Showing papers by "Leicester General Hospital published in 2006"

Conducting a critical interpretive synthesis of the literature on access to healthcare by vulnerable groups

Abstract: Conventional systematic review techniques have limitations when the aim of a review is to construct a critical analysis of a complex body of literature This article offers a reflexive account of an attempt to conduct an interpretive review of the literature on access to healthcare by vulnerable groups in the UK This project involved the development and use of the method of Critical Interpretive Synthesis (CIS) This approach is sensitised to the processes of conventional systematic review methodology and draws on recent advances in methods for interpretive synthesis Many analyses of equity of access have rested on measures of utilisation of health services, but these are problematic both methodologically and conceptually A more useful means of understanding access is offered by the synthetic construct of candidacy Candidacy describes how people's eligibility for healthcare is determined between themselves and health services It is a continually negotiated property of individuals, subject to multiple influences arising both from people and their social contexts and from macro-level influences on allocation of resources and configuration of services Health services are continually constituting and seeking to define the appropriate objects of medical attention and intervention, while at the same time people are engaged in constituting and defining what they understand to be the appropriate objects of medical attention and intervention Access represents a dynamic interplay between these simultaneous, iterative and mutually reinforcing processes By attending to how vulnerabilities arise in relation to candidacy, the phenomenon of access can be better understood, and more appropriate recommendations made for policy, practice and future research By innovating with existing methods for interpretive synthesis, it was possible to produce not only new methods for conducting what we have termed critical interpretive synthesis, but also a new theoretical conceptualisation of access to healthcare This theoretical account of access is distinct from models already extant in the literature, and is the result of combining diverse constructs and evidence into a coherent whole Both the method and the model should be evaluated in other contexts

Meta-analysis: colorectal and small bowel cancer risk in patients with Crohn's disease.

Abstract: Summary Background Crohn's disease is associated with small bowel cancer whilst risk of colorectal cancer is less clear Aim To ascertain the combined estimates of relative risk of these cancers in Crohn's disease Methods MEDLINE was searched to identify relevant papers Exploding references identified additional publications When two papers reviewed the same cohort, the later study was used Results Meta-analysis showed overall colorectal cancer relative risk in Crohn's disease as 25 (13–47), 45 (13–149) for patients with colonic disease and 11 (08–15) in ileal disease Meta-regression showed reduction in relative risk over the past 30 years Subgroup analysis showed Scandinavia had significantly lower colorectal cancer relative risk than the UK and North America Cumulative risk analysis showed 10 years following diagnosis of Crohn's disease relative risk of colorectal cancer is 29% (15%–53%) Meta-analysis showed small bowel cancer relative risk in Crohn's disease is 332 (159–609) Small bowel cancer relative risk has not significantly reduced over the last 30 years Conclusion Relative risk of colorectal and small bowel cancers are significantly raised in Crohn's disease Cumulative risk of colorectal cancer of 29% at 10 years suggests a potential benefit from routine screening However, the value of screening requires rigorous appraisal

CESAR: conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure

Abstract: Background: An estimated 350 adults develop severe, but potentially reversible respiratory failure in the UK annually Current management uses intermittent positive pressure ventilation, but barotrauma, volutrauma and oxygen toxicity can prevent lung recovery An alternative treatment, extracorporeal membrane oxygenation, uses cardio-pulmonary bypass technology to temporarily provide gas exchange, allowing ventilator settings to be reduced While extracorporeal membrane oxygenation is proven to result in improved outcome when compared to conventional ventilation in neonates with severe respiratory failure, there is currently no good evidence from randomised controlled trials to compare these managements for important clinical outcomes in adults, although evidence from case series is promising Methods/Design: The aim of the randomised controlled trial of Conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR) is to assess whether, for patients with severe, but potentially reversible, respiratory failure, extracorporeal membrane oxygenation will increase the rate of survival without severe disability ('confined to bed' and 'unable to wash or dress') by six months post-randomisation, and be cost effective from the viewpoints of the NHS and society, compared to conventional ventilatory support Following assent from a relative, adults (18–65 years) with severe, but potentially reversible, respiratory failure (Murray score ≥ 30 or hypercapnea with pH < 72) will be randomised for consideration of extracorporeal membrane oxygenation at Glenfield Hospital, Leicester or continuing conventional care in a centre providing a high standard of conventional treatment The central randomisation service will minimise by type of conventional treatment centre, age, duration of high pressure ventilation, hypoxia/hypercapnea, diagnosis and number of organs failed, to ensure balance in key prognostic variables Extracorporeal membrane oxygenation will not be available for patients meeting entry criteria outside the trial 180 patients will be recruited to have 80% power to be able to detect a one third reduction in the primary outcome from 65% at 5% level of statistical significance (2-sided test) Secondary outcomes include patient morbidity and health status at 6 months Discussion: Analysis will be based on intention to treat A concurrent economic evaluation will also be performed to compare the costs and outcomes of both treatments

