Predictors of 30-day readmission following hospitalisation with community-acquired pneumonia.

Background: There is a paucity of UK data to aid healthcare professionals in predicting which patients hospitalised with community-acquired pneumonia (CAP) are at greatest risk of 30-day readmission and to determine which readmissions may occur soonest.

Methods: An analysis of CAP cases admitted to nine UK hospitals participating in the Advancing Quality Pneumonia Programme.

Results: An analysis was performed of 12 157 subjects hospitalised with CAP in the Advancing Quality Programme Database.

ASSESSING THE VALUE OF INNOVATIVE MEDICAL DEVICES AND DIAGNOSTICS: THE IMPORTANCE OF CLEAR AND RELEVANT CLAIMS OF BENEFIT.

Objectives: Large numbers of new medical devices and diagnostics are developed and health services need to identify which ones offer real advantages. The National Institute for Health and Care Excellence (NICE) has introduced a system for assessing technologies that are often notified by companies, based on claims made for their benefits to patients, the National Health Service, and the environment.

Methods: Detailed scrutiny of claims made for the benefits of products and the corresponding evidence, seeking associations between these and the selection of products for full evaluation to produce NICE guidance.

A NEW HEALTH TECHNOLOGY ASSESSMENT SYSTEM FOR DEVICES: THE FIRST FIVE YEARS.

Objectives: The aim of this study was to review 5 years of activity from a new system devised by the National Institute for Health and Care Excellence (NICE), for assessing medical devices and diagnostics aimed at identifying and speeding adoption of technologies with clinical and cost advantages, compared with current practice in the United Kingdom healthcare system.

Methods: All eligible notified technologies were classified using the Food and Drug Administration and Global Medical Device Nomenclature nomenclatures. Decisions about selecting technologies for full assessment to produce NICE recommendations were reviewed, along with the reasons given to companies for not selecting products.

Virtual Touch™ Quantification to Diagnose and Monitor Liver Fibrosis in Hepatitis B and Hepatitis C: A NICE Medical Technology Guidance.

Virtual Touch™ Quantification (VTq) is a software application used with Siemens Acuson ultrasound scanners to assess the stiffness of liver tissue. The National Institute for Health and Care Excellence (NICE) Medical Technologies Advisory Committee (MTAC) selected VTq for evaluation and invited the company to submit clinical and economic evidence. King's Technology Evaluation Centre, an External Assessment Centre (EAC) commissioned by NICE, independently assessed the evidence submitted.

The MAGEC system for spinal lengthening in children with scoliosis: A NICE Medical Technology Guidance.

Scoliosis-structural lateral curvature of the spine-affects around four children per 1,000. The MAGEC system comprises a magnetically distractible spinal rod implant and an external remote controller, which lengthens the rod; this system avoids repeated surgical lengthening. Rod implants brace the spine internally and are lengthened as the child grows, preventing worsening of scoliosis and delaying the need for spinal fusion.

Enhanced antiretroviral therapy in rhesus macaques improves RT-SHIV viral decay kinetics.

Using an established nonhuman primate model, rhesus macaques were infected intravenously with a chimeric simian immunodeficiency virus (SIV) consisting of SIVmac239 with the human immunodeficiency virus type 1 (HIV-1) reverse transcriptase from clone HXBc2 (RT-SHIV). The impacts of two enhanced (four- and five-drug) highly active antiretroviral therapies (HAART) on early viral decay and rebound were determined. The four-drug combination consisted of an integrase inhibitor, L-870-812 (L-812), together with a three-drug regimen comprising emtricitabine [(-)-FTC], tenofovir (TFV), and efavirenz (EFV).

Analysis of multiply spliced transcripts in lymphoid tissue reservoirs of rhesus macaques infected with RT-SHIV during HAART.

Highly active antiretroviral therapy (HAART) can reduce levels of human immunodeficiency virus type 1 (HIV-1) to undetectable levels in infected individuals, but the virus is not eradicated. The mechanisms of viral persistence during HAART are poorly defined, but some reservoirs have been identified, such as latently infected resting memory CD4⁺ T cells. During latency, in addition to blocks at the initiation and elongation steps of viral transcription, there is a block in the export of viral RNA (vRNA), leading to the accumulation of multiply-spliced transcripts in the nucleus.

Variation of human immunodeficiency virus type-1 reverse transcriptase within the simian immunodeficiency virus genome of RT-SHIV.

RT-SHIV is a chimera of simian immunodeficiency virus (SIV) containing the reverse transcriptase (RT)-encoding region of human immunodeficiency virus type 1 (HIV-1) within the backbone of SIVmac239. It has been used in a non-human primate model for studies of non-nucleoside RT inhibitors (NNRTI) and highly active antiretroviral therapy (HAART). We and others have identified several mutations that arise in the "foreign" HIV-1 RT of RT-SHIV during in vivo replication.

Viral decay kinetics in the highly active antiretroviral therapy-treated rhesus macaque model of AIDS.

To prevent progression to AIDS, persons infected with human immunodeficiency virus type 1 (HIV-1) must remain on highly active antiretroviral therapy (HAART) indefinitely since this modality does not eradicate the virus. The mechanisms involved in viral persistence during HAART are poorly understood, but an animal model of HAART could help elucidate these mechanisms and enable studies of HIV-1 eradication strategies. Due to the specificity of non-nucleoside reverse transcriptase (RT) inhibitors (NNRTIs) for HIV-1, we have used RT-SHIV, a chimeric virus of simian immunodeficiency virus with RT from HIV-1.

