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Biomedical subjects

R Robinson

Publications and source records attributed to R Robinson.

At least 73 records · Page 4Linked to original sources

Managed care: US research evidence and its lessons for the NHS.

OBJECTIVES: To review the high quality US evidence on performance of managed health care organisations and the available US evidence on specific managed care techniques; namely, financial incentives, utilisation management and review, physician profiling and disease management. METHODS: Literature searches were conducted using numerous databases including Medline, Embase, the Social Sciences Citation Index and the National Health Service (NHS) Centre for Reviews and Dissemination library. For inclusion of evaluations of overall performance, studies had to use a comparison group (typically fee-for-service patients), make appropriate statistical adjustments for differences between groups, and be published in a peer-reviewed journal from 1980 forward. For assessments of techniques, less-demanding inclusion criteria reflected the paucity of generalisable literature; however, more current results were required (1990 forward). RESULTS: We identified 70 articles for systematic review, covering 18 dimensions of performance (e.g. utilisation, quality of care, consumer satisfaction, equity). The strength of the evidence varied by dimension. It was strongest for utilisation and quality. In general, managed care seems to reduce hospitalisation and use of high-cost discretionary services, to increase preventive screening, and to be neutral in terms of patient outcomes. As for specific techniques, we identified 19 articles for review, but limitations of these studies prevented our drawing any definite conclusions about techniques' effectiveness. This is an important, if somewhat negative, conclusion. CONCLUSIONS: Applying US evidence is complicated by an irrelevant comparator and a higher baseline of utilisation. Managed care brought Americans the familiar NHS practices of population-based health care and resource management through gatekeeping; hence, changes due to UK adoption of managed care techniques may be modest. US evidence should be used to generate hypotheses, not to predict UK behaviour.

Disease Management↗

Efficacy of a mouthrinse containing 0.05% cetylpyridinium chloride for the control of plaque and gingivitis: a 6-month clinical study in adults.

The objective of this 6-month, double-blind, clinical study, conducted following the American Dental Association (ADA) guidelines, was to provide an assessment of the effectiveness of a newly developed mouthrinse containing 0.05% cetylpyridinium chloride (CPC) for the control of supragingival dental plaque and gingivitis. Adult men and women from the Manchester, England, area were entered in the study, and stratified into two treatment groups (CPC mouthrinse and control mouthrinse), which were balanced for baseline Quigley-Hein Plaque Index scores and baseline Löe-Silness Gingival Index scores. Participants were given an oral prophylaxis and instructed to brush their teeth twice daily (morning and evening) for 1 minute with a soft-bristled toothbrush and fluoride dentifrice provided, immediately followed by rinsing for 30 seconds with 15 cc of their assigned mouthrinse. Examinations for supragingival plaque and gingivitis were conducted after 3 months' and again after 6 months' participation in the study. One hundred eleven participants complied with the protocol and completed the entire 6-month clinical study. At both the 3- and 6-month study examinations, the CPC mouthrinse group exhibited statistically significantly less supragingival plaque and gingivitis than did the control mouthrinse group. At the 6-month examination, the magnitude of these differences met or exceeded 24% for all 4 parameters measured (28.2% for Quigley-Hein Plaque Index, 63.4% for Plaque Severity Index, 24.0% for Löe-Silness Gingival Index, and 66.9% for Gingivitis Severity Index). The magnitude of the reductions in supragingival plaque and gingivitis were adequately large to support a claim of efficacy, in accordance with the criteria provided by the published guidelines of the ADA for the demonstration of the efficacy of a chemotherapeutic agent for the control of supragingival plaque and gingivitis. Thus, the results of this 6-month clinical study support the conclusion that a newly developed mouthrinse containing 0.05% cetylpyridinium chloride provides a statistically significant, clinically relevant level of efficacy for the control of supragingival plaque, and for the control of gingivitis, in accordance with the criteria provided by current ADA guidelines.

Adolescent↗

Statistical aspects of the normal visual field in short-wavelength automated perimetry.

