Conservative management versus open reduction and internal fixation for mid-shaft clavicle fractures in adults - The Clavicle Trial: Study protocol for a multicentre randomized controlled trial

Background: Clavicle fractures account for around 4% of all fractures and up to 44% of fractures of the shoulder girdle. Fractures of the middle third (or mid-shaft) account for approximately 80% of all clavicle fractures. Management of this group of fractures is often challenging and the outcome can be unsatisfactory. In particular it is not clear whether surgery produces better outcomes than non-surgical management. Currently there is much variation in the use of surgery and a lack of good quality evidence to inform our decision.Methods/Design: We aim to undertake a multicentre randomised controlled trial evaluating the effectiveness and safety of conservative management versus open reduction and internal fixation for displaced mid-shaft clavicle fractures in adults. Surgical treatment will be performed using the Acumed clavicle fixation system. Conservative management will consist of immobilisation in a sling at the side in internal rotation for 6 weeks or until clinical or radiological union. We aim to recruit 300 patients. These patients will be followed-up for at least 9 months. The primary endpoint will be the rate of non-union at 3 months following treatment. Secondary endpoints will be limb function measured using the Constant-Murley Score and the Disabilities of the Arm, Shoulder and Hand (DASH) Score at 3 and 9 months post-operatively.Discussion: This article presents the protocol for a multicentre randomised controlled trial. It gives extensive details of, and the basis for, the chosen methods, and describes the key measures taken to avoid bias and to ensure validity.Trial Registration: United Kingdom Clinical Research Network ID: 8665. The date of registration of the trial is 07/09/2006. The date the first patient was recruited is 18/12/2007. © 2011 Longo et al; licensee BioMed Central Ltd

CD36 and Fyn kinase mediate malaria-induced lung endothelial barrier dysfunction in mice infected with Plasmodium berghei.

PMC3744507Severe malaria can trigger acute lung injury characterized by pulmonary edema resulting from increased endothelial permeability. However, the mechanism through which lung fluid conductance is altered during malaria remains unclear. To define the role that the scavenger receptor CD36 may play in mediating this response, C57BL/6J (WT) and CD36-/- mice were infected with P. berghei ANKA and monitored for changes in pulmonary endothelial barrier function employing an isolated perfused lung system. WT lungs demonstrated a >10-fold increase in two measures of paracellular fluid conductance and a decrease in the albumin reflection coefficient (σalb) compared to control lungs indicating a loss of barrier function. In contrast, malaria-infected CD36-/- mice had near normal fluid conductance but a similar reduction in σalb. In WT mice, lung sequestered iRBCs demonstrated production of reactive oxygen species (ROS). To determine whether knockout of CD36 could protect against ROS-induced endothelial barrier dysfunction, mouse lung microvascular endothelial monolayers (MLMVEC) from WT and CD36-/- mice were exposed to H2O2. Unlike WT monolayers, which showed dose-dependent decreases in transendothelial electrical resistance (TER) from H2O2 indicating loss of barrier function, CD36-/- MLMVEC demonstrated dose-dependent increases in TER. The differences between responses in WT and CD36-/- endothelial cells correlated with important differences in the intracellular compartmentalization of the CD36-associated Fyn kinase. Malaria infection increased total lung Fyn levels in CD36-/- lungs compared to WT, but this increase was due to elevated production of the inactive form of Fyn further suggesting a dysregulation of Fyn-mediated signaling. The importance of Fyn in CD36-dependent endothelial signaling was confirmed using in vitro Fyn knockdown as well as Fyn-/- mice, which were also protected from H2O2- and malaria-induced lung endothelial leak, respectively. Our results demonstrate that CD36 and Fyn kinase are critical mediators of the increased lung endothelial fluid conductance caused by malaria infection.JH Libraries Open Access Fun

Cost-effectiveness of a cardiac output-guided haemodynamic therapy algorithm in high-risk patients undergoing major gastrointestinal surgery.

BACKGROUND: The use of cardiac output monitoring to guide intra-venous fluid and inotropic therapies may improve peri-operative outcomes, but uncertainty exists regarding clinical effectiveness and robust cost-effectiveness evidence is lacking. The objective of the study was to evaluate the cost-effectiveness of peri-operative cardiac output-guided haemodynamic therapy versus usual care in high-risk patients undergoing major gastrointestinal surgery. METHODS: The study undertook a cost-effectiveness analysis using data from a multi-centre randomised trial that recruited patients from 17 hospitals in the United Kingdom. The trial compared cardiac output-guided, haemodynamic therapy algorithm for intra-venous fluid and inotrope (dopexamine) infusion during and 6 h following surgery, with usual care. Resource use and outcome data on 734 high-risk trial patients aged over 50 years undergoing major gastrointestinal surgery were used to report cost-effectiveness at 6 months and to project lifetime cost-effectiveness. The cost-effectiveness analysis used information on health-related quality of life (QoL) at randomisation, 30 days, and 6 months combined with information on vital status to report quality-adjusted life years (QALYs). Each QALY was valued using the National Institute for Health and Care Excellence (NICE) recommended threshold of willingness to pay (£20,000 per QALY) in conjunction with the costs of each group to report the incremental net monetary benefits (INB) of the treatment algorithm versus usual care. RESULTS: The mean [SD] quality of life at 30 days and 6 months was similar between the treatment groups (at 6 months, intervention group 0.73 [0.28] versus usual care group 0.71 [0.30]; mean gain 0.03 [95 % confidence interval (CI) -0.01 to 0.08]). At 6 months, survival, mean QALYs and mean healthcare costs (intervention group £8574 versus usual care group £8974) were also similar. At the cost-effectiveness threshold of £20,000 per QALY gained, the incremental net benefit of haemodynamic therapy over the patients' lifetime was positive (£4168 [95 % CI -£3063 to £11,398]). This corresponds to an 87 % probability that this intervention is cost-effective. CONCLUSIONS: Cardiac output-guided haemodynamic therapy algorithm was associated with an average cost reduction and improvement in QALY and is likely to be cost-effective. Further research is needed to confirm the clinical and cost-effectiveness of this treatment. TRIAL REGISTRATION: ISRCTN04386758