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Biomedical subjects

Richard Bellamy

Publications and source records attributed to Richard Bellamy.

At least 19 recordsLinked to original sources
PubMed2007

WHO Rapid Advice Guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus.

Recent spread of avian influenza A (H5N1) virus to poultry and wild birds has increased the threat of human infections with H5N1 virus worldwide. Despite international agreement to stockpile antivirals, evidence-based guidelines for their use do not exist. WHO assembled an international multidisciplinary panel to develop rapid advice for the pharmacological management of human H5N1 virus infection in the current pandemic alert period. A transparent methodological guideline process on the basis of the Grading Recommendations, Assessment, Development and Evaluation (GRADE) approach was used to develop evidence-based guidelines. Our development of specific recommendations for treatment and chemoprophylaxis of sporadic H5N1 infection resulted from the benefits, harms, burden, and cost of interventions in several patient and exposure groups. Overall, the quality of the underlying evidence for all recommendations was rated as very low because it was based on small case series of H5N1 patients, on extrapolation from preclinical studies, and high quality studies of seasonal influenza. A strong recommendation to treat H5N1 patients with oseltamivir was made in part because of the severity of the disease. Similarly, strong recommendations were made to use neuraminidase inhibitors as chemoprophylaxis in high-risk exposure populations. Emergence of other novel influenza A viral subtypes with pandemic potential, or changes in the pathogenicity of H5N1 virus strains, will require an update of these guidelines and WHO will be monitoring this closely.

Animals↗
PubMed2006

Genome-wide approaches to identifying genetic factors in host susceptibility to tuberculosis.

Host genetic factors are important in determining susceptibility to Mycobacterium tuberculosis. Genome-wide linkage studies have been performed in humans and in murine models of tuberculosis susceptibility. These studies have identified several important candidate loci for susceptibility to tuberculosis. This is an important step in resolving the complex etiology of the disease.

Animals↗
PubMed2006

Cost and cost-effectiveness of antiretroviral therapy for HIV infection in Singapore.

The objective of this study was to determine the cost and cost-effectiveness of antiretroviral therapy (ART) in Singapore. The use and cost of HIV services was calculated for patients managed at the national HIV referral centre in Singapore between 1996 and 2001 from a hospital perspective. Three groups of patients were compared by Centers for Disease Control and Prevention (CDC) stage of HIV infection: those who had never received ART; those who had received only dual therapy; and those who had only received highly active antiretroviral therapy (HAART). Hospital charges were used to estimate the average hospital inpatient and outpatient care costs. Life years gained (LYG) were calculated for different stages of HIV infection and the incremental costs per LYG were calculated comparing those on dual ART and HAART with those who did not receive ART. Patients on ART progressed less rapidly across all CDC stages. For CDC stage A, the incremental cost per LYG was 17,007 dollars (Singaporean dollar) (interquartile range [IQR] 7963-25,113 dollars ) and 22,511 dollars (IQR 11,299-33,724 dollars) for those on dual therapy and HAART, respectively. The incremental cost per LYG in stage B was 10,868 dollars (IQR 4506-17,239 dollars) and 21,094 dollars (IQR 7774-34,431 dollars) for patients on dual therapy and HAART, respectively, while the incremental cost per LYG for stage C patients was 9,848 dollars (IQR 5256-14,419 dollars ) and 16,513 dollars (IQR 8677-24,337 dollars) for dual therapy and HAART, respectively. Dual ART therapy and HAART were cost-effective interventions in Singapore. Cost-effectiveness is likely to improve if drug prices continue to decrease.

Adult↗
PubMed2006

SARS: systematic review of treatment effects.

BACKGROUND: The SARS outbreak of 2002-2003 presented clinicians with a new, life-threatening disease for which they had no experience in treating and no research on the effectiveness of treatment options. The World Health Organization (WHO) expert panel on SARS treatment requested a systematic review and comprehensive summary of treatments used for SARS-infected patients in order to guide future treatment and identify priorities for research. METHODS AND FINDINGS: In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r), type I interferon (IFN), intravenous immunoglobulin (IVIG), and SARS convalescent plasma from both in vitro studies and in SARS patients. We also searched for clinical trial evidence of treatment for acute respiratory distress syndrome. Sources of data were the literature databases MEDLINE, EMBASE, BIOSIS, and the Cochrane Central Register of Controlled Trials (CENTRAL) up to February 2005. Data from publications were extracted and evidence within studies was classified using predefined criteria. In total, 54 SARS treatment studies, 15 in vitro studies, and three acute respiratory distress syndrome studies met our inclusion criteria. Within in vitro studies, ribavirin, lopinavir, and type I IFN showed inhibition of SARS-CoV in tissue culture. In SARS-infected patient reports on ribavirin, 26 studies were classified as inconclusive, and four showed possible harm. Seven studies of convalescent plasma or IVIG, three of IFN type I, and two of LPV/r were inconclusive. In 29 studies of steroid use, 25 were inconclusive and four were classified as causing possible harm. CONCLUSIONS: Despite an extensive literature reporting on SARS treatments, it was not possible to determine whether treatments benefited patients during the SARS outbreak. Some may have been harmful. Clinical trials should be designed to validate a standard protocol for dosage and timing, and to accrue data in real time during future outbreaks to monitor specific adverse effects and help inform treatment.

