Developing A Conceptual Framework for Early Intervention Vocational Rehabilitation for People Following Spinal Cord Injury.

PURPOSE: Early intervention vocational rehabilitation (EIVR) can improve return to work (RTW) outcomes for people with spinal cord injury (SCI). However, mechanisms explaining how and why EIVR works are not well understood. This study aims to develop a conceptual framework describing key mechanisms of EIVR intervention effect following SCI. METHODS: We synthesised data from a realist literature review with data from interviews of people with SCI (n = 30), a survey of people with SCI who had received EIVR (n = 37), a focus group of EIVR providers and a focus group of community vocational providers. We first synthesised the literature review and interviews to develop an initial programme theory describing the contexts in which mechanisms are activated to produce EIVR outcomes. Then we used data from the survey and focus groups to further refine the EIVR programme theory. Finally, a conceptual framework was developed to support knowledge dissemination. RESULTS: By ensuring consistent messaging across the multi-disciplinary team, EIVR programmes establish and maintain hope that work is possible following injury. Conversations about work allow individuals to determine the priority of work following injury. These conversations can also improve self-efficacy by providing individualized support to envisage pathways toward RTW goals and maintain worker identity. The synthesised study findings highlight the contexts and resources required to trigger activation of these mechanisms. CONCLUSIONS: EIVR key mechanisms of effect are not specific to SCI as a health condition, therefore enabling this framework to be applied to other populations who face similar impairments and return to work barriers.

Evaluation of the accuracy of common weight estimation formulae in a Zambian paediatric surgical population.

Limited resources and access to healthcare in sub-Saharan Africa are associated with high rates of malnourished children, although many countries globally are demonstrating increasing childhood obesity. This study evaluated how well current age- or height-based formulae estimate the weight of children undergoing surgery in Zambia. All children under 14 years of age presenting for elective surgery at the University Teaching Hospital, Lusaka, had both height and weight measured. Their actual weight was compared against estimated weight from various formulae. The Broselow tape outperformed all the age-based formulae, demonstrating the lowest median percentage error of -5.8%, with 46.0% of estimates falling within 10% of the actual measured weight (p < 0.001). Of the 1111 children who were eligible for World Health Organization growth standard appraisal, 88 (8%) met the weight criteria for severe acute malnutrition. Our results are consistent with other studies in finding that the Broselow tape is the best estimator of weight in a lower middle-income country, followed by the original Advanced Paediatric Life Support formula if the Broselow tape is unavailable.

An evaluation of inpatient morbidity and critical care provision in Zambia.

The aim of this study was to objectively measure demand for critical care services in a southern African tertiary referral centre. We carried out a point prevalence study of medical and surgical admissions over a 48-h period at the University Teaching Hospital, Lusaka, recording the following: age; sex; diagnosis; Human Immunodeficiency Virus (HIV) status and National Early Warning Score. One-hundred and twenty medical and surgical admissions were studied. Fifty-four patients (45%) had objective evidence of a requirement for critical care review and potential or probable admission to an intensive care unit, according to the Royal College of Physicians (UK) guidelines. A greater than expected HIV rate was also noted; 53 of 75 tested patients (71%). When applied to the estimated 17,496 annual acute admissions, this would equate to 7873 patients requiring critical care input annually at this hospital alone. In contrast to this demand, we identified 109 critical care beds nationally, and only eight at this institution.

Osmotic demyelination syndrome following rapid correction of hyponatraemia.

We report a case of a young male with adrenal hypoplasia who presented following water intoxication with severe hyponatraemia and seizures. He required a period of intensive care and over the initial 24 h his serum sodium corrected at average of 0.9 mmol x l(-1) h(-1). He subsequently developed osmotic demyelination syndrome. Following supportive treatment he made a full recovery. Severe hyponatraemia carries a risk of cerebral oedema with a significant mortality, yet correcting it too rapidly can result in osmotic demyelination syndrome, again with potentially disastrous consequences. It may be difficult to determine the duration and aetiology of the hyponatraemia and this is necessary to guide treatment. There is no consensus about the optimal rate of correction of hyponatraemia but formulae such as the Adrogue and Madias formula can be used to guide treatment with normal or hypertonic saline. Continuous veno-venous haemofiltration has been used effectively in this setting.

