2,655 research outputs found
Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in the SMART study: role of CD4+ Cell counts and HIV RNA levels during follow-up.
No full textVariable impact on mortality of AIDS‐Defining events diagnosed during combination antiretroviral therapy: Not All AIDS‐defining conditions are created equal
No full textBackground
The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)–defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy.
Methods
We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of anti-retroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in <50 patients were grouped together to form a “rare ADEs” category.
Results
During a median follow-up period of 43 months (interquartile range, 19–70 months), 2880 ADEs were diagnosed in 2262 patients; 1146 patients died. The most common ADEs were esophageal candidiasis (in 360 patients), Pneumocystis jiroveci pneumonia (320 patients), and Kaposi sarcoma (308 patients). The greatest mortality hazard ratio was associated with non-Hodgkin’s lymphoma (hazard ratio, 17.59; 95% confidence interval, 13.84–22.35) and progressive multifocal leukoencephalopathy (hazard ratio, 10.0; 95% confidence interval, 6.70–14.92). Three groups of ADEs were identified on the basis of the ranked hazard ratios with bootstrapped confidence intervals: severe (non-Hodgkin’s lymphoma and progressive multifocal leukoencephalopathy [hazard ratio, 7.26; 95% confidence interval, 5.55–9.48]), moderate (cryptococcosis, cerebral toxoplasmosis, AIDS dementia complex, disseminated Mycobacterium avium complex, and rare ADEs [hazard ratio, 2.35; 95% confidence interval, 1.76–3.13]), and mild (all other ADEs [hazard ratio, 1.47; 95% confidence interval, 1.08–2.00]).
Conclusions
In the combination antiretroviral therapy era, mortality rates subsequent to an ADE depend on the specific diagnosis. The proposed classification of ADEs may be useful in clinical end point trials, prognostic studies, and patient management
Discontinuation of secondary prophylaxis against Pneumocystis carinii pneumonia in patients with HIV infection who have a response to antiretroviral therapy
No full textBackground: Patients with human immunodeficiency virus (HIV) infection and a history of Pneumocystis carinii pneumonia are at high risk for relapse if they are not given secondary prophylaxis. Whether secondary prophylaxis against P. carinii pneumonia can be safely discontinued in patients who have a response to highly active antiretroviral therapy is not known.
Methods: We analyzed episodes of recurrent P. carinii pneumonia in 325 HIV-infected patients (275 men and 50 women) in eight prospective European cohorts. Between October 1996 and January 2000, these patients discontinued secondary prophylaxis during treatment with at least three anti-HIV drugs after they had at least one peripheral-blood CD4 cell count of more than 200 cells per cubic millimeter.
Results: Secondary prophylaxis was discontinued at a median CD4 cell count of 350 per cubic millimeter; the median nadir CD4 cell count had been 50 per cubic millimeter. The median duration of the increase in the CD4 cell count to more than 200 per cubic millimeter after discontinuation of secondary prophylaxis was 11 months. The median follow-up period after discontinuation of secondary prophylaxis was 13 months, yielding a total of 374 person-years of follow-up; for 355 of these person-years, CD4 cell counts remained at or above 200 per cubic millimeter. No cases of recurrent P. carinii pneumonia were diagnosed during this period; the incidence was thus 0 per 100 patient-years (99 percent confidence interval, 0 to 1.2 per 100 patient-years, on the basis of the entire follow-up period, and 0 to 1.3 per 100 patient-years, on the basis of the follow-up period during which CD4 cell counts remained at or above 200 per cubic millimeter).
