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Biomedical subjects

L Roberts

Publications and source records attributed to L Roberts.

At least 19 recordsLinked to original sources

Relationship between walking levels and perceptions of the local neighbourhood environment.

OBJECTIVE: To explore the relationship between frequency of walking trips, perceptions of the local environment and individual travel preferences in children. DESIGN: Cross-sectional questionnaire-based study. SETTING: Six primary schools in Birmingham, UK, range of socioeconomic classifications. PARTICIPANTS: 473 children aged 9-11 years (82% response rate), including 250 (52.9%) boys and 160 (33.8%) from ethnic minority populations. OUTCOME MEASURES: The primary outcome measure was level of walking (high or low) based on self-reported walking frequency in the past week. Secondary outcome measures included child perceptions of seven aspects of the local environment and individual travel preference. All outcomes were measured through questionnaires administered at school in the presence of a researcher. RESULTS: 198 (41.9%) children were classified as high walkers and 275 (58.1%) as low walkers. After adjusting for confounding factors, high walkers were more likely to perceive heavy traffic surrounding their homes (odds ratio (OR) 1.55, 95% confidence interval (CI) 1.03 to 2.33), unsafe streets (OR 1.88, 95% CI 1.27 to 2.80) and prefer healthier modes of travel (OR 1.67, 95% CI 2.56 to 1.08). High walkers were less likely to worry about strangers (OR 0.66, 95% CI 0.45 to 1.02) and less likely to report no parks or sports grounds nearby (OR 0.66, 95% CI 0.42 to 1.02). Children from ethnic minority groups walked significantly less than white children (mean number of walking trips 16.8 and 21.9, respectively, p<0.001). CONCLUSIONS: Certain environmental perceptions are related to walking levels in children. Awareness of these may help in the development of future interventions, and also enable healthcare professionals to encourage walking by providing case-specific and appropriate advice.

Child↗

Systematic review: the effectiveness of hypnotherapy in the management of irritable bowel syndrome.

AIM: To systematically review the literature evaluating hypnotherapy in the management of irritable bowel syndrome (IBS). METHODS: Electronic databases were searched (Cochrane Library, Medline, CINAHL, AMED, Embase, PsycINFO, CISCOM, TRIP and the Social Science Citation index), bibliographic references scanned and main authors contacted. No restrictions were placed on language or publication year. Eligible studies involved adults with IBS using single-component hypnotherapy. All studies, except single case or expert opinion, were sought and all patient-related outcomes eligible. RESULTS: Out of 299 unique references identified, 20 studies (18 trials of which four were randomized, two controlled and 12 uncontrolled) and two case series were eligible. These tended to demonstrate hypnotherapy as being effective in the management of IBS. Numbers of patients included were small. Only one trial scored more than four out of eight on internal validity. CONCLUSION: The published evidence suggests that hypnotherapy is effective in the management of IBS. Over half of the trials (10 of 18) indicated a significant benefit. A randomized placebo-controlled trial of high internal validity is necessary to establish the effectiveness of hypnotherapy in the management of IBS. Until such a trial is undertaken, this form of treatment should be restricted to specialist centres caring for the more severe forms of the disorder.

Adult↗

A Bayesian approach to analysing the cost-effectiveness of two primary care interventions aimed at improving attendance for breast screening.

AIMS: To assess the cost-effectiveness of two primary care interventions, a letter and a flag, aimed at improving attendance for breast screening among (i) all women invited for breast screening and (ii) non-attenders. METHODS: A probabilistic decision analytic model was developed using Markov chain Monte Carlo simulation implemented in WinBUGS. The model was populated using economic and effectiveness data collected alongside two randomised controlled trials. RESULTS: For all women invited, the incremental cost-effectiveness ratio (ICER) for the letter compared with no intervention is 27 pounds per additional attendance, and the ICER for the combined letter and flag intervention compared to the letter alone is 171 pounds. The corresponding ICERs for non-attenders are 41 pounds and 90 pounds. The flag intervention is an inefficient option in both settings. A large proportion of the costs fall on the practices (25-67%), depending on the intervention and target population. The total costs incurred do not, however, seem prohibitive. Expected value of perfect information suggests that there is greater value in carrying out further research on the intervention implemented among all women invited for breast screening rather than on non-attenders. CONCLUSIONS: The flag intervention alone does not appear to be an efficient option. The choice between the letter and both interventions combined is subjective, depending on the willingness to pay for an additional screening attendance.