Ten-year survival and seven-year functional results of cementless Oxford unicompartmental knee replacement: A prospective consecutive series of our first 1000 cases.

BACKGROUND: Cementless fixation is an alternative to cemented unicompartmental knee replacement (UKR), with several advantages over cementation. This study reports the ten-year survival and seven-year clinical outcome of cementless Oxford unicompartmental knee replacement (OUKR). METHODS: This prospective study describes the clinical outcome and survival of the first 1000 consecutive cementless medial OUKRs implanted at two centres for recommended indications. RESULTS: The 10-year survival was 97% (CI 95%: 92-100%), with 25 knees being revised. The commonest reason for revision was progression of arthritis laterally, which occurred in nine knees, followed by primary dislocation of the bearing, which occurred in six knees. There were two dislocations secondary to trauma and a ruptured ACL, and two tibial plateau fractures. Although there were no definite cases of aseptic loosening, two early revisions were related to tibial fixation: one for pain and a radiolucent line and one for incomplete seating of the component with a radiolucent line. There were four revisions for pain, but the cause of the pain was uncertain: in one there was tibial overhang and in two there was patellofemoral degeneration, which possibly contributed to the pain. There were no deep infections. The mean OKS improved from 23 (SD 8) to 42 (SD 7) at a mean follow-up of 7.0 years (p < 0.001). There was no significant difference in survival or clinical outcome between the designer and independent centre. CONCLUSIONS: The cementless OUKR is a safe and reproducible procedure with excellent 10-year survival and clinical results in the hands of both designer and independent surgeons.

The five-year radiological results of the uncemented Oxford medial compartment knee arthroplasty.

This study reports on the first 150 consecutive Oxford cementless unicompartmental knee arthroplasties (UKA) performed in an independent centre (126 patients). All eligible patients had functional scores (Oxford knee score and high activity arthroplasty score) recorded pre-operatively and at two- and five-years of follow-up. Fluoroscopically aligned radiographs were taken at five years and analysed for any evidence of radiolucent lines (RLLs), subsidence or loosening. The mean age of the cohort was 63.6 years (39 to 86) with 81 (53.1%) males. Excellent functional scores were maintained at five years and there were no progressive RLLs demonstrated on radiographs. Two patients underwent revision to a total knee arthroplasty giving a revision rate of 0.23/100 (95% confidence interval 0.03 to 0.84) component years with overall component survivorship of 98.7% at five years. There were a further four patients who underwent further surgery on the same knee, two underwent bearing exchanges for dislocation and two underwent lateral UKAs for disease progression. This was a marked improvement from other UKAs reported in New Zealand Joint Registry data and supports the designing centre's early results.

Selective, efficient modulation of activated CD4+ αßT cells by the novel humanized antibody GZ-αßTCR targeting human αßTCR.

Allograft rejection and immunosuppression are two major issues in transplantation medicine. The specific targeting of alloreactive T cells, the initiators and promoters of allograft rejection, would be a promising strategy to reduce unwanted T-cell responses and side effects of lifelong immunosuppression. The novel humanized monoclonal antibody GZ-αßTCR, specific for the human αßT-cell receptor, was tested in vitro and in vivo for its specificity and efficacy to modulate the αßT-cell compartment. GZ-αßTCR moderately induced apoptosis in resting αßT cells in vitro, an effect considerably amplified in activated T cells. A single dose of GZ-αßTCR significantly reduced human CD45(+)CD3(+) T cells in vivo, with a preferential modulation of CD4(+) αßT cells. Importantly, naive T cells, the T-cell subset from which alloreactivity emanates, were significantly reduced. Simultaneously, a significant, compensatory increase of γδ T cells was observed in vitro and in vivo in both humanized mouse models examined. GZ-αßTCR did not induce cytokines and was well tolerated. Thus, specificity and high efficacy make GZ-αßTCR a powerful tool to selectively eliminate putatively detrimental T-cell subsets, a major goal in transplantation medicine. At the same time, GZ-αßTCR spares γδ and natural killer cells, thus leaving the recipient's immune system competent for cell-mediated immunoregulation and cell-mediated immunity.

c-Cbl negatively regulates platelet activation by glycoprotein VI.

