Early versus delayed application of Thomas splints in patients with isolated femur shaft fractures: The benefits quantified

AIMS To investigate and quantify the clinical benefits of early versus delayed application of Thomas splints in patients with isolated femur shaft fractures. MATERIALS AND METHODS Level IV retrospective clinical and radiological analysis of patients presenting from January to December 2012 at a Level 1 Trauma Unit. All skeletally mature patients with isolated femur shaft fractures independently of their mechanism of injury were included. Exclusion criteria were: ipsilateral fracture of the lower limb, neck and supracondylar femur fractures, periprosthetic and incomplete fractures. Their clinical records were analysed for blood transfusion requirements, pulmonary complications, surgery time, duration of hospital stay and analgesic requirements. RESULTS A total of 106 patients met our inclusion criteria. There were 74 males and 32 females. Fifty seven (54%) patients were in the 'early splinted' group and 49 patients (46%) were in the 'delayed splinted' group (P>0.05). The need for blood transfusion was significantly reduced in the 'early splinted' group (P=0.04). There was a significantly higher rate of pulmonary complications in the 'delayed splinted' group (P=0.008). All other parameters were similar between the two groups. CONCLUSION The early application of Thomas splints for isolated femur fractures in non-polytraumatised patients has a clinically and statistically significant benefit of reducing the need for blood transfusions and the incidence of pulmonary complications.

Comparison between magnetic resonance imaging and computed tomography of the lung in patients with cystic fibrosis with regard to clinical, laboratory, and pulmonary functional parameters

OBJECTIVE To evaluate whether magnetic resonance imaging (MRI) is effective as computed tomography (CT) in determining morphologic and functional pulmonary changes in patients with cystic fibrosis (CF) in association with multiple clinical parameters. MATERIALS AND METHODS Institutional review board approval and patient written informed consent were obtained. In this prospective study, 30 patients with CF (17 men and 13 women; mean (SD) age, 30.2 (9.2) years; range, 19-52 years) were included. Chest CT was acquired by unenhanced low-dose technique for clinical purposes. Lung MRI (1.5 T) comprised T2- and T1-weighted sequences before and after the application of 0.1-mmol·kg gadobutrol, also considering lung perfusion imaging. All CT and MR images were visually evaluated by using 2 different scoring systems: the modified Helbich and the Eichinger scores. Signal intensity of the peribronchial walls and detected mucus on T2-weighted images as well as signal enhancement of the peribronchial walls on contrast-enhanced T1-weighted sequences were additionally assessed on MRI. For the clinical evaluation, the pulmonary exacerbation rate, laboratory, and pulmonary functional parameters were determined. RESULTS The overall modified Helbich CT score had a mean (SD) of 15.3 (4.8) (range, 3-21) and median of 16.0 (interquartile range [IQR], 6.3). The overall modified Helbich MR score showed slightly, not significantly, lower values (Wilcoxon rank sum test and Student t test; P > 0.05): mean (SD) of 14.3 (4.7) (range, 3-20) and median of 15.0 (IQR, 7.3). Without assessment of perfusion, the overall Eichinger score resulted in the following values for CT vs MR examinations: mean (SD), 20.3 (7.2) (range, 4-31); and median, 21.0 (IQR, 9.5) vs mean (SD), 19.5 (7.1) (range, 4-33); and median, 20.0 (IQR, 9.0). All differences between CT and MR examinations were not significant (Wilcoxon rank sum tests and Student t tests; P > 0.05). In general, the correlations of the CT scores (overall and different imaging parameters) to the clinical parameters were slightly higher compared to the MRI scores. However, if all additional MRI parameters were integrated into the scoring systems, the correlations reached the values of the CT scores. The overall image quality was significantly higher for the CT examinations compared to the MRI sequences. CONCLUSIONS One major diagnostic benefit of lung MRI in CF is the possible acquisition of several different morphologic and functional imaging features without the use of any radiation exposure. Lung MRI shows reliable associations with CT and clinical parameters, which suggests its implementation in CF for routine diagnosis, which would be particularly important in follow-up imaging over the long term.