Bayes Theorem↗

Usefulness of scintimammography as an adjunct to mammography and ultrasound in the diagnosis of breast diseases.

This study was undertaken to evaluate the diagnostic efficacy of 99mtechnetium methoxyisobutylisonitrile scintimammography (SM) and combined use of mammography and ultrasound in the detection of the breast lesions in the symptomatic breast. Histopathological findings were the gold standard. Eighty patients with symptomatic breasts underwent mammography and/or ultrasound breast followed by SM. In 25 patients there were 27 lesions that were malignant and 55 patients had 65 lesions that were benign. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of SM were found to be 92, 72, 58, 96 and 78%, respectively, as compared with the combined use of mammography and ultrasound, which showed these parameters to be 89, 94, 86, 95 and 92%, respectively. In this study, SM showed slightly better sensitivity than combined mammography and ultrasound, whereas the specificity was clearly shown as higher in the latter.

Adult↗

Clindamycin-resistance in methicillin-resistant Staphylococcus aureus isolated from animals.

Clindamycin is widely used in veterinary medicine to treat a variety of bacterial infections. Resistance to clindamycin amongst staphylococci may be due to modification of the ribosomal target site. Resistance due to this mechanism is encoded by the erm genes, which may be either constitutively or inducibly expressed. Inducible expression of resistance is not usually demonstrable by routine laboratory susceptibility testing, however, a relatively simple double disc agar diffusion test (D-test) may be used to detect the presence of inducible resistance. Two hundred and eighty-five isolates of methicillin-resistant Staphylococcus aureus (MRSA) isolated from infections in animals were tested using the D-test for the presence of inducible clindamycin resistance. One hundred and seven (71%) of the strains tested demonstrated inducible resistance to clindamycin, which were not detected on initial susceptibility testing. It has been shown that there is potential for staphylococci to develop resistance to clindamycin whilst on treatment when inducible resistance mechanisms are present. Therefore, routine screening for inducible resistance may be prudent.

Animals↗

A new dominant distal myopathy affecting posterior leg and anterior upper limb muscles.

OBJECTIVE: To report a dominant, slowly progressive early onset distal myopathy with sparing of the tibialis anterior. METHODS: Twelve affected and two possibly affected members from an Australian kindred were examined and investigated by EMG, imaging studies, histopathology, and genetic analysis. RESULTS: Affected patients had a slowly progressive condition with symmetric, distal weakness and wasting of the anterior upper and posterior lower limbs, with sparing of tibialis anterior, even in advanced disease. All patients remained ambulant and there was no evidence of cardiac or respiratory muscle involvement. Serum creatine kinase levels were either normal or mildly elevated. Imaging studies showed widespread involvement of the posterior and lateral leg compartments. Proximal muscles were radiologically abnormal only in advanced disease. Muscles that were mildly affected clinically appeared normal on imaging. EMG in nine patients showed widespread myopathic changes. Muscle histopathology in four patients showed either end stage muscle or nonspecific myopathic findings without inflammation or vacuoles. Microsatellite markers for distal myopathy loci were analyzed and all known distal myopathy phenotype genes and linkage regions were formally excluded by multipoint analysis. CONCLUSIONS: The affected patients in this kindred display a clinically distinct myopathy, with selective involvement of posterior lower and anterior upper limb muscles. The genetic analysis suggests the existence of one more distal myopathy locus.

Adolescent↗

Hyperpolarization-activated current (Ih): a characterization of subicular neurons in brain slices from socially and individually housed rats.

