Osteomyelitis of the humerus complicating BCG vaccination.
Explore the source record for details and available documents.
BCG Vaccine↗
Biomedical subjects
C Watts
Publications and source records attributed to C Watts.
Modelling the cost effectiveness of rapid point of care diagnostic tests for the control of HIV and other sexually transmitted infections among female sex workers.
BACKGROUND: In sub-Saharan Africa, gonococcal and chlamydial infections are usually managed using the syndromic approach. However, many infections are asymptomatic in women, and the syndromic algorithm has poor sensitivity and specificity for infections caused by Neisseria gonorrhoeae (Ng) and Chlamydia trachomatis (Ct). Because of this, rapid point of care (POC) tests for Ct/Ng could improve sexually transmitted infection (STI) management in women. This study uses mathematical modelling to estimate the incremental cost effectiveness of using POC tests to diagnose Ng/Ct instead of the current syndromic approach used by the SIDA2 HIV/STI prevention project for female sex workers in Cotonou, Benin. METHODS: A dynamic mathematical model was used with data from Cotonou to estimate the HIV impact of the existing SIDA2 project (1995-8), and to project how impact would change if POC tests had been used. As observed in test evaluations, the POC tests were assumed to have high specificity, but a range of sensitivities. The incremental economic cost effectiveness of using POC tests was modelled using data on intervention costs and an evaluation of an Ng POC test in Cotonou in 2004. All costs were in 2004 US dollars. RESULTS: The model estimated the STI treatment aspect of the intervention averted 18 553 Ng/Ct and 359 HIV infections over 4 years when the syndromic approach was used. In contrast, if Ng/Ct had been diagnosed with a 70-80% sensitive and 95% specific POC test then 24-31% fewer clinic attenders would have been treated, 40-60% more Ng/Ct and HIV infections would have been averted, and the incremental cost effectiveness of using them would have been 107-151 dollars per HIV infection averted if the POC tests cost 2 dollars and 58-81 dollars if they cost 1 dollar. CONCLUSIONS: POC tests can be a cost effective strategy for substantially increasing the impact on HIV transmission, and decreasing the degree of inappropriate treatment of STI treatment interventions that use syndromic management to diagnose Ng/Ct.
Benin↗
What is the achievable effectiveness of the India AIDS Initiative intervention among female sex workers under target coverage? Model projections from southern India.
BACKGROUND: The India AIDS Initiative (Avahan) prevention programme funded by the Bill and Melinda Gates Foundation aims to reduce HIV prevalence in high risk groups such as female and male sex workers and their clients, to limit HIV transmission in the general population. OBJECTIVES: To assess the potential effectiveness of the Avahan intervention at the level of coverage targeted, in different epidemiological settings in India. METHODS: A deterministic compartmental model of the transmission dynamics of HIV and two sexually transmitted infections, and sensitivity analysis techniques, were used, in combination with available behavioural and epidemiological data from Mysore and Bagalkot districts in the Indian state of Karnataka, to evaluate the syndromic sexually transmitted infection (STI) management (STI treatment), periodic presumptive treatment of STI (PPT), and condom components of the Avahan intervention targeted to female sex workers (FSW). RESULTS: If all components of the intervention reach target coverage (that is, PPT, STI treatment and condom use), the intervention is expected to prevent 22-35% of all new HIV infections in FSW and in the total population over 5 years in a low transmission setting like Mysore, and to be half as effective in high transmission settings such as Bagalkot. The results were sensitive to small variations in intervention coverage. The condom component alone is expected to prevent around 20% of all new HIV infections over 5 years in Mysore and around 6% for the STI component alone; compared with 7%-14% for the PPT component alone. Multivariate sensitivity analyses suggested that interventions may be more effective in settings with low FSW HIV prevalence and small FSW populations, whereas HIV prevalence was most influenced by sexual behaviour and condom use parameters for FSW. CONCLUSION: The Avahan intervention is expected to be effective. However, to be able to demonstrate effectiveness empirically in the different settings, it is important to achieve target coverage or higher, which in the case of PPT could take a number of years to achieve. These preliminary model predictions need to be validated with more detailed mathematical models, as better data on sexual behaviour, condom use, STI and HIV trends over time, and intervention coverage data accumulate over the course of the programme.