Diagnosis and management of colovesical fistulae; six-year experience of 90 consecutive cases.

Abstract: Introduction Colovesical fistulae are well-recognized but relatively uncommon presentation to colorectal surgery. As a result, few centres have sufficient experience in the investigation and surgical treatment of colovesical fistulae to develop clear protocols in its management. Methods This study examines the diagnostic and treatment pathways of 90 consecutive patients with colovesical fistulae presenting to a single surgeon, over a six-year period. Using the findings from this study and previously published data, the authors suggest tentative guidelines for the diagnosis and management of such patients. Results Pneumaturia and faecaluria were present in 90.1% of all cases. The diagnosis of colovesical fistula is predominately a clinical one, however, cystoscopy was the most accurate test to detect fistulae (46.2%) followed by barium enema (20.1%). Barium enema was the most sensitive test to detect stricture formation (70.6%). Colonic endoscopy was the most reliable means of excluding a colonic malignancy. The most common pathology was diverticular disease (72.2%), colonic carcinoma (15.3%) and Crohn's disease (9.7%). Left sided colonic resections were undertaken in 73.6% of patients, right hemicolectomy in 4.2% and defunctioning loop colostomies in 18.5%. Of the left sided resections, primary anastomosis was achieved in 92% of cases (n = 48) with one postoperative leak and no mortality. Discussion Resection and primary anastomosis should be the treatment of choice for colovesical fistulae, with an acceptable risk of anastomotic leak and mortality. Barium enema, colonic endoscopy and CT should be routine in the investigation of colovesical fistulae.

Physical health and schizophrenia.

Abstract: PURPOSE OF REVIEW Patients with schizophrenia have higher than expected rates of morbidity and mortality. It is debatable whether this is related to shared risk factors, antipsychotic medication or inherent to the condition itself. This review will describe this association and the recent advances in the field. RECENT FINDINGS The majority of patients with schizophrenia have at least one chronic comorbid medical condition. In the absence of systematic screening this may or may not be brought to the attention of health professionals. The cause of high rates of physical illness appears to be multifactorial involving shared vulnerability and genetic factors. Yet it is vascular risk factors and the adverse effects of prescribed medication that are most amenable to intervention. Current atypical antipsychotics may offer neurological and cognitive benefits, but there is accumulating evidence of problems with weight gain, diabetes, lipid dysregulation, metabolic syndrome and sexual side effects. SUMMARY The physical health of patients with schizophrenia remains a concern. Yet the quality of medical and psychiatric care of patients with comorbid physical and mental health disorders has been shown to be unsatisfactory in several areas. We suggest that clinicians routinely assess and monitor physical health needs of patients with serious mental illness.

Meta-analysis: colorectal and small bowel cancer risk in patients with Crohn's disease.