Preliminary evidence for the development of a stroke specific geriatric depression scale.

Unlabelled: Measuring depression among persons with stroke faces many challenges; diagnostic tools are lengthy and do not measure the extent of depression; screening tools are not stroke-specific; and metrics from the available indices do not provide a value that is mathematically or clinically meaningful.

Purpose: To provide evidence for the development of a stroke specific Geriatric Depression Scale screening measure (SS-GDS) through Rasch methodology.

Methods: Secondary analyses of a randomized controlled trial post-stroke.

Viral sanctuaries during highly active antiretroviral therapy in a nonhuman primate model for AIDS.

Highly active antiretroviral therapy (HAART) enables long-term suppression of plasma HIV-1 loads in infected persons, but low-level virus persists and rebounds following cessation of therapy. During HAART, this virus resides in latently infected cells, such as resting CD4(+) T cells, and in other cell types that may support residual virus replication. Therapeutic eradication will require elimination of virus from all reservoirs.

Suppression of virus load by highly active antiretroviral therapy in rhesus macaques infected with a recombinant simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1.

We have modeled highly active antiretroviral therapy (HAART) for AIDS in rhesus macaques infected with a chimera (RT-SHIV) of simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type-1 (HIV-1). Seven RT-SHIV-infected macaques were treated with a combination of efavirenz (200 mg orally once daily), lamivudine (8 mg/kg subcutaneously once daily), and tenofovir (30 mg/kg subcutaneously once daily). Plasma viral RNA levels in all animals were reduced by more than 1,000-fold after 4 weeks and, in six of the seven animals, were reduced to undetectable levels after 10 weeks.

Efavirenz therapy in rhesus macaques infected with a chimera of simian immunodeficiency virus containing reverse transcriptase from human immunodeficiency virus type 1.

The specificity of nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) for the RT of human immunodeficiency virus type 1 (HIV-1) has prevented the use of simian immunodeficiency virus (SIV) in the study of NNRTIs and NNRTI-based highly active antiretroviral therapy. However, a SIV-HIV-1 chimera (RT-SHIV), in which the RT from SIVmac239 was replaced with the RT-encoding region from HIV-1, is susceptible to NNRTIs and is infectious to rhesus macaques. We have evaluated the antiviral activity of efavirenz against RT-SHIV and the emergence of efavirenz-resistant mutants in vitro and in vivo.

16alpha-Bromo-epiandrosterone therapy modulates experimental feline immunodeficiency virus viremia: initial enhancement leading to long-term suppression.

16alpha-Bromo-epiandrosterone (epiBr), a synthetic derivative of the natural hormone dehyroepiandrosterone (DHEA), was evaluated for its effects on feline immunodeficiency virus (FIV) infection in experimental cats. The rationale for this study was based on the ability of DHEA to significantly reduce the mortality to viral infections in mice. DHEA and epiBr also have demonstrable in vitro anti-viral activity for both HIV-1 and FIV.

The effects of HHV-8 vMIP-II on SIVmac251 infection and replication competent and incompetent SIVmac239Delta3 vectors.

Human herpesvirus type 8 vMIP-II has one of the broadest ranges of chemokine receptor binding and therefore a multiplicity of biologic effects, both immunologic and antiviral. These properties make vMIP-II an attractive effector gene to be expressed from gene therapy vectors. The present studies were concerned with both therapeutic approaches: (1) an anti-simian immunodeficiency virus (SIV) biologic, and (2) an effector gene in SIV-based vectors.

Susceptibilities of simian immunodeficiency virus to protease inhibitors.

We used a focal infectivity assay with HeLa H1-JC.37 cells to directly compare susceptibilities of simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) to protease inhibitors. SIVmac239 was inhibited by indinavir, saquinavir, and ritonavir, with 50% effective concentrations (means +/- standard deviations) of 39 +/- 8, 55 +/- 3, and 13 +/- 5 nM, respectively.

Reversion of the M184V mutation in simian immunodeficiency virus reverse transcriptase is selected by tenofovir, even in the presence of lamivudine.

The methionine-to-valine mutation in codon 184 (M184V) in reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1) or simian immunodeficiency virus (SIV) confers resistance to (-)-2'-deoxy-3'-thiacytidine (3TC; lamivudine) and increased sensitivity to 9-[2-(phosphonomethoxy)propyl]adenine (PMPA; tenofovir). We have used the SIV model to evaluate the effect of the M184V mutation on the emergence of resistance to the combination of 3TC plus PMPA. A site-directed mutant of SIVmac239 containing M184V (SIVmac239-184V) was used to select for resistance to both 3TC and PMPA by serial passage in the presence of increasing concentrations of both drugs.

Virulence and reduced fitness of simian immunodeficiency virus with the M184V mutation in reverse transcriptase.

Drug-resistant mutants with a methionine-to-valine substitution at position 184 of reverse transcriptase (M184V) emerged within 5 weeks of initiation of therapy in four newborn macaques infected with simian immunodeficiency virus (SIVmac251) and treated with lamivudine (3TC) or emtricitabine [(-)-FTC] (two animals per drug). Thus, this animal model mimics the rapid emergence of M184V mutants of HIV-1 during 3TC therapy of human patients. One animal of each treatment group developed fatal immunodeficiency at 12 weeks of age, which is similar to the rapid disease course seen in most untreated SIVmac251-infected infant macaques.