Non-surgical treatment of pain associated with posterior tibial tendon dysfunction: study protocol for a randomised clinical trial

BACKGROUND Symptoms associated with pes planovalgus or flatfeet occur frequently, even though some people with a flatfoot deformity remain asymptomatic. Pes planovalgus is proposed to be associated with foot/ankle pain and poor function. Concurrently, the multifactorial weakness of the tibialis posterior muscle and its tendon can lead to a flattening of the longitudinal arch of the foot. Those affected can experience functional impairment and pain. Less severe cases at an early stage are eligible for non-surgical treatment and foot orthoses are considered to be the first line approach. Furthermore, strengthening of arch and ankle stabilising muscles are thought to contribute to active compensation of the deformity leading to stress relief of soft tissue structures. There is only limited evidence concerning the numerous therapy approaches, and so far, no data are available showing functional benefits that accompany these interventions. METHODS After clinical diagnosis and clarification of inclusion criteria (e.g., age 40-70, current complaint of foot and ankle pain more than three months, posterior tibial tendon dysfunction stage I & II, longitudinal arch flattening verified by radiography), sixty participants with posterior tibial tendon dysfunction associated complaints will be included in the study and will be randomly assigned to one of three different intervention groups: (i) foot orthoses only (FOO), (ii) foot orthoses and eccentric exercise (FOE), or (iii) sham foot orthoses only (FOS). Participants in the FOO and FOE groups will be allocated individualised foot orthoses, the latter combined with eccentric exercise for ankle stabilisation and strengthening of the tibialis posterior muscle. Participants in the FOS group will be allocated sham foot orthoses only. During the intervention period of 12 weeks, all participants will be encouraged to follow an educational program for dosed foot load management (e.g., to stop activity if they experience increasing pain). Functional impairment will be evaluated pre- and post-intervention by the Foot Function Index. Further outcome measures include the Pain Disability Index, Visual Analogue Scale for pain, SF-12, kinematic data from 3D-movement analysis and neuromuscular activity during level and downstairs walking. Measuring outcomes pre- and post-intervention will allow the calculation of intervention effects by 3×3 Analysis of Variance (ANOVA) with repeated measures. DISCUSSION The purpose of this randomised trial is to evaluate the therapeutic benefit of three different non-surgical treatment regimens in participants with posterior tibial tendon dysfunction and accompanying pes planovalgus. Furthermore, the analysis of changes in gait mechanics and neuromuscular control will contribute to an enhanced understanding of functional changes and eventually optimise conservative management strategies for these patients. TRIAL REGISTRATION ClinicalTrials.gov Protocol Registration System: ClinicalTrials.gov ID NCT01839669.

Prognostic Relevance of Palliative Primary Tumor Removal in 37,793 Metastatic Colorectal Cancer Patients: A Population-Based, Propensity Score-Adjusted Trend Analysis

OBJECTIVE To assess whether palliative primary tumor resection in colorectal cancer patients with incurable stage IV disease is associated with improved survival. BACKGROUND There is a heated debate regarding whether or not an asymptomatic primary tumor should be removed in patients with incurable stage IV colorectal disease. METHODS Stage IV colorectal cancer patients were identified in the Surveillance, Epidemiology, and End Results database between 1998 and 2009. Patients undergoing surgery to metastatic sites were excluded. Overall survival and cancer-specific survival were compared between patients with and without palliative primary tumor resection using risk-adjusted Cox proportional hazard regression models and stratified propensity score methods. RESULTS Overall, 37,793 stage IV colorectal cancer patients were identified. Of those, 23,004 (60.9%) underwent palliative primary tumor resection. The rate of patients undergoing palliative primary cancer resection decreased from 68.4% in 1998 to 50.7% in 2009 (P < 0.001). In Cox regression analysis after propensity score matching primary cancer resection was associated with a significantly improved overall survival [hazard ratio (HR) of death = 0.40, 95% confidence interval (CI) = 0.39-0.42, P < 0.001] and cancer-specific survival (HR of death = 0.39, 95% CI = 0.38-0.40, P < 0.001). The benefit of palliative primary cancer resection persisted during the time period 1998 to 2009 with HRs equal to or less than 0.47 for both overall and cancer-specific survival. CONCLUSIONS On the basis of this population-based cohort of stage IV colorectal cancer patients, palliative primary tumor resection was associated with improved overall and cancer-specific survival. Therefore, the dogma that an asymptomatic primary tumor never should be resected in patients with unresectable colorectal cancer metastases must be questioned.

