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

Unstated factors in orthopaedic decision-making: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Total joint replacement (TJR) of the hip or knee for osteoarthritis is among the most common elective surgical procedures. There is some inequity in provision of TJR. How decisions are made about who will have surgery may contribute to disparities in provision. The model of shared decision-making between patients and clinicians is advocated as an ideal by national bodies and guidelines. However, we do not know what happens within orthopaedic practice and whether this reflects the shared model. Our study examined how decisions are made about TJR in orthopaedic consultations.</p> <p>Methods</p> <p>The study used a qualitative research design comprising semi-structured interviews and observations. Participants were recruited from three hospital sites and provided their time free of charge. Seven clinicians involved in decision-making about TJR were approached to take part in the study, and six agreed to do so. Seventy-seven patients due to see these clinicians about TJR were approached to take part and 26 agreed to do so. The patients' outpatient appointments ('consultations') were observed and audio-recorded. Subsequent interviews with patients and clinicians examined decisions that were made at the appointments. Data were analysed using thematic analysis.</p> <p>Results</p> <p>Clinical and lifestyle factors were central components of the decision-making process. In addition, the roles that patients assigned to clinicians were key, as were communication styles. Patients saw clinicians as occupying expert roles and they deferred to clinicians' expertise. There was evidence that patients modified their behaviour within consultations to complement that of clinicians. Clinicians acknowledged the complexity of decision-making and provided descriptions of their own decision-making and communication styles. Patients and clinicians were aware of the use of clinical and lifestyle factors in decision-making and agreed in their description of clinicians' styles. Decisions were usually reached during consultations, but patients and clinicians sometimes said that treatment decisions had been made beforehand. Some patients expressed surprise about the decisions made in their consultations, but this did not necessarily imply dissatisfaction.</p> <p>Conclusions</p> <p>The way in which roles and communication are played out in decision-making for TJR may affect the opportunity for shared decisions. This may contribute to variation in the provision of TJR. Making the importance of these factors explicit and highlighting the existence of patients' 'surprise' about consultation outcomes could empower patients within the decision-making process and enhance communication in orthopaedic consultations.</p

Regulatory T Cells in γ Irradiation-Induced Immune Suppression

Sublethal total body γ irradiation (TBI) of mammals causes generalized immunosuppression, in part by induction of lymphocyte apoptosis. Here, we provide evidence that a part of this immune suppression may be attributable to dysfunction of immune regulation. We investigated the effects of sublethal TBI on T cell memory responses to gain insight into the potential for loss of vaccine immunity following such exposure. We show that in mice primed to an MHC class I alloantigen, the accelerated graft rejection T memory response is specifically lost several weeks following TBI, whereas identically treated naïve mice at the same time point had completely recovered normal rejection kinetics. Depletion in vivo with anti-CD4 or anti-CD25 showed that the mechanism involved cells consistent with a regulatory T cell (T reg) phenotype. The loss of the T memory response following TBI was associated with a relative increase of CD4+CD25+ Foxp3+ expressing T regs, as compared to the CD8+ T effector cells requisite for skin graft rejection. The radiation-induced T memory suppression was shown to be antigen-specific in that a third party ipsilateral graft rejected with normal kinetics. Remarkably, following the eventual rejection of the first MHC class I disparate skin graft, the suppressive environment was maintained, with markedly prolonged survival of a second identical allograft. These findings have potential importance as regards the immunologic status of T memory responses in victims of ionizing radiation exposure and apoptosis-inducing therapies

Clinical course and prognosis of musculoskeletal pain in patients referred for physiotherapy: does pain site matter?

Background: Danish patients with musculoskeletal disorders are commonly referred for primary care physiotherapy treatment but little is known about their general health status, pain diagnoses, clinical course and prognosis. The objectives of this study were to 1) describe the clinical course of patients with musculoskeletal disorders referred to physiotherapy, 2) identify predictors associated with a satisfactory outcome, and 3) determine the influence of the primary pain site diagnosis relative to those predictors. Methods: This was a prospective cohort study of patients (n = 2,706) newly referred because of musculoskeletal pain to 30 physiotherapy practices from January 2012 to May 2012. Data were collected via a web-based questionnaire 1–2 days prior to the first physiotherapy consultation and at 6 weeks, 3 and 6 months, from clinical records (including primary musculoskeletal symptom diagnosis based on the ICPC-2 classification system), and from national registry data. The main outcome was the Patient Acceptable Symptom State. Potential predictors were analysed using backwards step-wise selection during longitudinal Generalised Estimating Equation regression modelling. To assess the influence of pain site on these associations, primary pain site diagnosis was added to the model. Results: Of the patients included, 66% were female and the mean age was 48 (SD 15). The percentage of patients reporting their symptoms as acceptable was 32% at 6 weeks, 43% at 3 months and 52% at 6 months. A higher probability of satisfactory outcome was associated with place of residence, being retired, no compensation claim, less frequent pain, shorter duration of pain, lower levels of disability and fear avoidance, better mental health and being a non-smoker. Primary pain site diagnosis had little influence on these associations, and was not predictive of a satisfactory outcome. Conclusion: Only half of the patients rated their symptoms as acceptable at 6 months. Although satisfactory outcome was difficult to predict at an individual patient level, there were a number of prognostic factors that were associated with this outcome. These factors should be considered when developing generic prediction tools to assess the probability of satisfactory outcome in musculoskeletal physiotherapy patients, because the site of pain did not affect that prognostic association

