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Background: Systematic reviews of randomized, controlled trials in patients with influenza suggest a lack of evidence about the effects of antiviral therapy on several patient-important outcomes of influenza.Purpose: To systematically review observational studies for benefits and harms of oseltamivir, zanamivir, amantadine, or rimantadine in the treatment of influenza.Data Sources: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, CINAHL, SIGLE, the Chinese Biomedical Literature Database, Panteleimon, and LILACS up to November 2010; contact with pharmaceutical companies; and reference lists.Study Selection: Observational studies in any language that compared single antiviral therapy with no therapy or other antiviral therapy, or that had no comparator, for influenza or influenza-like illness.Data Extraction: Two independent investigators extracted data. Confidence in the estimates of the obtained effects (quality of evidence) was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach.Data Synthesis: 74 studies fulfilled the inclusion criteria. Meta-analyses of the few studies providing effects with adjustment for confounders suggest that, in high-risk populations, oral oseltamivir may reduce mortality (odds ratio, 0.23 [95% CI, 0.13 to 0.43]; low-quality evidence), hospitalization (odds ratio, 0.75 [CI, 0.66 to 0.89]; low-quality evidence), and duration of symptoms (33 hours [CI, 21 to 45 hours]; very low-quality evidence) compared with no treatment. Earlier treatment with oseltamivir was generally associated with better outcomes. Inhaled zanamivir may lead to shorter symptom duration (23 hours [CI, 17 to 28 hours]; moderate-quality evidence) and fewer hospitalizations (odds ratio, 0.66 [CI, 0.37 to 1.18]) but more complications than no treatment. Direct comparison of oral oseltamivir and inhaled zanamivir suggests no important differences in key outcomes. Data from 1 study suggest that oral amantadine may reduce mortality and pneumonia associated with influenza A. No included study evaluated rimantadine.Limitations: Mortality was assessed in high-risk patients, and generalizability is limited. The overall body of evidence is limited by risk for confounding and selection, reporting, and publication bias.Conclusion: Therapy with oral oseltamivir and inhaled zanamivir may provide a net benefit over no treatment of influenza. However, as with the randomized trials, the confidence in the estimates of the effects for decision making is low to very low. PRIMARY FUNDING SOURCES: World Health Organization and McMaster University. [ABSTRACT FROM AUTHOR]