The hyperpolarization and cyclic nucleotide activated current Ih is thought to have a role in rhythmic brain activity that is important in complex behaviors and might be perturbed in some neuropsychiatric diseases. We have used whole-cell voltage and current clamp techniques to characterize Ih in neurons from the subiculum-the major output region of the hippocampal formation. Subicular projection neurons are themselves classifiable as intrinsically bursting (IB) or regular spiking (RS) and Ih is present in both. Given the possible involvement of Ih in neuropsychiatric diseases, we have also characterized Ih in subicular neurons from rats that have been housed in individual cages (though still able to see, smell, and hear other rats) as these rats can display behavioral changes similar to those seen in schizophrenia. Individual housing is associated with a 4.4-mV depolarization of the Ih activation curve (P=0.0027) and an increase in mean firing rate measured in response to current injection (P=0.037) specifically in RS neurons and a change in the relative amplitude of Ih between IB and RS neurons. Thus, we have shown significant changes in a current thought to be relevant to psychiatric disease in a partial model of schizophrenia. Its further investigation might reveal chemical targets for novel antipsychotic drugs.

Action Potentials↗

Tumour necrosis factor inhibitors: risks and benefits in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis and can, if left untreated, result in significant disability and early death. It is also associated with large direct and indirect costs to the individual and to society. Early and aggressive disease modifying anti-rheumatic drug (DMARD) treatment of patients at risk of erosive disease has improved the outcome in the majority, but not all, RA patients. Tumour necrosis factor (TNF) appears to be a key mediator of the inflammatory and destructive process in RA, and consequently inhibitors of TNF action have been tested in randomized controlled trials in patients with RA. The results of these studies have suggested that TNF inhibitors are potent DMARD particularly when combined with methotrexate. They appear well tolerated with the commonest adverse events related to their parenteral route of administration, and the serious but rare side-effects being various infections, notably tuberculosis, multiple sclerosis, and worsening of cardiac failure. Treatment costs are high and range from $15 000 to $25 000 per patient per year. Etanercept, adalimumab and infliximab have recently been subsidised under the Pharmaceutical Benefits Scheme in Australia for patients with severe DMARD-resistant RA. The availability of TNF inhibitors in RA represents a significant advance in the treatment of patients with severe RA.

Antirheumatic Agents↗

Keeping clean water clean in a Malawi refugee camp: a randomized intervention trial.

OBJECTIVE: This study was undertaken to assess the ability of a water container with a cover and a spout to prevent household contamination of water in a Malawian refugee camp. METHODS: A randomized trial was conducted in a refugee population that had experienced repeated outbreaks of cholera and diarrhoea and where contamination of water in the home was found to be a significant cause of cholera. Four hundred Mozambican refugee households were systematically identified and followed over a 4-month period, one fourth of the households were randomly assigned to exclusively use the improved container for water collection. FINDINGS: Water flowing from the source wells had little or no microbial contamination although the water collectors quickly contaminated their water, primarily through contact with their hands. Analysis of water samples demonstrated that there was a 69% reduction in the geometric mean of faecal coliform levels in household water and 31% less diarrhoeal disease (P = 0.06) in children under 5 years of age among the group using the improved bucket. Regression models examining diarrhoea among under 5-year-olds confirmed the protective effect of the bucket and found that visible faeces in the family latrine and the presence of animals were significantly associated with an increased diarrhoeal incidence in children. CONCLUSION: Household contamination of drinking-water significantly contributed to diarrhoea in this population. Proper chlorination is a less expensive and more effective means of water quality protection in comparison with the improved bucket, but was unpopular and rarely utilized by the camp inhabitants.

Chlorine↗

Analysis of RPGR in a South African family with X-linked retinitis pigmentosa: research and diagnostic implications.

