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Biomedical subjects

S Davies

Publications and source records attributed to S Davies.

At least 91 records · Page 5Linked to original sources

Equity of service: a protocol for management of children with speech problems.

In an attempt to achieve equity of service, the level of consistency of speech and language therapists in making decisions about the management of children with phonological delay was examined. Six cases were created and the therapists were interviewed about their management and criteria for therapy for each case. Decisions were made about standardising practice within the team. A phonological care pathway was devised to consider the criteria outlined in the results. This pathway is now being piloted with the expectation that it will facilitate an equitable service for all children with sound system problems.

Child↗

An inter-disciplinary approach to swallowing problems in acute stroke.

Many speech and language therapy (SLT) departments are in danger of being swamped with dysphagia referrals, often to the detriment of other work. At the same time surveys have shown that large numbers of patients with acute stroke have swallowing problems which are poorly managed during the critical early phase, not referred or missed altogether. The Collaborative Dysphagia Audit (CODA) study, carried out in six British hospitals, showed that nurses could quickly be trained to carry out basic screening assessments for dysphagia and that implementation of a co-ordinated inter-disciplinary dysphagia management policy (DMP) could substantially improve the proportion of dysphagic patients in whom appropriate feeding precautions were taken. These early DMPs were limited by the need for ward staff to keep all patients with suspected swallowing impairment nil by mouth until assessed by SLT, so in some acute stroke units nurses have been trained to a higher level which allows them to manage most routine transient swallowing problems, leaving only complex or persistent cases for referral to SLT. This approach has been used successfully in our unit in Gateshead, where a dysphagia nurse specialist post has been set up to act as a link between ward staff and SLTs, to ensure that the necessary training levels are maintained and to co-ordinate the DMP.

Acute Disease↗

The influence of cytomegalovirus viraemia on the outcome of recurrent hepatitis C after liver transplantation.

BACKGROUND: Several interrelated host and hepatitis C virus (HCV) associated factors have been proposed to explain the variable outcomes in HCV recurrence. Recent evidence suggests that cytomegalovirus (CMV) infection not only is co-factor in progression of HCV recurrence but may precipitate allograft rejection. We investigated whether short-term CMV viremia influences HCV recurrence, the number and grade of acute rejection episodes, and the histological course of HCV recurrence during the first year after orthotopic liver transplantation (OLT) for HCV-related cirrhosis. METHODS: A cohort of 39 patients transplanted for cirrhosis HCV-related was analyzed. Patients were evaluated twice weekly for CMV infection by a blood polymerase chain reaction (PCR) assay. Triple therapy with cyclosporine or tacrolimus, azathioprine and prednisolone was the initial immunosuppressive regimen. Preemptive treatment with ganciclovir was started when two consecutive PCRs for CMV were positive. Liver biopsies were performed on day 7 after OLT or when indicated. A 3-day IV 1 g methilprednisolone was given to patients with moderate or severe rejection. Ishak's score was used to grade inflammation and to stage fibrosis. RESULTS: Neither CMV viremia nor CMV disease after OLT for HCV-related cirrhosis adversely influenced the incidence and grade of acute rejection episodes nor the histological outcome of post transplant HCV recurrence, during the first year after liver transplantation. CONCLUSION: CMV viremia as detected by PCR does not affect the progression of HCV recurrence in liver grafts.

Adult↗

Oral temazepam.

Explore the source record for details and available documents.

Anti-Anxiety Agents↗

Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors.

After the transplantation of unmodified marrow from human leukocyte antigen-matched unrelated donors receiving cyclosporine (CSP) and methotrexate (MTX), the incidence of acute graft-versus-host disease (GVHD) is greater than 75%. Tacrolimus is a macrolide compound that, in previous preclinical and clinical studies, was effective in combination with MTX for the prevention of acute GVHD. Between March 1995 and September 1996, 180 patients were randomized in a phase 3, open-label, multicenter study to determine whether tacrolimus combined with a short course of MTX (n = 90), more than CSP and a short course of MTX (n = 90), would reduce the incidence of acute GVHD after marrow transplantation from unrelated donors. There was a significant trend toward decreased severity of acute GVHD across all grades (P =.005). Based on the Kaplan-Meier estimate, the probability of grade II-IV acute GVHD in the tacrolimus group (56%) was significantly lower than in the CSP group (74%; P =.0002). Use of glucocorticoids for the management of GVHD was significantly lower with tacrolimus than with CSP (65% vs 81%, respectively; P =. 019). The number of patients requiring dialysis in the first 100 days was similar (tacrolimus, 9; CSP, 8). Overall and relapse-free survival rates for the tacrolimus and CSP arms at 2 years was 54% versus 50% (P =.46) and 47% versus 42% (P =.58), respectively. The combination of tacrolimus and MTX after unrelated donor marrow transplantation significantly decreased the risk for acute GVHD than did the combination of CSP and MTX, with no significant increase in toxicity, infections, or leukemia relapse.