Objectives To determine the severity of injection site reactions (ISRs), patient quality of life (QoL) and preference when enfuvirtide is administered by the Biojector® (Bioject, Medical Technologies, Inc., Tualatin, OR, USA) relative to standard needles. Methods A total of 201 HIV-positive patients on stable enfuvirtide-based therapy ( n=184) or initiating such therapy ( n=17) were evaluated prospectively after switching from standard needles to the Biojector® system. Patients used needles for a minimum of 2 weeks prior to switching to the Biojector®. Questionnaires to assess the incidence and severity of ISRs (31-item score) and QoL [Medical Outcomes Study HIV Health Survey (MOS-HIV)] were administered at baseline and following a minimum of 14 days of Biojector® use. Results The median changes in ISR score and number of ISRs following a median of 1.0 month [interquartile range (IQR) 0.9, 1.3] of Biojector® use were −3 (IQR −7, 1) and −1 (IQR −3, 1), respectively. The severity of pain ( P<0.0001), induration ( P<0.0001), pruritus ( P<0.0001), nodules ( P<0.0001) and erythema ( P<0.0001) all decreased with the Biojector®. Administration of enfuvirtide with the Biojector® was associated with an improved patient QoL ( P<0.0001), and was preferred by 72% of patients. Conclusions Compared with needles, the Biojector® was associated with a decreased severity of ISRs and improved QoL in patients taking enfuvirtide. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the cost effectiveness of a new product, oral ganciclovir, in comparison to a current therapy, intravenous (i.v.) ganciclovir, in the maintenance treatment of newly diagnosed cytomegalovirus (CMV) retinitis in patients with AIDS.Design: This was a retrospective economic study of a prospective non-blinded randomised clinical trial. The model included i.v. ganciclovir induction, i.v. or oral ganciclovir maintenance and i.v. ganciclovir reinduction for patients whose CMV retinitis progressed. Safety and efficacy data were derived from the trial. A panel of Canadian infectious disease physicians and family physicians estimated the following in relation to i.v. ganciclovir treatment for CMV retinitis and related adverse events: healthcare resource utilisation, clinical practice patterns, patient out-of-pocket expenses and time loss from work. The incremental cost-effectiveness analysis is reported from a societal and a Ministry of Health perspective.Setting: The trial was conducted in Canada (2 centres) and the US (13 centres) between March 1991 and November 1992. The model assumed that patients received either inpatient or outpatient care, or both. The model provided an analysis in a Canadian setting.Patients and Participants: Participants were patients with AIDS and newly diagnosed CMV retinitis.Interventions: All patients received induction therapy with i.v. ganciclovir 5 mg/kg, twice daily for 14 days then once daily for 7 days. Patients whose CMV retinitis stabilised were randomised to maintenance therapy with either i.v. ganciclovir (5 mg/kg/day; n = 57) or oral ganciclovir (3000 mg/day; n = 60) and were followed for up to 140 days after the start of maintenance therapy.Main Outcome Measures and Results: The trial demonstrated that the mean time to progression of CMV retinitis was 57 days for oral ganciclovir compared with 62 days for i.v. ganciclovir maintenance therapy, as measured by masked fundus photography, and 96 days with i.v. ganciclovir compared with 68 days with oral ganciclovir according to the funduscopy results. There were more adverse events in the i.v. ganciclovir group compared with the oral ganciclovir group. The cost-effectiveness results provide the dollar amount expended in order to continue to provide additional benefit using i.v. ganciclovir compared with oral ganciclovir. The incremental cost-effectiveness (C/E) ratio was 482 Canadian dollars ($Can: 1993 to 1995 values) per progression-free day gained with i.v. ganciclovir. Sensitivity analysis using funduscopy, rather than fundus photography, to document progression of CMV retinitis resulted in a C/E ratio of $Can42.Conclusions: This analysis found that i.v. ganciclovir provided additional days free of progression of CMV retinitis when compared with oral ganciclovir, but the costs were higher. [ABSTRACT FROM AUTHOR]

We sought to evaluate the relationship of CD8- T cell-mediated inhibition of autologous HIV replication in vitro to disease stage in HIV+ individuals, Depletion of CD8+ T cells from peripheral blood lymphocytes of lb HIV+ subjects increased the percentage of virus-producing cultures from 56% to 81%. CD4+ I cells were purified from 52 HIV+ individuals and cultured alone or in the presence of autologous CD8+ T cells. In 13 (25%) subjects HIV replication was only detected in the absence of CD8+ T cells (inhibition positive): in 26 (50%) viral replication occurred both in the absence and presence of CDS cells (inhibition negative). In the remaining 13 (25%) subjects. CD8+ T cell-mediated inhibitory activity could not be evaluated because stimulation of their purified CD4 T cells did not result in p24 production. In some virus culture-negative individuals. the inability to demonstrate HIV replication was due to the presence of low numbers of CD8+ T cells that co-purified with CD4+ T cells. Detection of inhibitory CDS T cells was associated with significantly higher CD4 counts and better clinical status compared with inhibition-negative subjects. These results demonstrate that cur T cell-mediated inhibition of HIV replication correlates with disease stage. and thus may play a role in preventing disease progression. CD8+ I cells did not inhibit autologous HIV replication across a semipermeable membrane. Further, the ability of CD8+ T cells to prevent HIV replication did not correlate with lysis of autologous CD4 T cells. Thus. CD8+ T cells inhibited autologous HIV replication in vitro through a contact- mediated non lytic mechanism. [ABSTRACT FROM AUTHOR]