Abstract: Summary Background Crohn's disease is associated with small bowel cancer whilst risk of colorectal cancer is less clear Aim To ascertain the combined estimates of relative risk of these cancers in Crohn's disease Methods MEDLINE was searched to identify relevant papers Exploding references identified additional publications When two papers reviewed the same cohort, the later study was used Results Meta-analysis showed overall colorectal cancer relative risk in Crohn's disease as 25 (13–47), 45 (13–149) for patients with colonic disease and 11 (08–15) in ileal disease Meta-regression showed reduction in relative risk over the past 30 years Subgroup analysis showed Scandinavia had significantly lower colorectal cancer relative risk than the UK and North America Cumulative risk analysis showed 10 years following diagnosis of Crohn's disease relative risk of colorectal cancer is 29% (15%–53%) Meta-analysis showed small bowel cancer relative risk in Crohn's disease is 332 (159–609) Small bowel cancer relative risk has not significantly reduced over the last 30 years Conclusion Relative risk of colorectal and small bowel cancers are significantly raised in Crohn's disease Cumulative risk of colorectal cancer of 29% at 10 years suggests a potential benefit from routine screening However, the value of screening requires rigorous appraisal

O-Glycosylation of Serum IgA1 Antibodies against Mucosal and Systemic Antigens in IgA Nephropathy

Abstract: In IgA nephropathy (IgAN), serum IgA1 with abnormal O-glycosylation deposits in the glomerular mesangium The underlying mechanism of this IgA1 O-glycosylation abnormality is poorly understood, but recent evidence argues against a generic defect in B cell glycosyltransferases, suggesting that only a subpopulation of IgA1-committed B cells are affected For investigation of whether the site of antigen encounter influences IgA1 O-glycosylation, the O-glycosylation of serum IgA1 antibodies against a systemic antigen, tetanus toxoid (TT), and a mucosal antigen, Helicobacter pylori (HP), was studied in patients with IgAN and control subjects Serum IgA1 was purified from cohorts of patients with IgAN and control subjects with HP infection and after systemic TT immunization The IgA1 samples were applied to HP- and TT-coated immunoplates to immobilize specific antibodies, and IgA1 O-glycosylation profiles were assessed by binding of the O-glycan–specific lectin Vicia villosa using a modified ELISA technique Although total serum IgA1 had raised lectin binding in IgAN, the O-glycosylation of the specific IgA1 antibodies to TT and HP did not differ between patients and control subjects In both groups, IgA1 anti-HP had higher lectin binding than IgA1 anti-TT This study demonstrates that IgA1 O-glycosylation normally varies in different immune responses and that patients produce the full spectrum of IgA1 O-glycoforms IgA1 with high lectin binding was produced in response to mucosal HP infection in all subjects The raised circulating level of this type of IgA1 in IgAN is likely to be a consequence of abnormal systemic responses to mucosally encountered antigens rather than a fundamental defect in B cell O-glycosylation pathways

O-Glycosylation of Serum IgD in IgA Nephropathy

Abstract: In IgA nephropathy (IgAN), serum IgA1 with abnormal O-glycosylation preferentially deposits in the glomerular mesangium. The control of O-glycosylation is poorly understood. Among Ig isotypes, only IgD, produced early in B cell development, and IgA1, produced by mature B cells, are O-glycosylated. For investigation of the stage of B cell maturation at which the defect seen in IgAN arises, the O-glycosylation of serum IgA1 and IgD was studied in IgAN and controls. Serum was obtained from 20 patients with IgAN and 20 control subjects. The O-glycosylation profiles of native and desialylated IgA1 and IgD were measured in an ELISA-type system using the lectins Helix aspersa and peanut agglutinin, which bind to alternative forms of O-glycan moieties. The lectin-binding patterns of the two immunoglobulins differed in all participants, with that of IgD suggesting that it is more heavily galactosylated than IgA1. Defective O-glycosylation of IgA1, probably taking the form of reduced galactosylation, was confirmed in IgAN in this study. This undergalactosylation was not shared by IgD; in contrast, IgD carried more galactosylated O-glycans in IgAN than controls. The contrasting lectin-binding patterns of IgA1 and IgD shows that Ig O-glycosylation is differentially controlled during B cell maturation. Compared with controls, O-glycosylation in IgAN is incomplete in IgA1 but more complete in IgD. These observations show that abnormal IgA1 O-glycosylation in IgAN is not due to an inherent defect in glycosylation mechanisms but arises only at a later stage in B cell development and may be secondary to aberrant immunoregulation.