Disease Outbreaks↗
PubMed2005

Genetic susceptibility to tuberculosis.

Host genetic factors are important in determining susceptibility and resistance to Mycobacterium tuberculosis. The etiology of tuberculosis is complex, and several host genes have been shown to contribute to the development of clinical disease. The success of the strategies used to investigate host genetic susceptibility to mycobacterial infections can serve as a model for the investigation of host susceptibility to other infectious diseases.

Animals↗
PubMed2005

A systematic review of educational interventions for promoting sun protection knowledge, attitudes and behaviour following the QUESTS approach.

A literature review was performed to identify studies of educational interventions to promote sun protection behaviour. Fifty-nine clinical trials were identified. These studies were assessed using the QUESTS model. The studies showed that a wide range of educational interventions in different settings with a variety of target groups can be effective in promoting sun protection knowledge, attitudes, intended and actual behaviour. Relatively few studies made direct comparisons between different educational interventions. Therefore there was little evidence to suggest that any one form of intervention was more effective than any other. This review shows that the QUESTS criteria can be used to evaluate the effectiveness of patient education in the same way they are used to assess evidence in medical education. Performing systematic reviews on patient education topics should prove useful for health professionals developing educational interventions.

Health Behavior↗
PubMed2004

AIDS-defining illnesses among patients with HIV in Singapore, 1985 to 2001: results from the Singapore HIV Observational Cohort Study (SHOCS).

BACKGROUND: The objective was to describe the causes of initial and overall AIDS-defining disease episodes among HIV patients in Singapore. METHODS: A retrospective observational cohort study was performed of all adult patients seen at the national HIV referral center between 1985 and 2001. Data were extracted from the patients' records by ten trained healthcare workers. AIDS-defining conditions were established using predefined criteria. RESULTS: Among 1504 patients, 834 had experienced one or more AIDS-defining diseases. The most frequent causes of the initial AIDS-defining episode were Pneumocystis carinii pneumonia (35.7%), Mycobacterium tuberculosis (22.7%) and herpes simplex (7.4%). In total 1742 AIDS-defining episodes occurred. The most frequent causes were Pneumocystis carinii pneumonia (25.1%), Mycobacterium tuberculosis (16.2%) and cytomegalovirus retinitis (9.5%). CONCLUSIONS: The most frequent causes of AIDS-defining illnesses in Singapore are similar to those reported in the West, prior to the introduction of anti-retroviral therapy. Opportunistic infections remain the most frequent AIDS-defining illnesses.

AIDS-Related Opportunistic Infections↗
PubMed2004

An introduction to patient education: theory and practice.

Patient education is the process of enabling individuals to make informed decisions about their personal health-related behaviour. It aims to improve health by encouraging compliance with medical treatment regimens and promoting healthy lifestyles. Behavioural change for patients is a complex process and requires more than the simple acquisition of knowledge. Several educational models based on behavioural theories have been developed to explain individuals' health-related behaviour. The health belief model is the one most commonly used in research. The four principal components of this model are the individual's perception of his or her personal susceptibility to disease, perception of the severity of the disease and perception of the benefits from and barriers to modifying behaviour. The health belief model can be used to design educational interventions that are most likely to be effective. Patient education is a duty for all health practitioners and it should be a core component of medical school curricula.

Ghana↗
PubMed2004

Characterization of ancestral Mycobacterium tuberculosis by multiple genetic markers and proposal of genotyping strategy.

Sixty-eight ancestral Mycobacterium tuberculosis isolates were previously identified by using the tuberculosis-specific deletion 1 (TbD1) PCR and mycobacterial interspersed-repetitive-unit-variable-number tandem repeat (MIRU-VNTR) typing (Y. J. Sun, R. Bellamy, A. S. G. Lee, S. T. Ng, S. Ravindran, S.-Y. Wong, C. Locht, P. Supply, and N. I. Paton, J. Clin. Microbiol. 42:1986-1993, 2004). These TbD1(+) ancestral isolates were further characterized and typed in this study by IS6110 restriction fragment length polymorphism (RFLP) typing, VNTR typing using exact tandem repeats (VNTR-ETR), and spoligotyping of the direct-repeat region. To our knowledge, this is the first characterization of this genogroup by multiple genetic markers based on a fairly large sample size. In this genogroup, all spoligotypes were characterized by the absence of spacers 29 to 32 and 34. In addition, VNTR-ETR typing could add further resolution to the clustered isolates identified by MIRU-VNTR, and the combination of MIRU-VNTR and VNTR-ETR, called MIRU-ETR, showed the highest discriminatory power for these strains compared to IS6110 RFLP typing and spoligotyping alone. However, MIRU-ETR appeared to still cluster some probably epidemiologically unrelated strains, as judged by IS6110 RFLP divergence. Therefore, a typing strategy based on stepwise combination of MIRU-ETR and IS6110 RFLP is proposed to achieve maximal discrimination for unrelated TbD1(+) strains. This typing strategy may be useful in areas where TbD1(+) ancestral strains are prevalent.