Dysregulated Expression of Glycolipids in Tumor Cells: From Negative Modulator of Anti-tumor Immunity to Promising Targets for Developing Therapeutic Agents

Glycolipids are complex molecules consisting of a ceramide lipid moiety linked to a glycan chain of variable length and structure. Among these are found the gangliosides, which are sialylated glycolipids ubiquitously distributed on the outer layer of vertebrate plasma membranes. Changes in the expression of certain species of gangliosides have been described to occur during cell proliferation, differentiation and ontogenesis. However, the aberrant and elevated expression of gangliosides has been also observed in different types of cancer cells, thereby promoting tumor survival. Moreover, gangliosides are actively released from the membrane of tumor cells, having a strong impact on impairing anti-tumor immunity. Beyond the undesirable effects of gangliosides in cancer cells, a substantial number of cancer immunotherapies have been developed in recent years that have used gangliosides as the main target. This has resulted in successful immune cell- or antibody-responses against glycolipids, with promising results having been obtained in clinical trials. In this review, we provide a general overview on the metabolism of glycolipids, both in normal and tumor cells, as well as examining glycolipid-mediated immune modulation and the main successes achieved in immunotherapies using gangliosides as molecular targets

Displaced midshaft fractures of the clavicle: non-operative treatment versus plate fixation (Sleutel-TRIAL). A multicentre randomised controlled trial

Contains fulltext : 96826.pdf (publisher's version ) (Open Access)BACKGROUND: The traditional view that the vast majority of midshaft clavicular fractures heal with good functional outcomes following non-operative treatment may be no longer valid for all midshaft clavicular fractures. Recent studies have presented a relatively high incidence of non-union and identified speciic limitations of the shoulder function in subgroups of patients with these injuries. AIM: A prospective, multicentre randomised controlled trial (RCT) will be conducted in 21 hospitals in the Netherlands, comparing fracture consolidation and shoulder function after either non-operative treatment with a sling or a plate fixation. METHODS/DESIGN: A total of 350 patients will be included, between 18 and 60 years of age, with a dislocated midshaft clavicular fracture. The primary outcome is the incidence of non-union, which will be determined with standardised X-rays (Antero-Posterior and 30 degrees caudocephalad view). Secondary outcome will be the functional outcome, measured using the Constant Score. Strength of the shoulder muscles will be measured with a handheld dynamometer (MicroFET2). Furthermore, the health-related Quality of Life score (ShortForm-36) and the Disabilities of Arm, Shoulder and Hand (DASH) Outcome Measure will be monitored as subjective parameters. Data on complications, bone union, cosmetic aspects and use of painkillers will be collected with follow-up questionnaires. The follow-up time will be two years. All patients will be monitored at regular intervals over the subsequent twelve months (two and six weeks, three months and one year). After two years an interview by telephone and a written survey will be performed to evaluate the two-year functional and mechanical outcomes. All data will be analysed on an intention-to-treat basis, using univariate and multivariate analyses. DISCUSSION: This trial will provide level-1 evidence for the comparison of consolidation and functional outcome between two standardised treatment options for dislocated midshaft clavicular fractures. The gathered data may support the development of a clinical guideline for treatment of clavicular fractures. TRIAL REGISTRATION: Netherlands National Trial Register NTR2399

Are Physicians Ready for Patients With Internet-Based Health Information?

Background: An increasing number of patients bring Internet-based health information to medical consultations. However, little is known about how physicians experience, manage, and view these patients. Objective: This study aimed to advance the understanding of the effects of incorporating Internet-based health information into routine medical consultations from physicians’ perspectives, using a qualitative approach. Methods: Six focus groups were conducted with 48 family physicians practising in Toronto. The data were analyzed using qualitative methods of content analysis and constant comparison, derived from grounded theory approach. Results: Three overarching themes were identified: (1) perceived reactions of patients, (2) physician burden, and (3) physician interpretation and contextualization of information. Physicians in our study generally perceived Internet-based health information as problematic when introduced by patients during medical consultations. They believed that Internet information often generated patient misinformation, leading to confusion, distress, or an inclination towards detrimental self-diagnosis and/or self-treatment. Physicians felt these influences added a new interpretive role to their clinical responsibilities. Although most of the physicians felt obliged to carry out this new responsibility, the additional role was often unwelcome. Despite identifying various reactions of patients to Internet-based health information, physicians in our study were unprepared to handle these patients. Conclusion: Effective initiatives at the level of the health care system are needed. The potential of Internet-based health information to lead to better physician-patient communication and patient outcomes could be facilitated by promoting physician acknowledgment of increasing use of the Internet among patients and by developing patient management guidelines and incentives for physicians.Funds for this research were provided by a grant from Merck Frosst Pharmaceutical. The opinions are those of authors. During this work, Dr. Ahmad was funded by fellowship awards from the CIHR Institute of Gender and Health & Ontario Women’s Health Council, and a doctoral award from the Health Care Technology and Place, CIHR Strategic Training Program. All support provided by the Centre for Research on Inner City Health, St. Michael’s Hospital is much appreciated