PURPOSE: To determine the intraindividual and interindividual characteristics of normal sensitivity derived by short-wavelength automated perimetry (SWAP) as a function of threshold algorithm. To determine also the influence of ocular media absorption on the magnitude of the interindividual variation in normal sensitivity, and hence the confidence limits, derived by SWAP. METHODS: The sample comprised 51 normal subjects, stratified for age by decade (mean age, 55.5 years; range, 24-83 years) and experienced in white-on-white (W-W) perimetry and SWAP. One randomly assigned eye of each subject was examined on three occasions with Program 30-2 of the 640 Humphrey Field Analyzer using the Full Threshold and FASTPAC strategies for SWAP and W-W perimetries. Ocular media absorption (OMA) was assessed by the difference in scotopic sensitivity to stimuli of 410 and 560 nm. RESULTS: The group mean examination time (P < 0.001) was greater for SWAP than for W-W perimetry for both the Full Threshold (15.0% longer) and FASTPAC strategies (16.8% longer). The gradient of the age-decline in Mean Sensitivity for SWAP was approximately 25% less steep when corrected for OMA than when uncorrected. The interindividual normal variability, expressed as the coefficient of variation, for SWAP without correction for OMA was 2.7 times greater (range 2.0-3.9), and with correction 1.9 times greater (range 1.4-2.9), than that for W-W perimetry. CONCLUSIONS: The increased interindividual normal variability of SWAP, exacerbated by the lack of correction for OMA, currently limits the utility of SWAP in that the reduction in sensitivity required to indicate abnormality was proportionately greater than for W-W perimetry.

Absorption↗

Have his body.

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Autistic Disorder↗

Obsessive-compulsive disorder in children and adolescents.

Significant progress has occurred over the past 10 years in the understanding and treatment of obsessive-compulsive disorder. With the recognition that one half to one third of adults experience onset of the disorder in childhood and adolescence, early identification and treatment of the disorder become essential to reduce potential long-term ramifications. Models for etiopathogenesis suggest a neuropsychiatric disorder and are supported by identification of an immune-related subtype, association with other neurological diseases, brain-imaging studies, and peripheral blood findings. Pharmacological and behavioral treatments have been shown to have efficacy in reducing compulsive behaviors and obsessive thoughts. Although treatable, many children have only a partial response. Based on the current child and adolescent literature, an overview of childhood obsessive-compulsive disorder is presented.

Adolescent↗

Health policy. Managed care--just ask US.

Managed care in the US reduces use of health services and hospital admissions. Concerns that cost control could jeopardize quality are widespread. But there is no significant evidence to suggest that this is the case. Managed care produces low patient satisfaction ratings. The US evidence on managed care has little direct relevance to the UK, but elements of it might be usefully tested here.

Cost Control↗

Primary care. Cracks in the edifice.

The cost-effectiveness of the shift towards primary care is unproven, despite studies claiming otherwise. Existing studies show serious methodological shortcomings. One fifth of studies failed to control for differences in case-mix and demographic make-up. Nearly half of studies made no attempt to measure outcomes. There is an urgent need for an improved evaluation agenda to cover both long- and short-term needs.

Cost-Benefit Analysis↗

Managed care.

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Diffusion of Innovation↗

Inhibition of nuclear factor kappa B (NFkappaB) activity induces nerve growth factor-resistant apoptosis in PC12 cells.

The mechanism(s) underlying nerve growth factor (NGF)-mediated rescue of neurons from apoptosis is poorly understood, although it is well established that the high-affinity NGF receptor (TrkA) plays a pivotal role in mediating NGF effects. The report that the low-affinity NGF receptor (p75NGFR) can induce apoptosis prompted us to analyze the role played by a putative p75NGFR-associated signal-transduction element, the transcription factor nuclear factor kappa B (NFkappaB), in the modulation of apoptosis in PC12 cells. Here, we report that inhibition of NFkappaB function results in apoptosis of rat PC12 cells, a neuroblast-like cell line model of NGF-responsive neural tissues. Furthermore, NGF did not protect PC12 cells from cell death induced by the inhibition of NFkappaB. These results indicate that NFkappaB function is essential to maintain PC12 cell survival and to permit NGF-mediated rescue, consistent with the idea that signaling elements potentially associated with both TrkA- and p75NGFR are involved in the regulation of apoptosis.

Analysis of Variance↗

The acetylcholine releaser linopirdine increases parietal regional cerebral blood flow in Alzheimer's disease.