Acute Disease↗

1-[2-[(Heteroaryloxy)heteroaryl]carbamoyl]indolines: novel and selective 5-HT2C receptor inverse agonists with potential as antidepressant/anxiolytic agents.

Bisaryl ethers have been identified with excellent 5-HT2C affinity and selectivity over both 5-HT2A and 5-HT2B receptors. Compounds such as 11, 27 and 38 have potent oral activity in a centrally mediated pharmacodynamic model of 5-HT2C function and their potential as novel non-sedating anxiolytic and antidepressants is under investigation.

Administration, Oral↗

Ciprofibrate therapy improves endothelial function and reduces postprandial lipemia and oxidative stress in type 2 diabetes mellitus.

BACKGROUND: Exaggerated postprandial lipemia (PPL) is a factor in atherogenesis, involving endothelial dysfunction and enhanced oxidative stress. We examined the effect of ciprofibrate therapy on these parameters in type 2 diabetes mellitus. METHODS AND RESULTS: Twenty patients entered a 3-month, double-blind, placebo-controlled study. Each subject was studied fasting and after a fatty meal, at baseline, and after 3 months of treatment. Glucose and lipid profiles were measured over an 8-hour postprandial period. Endothelial function (flow-mediated endothelium-dependent vasodilatation [FMD]) and oxidative stress (electron paramagnetic resonance spectroscopy) were measured after fasting and 4 hours postprandially. At baseline, both groups exhibited similar PPL and deterioration in endothelial function. After ciprofibrate, fasting and postprandial FMD values were significantly higher (from 3.8+/-1. 8% and 1.8+/-1.3% to 4.8+/-1.1% and 3.4+/-1.1%; P<0.05). This was mirrored by a fall in fasting and postprandial triglycerides (3. 1+/-2.1 and 6.6+/-4.1 mmol/L to 1.5+/-0.8 and 2.8+/-1.3 mmol/L, P<0. 05). Fasting and postprandial HDL cholesterol was also elevated (0. 9+/-0.1 and 0.8+/-0.1 mmol/L and 1.2+/-0.2 and 1.2+/-0.1 mmol/L, P<0. 05). There were no changes in total or LDL cholesterol. Fasting and postprandial triglyceride enrichment of all lipoproteins was attenuated, with cholesterol depletion of VLDL and enrichment of HDL. There were similar postprandial increases in oxidative stress in both groups at baseline, which was significantly attenuated by ciprofibrate (0.3+/-0.6 versus 1.5+/-1.1 U, P<0.05). CONCLUSIONS: This study demonstrates that fibrate therapy improves fasting and postprandial endothelial function in type 2 diabetes. Attenuation of PPL and the associated oxidative stress, with increased HDL cholesterol levels, may be important.

Adult↗

Biarylcarbamoylindolines are novel and selective 5-HT(2C) receptor inverse agonists: identification of 5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]- 5-pyridyl]carbamoyl]-6-trifluoromethylindoline (SB-243213) as a potential antidepressant/anxiolytic agent.

The evolution, synthesis, and biological activity of a novel series of 5-HT(2C) receptor inverse agonists are reported. Biarylcarbamoylindolines have been identified with excellent 5-HT(2C) affinity and selectivity over 5-HT(2A) receptors. In addition, (pyridyloxypyridyl)carbamoylindolines have been discovered with additional selectivity over the closely related 5-HT(2B) receptor. Compounds from this series are inverse agonists at the human cloned 5-HT(2C) receptor, completely abolishing basal activity in a functional assay. The new series have reduced P450 inhibitory liability compared to a previously described series of 1-(3-pyridylcarbamoyl)indolines (Bromidge et al. J. Med. Chem. 1998, 41, 1598) from which they evolved. Compounds from this series showed excellent oral activity in a rat mCPP hypolocomotion model and in animal models of anxiety. On the basis of their favorable biological profile, 32 (SB-228357) and 40 (SB-243213) have been selected for further evaluation to determine their therapeutic potential for the treatment of CNS disorders such as depression and anxiety.

Administration, Oral↗

Reality orientation for dementia.