Fluconazole (FLU) is an alternative to amphotericin B (AMB) for the treatment of candidemia in non-neutropenic patients. This agent has similar clinical efficacy but significantly reduced adverse effects compared with AMB. Using the database from a Canadian randomised multicentre comparative trial of FLU versus AMB in the treatment of non-neutropenic patients with candidemia, an economic analysis of antifungal therapy was conducted from a Canadian hospital perspective. Patient records were examined for information containing hospital resource consumption. This included the costs for primary intravenous therapy with either AMB or FLU, laboratory tests, patient clinical monitoring and adverse effects management. The robustness of the baseline results were then tested by a comprehensive sensitivity analysis. The mean duration of therapy in the AMB and FLU arms was 17.1 and 23.7 days, respectively (p < 0.001). Assuming that all of the FLU was administered intravenously, the outcomes of the baseline economic analysis revealed that the treatment cost for patients randomized to receive FLU was approximately 50% higher than that for patients treated with AMB [AMB: $Can2370 vs FLU: $Can3578; p = 0.001 ($Can = Canadian dollars)]. In the sensitivity analysis, substitution to oral FLU after 7 days of intravenous therapy produced economic differences that were no longer statistically significant (AMB: $Can2370 vs FLU: $Can2705; p = 0.10). These results suggest that the FLU administration regimen used in the Canadian randomized trial for the treatment of candidemia in non-neutropenic patients may result in increased hospital costs compared with AMB. However, comparable expenditures could be realized if FLU is administered intravenously for the first 7 days and then orally in patients whose condition allows for reliable oral therapy. [ABSTRACT FROM AUTHOR]

Fluconazole (FLU) is an alternative to amphotericin B (AMB) for the treatment of candidemia in non-neutropenic patients. This agent has similar clinical efficacy but significantly reduced adverse effects compared with AMB. Using the database from a Canadian randomised multicentre comparative trial of FLU versus AMB in the treatment of non-neutropenic patients with candidemia, an economic analysis of antifungal therapy was conducted from a Canadian hospital perspective. Patient records were examined for information containing hospital resource consumption. This included the costs for primary intravenous therapy with either AMB or FLU, laboratory tests, patient clinical monitoring and adverse effects management. The robustness of the baseline results were then tested by a comprehensive sensitivity analysis. The mean duration of therapy in the AMB and FLU arms was 17.1 and 23.7 days, respectively (p < 0.001). Assuming that all of the FLU was administered intravenously, the outcomes of the baseline economic analysis revealed that the treatment cost for patients randomised to receive FLU was approximately 50% higher than that for patients treated with AMB [AMB: $Can2370 vs FLU: $Can3578; p = 0.001 ($Can = Canadian dollars)]. In the sensitivity analysis, substitution to oral FLU after 7 days of intravenous therapy produced economic differences that were no longer statistically significant (AMB: $Can2370 vs FLU: $Can2705; p = 0.10). These results suggest that the FLU administration regimen used in the Canadian randomised trial for the treatment of candidemia in non-neutropenic patients may result in increased hospital costs compared with AMB. However, comparable expenditures could be realised if FLU is administered intravenously for the first 7 days and then orally in patients whose condition allows for reliable oral therapy. [ABSTRACT FROM AUTHOR]

Abstract Background The purpose of this study was to examine the relationship between the Medical Outcomes Study-HIV Health Survey (MOS-HIV) and the SF-12v2 to determine if the latter is adequate to assess the health-related quality of life (HRQoL) of men and women living with HIV/AIDS. 112 men and women living with HIV/AIDS who access care at a tertiary HIV clinic in Hamilton, Ontario were included in this cross-sectional analysis. Correlation coefficients of the MOS-HIV physical and mental health summary scores (PHS and MHS) and the SF-12v2 physical and mental component summary scales (PCS and MCS) were calculated along with common sub-domains of the measures including physical functioning (PF), bodily pain (BP), general health perceptions (GH), vitality (VT), social functioning (SF) and mental health (MH) to explore the relationship between these two HRQoL measures. The sub-domains role physical (RP) and role emotional (RE) of the SF-12v2 were compared separately to the sub-domain role functioning (RF) of the MOS-HIV. Weighted kappa scores were calculated to determine agreement beyond chance between the MOS-HIV and SF-12v2 in assigning a HRQoL state (i.e. low, moderate, good, very good). Results The MOS-HIV had mean PHS and MHS summary scores of 47.3 (SD = 11.5) and 49.2 (SD = 10.7) respectively. The mean SF-12v2 PCS and MCS scores were 47.7 (SD = 11.0) and 44.0 (SD = 10.4). The MOS-HIV and SF-12v2 physical and mental health summary scores were positively correlated (r = 0.84, p < 0.001 and r = 0.76, p < 0.001). All common sub-domains were significantly correlated at p values from < 0.001 to 0.034. Substantial agreement was observed in assigning a HRQoL state (Physical: κ = 0.788, SE = 0.095; Mental: κ = 0.707, SE = 0.095). Conclusions This analysis validates the SF-12v2 for measuring HRQoL in adult men and women living with HIV/AIDS.

