Different Levels Of Adherence Research Articles

A practical framework for eliciting and modeling system dependability requirements: Experience from the NASA high dependability computing project

The dependability of a system is contextually subjective and reflects the particular stakeholder’s needs. In different circumstances, the focus will be on different system properties, e.g., availability, real-time response, ability to avoid catastrophic failures, and prevention of deliberate intrusions, as well as different levels of adherence to such properties. Close involvement from stakeholders is thus crucial during the elicitation and definition of dependability requirements. In this paper, we suggest a practical framework for eliciting and modeling dependability requirements devised to support and improve stakeholders’ participation. The framework is designed around a basic modeling language that analysts and stakeholders can adopt as a common tool for discussing dependability, and adapt for precise (possibly measurable) requirements. An air traffic control system, adopted as testbed within the NASA High Dependability Computing Project, is used as a case study.

Pharmacy-based assessment of adherence to HAART predicts virologic and immunologic treatment response and clinical progression to AIDS and death

Although adherence to HAART at a level above 95% has been associated with optimal viral suppression, the impact of different levels of adherence on long-term clinical outcomes has not been determined. We used an objective pharmacy-based measure to examine the association between three levels of adherence to HAART and disease progression among a population-based cohort of HIV-infected patients attending an urban HIV specialty clinic. Higher levels of adherence to HAART were significantly associated with longer time to virologic failure (P < 0.001), greater increase in CD4 cell count (P = 0.04), and lower risk of progression to clinical AIDS or death (P < 0.007). After controlling for other factors, patients with low adherence had over five times the risk of disease progression than patients with moderate adherence (P = 0.007) or patients with high adherence (P = 0.001). There was no significant difference in the risk of progression between patients with moderate and high levels of adherence (P > 0.2). Patients who progressed to AIDS or death had significantly higher viral loads (P = 0.01) and lower CD4 cell counts (P = 0.03) than patients who experienced virologic failure, but did not progress.

Nursing adherence with evidence-based guidelines for preventing ventilator-associated pneumonia.

To review barriers to nursing adherence to nonpharmacologic evidence-based guidelines for preventing ventilator-associated pneumonia. Descriptive study. Intensive care units. Subjects were 110 nurses approached at two critical care nursing meetings. A questionnaire was administered to nurses to assess their adherence to 19 nonpharmacologic prevention strategies and to identify barriers to adherence to evidence-based guidelines. Fifty-one nurses responded, and overall nonadherence was 22.3%. Significant differences of adherence were identified when compared with the rates previously reported by physicians in nine of the 19 strategies investigated. The most important reasons for nonadherence were unavailability of resources (37.0%), patient discomfort (8.2%), disagreement with reported trial results (7.8%), fear of potential adverse effects (5.8%), and costs (3.4%). Nurses were more likely (p <.05) to identify patient discomfort (odds ratio, 4.8) and fear of adverse events (odds ratio, 3.3), whereas physicians were more likely to report costs (odds ratio, 5.4) and disagreement with interpretation of trials (odds ratio, 3.7) as reasons for nonadherence. Nurses had different levels of adherence than physicians for many nonpharmacologic strategies. The most important barriers to implementation were environment-related. Other reasons for nonadherence show significant variability between nurse and physician opinion leaders, patient-related barriers being significantly more important for nurses. Our findings suggest the need for development of multinational guidelines to reduce variability and the need to include the nursing point of view in these guidelines.

High levels of adherence do not prevent accumulation of HIV drug resistance mutations

To assess the relationship between development of antiretroviral drug resistance and adherence by measured treatment duration, virologic suppression, and the rate of accumulating new drug resistance mutations at different levels of adherence. Adherence was measured with unannounced pill counts performed at the participant's usual place of residence in a prospective cohort of HIV-positive urban poor individuals. Two genotypic resistance tests separated by 6 months (G1 and G2) were obtained in individuals on a stable regimen and with detectable viremia (> 50 copies/ml). The primary resistance outcome was the number of new HIV antiretroviral drug resistance mutations occurring over the 6 months between G1 and G2. High levels of adherence were closely associated with greater time on treatment (P < 0.0001) and viral suppression (P < 0.0001) in 148 individuals. In a subset of 57 patients with a plasma viral load > 50 copies/ml on stable therapy, the accumulation of new drug resistance mutations was positively associated with the duration of prior treatment (P = 0.03) and pill count adherence (P = 0.002). Assuming fully suppressed individuals (< 50 copies/ml) do not develop resistance, it was estimated that 23% of all drug resistance occurs in the top quintile of adherence (92-100%), and over 50% of all drug resistance mutations occur in the top two quintiles of adherence (79-100%). Increasing rates of viral suppression at high levels of adherence is balanced by increasing rates of drug resistance among viremic patients. Exceptionally high levels of adherence will not prevent population levels of drug resistance.

