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Biomedical subjects

J Bradley

Publications and source records attributed to J Bradley.

At least 19 recordsLinked to original sources
PubMed2006

Challenges in implementing a cervical screening program in South Africa.

BACKGROUND: The Cervical Health Implementation Project was initiated with the aim of developing and evaluating health system interventions for improving public sector cervical screening services. The project was conducted between January 2001 and May 2003 in three districts in South Africa. This paper describes the districts, interventions and their evaluation, and discusses the implications of these findings for the roll out of a national cervical screening program. METHODS: A pretest/post-test study design was employed. The following interventions were developed and implemented: health worker training workshops, health system tools and protocols and a community awareness program. Pre- and post-intervention facility audits, key informant interviews, staff knowledge, attitude and practice (KAP) surveys and client KAP surveys were conducted. Clinic records and cytology laboratory data were reviewed. RESULTS: Service organization, availability of screening equipment and education and communication materials improved. The proportion of staff who knew the screening policy increased from 43% to 82%; and 68% of staff agreed with the screening policy after, as opposed to 23% before the intervention. In two of the districts, cytology turnaround times continued to be long. Only 50% of women with a high-grade squamous intraepithelial lesion had a colposcopy and biopsy within 6 months of a Pap smear. Although the number of new smears performed in the three districts increased from 1544 in 2001 to 2801 in 2002, overall the coverage remained less than 4%. CONCLUSION: This project highlights the considerable challenges that need to be addressed to effectively implement the national screening policy.

Adult↗
PubMed2005

Delivering cervical cancer prevention services in low-resource settings.

The goals of any cervical cancer prevention program should be threefold: to achieve high coverage of the population at risk, to screen women with an accurate test as part of high-quality services, and to ensure that women with positive test results are properly managed. This article focuses on the experiences of the Alliance for Cervical Cancer Prevention (ACCP) in delivery of screening and treatment services as part of cervical cancer prevention projects in Africa, Latin America, and Asia. Research and experience show that cervical cancer can be prevented when strategies and services are well planned and well managed and when attention is paid to program monitoring and evaluation. Coordination of program components, reduction of the number of visits, improvement of service quality, and flexibility in how services are delivered are all essential features of an effective service.

Africa↗
PubMed2005

Involving the community in cervical cancer prevention programs.

Underutilization of cervical cancer prevention services by women in the high-risk age group of 30-60 years can be attributed to health service factors (such as poor availability, poor accessibility, and poor quality of care provided), to women's lack of information, and to cultural and behavioral barriers. The Alliance for Cervical Cancer Prevention (ACCP) partners have been working to identify effective ways to increase women's voluntary participation in prevention programs by testing strategies of community involvement in developing countries. The ACCP experiences include developing community partnerships to listen to and learn from the community, thereby enhancing appropriateness of services; developing culturally appropriate messages and educational materials; making access to high-quality screening services easier; and identifying effective ways to encourage women and their partners to complete diagnosis and treatment regimens. Cervical cancer prevention programs that use these strategies are more likely to increase demand, ensure follow-through for treatment, and ultimately reduce disease burden.

Ambulatory Care↗
PubMed2005

Regional differences in the provision of adult renal dialysis services in the UK.

BACKGROUND: Provision of renal dialysis varies between UK regions. AIM: To analyse these differences in provision and investigate their causes. DESIGN: Questionnaire-based survey. METHODS: A questionnaire was posted to all renal provider units and renal commissioning groups in the UK. Questions covered issues such as dialysis modalities and patient choice. Data were collected by telephone interview (or post in some cases) and analysed using SPSS. RESULTS: All renal provider units in the UK responded. A full range of modalities was provided by the majority of units. Clear variations in the level and quality of dialysis provision were seen between the UK regions. These included variation in choice of dialysis modality, provision of high-cost drugs, vascular access waiting times, number of support staff and availability of spare dialysis slots. DISCUSSION: The considerable variation between UK regions in the provision of adult renal dialysis services cannot be entirely explained by age or ethnic variation, and is in part due to limited bed space, dialysis machines and support staff, as well as changes in commissioning arrangements. To meet the requirements of the renal national service framework in most regions, changes to policy and funding will be required, such that the relatively new commissioning groups implement more appropriate funding structures in closer dialogue with their provider units.

