PubMed Health⌕ Search

Biomedical subjects

D Weller

Publications and source records attributed to D Weller.

At least 19 recordsLinked to original sources

Systematic review of factors influencing patient and practitioner delay in diagnosis of upper gastrointestinal cancer.

As knowledge on the causation of cancers advances and new treatments are developed, early recognition and accurate diagnosis becomes increasingly important. This review focused on identifying factors influencing patient and primary care practitioner delay for upper gastrointestinal cancer. A systematic methodology was applied, including extensive searches of the literature published from 1970 to 2003, systematic data extraction, quality assessment and narrative data synthesis. Included studies were those evaluating factors associated with the time interval between a patient first noticing a cancer symptom and presenting to primary care, between a patient first presenting to primary care and being referred to secondary care, or describing an intervention designed to reduce those intervals. Twenty-five studies were included in the review. Studies reporting delay intervals demonstrated that the patient phase of delay was greater than the practitioner phase, whilst patient-related research suggests that recognition of symptom seriousness is more important than recognition of the presence of the symptom. The main factors related to practitioner delay were misdiagnosis, application and interpretation of tests, and the confounding effect of existing disease. Greater understanding of patient factors is required, along with evaluation of interventions to ensure appropriate diagnosis, examination and investigation.

Attitude to Health↗

How should we measure informed choice? The case of cancer screening.

Informed choice is increasingly recognised as important in supporting patient autonomy and ensuring that people are neither deceived nor coerced. In cancer screening the emphasis has shifted away from just promoting the benefits of screening to providing comprehensive information to enable people to make an informed choice. Cancer screening programmes in the UK now have policies in place which state that it is their responsibility to ensure that individuals are making an individual informed choice. There is a need to evaluate whether such policies mean that those people invited for screening are making informed choices, and how comprehensive information affects other variables such as uptake, cost effectiveness, and satisfaction. At the present time, there is no validated measure of informed choice in cancer screening. Such a measure could be used to evaluate the effectiveness of interventions to increase informed choice and levels of informed choice in a population invited for screening. It could encourage health professionals to be accountable. Factors important when measuring informed choice in cancer screening include an individual's understanding of the limitations of screening, the ability to make an autonomous choice, and the difference between choice and behaviour.

Attitude of Health Personnel↗

The ultimate speed of magnetic switching in granular recording media.

In magnetic memory devices, logical bits are recorded by selectively setting the magnetization vector of individual magnetic domains either 'up' or 'down'. In such devices, the fastest and most efficient recording method involves precessional switching: when a magnetic field B(p) is applied as a write pulse over a period tau, the magnetization vector precesses about the field until B(p)tau reaches the threshold value at which switching occurs. Increasing the amplitude of the write pulse B(p) might therefore substantially shorten the required switching time tau and allow for faster magnetic recording. Here we use very short pulses of a very high magnetic field to show that under these extreme conditions, precessional switching in magnetic media supporting high bit densities no longer takes place at well-defined field strengths; instead, switching occurs randomly within a wide range of magnetic fields. We attribute this behaviour to a momentary collapse of the ferromagnetic order of the spins under the load of the short and high-field pulse, thus establishing an ultimate limit to the speed of deterministic switching and magnetic recording.

Journal Article↗

Promoting better use of the PSA test in general practice: randomized controlled trial of educational strategies based on outreach visits and mailout.