Long-term prognosis in Crohn's disease: factors that affect quality of life.

Abstract: Summary Background There are many studies investigating quality of life in recently diagnosed patients and following surgery for Crohn's disease, but there are none investigating quality of life changes with disease duration. The response shift model suggests quality of life improves with time following diagnosis. Aim To assess how well the model applies to patients with Crohn's disease. Methods The Cardiff Crohn's disease database contains data on all patients diagnosed there since 1934. Three hundred and ninety four patients diagnosed before 1 January 1985 were traced and the mortality status on 31 December 2004 established. Two hundred and eleven still living were sent quality of life questionnaires. Two hundred and eighty five questionnaires were sent to patients with varying disease duration attending out-patient clinics in Leicester. Results Eighty-nine valid replies were received from Cardiff, 63 from Leicester patients diagnosed over 20 years, 69 from Leicester patients diagnosed <10 years. There was no difference in quality of life between newly diagnosed and established patients. Of greatest concern was possible need for ostomy, uncertain nature of disease, and lack of energy. Stepwise regression showed that increased disease severity, older age and smoking adversely affect quality of life. Discussion Quality of life is equally poor in patients with established disease as in those newly diagnosed, and directly correlates with disease severity. The response shift model may not be applicable in Crohn's disease.

Essential tremor-the most common movement disorder in older people.

Abstract: Essential tremor (ET) affects approximately 4% of the population above 65 years of age. The traditional view that ET is a familial monosymptomatic disorder with a benign prognosis has recently been challenged, as it is now known to be a progressive and clinically heterogeneous condition with sporadic and familial forms. The pathogenesis of ET is not fully understood, though a disordered central mechanism is the most likely site of origin with possible modulation by muscle adrenoreceptors. The limited post-mortem studies have not shown consistent abnormalities in the brains of ET patients. ET is often misdiagnosed as Parkinson's disease, particularly in the older population. Tremor amplitude increases with age, accounting for substantial disability in older people. Current therapy (drugs and neurosurgery) has significant limitations in older people. A better understanding of its pathophysiology in the future will help in developing more effective therapy, including neuroprotective strategies.

Leucocyte depletion improves renal function during reperfusion using an experimental isolated haemoperfused organ preservation system.

Abstract: Background: Leucocytes have been implicated as mediators of renal ischaemia–reperfusion injury. This study aimed to demonstrate the effect of white cells in early renal reperfusion injury using an isolated haemoperfused porcine kidney model. Methods: After 2 h cold storage, porcine kidneys were perfused with normothermic autologous blood using an isolated organ preservation system. This was designed using cardiopulmonary bypass technology, and perfusion commenced with a circulating serum creatinine level of 1000 µmol/l. In group 1 (n = 6) a leucocyte filter was included in the circuit and in group 2 (n = 6) non-filtered blood was used. Results: The mean(s.d.) area under the curve for serum creatinine was lower in the leucocyte-depleted experiments (1286(214) versus 2627(418); P = 0·002). Leucocyte depletion also led to improved urine output (191(75) versus 70(32) ml/h; P = 0·002) and higher creatinine clearance (10·6(2·8) versus 1·9(1·0) ml/min; P = 0·002). Renal blood flow, oxygen consumption and acid–base homeostasis were all improved by perfusion with leucocyte-depleted blood, and histological tubular damage was ameliorated. Conclusion: These data show that the depletion of leucocytes from blood used to perfuse porcine kidneys improved postschaemic renal function, indicating that white cells play an important role in renal ischaemia–reperfusion injury. Copyright © 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Apoptosis and caspase-3 in long-term renal ischemia/reperfusion injury in rats and divergent effects of immunosuppressants.

