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Elisa F. Long Roshni Mandalia Sundhiya Mandalia Sabina S. Alistar Eduard J. Beck Margaret L. Brandeau 《PloS one》2014,9(4)
Objective
In many high-income countries with low HIV prevalence, significant numbers of persons living with HIV (PLHIV) remain undiagnosed. Identification of PLHIV via HIV testing offers timely access to lifesaving antiretroviral therapy (ART) and decreases HIV transmission. We estimated the effectiveness and cost-effectiveness of HIV testing in the United Kingdom (UK), where 25% of PLHIV are estimated to be undiagnosed.Design
We developed a dynamic compartmental model to analyze strategies to expand HIV testing and treatment in the UK, with particular focus on men who have sex with men (MSM), people who inject drugs (PWID), and individuals from HIV-endemic countries.Methods
We estimated HIV prevalence, incidence, quality-adjusted life years (QALYs), and health care costs over 10 years, and cost-effectiveness.Results
Annual HIV testing of all adults could avert 5% of new infections, even with no behavior change following HIV diagnosis because of earlier ART initiation, or up to 18% if risky behavior is halved. This strategy costs £67,000–£106,000/QALY gained. Providing annual testing only to MSM, PWID, and people from HIV-endemic countries, and one-time testing for all other adults, prevents 4–15% of infections, requires one-fourth as many tests to diagnose each PLHIV, and costs £17,500/QALY gained. Augmenting this program with increased ART access could add 145,000 QALYs to the population over 10 years, at £26,800/QALY gained.Conclusions
Annual HIV testing of key populations in the UK is very cost-effective. Additional one-time testing of all other adults could identify the majority of undiagnosed PLHIV. These findings are potentially relevant to other low-prevalence, high-income countries. 相似文献3.
Define and identify long-term non-progressors (LTNP) and HIV controllers (HIC), and estimate time until disease progression. LTNP are HIV-1+ patients who maintain stable CD4+ T-cell counts, with no history of opportunistic infection or antiretroviral therapy (ART). HIC are a subset of LTNP who additionally have undetectable viraemia. These individuals may provide insights for prophylactic and therapeutic development. Records of HIV-1+ individuals attending Chelsea and Westminster Hospital (1988–2010), were analysed. LTNP were defined as: HIV-1+ for >7 years; ART-naïve; no history of opportunistic infection and normal, stable CD4+ T-cell counts. MIXED procedure in SAS using random intercept model identified long-term stable CD4+ T-cell counts. Survival analysis estimated time since diagnosis until disease progression. Subjects exhibiting long-term stable CD4+ T-cell counts with history below the normal range (<450 cells/µl blood) were compared to LTNP whose CD4+ T-cell count always remained normal. Within these two groups subjects with HIV-1 RNA load below limit of detection (BLD) were identified. Of 14,227 patients, 1,204 were diagnosed HIV-1+ over 7 years ago and were ART-naïve. Estimated time until disease progression for the 20% (239) whose CD4+ T-cell counts remained within the normal range, was 6.2 years (IQR: 2.0 to 9.6); significantly longer than 4.0 years (IQR: 1.0 to 7.3) for patients with historical CD4+ T-cell count below normal (Logrank chi-squared = 21.26; p<0.001). Within a subpopulation of 312 asymptomatic patients, 50 exhibited long-term stable CD4+ T-cell counts. Of these, 13 were LTNP, one of whom met HIC criteria. Of the remaining 37 patients with long-term stable low CD4+ T-cell counts, 3 controlled HIV-1 RNA load BLD. Individuals with stable, normal CD4+ T-cell counts progressed less rapidly than those with low CD4+ T-cell counts. Few LTNP and HIC identified in this and other studies, endorse the need for universal definitions to facilitate comparison. 相似文献
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Samantha J Westrop Graeme Moyle Akil Jackson Mark Nelson Sundhiya Mandalia Nesrina Imami 《Molecular medicine (Cambridge, Mass.)》2012,18(1):1240-1248
Maraviroc (MVC) is the first licensed antiretroviral therapeutic agent to target a host cell surface molecule, and successful HIV-1 entry blockade by this C-C chemokine receptor type 5 (CCR5)-antagonist potentiates immunomodulation. We hypothesized that MVC intensification impacts immunization responses, T-cell phenotype, function and delayed type hypersensitivity (DTH) in HIV-1+ subjects. A 24-wk, double-blinded, placebo-controlled study of the addition of MVC to suppressive antiretroviral therapy in HIV-1+ persons was performed. Subjects received DTH tests, intramuscular tetanus, meningococcal and oral cholera immunizations. Antibody titers, T-cell function and phenotype were assessed. Of 157 patients referred, 47 were randomized 1:1; MVC:placebo. MVC enhanced meningococcal neo-immunization, blunted cholera response and expedited lymphoproliferation to tetanus boost, without affecting recall humoral response. Anti-HIV-1 group-specific antigen (Gag) and tetanus toxoid (TTox) function improved significantly, HIV-1-associated CD8 T-cell skewing normalized, and the percentage of late-stage and major histocompatibility complex (MHC) class II expressing CD4 T-cells increased. Activated CD4+ CD38+ human leukocyte antigen (HLA)-DR+ T-cells declined, and costimulation shifted to coinhibition. DTH was unchanged. Maraviroc intensification, through antagonism of the cell surface molecule CCR5, favorably influences immune profiles of HIV-1+ patients, supporting its immunomodulatory use in HIV-1 infection and potentially in other immunologically relevant settings. 相似文献