Adherence to directly observed antiretroviral therapy among human immunodeficiency virus-infected prison inmates.

Directly observed therapy (DOT) for human immunodeficiency virus (HIV) infection is commonly used in correctional settings; however, the efficacy of DOT for treating HIV infection has not been determined. We prospectively assessed adherence to antiretroviral therapy regimens among 31 HIV-infected prison inmates who were receiving >or=1 antiretrovirals via DOT. Adherence was measured by self-report, pill count, electronic monitoring caps, and, for DOT only, medication administration records. Overall, median adherence was 90%, as measured by pill count; 86%, by electronic monitoring caps; and 100%, by self-report. Adherence, as measured by electronic monitoring caps, was >90% in 32% of the subjects. In 91% of cases, adherence, as measured by medication administration records, was greater than that recorded by electronic monitoring caps for the same medications administered by DOT. Objective methods of measurement revealed that adherence to antiretroviral regimens administered wholly or in part by DOT was <or=90% in more than one-half of the patients. Different methods used to measure adherence revealed significantly different levels of adherence. These findings suggest that use of DOT does not ensure adherence to antiretroviral therapy.

Adherence to HIV treatment: results from a 1-year follow-up study.

We evaluated adherence to HIV treatments every 4 months during one year in 63 HIV-infected subjects using combination therapies including a protease inhibitor. A total of 18 subjects reported a high level of adherence, 14 in two evaluations, and eight a low level of adherence in all the three evaluations. The remaining 23 subjects (36.5%) reported different levels of adherence to treatment in the three evaluations. These findings suggest that the level of adherence to treatment changes markedly for each patient over time.

Adherence to protease inhibitor therapy and outcomes in patients with HIV infection.

Combination antiretroviral therapy with protease inhibitors has transformed HIV infection from a terminal condition into one that is manageable. However, the complexity of regimens makes adherence to therapy difficult. To assess the effects of different levels of adherence to therapy on virologic, immunologic, and clinical outcome; to determine modifiable conditions associated with suboptimal adherence; and to determine how well clinicians predict patient adherence. Prospective, observational study. HIV clinics in a Veterans Affairs medical center and a university medical center. 99 HIV-infected patients who were prescribed a protease inhibitor and who neither used a medication organizer nor received their medications in an observed setting (such as a jail or nursing home). Adherence was measured by using a microelectronic monitoring system. The adherence rate was calculated as the number of doses taken divided by the number prescribed. Patients were followed for a median of 6 months (range, 3 to 15 months). During the study period, 45,397 doses of protease inhibitor were monitored in 81 evaluable patients. Adherence was significantly associated with successful virologic outcome (P < 0.001) and increase in CD4 lymphocyte count (P = 0.006). Virologic failure was documented in 22% of patients with adherence of 95% or greater, 61% of those with 80% to 94.9% adherence, and 80% of those with less than 80% adherence. Patients with adherence of 95% or greater had fewer days in the hospital (2.6 days per 1000 days of follow-up) than those with less than 95% adherence (12.9 days per 1000 days of follow-up; P = 0.001). No opportunistic infections or deaths occurred in patients with 95% or greater adherence. Active psychiatric illness was an independent risk factor for adherence less than 95% (P = 0.04). Physicians predicted adherence incorrectly for 41% of patients, and clinic nurses predicted it incorrectly for 30% of patients. Adherence to protease inhibitor therapy of 95% or greater optimized virologic outcome for patients with HIV infection. Diagnosis and treatment of psychiatric illness should be further investigated as a means to improve adherence to therapy.

Investigations into the molecular basis of meningococcal toxicity for human endothelial and epithelial cells: the synergistic effect of LPS and pili

Using human umbilical vein endothelial cells as an in vitro model of toxicity, it was found that Neisseria meningitidis, Neisseria gonorrhoeae, Neisseria lactamica and Neisseria sicca caused damage to these cells, in contrast to the lack of cytotoxicity exhibited by Haemophilus influenzae type b. N. meningitidis was also found to be toxic for human epithelial cells. The major toxic factor of N. meningitidis was found to be a heat-stable component of outer membrane vesicles, and could be inhibited by polymyxin B, suggesting that lipopolysaccharide plays a major role in toxicity. However, the toxicity mediated by lipopolysaccharide was modulated significantly by pilus-dependent adherence. Intra-strain variants expressing altered pilins which exhibited different levels of adherence to epithelial and endothelial cells were used to study the role of pilus. The degree of toxicity observed correlated with their relative level of adherence to cultured cells. In contrast, Opc-dependent increased adherence did not result in increased toxicity for endothelial cells, suggesting that pili have a synergistic effect, contributing to the overall damage.