Abstract: Background Caspase-3 plays a key role in apoptosis, but the involvement of apoptosis and caspase-3 in mediating long-term ischemia/reperfusion (I/R) and immunosuppressive injury are not fully defined. The present study was undertaken to investigate apoptosis and caspase-3 in a renal I/R injury rat model with or without immunosuppression. Methods The right renal pedicle was clamped for 45 minutes and left nephrectomy was induced. Cyclosporin A (CsA), tacrolimus (Tac), rapamycin (Rap), or mycophenolate mofetil (MMF) were administered daily. Animals were killed at 16 weeks, and the levels of apoptosis (with in situ end-labeling fragmented DNA), caspase-3 protein (with immunohistochemistry, Western blotting, and activity assay), and messenger RNA (mRNA; with quantitative reverse-transcriptase polymerase chain reaction) were evaluated. Results Kidneys with I/R injury showed increased apoptosis in tubular and interstitial areas compared with control kidneys. Tacrolimus, Rap, and MMF significantly reduced apoptosis, but CsA did not. Distribution of full-length caspase-3 widened in I/R-injured kidneys from normal distal tubules and collecting ducts to dilated proximal tubules and expanded interstitium, whereas active caspase-3 was mainly scattered in damaged tubules and interstitium. Active caspase-3 staining and 24-kDa active caspase-3 protein was enhanced in I/R-injured and CsA-treated kidneys, but decreased by Tac, Rap, and MMF. These results were also consistent with changes in caspase-3 activity. Although caspase-3 mRNA levels were significantly increased in uninephrectomy and I/R-injured kidneys, they were not significantly affected by the immunosuppressants. In addition, all changes detected were positively correlated with renal structure and function. Conclusion Apoptosis and caspase-3 are not only involved in the long-term renal I/R injury, but also mediate the divergent effects of immunosuppression in this model.

C-peptide signals via Galpha i to protect against TNF-alpha-mediated apoptosis of opossum kidney proximal tubular cells.

Abstract: Cell loss by apoptosis occurs in renal injury such as diabetic nephropathy. TNF-alpha is a cytokine that induces apoptosis and has been implicated in the pathogenesis of diabetic nephropathy. The aim was to investigate whether C-peptide or insulin could modulate TNF-alpha-mediated cell death in opossum kidney proximal tubular cells and to examine the mechanism(s) of any effects observed. C-peptide and insulin protect against TNF-alpha-induced proximal tubular cell toxicity and apoptosis. Cell viability was analyzed by methylthiazoletetrazolium assay; cell viability was reduced to 60.8 +/- 2.7% of control after stimulation with 300 ng/ml TNF-alpha. Compromised cell viability was reversed by pretreatment with 5 nM C-peptide or 100 nM insulin. TNF-alpha-induced apoptosis was detected by DNA nick-end labeling and by measuring histone associated DNA fragments using ELISA. By ELISA assay, 300 ng/ml TNF-alpha increased apoptosis by 145.8 +/- 4.9% compared with controls, whereas 5 nM C-peptide and 100 nM insulin reduced apoptosis to 81.6 +/- 4.8 and 77.4 +/- 3.1% of control, respectively. The protective effects of C-peptide and insulin were associated with activation of NF-kappaB. Activation of NF-kappaB by C-peptide was pertussis toxin sensitive and dependent on activation of Galpha(i). Phosphatidylinositol 3-kinase but not extracellular signal regulated mitogen-activated protein kinase mediated C-peptide and insulin activation of NF-kappaB. The cytoprotective effects of both C-peptide and insulin were related to increased expression of TNF receptor-associated factor 2, the product of an NF-kappaB-dependent survival gene. These data suggest that C-peptide and/or insulin activation of NF-kappaB-regulated survival genes protects against TNF-alpha-induced renal tubular injury in diabetes. The data further support the concept of C-peptide as a peptide hormone in its own right and suggest a potential therapeutic role for C-peptide.

The costs of epilepsy misdiagnosis in England and Wales.