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L Ridsdale A Evans W Jerrett S Mandalia K Osler H Vora 《BMJ (Clinical research ed.)》1993,307(6896):103-106
OBJECTIVE--To describe the characteristics of patients attending their general practitioners and complaining of fatigue or being "tired all the time." DESIGN--Prospective study of cohort aged 16 years and older with follow up at two weeks and by questionnaires at two and six months. SUBJECTS--220 patients (164 women) with mean age 43 years and an age-sex matched comparison group. SETTINGS--Doctors and patients in four practices in Lancashire, Mid Glamorgan, Suffolk, and Surrey. MAIN OUTCOME MEASURES--General clinical data, results from standard group of laboratory tests, fatigue questionnaire, and 12 item general health questionnaire. RESULTS--Over twice as many patients with fatigue had high scores on the health questionnaire compared with the comparison group (156 (75%) v 69 (34%)). Results of laboratory tests were abnormal and contributed to the diagnosis in 19 patients. 59 out of 102 patients who responded had high fatigue scores six months later. Patients with persistent fatigue were more likely to have a history of anxiety or depression and to have had fatigue for more than three months on entry to the study. CONCLUSIONS--Women are particularly at risk of fatigue. The outcome is better if patients have had symptoms for three months or less or there is no history of emotional illness. 相似文献
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Milad Masjedi Rakhee Mandalia Adeel Aqil Justin Cobb 《Computer methods in biomechanics and biomedical engineering》2016,19(1):67-73
Impingement resulting from a cam deformity may cause pain, limit the hip joint range of motion (RoM) and lead to osteoarthritis. We have previously developed FeMorph software to quantify and plan corrective surgery and predict hip RoM post surgery. This study aimed to validate the software and evaluate the influence of the acetabular labrum on hip RoM. Computed tomography data from 92 femur-pelvis pairs were analysed in conjunction with the inter/intra-observer reliability. Four cadaveric hips were dissected, and the three-dimensional (3D) shape and size of the acetabular labrum for these hips was obtained using laser scan. The influence of the acetabular labrum in the RoM and subsequent planning for corrective surgery were then evaluated in cadavers for models with and without a labrum, and used as a first step towards validation of FeMorph RoM prediction. FeMorph was successfully used to model cam deformities and plan corrective surgery. Three-dimensional alpha angles were reduced to below 50° after virtual surgery without an excessive reduction in femoral neck cross-sectional area, which could increase fracture risk. A mean increase of 8° ± 2° in permitted internal rotation was observed during impingement testing following removal of the labrum. FeMorph provides a reliable and useful method to model and plan cam deformity correction. This study indicates that the presence of the labrum is responsible for a substantial decrease in permitted internal rotation at the hip joint. This has implications for surgical planning models which often only account for bony impingement. 相似文献
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Beck EJ Mandalia S Sangha R Sharott P Youle M Baily G Brettle R Gompels M Johnson M McCarron B Ong E Pozniak A Schwenk A Taylor S Walsh J Wilkins E Williams I Gazzard B;NPMS-HHC Steering Group 《PloS one》2011,6(12):e27830
Aim
To calculate use, cost and cost-effectiveness of people living with HIV (PLHIV) starting routine treatment and care before starting combination antiretroviral therapy (cART) and PLHIV starting first-line 2NRTIs+NNRTI or 2NRTIs+PIboosted, comparing PLHIV with CD4≤200 cells/mm3 and CD4>200 cells/mm3. Few studies have calculated the use, cost and cost-effectiveness of routine treatment and care before starting cART and starting cART above and below CD4 200 cells/mm3.Methods
Use, costs and cost-effectiveness were calculated for PLHIV in routine pre-cART and starting first-line cART, comparing CD4≤200 cells/mm3 with CD4>200 cells/mm3 (2008 UK prices).Results
cART naïve patients CD4≤200 cells/mm3 had an annual cost of £6,407 (95%CI £6,382 to £6,425) PPY compared with £2,758 (95%CI £2,752 to £2,761) PPY for those with CD4>200 cells/mm3; cost per life year gained of pre-cART treatment and care for those with CD4>200 cells/mm3 was £1,776 (cost-saving to £2,752). Annual cost for starting 2NRTIs+NNRTI or 2NRTIs+PIboosted with CD4≤200 cells/mm3 was £12,812 (95%CI £12,685–£12,937) compared with £10,478 (95%CI £10,376–£10,581) for PLHIV with CD4>200 cells/mm3. Cost per additional life-year gained on first-line therapy for those with CD4>200 cells/mm3 was £4639 (£3,967 to £2,960).Conclusion
PLHIV starting to use HIV services before CD4≤200 cells/mm3 is cost-effective and enables them to be monitored so they start cART with a CD4>200 cells/mm3, which results in better outcomes and is cost-effective. However, 25% of PLHIV accessing services continue to present with CD4≤200 cells/mm3. This highlights the need to investigate the cost-effectiveness of testing and early treatment programs for key populations in the UK. 相似文献10.
Mandalia S Mandalia R Lo G Chadborn T Sharott P Youle M Anderson J Baily G Brettle R Fisher M Gompels M Kinghorn G Johnson M McCarron B Pozniak A Tang A Walsh J White D Williams I Gazzard B Beck EJ;NPMS-HHC Steering Group 《PloS one》2010,5(12):e15677