Showing papers by "St Thomas' Hospital published in 2007"

The standardization of terminology of lower urinary tract function in children and adolescents: Update report from the standardization committee of the International Children's Continence Society

Abstract: Purpose: We updated the terminology in the field of pediatric lower urinary tract function. Materials and Methods: Discussions were held in the board of the International Children's Continence Society and an extensive reviewing process was done involving all members of the International Children's Continence Society, the urology section of the American Academy of Pediatrics, the European Society of Pediatric Urology, as well as other experts in the field. Results and Conclusions: New definitions and a standardized terminology are provided, taking into account changes in the adult sphere and new research results.

The metric properties of a novel non-motor symptoms scale for Parkinson's disease: Results from an international pilot study.

Abstract: Non-motor symptoms (NMS) in Parkinson's disease (PD) are common, significantly reduce quality of life and at present there is no validated clinical tool to assess the progress or potential response to treatment of NMS. A new 30-item scale for the assessment of NMS in PD (NMSS) was developed. NMSS contains nine dimensions: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems, attention/memory, gastrointestinal, urinary, sexual function, and miscellany. The metric attributes of this instrument were analyzed. Data from 242 patients mean age 67.2 +/- 11 years, duration of disease 6.4 +/- 6 years, and 57.3% male across all stages of PD were collected from the centers in Europe, USA, and Japan. The mean NMSS score was 56.5 +/- 40.7, (range: 0-243) and only one declared no NMS. The scale provided 99.2% complete data for the analysis with the total score being free of floor and ceiling effect. Satisfactory scaling assumptions (multitrait scaling success rate >95% for all domains except miscellany) and internal consistency were reported for most of the domains (mean alpha, 0.61). Factor analysis supported the a prori nine domain structure (63% of the variance) while a small test-retest study showed satisfactory reproducibility (ICC > 0.80) for all domains except cardiovascular (ICC = 0.45). In terms of validity, the scale showed modest association with indicators of motor symptom severity and disease progression but a high correlation with other measures of NMS (NMSQuest) and health-related quality of life measure (PDQ-8) (both, rS = 0.70). In conclusion, NMSS can be used to assess the frequency and severity of NMS in PD patients across all stages in conjunction with the recently validated non-motor questionnaire.

Cardiac-Resynchronization Therapy in Heart Failure with Narrow QRS Complexes

Abstract: Background Indications for cardiac-resynchronization therapy (CRT) in patients with heart failure include a prolonged QRS interval (≥120 msec), in addition to other functional criteria. Some patients with narrow QRS complexes have echocardiographic evidence of left ventricular mechanical dyssynchrony and may also benefit from CRT. Methods We enrolled 172 patients who had a standard indication for an implantable cardioverter–defibrillator. Patients received the CRT device and were randomly assigned to the CRT group or to a control group (no CRT) for 6 months. The primary end point was the proportion of patients with an increase in peak oxygen consumption of at least 1.0 ml per kilogram of body weight per minute during cardiopulmonary exercise testing at 6 months. Results At 6 months, the CRT group and the control group did not differ significantly in the proportion of patients with the primary end point (46% and 41%, respectively). In a prespecified subgroup with a QRS interval of 120 msec or more, the pea...

Acute kidney injury in the intensive care unit according to RIFLE

Abstract: Objectives:To apply the RIFLE criteria “risk,” “injury,” and “failure” for severity of acute kidney injury to patients admitted to the intensive care unit and to evaluate the significance of other prognostic factors.Design:Retrospective analysis of the Riyadh Intensive Care Program database.Setting:

Optic pathway gliomas in neurofibromatosis-1: Controversies and recommendations

Abstract: Optic pathway glioma (OPG), seen in 15% to 20% of individuals with neurofibromatosis type 1 (NF1), account for significant morbidity in young children with NF1. Overwhelmingly a tumor of children younger than 7 years, OPG may present in individuals with NF1 at any age. Although many OPG may remain indolent and never cause signs or symptoms, others lead to vision loss, proptosis, or precocious puberty. Because the natural history and treatment of NF1-associated OPG is different from that of sporadic OPG in individuals without NF1, a task force composed of basic scientists and clinical researchers was assembled in 1997 to propose a set of guidelines for the diagnosis and management of NF1-associated OPG. This new review highlights advances in our understanding of the pathophysiology and clinical behavior of these tumors made over the last 10 years. Controversies in both the diagnosis and management of these tumors are examined. Finally, specific evidence-based recommendations are proposed for clinicians caring for children with NF1.

