. K. 
Published: February 2013

The practice of removing a well-fixed cementless femoral component is associated with high morbidity. Ceramic bearing couples are low wearing and their use minimises the risk of subsequent further revision due to the production of wear debris. A total of 165 revision hip replacements were performed, in which a polyethylene-lined acetabular component was revised to a new acetabular component with a ceramic liner, while retaining the well-fixed femoral component. A titanium sleeve was placed over the used femoral trunnion, to which a ceramic head was added. There were 100 alumina and 65 Delta bearing couples inserted.The mean Harris hip score improved significantly from 71.3 (9.0 to 100.0) pre-operatively to 91.0 (41.0 to 100.0) at a mean follow up of 4.8 years (2.1 to 12.5) (p < 0.001). No patients reported squeaking of the hip.There were two fractures of the ceramic head, both in alumina bearings. No liners were seen to fracture. No fractures were observed in components made of Delta ceramic. At 8.3 years post-operatively the survival with any cause of failure as the endpoint was 96.6% (95% confidence interval (CI) 85.7 to 99.3) for the acetabular component and 94.0% (95% CI 82.1 to 98.4) for the femoral component.The technique of revising the acetabular component in the presence of a well-fixed femoral component with a ceramic head placed on a titanium sleeve over the used trunnion is a useful adjunct in revision hip practice. The use of Delta ceramic is recommended.Cite this article: Bone Joint J 2013;95-B:333–8.
Single-stage revision for peri-prosthetic shoulder infection
Authors: Klatte T. O. , Junghans K. , Al-Khateeb H. , Rueger J. M. , Gehrke T. , Kendoff D. , Neumann J. 
Published: February 2013

There have been only a few small studies of patients with an infected shoulder replacement treated with a single-stage exchange procedure. We retrospectively reviewed 35 patients (19 men and 16 women) with a peri-prosthetic infection of the shoulder who were treated in this way. A total of 26 were available for clinical examination; three had died, two were lost to follow-up and four patients had undergone revision surgery. The mean follow-up time was 4.7 years (1.1 to 13.25), with an infection-free survival of 94%.The organisms most commonly isolated intra-operatively were Staphylococcus epidermidis and Propionibacterium acnes; two patients developed a recurrent infection. Three different types of prosthesis were used: a hemiarthroplasty, a hemiarthroplasty with a bipolar head and reverse prosthesis. The mean Constant-Murley score at final follow-up was 43.3 (14 to 90) for patients with a hemiarthroplasty, 56 (40 to 88) for those with a hemiarthroplasty with a bipolar head and 61 (7 to 90) for those with a reverse prosthesis. The mean hospital stay was 10.6 days (5 to 29).Single-stage exchange is a successful and practical treatment for patients with peri-prosthetic infection of the shoulder.Cite this article: Bone Joint J 2013;95-B:391–5.
Diffuse pigmented villonodular synovitis (diffuse-type giant cell tumour) of the foot and ankle
Authors: Stevenson J. D. , Jaiswal A. , Gregory J. J. , Mangham D. C. , Cribb G. , Cool P. 
Published: February 2013

Pigmented villonodular synovitis (PVNS) is a rare benign disease of the synovium of joints and tendon sheaths, which may be locally aggressive. We present 18 patients with diffuse-type PVNS of the foot and ankle followed for a mean of 5.1 years (2 to 11.8). There were seven men and 11 women, with a mean age of 42 years (18 to 73). A total of 13 patients underwent open or arthroscopic synovectomy, without post-operative radiotherapy. One had surgery at the referring unit before presentation with residual tibiotalar PVNS. The four patients who were managed non-operatively remain symptomatically controlled and under clinical and radiological surveillance. At final follow-up the mean Musculoskeletal Tumour Society score was 93.8% (95% confidence interval (CI) 85 to 100), the mean Toronto Extremity Salvage Score was 92 (95% CI 82 to 100) and the mean American Academy of Orthopaedic Surgeons foot and ankle score was 89 (95% CI 79 to 100). The lesion in the patient with residual PVNS resolved radiologically without further intervention six years after surgery. Targeted synovectomy without adjuvant radiotherapy can result in excellent outcomes, without recurrence. Asymptomatic patients can be successfully managed non-operatively. This is the first series to report clinical outcome scores for patients with diffuse-type PVNS of the foot and ankle.Cite this article: Bone Joint J 2013;95-B:384–90.
Evaluation of project P.A.T.H.S. by the program implementers: findings based on the extension phase
Authors: Shek Daniel T.L. , Sun Rachel C.F. 
Published: February 2013