Centrally acting cholinergic drugs have been reported to increase regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT) in brain regions affected by Alzheimer's disease (AD). We studied the effects of the acetylcholine releaser linopirdine (LPD) on SPECT rCBF in patients with probable AD. Twenty-four AD patients (12 M, 12 F; mean age +/- SD = 68.9 +/- 8.2 years) and 13 healthy controls (8 M, 5 F; 68.4 +/- 8.0 years) participated. AD patients were scanned with 20 mCi of Tc99m-ECD at baseline and following 4 weeks of treatment with LPD 40 mg TID (n = 15) or placebo TID (n = 9) in a double-blind trial. Healthy subjects were scanned for comparison with baseline AD scans. Cortical/cerebellar rCBF ratios were derived for nine cortical structures. The combined parietal association cortex showed a 20.6% reduction in patients relative to controls. Patients treated with LPD showed an increase in parietal rCBF of 4.1 +/- 5.8%; whereas those treated with placebo showed a decrease of -2.0 +/- 7.4% (F = 5.13; df = 1, 22; P = 0.03). These data support the conclusion that rCBF abnormalities in AD are, in part, truly "functional" and can be selectively altered with pharmacological interventions. The parietal activation seen with LPD and other cholinergic AD drug therapies suggests the importance of measuring parietal lobe neuropsychological function in the course of evaluating these drugs.

Acetylcholine↗

Selective inhibition of oncogenic ras-p21 in vivo by agents that block its interaction with jun-N-kinase (JNK) and jun proteins. Implications for the design of selective chemotherapeutic agents.

We have obtained evidence that oncogenic and activated normal ras-p21 proteins utilize overlapping but distinct signal transduction pathways. Recently, we found that ras-p21 binds to both jun and its kinase, jun kinase (JNK). We now present evidence that suggests that oncogenic but not normal activated p21 depends strongly on early activation of JNK/jun. This early activation most likely involves direct interaction between oncogenic p21 and JNK/jun because p21 peptides that blocked the binding of p21 to JNK and jun strongly inhibited oncogenic p21-induced oocyte maturation while they did not inhibit insulin-activated normal cellular p21-induced maturation. Very similar results were also obtained for a newly characterized specific inhibitor of JNK which blocked oncogenic but not normal activated p21-induced oocyte maturation. We also found that both jun and JNK strongly enhanced oncogenic p21-induced oocyte maturation while they inhibited insulin-activated normal p21-induced oocyte maturation. These results suggest that the peptides and JNK inhibitor may be useful agents in selectively blocking the effects of oncogenic but not normal p21 in cells.

Animals↗

Nerve growth factor, central nervous system apoptosis, and adrenocortical activity in aged Fischer-344/brown Norway F1 hybrid rats.

During aging there is a progressive loss of neuronal function in the basal forebrain that results in cognitive impairment and cholinergic deficits. While altered neurotrophin (NT)-mediated signal transduction may account for some age-associated deficits, there are differences in the extent of NT responsiveness among different laboratory rat strains. Here we measured nerve growth factor (NGF) protein levels and fragmented DNA in the CNS, and basal and NGF-stimulated activity levels of the hypothalamus-pituitary-adrenocortical axis (HPAA) in 3-, 18-, and 30-month-old Fischer-344/Brown Norway rats. Our results show that while there is no age-associated differences in NGF protein levels, in aged Fischer-344/Brown Norway rats, there are increases in levels of immunoreactive fragmented DNA in the CNS and in adrenocortical responses to the peripheral administration of NGF. These data contribute to the characterization of the Fischer-344/Brown Norway F1 hybrid rat and provide baseline values useful for future studies on aged CNS.

Aging↗

Inhibition of oncogenic and activated wild-type ras-p21 protein-induced oocyte maturation by peptides from the ras-binding domain of the raf-p74 protein, identified from molecular dynamics calculations.