Bacterial Typing Techniques↗
PubMed2004

Use of mycobacterial interspersed repetitive unit-variable-number tandem repeat typing to examine genetic diversity of Mycobacterium tuberculosis in Singapore.

Strain typing using variable-number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR) is a powerful tool for studying the epidemiology and genetic relationships of Mycobacterium tuberculosis isolates. For this study, isolates from 291 patients in Singapore were genotyped by this method. One hundred sixty-six distinct MIRU-VNTR patterns were detected. One hundred sixty-two strains were grouped into 1 of 35 different MIRU-VNTR clusters and 131 isolates were unique. In this sample collection, 9 of the 12 MIRU-VNTR loci were moderately or highly discriminative according to their allelic diversities. The Hunter-Gaston discriminatory index was 0.975, indicating the high power of discrimination of MIRU-VNTR typing. By direct comparisons with previously typed MIRU-VNTR patterns and by genetic relationship analyses, we could identify and clearly define four epidemic groups of M. tuberculosis in our sample, corresponding to the W/Beijing, East-Africa-Indian, Haarlem, and Delhi genotype families. Furthermore, MIRU-VNTR typing was able to clearly distinguish ancestral and modern M. tuberculosis strains as defined by TbD1 genomic deletion analysis. These results indicate that MIRU-VNTR typing can be a useful first-line tool for studying the genetic diversity of M. tuberculosis isolates in a large urban setting such as Singapore.

Alleles↗
PubMed2003

Variants of the CD40 ligand gene are not associated with increased susceptibility to tuberculosis in West Africa.

Evidence for linkage between tuberculosis and human chromosomal region Xq26 has previously been described. The costimulatory molecule CD40 ligand, encoded by TNFSF5 and located at Xq26.3, is a promising positional candidate. Interactions between CD40 ligand and CD40 are involved in the development of humoral- and cell-mediated immunity, as well as the activation of macrophages, which are the primary host and effector cells for Mycobacterium tuberculosis. We hypothesised that common variation within TNFSF5 might affect susceptibility to tuberculosis disease and, thus, might be responsible for the observed linkage to Xq26. Sequencing 32 chromosomes from a Gambian population identified nine common polymorphisms within the coding, 3' and 5' regulatory sequences of the gene. Six single nucleotide polymorphisms (SNPs) and a 3' microsatellite were genotyped in 121 tuberculosis patients and their available parents. No association with tuberculosis was detected for these variants using a transmission disequilibrium test, although one SNP at -726 showed some evidence of association in males. This finding, however, did not replicate in a separate case control study of over 1,200 West African individuals. We conclude that common genetic variation in TNFSF5 is not likely to affect tuberculosis susceptibility in West Africa and the linkage observed in this region is not due to variation in TNFSF5.

Africa, Western↗
PubMed2002

Association of a polymorphism in the P2X7 gene with tuberculosis in a Gambian population.

Adenosine triphosphate (ATP) ligation of P2X(7) receptors expressed on human macrophages that are infected with mycobacteria induces cell death and subsequent loss of intracellular bacterial viability. Marked heterogeneity observed in cell donor ATP responsiveness suggests that this antimycobacterial mechanism may be genetically regulated. Five single-nucleotide polymorphisms (SNPs) previously identified in a putative 1.8-kb promoter region upstream of P2RX7 exon 1 were screened for associations with clinical tuberculosis. The frequencies of these promoter SNPs and a polymorphism in P2RX7 exon 13 at position 1513 were compared among >300 Gambian patients with tuberculosis and >160 ethnically matched control subjects by sequence-specific oligonucleotide hybridization and ligation detection reaction analysis. A significant protective association against tuberculosis was found for 1 promoter SNP, at nucleotide position -762 (odds ratio [OR] for variant C allele, 0.70; 95% confidence interval [CI], 0.54-0.89; P=.003; OR for CC genotype, 0.545; 95% CI, 0.318-0.934; P=.027). This association supports a role for ATP/P2X(7)-mediated host regulation of Mycobacterium tuberculosis infection.

Adult↗