Adult↗
PubMed2004

Onchocerca ochengi acquisition in zebu Gudali cattle exposed to natural transmission: parasite population dynamics and IgG antibody subclass responses to Ov10/Ov11 recombinant antigens.

Ngaoundere Gudali zebu cattle naturally exposed to Simulium damnosum s.l. and Culicoides spp. bites were examined during 4 years for O. ochengi adult worm acquisition, Onchocerca ochengi and Onchocerca gutturosa skin microfilaria dynamics, and IgG1 and IgG2 antibody subclass responses. Eleven animals acquired a total of 465 O. ochengi nodules (average of 17 per female and 72 per male). The O. ochengi nodule load was highly variable in individual animals and exacerbated in mature male cattle. Three patterns of acquisition of O. ochengi (resistant to new infestation, early susceptibility and late susceptibility), not associated with Simulium biting intensity (P > 0.05), were distinguished. The minimum prepatent periods for O. ochengi nodules, O. ochengi microfilariae and O. gutturosa microfilariae were 10, 20 and 21 months, respectively. The O. ochengi microfilaria density significantly (P < 0.001) increased with age, was higher in young mature bulls than female animals (P < 0.001) and finally reached highest levels (P < 0.005) during the dry season. Antibody responses to Ov10/Ov11 recombinant O. volvulus antigens were predominantly of the IgG1 subclass. High levels of this subclass (not IgG2) observed in new born calves declined to almost zero levels at the age of 5-8 months but IgG1 levels significantly increased (P < 0.05) with age subsequently during patency. Put together the acquisition and accumulation of O. ochengi parasites in zebu cattle, apart from being season, sex (gender) and host age associated, may also suggest a density-dependent regulation of parasite establishment in a proportion of the exposed population.

Age Factors↗
PubMed2004

Media interventions to increase cervical screening uptake in South Africa: an evaluation study of effectiveness.

Successful cervical cancer prevention depends on reaching, screening and treating women with pre-invasive disease. We aimed to evaluate the effectiveness of two media interventions-a photo-comic and a radio-drama-in increasing cervical screening uptake. A randomized controlled trial compared a photo-comic on cervical cancer screening with a placebo comic. One month after the comics were distributed a radio-drama paralleling the photo-comic was broadcast on the community radio station and a retrospective evaluation was carried out. The trial was set in Khayelitsha, a peri-urban squatter community near Cape Town, South Africa. A random sample consisted of 658 women between the ages of 35 and 65 years, from a stratified sample of census areas. The main outcome measure was self-reported cervical screening uptake 6 months after distribution of the comics. Seven percent (18 of 269) of women who received the intervention photo-comic reported cervical screening during the 6 months follow-up, compared with 6% (25 of 389) of controls (P = 0.89). Women who recalled hearing the radio-drama were more likely to report attending screening (nine of 53, 17%) than those who did not (19 of 429, 4%; P < 0.001). We conclude that the photo-comic was ineffective in increasing cervical screening uptake in this population. The radio-drama may have had more impact, but only a minority of women recalled being exposed to it. Future research must concentrate not only on achieving high level of exposure to health messages, but also on investigating the links between exposure and action.

Adult↗
PubMed2004

An enema formulation of alicaforsen, an antisense inhibitor of intercellular adhesion molecule-1, in the treatment of chronic, unremitting pouchitis.