Prevalence of nonmotor symptoms in Parkinson's disease in an international setting; Study using nonmotor symptoms questionnaire in 545 patients

Abstract: 2006, there was, no single instrument (questionnaire or scale) for attempting a comprehensive assessment of the wide range of nonmotor symptoms (NMS) of Parkinson's disease (PD). The PD nonmotor group, a multidisciplinary group of experts including patient group representatives developed and validated the NMS screening questionnaire (NMSQuest) comprising 30 items. The NMSQuest is a self completed screening tool designed to draw attention to the presence of NMS. In this paper, we present the results gathered from 545 patients using the definitive version of the NMSQuest highlighting the prevalence of the wide range of NMS flagged in the NMSQuest from consecutive PD patients in an international setting.

Silicon and bone health.

Abstract: Low bone mass (osteoporosis) is a silent epidemic of the 21st century, which presently in the UK results in over 200,000 fractures annually at a cost of over one billion pounds. Figures are set to increase worldwide. Understanding the factors which affect bone metabolism is thus of primary importance in order to establish preventative measures or treatments for this condition. Nutrition is an important determinant of bone health, but the effects of the individual nutrients and minerals, other than calcium, is little understood. Accumulating evidence over the last 30 years strongly suggest that dietary silicon is beneficial to bone and connective tissue health and we recently reported strong positive associations between dietary Si intake and bone mineral density in US and UK cohorts. The exact biological role(s) of silicon in bone health is still not clear, although a number of possible mechanisms have been suggested, including the synthesis of collagen and/or its stabilization, and matrix mineralization. This review gives an overview of this naturally occurring dietary element, its metabolism and the evidence of its potential role in bone health.

Cysteine Redox Sensor in PKGIa Enables Oxidant-Induced Activation

Abstract: Changes in the concentration of oxidants in cells can regulate biochemical signaling mechanisms that control cell function. We have found that guanosine 3',5'-monophosphate (cGMP)-dependent protein kinase (PKG) functions directly as a redox sensor. The Ialpha isoform, PKGIalpha, formed an interprotein disulfide linking its two subunits in cells exposed to exogenous hydrogen peroxide. This oxidation directly activated the kinase in vitro, and in rat cells and tissues. The affinity of the kinase for substrates it phosphorylates was enhanced by disulfide formation. This oxidation-induced activation represents an alternate mechanism for regulation along with the classical activation involving nitric oxide and cGMP. This mechanism underlies cGMP-independent vasorelaxation in response to oxidants in the cardiovascular system and provides a molecular explantion for how hydrogen peroxide can operate as an endothelium-derived hyperpolarizing factor.

Systematic review and evaluation of physiological track and trigger warning systems for identifying at-risk patients on the ward

Abstract: Physiological track and trigger warning systems (TTs) are used to identify patients outside critical care areas at risk of deterioration and to alert a senior clinician, Critical Care Outreach Service, or equivalent. The aims of this work were: to describe published TTs and the extent to which each has been developed according to established procedures; to review the published evidence and available data on the reliability, validity and utility of existing systems; and to identify the best TT for timely recognition of critically ill patients. Systematic review of studies identified from electronic, citation and hand searching, and expert informants. Cohort study of data from 31 acute hospitals in England and Wales. Thirty-six papers were identified describing 25 distinct TTs. Thirty-one papers described the use of a TT, and five were studies examining the development or testing of TTs. None of the studies met all methodological quality standards. For the cohort study, outcome was measured by a composite of death, admission to critical care, ‘do not attempt resuscitation’ or cardiopulmonary resuscitation. Fifteen datasets met pre-defined quality criteria. Sensitivities and positive predictive values were low, with median (quartiles) of 43.3 (25.4–69.2) and 36.7 (29.3–43.8), respectively. A wide variety of TTs were in use, with little evidence of reliability, validity and utility. Sensitivity was poor, which might be due in part to the nature of the physiology monitored or to the choice of trigger threshold. Available data were insufficient to identify the best TT.

The isolation of nucleic acids from fixed, paraffin-embedded tissues-which methods are useful when?