BACKGROUND: Prostate-specific antigen (PSA) testing for prostate cancer is controversial. Demand for PSA testing is likely to rise in the UK, Australia and other western countries. Primary care needs to develop appropriate strategies to respond to this demand. OBJECTIVES: Our aim was to compare the effectiveness of educational outreach visits (EOVs) and mailout strategies targeting PSA testing in Australian primary care. METHODS: A randomized controlled trial was conducted in general practices in southern Adelaide. The main outcome measures at baseline, 6 months and 12 months post-intervention were PSA testing rates and GP knowledge in key areas relating to prostate cancer and PSA testing. RESULTS: The interventions were able to demonstrate a change in clinical practice. In the 6 months post-intervention, median PSA testing rate in the EOV group was significantly lower than in the postal group, which in turn was significantly lower than the control group (P < 0.001). Statistically significant differences were not, however, maintained in the 6-12 month post-intervention period. The EOV group, at 6 months follow-up, had a significantly greater proportion of "correct" responses than the control group to questions about prostate cancer treatment effectiveness (P = 0.004) and endorsement of PSA screening by professional bodies (P = 0.041). CONCLUSIONS: Primary care has a central role in PSA testing for prostate cancer. Clinical practice in this area is receptive to evidence-based interventions.

Adult↗

Deroughening of a 1D domain wall in an ultrathin magnetic film by a correlated defect.

Interaction of a field-driven magnetic domain wall with a correlated (line) defect is examined by Kerr imaging in subnanometer thin Co films. The line defect directs and confines the wall near the bottom of the effective potential trough U(eff), which competes with underlying random disorder that roughens the wall. We observe a kinetic "deroughening" with roughness exponent zeta approximately 0.1 well below zeta = 2/3 characteristic of random defects. Deroughening occurs on lengths greater than an inherent elastic screening length L(el), which is consistently explained by the restoring action of U(eff).

Journal Article↗

Feasibility of an evidence-based literature search service for general practitioners.

OBJECTIVE: To test the feasibility of an evidence-based clinical literature search service to help answer general practitioners' (GPs') clinical questions. DESIGN: Two search services supplied GPs who submitted questions with the best available empirical evidence to answer these questions. The GPs provided feedback on the value of the service, and concordance of answers from the two search services was assessed. SETTING: Two literature search services (Queensland and Victoria), operating for nine months from February 1999. MAIN OUTCOME MEASURES: Use of the service; time taken to locate answers; availability of evidence; value of the service to GPs; and consistency of answers from the two services. RESULTS: 58 GPs asked 160 questions (29 asked one, 11 asked five or more). The questions concerned treatment (65%), aetiology (17%), prognosis (13%), and diagnosis (5%). Answering a question took a mean of 3 hours 32 minutes of personnel time (95% CI, 2.67-3.97); nine questions took longer than 10 hours each to answer, the longest taking 23 hours 30 minutes. Evidence of suitable quality to provide a sound answer was available for 126 (79%) questions. Feedback data for 84 (53%) questions, provided by 42 GPs, showed that they appreciated the service, and asking the questions changed clinical care. There were many minor differences between the answers from the two centres, and substantial differences in the evidence found for 4/14 questions. However, conclusions reached were largely similar, with no or only minor differences for all questions. CONCLUSIONS: It is feasible to provide a literature search service, but further assessment is needed to establish its cost effectiveness.

Attitude of Health Personnel↗

Antidepressant drugs and generic counselling for treatment of major depression in primary care: randomised trial with patient preference arms.

OBJECTIVES: To compare the efficacy of antidepressant drugs and generic counselling for treating mild to moderate depression in general practice. To determine whether the outcomes were similar for patients with randomly allocated treatment and those expressing a treatment preference. DESIGN: Randomised controlled trial, with patient preference arms. Follow up at 8 weeks and 12 months and abstraction of GP case notes. SETTING: 31 general practices in Trent region. PARTICIPANTS: Patients aged 18-70 who met research diagnostic criteria for major depression; 103 patients were randomised and 220 patients were recruited to the preference arms. MAIN OUTCOME MEASURES: Difference in mean Beck depression inventory score; time to remission; global outcome assessed by a psychiatrist using all data sources; and research diagnostic criteria. RESULTS: At 12 months there was no difference between the mean Beck scores in the randomised arms. Combining the randomised and patient preference groups, the difference in Beck scores was 0.4 (95% confidence interval -2.7 to 3.5). Patients choosing counselling did better than those randomised to it (mean difference in Beck score 4.6, 0.0 to 9.2). There was no difference in the psychiatrist's overall assessment of outcome between any of the groups. 221/265 (83%) of participants with a known outcome had a remission. Median time to remission was shorter in the group randomised to antidepressants than the other three groups (2 months v 3 months). 33/221 (15%) patients had a relapse. CONCLUSIONS: Generic counselling seems to be as effective as antidepressant treatment for mild to moderate depressive illness, although patients receiving antidepressants may recover more quickly. General practitioners should allow patients to have their preferred treatment.

