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Biomedical subjects

T Williamson

Publications and source records attributed to T Williamson.

At least 19 recordsLinked to original sources
PubMed2006

Interventions for ear discharge associated with grommets (ventilation tubes).

BACKGROUND: The insertion of grommets (also known as ventilation or tympanostomy tubes) is one of the most common surgical procedures performed on children. Postoperative otorrhoea (discharge) is the most common complication with a reported incidence ranging from 10% to 50%. In the UK, many ENT surgeons treat with topical antibiotics/steroid combinations, but general practitioners, mainly through fears of ototoxicity, are unlikely to prescribe these and choose systemic broad-spectrum antibiotics. OBJECTIVES: 1. To identify the most effective non-surgical management of discharge from ears with grommets in place.2. To identify the risks of non-surgical management for this condition (e.g. ototoxicity), and to set benefits of treatment against these risks. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2005), MEDLINE (1966 to 2005) and EMBASE (1974 to 2005). We also searched the CINAHL, AMED, LILACS, ISI WEB OF KNOWLEDGE, ISI PROCEEDINGS, mRCT, NNR, ZETOC, KOREAMED, CSA, MEDCARIB, INDMED and SAMED databases. The date of the last search was February 2005. SELECTION CRITERIA: Randomised controlled trials of adults or children, with any type of grommet and an ear with discharge were included. The trials compared treatment with placebo or one treatment with another. The primary outcome measure was the duration of the discharge. DATA COLLECTION AND ANALYSIS: The trials were selected independently according to the above criteria by the four reviewers. Differences in opinion over the inclusion of studies were resolved by discussion. The studies were graded using the CASP critical appraisal tool. Analyses were based on the presence of discharge seven days from the onset of treatment. MAIN RESULTS: There was very little good quality evidence. Four studies were included, all of them investigating different interventions and therefore a meta-analysis was not possible. Only one study demonstrated a significant difference. Oral amoxicillin clavulanate was compared to placebo in 79 patients. The odds of having a discharge persisting eight days after starting treatment was 0.19 (95% CI 0.07 to 0.49) . The number needed to treat to achieve that benefit is 2.5. Participants in both arms of this study also received daily aural toilet. The results will therefore not be applicable to most settings including primary care. No significant benefit was shown in the two studies investigating steroids (oral prednisolone with oral amoxicillin clavulanate and topical dexamethasone with topical ciprofloxacin ear drops), or the one study comparing an antibiotic-steroid combination (Otosporin(R)) drops versus spray (Otomize(R)) (although more patients preferred the spray form). AUTHORS' CONCLUSIONS: The authors of this review have been unable to identify the most effective intervention or to assess the associated risks. Research is urgently needed into the effectiveness of oral versus topical antibiotics in this group of patients. Clinicians considering antibiotic treatment need to balance any potential benefit against the risks of side effects and antibiotic resistance.

Adult↗
PubMed2001

Cost-Effectiveness of tolterodine for patients with urge incontinence who discontinue initial therapy with oxybutynin: a Canadian perspective.

BACKGROUND: Tolterodine is a novel muscarinic receptor antagonist for the treatment of overactive bladder. OBJECTIVE: The purpose of this study was to examine the cost-effectiveness of tolterodine for patients with urge incontinence (UI) who discontinue initial therapy with oxybutynin in a Canadian setting. METHODS: We compared 2 treatment strategies for the management of adult patients with UI: (1) generic oxybutynin with no further treatment for patients who discontinue and (2) generic oxybutynin with switch to tolterodine (2 mg BID) for patients who discontinue. We developed a 1-year Markov model (4-week cycle length) with transitions between disease states of normal, mild, moderate, and severe. Transition probabilities over 12 weeks were obtained from randomized trial data, and drug discontinuation rates were obtained from Quebec prescription claims data. Outcome measures were time in "normal" health state and quality-adjusted life-years (QALYs) using EuroQol-5D utility scores from a survey of Swedish patients with overactive bladder. Costs to the health care payer and patient out-of-pocket costs (in Canadian dollars) were included. RESULTS: For patients who discontinue oxybutynin, the use of tolterodine is associated with approximately 6 months per year in a normal health or mild disease state, compared with approximately 3 months for those who do not receive further drug therapy after discontinuation. Tolterodine use resulted in an annual additional cost per patient of Can $163. The incremental cost per QALY was Can $9,982 and appeared to be robust to alternative model parameter assumptions. CONCLUSION: Use of tolterodine in patients with UI who discontinue initial therapy with generic oxybutynin lies within currently accepted benchmarks for cost-effectiveness.