Acquired Immunodeficiency Syndrome↗
Modelling the cost-effectiveness of introducing rapid syphilis tests into an antenatal syphilis screening programme in Mwanza, Tanzania.
OBJECTIVES: A study found screening (with rapid plasma reagin (RPR)) pregnant women for maternal syphilis was cost-effective in Mwanza, Tanzania. Recently, four rapid point-of-care (POC) syphilis tests were evaluated in Mwanza, and found to have reasonable sensitivity/specificity. This analysis estimates the relative cost-effectiveness of using these POC tests in the Mwanza syphilis screening intervention. METHODS: Empirical cost and epidemiological data were used to model the potential benefit of using POC tests instead of RPR. Reductions in costs relating to training, supplies, and equipment were estimated, and any changes in impact due to test sensitivity were included. Additional modelling explored how the results vary with prevalence of past infection, misclassified RPR results, and if not all women return for treatment. RESULTS: The cost-effectiveness of using POC tests is mainly dependent on their cost and sensitivity for high titre active syphilis (HTAS). Savings due to reductions in training and equipment are small. Current POC tests may save more disability-adjusted life years (DALYs) than the RPR test in Mwanza, but the test cost needs to be <0.63 US dollars to be as cost-effective as RPR. However, the cost-effectiveness of the RPR test worsens by 15% if its HTAS sensitivity had been 75% instead of 86%, and by 25-65% if 20-40% of women had not returned for treatment. In such settings, POC tests could improve cost-effectiveness. Lastly, the cost-effectiveness of POC tests is affected little by the prevalence of syphilis, false RPR-positives, and past infections. DISCUSSION: Although the price of most POC tests needs to be reduced to make them as cost-effective as RPR, their simplicity and limited requirements for electricity/equipment suggest their use could improve the coverage of antenatal syphilis screening in developing countries.
Cost-Benefit Analysis↗
Validity and responsiveness of the patient evaluation measure as an outcome measure for carpal tunnel syndrome.
The aim of this study was to assess the validity of the Patient Evaluation Measure questionnaire (PEM) as an outcome measure in carpal tunnel syndrome. The PEM was compared to the DASH questionnaire and to objective measurements of hand function. We also compared its responsiveness to changes following carpal tunnel release with that of the DASH score. Twenty-four patients completed the PEM and DASH questionnaires before and 3 months after open carpal tunnel release. Grip strength, static two-point discrimination and the nine-hole peg test were measured. There was a significant correlation between individual items of the PEM and the objective measures. There was also strong correlation between PEM and DASH scores. The PEM showed a greater responsiveness to change (effect size 0.97) than the DASH score (effect size 0.49). The PEM correlates well with objective measures of hand function and the DASH score when used in carpal tunnel syndrome. It is more responsive to change than the DASH score. It is very simple to complete and score and is an appropriate and practical outcome measure in carpal tunnel syndrome.
Adult↗
Anatomical perspectives on adult neural stem cells.
The concept of stem cells within the adult brain is not new. However, only recently have scientific techniques become sufficiently advanced to identify them although this remains problematic and the technology is still developing. Nevertheless, it is now generally recognized that stem cells are restricted to two germinal regions within the intact brain. From here they can migrate to specific destinations where they integrate with existing circuitry. Their identity remains controversial but a growing body of evidence suggests it may have an astrocytic phenotype. Within the germinal regions the stem cells are confined to a niche environment and are capable of responding to environmental signals generated locally in an autocrine or paracrine fashion. The niche environment is also modulated by more generalized systemic and physiological activity. These observations are exciting in their own right and form the basis of this review. They are also beginning to alter how we think about neural injury and disease and to impact on the development of novel therapies.