Adult↗

Stable ultrahigh-density magneto-optical recordings using introduced linear defects.

The stability of data bits in magnetic recording media at ultra-high densities is compromised by the thermal 'flips'--magnetic spin reversals--of nano-sized spin domains, which erase the stored information. Media that are magnetized perpendicular to the plane of the film, such as ultrathin cobalt films or multilayered structures, are more stable against thermal self-erasure than conventional memory devices. In this context, magneto-optical memories seem particularly promising for ultrahigh-density recording on portable disks, and bit densities of approximately 100 Gbit inch(-2) (ref. 7) have been demonstrated using recent advances in the bit writing and reading techniques. But the roughness and mobility of the magnetic domain walls prevents closer packing of the magnetic bits, and therefore presents a challenge to reaching even higher bit densities. Here we report that the strain imposed by a linear defect in a magnetic thin film can smooth rough domain walls over regions hundreds of micrometres in size, and halt their motion. A scaling analysis of this process, based on the generic physics of disorder-controlled elastic lines, points to a simple way by which magnetic media might be prepared that can store data at densities in excess of 1 Tbit inch(-2).

Journal Article↗

Primary care-based physical activity programs: effectiveness in sedentary older patients with osteoarthritis symptoms.

OBJECTIVE: This study examined, in a group of older patients, (a) the effectiveness of an invitation to participate in a program providing individualized physical activity advice in a primary care setting and (b) the changes in self-reported physical activity and symptoms in patients with osteoarthritis (OA). METHODS: Healthy, sedentary community-dwelling men and women aged 60 years or more were invited to participate. Following random allocation, the intervention group received individualized physical activity advice at baseline and at 3, 6, and 12 months followup. RESULTS: Of the 299 people who satisfied the study's inclusion criteria, a subgroup of 69 people reported pain and stiffness of the hip or knee at baseline. These patients reported increases in frequency and time of walking and vigorous exercise (all P < 0.001), with no change to OA symptom scores (pain and stiffness), and a small decline in physical functioning was reported at 12 months followup in the control group only (P = 0.027). At the 12-month followup more intervention participants than control participants (P = 0.013) reported a greater intention to exercise. CONCLUSIONS: An offer of primary care-based physical activity advice, with an emphasis on the benefits for general health (rather than "treatment" for OA), will attract individuals with OA symptoms. Although the present study was unable to demonstrate intervention-control group differences for the majority of outcomes, intention to exercise did appear to be positively influenced.

Age Factors↗

A comparison of the prevalence of respiratory illness and non-specific health symptoms in two Victorian cities.

OBJECTIVE: To compare the prevalence of respiratory illness and non-specific health symptoms among adults and children aged 4-15 years living in Portland and Warrnambool, Victoria. METHODS: A postal survey of 3,903 adults in Portland and Warrnambool systematically selected from the electoral roll was undertaken. Both an adults and children's questionnaire were enclosed in the mailing to each adult. If there were children aged 4-15 years in the household, an adult was asked to complete a questionnaire for the child who would next celebrate a birthday. Questionnaires were returned by 2,111 adults (54%) and for 585 children. RESULTS: No significant differences in the prevalence of self-reported asthma or wheeze were observed among adults or children residing in Portland and Warrnambool. The likelihood of itchy eyes, skin rash and stuffy nose was significantly higher in Portland adults and children compared with those in Warrnambool. Dry cough at night was increased among Portland children, but not significantly so. CONCLUSIONS: Higher rates of non-specific symptoms were observed in Portland but from a cross-sectional survey such as this, it is not possible to identify the cause of these higher rates. They may be related to environmental factors such as pollens or emissions from aluminium production, fertiliser production or bulk handling activities on the wharf, or they may be attributable to other factors such as response or recall bias.