BACKGROUND: Pouchitis is the major long-term complication of ileal pouch-anal anastomosis for ulcerative colitis. The incidence of pouchitis is as high as 50% several years after surgery. Two-thirds of pouchitis patients suffer recurrence. Of those who recur, one-quarter suffer from chronic, unremitting pouchitis. Current treatments for this disorder are disappointing. AIM: To determine whether a topically administered enema formulation of ISIS 2302 (alicaforsen), an antisense inhibitor of intercellular adhesion molecule-1, can improve the clinical symptoms, endoscopic mucosal appearance and mucosal histology in patients with chronic, unremitting pouchitis, a disorder in which this molecule is over-expressed. METHODS: In an open-label, uncontrolled study, 12 patients with chronic, unremitting pouchitis were treated with 240 mg alicaforsen antisense enema nightly for 6 weeks. Clinical evaluation and endoscopy were performed at baseline and at weeks 3, 6 and 10. Pouchoscopy with biopsy was carried out at baseline and at weeks 6 and 10. The primary end-point was the reduction from baseline of the Pouchitis Disease Activity Index (PDAI) at week 6. Secondary end-points included the PDAI at week 10. Safety was evaluated by analysing the adverse events, vital signs and laboratory parameters. RESULTS: After 6 weeks of nightly alicaforsen enema, a statistically significant (n = 12, P = 0.001) reduction in the PDAI from baseline (11.42) to week 6 (6.83) was observed. Mean reductions in the endoscopy sub-score from baseline (5.25) to week 3 (3.08) and week 6 (2.58) were statistically significant (P = 0.0039 and P = 0.0005, respectively). The mean reductions in clinical symptom sub-score from baseline (3.75) to week 3 (2.33) and week 6 (2.25) were also statistically significant (P = 0.0156 and P = 0.0117, respectively). Ten of the 12 patients achieved a mucosal appearance score of 0 or 1 at endoscopy. Five of the 12 patients (42%) had a non-statistically significant decrease in the histology component of their PDAI from baseline to week 6. By week 6, seven of the 12 patients (58%) were in remission, as defined by PDAI < 7, with a mean decrease from baseline in PDAI score of six points. The alicaforsen enemas were well tolerated and no serious side-effects were noted. CONCLUSIONS: Antisense enema to intercellular adhesion molecule-1 is safe and well tolerated. In an open-label trial, it appeared to improve the PDAI score, clinical symptoms and endoscopic mucosal appearance. It may also improve the histology. In the light of the responses observed in this trial, a randomized, placebo-controlled trial is warranted.

Administration, Rectal↗
PubMed2003

Non-invasive ventilation for cystic fibrosis.

BACKGROUND: The use of non-invasive ventilation (NIV) has been proposed as a means to temporarily reverse or slow the progression of worsening respiratory failure in cystic fibrosis (CF). OBJECTIVES: To compare the effect of NIV versus no NIV in people with CF. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings. The reference lists of each trial were searched for additional publications that may contain other trials. Date of most recent search: January 2002. SELECTION CRITERIA: Relevant randomised controlled trials in which a form of pressure preset or volume preset NIV versus no NIV was used in people with acute or chronic respiratory failure in CF. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for inclusion criteria, methodological quality and data extraction. MAIN RESULTS: Six trials were identified and four trials met the inclusion criteria with a total of 55 participants. All of these trials only evaluated single treatment sessions. Two trials (36 participants) evaluated the use of NIV for airway clearance compared with an alternative physiotherapy method. These trials showed that airway clearance may be easier and people with CF may prefer to use NIV for airway clearance. There was no evidence that NIV increases sputum expectoration or improves lung function. Two trials (19 participants) evaluated the use of NIV for overnight ventilatory support. Of the primary outcomes examined in this review, only lung function was evaluated within the two trials. Due to the small numbers of participants and the differing statistical techniques used within the review and the primary trials, there were discrepancies in the results obtained by the RevMan analysis and the original trial analysis. No clear differences were found between NIV compared with either oxygen or room air. REVIEWER'S CONCLUSIONS: Non-invasive ventilation may be a useful adjunct to other airway clearance techniques, particularly in people with CF who have difficulty expectorating sputum. Non-invasive ventilation when used in addition to oxygen may improve gas exchange during sleep to a greater extent than oxygen therapy alone in moderate to severe disease. These benefits of NIV have only been demonstrated in single treatment sessions and its efficacy, safety and acceptability in the longer term are unknown. There is a need for long-term randomised controlled trials to determine the clinical effects of non-invasive ventilation in CF.