BACKGROUND: Reality Orientation (RO) was first described as a technique to improve the quality of life of confused elderly people, although its origins lie in an attempt to rehabilitate severely disturbed war veterans, not in geriatric work. It operates through the presentation of orientation information (eg time, place and person-related) which is thought to provide the person with a greater understanding of their surroundings, possibly resulting in an improved sense of control and self-esteem. There has been criticism of RO in clinical practice, with some fear that it has been applied in a mechanical fashion and has been insensitive to the needs of the individual. There is also a suggestion that constant relearning of material can actually contribute to mood and self-esteem problems. There is often little consistent application of psychological therapies in dementia services, so a systematic review of the available evidence is important in order to identify the effectiveness of the different therapies. Subsequently, guidelines for their use can be made on a sound evidence base. OBJECTIVES: To assess the evidence of effectiveness for the use of Reality Orientation (RO) as a classroom-based therapy on elderly persons with dementia. SEARCH STRATEGY: Computerised databases were searched independently by 2 reviewers entering the terms 'Reality Orientation, dementia, control, trial or study'. Relevant websites were searched and some handsearching was conducted by the reviewer. Specialists in the field were approached for undocumented material, and all publications found were searched for additional references. SELECTION CRITERIA: All randomised controlled trials (RCTs), and all controlled trials with some degree of concealment, blinding or control for bias (second order evidence) of Reality Orientation as an intervention for dementia were included. The criteria for inclusion/exclusion involved systematic assessment of the quality of study design and the risk of bias, using a standard data extraction form. A measure of cognitive and/or behavioural change was needed. DATA COLLECTION AND ANALYSIS: Data were extracted independently by both reviewers, using a previously tested data extraction form. Authors were contacted for data not provided in the papers. Psychological scales measuring cognitive and behavioural changes were examined. MAIN RESULTS: 6 RCTs were entered in the analysis, with a total of 125 subjects (67 in experimental groups, 58 in control groups). Results were divided into 2 subsections: cognition and behaviour. Change in cognitive and behavioural outcomes showed a significant effect in favour of treatment. REVIEWER'S CONCLUSIONS: There is some evidence that RO has benefits on both cognition and behaviour for dementia sufferers. Further research could examine which features of RO are particularly effective. It is unclear how far the benefits of RO extend after the end of treatment, but and it appears that a continued programme may be needed to sustain potential benefits.

Aged↗

Reminiscence therapy for dementia.

BACKGROUND: Reminiscence Therapy (RT) has been defined as vocal or silent recall of events in a person's life, either alone, or with another person or group of people. It typically involves group meetings, at least once a week. in which participants are encouraged to talk about past events, often assisted by aids such as photos, music, objects and videos of the past. There is, often, little consistent application of psychological therapies in dementia services. A number of these 'therapies' were greeted with enthusiasm by health care practitioners in understimulating care environments. They were expected to work miracles and their 'failure' to do this has led to their widespread disuse. A systematic review of the available evidence is important in order to identify the effectiveness of the different therapies. Subsequently, guidelines for their use can be made on a sound evidence base. OBJECTIVES: RT involves groups of elderly people talking of past events, assisted by aids such as videos, pictures and archives, as a means of communicating and reflecting upon their life experiences. The objective of the review is to assess the effects of RT for dementia. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, MEDLINE, PSYCHLIT, EMBASE, OMNI, BIDS, Dissertation Abstracts International, SIGLE and reference lists of relevant articles up to 1998, and we contacted specialists in the field. We also searched relevant internet sites and we handsearched Aging and Mental Health, the Gerontologist, Journal of Gerontology, Current Opinion in Psychiatry, Current Research in Britain: Social Sciences, British Psychological Society conference proceedings and Reminiscence database. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised trials of RT for dementia in elderly people. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Two trials are included in the review, but only one trial with 15 participants had extractable data. The results were statistically non-significant for both cognition and behaviour. REVIEWER'S CONCLUSIONS: No firm conclusions could be reached regarding the effectiveness of RT for dementia. The review highlighted the urgent need for more systematic research in the area.

Dementia↗

Neonatal screening for sickle cell disease.