Adolescent↗

Zidovudine triphosphate and lamivudine triphosphate concentration-response relationships in HIV-infected persons.

OBJECTIVE: To quantitate intracellular concentrations of zidovudine and lamivudine triphosphate and explore relationships with virologic and immunologic responses to antiretroviral therapy. DESIGN: Eight antiretroviral-naive, HIV-infected persons with CD4 T cell counts > 100 x 10(6) cells/l, and HIV RNA in plasma > 5000 copies/ml participating in a prospective, randomized, open-label study of standard dose versus concentration-controlled therapy with zidovudine, lamivudine, and indinavir. METHODS: Peripheral blood mononuclear cells and plasma were collected frequently throughout the study for quantitation of intracellular zidovudine triphosphate and lamivudine triphosphate concentrations, and zidovudine and lamivudine concentrations in plasma. CD4 T cells and HIV RNA in plasma (Roche Amplicor Ultrasensitive Assay) were measured at baseline and every 4 weeks throughout the study. Relationships among intracellular and plasma concentrations, and CD4 T cells and HIV RNA in plasma were investigated with regression analyses. RESULTS: Significant relationships were observed between the intracellular concentrations of zidovudine triphosphate and lamivudine triphosphate and the baseline level of CD4 cells. Lamivudine triphosphate concentrations were related in a linear manner to the apparent oral clearance of lamivudine from plasma. A direct linear relationship was found between the intracellular concentrations of zidovudine triphosphate and lamivudine triphosphate. The percent change in CD4 cells during therapy and the rate of decline in HIV RNA in plasma were related to the intracellular concentrations of zidovudine triphosphate and lamivudine triphosphate. CONCLUSION: These studies into the intracellular clinical pharmacology of nucleoside reverse transcriptase inhibitors illustrate potential clinical implications as determinants of therapeutic success. Moreover, these findings provide several leads and a strong impetus for future investigations with nucleoside reverse transcriptase inhibitors particularly when given in combination and sequentially.

Adolescent↗

Restoration of hemoglobin A synthesis in erythroid cells from peripheral blood of thalassemic patients.

Mononuclear cells from peripheral blood of thalassemic patients were treated with morpholino oligonucleotides antisense to aberrant splice sites in mutant beta-globin precursor mRNAs (pre-mRNAs). The oligonucleotides restored correct splicing and translation of beta-globin mRNA, increasing the hemoglobin (Hb) A synthesis in erythroid cells from patients with IVS2-654/beta(E), IVS2-745/IVS2-745, and IVS2-745/IVS2-1 genotypes. The maximal Hb A level for repaired IVS2-745 mutation was approximately 30% of normal; Hb A was still detectable 9 days after a single treatment with oligonucleotide. Thus, expression of defective beta-globin genes was repaired and significant level of Hb A was restored in a cell population that would be targeted in clinical applications of this approach.

Cell Nucleus↗

Monodisperse FePt nanoparticles and ferromagnetic FePt nanocrystal superlattices

Synthesis of monodisperse iron-platinum (FePt) nanoparticles by reduction of platinum acetylacetonate and decomposition of iron pentacarbonyl in the presence of oleic acid and oleyl amine stabilizers is reported. The FePt particle composition is readily controlled, and the size is tunable from 3- to 10-nanometer diameter with a standard deviation of less than 5%. These nanoparticles self-assemble into three-dimensional superlattices. Thermal annealing converts the internal particle structure from a chemically disordered face-centered cubic phase to the chemically ordered face-centered tetragonal phase and transforms the nanoparticle superlattices into ferromagnetic nanocrystal assemblies. These assemblies are chemically and mechanically robust and can support high-density magnetization reversal transitions.