Abstract: Summary Background The management of epilepsy incurs significant costs to the United Kingdom (UK) National Health Service (NHS). Making a diagnosis of epilepsy can, however, be difficult and misdiagnosis frequently occurs when patients are seen by non-specialists. This study estimates the financial costs of epilepsy misdiagnosis in the NHS in England and Wales. Methods Standard costing methods were applied to estimate the costs attributable to epilepsy misdiagnosis. The primary data were published in UK studies on the prevalence of epilepsy, epilepsy misdiagnosis and costs identified from Medline, Cinahl and Embase (1996–May 2006). Results An estimated total of 92,000 people were misdiagnosed with epilepsy in England and Wales in 2002. The average medical cost per patient per year of misdiagnosis was £316, with the chief economic burdens being inpatient admissions (45%), inappropriate prescribing of antiepileptic drugs (AEDs) (26%), outpatient attendances (16%) and general practitioner (GP) care (8%). The estimated annual medical costs in England and Wales were £29,000,000, while total costs could reach up to £138,000,000 a year. Conclusions Allowing for uncertainty, and considering the analysis exclusively from the NHS/CBS (community based services) perspective the opportunity costs of misdiagnosis are substantial. There is a need for health care commissioners to ensure that misdiagnosis is kept to a minimum by ensuring that individuals with a recent onset suspected seizure are seen as soon as possible by a specialist medical practitioner with training and expertise in epilepsy.

Dose of intravenous immunoglobulins in chronic inflammatory demyelinating polyneuropathy

Abstract: The usual initiating dose of intravenous immunoglobulins (IVIg) in the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) is 2 g/kg/course. Although not evidence based, subsequent reductions are advised to the lowest possible level for maintenance. In practice, the achievable levels of such reductions and their impact on treatment frequency have not been studied. Factors determining maximal dosage reduction are unknown. We retrospectively reviewed data concerning IVIg therapy for 15 patients with CIDP, from their medical records between 1997 and 2005. Lowest effective dose and treatment frequency were determined. The following correlations were ascertained: dose to frequency, dose to weight, dose to disease duration, amplitude of dose reduction to disease duration, and dose to pre-therapeutic disease severity. Dose reductions were possible in all (mean: 63.3%, range: 42.4-88%). The lowest effective dose of IVIg per course and treatment frequency were both very variable (18-108 g and 2-17 weeks, respectively). Lowest dose per course did not correlate to weight, frequency of administration, disease duration, or pre-therapeutic degree of disability. Amplitude of dose reduction achieved was independent of disease duration. Treatment frequency could not be lowered in any patient. Our findings show that IVIg target doses should be titrated individually but suggest that infusion frequencies are fixed in each case in relapsing CIDP. Importantly, lower dose treatment is not associated with shorter intervals between courses, and lowest effective dose is independent of weight and disease duration. Initial level of disability does not appear to influence dose required. These results suggest considerably lower, standardized, initiating, and maintenance doses might be effective and highlight the need for prospective dose comparative trials.

Effects of arterial pressure in an experimental isolated haemoperfused porcine kidney preservation system

Abstract: Background: Normothermic preservation provides metabolic support to an ischaemically damaged organ before use as a kidney transplant. Optimal conditions for ex vivo preservation have not yet been established. This study examined the effects of arterial pressure on renal preservation using isolated haemoperfused kidneys. Methods: An isolated organ preservation system, developed using cardiopulmonary bypass technology, was used to perfuse porcine kidneys with normothermic oxygenated blood. Groups of kidneys (n = 6) were perfused at a mean arterial pressure of 95, 75 or 55 mmHg. Results: Kidneys perfused at the higher mean arterial pressures of 95 and 75 mmHg demonstrated improved renal function: mean(s.d.) area under the curve (AUC) for creatinine clearance 71(19) and 55(30) respectively versus 14(12) in the 55-mmHg group, P = 0·002; AUC for serum creatinine 938(140) and 1290(394) versus 2404(595), P = 0·003. The higher perfusion pressures were also associated with better acid–base homeostasis and improved renal haemodynamics. Conclusion: Mean arterial pressures of either 95 or 75 mmHg were capable of sustaining physiological renal function, but kidneys in the 95-mmHg group demonstrated superior renal function overall. Copyright © 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Sporadic cerebral amyloid angiopathy--an important cause of cerebral haemorrhage in older people