Cystic Fibrosis↗
PubMed2002

Physical training for bronchiectasis.

BACKGROUND: The pathophysiology of bronchiectasis may result in the development of dyspnoea and decreased exercise tolerance, both of which can impact on a patient's quality of life and ability to perform activities of daily living. There is little information regarding the benefits of physical training in bronchiectasis: however it is probable that the benefits of physical training in bronchiectasis are at least comparable to benefits demonstrated in other respiratory conditions. There is also no information regarding the effects of non-adherence to prescribed physical training in bronchiectasis. However as in patients with COPD non-adherence may contribute to a deterioration in the patient's condition and conceivably the long term prognosis. OBJECTIVES: The objective of this review is to determine whether a prescribed regime of physical training produces improvements or prevents deterioration in physiological and clinical outcomes in bronchiectasis compared to no physical training. SEARCH STRATEGY: We searched the Cochrane Airways Group specialised register and the Cochrane Controlled Clinical Trials Register. SELECTION CRITERIA: Randomised or quasi randomised controlled trials in which a prescribed regime of physical training are compared to no physical training in patients with bronchiectasis. DATA COLLECTION AND ANALYSIS: Three studies were identified. One was did not meet the inclusion criteria and two appeared in abstract form only. More comprehensive data will be incorporated into this review once data from those two trials are published, and when further data is made available to the authors of this review. MAIN RESULTS: Results from the two studies published in abstract showed that inspiratory muscle training compared to sham or no inspiratory muscle training improved endurance exercise capacity: Weighted Mean Difference (WMD) 264 metres (95% CI 16.4 to 512 metres). PiMax improved: WMD 25 cms H20 (95% CI 11.6 to 38.4 cms H2O )as did quality of life measured with the CRQ: WMD 12.4 units (95% CI 2.4 to 22.5 units). REVIEWER'S CONCLUSIONS: This review only provides evidence of the benefits of inspiratory muscle training and provides no evidence of the effect of other types of physical training (including pulmonary rehabilitation) in bronchiectasis.

Bronchiectasis↗
PubMed2002

Physical training for cystic fibrosis.

BACKGROUND: Physical training may form an important part of the care package for patients with cystic fibrosis. OBJECTIVES: To determine whether a prescribed regime of physical training produces improvement or prevents deterioration in physiological and clinical outcomes in cystic fibrosis compared to no training. SEARCH STRATEGY: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings. Date of the most recent search: August 2001. SELECTION CRITERIA: All randomised controlled clinical trials in which a prescribed regime of physical training is compared to no physical training in patients with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed methodological quality and extracted data. MAIN RESULTS: Of the sixteen trials identified six trials, which included 184 patients, met the inclusion criteria. Exercise tolerance in the short term, during an acute admission was improved in patients who received physical training. In a three year study there was no improvement in exercise tolerance at the end of the study period. Over three years there was a significantly greater mean annual rate of decline in FVC in the control group compared to the exercise group WMD 2.17 (95%CI 0.47, 3.87). Changes in other lung function parameters showed a similar trend, but these were not statistically significant. REVIEWER'S CONCLUSIONS: Conclusions about the efficacy of physical training in cystic fibrosis are limited by the small size, short duration and incomplete reporting of most of the trials included in this review. Physical training is already part of the care package offered to most patients with cystic fibrosis and there is no evidence to actively discourage this. Further research is needed to assess comprehensively the net benefit of the addition of physical training to the care of cystic fibrosis patients.

Cystic Fibrosis↗
PubMed2002

Cochlear implants in children with craniofacial syndromes: assessment and outcomes.