Abstract: Museums and pathology collections around the world represent an archive of genetic material to study populations and diseases. For preservation purposes, a large portion of these collections has been fixed in formalin-containing solutions, a treatment that results in cross-linking of biomolecules. Cross-linking not only complicates isolation of nucleic acid but also introduces polymerase "blocks" during PCR. A wide variety of methods exists for the recovery of DNA and RNA from archival tissues, and although a number of previous studies have qualitatively compared the relative merits of the different techniques, very few have undertaken wide scale quantitative comparisons. To help address this issue, we have undertaken a study that investigates the quality of nucleic acids recovered from a test panel of fixed specimens that have been manipulated following a number of the published protocols. These include methods of pre-treating the samples prior to extraction, extraction and nucleic acid purification methods themselves, and a post-extraction enzymatic repair technique. We find that although many of the published methods have distinct positive effects on some characteristics of the nucleic acids, the benefits often come at a cost. In addition, a number of the previously published techniques appear to have no effect at all. Our findings recommend that the extraction methodology adopted should be chosen carefully. Here we provide a quick reference table that can be used to determine appropriate protocols for particular aims.

European guidelines for quality assurance in cervical cancer screening: recommendations for cervical cytology terminology

Abstract: There are many different systems of cytology classification used in the member states of the European Union (EU) and many different languages. The following short annexe to Chapter 3 of the European Guidelines for Quality Assurance in Cervical Cancer Screening provides a framework that will allow different terminologies and languages to be translated into standard terminology based on the Bethesda system (TBS) for cytology while retaining the cervical intraepithelial neoplasia (CIN) classification for histology. This approach has followed extensive consultation with representatives of many countries and professional groups as well as a discussion forum published in Cytopathology (2005;16:113). This article will describe the reporting of specimen adequacy, which is dealt with in more detail elsewhere in Chapter 3 of the guidelines, the optional general categorization recommended in TBS, the interpretation/cytology result and other comments that may be made on reports such as concurrent human papillomavirus testing and the use of automation review and recommendations for management. The main categories in TBS will be described in the context of CIN, dyskaryosis and dysplasia terminologies so that all may be translated into the same framework. These guidelines should allow European countries to adapt their terminology in such a way as to make their screening programmes comparable with each other as well as with programmes elsewhere in the world.

Homocysteine and cardiovascular disease: a review of the evidence.

Abstract: Elevated homocysteine (HCY) levels can be caused by a number of factors, including folate and B-vitamin deficiency, pre-existing atherosclerotic disease, diabetes and various drugs. Epidemiological evidence, as well as data from retrospective and prospective studies, supports an association between elevated HCY levels and increased risk of cardiovascular disease (CVD). However, whether lowering HCY levels by administration of folate and vitamins B6 and B12 is associated with any significant decrease in vascular risk remains the subject of ongoing debate. Although the major studies that have reported to date show that vitamin supplementation was associated with a decrease in HCY levels, this failed to have any significant effect on cardiovascular risk. Furthermore, although some lipid-modifying treatments have been shown to increase HCY levels, there is no evidence that this attenuates or compromises the beneficial effects of such treatments on cardiovascular risk. Taken together, these data suggest that HCY is a marker, rather than a cause, of CVD and therefore do not provide support for routine screening for and treatment of elevated HCY to prevent CVD. Data from ongoing clinical trials are awaited to clarify this issue.

Proactive care of older people undergoing surgery (‘POPS’): Designing, embedding, evaluating and funding a comprehensive geriatric assessment service for older elective surgical patients

Abstract: Background: older people undergoing elective surgery have significant post-operative problems prolonging hospitalisation. Objective: to design, embed, and evaluate an evidence-based comprehensive geriatric assessment (CGA) service for at-risk older patients undergoing elective surgery. Setting: urban teaching hospital. Subjects: elective surgical patients aged 65+. Intervention: multidisciplinary preoperative CGA service with post-operative follow-through (proactive care of older people undergoing surgery ['POPS']). Methods: observational cohort study and multilevel surveys (development and modelling phase). Prospective 'before and after' comparison (exploratory evaluation). Results: findings from the development phase showed high levels of preoperative co-morbidity, no multidisciplinary preoperative input, and multiple potentially preventable post-operative problems delaying discharge in older elective surgery patients. Comparison of 2 cohorts of elective orthopaedic patients (pre-POPS vs POPS, N = 54) showed the POPS group had fewer post-operative medical complications including pneumonia (20% vs 4% \p = 0.008]) and delirium (19% vs 6% \p = 0.036]), and significant improvements in areas reflecting multidisciplinary practice including pressure sores (19% vs 4% \p = 0.028]), poor pain control (30% vs 2% [p<0.001]), delayed mobilisation (28% vs 9% \p = 0.012]) and inappropriate catheter use (20% vs 7% \p = 0.046]). Length of stay was reduced by 4.5 days. There were fewer delayed discharges relating to medical complications (37% vs 13%) or waits for OT assessment or equipment (20% vs 4%). Conclusion: a proactive evidence-based CGA service for at-risk older elective surgical patients was developed according to MRC framework for complex interventions. Pre/post comparison in elective orthopaedic patients showed improved (within methodological limitations) post-operative outcomes indicative of better clinical effectiveness and efficiency, and contributed to the service obtaining mainstream funding. Informed by the present study, a randomised controlled trial is ongoing.