Journal Article↗

Screening for colorectal cancer using the faecal occult blood test, hemoccult.

BACKGROUND: Colorectal cancer is a leading cause of illness and death in the Western world. In Australia, the United Kingdom and the United States, it is the second commonest cancer for women after breast cancer (age-standardised incidence 22-33 per 100,000), and men after prostate or lung cancer (age-standardised incidence 31-47 per 100,000) (Jeffs et al, 1996; Parkin et al, 1992). Just under half of all persons affected will die from their disease (Jeffs et al, 1996; Parkin et al, 1992) The human and financial costs of this disease have prompted considerable research efforts to evaluate the ability of screening tests to detect the cancer at an early curable stage. Tests which have been considered for screening include faecal occult blood tests, sigmoidoscopy and colonoscopy. OBJECTIVES: To determine whether screening for colorectal cancer using the faecal occult blood test, Hemoccult reduces colorectal cancer mortality and to consider the benefits and harms of screening. SEARCH STRATEGY: Published and unpublished data for this review were identified by: * retrieving studies included in a systematic review conducted by some of the authors in 1995, * searches of MEDLINE, Current Contents and the Cochrane Controlled Trials Register, * writing to trial lists. SELECTION CRITERIA: All controlled trials of screening for colorectal cancer using Hemoccult were eligible for inclusion in the review. DATA COLLECTION AND ANALYSIS: Data from the trials were independently extracted by two authors. Data analysis was performed using the group subjects were randomised to ('intention to screen'), whether or not they were ever screened. To estimate the effect of Hemoccult screening on colorectal cancer mortality, we calculated relative risks and risk differences for each trial, and then overall, using fixed and random effects models and tested for heterogeneity of effects. We calculated summary measures of effect including all trials and also for just the randomised controlled trials. We also calculated a summary measure of effect, adjusted for attendance at screening in each trial (not shown in Meta-view). MAIN RESULTS: Meta-analysis of mortality results from the randomised controlled trials shows that those allocated to screening had a reduction in colorectal cancer mortality of 16% (RR 0.84, CI: 0.77-0.93). When adjusted for screening attendance in the individual studies, the mortality reduction is 23% (RR 0.77, CI: 0.57-0.89). Overall, if 10 000 people were offered a biennial Hemoccult screening program and two-thirds attended for at least one Hemoccult test, there would be 8.5 deaths (CI: 3.6-13.5) from colorectal cancer prevented over 10 years. However, the screening program would also result in 2 800 participants having at least one colonoscopy, if screening harms from the Minnesota trial are considered, and there would be 3.4 colonoscopy complications (perforation or haemorrhage). If screening harms from the Gothenburg trial are considered, approximately 600 participants would need at least one sigmoidoscopy and double contrast barium enema, resulting in 1.8 perforations or haemorrhages. REVIEWER'S CONCLUSIONS: Screening benefits include reduction in colorectal cancer mortality, possible reduction in cancer incidence through detection and removal of colorectal adenomas and potentially, treatment of early colorectal cancers may involve less invasive surgery. Harmful effects of screening include the physical complications of colonoscopy, disruption to lifestyle, stress and discomfort of testing and investigations, and the anxiety caused by falsely positive screening tests. Although screening benefits are likely to outweigh harms for populations at increased risk of colorectal cancer, we need more information about the harmful effects of screening, the community's responses to screening and screening costs for different health care systems before widespread screening can be recommended.

Colorectal Neoplasms↗

Pharmacologic characteristics of indinavir, didanosine, and stavudine in human immunodeficiency virus-infected children receiving combination therapy.