Abstract: Cerebral amyloid angiopathy (CAA) is an important cause of primary intracerebral haemorrhage (PICH) in older people, accounting for approximately 10% of all types of PICH. The amount of amyloid deposition in the vessels and vasculopathic changes determine the propensity to PICH. The risk factors of CAA include advanced age and the presence of certain alleles of apolipoprotein E. There are no specific clinical features of CAA-related PICH, although lobar, recurrent or multiple simultaneous haemorrhages in older patients should raise suspicion of its diagnosis. A definitive diagnosis of CAA requires pathological examination of the affected tissue. However, with modern imaging techniques, it is possible to make a diagnosis of 'probable CAA' in patients presenting with PICH. Gradient-echo magnetic resonance imaging is a sensitive, non-invasive technique for identifying small haemorrhages in life. Currently, there is no specific treatment available for CAA. Recent advances in the immunopathology and pathogenesis of CAA are expected to help in developing specific anti-amyloid therapy.

Worry content across the lifespan: an analysis of 16- to 74-year-old participants in the British National Survey of Psychiatric Morbidity 2000.

Abstract: Background. Previous studies suggest that worry content and prevalence may vary as a function of age, but evidence is limited. Method. Cross-sectional national survey of 8580 householders in Great Britain aged between 16 and 74 years. This analysis examined the relationship between age, worry content (relationships/ family, financial/housing, work, health, miscellaneous), common mental disorders, and functional limitation, adjusting for other sociodemographic factors. Results. Overall, the prevalence of worries declined with age. However, with the exception of worry about relationships, the strength of associations between worry types and mental disorder either remained constant or increased in the older age groups. Compared to the 16-24 years reference group, worries about relationships/family, finances/housing and work were lower in the 55-74 years age groups. Financial/housing worries were increased in the 25-44 years group, and health worries were increased in the 25-64 years groups. There were independent associations between all worry items and the categories of mental disorder. All worry types apart from miscellaneous worries were independently associated, positively or negatively, with functional limitation. Conclusions. Worry content in the general population varies as a function of age, gender, marital status, and educational attainment. All categories of worry are more prevalent in individuals with common mental disorders. The lower prevalence of worries and their stronger association with mental disorder in old age emphasize the clinical significance of these symptoms in this age group.

Hypoxia and angiogenesis in pancreatic cancer

Abstract: Background: Pancreatic cancer remains one of the most lethal of all solid tumours of the gastrointestinal tract. It is characterized by late diagnosis, aggressive local invasion, early metastasis and resistance to chemoradiotherapy. Increasing knowledge regarding the molecular events behind the growth and invasion of pancreatic cancer may lead to new targets for intervention. Methods: A search of Pubmed and Medline databases was undertaken using the keywords pancreatic cancer, gastrointestinal cancer, hypoxia, angiogenesis and anti-angiogenesis therapy. Results: Hypoxia is the driving force behind angiogenesis in pancreatic cancers. Research into angiogenesis has shown many different sites that can be targeted by agents such as tyrosine kinase inhibitors. Conclusion: Anti-angiogenic therapy could be an important adjunct to conventional chemotherapy treatment of gastrointestinal neoplasia. Abbreviations: CA, carbonic anhydrase; 5-FU, 5-fluorouracil; HO, haem oxygenase; MAPK, mitogen-activated protein kinase; HIF-1, hypoxia-inducible factor-1; IGF, insulin-like growth factor; IL-6, interleukin-6; MVD, microvessel density; mRNA, messenger RNA; NRP-1, neuropilin-1; PD-ECGF, platelet-derived endothelial cell growth factor; PGF, placenta growth factor; TSP, thrombospondin; VEGFR, vascular endothelial growth factor receptor.

Randomised controlled trial of near-patient testing for glycated haemoglobin in people with type 2 diabetes mellitus.