BACKGROUND: The adapter protein c-Cbl has emerged as having a potential role in negative regulation of immune receptor signaling. The major platelet-signaling receptor for collagen, glycoprotein VI (GpVI), is associated with the Fc receptor (FcR) gamma-chain, and signals through a similar pathway to immune receptors. c-Cbl is tyrosine-phosphorylated in response to stimulation of GpVI, whereas phosphorylation of c-Cbl in thrombin-activated platelets is dependent on fibrinogen binding to the integrin GpIIb/IIIa. OBJECTIVE: To investigate the role of c-Cbl in platelet signaling. METHODS: Murine platelets lacking functional c-Cbl or Src family kinases were analyzed. RESULTS: Phosphorylation of c-Cbl through GpVI is reduced in murine platelets deficient in the Src-family kinases Fyn and Lyn, demonstrating that they lie upstream of c-Cbl phosphorylation. Phosphorylation of several proteins of the GpVI-signaling pathway, including the FcR gamma-chain, Syk and phospholipase Cgamma2 (PLCgamma2), is increased in the absence of c-Cbl. In line with this, aggregation is potentiated in response to the GpVI-specific collagen-related peptide (CRP) after a slight delay. A delay in potentiation is also seen in response to stimulation by thrombin. CONCLUSIONS: These observations demonstrate that c-Cbl negatively regulates platelet responses to GpVI agonists and to thrombin, with the latter effect possibly being mediated downstream of GpIIb/IIIa. c-Cbl may play a physiological role in helping to prevent unwanted platelet activation in vivo.

The role of ITAM- and ITIM-coupled receptors in platelet activation by collagen.

The major activation-inducing collagen receptor glycoprotein VI (GPVI) has been cloned within the last two years. It is a member of the Ig superfamily of proteins and is constitutively associated with the ITAM-bearing Fc receptor gamma-chain (FcR gamma-chain). GPVI signals through a pathway that involves several of the proteins used by Fc, B- and T-lymphocyte receptors and which takes place in glycolipid-enriched membrane domains in the plasma membrane known as GEMs. Responses to GPVI are regulated by PECAM-1 (CD31) and possibly other ITIM-bearing receptors. Despite a pivotal role for GPVI, there are important differences between signalling events to collagen and GPVI-specific ligands. This may reflect a role for co-receptors in the response to collagen.

Impairment of avoidance behavior following short-term ingestion of alcohol.

Acquisition and retention of a shock avoidance task were impaired in mice at 5 h and 5 days but not at 14 days after withdrawal from 5 days of chronic alcohol consumption. Mice trained before ingestion of an alcohol-containing diet showed impairment in retention of the shock avoidance procedure 5 h after withdrawal from the diet but not during ingestion or 5 days after withdrawal. At 5 h after withdrawal from the alcohol-containing diet, motor activity and sensitivity to shock were not affected, but there was a decreased motor response to shock. There was no correlation between performance of the avoidance task and the severity of withdrawal signs, as measured by hypothermia or convulsions on handling. The hypothermia and other withdrawal signs were reversed by acute injection of alcohol, but the impairment in avoidance responding was not. These results demonstrate that consumption of an ethanol-containing diet for periods as short as 5 days results in relatively long-lasting alterations in avoidance behavior after withdrawal of the diet. This behavioral impairment appears to be distinct from other signs of alcohol withdrawal.