The aim of this retrospective study was to review the outcomes for children with craniofacial syndromes who had received a cochlear implant. The group comprised four children (three girls, one boy) aged between 3.3 and 10.1 years (mean 6.3 years) at time of implantation with the Cochlear CI-22M device. Two children had the CHARGE association. one had Goldenhar's syndrome and one had brachio-oculo-facial syndrome. All had full electrode insertion at time of surgery. At follow-up, three of the children demonstrated benefit in detection, recognition and identification of environmental sounds, and they continued to gain receptive spoken language skills, although none had intelligible speech. The group required careful mapping and higher levels of electrical stimulation of the implant compared to normal child implantees. Stimulation of the facial nerve was a problem with one child. The pre-implantation assessment of these children requires extensive interdisciplinary discussion and careful radiological investigation. Cases should be carefully selected. Parents should receive realistic counselling about outcomes and the time commitment necessary, as habilitation of these children can take twice as long as that of children without additional special needs. Post-implantation, these children continue to require well-coordinated medical and interdisciplinary management.

Auditory Threshold↗
PubMed2001

Facilitation of calmodulin-mediated odor adaptation by cAMP-gated channel subunits.

Calcium (Ca2+) influx through Ca2+-permeable ion channels plays a pivotal role in a variety of neuronal signaling processes, and negative-feedback control of this influx by Ca2+ itself is often equally important for modulation of such signaling. Negative modulation by Ca2+ through calmodulin (CaM) on cyclic nucleotide-gated (CNG) channels underlies the adaptation of olfactory receptor neurons to odorants. We show that this feedback requires two additional subunits of the native olfactory channel, CNGA4 and CNGB1b, even though the machinery for CaM binding and modulation is present in the principal subunit CNGA2. This provides a rationale for the presence of three distinct subunits in the native olfactory channel and underscores the subtle link between the molecular make-up of an ion channel and the physiological function it subserves.

Adaptation, Physiological↗
PubMed2001

Modulation of human T cell responses and macrophage functions by onchocystatin, a secreted protein of the filarial nematode Onchocerca volvulus.

Immune responses of individuals infected with filarial nematodes are characterized by a marked cellular hyporesponsiveness and a shift of the cytokine balance toward a Th2/Th3 response. This modulation of cellular immune responses is considered as an important mechanism to avoid inflammatory immune responses that could eliminate the parasites. We investigated the immunomodulatory potential of a secreted cysteine protease inhibitor (onchocystatin) of the human pathogenic filaria Onchocerca volvulus. Recombinant onchocystatin (rOv17), a biologically active cysteine protease inhibitor that inhibited among others the human cysteine proteases cathepsins L and S, suppressed the polyclonally stimulated and the Ag-driven proliferation of human PBMC. Stimulated as well as unstimulated PBMC in the presence of rOv17 produced significantly more IL-10, which was paralleled in some situations by a decrease of IL-12p40 and preceded by an increase of TNF-alpha. At the same time, rOv17 reduced the expression of HLA-DR proteins and of the costimulatory molecule CD86 on human monocytes. Neutralization of IL-10 by specific Abs restored the expression of HLA-DR and CD86, whereas the proliferative block remained unaffected. Depletion of monocytes from the PBMC reversed the rOv17-induced cellular hyporeactivity, indicating monocytes to be the target cells of immunomodulation. Therefore, onchocystatin has the potential to contribute to a state of cellular hyporesponsiveness and is a possible pathogenicity factor essential for the persistence of O. volvulus within its human host.

Animals↗
PubMed2001

Polyglutamine expansions cause decreased CRE-mediated transcription and early gene expression changes prior to cell death in an inducible cell model of Huntington's disease.