Analysis of exon ORF15 of the RPGR gene has revealed a novel mutation in a South African family with X-linked retinitis pigmentosa (XLRP), which has implications for the rest of the family in terms of pre-symptomatic testing. The ability to test for this mutation will be beneficial for the accurate determination of carrier status in female relatives who may have been unaware of their risk before this study was performed. This work also highlights the need to be aware of the ramifications of mutation testing in what may appear to be small families. This is the first report of an RPGR ORF15 mutation in a South African family of mixed ancestry.

Base Sequence↗

A rare homozygous rhodopsin splice-site mutation: the issue of when and whether to offer presymptomatic testing.

Having identified a disease-associated rhodopsin mutation in a patient with retinitis pigmentosa (RP), the issue is to address the question of whether to offer genetic testing to at-risk family members. Two members of a South African (SA) family, one of whom suffers from RP, as well as 54 unrelated SA RP patients from the same population group were investigated using single-stranded conformational polymorphism analysis followed by DNA sequencing. A rare homozygous mutation at the intron-exon boundary of exon 4 in the rhodopsin gene was identified in the proband. One of his siblings was found to be heterozygous for the same mutation. The mutation was not detected in the 54 unrelated SA RP patients examined, 11 of whom were sporadic cases. A low incidence of RP amongst heterozygous carriers of this mutation has been reported; however, in the past it has been unclear whether the mutation has an effect in single copy or dual copy. To the best of our knowledge, this is the first time that this mutation has been reported as homozygous in an affected individual, thereby resolving the issue and confirming that it is a recessive disease-associated mutation. This is also the first autosomal recessive RP disease-causing rhodopsin mutation that has been identified in Southern Africa. Analysis of the extended pedigree indicated obligate heterozygous carriers of the mutation, without obvious signs of visual impairment in early adulthood. The extent to which potential heterozygous carriers should be pursued and clinically examined is discussed and the question is addressed as to whether to inform the family of these molecular findings.

Aged↗

Uptake and effectiveness of the Australian telephone Quitline service in the context of a mass media campaign.

OBJECTIVES: Since June 1997, Australia has run its first nationally coordinated mass media anti-smoking campaign, with all States collaborating to offer a standard Quitline service. An overview of the Australian national Quitline service is presented as well as two studies describing (a) the relationship between television advertising and call volume and type, and (b) the quit rates of callers over time. DESIGN: Data on extent of advertising, as measured by weekly television target audience rating points (TARPs), is compared with weekly call volume and disposition. A randomly selected sample of callers was followed up at 3 weeks, 6 months and 12 months to assess caller appraisal and quit rates. SETTING: The Australian Quitline service, in the context of a nationally coordinated, major anti tobacco campaign. RESULTS: In a one year period from June 1997, 3.6% of adult Australian smokers called the Quitline. Weekly call volume was strongly related to TARPs and increased further when an advertisement specifically promoting the Quitline was broadcast. Calls involving requests for counselling, as opposed to brief calls to request quit materials, were more likely with lower TARPs. Of the cohort who were smoking at baseline, 28% reported they had quit smoking at a one year follow up and 5% had been quit for an entire year. CONCLUSIONS: In the context of a national mass media campaign, this study illustrates that it is possible to bring together differing State based services to provide an accessible, acceptable, and effective quit smoking service.

Adolescent↗

Growth inhibition of established B16-F10 lung metastases by sequential aerosol delivery of p53 gene and 9-nitrocamptothecin.