EACTS expert consensus statement for surgical management of pleural empyema

Pleural infection is a frequent clinical condition. Prompt treatment has been shown to reduce hospital costs, morbidity and mortality. Recent advances in treatment have been variably implemented in clinical practice. This statement reviews the latest developments and concepts to improve clinical management and stimulate further research. The European Association for Cardio-Thoracic Surgery (EACTS) Thoracic Domain and the EACTS Pleural Diseases Working Group established a team of thoracic surgeons to produce a comprehensive review of available scientific evidence with the aim to cover all aspects of surgical practice related to its treatment, in particular focusing on: surgical treatment of empyema in adults; surgical treatment of empyema in children; and surgical treatment of post-pneumonectomy empyema (PPE). In the management of Stage 1 empyema, prompt pleural space chest tube drainage is required. In patients with Stage 2 or 3 empyema who are fit enough to undergo an operative procedure, there is a demonstrated benefit of surgical debridement or decortication [possibly by video-assisted thoracoscopic surgery (VATS)] over tube thoracostomy alone in terms of treatment success and reduction in hospital stay. In children, a primary operative approach is an effective management strategy, associated with a lower mortality rate and a reduction of tube thoracostomy duration, length of antibiotic therapy, reintervention rate and hospital stay. Intrapleural fibrinolytic therapy is a reasonable alternative to primary operative management. Uncomplicated PPE [without bronchopleural fistula (BPF)] can be effectively managed with minimally invasive techniques, including fenestration, pleural space irrigation and VATS debridement. PPE associated with BPF can be effectively managed with individualized open surgical techniques, including direct repair, myoplastic and thoracoplastic techniques. Intrathoracic vacuum-assisted closure may be considered as an adjunct to the standard treatment. The current literature cements the role of VATS in the management of pleural empyema, even if the choice of surgical approach relies on the individual surgeon's preference.

Safety and Efficacy of New-Generation Drug-Eluting Stents in Women at High Risk for Atherothrombosis: From the Women in Innovation and Drug-Eluting Stents Collaborative Patient-Level Pooled Analysis

BACKGROUND The safety and efficacy of new-generation drug-eluting stents (DES) in women with multiple atherothrombotic risk (ATR) factors is unclear. METHODS AND RESULTS We pooled patient-level data for women enrolled in 26 randomized trials. Study population was categorized based on the presence or absence of high ATR, which was defined as having history of diabetes mellitus, prior percutaneous or surgical coronary revascularization, or prior myocardial infarction. The primary end point was major adverse cardiovascular events defined as a composite of all-cause mortality, myocardial infarction, or target lesion revascularization at 3 years of follow-up. Out of 10 449 women included in the pooled database, 5333 (51%) were at high ATR. Compared with women not at high ATR, those at high ATR had significantly higher risk of major adverse cardiovascular events (15.8% versus 10.6%; adjusted hazard ratio: 1.53; 95% confidence interval: 1.34-1.75; P=0.006) and all-cause mortality. In high-ATR risk women, the use of new-generation DES was associated with significantly lower risk of 3-year major adverse cardiovascular events (adjusted hazard ratio: 0.69; 95% confidence interval: 0.52-0.92) compared with early-generation DES. The benefit of new-generation DES on major adverse cardiovascular events was uniform between high-ATR and non-high-ATR women, without evidence of interaction (Pinteraction=0.14). At landmark analysis, in high-ATR women, stent thrombosis rates were comparable between DES generations in the first year, whereas between 1 and 3 years, stent thrombosis risk was lower with new-generation devices. CONCLUSIONS Use of new-generation DES even in women at high ATR is associated with a benefit consistent over 3 years of follow-up and a substantial improvement in very-late thrombotic safety.