Conclusions: It is safe to discontinue secondary prophylaxis against P. carinii pneumonia in patients with HIV infection who have an immunologic response to highly active antiretroviral therapy
Consideration of Interference Correlation Properties in a JD-CDMA Mobile Radio System with Coherent Receiver Antenna Diversity
No full textIn code division multiple access (CDMA) mobile radio systems, both intersymbol interference and multiple access interference arise which can be combatted by using Joint Detection (JD) techniques, to reduce the degradation in performance resulting from time variance, coherent receiver antenna diversity (CRAD) can be used. The application of JD techniques offers the possibility to exploit the knowledge of noise covariances at the receiver. If only intercell (cochannel) interference is considered, the noise covariances in the uplink receiver of a multiple receiver antenna CDMA mobile radio system depend mainly on the directions of arrival (DOAs) of the interfering signals and the receiver antenna placement. Therefore, if the interferer DOAs are known at the base station, these covariances could be estimated. In this thesis, a realistic model of the uplink of a JD CDMA mobile radio system with CRAD is described in which the above mentioned interference cancelling method is used. Simulation results according to this model are given and evaluated.Applied SciencesElectrical EngineeringTelecommunications and Traffic Control Systems Grou
Dairy farmers’ perceptions toward the implementation of on-farm Johne’s disease prevention and control strategies
No full textmplementation of specific management strategies on dairy farms is currently the most effective way to reduce the prevalence of Johne’s disease (JD), an infectious chronic enteritis of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). However, dairy farmers often fail to implement recommended strategies. The objective of this study was to assess perceptions of farmers participating in a JD prevention and control program toward recommended practices, and explore factors that influence whether or not a farmer adopts risk-reducing measures for MAP transmission. Semi-structured interviews were conducted with 25 dairy farmers enrolled in a voluntary JD control program in Alberta, Canada. Principles of classical grounded theory were used for participant selection, interviewing, and data analysis. Additionally, demographic data and MAP infection status were collected and analyzed using quantitative questionnaires and the JD control program database. Farmers’ perceptions were distinguished according to 2 main categories: first, their belief in the importance of JD, and second, their belief in recommended JD prevention and control strategies. Based on these categories, farmers were classified into 4 groups: proactivists, disillusionists, deniers, and unconcerned. The first 2 groups believed in the importance of JD, and proactivists and unconcerned believed in proposed JD prevention and control measures. Groups that regarded JD as important had better knowledge about best strategies to reduce MAP transmission and had more JD risk assessments conducted on their farm. Although not quantified, it also appeared that these groups had more JD prevention and control practices in place. However, often JD was not perceived as a problem in the herd and generally farmers did not regard JD control as a “hot topic” in communications with their herd veterinarian and other farmers. Recommendations regarding how to communicate with farmers and motivate various groups of farmers according to their specific perceptions were provided to optimize adoption of JD prevention and control measures and thereby increase success of voluntary JD control programs
Knowledge gaps that hamper prevention and control of Mycobacterium avium subspecies paratuberculosis infection
No full textIn the last decades, many regional and country‐wide control programmes for Johne's disease (JD ) were developed due to associated economic losses, or because of a possible association with Crohn's disease. These control programmes were often not successful, partly because management protocols were not followed, including the introduction of infected replacement cattle, because tests to identify infected animals were unreliable, and uptake by farmers was not high enough because of a perceived low return on investment. In the absence of a cure or effective commercial vaccines, control of JD is currently primarily based on herd management strategies to avoid infection of cattle and restrict within‐farm and farm‐to‐farm transmission. Although JD control programmes have been implemented in most developed countries, lessons learned from JD prevention and control programmes are underreported. Also, JD control programmes are typically evaluated in a limited number of herds and the duration of the study is less than 5 year, making it difficult to adequately assess the efficacy of control programmes. In this manuscript, we identify the most important gaps in knowledge hampering JD prevention and control programmes, including vaccination and diagnostics. Secondly, we discuss directions that research should take to address those knowledge gaps
Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration.
No full textBackground With the advent of effective antiretroviral treatment, the life expectancy for people with HIV is now approaching that seen in the general population. Consequently, the relative importance of other traditionally non-AIDS-related morbidities has increased. We investigated trends over time in all-cause mortality and for specific causes of death in people with HIV from 1999 to 2011.