A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease.

Abstract: Deferasirox is a once-daily, oral iron chelator developed for treating transfusional iron overload. Preclinical studies indicated that the kidney was a potential target organ of toxicity. As patients with sickle cell disease often have abnormal baseline renal function, the primary objective of this randomised, open-label, phase II trial was to evaluate the safety and tolerability of deferasirox in comparison with deferoxamine in this population. Assessment of efficacy, as measured by change in liver iron concentration (LIC) using biosusceptometry, was a secondary objective. A total of 195 adult and paediatric patients received deferasirox (n = 132) or deferoxamine (n = 63). Adverse events most commonly associated with deferasirox were mild, including transient nausea, vomiting, diarrhoea, abdominal pain and skin rash. Abnormal laboratory studies with deferasirox were occasionally associated with mild non-progressive increases in serum creatinine and reversible elevations in liver function tests. Discontinuation rates from deferasirox (11·4%) and deferoxamine (11·1%) were similar. Over 1 year, similar dose-dependent LIC reductions were observed with deferasirox and deferoxamine. Once-daily oral deferasirox has acceptable tolerability and appears to have similar efficacy to deferoxamine in reducing iron burden in transfused patients with sickle cell disease.

Statins and sepsis: multiple modifications at multiple levels.

Abstract: Sepsis, an infection-induced inflammatory syndrome, is a leading and increasing cause of mortality worldwide. Animal and human observational studies suggest statins may prevent the morbidity and mortality associated with the sepsis syndrome. In this Review, we describe the demonstrated mechanisms through which statins modulate the inflammatory response associated with sepsis. These mechanisms include effects on cell signalling with consequent changes at the transcriptional level, the induction of haem oxygenase, the direct alteration of leucocyte-endothelial cell interaction, and the reduced expression of MHC II. Since statins do not target individual inflammatory mediators, but possibly reduce the overall magnitude of the systemic response, this effect could prove an important distinguishing feature modulating the host response to septic insults. This work establishes the biological plausibility needed for future trials of statins in critical illness.

Guidelines on the insertion and management of central venous access devices in adults

Abstract: Central venous access devices are used in many branched of medicine where venous access is required for either long-term or a short-term care. These guidelines review the types of access devices available and make a number of major recommendations. Their respective advantages and disadvantages in various clinical settings are outlined. Patient care prior to, and immediately following insertion is discussed in the context of possible complications and how these are best avoided. There is a section addressing long-term care of in-dwelling devices. Techniques of insertion and removal are reviewed and management of the problems which are most likely to occur following insertion including infection, misplacement and thrombosis are discussed. Care of patients with coagulopathies is addressed and there is a section addressing catheter-related problems.

Serum adiponectin and bone mineral density in women

Abstract: Context: Bone mineral density (BMD) is positively associated with body weight. This association persists even at non-load bearing sites, suggesting that a nonmechanical factor such as an adipocyte-derived hormone may modulate BMD. Objective: The objective of the study was to evaluate the relationship between adiponectin, an adipocyte-derived hormone, and BMD. Design, Setting, Participants: A total of 1735 nondiabetic women were recruited from a large, population-based cohort (mean age, 50.0 yr). We employed linear regression methods to estimate the relationship between adiponectin and BMD. Main Outcome Measures: Percentage change in BMD (as measured at total hip, spine, femoral neck, and forearm) and markers of bone turnover associated with a doubling of fasting serum adiponectin levels were measured. Results: Employing age-adjusted analysis, each doubling of serum adiponectin was associated with a mean 2.7% decrease in BMD [total hip, −3.2% (95% confidence interval, −4.1, −2.3); femoral neck, −3.1% (−4.0...

Non-HACEK gram-negative bacillus endocarditis.

Abstract: Endocarditis caused by non-HACEK organisms (species other than Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) has lon...