Adult↗
Patients treated by dental students in outreach: the first year of a pilot project.
This paper describes the patients treated by 4th year undergraduate students during the first year of a pilot outreach course to teach Restorative Dentistry in community clinics in 2001-02. Data were collected from 908 summaries of patient treatment completed by the students, and from 139 patient questionnaires. Some 75% of patients were aged between 16 and 64, 58% were female, and 16% had dental phobia or anxiety. Most lived locally to the clinic and 41% made their initial contact as an emergency or drop-in. Some 37% made only a single visit (including children treated as emergencies) but 22% made six or more visits. Did not attend (DNA) was a problem and 18% of patients DNA to complete their treatment. Students undertook the full range of restorative procedures, with the emphasis on direct restorations, preventive treatment and advice, scaling, extractions and emergency treatment. Patients' main reasons for attending the clinic were lay recommendation, the need for treatment, convenience, free treatment, or the lack of access to a dentist. Some 30% said they did not have or did not know of an alternative source of dental care, and half had not seen a dentist for at least 2 years. The study demonstrates that despite difficulties related to attendance, a suitable patient base can be established offering students the opportunity to provide comprehensive care for adults in a primary care setting.
Adolescent↗
Elevated levels of some neuroactive progesterone metabolites, particularly isopregnanolone, in women with chronic fatigue syndrome.
Chronic fatigue syndrome (CFS) is a controversial entity whose cause is unknown. In this study we have explored the possibility that progesterone metabolites may be involved. Plasma levels of the progesterone precursor pregnenolone, progesterone itself, and five ring A-reduced metabolites of progesterone were measured in 20 women with CFS and in 13 age-matched controls. To minimize the contribution of the ovary, women were either post-menopausal or in the follicular phase of the menstrual cycle (day 4-8), and progesterone levels were all well within the expected range (< or = 3.5 nmol/l). Mean values for progesterone and all of its metabolites were higher in CFS patients, the most marked being a 2.3-fold elevation in isopregnanolone (3beta,5alpha-tetrahydroprogesterone; p < or = 0.001). Progesterone levels were correlated with those of its metabolites, but even after controlling for progesterone by ANCOVA, isopregnanolone levels were still elevated (p < or = 0.001). These elevated levels of isopregnanolone could not be attributed to medications (antidepressants and anxiolytics). When the CFS patients were divided into two groups according to their Hamilton depression scale ratings, mean (+/-SD) isopregnanolone levels were higher (274+/-160 vs 197+/-119 pmol/l) in the less depressed group (ratings 2-14) than in the more depressed group (ratings 17-28), although this difference did not reach significance. Progesterone levels were negatively correlated with Hamilton depression rating scores (r=-0.56; p<0.01). These results suggest that increases in ring A-reduced progesterone metabolites, particularly isopregnanolone, are associated with CFS, and that the pathophysiology of CFS is unlikely to be due to depression.
Adult↗
Short-term repeatability of a food frequency questionnaire in New Zealand children aged 1-14 y.
OBJECTIVE: To evaluate the repeatability of a children's food frequency questionnaire (FFQ) by gender, ethnicity, and age group. DESIGN: A 117-item FFQ asking about food intake patterns over the past 4 weeks was developed using food records from 428 children (204 boys and 224 girls) and the reproducibility on average 13 days apart was tested in 130 children (78 boys and 52 girls). Children were recruited using clustered probability sampling (n=103), and a convenience sample of 25 Maori children. SETTING: Children aged 1-14 y from Auckland, Feilding and Shannon, New Zealand. SUBJECTS: There were 71 Maori, 20 Pacific, and 39 Other children. RESULTS: Spearman correlations between the two FFQs ranged from 0.50 for bread to 0.82 for fruit, with a median of 0.76 for spreads and nonmilk drinks, and Cronbach's coefficient alpha's ranged from 0.59 for bread to 0.92 for nonmilk drinks, with a median of 0.85 for mixed meat dishes. There were no significant differences between the two administrations, apart from reporting higher intakes of vegetables and snacks & sweets in the first FFQ. Correlation coefficients tended to be slightly higher in boys than in girls, and in Other ethnic groups compared to Maori and Pacific children. Correlations were slightly higher for the 1-4 y age group, intermediate in the 10-14 y age group, and lowest in the 5-9 y-old age group. CONCLUSIONS: Overall, the FFQ described here shows similar or better repeatability in New Zealand children of all major ethnic groups compared to other child or adolescent FFQs.