Abstract Background Smoking prevalence in human immunodeficiency virus (HIV) positive subjects is about three times of that in the general population. However, whether the extremely high smoking prevalence in HIV-positive subjects affects their lung function is unclear, particularly whether smoking decreases lung function more in HIV-positive subjects, compared to the general population. We conducted this study to determine the association between smoking and lung function, respiratory symptoms and diseases amongst HIV-positive subjects. Results Of 120 enrolled HIV-positive subjects, 119 had an acceptable spirogram. Ninety-four (79%) subjects were men, and 96 (81%) were white. Mean (standard deviation [SD]) age was 43.4 (8.4) years. Mean (SD) of forced expiratory volume in one second (FEV1) percent of age, gender, race and height predicted value (%FEV1) was 93.1% (15.7%). Seventy-five (63%) subjects had smoked 24.0 (18.0) pack-years. For every ten pack-years of smoking increment, %FEV1 decreased by 2.1% (95% confidence interval [CI]: -3.6%, -0.6%), after controlling for gender, race and restrictive lung function (R2 = 0.210). The loss of %FEV1 in our subjects was comparable to the general population. Compared to non-smokers, current smokers had higher odds of cough, sputum or breathlessness, after adjusting for highly active anti-retroviral therapy (HAART) use, odds ratio OR = 4.9 (95% CI: 2.0, 11.8). However respiratory symptom presence was similar between non-smokers and former smokers, OR = 1.0 (95% CI: 0.3, 2.8). All four cases of COPD (chronic obstructive pulmonary disease) had smoked. Four of ten cases of restrictive lung disease had smoked (p = 0.170), and three of five asthmatic subjects had smoked (p = 1.000). Conclusions Cumulative cigarette consumption was associated with worse lung function; however the loss of %FEV1 did not accelerate in HIV-positive population compared to the general population. Current smokers had higher odds of respiratory symptoms than non-smokers, while former smokers had the same odds of respiratory symptoms as non-smokers. Cigarette consumption was likely associated with more COPD cases in HIV-positive population; however more participants and longer follow up would be needed to estimate the effect of smoking on COPD development. Effective smoking cessation strategies are required for HIV-positive subjects.

Abstract Background Non-invasive surrogate measures which are valid and responsive to change are needed to study cardiovascular risks in HIV. We compared the construct validity of two noninvasive arterial measures: carotid intima medial thickness (IMT), which measures anatomic disease; and brachial flow-mediated vasodilation (FMD), a measure of endothelial dysfunction. Methods A sample of 257 subjects aged 35 years or older, attending clinics in five Canadian centres, were prospectively recruited into a study of cardiovascular risk among HIV subjects. The relationship between baseline IMT or FMD and traditional vascular risk factors was studied using regression analysis. We analyzed the relationship between progression of IMT or FMD and risk factors using fixed-effects models. We adjusted for use of statin medication and CD4 count in both models. Results Baseline IMT was significantly associated with age (p < 0.001), male gender (p = 0.034), current smoking status (p < 0.001), systolic blood pressure (p < 0.001) and total:HDL cholesterol ratio (p = 0.004), but not statin use (p = 0.904) and CD4 count (p = 0.929). IMT progression was significantly associated with age (p < 0.001), male gender (p = 0.0051) and current smoking status (p = 0.011), but not statin use (p = 0.289) and CD4 count (p = 0.927). FMD progression was significantly associated with current statin use (p = 0.019), but not CD4 count (p = 0.84). Neither extent nor progression of FMD was significantly associated with any of the examined vascular risk factors. Conclusion IMT correlates better than FMD with established cardiovascular risk factors in this cohort of HIV patients. Standardization of protocols for FMD and IMT will facilitate the comparison of results across studies.