BACKGROUND: Sickle cell disease is an inherited disorder that occurs throughout the world with its highest incidence in areas of Africa where malaria is endemic. It affects up to one in 60 infants born in some areas of Africa. There are a number of potentially serious complications associated with the condition, and it is suggested that early treatment (before symptoms develop) can improve both morbidity and mortality. Screening for the condition in the neonatal period would enable early diagnosis and therefore early treatment. OBJECTIVES: To assess whether there is evidence that neonatal screening for sickle cell disease rather than symptomatic diagnosis reduces adverse short and long term outcomes for those in whom the disease is detected, without adverse outcomes in the population screened. SEARCH STRATEGY: We searched the Controlled Trials Register of the Cochrane Cystic Fibrosis and Genetic Disorders Group (See Group search strategy). Contact was made with experts in the field for any work as yet unpublished and reference lists of published studies were also searched. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: Any randomised or pseudorandomised trial, published or unpublished comparing diagnosis by screening to clinical diagnosis would have been considered eligible for inclusion. DATA COLLECTION AND ANALYSIS: No trials of neonatal screening for sickle cell disease were found. MAIN RESULTS: No trials of neonatal screening for sickle cell disease were found. REVIEWER'S CONCLUSIONS: There is a lack of evidence from trials of neonatal screening for sickle cell disease. There is evidence of benefit from early treatment which is made possible by screening and there are a number of reviews and economic analyses of non-trial literature suggesting that screening is appropriate. Health care providers must therefore assess whether the information provided by these documents is relevant to their practice and situation when making decisions regarding neonatal screening for sickle cell disease. Systematic reviews of early treatments/interventions, including penicillin prophylaxis, pneumococcal vaccine and parental education should be considered.

Anemia, Sickle Cell↗

[A retinoid constituent of lipofuscin, A2-E, is a photosensitizer in human retinal pigment epithelial cells].

BACKGROUND: A fluorescent compound of lipofuscin, A2-E, has been shown to impair lysosomal function and to increase the intralysosomal pH of human retinal pigment epithelial (RPE) cells. This study addressed the phototoxic potential of A2-E on RPE cells. METHODS: A2-E accumulation was confirmed by fluorescence microscopy and fluorescence-activated cell sorter analysis. Acridine orange staining allowed assessment of lysosomal integrity and intralysosomal pH. Phototoxic properties of A2-E were determined by exposing A2-E-free and A2-E-fed RPE cell cultures to short-wavelength visible light and assessing cell viability and lysosomal integrity. RESULTS: Intralysosomal accumulation of A2-E was confirmed. Acridine orange staining showed that the A2-E was located in the lysosomal compartment and induced an elevation of intralysosomal pH. Exposure of A2-E fed cells to light resulted in a significant loss of cell viability by 72 h which was not observed in either RPE cells maintained in the dark or A2-E-free cultures exposed to light. Toxicity was associated with a loss of lysosomal integrity. CONCLUSION: A2-E is detrimental to RPE cell function by a variety of mechanisms including inhibition of lysosomal degrading capacity, loss of membrane integrity, and phototoxicity. Such mechanisms could contribute to retinal aging and to retinal diseases associated with excessive lipofuscin accumulation.

Cell Survival↗

The clinical indications for plain radiography in acute knee trauma.

OBJECTIVES: to assess the key symptoms and physical signs in the acutely injured knee that are significantly associated with fracture and utilise these to develop an algorithm for the use of radiography in acute knee trauma. DESIGN: retrospective review of all acute knee injuries presenting to the accident and emergency unit at a District General Hospital over a 6-month period in 1998 (over 500 cases). After exclusions, a study group of 370 eligible adults was obtained. These patients were reviewed for the key symptoms and physical signs, and radiological evidence of fracture. OUTCOME MEASURES: the X-ray films were interpreted by a consultant radiologist. Of those patients on whom radiographs were not performed, follow up was assessed by a review of any re-attendance to the A&E department. RESULTS: there was a statistically significant correlation, using chi-square (Mantel-Haentzel) and linear regression analysis, between the presence of a fracture and each of the following variables: age, non-weightbearing in the department (p<0.05), haemarthrosis, point bony tenderness, effusion (p<0.001). CONCLUSION: these key symptoms and physical signs may form the basis of an algorithm for examining knees radiologically, with acceptable positive and negative predictive values. (This is currently being tested prospectively).

Adult↗

Ataque de nervios and history of childhood trauma.

OBJECTIVE: Ataque de nervios is a common, self-labeled Hispanic folk diagnosis. It typically describes episodic, dramatic outbursts of negative emotion in response to a stressor, sometimes involving destructive behavior. Dissociation and affective dysregulation during such episodes suggested a link to childhood trauma. We therefore assessed psychiatric diagnoses, history of ataque, and childhood trauma in treatment-seeking Hispanic outpatients (N = 70). Significantly more subjects with an anxiety or affective disorder plus ataque reported a history of physical abuse, sexual abuse, and/or or a substance-abusing caretaker than those with psychiatric disorder but no ataque. In some Hispanic individuals, ataque may represent a culturally sanctioned expression of extreme affect dysregulation associated with childhood trauma. Patients with ataque de nervios should receive a thorough traumatic history assessment.

Adult↗