Growth inhibition of established tumor metastases in the lungs poses a difficult challenge for most clinical settings in spite of extensive multi-modality approaches. Aerosol delivery of drugs and genes holds promise for the treatment of disseminated lung metastases, since aerosol delivery can target the lungs specifically and uniformly. We previously demonstrated that aerosol delivery of dilauroylphosphatidylcholine liposome formulation of 9-nitrocamptothecin (9NC-DLPC) inhibits B16-F10 melanoma lung metastases. Aerosol delivery of polyethleneimine-p53 DNA (PEI-p53) complexes results in a similar anti-tumor effect in the B16-F10 model. In both these previous studies, the protocols were designed to inhibit development of lung metastases. In this study we demonstrate, using the B16-F10 melanoma lung metastasis model, that sequential aerosol delivery of PEI-p53 and 9NC-DLPC acts additively to inhibit growth of established B16-F10 tumor metastases in the lungs. Mice injected with B16-F10 cells and treated with a combination of 9NC-DLPC (twice weekly) and PEI-p53 (once weekly) aerosol complexes starting on day 11 after tumor inoculation, exhibited a highly significant (P < 0.01) reduction in the number of visible tumor foci as compared with untreated mice or mice treated with either single agent alone, or with a combination of 9NC and a control plasmid. There was a highly significant reduction in the tumor burden, as well as the lung weights for the 9NC and p53 combination group (P < 0.001 as compared with other groups). Moreover, the doses of p53 gene and 9NC in the combination group were reduced at least two-fold as compared with our previous single agent studies, but still achieved significant tumor inhibition. Furthermore, the sequential aerosol delivery of p53 and 9NC lead to a 30-40% increase in the mean survival time of these mice, as compared with animals in different control groups. The data suggest that the combination of 9NC and p53 gene delivered by aerosol is an attractive strategy for growth inhibition of established tumor metastases in the lungs.

Aerosols↗

Should we give detailed advice and information booklets to patients with back pain? A randomized controlled factorial trial of a self-management booklet and doctor advice to take exercise for back pain.

STUDY DESIGN: Randomized controlled factorial trial. OBJECTIVE: To assess the effectiveness of a booklet and of physician advice to take regular exercise. SUMMARY OF BACKGROUND DATA: Educational booklets are one of the simplest interventions for back pain but have not been shown to alter pain and function. Although there is evidence that advice to mobilize is effective, doctors have also been advised to encourage regular exercise-but there is no evidence that such advice alone improves outcomes. METHOD: Eight doctors from six practices randomized 311 patients with a new episode of back pain using sealed numbered opaque envelopes to receive a detailed self-management booklet, advice to take regular exercise, both, or neither. All groups were advised to mobilize and to use simple analgesia. Patients were telephoned during the first week after entry into the study, and after 3 weeks to assess a validated numerical pain/function score (0 = no pain normal activities to 100 = extreme pain no normal activities). Patients also returned a postal questionnaire in the first week with the Aberdeen pain and function scale, a knowledge score, and a reliable satisfaction scale (mean score of 4 items: 0 = not satisfied to 100 = extremely satisfied). RESULTS: Pain/function scores were obtained in 239 (77%) patients. There were interactions between exercise and booklet groups for both pain/function scores and the Aberdeen scale, which are unlikely to have been chance findings (P = 0.009 and P = 0.012, respectively). In comparison with the control group, there were reductions in the pain/function score in the first week with a booklet (-8.7, 95% CI -17.4 to -0.03) or advice to exercise (-7.9; -16.7 to 0.8) but much less effect with both together (-0.08, -9.0 to 8.9). Similarly, the Aberdeen scale was lower in the booklet group (-3.8, -7.7 to 0.07) and in the exercise advice group (-5.3; -9.3 to -1.38) but much less with both combined (-1.9, -5.8 to 2.1). There was no significant difference between groups in pain/function scores by week 3, when 58% reported being back to normal. Satisfaction was increased in booklet (7.9, 1.3 to 14.4) and exercise groups (7.4, 0.8 to 13.9)), and a booklet also increased knowledge (Kruskal-Wallis chi2 27.2, P = 0.001). CONCLUSION: Doctors can increase satisfaction and moderately improve functional outcomes in the period immediately after the consultation when back pain is worst, by using very simple interventions: either by endorsing a self-management booklet or by giving advice to take exercise. Previous studies suggest that simple advice and the same written information provide reinforcement. This study supports evidence that it may not be helpful to provide a detailed information booklet and advice together, where the amounts or formats of information differ.

Activities of Daily Living↗