A Randomized Comparison of Reservoir-Based Polymer-Free Amphilimus-Eluting Stents Versus Everolimus-Eluting Stents With Durable Polymer in Patients With Diabetes Mellitus: The RESERVOIR Clinical Trial.

OBJECTIVES The aim of this study was to compare the efficacy of amphilimus-eluting stents (AES) with that of everolimus-eluting stents (EES) in patients with diabetes mellitus (DM). BACKGROUND The AES is a polymer-free drug-eluting stent that elutes sirolimus formulated with an amphiphilic carrier from laser-dug wells. This technology could be associated with a high efficacy in patients with DM. METHODS This was a multicenter, randomized, noninferiority trial. Patients with DM medically treated with oral glucose-lowering agents or insulin and de novo coronary lesions were randomized in a 1:1 fashion to AES or EES. The primary endpoint was the neointimal (NI) volume obstruction assessed by optical coherence tomography at 9-month follow-up. RESULTS A total of 116 lesions in 112 patients were randomized. Overall, 40% were insulin-treated patients, with a median HbA1c of 7.3% (interquartile range: 6.7% to 8.0%). The primary endpoint, NI volume obstruction, was 11.97 ± 5.94% for AES versus 16.11 ± 18.18% for EES, meeting the noninferiority criteria (p = 0.0003). Pre-specified subgroup analyses showed a significant interaction between stent type and glycemic control (p = 0.02), with a significant reduction in NI hyperplasia in the AES group in patients with the higher HbA1c (p = 0.03). By quantitative coronary angiography, in-stent late loss was 0.14 ± 0.24 for AES versus 0.24 ± 0.57 mm for EES (p = 0.27), with a larger minimal lumen diameter at follow-up for AES (p = 0.02), mainly driven by 2 cases of occlusive restenosis in the EES group. CONCLUSIONS AES are noninferior to EES for the coronary revascularization of patients with DM. These results suggest a high efficacy of the AES and may support the potential benefit of this stent in patients with DM. (A Randomized Comparison of Reservoir-Based Polymer-Free Amphilimus-Eluting Stents Versus Everolimus-Eluting Stents With Durable Polymer in Patients With Diabetes Mellitus [RESERVOIR]; NCT01710748).

Functional evidence for continued alveolarisation in former preterms at school age?

Prematurity is the most common disruptor of lung development. The aim of our study was to examine the function of the more vulnerable peripheral airways in former preterm children by multiple-breath washout (MBW) measurements.86 school-aged children, born between 24 and 35 weeks of gestation and 49 term-born children performed nitrogen MBW. Lung clearance index (LCI), and slope III-derived Scond and Sacin were assessed as markers for global, convection-dependent and diffusion-convection-dependent ventilation inhomogeneity, respectively.We analysed the data of 77 former preterm (mean (range) age 9.5 (7.2-12.8) years) and 46 term-born children (mean age 9.9 (6.0-15.9) years). LCI and Sacin did not differ between preterm and term-born children. Scond was significantly elevated in preterm compared to term-born participants (mean difference z-score 1.74, 95% CI 1.17-2.30; p<0.001), with 54% of former preterm children showing elevated Scond. In multivariable regression analysis Scond was significantly related only to gestational age (R(2)=0.37).Normal Sacin provides evidence for a functionally normal alveolar compartment, while elevated Scond indicates impaired function of more proximal conducting airways. Together, our findings support the concept of continued alveolarisation, albeit with "dysanaptic" lung growth in former preterm children.

The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children.

Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2 years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.

Expert Opinion on the Perceived Effectiveness and Importance of On-Farm Biosecurity Measures for Cattle and Swine Farms in Switzerland.