Management of chronic hand eczema

Abstract: Hand eczema (HE) is one of the most frequent skin diseases and has often a chronically relapsing course with a poor prognosis resulting in a high social and economic impact for the individual and the society. In this article, we highlight the results of an expert workshop on the 'management of severe chronic hand eczema' with the focus on the epidemiology, the burden of severe HE, its classification and diagnostic procedures, and the current status of treatment options according to an evidence-based approach (randomized controlled clinical trials, RCTs). We conclude that despite the abundance of topical and systemic treatment options, disease management in patients with severe chronic HE is frequently inadequate. There is a strong need for RCTs of existing and new treatment options based on clearly diagnosed subtypes of HE and its severity.

Mutations in LCA5, encoding the ciliary protein lebercilin, cause Leber congenital amaurosis

Abstract: Leber congenital amaurosis (LCA) causes blindness or severe visual impairment at or within a few months of birth. Here we show, using homozygosity mapping, that the LCA5 gene on chromosome 6q14, which encodes the previously unknown ciliary protein lebercilin, is associated with this disease. We detected homozygous nonsense and frameshift mutations in LCA5 in five families affected with LCA. In a sixth family, the LCA5 transcript was completely absent. LCA5 is expressed widely throughout development, although the phenotype in affected individuals is limited to the eye. Lebercilin localizes to the connecting cilia of photoreceptors and to the microtubules, centrioles and primary cilia of cultured mammalian cells. Using tandem affinity purification, we identified 24 proteins that link lebercilin to centrosomal and ciliary functions. Members of this interactome represent candidate genes for LCA and other ciliopathies. Our findings emphasize the emerging role of disrupted ciliary processes in the molecular pathogenesis of LCA.

Management of spontaneous and iatrogenic retroperitoneal haemorrhage: conservative management, endovascular intervention or open surgery?

Abstract: Summary Background: Retroperitoneal haematoma is a rare clinical entity with variable aetiology, which is increasing in incidence mainly due to complications related to interventional procedures. There is no general consensus as to the best management plan for patients with retroperitoneal haematoma. Methods: A literature review was undertaken using MEDLINE, all relevant papers on retroperitoneal haemorrhage or haematoma were used. Results: The diagnosis is often delayed as symptoms are nonspecific. Retroperitoneal haematoma should be suspected in patients with significant groin, flank, abdominal, back pain or haemodynamic instability following an interventional procedure. Spontaneous haemorrhage usually occurs in patients who are anticoagulated. Multi-slice CT and arteriography are important for diagnosis. Most haemodynamically stable patients can be managed with fluid resuscitation, correction of coagulopathy and blood transfusion. Endovascular treatment involving selective intra-arterial embolisation or the deployment of stent-grafts over the punctured vessel is attaining an increasingly important role. Open repair of retroperitoneal bleeding vessels should be reserved for cases when there is failure of conservative or endovascular measures to control the bleeding. Open repair is also required if endovascular facilities or expertise is unavailable and in cases where the patient is unstable. If treated inappropriately, the mortality of patients with retroperitoneal haematoma remains high. Conclusion: There is a lack of level I evidence for the best management plans for retroperitoneal haematoma, and evidence is based on small cohort series or isolated case reports. Conservative management should only be reserved for patients who are stable. Interventional radiology with intra-arterial embolisation or stent-grafting is the treatment of choice. Open surgery is now rarely required.

Evidence for oxidative stress in the frontal cortex in patients with recurrent depressive disorder--a postmortem study.

Abstract: Prefrontal cortical (PFC) and hippocampal (HI) volume reductions have been consistently found in patients with recurrent depressive disorder (DD). Here we examine the possibility that oxidative stress, widely implicated in neuronal cell damage, may contribute to these brain structural changes. We compared manganese (Mn) and copper/zinc (Cu/Zn) superoxide dismutase (SOD) coenzyme concentrations in postmortem PFC and hippocampal brain tissue from 7 patients with DD and 7 neuropsychiatrically healthy controls using sandwich-type enzyme-linked immunosorbent assay (ELISA) technique. The concentration of Cu/Zn-SOD was significantly increased in the PFC but not in the hippocampus of patients. There was no significant change in Mn-SOD enzyme concentration in either region. Our findings contribute to the growing body of evidence implicating oxidative stress in the pathophysiology of depressive disorder.

Language and communication difficulties in juvenile offenders

Abstract: Background: Studies of the prison population suggest that the numbers of prisoners with language and communication disorders is higher than that of the overall population. However, the prison popul...