Adolescent↗
Stereotactic MR imaging for planning neural transplantation: a reliable technique at 3 Tesla?
The purpose of this study was to assess the accuracy of high field (3 Tesla) MR in target localization for stem cell transplantation. Three patients with Huntington's disease were imaged with a stereotactic frame in place for both MRI and CT. Quality assurance procedures and manual shimming were performed before each MRI study to minimize image distortion. The images were fused using multi-modality rigid body image registration software. Image fusion demonstrated the MR images to be in agreement with CT to within 1.5 mm, as assessed by measuring the coordinates of markers on the frame and on the shape and size of the lateral ventricles. Target coordinates for transplantation were selected from the MR images. Postoperative imaging confirmed accurate graft placement.
Brain Tissue Transplantation↗
Creation versus destruction of T cell epitopes in the class II MHC pathway.
Proteases perform two key roles in the class II MHC antigen processing pathway. They initiate removal of the invariant chain chaperone for class II MHC and they generate peptides from foreign and self proteins for eventual capture and display to T cells. How a balance is achieved between generation of suitable peptides versus their complete destruction in an aggressive proteolytic environment is not known. Nor is it known in most cases which proteases are actually involved in antigen processing. Our recent studies have identified asparagine endopeptidase (AEP or legumain) as an enzyme that contributes to both productive and destructive antigen processing in the class II MHC pathway. The emerging consensus seems to be that individual proteolytic enzymes make clear and non-redundant contributions to antigen processing.
Animals↗
Sensitivity requirements for the point of care diagnosis of Chlamydia trachomatis and Neisseria gonorrhoeae in women.
BACKGROUND/OBJECTIVES: Most current tests for Neisseria gonorrhoeae and Chlmydia trachomatis require the support of a laboratory, and results are not usually available before the patient has left the clinic. This delay can lead to patients not returning for treatment and may allow further STI transmission to occur. Current rapid point of care (POC) STI tests and the syndromic approach are less sensitive than gold standard tests, but allow treatment at the initial visit. This study estimates the required sensitivity of POC tests that ensures as many STIs are averted as with current gold standard tests. METHODS: A mathematical model is developed to compare the STIs averted using different STI diagnostic methods. Data from Benin, South Africa, Tanzania, and England are used to explore how the required sensitivity differs between settings. RESULTS: The required sensitivity of a POC test is low if there is significant STI transmission during the delay in treatment for the gold standard test and/or few women return for treatment. For example, the required sensitivity of a POC test for C trachomatis is 50% (gold standard test sensitivity is 90%) if either 55% return for treatment and there is no STI transmission, or 80% return for treatment and 50% of infected women infect their partner during the delay in treatment. Furthermore, in these settings a POC test of moderate sensitivity can lead to significantly more STI averted than the gold standard test. CONCLUSIONS: These results support the use of moderate sensitivity POC tests in scenarios where many women will not return for treatment, and in populations where the delay in treatment would result in significant STI transmission.
Benin↗
Evaluation of an MRI-based protocol for cell implantation in four patients with Huntington's disease.
The purpose of this study was to evaluate our surgical protocol for the preparation and delivery of suspensions of fetal tissue into the diseased human brain. We implanted suspensions of human fetal striatal anlage into the right caudate and putamen of four patients with Huntington's disease. Postoperative 3 tesla MR imaging confirmed accurate graft placement. Variability in graft survival was noted and the MR signal changes over 6 months revealed persistent hyperintense signal on T2-weighted images. Our results are consistent with those described by other groups and indicate that our surgical protocol is safe, accurate, and reproducible.