Huntington's disease (HD) is one of 10 known diseases caused by a (CAG)(n) trinucleotide repeat expansion that is translated into an abnormally long polyglutamine tract. We have developed stable inducible neuronal (PC12) cell lines that express huntingtin exon 1 with varying CAG repeat lengths under doxycycline (dox) control. The expression of expanded repeats is associated with aggregate formation, caspase-dependent cell death and decreased neurite outgrowth. Post-mitotic cells expressing mutant alleles were more prone to cell death compared with identical cycling cells. To determine early metabolic changes induced by this mutation in cell models, we studied changes in gene expression after 18 h dox induction, using Affymetrix arrays, cDNA filters and adapter-tagged competitive PCR (ATAC-PCR). At this time point there were low rates of inclusion formation, no evidence of mitochondrial compromise and no excess cell death in the lines expressing expanded compared with wild-type repeats. The expression profiles suggest novel targets for the HD mutation and were compatible with impaired cAMP response element (CRE)-mediated transcription, which we confirmed using CRE-luciferase reporter assays. Reduced CRE-mediated transcription may contribute to the loss of neurite outgrowth and cell death in polyglutamine diseases, as these phenotypes were partially rescued by treating cells with cAMP or forskolin.

Animals↗
PubMed2001

Preliminary results of a liver allocation plan using a continuous medical severity score that de-emphasizes waiting time.

Liver allocation remains problematic because current policy prioritizes status 2B or 3 patients by waiting time rather than medical urgency. On February 21, 2000, we implemented a variance to the United Network for Organ Sharing liver allocation policy that redefined status 2A by much more rigid, definable criteria and prioritized status 2B patients by using a continuous medical urgency score based on the Child-Turcotte-Pugh score and other medical conditions. In this system, waiting time is used only to differentiate status 2B candidates with equal medical urgency scores. Comparing the 6-month period (period 1; n = 67) before implementation of this system to the 6-month period after implementation (period 2; n = 75), there was a significant reduction in the number of transplantations performed for patients listed as status 2A (46.3% to 14.7%; P =.002) and an increase in the number of patients listed as status 2B who received transplants (44.8% to 70.7%; P =.10). Most dramatically, there was a 37.1% reduction in overall deaths on the waiting list from 94 deaths in period 1 to 62 deaths in period 2 (P =.005), with the most significant reduction for patients removed from this list at status 2B (52 v 18 patients; P =.04). There were 3 postoperative deaths in each period, with only 1 graft lost in period 2. Status 2B patients with the greatest degree of medical urgency received transplants without multiple peer reviews requesting elevation to 2A status. We conclude that a continuous medical urgency score system allocates donor livers much more fairly to those in medical need and reduces waiting list mortality without sacrificing efficacy.

Health Care Rationing↗
PubMed2001

A study of the application of a frequency transposition hearing system in children.

The aim of this retrospective study was to investigate the use of the frequency transposition Transonic FT 40 system in a group of 36 children with profound sensorineural hearing loss. The group comprised 36 children (11 boys, 25 girls) aged between 2.8 and 15.6 years (mean 7.6 years) at fitting of the FT 40 device. At 48 months post-FT 40 fitting, only 11 children (30%) were still wearing the device. The children discontinued wearing the FT 40 for the following reasons: ergonomic (11%); no perceived benefit from the system (11%); cosmetic (17%); and subsequent cochlear implantation (30%). The performance of the long-term FT 40 users was investigated using the following outcome measures: aided soundfield hearing thresholds: closed set speech tests (the E2L toy test and the Manchester Picture Test discrimination test) and a speech intelligibility rating score. The 11 long-term FT 40 users (three boys, eight girls) were aged from 5.3 to 12.9 years (mean 7.2 years) at the time of initial fitting of the FT 40 device. At time of fitting, the aided soundfield thresholds with the FT 40 were significantly better at 500 Hz (p<0.04), 1 kHz (p<0.019), 2 kHz (p<0.001) and 4 kHz (p <0.001) compared to thresholds with conventional hearing aids. Six of 11 children did not show any change in performance on the closed set speech tests and two children had intelligible speech at 48 months' follow-up. A small subgroup of good performers was identified. These children were younger at age of fitting (mean 6.2 years compared to a mean of 7.7 years for the remainder of the group), were predominantly oral communicators and had identified aetiologies for their deafness. The present study suggests that there is a small subgroup of hearing-impaired children who benefit from frequency transposition hearing systems, and future suggested fitting criteria and outcome measures are listed.

Acoustic Stimulation↗