Benzhydryl Compounds↗
PubMed2001

Economic evaluation of systemic treatments for cytomegalovirus retinitis in patients with AIDS.

OBJECTIVE: To determine the cost of using systemic therapy to treat newly diagnosed cytomegalovirus (CMV) retinitis in persons with AIDS. DESIGN: Incidence-based simulation model of CMV treatment from a government payer perspective. SETTING: Swiss healthcare system. PATIENTS AND PARTICIPANTS: Patients with AIDS and newly diagnosed CMV retinitis. INTERVENTIONS: Patients were assigned to 1 of 4 treatment regimens for induction and maintenance therapy: (i) intravenous (IV) cidofovir induction and maintenance (cidofovir IV/IV); (ii) IV foscarnet induction and maintenance (foscarnet IV/IV); (iii) IV ganciclovir induction and maintenance (ganciclovir IV/IV); and (iv) IV ganciclovir induction and oral (PO) ganciclovir maintenance (ganciclovir IV/PO). Following a second relapse, patients were assigned to one of the other regimens. MAIN OUTCOME MEASURES: Time to first and subsequent progression, duration of maintenance treatment and direct medical expenditures [1998 Swiss francs (SwF)] . RESULTS: The median time to first progression was longest for cidofovir IV/IV, followed by foscarnet IV/IV, ganciclovir IV/IV and ganciclovir IV/PO. Mean survival was 13 months and mean costs for this period in the base case were lowest in those initially treated with cidofovir (SwF146,742), followed by initial treatment with foscarnet IV/IV (SwF194,809), ganciclovir IV/PO (SwF195,190) and ganciclovir IV/IV (SwF243,964). Costs were most sensitive to changes in efficacy estimates. CONCLUSIONS: Of the regimens studied, initiation of treatment with systemic cidofovir appears least costly over a 13-month period.

AIDS-Related Opportunistic Infections↗
PubMed2001

Costs and resources associated with the treatment of overactive bladder using retrospective medical care claims data.

The objectives of this study were to determine age- and gender-specific drug treatment prevalence rates for overactive bladder (OAB), and to compare resource use and costs among MCO members receiving drug treatment for OAB. Administrative claims data from seven affiliated health plans were analyzed for 8,661 members with a diagnosis or treatment indicative of OAB during 1998. Resource use and associated costs were analyzed over a four-month follow-up. In 1998, the prevalence of OAB among plan members was 1.1%. Of the patients with OAB, 71% did not receive pharmacotherapy. After multivariate analysis, treatment with tolterodine, oxybutynin, or other OAB treatment did not significantly affect the percent change in total per patient per month (PPPM) costs compared with the group not receiving a pharmacologic agent. Although the adjusted percent change in PPPM pharmacy costs was significantly higher within the tolterodine group, medical and total PPPM costs were not.

Benzhydryl Compounds↗
PubMed2000

The impact of antidepressant use on social functioning: reboxetine versus fluoxetine.