Brain↗
Multiple cerebral aneurysms and the Diamond-Blackfan syndrome.
Explore the source record for details and available documents.
Adolescent↗
Unilateral transplantation of human primary fetal tissue in four patients with Huntington's disease: NEST-UK safety report ISRCTN no 36485475.
OBJECTIVES: Huntington's disease (HD) is an inherited autosomal dominant condition in which there is a CAG repeat expansion in the huntingtin gene of 36 or more. Patients display progressive motor, cognitive, and behavioural deterioration associated with progressive cell loss and atrophy in the striatum. Currently there are no disease modifying treatments and current symptomatic treatments are only partially effective in the early to moderate stages. Neural transplantation is effective in animal models of HD and offers a potential strategy for brain repair in patients. The authors report a safety study of unilateral transplantation of human fetal striatal tissue into the striatum of four patients with HD. SUBJECTS AND METHODS: Stereotaxic placements of cell suspensions of human fetal ganglionic eminence were made unilaterally into the striatum of four patients with early to moderate HD. All patients received immunotherapy with cyclosporin A, azathioprine, and prednisolone for at least six months postoperatively. Patients were assessed for safety of the procedure using magnetic resonance imaging (MRI), regular recording of serum biochemistry and haematology to monitor immunotherapy, and clinical assessment according to the Core Assessment Protocol For Intrastriatal Transplantation in HD (CAPIT-HD). RESULTS: During the six month post-transplantation period, the only adverse events related to the procedure were associated with the immunotherapy. MRI demonstrated tissue at the site of implantation, but there was no sign of tissue overgrowth. Furthermore, there was no evidence that the procedure accelerated the course of the disease. CONCLUSIONS: Unilateral transplantation of human fetal striatal tissue in patients with HD is safe and feasible. Assessment of efficacy will require longer follow up in a larger number of patients.
Adult↗
Immunology. Antigen presentation--losing its shine in the absence of GILT.
Explore the source record for details and available documents.
Animals↗
AIDS. Resource needs for HIV/AIDS.
Explore the source record for details and available documents.
Acquired Immunodeficiency Syndrome↗
Effect of postoperative atrial fibrillation on length of stay after cardiac surgery (The Postoperative Atrial Fibrillation in Cardiac Surgery study [PACS(2)].
Atrial fibrillation (AF) after cardiac surgery is thought to increase length of stay (LOS). A clinical pathway focused on the management of postoperative AF, including prophylaxis with beta blockers, was implemented to assess the effect of AF on LOS after cardiac surgery. Data were obtained on consecutive cardiac surgery patients in preoperative normal sinus rhythm, no prior history of AF, and no chronic antiarrhythmic therapy from January to May 1995 (control) and November 1996 to June 1997 (pathway). Statistical analysis was performed to assess the effect of postoperative AF on the LOS, clinical outcomes, and cost after cardiac surgery. Despite the clinical pathway, the LOS (7 days for both periods; p = 0.12) and incidence of AF (28.9% vs 28.4%; p = 0.92) remained unchanged. Unadjusted direct costs were 15% higher in the pathway period (p <0.001). Increased rates of beta-blocker therapy had a marginal effect on the incidence of postoperative AF, except in the group who only underwent primary coronary artery bypass graft surgery (31.2% vs 25.3%; p = 0.31). Multivariate analysis revealed that AF contributed only 1 to 1.5 days to the LOS. Thus, this investigation represents the most recent analysis of the effects of postoperative AF on LOS, clinical outcomes, and cost after cardiac surgery. Unlike prior studies, the impact of postoperative AF is less prominent in the current era of cardiac surgical care regardless of the presence of a clinical pathway addressing AF.
Adrenergic beta-Antagonists↗