Abstract: Background Tight glycaemic control in people with type 2 diabetes can lead to a reduction in microvascular and possibly macrovascular complications. The use of near-patient (rapid) testing offers a potential method to improve glycaemic control. Aim To assess the effect and costs of rapid testing for glycated haemoglobin (HbA1c) in people with type 2 diabetes. Design of study Pragmatic open randomised controlled trial. Setting Eight practices in Leicestershire, UK. Method Patients were randomised to receive instant results for HbA1c or to routine care. The principal outcome measure was the proportion of patients with an HbA1c Results Of the 681 patients recruited to the study 638 (94%) were included in the analysis. The mean age at baseline was 65.7 years (SD = 10.8 years) with a median (interquartile range) duration of diabetes of 4 (1–8) years. The proportion of patients with HbA1c Conclusion Near-patient testing for HbA1c alone does not lead to outcome or cost benefits in managing people with type 2 diabetes in primary care. Further research is required into the use of rapid testing as part of an optimised patient management model including arrangements for patient review and testing.

Self harm and attempted suicide in adults: 10 practical questions and answers for emergency department staff

Abstract: Self harm is a complex behaviour that can be best thought of as a maladaptive response to acute and chronic stress, often but not exclusively linked with thoughts of dying. Patients presenting with self harm usually have current psychosocial difficulties, are likely to be suffering from mental health problems, and are at significant risk of further self harm and suicide. Recent guidelines suggest that all self harm attendees should receive an initial risk assessment at triage in the emergency department. A more detailed mental health assessment and an assessment of psychological and social needs should then be performed by trained staff, ideally specialist mental professionals experienced in this area. Risk of subsequent suicide is particularly high in those with high unresolved suicidal intent, depressive disorder, chronic alcohol and drug misuse, social isolation, and current physical illness. Patients with one or more of these risk factors should be offered enhanced care that may include inpatient or outpatient follow up care, a list of local support resources, and, where possible, self help material. Frequent repeaters, those with alcohol and substance use problems, those with physical or mental illness, and those who are isolated also require input from specialist mental health professionals. It is also recommended that adolescents and elderly people warrant a mandatory specialist assessment.

Clinical and radiological outcome following total hip arthroplasty with an uncemented trabecular metal monoblock acetabular cup

Abstract: Uncemented acetabular components are associated with a significant incidence of polyethylene wear and secondary osteolysis. The new tantalum/polyethylene composite (Hedrocel) acetabular component is designed to reduce the polyethylene wear and to increase the longevity of the acetabular cups. We report our short- term clinical outcome and patient satisfaction following use of an uncemented tantalum acetabular component in a single centre. During 1999 to 2002, 113 uncemented tantalum acetabular cups were implanted in 105 patients in our institution. The average age at operation was 56.8 years. All patients were assessed pre- and post-operatively with the Oxford 12 item hip questionnaire and standard radiographs of the pelvis. At a mean follow-up of 32 months (range: 18 to 48), 112 Hedrocel cups were assessed in 104 patients. Subjective patient's satisfaction was also assessed. At the time of evaluation, one patient had died due to an unrelated cause. Eight patients had bilateral acetabular cups implanted. The mean Oxford hip score improved from 45 preoperatively to 14 post-operatively. Subjectively 99% were very satisfied or satisfied. Only one patient expressed dissatisfaction about the outcome of this surgery. Radiologically, there were no signs of cup loosening or wear. This study shows that at short-term the new uncemented tantalum/polyethylene composite (Hedrocel) acetabular component can yield a satisfactory clinical and radiological outcome and has a high patient satisfaction. Although the short-term result from our centre is very encouraging, similar results from other centres and longer follow-up are required.

Nurse-led management of carpal tunnel syndrome: an audit of outcomes and impact on waiting times.

Abstract: We became aware of a significant number of patients in the system with a presumptive diagnosis of carpal tunnel syndrome. Whilst being high in numbers, these patients were historically considered a low priority leading to a considerable wait from referral to operation and subsequent discharge. An analysis of our waiting times suggested that this was as much as 100 weeks. We, therefore, decided to address what appeared to be a significant problem through the development of a rapidaccess carpal tunnel service. Many of these problems had been identified by one of our senior nurses who was an experienced and highly motivated individual. We believed that he could be trained in the management of these patients and consequently the concept was developed as a nurse-led service. Whilst the extended role of nurses is recognised and accepted in the out-patient setting, there remains great resistance to developing their role as surgical operators although there is also support. 1 This article looks at the service we have developed, we have deliberately focusing on the role of the nurse-operator.