Biosecurity is crucial for safeguarding livestock from infectious diseases. Despite the plethora of biosecurity recommendations, published scientific evidence on the effectiveness of individual biosecurity measures is limited. The objective of this study was to assess the perception of Swiss experts about the effectiveness and importance of individual on-farm biosecurity measures for cattle and swine farms (31 and 30 measures, respectively). Using a modified Delphi method, 16 Swiss livestock disease specialists (8 for each species) were interviewed. The experts were asked to rank biosecurity measures that were written on cards, by allocating a score from 0 (lowest) to 5 (highest). Experts ranked biosecurity measures based on their importance related to Swiss legislation, feasibility, as well as the effort required for implementation and the benefit of each biosecurity measure. The experts also ranked biosecurity measures based on their effectiveness in preventing an infectious agent from entering and spreading on a farm, solely based on transmission characteristics of specific pathogens. The pathogens considered by cattle experts were those causing Bluetongue (BT), Bovine Viral Diarrhea (BVD), Foot and Mouth Disease (FMD) and Infectious Bovine Rhinotracheitis (IBR). Swine experts expressed their opinion on the pathogens causing African Swine Fever (ASF), Enzootic Pneumonia (EP), Porcine Reproductive and Respiratory Syndrome (PRRS), as well as FMD. For cattle farms, biosecurity measures that improve disease awareness of farmers were ranked as both most important and most effective. For swine farms, the most important and effective measures identified were those related to animal movements. Among all single measures evaluated, education of farmers was perceived by the experts to be the most important and effective for protecting both Swiss cattle and swine farms from disease. The findings of this study provide an important basis for recommendation to farmers and policy makers.

Incorporation of tissue-based genomic biomarkers into localized prostate cancer clinics.

Localized prostate cancer (PCa) is a clinically heterogeneous disease, which presents with variability in patient outcomes within the same risk stratification (low, intermediate or high) and even within the same Gleason scores. Genomic tools have been developed with the purpose of stratifying patients affected by this disease to help physicians personalize therapies and follow-up schemes. This review focuses on these tissue-based tools. At present, four genomic tools are commercially available: Decipher™, Oncotype DX®, Prolaris® and ProMark®. Decipher™ is a tool based on 22 genes and evaluates the risk of adverse outcomes (metastasis) after radical prostatectomy (RP). Oncotype DX® is based on 17 genes and focuses on the ability to predict outcomes (adverse pathology) in very low-low and low-intermediate PCa patients, while Prolaris® is built on a panel of 46 genes and is validated to evaluate outcomes for patients at low risk as well as patients who are affected by high risk PCa and post-RP. Finally, ProMark® is based on a multiplexed proteomics assay and predicts PCa aggressiveness in patients found with similar features to Oncotype DX®. These biomarkers can be helpful for post-biopsy decision-making in low risk patients and post-radical prostatectomy in selected risk groups. Further studies are needed to investigate the clinical benefit of these new technologies, the financial ramifications and how they should be utilized in clinics.

Physician adoption of a practice guideline: Effect on the cost of medical care for adult patients with diabetes

In the demanding environment of healthcare reform, reduction of unwanted physician practice variation is promoted, often through evidence-based guidelines. Guidelines represent innovations that direct change(s) in physician practice; however, compliance has been disappointing. Numerous studies have analyzed guideline development and dissemination, while few have evaluated the consequences of guideline adoption. The primary purpose of this study was to explore and analyze the relationship between physician adoption of the glycated hemoglobin test guideline for management of adult patients with diabetes, and the cost of medical care. The study also examined six personal and organizational characteristics of physicians and their association with innovativeness, or adoption of the guideline. ^ Cost was represented by approved charges from a managed care claims database. Total cost, and diabetes and related complications cost, first were compared for all patients of adopter physicians with those of non-adopter physicians. Then, data were analyzed controlling for disease severity based on insulin dependency, and for high cost cases. There was no statistically significant difference in any of eight cost categories analyzed. This study represented a twelve-month period, and did not reflect cost associated with future complications known to result from inadequate management of glycemia. Guideline compliance did not increase annual cost, which, combined with the future benefit of glycemic control, lends support to the cost effectiveness of the guideline in the long term. Physician adoption of the guideline was recommended to reduce the future personal and economic burden of this chronic disease. ^ Only half of physicians studied had adopted the glycated hemoglobin test guideline for at least 75% of their diabetic patients. No statistically significant relationship was found between any physician characteristic and guideline adoption. Instead, it was likely that the innovation-decision process and guideline dissemination methods were most influential. ^ A multidisciplinary, multi-faceted approach, including interventions for each stage of the innovation-decision process, was proposed to diffuse practice guidelines more effectively. Further, it was recommended that Organized Delivery Systems expand existing administrative databases to include clinical information, decision support systems, and reminder mechanisms, to promote and support physician compliance with this and other evidence-based guidelines. ^