Abstract
A total of 236 schools participated in the Project P.A.T.H.S. in the 2010/2011 school year. After completion of the Tier 1 Program, subjective outcome evaluation data were collected from 3275 program implementers. Based on the consolidated findings based on schools as units, results showed that participants had positive perceptions of the program, implementers, and benefits of the program. More than four-fifths of the implementers regarded the program as helpful to the program participants. Multiple regression analysis revealed that perceived qualities of the program and the program implementers predicted perceived effectiveness of the program. Grade differences were not significant. The present study provides additional support for the effectiveness of the Tier 1 Program of the Project P.A.T.H.S. in Hong Kong.
Perception of collaborative learning in associate degree students in Hong Kong
Authors: Shek Daniel T.L. , Shek Moses M.W. 
Published: February 2013

Abstract
Although collaborative learning has been widely researched in Western contexts, no study has been carried out to understand how associate degree students look at collaborative learning in Hong Kong. In this study, perceptions of and attitudes to collaborative learning among associate degree students were studied. A total of 44 associate degree students completed an online questionnaire including measures of perceived benefits and attitudes to collaborative learning, and social-emotional competence. Results showed that there were no significant differences between male and female students on perceived benefits of and attitudes towards collaborative learning. Social-emotional competence was related to perceived benefits of and attitudes to collaborative learning. Attitudes were also related to perceived benefits of collaborative learning. This paper is the first known study looking at the relationships among perceived benefits and attitudes to collaborative learning and social-emotional competence in Chinese associate degree students in different Chinese contexts.
Implementation of the extension phase of the project P.A.T.H.S. in Hong Kong: observations based on the Co-Walker Scheme
Authors: Shek Daniel T.L. , Law Moon Y.M. 
Published: February 2013

Abstract
The implementation quality of the Tier 1 Program (Secondary 1 Program) of the Project P.A.T.H.S. in the second year of the Extension Phase was examined in this study, with classroom observations of 218 units in 172 schools. Results demonstrated that the overall level of program adherence was generally high with an average of over 90%. Different aspects regarding program delivery were significantly correlated, suggesting that different aspects of program implementation were intimately related. Regarding predictors of global implementation quality, analyses indicated that overall implementation quality was significantly predicted by interactive delivery method, achievement of objectives, time management, and lesson preparation; success of implementation was predicted by student participation and involvement, interactive delivery method, achievement of objectives, and time management. The present study replicated the findings in previous studies.
Mineralogy, provenance, and dispersal history of late Quaternary deep-sea sands in Cascadia Basin and Blanco fracture zone off Oregon
Authors: Duncan John R. , Kulm L. D. 
Published: February 2013

Abstract
The mineralogy of sandy sediments deposited during the late Pleistocene and Holocene in southern Cascadia Basin and the adjoining Blanco Fracture Zone displays systematic regional and temporal trends. The light-mineral constituents of these sands are lithic, arkosic, or volcanic in composition. They are mainly derived from extrusive and intrusive basic igneous rocks. Four deep-sea heavy-mineral provinces (A, B, C, and D) are distinguishable in the area investigated. Province A lies in the Blanco Fracture Zone--Gorda Ridge transition area. Textural and mineralogical compositions of these deposits suggest local submarine volcanism. The volcanism may be associated with sea-floor spreading along the young crestal zone of Gorda Ridge. Province B is restricted to the late Pleistocene sediments of western Cascadia Abyssal Plain and Vancouver Valley; the most probable sediment source is Vancouver Island and vicinity. Sandy sediments from the island no longer reach the deep-sea environments, because they are presently being trapped behind the sills of the glacially-scoured inlets of the island. Province C includes the late Pleistocene and Holocene deposits in southeastern Cascadia Basin and Cascadia Channel; the sediments were derived from the Columbia River drainage. During Holocene time, the supply of coarse-grained detritals from the Columbia River diminished as sea level rose, and locally derived sediments from the metamorphic terrane of the Klamath Mountains were deposited at the base of the continental slope off southern Oregon and northern California (Province D), overriding the influence of the Columbia River sedimentation.