Depression compromises affected individuals' functional well-being and impairs their level of social and workplace performance. Improved social functioning in depressed patients may improve their work productivity. This study evaluated the differential effects of two antidepressants on social functioning outcomes for patients with major depression comparing reboxetine, a non-tricyclic, selective noradrenaline reuptake inhibitor and fluoxetine, a commonly prescribed selective serotonin reuptake inhibitor. A model using data from 284 depressed patients (138 reboxetine, 146 fluoxetine) in two 8-week clinical trials was developed to predict the percentage change over time in continuous outcome assessments as measured by a 21-item self-rating scale called the Social Adaptation Self-evaluation Scale (SASS). The percentage change from baseline SASS score was modelled as a function of both time-invariant and time-varying covariates. Results suggest that, by mid-study, the more severely ill subjects benefitted more from reboxetine treatment in terms of the outcome improvement rate and, by study-end, this effect also extended into the less severely ill population. In addition, a significant relationship was identified between the change in depression symptom severity as measured by the standard Hamilton Depression Rating Scale score and the change in social functioning per the SASS.

Adrenergic Uptake Inhibitors↗
PubMed2000

Community-based validation of the McCormick Toy Test.

The aim of the present study was to investigate the validity of a community-based hearing test to detect conductive hearing loss in 3-year-old children. Sixty-five children had their hearing tested using standard audiological tests at the same time as they underwent their 3-year-old health checks. The checks were performed by health visitors at community health clinics, and included the McCormick Toy Test (MCTT) for hearing. Fourteen children failed both tests and none passed the MCTT and failed the standard tests, giving a sensitivity of 100%. Forty-eight children passed both tests and three children failed the MCTT but passed the standard tests, giving a specificity of 94%. Positive predictive value was 82%. The results from this sample indicate that the MCTT may be used as a valid test for conductive hearing loss for 3-year-old children in the community setting.

Acoustic Impedance Tests↗
PubMed1996

Microtubule reorganization is obligatory for growth cone turning.

To examine the role of microtubules in growth cone turning, we have compared the microtubule organization in growth cones advancing on uniform laminin substrates with their organization in growth cones turning at a laminin-tenascin border. The majority (82%) of growth cones on laminin had a symmetrical microtubule organization, in which the microtubules entering the growth cone splay out toward the periphery of the growth cone. Growth cones at tenascin borders had symmetrically arranged microtubules in only 34% of cases, whereas in the majority of cases the microtubules were displaced toward one-half of the growth cone, presumably stabilizing in the direction of the turn along the tenascin border. These results suggest that reorganization of microtubules could underlie growth cone turning. Further evidence for the involvement of microtubule rearrangement in growth cone turning was provided by experiments in which growth cones approached tenascin borders in the presence of nanomolar concentrations of the microtubule stabilizing compound, Taxol. Taxol altered the organization of microtubules in growth cones growing on laminin by restricting their distribution to the proximal regions of the growth cone and increasing their bundling. Taxol did not stop growth cone advance on laminin. When growing in the presence of Taxol, growth cones at tenascin borders were not able to turn and grow along the laminin-tenascin border, and consequently stopped at the border. Growth cones were arrested at borders for as long as Taxol was present (up to 6 h) without showing any signs of drug toxicity. These effects of Taxol were reversible. Together, these results suggest that microtubule reorganization in growth cones is a necessary event in growth cone turning.

Actins↗
PubMed1996

The role of heparan sulfate proteoglycans in the pathogenesis of Alzheimer's disease.