A New Economic Analysis of the American Revolution

We offer an analysis of the American Revolution in which actors are modeled as choosing the sovereign organization that maximizes their net expected benefits. Benefits of secession derive from satisfaction of greed and settlement of grievance. Costs derive from the cost of civil war and lost benefit of Empire membership. When expected net benefits are positive for both secessionists and the Empire civil war ensues, otherwise it is settled or never begins in the first place. The novelty of our discussion is to show how diverse economic and non-economic factors (such as pamphleteering by Thomas Paine and the morale of the Revolutionary forces) can be integrated into a single economic model.

Making A Story Move: The Art of Film Editing

An in-depth treatise on the process of film editing, featuring 16 original interviews from renowned editors. These editors share insight and anecdotes about the daily joys and difficulties of their careers (and the professional principles they subscribe to), as well as the creative, interpersonal, and technical challenges they constantly face. Discussion of the “MTV influence” behind modern film editing is offered, and this influence is explored in filmmaking history. Advice and inspiration is also shared for the benefit of future film editors; Hollywood editors tell their own stories about how they thrived in a notoriously-difficult field, and what it would take for an aspiring editor to do the same.

Molecular mechanisms of response in gastrointestinal stromal tumors treated with imatinib mesylate

Gastrointestinal stromal tumors (GIST) represent 80% of sarcoma arising from the GI tract. The inciting event in tumor progression is mutation of the kit or, rarely, platelet derived growth factor receptor-α (PDGFR) gene. These mutations encode ligand independent, constitutively active proteins: Kit or PDGFR. ^ These tumors are notoriously chemo and radio resistant. Historically, patients with advanced disease realized a median overall survival of 9 months. However, with modern management of GIST with imatinib mesylate (Novartis), a small molecule inhibitor of the Kit, PDGFR, and Abl tyrosine kinases, patients now realize a median overall survival greater than 30 months. However, almost half of patients present with surgically resectable GIST and the utility of imatinib in this context has not been prospectively studied. Also, therapeutic benefit of imatinib is variable from patient to patient and alternative targeted therapy is emerging as potential alternatives to imatinib. Thus, elucidating prognostic factors for patients with GIST in the imatinib-era is crucial to providing optimal care to each particular patient. Moreover, the exact mechanism of action of imatinib in GIST is not fully understood. Therefore, physicians find difficulty in accurately predicting which patient will benefit from imatinib, how to assess response to therapy, and the time at which to assess response. ^ I have hypothesized that imatinib is tolerable and clinically beneficial in the context of surgery, VEGF expression and kit non-exon 11 genotypes portend poor survival on imatinib therapy, and imatinib's mechanism of action is in part due to anti-vascular effects and inhibition of the Kit/SCF signaling axis of tumor-associated endothelial cells. ^ Results herein demonstrate that imatinib is safe and increases the duration of disease-free survival when combined with surgery. Radiographic and molecular (namely, apoptosis) changes occur within 3 days of imatinib initiation. I illustrate that non-exon 11 mutant genotypes and VEGF are poor prognostic factors for patients treated with imatinib. These findings may allow for patient stratification to emerging therapies rather than imatinib. I show that imatinib has anti-vascular effects via inducing tumor endothelial cell apoptosis perhaps by abrogation of the Kit/SCF signaling axis. ^