In the preceding paper we found from molecular dynamics calculations that the structure of the ras-binding domain (RBD) of raf changes predominantly in three regions depending upon whether it binds to ras-p21 or to its inhibitor protein, rap-1A. These three regions of the RBD involve residues from the protein-protein interaction interface, e.g., between residues 60 and 72, residues 97-110, and 111-121. Since the rap-1A-RBD complex is inactive, these three regions are implicated in ras-p21-induced activation of raf. We have therefore co-microinjected peptides corresponding to these three regions, 62-76, 97-110, and 111-121, into oocytes with oncogenic p21 and microinjected them into oocytes incubated in in insulin, which activates normal p21. All three peptides, but not a control peptide, strongly inhibit both oncogenic p21- and insulin-induced oocyte maturation. These findings corroborate our conclusions from the theoretical results that these three regions constitute raf effector domains. Since the 97-110 peptide is the strongest inhibitor of oncogenic p21, while the 111-121 peptide is the strongest inhibitor of insulin-induced oocyte maturation, the possibility exists that oncogenic and activated normal p21 proteins interact differently with the RBD of raf.

Amino Acid Sequence↗

Psoralen-mediated photodecontamination of platelet concentrates: inactivation of cell-free and cell-associated forms of human immunodeficiency virus and assessment of platelet function in vivo.

BACKGROUND: Treatment of platelet concentrates (PCs) with psoralens and broad-band ultraviolet A (UVA) radiation is being examined for the elimination of pathogens that might be present in donated blood. Previous studies have demonstrated the inactivation of cell-free viruses and the maintenance of platelet integrity with common in vitro assays. STUDY DESIGN AND METHODS: Human immunodeficiency virus (HIV) in three forms-cell-free, activity replicating, and latently infected cell lines-was added to PCs and treated with 50-microgram per mL of 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT), 0.35 mM rutin, and broad- and narrow-band UVA light (320-400 nm and 360-370 nm [UVA1], respectively). The inactivation of added HIV was assessed in tissue culture; platelet hemostatic activity was assessed in thrombocytopenic rabbits. RESULTS: Each form of HIV was inactivated completely (> or = 10(5) infectious units) on treatment with 30 J per cm2 of UVA1 light. Similar results were obtained on treatment of 2.5 mL of PCs in test tubes or intact PC units (50 mL) in blood bags. Latently infected cell lines were substantially more sensitive than cell-free HIV or HIV that was actively replicating. Human platelets treated with 40 J per cm2 of UVA1 light had a fully corrected bleeding time shortly after treatment or after 5 days' storage, as assessed in thrombocytopenic rabbits. Platelet hemostatic function began to decrease with 81 J per cm2 of UVA1 light and was abolished with 113 J per cm2. At similar fluences, broad-band UVA light was more injurious to platelets than was UVA1 light. CONCLUSION: HIV transmission might be eliminated by PCs after treatment with AMT and UVA1 light and without a reduction in platelet hemostatic function.

Animals↗

Progressive facial hemiatrophy: MRI appearances.

The cranial CT and MRI appearances of a 14-year-old girl with Parry-Romberg syndrome and epilepsy are described. The findings are compared with the two published descriptions of MRI and CT in such patients. MRI appearances in our patient differ from those published and may be consistent with a vascular malformation. The one published report on the intracranial histopathology of a patient with Parry-Romberg syndrome and epilepsy states that a microscopic vascular malformation was found. We discuss the relationship between radiological and pathological findings. The possible aetiologies of Parry-Romberg syndrome (vascular malformation, immunological, trauma, sympathetic innervation, hereditary, slow virus) are discussed. We suggest that Parry-Romberg syndrome could be regarded as a neurocutaneous syndrome, a component of which includes intracerebral vascular dysplasia. In this and the other three cases of Parry-Romberg syndrome with epilepsy, the sensitivity of MRI in detecting intracranial lesions is demonstrated. Recommendations for imaging these patients are proposed.

Brain Diseases↗

Retinal haemorrhages and convulsions.

AIMS: To evaluate the incidence of retinal haemorrhages after convulsions in children. PATIENTS AND METHODS: All children who required hospital admission after an episode of convulsions were included in the study. Complete neurological and ocular examinations, including ophthalmoscopy, were undertaken within 48 hours of hospital admission. RESULTS: Thirty three children were examined according to the protocol and their seizures were classified by a paediatric neurologist. Despite the fact that some of the children also vomited or underwent cardiopulmonary resuscitation, none of the 33 children developed retinal haemorrhages. CONCLUSIONS: Convulsions rarely (if ever) give rise to retinal haemorrhages. The finding of retinal haemorrhages should stimulate a detailed assessment to exclude non-accidental injury, whatever the nature of the associated or antecedent events.

Adolescent↗