The hallmark of Alzheimer's disease (AD) is the deposition of amyloid plaques and neurofibrillary tangles in the brain. The relationship between amyloid deposition and the cognitive deficit is still unclear. The amyloid beta A4 protein is produced by proteolytic cleavage of the amyloid protein precursor (APP). Very little is known about the normal function of APP and the role the protein may play in pathogenesis. Several studies have shown that APP is important for the regulation of neurite outgrowth. Our studies support these findings and indicate that the neurite outgrowth-promoting effects of APP are stimulated by an interaction between APP and specific proteoglycans. Using site-directed mutagenesis, a heparan sulfate binding site which mediates this effect has been mapped to the N-terminus of APP (residues 96-110, HBD-1). A peptide homologous to HBD-1 blocks the trophic effects of APP in cell culture. To purify specific proteoglycans which stimulate the action of APP, an affinity column was constructed using a biotinylated peptide homologous to HBD-1 coupled to streptavidin-agarose. Two proteoglycans were isolated from a crude brain cell conditioned medium by affinity chromatography. The purified proteoglycans bound APP saturably with high affinity and stimulated the action of APP on neurite outgrowth from chick sympathetic neurons. Digestion of the proteoglycan fraction with heparitinase I or chondroitinase ABC demonstrated the presence of two major proteins, a heparan sulfate proteoglycan with a core protein of 63-67 kD molecular mass and a chondroitin sulfate proteoglycan with a core protein of 100-110 kD molecular mass. The results demonstrate that APP binds to at least two proteoglycans and that this interaction may regulate the trophic effects of the protein. The interaction of specific APP-binding proteoglycans with amyloid plaques may disturb the normal function of APP and contribute to the neuritic degeneration that is commonly seen around the amyloid plaque cores.

Alzheimer Disease↗
PubMed1996

Dexrazoxane cardioprotection for patients receiving FAC chemotherapy: a pharmacoeconomic evaluation.

Anthracyclines are among the most effective and commonly-prescribed antitumor agents but have dose-limiting cumulative cardiotoxicity. We performed a pharmacoeconomic evaluation of the ability of dexrazoxane to prevent cardiac-related adverse events in patients with Stage IIIB or IV metastatic breast cancer who were treated with a median of 10 cycles of intravenous FAC (5-fluorouracil, doxorubicin and cyclophosphamide) at doses of 500/50/500 mg/m2 respectively. Dexrazoxane was given at 500 mg/m2 commencing at the seventh cycle of treatment. We determined the cost of each cardiac event prevented and the cost of each additional life-year saved by dexrazoxane use. The cost per cardiac event prevented was CDN $5745 and the cost per additional life-year saved was CDN $2856. With the increasing use of anthracyclines in Stages I and II breast cancer, these favorable clinical and economic results may broaden the range of therapeutic possibilities for anthracyclines in adjuvant and metastatic therapy of breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Characterization of 4-nitro-o-phenylenediamine activation by plant systems.

4-Nitro-o-phenylenediamine (NOP) is a powerful direct-acting mutagen which demonstrates significant enhancement in mutagenicity when exposed to plant enzymatic systems. Evidence implicating the involvement of peroxidactic oxidation in NOP activation has been obtained from plant-cell suspension and isolated enzyme experiments. Using selected cytochrome P450 and peroxidase enzyme inhibitors in conjunction with Salmonella typhimurium strain TA98 and intact plant-cell activating systems as well as isolated horseradish peroxidase enzyme we have further investigated NOP activation by plant systems. The activation of NOP by both plant cells and by horseradish peroxidase was suppressed by the P450 inhibitors methimazole and (+)-catechin and by the peroxidase inhibitors diethyldithiocarbamate and potassium cyanide, but was not suppressed by the P450 inhibitors metyrapone and 7,8-benzoflavone. In addition, peroxidase enzymatic activity was measured and found to be inhibited by methimazole, diethyldithiocarbamate and potassium cyanide but not by (+)-catechin. The data strongly support the involvement of exogenous peroxidase in the plant activation of NOP, but point to a complex metabolic system that requires multistep processing before full mutagenic potential of the plant-activated component of NOP is expressed.

Analysis of Variance↗
PubMed1992

Health care interviews by school nurses.

A health care interview (HCI) carried out by school nurses was piloted in Bath health authority for pupils entering secondary school. Tim Williamson reports the results of an evaluation study involving 99 pupils who had previously had a check with the school doctor at the age of ten. The HCI significantly improved the children's knowledge of who the school nurse was and how to contact her, but failed to improve knowledge of what the school nurse did. A total of 39 problems requiring some action were identified.

Adolescent↗