The use of human immunodeficiency virus (HIV) protease inhibitors in children has lagged behind that in adults because of the lack of suitable pediatric formulations and information on safe and effective dosing regimens. This study was designed to obtain pharmacokinetic information on indinavir, administered to HIV-infected children also receiving therapy with two nucleoside agents, and to explore relationships between pharmacokinetic parameters and anti-HIV effect. Indinavir was initiated at a dose of 500 mg/m(2) every 8 h. Plasma indinavir concentrations were measured every 4 weeks; the dose or dosing interval was adjusted to maintain trough concentrations of > or =0.1 mg/liter. All children were evaluated clinically at baseline and every 4 weeks. Plasma HIV RNA was quantitated at baseline and at weeks 4, 12, and 24. Eighteen children participated in this study. The average daily dose of indinavir was 2,043 mg/m(2); nine children received indinavir at 6-h intervals. Pharmacokinetic characteristics of indinavir (mean +/- standard deviation) were the following: oral clearance, 1.4 +/- 0.5 liters/h/kg; half-life, 1.1 +/- 0.43 h; and trough concentration, 0. 29 +/- 0.32 mg/liter. In nine children that completed 24 weeks of therapy, the baseline-to-week-24 change in HIV RNA level was related to indinavir trough concentration and didanosine area under the curve. This study illustrates the ability to obtain pharmacokinetic information from children during routine clinic visits and to use this information to provide a safeguard against underdosing. The incorporation of pharmacologic knowledge with virologic, immunologic, and behavioral considerations should result in improved clinical outcomes for children infected with HIV.

Anti-HIV Agents↗

Simultaneous HPLC assay for quantification of indinavir, nelfinavir, ritonavir, and saquinavir in human plasma.

BACKGROUND: HIV protease inhibitors are recommended as part of combination antiretroviral therapy. Dual protease inhibitor therapy is also being used clinically. Consequently, a simultaneous assay for indinavir, nelfinavir, ritonavir, and saquinavir was developed. METHODS: Indinavir, nelfinavir, ritonavir, and saquinavir were extracted from plasma (250 microL) with methyl-t-butyl ether at basic pH after addition of an internal standard (A-86093). The compounds were separated on a Keystone BetaBasic C4 column (250 x 3 mm i.d.) at 40 degrees C with a mobile phase of acetonitrile-50 mmol/L ammonium formate buffer, pH 4.1 (52:48, by volume) at a flow rate of 0.5 mL/min. Indinavir, nelfinavir, ritonavir, and the internal standard (A-86093) were detected at 218 nm, and saquinavir was detected at 235 nm. The method was validated by analysis of five triplicate analyses of calibrators along with quality-control samples at three different concentrations prepared in human plasma. RESULTS: The extraction recovery was 87-92%. Within-run accuracy for quality-control samples was 6-8%, with CVs of 2-8%. Limits of quantification were 40-50 microg/L for indinavir, nelfinavir, and ritonavir, and 20 microg/L for saquinavir. Cross-validation with a liquid chromatography-mass spectroscopy method for saquinavir and nelfinavir was conducted with patient samples. Regression analysis revealed a good correlation (r(2) >0.94) between methods. Larger variations at concentrations >4000 microg/L were observed with nelfinavir. Interference with drugs commonly used in AIDS patients was not observed. Pharmacokinetic profiles for two patients on dual protease therapy were determined. CONCLUSIONS: A reliable and rugged simultaneous HPLC assay for four HIV protease inhibitors was developed. The assay method is convenient for clinical laboratories involved in therapeutic drug monitoring for HIV protease inhibitors. The assay has enough sensitivity to conduct pharmacokinetic studies in patients taking more than one HIV protease inhibitor along with other antiretroviral medications.

Chromatography, High Pressure Liquid↗

Minimum field strength in precessional magnetization reversal

Ultrafast magnetic field pulses as short as 2 picoseconds are able to reverse the magnetization in thin, in-plane, magnetized cobalt films. The field pulses are applied in the plane of the film, and their direction encompasses all angles with the magnetization. At a right angle to the magnetization, maximum torque is exerted on the spins. In this geometry, a precessional magnetization reversal can be triggered by fields as small as 184 kiloamperes per meter. Applications in future ultrafast magnetic recording schemes can be foreseen.

Journal Article↗