Methods Individuals from the Data collection on Adverse events of anti-HIV Drugs (D: A: D) study were followed up from March, 1999, until death, loss to follow-up, or Feb 1, 2011, whichever occurred first. The D: A: D study is a collaboration of 11 cohort studies following HIV-1-positive individuals receiving care at 212 clinics in Europe, USA, and Australia. All fatal events were centrally validated at the D: A: D coordinating centre using coding causes of death in HIV (CoDe) methodology. We calculated relative rates using Poisson regression.
Findings 3909 of the 49 731 D: A: D study participants died during the 308 719 person-years of follow-up (crude incidence mortality rate, 12 7 per 1000 person-years [95% CI 12.3-13.1]). Leading underlying causes were: AIDS-related (1123 [29%] deaths), non-AIDS-defining cancers (590 [15%] deaths), liver disease (515 [13%] deaths), and cardiovascular disease (436 [11%] deaths). Rates of all-cause death per 1000 person-years decreased from 17 5 in 1999-2000 to 9 1 in 2009-11; we saw similar decreases in death rates per 1000 person-years over the same period for AIDS-related deaths (5 9 to 2 0), deaths from liver disease (2 7 to 0 9), and cardiovascular disease deaths (1 8 to 0 9). However, non-AIDS cancers increased slightly from 1 6 per 1000 person-years in 1999-2000 to 2 1 in 2009-11 (p=0.58). After adjustment for factors that changed over time, including CD4 cell count, we detected no decreases in AIDS-related death rates (relative rate for 2009-11 vs 1999-2000: 0 92 [0.70-1.22]). However, all-cause (0 72 [0.61-0.83]), liver disease (0 48 [0.32-0.74]), and cardiovascular disease (0 33 [0.20-0.53) death rates still decreased over time. The percentage of all deaths that were AIDS-related (87/256 [34%] in 1999-2000 and 141/627 [22%] in 2009-11) and liver-related (40/256 [16%] in 1999-2000 and 64/627 [10%] in 2009-11) decreased over time, whereas non-AIDS cancers increased (24/256 [9%] in 1999-2000 to 142/627 [23%] in 2009-11).
Interpretation Recent reductions in rates of AIDS-related deaths are linked with continued improvement in CD4 cell count. We hypothesise that the substantially reduced rates of liver disease and cardiovascular disease deaths over time could be explained by improved use of non-HIV-specific preventive interventions. Non-AIDS cancer is now the leading non-AIDS cause and without any evidence of improvement
Evaluation of an alternative method of herd classification for infection with paratuberculosis in cattle herds in the United States
No full textObjective - To develop a better system for classification of herd infection status for paratuberculosis (Johne's disease JD]) in US cattle herds on the basis of the risk of potential transmission of Mycobacterium avium subsp paratubeculosis. Sample - Simulated data for herd size and within-herd prevalence; sensitivity and specificity for test methods obtained from consensus-based estimates. Procedures - Interrelationships among variables influencing interpretation and classification of herd infection status for JD were evaluated by use of simulated data for various herd sizes, true within-herd prevalences, and sampling and testing methods. The probability of finding ≥1 infected animal in herds was estimated for various testing methods and sample sizes by use of hypergeometric random sampling. Results - 2 main components were required for the new herd JD classification system: the probability of detection of infection determined on the basis of test results from a sample of animals and the maximum detected number of animals with positive test results. Tables were constructed of the estimated probability of detection of infection, and the maximum number of cattle with positive test results or fecal pools with positive culture results with 95% confidence for classification of herd JD infection status were plotted. Herd risk for JD was categorized on the basis of 95% confidence that the true within-herd prevalence was ≤15%, ≤10%, ≤5%, or ≤2%. Conclusions and Clinical Relevance - Analysis of the findings indicated that a scientifically rigorous and transparent herd classification system for JD in cattle is feasible.Source type: Electronic(1
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